ORCID Profile
0000-0001-5865-489X
Current Organisation
The University of Newcastle
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Publisher: Springer Science and Business Media LLC
Date: 18-03-2020
DOI: 10.1186/S12890-020-1101-6
Abstract: Uncontrolled severe asthma in children is burdensome and challenging to manage. This study aims to describe outcomes in children with uncontrolled severe asthma managed in a nurse-led severe asthma clinic (SAC). This retrospective analysis uses data collected from children referred by a paediatric respiratory specialist to a nurse-led SAC for uncontrolled severe asthma between 2014 and 2019. The pre-clinical assessments included a home visit to assess modifiable factors that could be addressed to improve control. A comprehensive lung function analysis was conducted at each visit. Interventions were personalised and included biologic agents. Statistical analysis was performed using nonparametric, two-tailed Mann-Whitney U-test, the parametric Student’s t-test, or analysis of variance (ANOVA) as appropriate. Twenty-three children with a median age of 12 years were seen once, and 16 were followed up. Compared to a non-asthmatic (NA) and asthmatic (A) age-matched cohort, children with severe asthma (SA) had a lower FEV1, and FVC% predicted before and after bronchodilator inhalation, and a higher mean Lung Clearance Index [LCI] (10.5 [SA] versus 7.3 [NA] versus 7.6 [A], p = 0.003). Almost 80% of children with SA had an abnormal LCI, and 48% had a reduced FEV1% at the first SAC visit. Asthma control and FEV1% predicted significantly improved at a follow-up visit, while LCI remained abnormal in the majority of children (83%). Over time, many children with severe asthma showed improved clinical outcomes and lung function while lung ventilation inhomogeneities persisted. Future appropriately controlled studies are required to determine if a nurse-led multidisciplinary SAC is associated with better outcomes.
Publisher: Wiley
Date: 24-03-2018
DOI: 10.1002/PPUL.23984
Abstract: Protracted bacterial bronchitis (PBB) is a common cause of prolonged cough in young children, and may be a precursor of bronchiectasis. Bacteria are often present in the lower airways in both PBB and bronchiectasis and may cause persistent infections. However, there is a paucity of information available on the pathogenesis of PBB and the factors associated with persistent bacterial infection and progression to bronchiectasis. This study hypothesised that lung immune cells in recurrent PBB and bronchiectasis differentially express genes related to immune cell dysfunction compared to lung immune cells from control subjects. Cells isolated from bronchoalveolar lavage (adult-control and PBB BAL cells) were stimulated with nontypeable Haemophilus influenzae (NTHi), and expression of genes involved in various inflammatory pathways was assessed. NTHi induced production of large amounts of IL-1β, IL-6, and IL-8 in adult-control BAL cells, however BAL cells from PBB airways appeared refractory to NTHi stimulation. BAL cells from PBB and bronchiectasis showed differential expression of several genes relative to control cells, including CCL20, MARCO, CCL24, IL-10, PPAR-γ, CD200R, TREM2, RelB. Expression of genes involved in resolution of inflammation and anti-inflammation response, such as CD200R and IL-10, was associated with the number of pathogenic bacteria found in the airways. In summary, we have shown that the expression of genes related to macrophage function and resolution of inflammation are similar in PBB and bronchiectasis. Lung immune cell dysfunction in PBB and bronchiectasis may contribute to poor bacterial clearance and prolonged resolution of inflammation.
Publisher: Wiley
Date: 2007
DOI: 10.1002/PPUL.20592
Abstract: Neuro-immune interactions are increasingly relevant to human health and disease. The neuropeptide Substance P also has antibacterial activity and bears similarities to the innate immune antibacterial defensins. This suggests possible co-regulation of neuropeptide and innate immune mediators. In this study, non-bronchoscopic bronchoalveolar lavage (BAL) was performed on 69 children. BAL was examined for cellular profile, microbiology (bacteria, virus) and gene expression for TLRs 2, 3, 4 chemokine receptors (CCR3, CCR5, CXCR1) neurotrophins and neurokinin genes (TAC1, TAC3, CGRP, NGF). In children with bacterial colonization (n=10) there was an airway inflammatory response with increased BAL neutrophils, IL-8 protein, and CXCR1 expression. Substance P (TAC1) and TLR4 RNA expression were reduced in children with bacterial colonization. TLR3 mRNA was increased in 7.2% (n=5) children with rhinovirus, and there was a non-significant trend to increased TLR2. There is evidence for co-regulation of neurokinin (TAC1) and TLR4 gene expression in airway cells from children with airway bacterial colonization and their reduced expression may be associated with an impaired bacterial clearance.
Publisher: Elsevier BV
Date: 03-0012
DOI: 10.1016/J.JACI.2018.02.039
Abstract: The single-center double-blind, randomized controlled Managing Asthma in Pregnancy (MAP) trial in Newcastle, Australia, compared a treatment algorithm using the fraction of exhaled nitric oxide (FENO) in combination with asthma symptoms (FENO group) against a treatment algorithm using clinical symptoms only (clinical group) in pregnant asthmatic women (Australian New Zealand Clinical Trials Registry, no. 12607000561482). The primary outcome was a 50% reduction in asthma exacerbations during pregnancy in the FENO group. However, the effect of FENO-guided management on the development of asthma in the offspring is unknown. We sought to investigate the effect of FENO-guided asthma management during pregnancy on asthma incidence in childhood. A total of 179 mothers consented to participate in the Growing into Asthma (GIA) double-blind follow-up study with the primary aim to determine the effect of FENO-guided asthma management on childhood asthma incidence. A total of 140 children (78%) were followed up at 4 to 6 years of age. FENO-guided as compared to symptoms-only approach significantly reduced doctor-diagnosed asthma (25.9% vs 43.2% odds ratio [OR], 0.46, 95% CI, 0.22-0.96 P = .04). Furthermore, frequent wheeze (OR, 0.27 95% CI, 0.09-0.87 P = .03), use of short-acting β-agonists (OR, 0.49 95% CI, 0.25-0.97 P = .04), and emergency department visits for asthma (OR, 0.17 95% CI, 0.04-0.76 P = .02) in the past 12 months were less common in children born to mothers from the FENO group. Doctor-diagnosed asthma was associated with common risk alleles for early onset asthma at gene locus 17q21 (P = .01 for rs8069176 P = .03 for rs8076131), and higher airways resistance (P = .02) and FENO levels (P = .03). A causal mediation analysis suggested natural indirect effects of FENO-guided asthma management on childhood asthma through "any use" and "time to first change in dose" of inhaled corticosteroids during the MAP trial (OR: 0.83 95% CI: 0.59-0.99, and OR: 0.90 95% CI: 0.70-1.03, respectively). FENO-guided asthma management during pregnancy prevented doctor-diagnosed asthma in the offspring at preschool age, in part mediated through changes in use and dosing of inhaled corticosteroids during the MAP trial.
Publisher: American Thoracic Society
Date: 07-1998
DOI: 10.1164/AJRCCM.158.1.9705031
Abstract: The role of airway inflammation in childhood asthma is not well defined, despite modern treatment approaches recommending potent anti-inflammatory therapy for an increasing number of children. In this study, induced sputum analysis was used to investigate the relationships among sputum inflammatory cells (eosinophils and mast cells), asthma symptoms, and airway hyperresponsiveness to hypertonic saline in a cohort of 170 children aged 8-14 years. Children who reported asthma symptoms in the past 2 wk had a 2. 25-fold (95% to CI, 1.20-4.24) increased odds of having significant sputum eosinophilia. Hyperresponsiveness to hypertonic saline was strongly associated with higher levels of sputum eosinophils ([OR] 4. 36, 1.70-11.20), sputum mast cells (OR 7.46, 2.48-22.75), and nasal eosinophils (OR 4.73, 1.89-11.86). Interestingly, boys were more likely than girls to have features of airway inflammation (sputum mast cells, OR 3.33, 1.15-9.65 nasal eosinophils, OR 3.25, 1.72-5. 97), which is consistent with the known increase in asthma prevalence in boys in this age group. Airway inflammation with eosinophils and mast cells is likely to be important in the pathogenesis of asthma in childhood. Induced sputum analysis can be used to evaluate this problem and has the potential to be a useful tool for monitoring therapy.
Publisher: Wiley
Date: 20-04-2012
DOI: 10.1111/J.1365-2222.2012.03981.X
Abstract: Exacerbations occur frequently in severe asthma. They result in significant morbidity and can lead to hospitalization and death. Severe exacerbations can also lead to an accelerated decline in lung function. Phenotyping severe asthma can aid with both prognostication of exacerbation risk and maintenance treatment selection to minimize future risks of exacerbations in severe asthma. The rate of exacerbations differs by phenotype, and is most frequent in refractory eosinophilic asthma and early onset allergic asthma. Phenotype specific therapy can reduce exacerbations in both these forms of severe asthma. Exacerbations are multi-component events. Each exacerbation represents an opportunity to assess and target treatment to the domains of airway pharmacotherapy, self-management behaviour, risk factors, and relevant co-morbidities.
Publisher: BMJ
Date: 03-12-2022
DOI: 10.1136/THORAXJNL-2021-217299
Abstract: Nitric oxide in exhaled air (eNO) is used as a marker of type 2 immune response-induced airway inflammation. We aimed to investigate the association between eNO and bronchiolitis incidence and respiratory symptoms in infancy, and its correlation with eosinophil protein X (EPX). We followed up infants at 6 weeks of age born to mothers with asthma in pregnancy and measured eNO during natural sleep using a rapid response chemiluminescense analyser (CLD88 EcoMedics), collecting at least 100 breaths, interpolated for an expiratory flow of 50 mL/s. EPX normalised to creatinine was measured in urine s les (uEPX/c). A standardised questionnaire was used to measure symptoms in first year of life. Associations were investigated using multiple linear regression and robust Poisson regression models. eNO levels were obtained in 184 infants, of whom 125/184 (68%) had 12 months questionnaire data available and 51/184 (28%) had uEPX/c measured. Higher eNO was associated with less respiratory symptoms during the first 6 weeks of life (n=184, ß-coefficient: –0.49, 95% CI –0.95 to –0.04, p=0.035). eNO was negatively associated with uEPX/c (ß-coefficient: –0.004, 95% CI –0.008 to –0.001, p=0.021). Risk incidence of bronchiolitis, wheeze, cold or influenza illness and short-acting beta-agonist use significantly decreased by 18%–24% for every unit increase in eNO ppb. Higher eNO levels at 6 weeks of age may be a surrogate for an altered immune response that is associated with less respiratory symptoms in the first year of life.
Publisher: Wiley
Date: 05-1992
DOI: 10.1111/J.1365-2222.1992.TB00161.X
Abstract: This study evaluated a research method to examine an exacerbation of asthma induced by corticosteroid withdrawal. Ten non-smoking adult asthmatics who were stable on treatment with inhaled steroid underwent a graded reduction of the daily dose by 200 micrograms at weekly intervals until an exacerbation of symptoms occurred. A daily symptom, peak expiratory flow rate (PEF) and medication diary was kept. Weekly clinic visits were used to assess symptoms, spirometry, methacholine airway responsiveness (expressed as the provocative concentration to cause a fall in FEV1 of 20%, PC20), circulating eosinophils, basophils and their progenitors (Eo/B-CFU), and sputum inflammatory cells. The laboratory tests were performed blind to the clinical details. Each subject developed an exacerbation of symptoms, on average at 16 (7-26) days after the onset of steroid reduction. This was accompanied by a deterioration in each of the objective measures. There was a fall in FEV1 by 320 ml (s.e.m. 9.5) and in PC20 from 0.8 to 0.43 mg/ml. Circulating eosinophils rose from 114 (24) x 10(3)/ml to 227 (50) x 10(3)/ml and Eo/B-CFU rose from 31 (5.6) to 44 (11.3)/10(6) cells. Sputum developed in five subjects and contained 36 (5.2)% eosinophils and 1.98 (0.21)% metachromatic cells (mast cells or basophils). The symptom diary and weekly questionnaire were demonstrated to be valid and responsive to change. A deterioration indicated by the daily symptom score preceded changes in PEF. Treatment by an increase in steroid was followed by reversal of each of the changes.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: European Respiratory Society (ERS)
Date: 2022
DOI: 10.1183/23120541.00667-2021
Abstract: Cough symptom severity represents an important subjective end-point to assess the impact of therapies for patients with refractory or unexplained chronic cough (RCC/UCC). As existing instruments assessing the severity of cough are neither widely available nor tested for measurement properties, we aim to develop a new patient-reported outcome measure addressing cough severity. The aim of this study was to establish items and domains that would inform development of a new cough severity instrument. Three focus groups involving 16 adult patients with RCC/UCC provided data that we analysed using directed content analysis. Discussions led to consensus among an international panel of 15 experts on candidate items and domains to assess cough severity. The patient focus group provided 48 unique items arranged under broad domains of urge-to-cough sensations and cough symptom. Feedback from expert panel members confirmed the appropriateness of items and domains, and provided an additional subdomain related to cough triggers. The final conceptual framework comprised 51 items in the following domains: urge-to-cough sensations (subdomains: frequency and intensity) and cough symptom (subdomains: triggers, control, frequency, fit/bout duration, intensity, quality and associated features/sequelae). Consensus findings from patients and international experts established domains of urge-to-cough and cough symptom with associated subdomains and relevant items. The results support item generation and content validity for a novel patient-reported outcome measure for use in health research and clinical practice.
Publisher: American Thoracic Society
Date: 11-2016
Publisher: European Respiratory Society (ERS)
Date: 02-10-2021
DOI: 10.1183/13993003.02436-2020
Abstract: Add-on azithromycin (AZM) results in a significant reduction in exacerbations among adults with persistent uncontrolled asthma. The aim of this study was to assess the cost-effectiveness of add-on AZM in terms of healthcare and societal costs. The AMAZES trial randomly assigned 420 participants to AZM or placebo. Healthcare use and asthma exacerbations were measured during the treatment period. Healthcare use included all prescribed medicine and healthcare contacts. Costs of antimicrobial resistance (AMR) were estimated based on overall consumption and published estimates of costs. The value of an avoided exacerbation was based on published references. Differences in cost between the two groups were related to differences in exacerbations in a series of net monetary benefit estimates. Societal costs included lost productivity, over the counter medicines, steroid induced morbidity and AMR costs. Add-on AZM resulted in a reduction in healthcare costs (mean (95% CI)) including nights in hospital (AUD 433.70 (AUD 48.59–818.81) or EUR 260.22 (EUR 29.15–491.29)), unplanned healthcare visits (AUD 20.25 (AUD 5.23–35.27) or EUR 12.15 (EUR 3.14–21.16)), antibiotic costs (AUD 14.88 (AUD 7.55–22.21) or EUR 8.93 (EUR 4.53–13.33)) and oral corticosteroid costs (AUD 4.73 (AUD 0.82–8.64) or EUR 2.84 (EUR 0.49–5.18)) all p .05. Overall healthcare and societal costs were lower (AUD 77.30 (EUR 46.38) and AUD 256.22 (EUR 153.73) respectively) albeit not statistically significant. The net monetary benefit of add-on AZM was estimated to be AUD 2072.30 (95% CI AUD 1348.55–2805.23) or (EUR 1243.38 (EUR 809.13–1683.14) assuming a willingness to pay per exacerbation avoided of AUD 2651 (EUR 1590.60). Irrespective of the sensitivity analysis applied, the net monetary benefit for total, moderate and severe exacerbations remained positive and significant. Add-on AZM therapy in poorly controlled asthma was a cost-effective therapy. Costs associated with AMR did not influence estimated cost-effectiveness.
Publisher: Elsevier BV
Date: 02-2013
Publisher: European Respiratory Society (ERS)
Date: 10-02-2011
DOI: 10.1183/09031936.00139810
Abstract: Obesity and asthma are associated, but the mechanism(s) of the association have yet to be elucidated. The aim of this study was to assess airway inflammation in relation to obesity and plasma fatty acids in males and females with and without asthma. Obese (n=68) and nonobese (n=47) adults with asthma, and obese (n=16) and nonobese (n=63) healthy controls had induced sputum and venous blood s les analysed for inflammatory markers. There was a positive interaction between obesity and asthma on sputum neutrophil percentage (p=0.012) and C-reactive protein level (p=0.003). Although sputum eosinophil percentage was elevated in asthma (p=0.001), there was no effect of obesity (p=0.16). Sputum neutrophil percentage was positively associated with body mass index in females with asthma (β=1.015, 95% CI 0.258-1.772 p=0.009) and neutrophilic asthma was present in a greater proportion of obese compared with non-obese females (42.9% versus 16.2% p=0.017). In males with asthma, sputum neutrophil percentage was positively associated with total plasma saturated fatty acids (β=0.108, 95% CI 0.036-0.180 p=0.004) and negatively with monounsaturated fatty acids (β= -0.068, 95% CI -0.131- -0.005 p=0.035). This was the first study to demonstrate an increase in neutrophilic airway inflammation in obese asthma. This relationship was significant only in females with asthma. In males, saturated and monounsaturated fatty acids were important predictors of neutrophilic airway inflammation in asthma.
Publisher: Elsevier BV
Date: 2011
DOI: 10.1016/J.JACI.2010.10.024
Abstract: Previous studies have identified clinical or inflammatory phenotypes of asthma on the basis of clinical and demographic parameters or sputum cell counts however, few studies have defined transcriptional phenotypes of asthma. To investigate asthma phenotypes at a transcriptional level by using gene expression profiling of induced sputum. Induced sputum s les were collected from 59 people with asthma with a mean age of 58 years and an FEV(1)% predicted of 76%, and 69% were taking inhaled corticosteroids. Thirteen healthy controls without asthma were also assessed. Inflammatory cell counts were performed, and RNA was extracted from selected sputum. Transcriptional profiles were generated (Illumina Humanref-8 V2) and analyzed by using GeneSpring GX11. Unsupervised hierarchical clustering of gene expression profiles in asthma revealed 3 distinct groups. The first transcriptional phenotype (n = 21) had lower FEV(1)% predicted and higher asthma control questionnaire scores, exhaled nitric oxide, and sputum eosinophils. The second transcriptional phenotype (n = 14) had lower FEV(1)% predicted and forced vital capacity % predicted and higher sputum neutrophils compared with a third transcriptional phenotype (n = 24) that had higher sputum macrophages and resembled healthy controls. Differentially expressed genes between transcriptional asthma phenotypes were related to inflammatory and immune responses. Genes in the IL-1 and TNF-α/nuclear factor-κB pathways were overexpressed and correlated with clinical parameters and neutrophilic airway inflammation. Gene expression profiling provides a novel means to investigate the molecular mechanisms and classifications of asthma phenotypes. There are 3 distinct transcriptional phenotypes of asthma that relate to both clinical and inflammatory parameters.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2015
DOI: 10.1038/NCOMMS8320
Abstract: Asthma is prevalent in Western countries, and recent explanations have evoked the actions of the gut microbiota. Here we show that feeding mice a high-fibre diet yields a distinctive gut microbiota, which increases the levels of the short-chain fatty acid, acetate. High-fibre or acetate-feeding led to marked suppression of allergic airways disease (AAD, a model for human asthma), by enhancing T-regulatory cell numbers and function. Acetate increases acetylation at the Foxp3 promoter, likely through HDAC9 inhibition. Epigenetic effects of fibre/acetate in adult mice led us to examine the influence of maternal intake of fibre/acetate. High-fibre/acetate feeding of pregnant mice imparts on their adult offspring an inability to develop robust AAD. High fibre/acetate suppresses expression of certain genes in the mouse fetal lung linked to both human asthma and mouse AAD. Thus, diet acting on the gut microbiota profoundly influences airway responses, and may represent an approach to prevent asthma, including during pregnancy.
Publisher: Wiley
Date: 09-2005
DOI: 10.1111/J.1365-2222.2005.02327.X
Abstract: Airway inflammation is assessed to monitor progression, control and treatment of asthma. The collection of exhaled breath condensate (EBC) provides a non-invasive alternative to induced sputum s les for the monitoring of airway inflammation. Both s les can be confounded by salivary contamination. The aim of this study was to compare the levels of inflammatory mediators in s les of EBC, induced sputum and saliva s les from subjects with asthma. EBC, saliva and induced sputum s les were collected from subjects with asthma (n=10). Total protein, IL-8, 8-isoprostane and surfactant protein A (SPA) were assessed in each s le. Total protein, IL-8, 8-isoprostane and SPA were detected in all sputum s les. Only total protein and SPA were consistently measured in EBC, with levels at least 100-fold lower than those measured in induced sputum. In saliva, total protein, SPA and 8-isoprostane were detected in all s les, with IL-8 detected in 60% of s les. Induced sputum is a reliable technique that can be used to assess markers of airway inflammation. While EBC is a simple and inexpensive technique to collect lower airway secretions, the detection of inflammatory mediators is variable, and further work is required to validate this technique to assess inflammatory mediators.
Publisher: European Respiratory Society (ERS)
Date: 12-12-2013
DOI: 10.1183/09031936.00202013
Abstract: Severe or therapy-resistant asthma is increasingly recognised as a major unmet need. A Task Force, supported by the European Respiratory Society and American Thoracic Society, reviewed the definition and provided recommendations and guidelines on the evaluation and treatment of severe asthma in children and adults. A literature review was performed, followed by discussion by an expert committee according to the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach for development of specific clinical recommendations. When the diagnosis of asthma is confirmed and comorbidities addressed, severe asthma is defined as asthma that requires treatment with high dose inhaled corticosteroids plus a second controller and/or systemic corticosteroids to prevent it from becoming “uncontrolled” or that remains “uncontrolled” despite this therapy. Severe asthma is a heterogeneous condition consisting of phenotypes such as eosinophilic asthma. Specific recommendations on the use of sputum eosinophil count and exhaled nitric oxide to guide therapy, as well as treatment with anti-IgE antibody, methotrexate, macrolide antibiotics, antifungal agents and bronchial thermoplasty are provided. Coordinated research efforts for improved phenotyping will provide safe and effective biomarker-driven approaches to severe asthma therapy.
Publisher: Informa UK Limited
Date: 29-12-2022
Publisher: Informa UK Limited
Date: 12-09-2015
DOI: 10.3109/02770903.2015.1054403
Abstract: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pregnant women with asthma. Two hundred and eighteen non-smoking pregnant women with asthma were participants in a randomised controlled trial of exhaled nitric oxide guided treatment adjustment. Rhinitis was assessed using a visual analogue scale (VAS) scored from 0 to 10 and classified as current (VAS > 2.5), moderate/severe versus mild (VAS > 6 vs <5), atopic versus non-atopic and pregnancy rhinitis. At baseline, women completed the 20-Item Sino-Nasal Outcome Test (SNOT20), asthma-specific (AQLQ-M) QoL questionnaires and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Asthma control was assessed using the asthma control questionnaire (ACQ). Perinatal outcomes were collected after delivery. Current rhinitis was present in 142 (65%) women including 45 (20%) women who developed pregnancy rhinitis. Women with current rhinitis had higher scores for ACQ (p = 0.004), SNOT20 (p < 0.0001) and AQLQ-M (p < 0.0001) compared to women with no rhinitis. Current rhinitis was associated with increased anxiety symptoms (p = 0.002), rhinitis severity was associated with higher ACQ score (p = 0.004) and atopic rhinitis was associated with poorer lung function (p = 0.037). Rhinitis symptom severity improved significantly during gestation (p < 0.0001). There was no impact on perinatal outcomes. Improved asthma control was associated with improvement in rhinitis. Rhinitis in pregnant women with asthma is common and associated with poorer asthma control, sino-nasal and asthma-specific QoL impairment and anxiety. In the context of active asthma management there was significant improvement in rhinitis symptoms and severity as pregnancy progressed.
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0091-6749(98)70039-9
Abstract: Airway inflammation is important in the pathogenesis of asthma, during which it may lead to symptomatic exacerbations and increases in asthma severity, as well as contribute to future decline in asthma status. The use of induced sputum has emerged as an important and useful technique to study airway inflammation. It has particular advantages in the study of childhood asthma because it is noninvasive and allows s les to be collected on repeated occasions in children over 7 years of age. The results of cell counts are reliable when the sputum is processed in a standardized manner involving selection from saliva, cell dispersion, and quantitative cytology. Children with asthma have increased eosinophils and mast cells, which may persist even with high doses of inhaled corticosteroid therapy. During a severe exacerbation of asthma, there is an intense and heterogeneous inflammatory response involving eosinophil and neutrophil accumulation and activation. Characterization of the relevance of airway inflammation in children with asthma is important.
Publisher: Informa UK Limited
Date: 03-2021
DOI: 10.2147/JAA.S296147
Publisher: Wiley
Date: 27-01-2011
Publisher: European Respiratory Society (ERS)
Date: 05-12-2020
DOI: 10.1183/13993003.01509-2019
Abstract: Treatable traits have been proposed as a new paradigm for airway disease management. To characterise treatable traits in a severe asthma population and to determine the efficacy of targeting treatments to these treatable traits in severe asthma. Participants (n=140) with severe asthma were recruited to a cross-sectional study and underwent a multidimensional assessment to characterise treatable traits. Eligible participants with severe asthma (n=55) participated in a 16-week parallel-group randomised controlled trial to determine the feasibility and efficacy of management targeted to predefined treatable traits, compared to usual care in a severe asthma clinic. The patient-reported outcome of health-related quality of life was the trial's primary end-point. Participants with severe asthma had a mean± sd of 10.44±3.03 traits per person, comprising 3.01±1.54 pulmonary and 4.85±1.86 extrapulmonary traits and 2.58±1.31 behavioural/risk factors. In idualised treatment that targeted the traits was feasible and led to significantly improved health-related quality of life (0.86 units, p .001) and asthma control (0.73, p=0.01). Multidimensional assessment enables detection of treatable traits and identifies a significant trait burden in severe asthma. Targeting these treatable traits using a personalised-medicine approach in severe asthma leads to improvements in health-related quality of life, asthma control and reduced primary care acute visits. Treatable traits may be an effective way to address the complexity of severe asthma.
Publisher: Informa UK Limited
Date: 09-11-2009
DOI: 10.3109/01902140902906412
Abstract: Oncostatin M, a unique member of the interleukin (IL)-6 cytokine family, is thought to be involved in airway remodeling. The expression of oncostatin M in the lower airways is unknown. The aim of this study was to measure the sputum expression of oncostatin M in patients with asthma with and without irreversible airflow obstruction. Induced sputum was collected from nonsmoking adults with stable asthma (n = 53), 31 with incomplete reversibility of airflow obstruction. Peripheral blood cells were isolated and stimulated with lipopolysaccharide in 10 participants with asthma and irreversible airflow obstruction. Oncostatin M protein levels were determined in supernatant, whereas RNA was extracted to determine Oncostatin M mRNA expression using real-time polymerase chain reaction (PCR). Oncostatin M mRNA expression and protein levels were significantly higher in the sputum of asthmatics with irreversible airflow obstruction. Sputum oncostatin M levels were highest in people with severe airflow obstruction and were localized to airway neutrophils and macrophages. Peripheral blood neutrophils released more oncostatin M when stimulated with lipopolysaccharide compared with unstimulated neutrophils. Sputum oncostatin M is increased in asthma with irreversible airflow obstruction and is present in airway neutrophils and macrophages. Oncostatin M may link airway inflammation to remodeling in asthma.
Publisher: Ivyspring International Publisher
Date: 2019
DOI: 10.7150/IJMS.29433
Publisher: Wiley
Date: 06-1995
DOI: 10.1111/J.1440-1746.1995.TB01101.X
Abstract: The amount and type of dietary fibre ingested influences colonic luminal characteristics, especially the concentration of carbohydrate fermentation products such as butyrate. This study aimed to assess whether diets supplemented with fibres of differing fermentability (delivering different amounts of butyrate to the colon) influence mucosal activities of urokinase and brush border hydrolases, and epithelial turnover. Groups of five rats were fed one of four diets containing low (2%), highly fermented (guar 10% or oat bran 10%) or slowly fermented fibre (wheat bran 10%) for 4 weeks. Activities of urokinase, alkaline phosphatase, dipeptidyl peptidase IV and maltase were measured in mucosal homogenates of proximal and distal colon and from rectum. Proliferative kinetics were assessed in distal and proximal colon by the metaphase arrest technique. Hydrolase activities were similar across all four dietary groups but a significant difference was found for urokinase (P = 0.014). This was due to a reduction in urokinase activities of > 30% at the three sites in the wheat bran group compared with the other groups. Of proliferative indices, only crypt column height differed across the groups (P = 0.038) and was highest in rats fed wheat bran and lowest in those fed the low fibre diet (P = 0.047). The proportion of mitoses in the top one-fifth of the crypt also differed across groups (P = 0.038) due to the high values in the distal colon of the low fibre group. Thus, addition of a slowly fermented (but not highly fermented) fibre to the diet of rats reduces net urokinase activity in large bowel mucosa and increases the life span of colonic epithelial cells without changing activities of brush border hydrolases.
Publisher: European Respiratory Society (ERS)
Date: 05-2019
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 13-07-2011
DOI: 10.1111/J.1471-0528.2011.03055.X
Abstract: Asthma is a common condition during pregnancy and may be associated with adverse perinatal outcomes. This meta-analysis sought to establish if maternal asthma is associated with an increased risk of adverse perinatal outcomes, and to determine the size of these effects. Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between 1975 and March 2009 were considered for inclusion. Studies were included if they reported at least one perinatal outcome in pregnant women with and without asthma. A total of 103 articles were identified, and of these 40 publications involving 1,637,180 subjects were included. Meta-analysis was conducted with subgroup analyses by study design and active asthma management. Maternal asthma was associated with an increased risk of low birthweight (RR 1.46, 95% CI 1.22-1.75), small for gestational age (RR 1.22, 95% CI 1.14-1.31), preterm delivery (RR 1.41, 95% CI 1.22-1.61) and pre-ecl sia (RR 1.54, 95% CI 1.32-1.81). The relative risk of preterm delivery and preterm labour were reduced to non-significant levels by active asthma management (RR 1.07, 95% CI 0.91-1.26 for preterm delivery RR 0.96, 95% CI 0.73-1.26 for preterm labour). Pregnant women with asthma are at increased risk of perinatal complications, including pre-ecl sia and outcomes that affect the baby's size and timing of birth. Active asthma management with a view to reducing the exacerbation rate may be clinically useful in reducing the risk of perinatal complications, particularly preterm delivery.
Publisher: Elsevier BV
Date: 08-2013
Publisher: American Thoracic Society
Date: 07-1996
DOI: 10.1164/AJRCCM.154.1.8680686
Abstract: Asthma is accompanied by the accumulation of potentially damaging eosinophils within inflamed airways. How eosinophils may be removed from the airways is not clear. The phagocytic removal of eosinophils in vitro requires that they undergo apoptosis, a form of cell death. We postulated that eosinophil apoptosis may occur in vivo, promoting the removal of airway eosinophils and the resolution of inflammation in asthma. We examined eosinophil apoptosis in sputum s les obtained from 11 subjects during an asthma exacerbation and 2 wk after corticosteroid treatment of the exacerbation. Airway function improved following corticosteroid treatment, and eosinophilic inflammation subsided, with significant decreases occurring in the number of airway eosinophils and the percentage of activated eosinophils. The proportion of apoptotic airway eosinophils increased significantly following corticosteroid treatment, and eosinophil products were apparent within macrophages. Our findings indicate that eosinophil apoptosis is clinically relevant in asthma. Apoptosis may represent a mechanism that promotes the resolution of eosinophilic inflammation in asthma.
Publisher: Wiley
Date: 04-08-2003
DOI: 10.1002/PPUL.10323
Abstract: The prevalence of asthma symptoms varies markedly throughout the world. However, the asthma mechanisms involved are not defined. Studying the effects of migration can help identify the reasons for this geographic variation. The aims of this study were to examine the prevalence of asthma symptoms, airway hyperresponsiveness (AHR), and induced sputum eosinophils in adolescents who migrate to Australia. The study was conducted in Sydney, Australia, where adolescent students completed a video symptom questionnaire, hypertonic saline challenge, sputum induction, and allergy skin testing. The 211 students had widely different cultural backgrounds, including Asian, South Pacific, Middle Eastern, European, and African countries. Among adolescents who were migrants to Australia, the prevalence of asthma symptoms was higher than that reported using a similar methodology in their country of origin. Asthma symptom prevalence was related to residence time in Australia. The prevalence of wheeze was 17.2% in recent arrivals, 20.5% in adolescents living in Australia for >2 years, and 36.3% in those living all their lifetime in Australia (P = 0.013). For every year of residence in Australia, there was an 11% increase in prevalence of current wheeze (odds ratio, 1.11 P = 0.02). This effect was not related to atopy, AHR, or eosinophilic airway inflammation. Sputum neutrophils were elevated in recent arrivals. In conclusion, adolescents who migrate to Australia report increased asthma symptoms, compared to their country of origin, and asthma symptoms are further increased for every additional year of residence in Australia. The development of wheeze after migration to Australia was independent of eosinophilic inflammation and consistent with noneosinophilic asthma mechanisms.
Publisher: Elsevier BV
Date: 11-2017
Publisher: European Respiratory Society (ERS)
Date: 10-1995
DOI: 10.1183/09031936.95.08101731
Abstract: The relevance of increased methacholine airway responsiveness detected in children with no current or past symptoms of asthma is not known. We wished to determine whether the presence of airway hyperresponsiveness in asymptomatic children is also associated with abnormal variability of peak expiratory flow (PEF). In 12 asymptomatic children with methacholine hyperresponsiveness, we examined the diurnal variation of peak expiratory flow (PEF) and response to inhaled bronchodilator. Twelve asthmatic children with a comparable range of methacholine hyperresponsiveness, and 12 normal children without methacholine responsiveness, were used as positive and negative controls. The children were aged 11 (range 9-14) yrs. The mean diurnal variation of PEF in those children with asymptomatic hyperresponsiveness was increased at 9.3%, to a degree comparable to the symptomatic asthmatic children (10.7%), and greater than the normal children (5.7%). Methacholine stimulated airway constriction was associated with symptoms in subjects from each group, indicating that the children were capable of perceiving airway constriction. We conclude that asymptomatic children with methacholine airway hyperresponsiveness have other evidence of mild variable airflow obstruction with increased diurnal PEF variability, and can perceive airflow limitation. The lack of symptoms in the children with airway hyperresponsiveness could be due to an insufficient stimulus to cause symptomatic obstruction, or the absence of eosinophilic airway inflammation, which may be a requirement for the development of symptomatic airway hyperresponsiveness.
Publisher: Elsevier BV
Date: 09-2010
Publisher: Elsevier BV
Date: 07-2009
DOI: 10.1016/J.PHARMTHERA.2009.03.015
Abstract: The dramatic increase in asthma prevalence in westernised countries in recent decades, and the development of asthma in susceptible in iduals who have migrated to a western country, suggests that environmental factors, such as dietary intake, must play a role in the onset and development of the disease. Key features of a westernised diet are low antioxidant intake, high fat intake and chronic metabolic surplus, resulting in obesity. Each of these may be contributing to increased asthma prevalence, due to their ability to modulate the innate immune response. A low antioxidant intake impairs the host's ability to scavenge reactive oxygen species, thereby promoting an NFkappaB-mediated innate immune response, resulting in oxidative damage. A high dietary intake of saturated fat can also activate the innate immune response, as saturated fatty acids can directly activate toll-like receptor 4 (TLR4), which also leads to a NFkappaB-driven inflammatory cascade. Also characteristic of a western diet is chronic metabolic surplus. Continual overeating results in a chronic excess of nutrients. In order to regain metabolic homeostasis, excess energy is stored as adipose tissue, which results in obesity. Adipose tissue is metabolically active and releases proinflammatory mediators such as IL-6, TNFalpha and CRP, as well as adipokines such as leptin, which are central to innate immune pathways. Thus, a western dietary pattern may be highly relevant to activation of the innate immune response, which drives a neutrophilic pattern of airway inflammation, which is increasingly recognised in asthma. Therapeutic strategies aimed at addressing diet-induced innate immune activation are warranted.
Publisher: Wiley
Date: 07-1998
DOI: 10.1002/(SICI)1099-0496(199807)26:1<74::AID-PPUL11>3.0.CO;2-5
Abstract: Inflammation with infiltrations of eosinophils and mast cells into the walls of airways is considered to increase airway hyperresponsiveness (AHR), which in turn characterizes asthma. We present a child with AHR in whom the clinical course of asthma was related to eosinophilic bronchitis. Our patient was admitted at age 6 months with bronchiolitis and at age 4 years with asthma. Inhaled corticosteroids were begun at age 7 years. At age 8 he developed a meningeal sarcoma. While on chemotherapy, his asthma symptoms resolved and he no longer required prophylactic asthma treatment. After 14 months off all chemotherapy, he again had mild episodic asthma. While receiving chemotherapy for malignancy, he had an admission with a coagulase negative staphylococcal bacteremia. During sputum induction with 4.5% saline, he developed cough, wheeze, and a 20% reduction in peak expiratory flow (220 to 180 L/min) that reversed after treatment with salbutamol. The sputum cell count was 1.7 x 10(6)/ml with 1.1 x 10(6) being neutrophils. Two weeks later and prior to the induction of the second sputum, a 21% increase in FEV1 was recorded after bronchodilator inhalation (82% to 99% of predicted). The second sputum contained 2.7 x 10(6)/ml cells with 1.6 x 10(6)/ml neutrophils. Neither eosinophils nor mast cells were identified in the sputum. A third sputum obtained 14 months after the cessation of chemotherapy showed a sputum cell count of 16 x 10(6)/ml, with 11.6 x 10(6) neutrophils and 0.4 x 10(6) eosinophils no mast cells were detected. A reversible 15% reduction in FEV1 was detected on hypertonic saline challenge testing. This boy had persistent airway hyperreactivity and reversible airways obstruction on three occasions during and following chemotherapy. When he developed asthma symptoms, his sputum contained neutrophils and eosinophils while on chemotherapy his sputum did not contain eosinophils and he was symptom-free and off all asthma therapy. One can speculate that chemotherapy for malignancy can induce a remission in asthma symptoms but not AHR, and remission in symptoms is associated with a lack of eosinophilic or mast cell infiltrates in the sputum.
Publisher: Elsevier BV
Date: 2022
Publisher: European Respiratory Society (ERS)
Date: 09-2005
DOI: 10.1183/09031936.05.00135604
Abstract: During pregnancy, patients with asthma are at risk of poor outcomes, particularly when asthma is poorly controlled. The aim of this study was to determine the level of asthma self-management skills and knowledge among pregnant subjects and describe the implementation of an asthma education programme delivered in an antenatal clinic setting. Pregnant subjects with asthma were assessed by an asthma educator at 20 (n = 211) and 33 weeks gestation (n = 149). Lung function, symptoms, medication use, adherence, knowledge and inhaler technique were assessed. They were asked whether they had a written asthma action plan, or performed peak flow monitoring. Asthma was classified as mild, moderate or severe. At the first visit with the asthma educator, 40% of females reported nonadherence to inhaled corticosteroids, inhaler technique was assessed as inadequate in 16% and 42% had inadequate medication knowledge. Peak flow monitoring was performed by 3% and 15% had a written action plan. There were significant improvements in all aspects of asthma self-management following education. In females with severe asthma, night symptoms and reliever medication use significantly decreased after education. In conclusion, during pregnancy, patients with asthma have poor asthma knowledge and skills, and may benefit from self-management education as part of their obstetric care.
Publisher: Springer Science and Business Media LLC
Date: 25-03-2015
Publisher: Springer Science and Business Media LLC
Date: 12-2005
Abstract: Inhaled mannitol is a new bronchial provocation test (BPT) developed to improve portability and standardisation of osmotic challenge testing. Osmotic challenge tests have an advantage over the traditional methods of measuring airway hyperresponsiveness using methacholine as they demonstrate higher specificity to identify asthma and thus the need for treatment with inhaled corticosteroids (ICS). The safety and the efficacy of mannitol (M) as a BPT to measure airway hyperresponsiveness were compared to hypertonic (4.5%) saline (HS) in people both with and without signs and symptoms of asthma. A phase III, multi-centre, open label, operator-blinded, crossover design, randomised trial, with follow-up. Asthmatics and non-asthmatics (6–83 yr) were recruited and 592 subjects completed the study. Mannitol was delivered using a low resistance dry powder inhaler and HS was delivered using an ultrasonic nebuliser. The FEV 1 was measured 60 seconds after each dose of mannitol (5,10,20,40,80,160,160,160 mg) and after each exposure to HS (0.5,1.0,2.0,4.0,8.0 minutes). A 15% fall in FEV 1 defined a positive test. Adverse events were monitored and diaries kept for 7 days following the tests. Mean pre-test FEV1 (mean ± SD) was 95.5 ± 14% predicted. 296 were positive to mannitol (M+) and 322 positive to HS (HS+). A post study physician conducted clinical assessment identified 82.3% asthmatic (44% classified mild) and 17.7% non-asthmatic. Of those M+, 70.1% were taking ICS and of those mannitol negative (M-), 81.1 % were taking ICS. The % fall in FEV1 for mannitol in asthmatics was 21.0% ± 5.7 and for the non-asthmatics, 5.5% ± 4.8. The median PD15 M was 148 mg and PD15 HS 6.2 ml. The sensitivity of M to identify HS+ was 80.7% and the specificity 86.7%. The sensitivity of M compared with the clinical assessment was 59.8% and specificity 95.2% and increased to 88.7% and 95.0% respectively when the M- subjects taking ICS were excluded. Cough was common during testing. There were no serious adverse events. The diarised events were similar for mannitol and HS, the most common being headache (17.2%M, 19%HS), pharyngolaryngeal pain (5.1%M, 3%HS), nausea (4.3%M, 3%HS), and cough (2.2%M, 2.4%HS). The efficacy and safety of mannitol was demonstrated in non-asthmatic and clinically diagnosed asthmatic adults and children.
Publisher: European Respiratory Society (ERS)
Date: 05-03-2020
DOI: 10.1183/13993003.02420-2019
Abstract: Severe asthma is a high-burden disease. Real-world data on mepolizumab in patients with severe eosinophilic asthma is needed to assess whether the data from randomised controlled trials are applicable in a broader population. The Australian Mepolizumab Registry (AMR) was established with an aim to assess the use, effectiveness and safety of mepolizumab for severe eosinophilic asthma in Australia. Patients (n=309) with severe eosinophilic asthma (median age 60 years, 58% female) commenced mepolizumab. They had poor symptom control (median Asthma Control Questionnaire (ACQ)-5 score of 3.4), frequent exacerbations (median three courses of oral corticosteroids (OCS) in the previous 12 months), and 47% required daily OCS. Median baseline peripheral blood eosinophil level was 590 cells·µL −1 . Comorbidities were common: allergic rhinitis 63%, gastro-oesophageal reflux disease 52%, obesity 46%, nasal polyps 34%. Mepolizumab treatment reduced exacerbations requiring OCS compared with the previous year (annualised rate ratio 0.34 (95% CI 0.29–0.41) p .001) and hospitalisations (rate ratio 0.46 (95% CI 0.33–0.63) p .001). Treatment improved symptom control (median ACQ-5 reduced by 2.0 at 6 months), quality of life and lung function. Higher blood eosinophil levels (p=0.003) and later age of asthma onset (p=0.028) predicted a better ACQ-5 response to mepolizumab, whilst being male (p=0.031) or having body mass index ≥30 (p=0.043) predicted a lesser response. Super-responders (upper 25% of ACQ-5 responders, n=61, 24%) had a higher T2 disease burden and fewer comorbidities at baseline. Mepolizumab therapy effectively reduces the significant and long-standing disease burden faced by patients with severe eosinophilic asthma in a real-world setting.
Publisher: Springer Science and Business Media LLC
Date: 2014
Publisher: Oxford University Press (OUP)
Date: 12-2021
Publisher: Informa UK Limited
Date: 18-11-2011
DOI: 10.3109/02770903.2011.631239
Abstract: Little is known about the psychosocial impact and perceived teratogenic (fetal harm due to medication) risks of asthma treatment (inhaled/oral corticosteroids and β-agonist) during pregnancy. To assess the perception of asthma control, quality of life (QoL), and perceived risks of therapy in pregnant women with asthma. Pregnant women with asthma (n = 125) were recruited between 12 and 20 weeks gestation. QoL (generic: Short Form-12 Health Survey v1, and asthma specific: Asthma Quality of Life Questionnaire-Marks (AQLQ-M)) and psychological variables were assessed using the Perceived Control of Asthma Questionnaire (PCAQ), the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Women's perceptions of the teratogenic risks of asthma therapy were also assessed and analyzed for adherence to maintenance inhaled corticosteroids (ICSs), poor asthma control, and QoL. Women reported good QoL (median AQLQ-M total score/maximum score = 0.88/10), moderate ability to deal with asthma symptoms (mean PCAQ score = 42.6/55), positive beliefs about their asthma and low anxiety (median STAI score = 26.7/80). Perceived teratogenic risks for asthma drugs were excessive and class dependent. Women perceived there was a 42% teratogenic risk for oral corticosteroid, a 12% risk for ICSs, and a 5% risk with short-acting β-agonist. Illness beliefs, emotional response to illness (p = .030), age ≥ 30 years (p = .046), and maintenance ICS use (p = .045) were significantly associated with uncontrolled asthma, while maintenance ICS use (p = .023), illness beliefs, consequences (p = .044), timeline (p = .016), and emotional response (p = .015) and anxiety (p ≤ .0001) were significantly associated with reduced QoL. In pregnancy, women with asthma experience good QoL but overestimate teratogenic risks of asthma medication. Maintenance ICS use, illness beliefs, and anxiety are associated with impaired QoL and asthma control.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2007
Publisher: Springer Science and Business Media LLC
Date: 2008
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2014
Publisher: BMJ
Date: 10-2006
Publisher: Wiley
Date: 20-01-2022
DOI: 10.1002/PPUL.25820
Publisher: Wiley
Date: 04-1996
DOI: 10.1111/J.1440-1754.1996.TB00911.X
Abstract: Chronic middle ear disease is common in Aboriginal children, and may be linked to nasal inflammation and Eustachian tube dysfunction. The pattern of nasal inflammation is unknown. The study reported here was performed to define the role of allergy and infection in causing nasal inflammation in Aboriginal children with chronic middle ear disease. Thirty-one Aboriginal children aged between 3 and 7 years underwent clinical assessment, audiometry and allergy skin tests. Nasal swabs for bacterial culture and cytology were performed during the winter and again in spring to identify any seasonal variation. A randomized trial of nasal beclomethasone for 8 weeks was conducted in children with abnormal tympanometry to identify the effect of therapy upon nasal cytology. Twenty-six of the 31 children had abnormal tympanograms. Average hearing levels were reduced in nine children. Pathogenic organisms were isolated from most children: Streptococcus pneumoniae (82%), Haemophilus influenzae (79%), Moraxella catarrhalis (39%) and Staphylococcus aureus (29%). Eight of the 31 children (26%) were atopic. Nasal cytology disclosed a marked neutrophil infiltrate (80% of cells) during the winter, which fell significantly in spring to 52% of cells. Only two subjects had nasal eosinophilia of >10%. There was no effect of beclomethasone on nasal cytology. Chronic ear disease in Aboriginal children is associated with nasal inflammation, neutrophil infiltration and the presence of bacteria. These features suggest respiratory infection as the main cause of chronic nasal inflammation in Aboriginal children with middle ear disease. There is a seasonal variation in the severity of the nasal infiltrate, consistent with increased infections during winter. Despite a high prevalence of atopy, allergic nasal disease was uncommon.
Publisher: Springer Science and Business Media LLC
Date: 12-10-2011
DOI: 10.1007/S00408-011-9333-0
Abstract: Cough remains refractory to medical treatment in approximately 20% of cases. Speech pathology intervention is a useful treatment option for patients with chronic cough that is refractory to treatment based on the anatomic diagnostic protocol. One of the reasons for this is that the larynx can be implicated in the pathogenesis of chronic refractory cough. There is an overlap in symptoms and clinical findings in patients with cough and those with laryngeal conditions such as paradoxical vocal fold movement. Furthermore, there is a high prevalence of voice symptoms in patients with chronic cough. Speech pathology intervention for cough comprises four components: (1) education, (2) strategies to control cough, (3) vocal hygiene training, and (4) psychoeducational counselling. The efficacy of speech pathology intervention has been examined in a single blind randomised control trial. In this trial 87% of patients in the treatment group improved, whereas 14% on the placebo group improved. Cough reflex sensitivity has also been shown to improve following speech pathology intervention for cough. This review outlines the potential mechanisms for improvement in cough, indicators for referral to speech pathology for cough, and exclusion criteria.
Publisher: European Respiratory Society (ERS)
Date: 13-01-2011
DOI: 10.1183/09031936.00170110
Abstract: Inflammatory phenotypes are recognised in stable adult asthma, but are less well established in childhood and acute asthma. Additionally, Chlamydophila pneumoniae infection as a cause of noneosinophilic asthma is controversial. This study examined the prevalence of inflammatory phenotypes and the presence of current C. pneumoniae infection in adults and children with stable and acute asthma. Adults with stable (n=29) or acute (n=22) asthma, healthy adults (n=11), children with stable (n=49) or acute (n=28) asthma, and healthy children (n=9) underwent clinical assessment and sputum induction. Sputum was assessed for inflammatory cells, and DNA was extracted from sputum cell suspensions and supernatants for C. pneumoniae detection using real-time PCR. The asthma phenotype was predominantly eosinophilic in children with acute asthma (50%) but neutrophilic in adults with acute asthma (82%). Paucigranulocytic asthma was the most common phenotype in both adults and children with stable asthma. C. pneumoniae was not detected in 99% of s les. The pattern of inflammatory phenotypes differs between adults and children, with eosinophilic inflammation being more prevalent in both acute and stable childhood asthma, and neutrophilic inflammation being the dominant pattern of acute asthma in adults. The aetiology of neutrophilic asthma is unknown and is not explained by the presence of current active C. pneumoniae infection.
Publisher: Elsevier BV
Date: 09-2016
Publisher: BMJ
Date: 19-03-2014
DOI: 10.1136/THORAXJNL-2013-204815
Abstract: There is epidemiological evidence to suggest that events in childhood influence lung growth and constitute a significant risk for adult COPD. The aim of the study is to evaluate for an association between childhood asthma and adult COPD. This longitudinal, prospective study of 6-7-year-old children with asthma has been regularly reviewed every 7 years to the current analysis at 50 years of age. Participants completed respiratory questionnaires and lung function spirometry with postbronchodilator response. At the age of 50, subjects were classified to the following subgroups: non-asthmatics, asthma remission, current asthma and COPD which was defined by FEV1 to FVC ratio postbronchodilator of less than 0.7. Of the remaining survivors, 346 participated in the current study (participation rate of 76%) of whom 197 completed both questionnaire and lung function testing. As compared with children without symptoms of wheeze to the age of 7, (non-asthmatics) children with severe asthma had an adjusted 32 times higher risk for developing COPD (95% CI 3.4 to 269). In this cohort, 43% of the COPD group had never smoked. There was no evidence of a difference in the rate of decline in FEV1 (mL/year, 95th CI) between the COPD group (17, 10 to 23) and the other groups: non-asthmatics (16, 12 to 21), asthma remission (20, 16 to 24) and current asthma (19, 13 to 25). Children with severe asthma are at increased risk of developing COPD.
Publisher: The Korean Academy of Asthma, Allergy and Clinical Immunology and The Korean Academy of Pediatric Al
Date: 2021
Publisher: Wiley
Date: 17-05-2018
DOI: 10.1111/CEA.13153
Abstract: Severe asthma affects quality of life however, its impact on workplace productivity is poorly understood. To compare workplace productivity-absenteeism and presenteeism-and impairment in daily activities in severe and non-severe asthma over time and identify characteristics associated with presenteeism in severe asthma. The Severe Asthma Web-based Database is an ongoing observational registry from Australia, New Zealand and Singapore. At April 2017, 434 patients with severe asthma and 102 with non-severe asthma were enrolled (18-88 years 59% female). Participants provided comprehensive clinical and questionnaire data at baseline and were followed-up every 6 months for 24 months. Absenteeism (percentage of time not at work), presenteeism (self-reported impairment at work) and impairment in daily activities outside work due to health problems in the last week were calculated. At baseline, 61.4% of participants with severe asthma and 66.2% with non-severe asthma under 65 years were employed. At younger ages (30-50 years), fewer severe asthma participants were employed (69% vs 100%). Presenteeism and impairment in daily activity were more frequently reported in severe asthma and in participants with poorer asthma control, poorer lung function and more past-year exacerbations (P < .01). Over time, deteriorating asthma control was associated with increasing presenteeism. Although absenteeism was not different between severe and non-severe asthma, worse asthma control was associated with absenteeism (P < .001). In participants with severe asthma, presenteeism was reported more frequently in those with poorer asthma control, poorer asthma-related quality of life and symptoms of depression or anxiety (P < .01). Severe asthma was associated with impairment at work and outside the workplace. Improving asthma control and mental health may be important targets for optimizing workplace productivity in severe asthma. Presenteeism and absenteeism may represent key metrics for assessing intervention efficacy in people with severe asthma of working age.
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.CHEST.2019.12.021
Abstract: Asthma and non-asthmatic eosinophilic bronchitis (NAEB) are among the commonest causes of chronic cough in adults. We sought to determine the role of non-invasive measurements of airway inflammation, including induced sputum and fractional exhaled nitric oxide, in the evaluation of cough associated with asthma, and what the best treatment is for cough due to asthma or NAEB. We undertook three systematic reviews of randomized controlled trials and observational trials of adults and adolescents > 12 years of age with a chronic cough due to asthma or NAEB. Eligible studies were identified in MEDLINE, CENTRAL, and SCOPUS and assessed for relevance and quality. Guidelines were developed and voted upon using CHEST guideline methodology. Of the citations reviewed, 3/1,175, 53/656, and 6/134 were identified as being eligible for inclusion in the three systematic reviews, respectively. In contrast to established guidelines for asthma therapies in general and the inclusion in some guidelines for a role of biomarkers of airway inflammation to guide treatment in severe disease, the evidence of specific benefit related to the use of non-invasive biomarkers in patients with chronic cough due to asthma was weak. The best therapeutic option for cough in asthma or NAEB is inhaled corticosteroids followed by leukotriene receptor antagonism. This guideline offers recommendations on the role of non-invasive measurements of airway inflammation and treatment for cough due to asthma or NAEB based on the available literature, and identifies gaps in knowledge and areas for future research.
Publisher: Oceanside Publications Inc.
Date: 07-07-2014
Abstract: It has proven efficacy in reducing asthma exacerbations, but the effect size of montelukast (a leukotriene receptor antagonist) for varied severity of asthma exacerbations is not systematically assessed. This study was designed to systematically explore the evidence for montelukast, as first-line or add-on therapy, in preventing and treating asthma exacerbations in adult patients with asthma. Randomized controlled trials were searched in PubMed, CENTRAL, Web of Science, Embase, and OVID up to March 2013, where montelukast prevented or treated asthma exacerbations in adults. Primary outcomes were the number of patients experiencing exacerbations in chronic asthma and hospitalizations in acute asthma. Odds ratio (OR) with 95% confidence intervals (CI), risk difference, and number needed to treat (NNT) were calculated and pooled. Adverse events were also assessed in chronic asthma. Twenty trials for chronic asthma and six for acute asthma were identified. In comparison with placebo, adults with chronic asthma receiving montelukast had significantly reduced number of exacerbations (OR = 0.60 and 95% CI, 0.49, 0.74 NNT = 17 and 95% CI, 12, 29). However, montelukast was inferior to inhaled corticosteroids (ICSs) (OR = 1.63 95% CI, 1.29, 2.0) and ICS plus long-acting beta2-agonist (LABA OR = 3.94 95% CI, 1.64, 9.48) as the first-line therapies and LABA (OR = 1.22 95% CI, 1.05, 1.42) as the add-on therapies in reducing asthma exacerbations. In acute asthma, montelukast could statistically improve peak expiratory flow percent predicted (p = 0.008) and reduce systemic corticosteroid intake (p = 0.005). Montelukast had low risk in hoarseness and insomnia. Our meta-analysis suggests that montelukast significantly reduces mild, moderate, and part of severe exacerbations in chronic mild to moderate asthma, but it has inferior efficacy to ICS or ICS plus LABA.
Publisher: John Wiley & Sons, Ltd
Date: 18-10-2006
Publisher: Therapeutic Guidelines Limited
Date: 12-2001
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.CHEST.2016.07.029
Abstract: In response to occupational and environmental exposures, cough can be an isolated symptom reflecting exposure to an irritant with little physiological consequence, or it can be a manifestation of more significant disease. This document reviews occupational and environmental contributions to chronic cough in adults, focusing on aspects not previously covered in the 2006 ACCP Cough Guideline or our more recent systematic review, and suggests an approach to investigation of these factors when suspected. MEDLINE and TOXLINE literature searches were supplemented by articles identified by the cough panel occupational and environmental subgroup members, to identify occupational and environmental aspects of chronic cough not previously covered in the 2006 ACCP Cough Guideline. Based on the literature reviews and the Delphi methodology, the cough panel occupational and environmental subgroup developed guideline suggestions that were approved after review and voting by the full cough panel. The literature review identified relevant articles regarding: mechanisms allergic environmental causes chronic cough and the recreational and involuntary inhalation of tobacco and marijuana smoke nonallergic environmental triggers laryngeal syndromes and occupational diseases and exposures. Consensus-based statements were developed for the approach to diagnosis due to a lack of strong evidence from published literature. Despite increased understanding of cough related to occupational and environmental triggers, there remains a gap between the recommended assessment of occupational and environmental causes of cough and the reported systematic assessment of these factors. There is a need for further documentation of occupational and environmental causes of cough in the future.
Publisher: BMJ
Date: 21-10-2010
Abstract: Infections with some bacteria, including Streptococcus pneumoniae, have been associated with a reduced incidence of asthma. Components of S pneumoniae may have the potential to modulate allergic inflammatory responses and suppress the development of asthma. To determine if human S pneumoniae vaccines have the potential to suppress asthma by elucidating their effect on allergic airways disease (AAD) in mouse models. AAD was induced in BALB/c mice by intraperitoneal sensitisation and intranasal challenge with ovalbumin. Pneumococcal conjugate or polysaccharide vaccines were administered at the time of sensitisation or during established AAD. Hallmark features of AAD were assessed. Levels of regulatory T cells (Tregs) were quantified by fluorescence-activated cell sorting, and their immunoregulatory capacity was assessed using proliferation assays and anti-CD25 antibody treatment. Intranasal administration of the conjugate vaccine, but not the polysaccharide vaccine, suppressed the hallmark features of AAD, including: eosinophilic and T helper 2-mediated inflammation airway hyper-responsiveness circulating immunoglobulin E (IgE) levels and mucus hypersecretion. Intramuscular administration of the conjugate vaccine had limited protective effects. The conjugate vaccine increased Tregs in the lung-draining lymph nodes, lung and spleen. Furthermore, conjugate vaccine-induced Tregs had an enhanced capacity to suppress T effector responses. Anti-CD25 administration reversed the suppressive effects of the conjugate vaccine. A currently available human conjugate vaccine suppresses the hallmark features of AAD through the induction of Tregs. Thus targeted administration may provide a novel immunoregulatory treatment for asthma.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.RMED.2022.106924
Abstract: Given that airway obstruction in asthma is not always fully reversible, reduced bronchodilator reversibility (BDR) may be a special asthma phenotype. To explore the characteristics of BDR After baseline assessments, all patients were classified into BDR Subjects with BDR We identified that BDR
Publisher: Wiley
Date: 03-2003
DOI: 10.1002/BMC.248
Abstract: Signals from the epidermal growth factor (EGF) receptor family are thought to combine with integrin‐dependent adhesion to laminins to contribute to disease progression and metastasis in cancer. To date, little is known about the mechanisms by which these signals interact. Recently, we have shown that the colon cancer cell line LIM1215 secretes and adheres to laminin‐10 through multiple integrin receptors, and that EGF stimulates spreading and migration of these cells on the same substrate. Additionally laminin‐10/11 has been shown by immunohistochemistry to be present at the invasive edge of moderately differentiated colon cancers. To enable detailed structure–function studies to be undertaken, it is important to be able to rapidly obtain highly purified native laminin‐10 from bulk biological s les in reasonable yield. The development of a multidimensional micropurification scheme to achieve this is presented and compared with other reported methods for the purification of laminins. Copyright © 2003 John Wiley & Sons, Ltd.
Publisher: European Respiratory Society (ERS)
Date: 31-07-2014
Publisher: BMJ
Date: 11-2006
Publisher: European Respiratory Society (ERS)
Date: 04-05-2020
Publisher: Wiley
Date: 12-1996
DOI: 10.1111/J.1440-1754.1996.TB00968.X
Abstract: To determine whether a single assessment of children at the time of presentation to the emergency department would discriminate accurately between those requiring admission and those who could be managed at home and to examine the appropriateness of these decisions. Fifty-three children were assessed using a table recommended by Australian and New Zealand respiratory paediatricians, which categorizes children as probably being able to manage at home (group 1), may need admission to hospital (group 2) and certainly need admission to hospital (group 3) on the basis of oximetry, presence of wheeze and pulsus paradoxus. Nine out of 11 children assigned to group 1 were managed at home and 15/17 who were predicted to require admission were admitted. No in idual component of the assessment dominated the decision made. Of the 25 children allocated to group 2, 18 were admitted. The method employed was highly predictive of outcome for half of the children who presented with asthma. However, 25/53 (47%) were assigned by the table to a recommendation for further assessment this limits its usefulness.
Publisher: American Thoracic Society
Date: 15-09-2001
DOI: 10.1164/AJRCCM.164.6.9910053
Abstract: The role of eosinophilic airway inflammation in the variant asthma syndromes of cough and chest colds is not well defined. We tested the hypothesis that children with persistent cough and chest colds have increased sputum eosinophils, similar to those with wheeze. The parents of 390 primary school children completed a symptoms questionnaire. Children with wheeze (n = 28), cough (n = 12), recurrent chest colds (n = 17), and no symptoms (control subjects, n = 26), underwent allergy skin prick tests, spirometry, hypertonic saline inhalation challenge, and sputum induction, and then completed a peak expiratory flow (PEF) and symptoms diary over a 2-mo period. Children with wheeze had significantly reduced PEF (p = 0.001) and higher sputum eosinophils when compared with the cough, chest cold, and control groups (3.1% versus 0.5%, 0%, 0% p = 0.03). The prevalence of eosinophilic bronchitis (sputum eosinophils > 2.5%) was 45% in the wheeze group, which was significantly higher than the control group (9.35%, p = 0.04). Eosinophilic bronchitis was present in two children with cough (20%) and two with chest colds (15%, p > 0.05 versus control). In these groups, eosinophilic bronchitis was not associated with airway hyperresponsiveness (AHR) to hypertonic saline (p > 0.05). Children with cough and chest colds reported greater exposure to environmental tobacco smoke. In conclusion, this community-based survey of children with chronic respiratory symptoms has shown that wheeze is a good discriminator for the presence of eosinophilic bronchitis, and that persistent cough and recurrent chest colds without wheeze should not be considered a variant of asthma. Eosinophilic bronchitis did occur in a significant minority of these "variant asthma" syndromes.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 2007
DOI: 10.1016/J.JACI.2006.08.021
Abstract: The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products. Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism. Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting. S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and lified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor. This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases. MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma.
Publisher: Wiley
Date: 20-12-2014
DOI: 10.1111/CEA.12168
Abstract: Histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate gene expression, yet differences in the activity of these enzymes in the inflammatory phenotypes of asthma are unknown. We hypothesized that neutrophilic asthma (NA) would be associated with increased HAT and decreased HDAC activity. To investigate total HAT/HDAC activity and gene expression in isolated blood monocytes and sputum macrophages from healthy and patients with asthma. Peripheral blood and induced sputum were collected from adults with asthma (n = 52) and healthy controls (n = 9). Sputum inflammatory cell counts were performed and asthma inflammatory phenotypes were classified according to sputum eosinophil and neutrophil cut-off's of > 3% and > 61% respectively. Peripheral blood monocytes were isolated (n = 61) and sputum macrophages were isolated from a subgroup of patients with asthma (n = 14), using immunomagnetic cell separation. RNA and nuclear proteins were extracted and quantified. Enzyme activity was assessed using fluorescent assays and gene expression of EP300, KAT2B, CREBBP, and HDACs 1, 2 and 3 were measured by qPCR. There was a significant inverse association between blood monocyte HAT and HDAC activity (r = -0.58, P < 0.001). NA was associated with increased blood monocyte HAT enzyme activity (P = 0.02), decreased HDAC activity (P = 0.03), and increased HAT: HDAC ratio (P < 0.01) compared with eosinophilic asthma. There were no differences in gene expression of EP300, KAT2B, CREBBP, or HDACs 1, 2 and 3 in blood monocytes from subjects with asthma or inflammatory phenotypes of asthma. There was no effect of inhaled corticosteroid use, poor asthma control, or asthma severity on HAT/HDAC activities. Sputum macrophages had increased expression of KAT2B in eosinophilic compared with paucigranulocytic asthma. Neutrophilic airway inflammation is associated with increased HAT and reduced HDAC activity in blood monocytes, demonstrating further systemic manifestations relating to the altered inflammatory gene transcription profile of neutrophilic asthma.
Publisher: Wiley
Date: 28-11-2022
DOI: 10.1111/RESP.14190
Abstract: See related article
Publisher: Elsevier BV
Date: 06-2021
DOI: 10.1093/AJCN/NQAA442
Publisher: European Respiratory Society (ERS)
Date: 31-03-2022
DOI: 10.1183/13993003.02583-2021
Abstract: Asthma treatment goals currently focus on symptom and exacerbation control rather than remission. Remission is not identical to cure, but is a step closer. This review considers the current definitions of remission in asthma, the prevalence and predictors, the pathophysiology of remission, the possibility of achieving it using the available treatment options, and the future research directions. Asthma remission is characterised by a high level of disease control, including the absence of symptoms and exacerbations, and normalisation or optimisation of lung function with or without ongoing treatment. Even in those who develop a symptomatic remission of asthma, persistent pathological abnormalities are common, leading to a risk of subsequent relapse at any time. Complete remission requires normalisation or stabilisation of any underlying pathology in addition to symptomatic remission. Remission is possible as part of the natural history of asthma, and the prevalence of remission in the adult asthma population varies between 2% and 52%. The factors associated with remission include mild asthma, better lung function, better asthma control, younger age, early-onset asthma, shorter duration of asthma, milder bronchial hyperresponsiveness, fewer comorbidities and smoking cessation or never smoking. Although previous studies have not targeted treatment-induced remission, there is some evidence to show that the current long-term add-on therapies such as biologics and azithromycin can achieve some criteria for asthma remission on treatment, at least in a subgroup of patients. However, more research is required. Long-term remission could be included as a therapeutic goal in studies of asthma treatments.
Publisher: Elsevier BV
Date: 2018
Publisher: European Respiratory Society (ERS)
Date: 2003
DOI: 10.1183/09031936.03.00017003A
Abstract: Oxidative stress, specifically lipid peroxidation, is believed to contribute to the pathophysiology of asthma. This review highlights the pathways through which reactive oxygen species (ROS) may lead to lipid peroxidation. The potential of both the innate and acquired immune systems to activate inflammatory cells and release ROS that may overwhelm the host antioxidant defences and cause lipid peroxidation, accompanied by detrimental pathophysiological effects, are discussed. Despite the evidence demonstrating the importance of lipid peroxidation, systematic characterisation of oxidative stress and antioxidant defences has not been undertaken, largely due to the lack of appropriate biomarkers. This review discusses the emergence of isoprostanes (specifically 8-iso-prostaglandin F2alpha) as reliable, in vivo markers of lipid peroxidation, which provides an appropriate tool for studying oxidative stress. Furthermore, the development of techniques to study induced sputum and breath condensate, derived directly from the airway surface, enables the site of oxidative damage to be closely assessed. Evidence suggests that dietary changes that have occurred over recent years have increased susceptibility to lipid peroxidation, due to reduced antioxidant defences. To date, the limited number of long-term (>1 week) supplementation trials have been promising. However, the development of techniques to study isoprostanes in airway-lining fluid pave the way for further studies investigating the potential for antioxidant supplements to be used as routine therapy in asthma.
Publisher: European Respiratory Society (ERS)
Date: 02-12-2016
DOI: 10.1183/13993003.00405-2015
Abstract: Asthma is a chronic inflammatory disorder of the airways where bacteria may act as protagonists of chronic inflammation. Little is known about the relation of airway inflammation to the presence of specific bacterial taxa. We sought to describe the sputum microbiome in adults with poorly controlled asthma. DNA was extracted from induced sputum and microbial communities were profiled using 16S rRNA pyrosequencing. Bacterial species were characterised, and the relationship between microbial populations, asthma inflammatory subtypes and other covariates was explored. Real-time PCR was used to identify Tropheryma whipplei and Haemophilus influenzae in sputum. Adults with neutrophilic asthma had reduced bacterial ersity and species richness. Tropheryma was identified and confirmed with real-time PCR in 12 (40%) participants. Haemophilus occurred most often in a group of younger atopic males with an increased proportion of neutrophils. PCR confirmed the presence of H. influenzae in 35 (76%) participants with poorly controlled asthma. There are phenotype-specific alterations to the airway microbiome in asthma. Reduced bacterial ersity combined with a high prevalence of H. influenzae was observed in neutrophilic asthma, whereas eosinophilic asthma had abundant T. whipplei .
Publisher: Elsevier BV
Date: 09-2022
DOI: 10.1016/J.RMED.2022.106935
Abstract: Identification of eosinophilic asthma (EA) using sputum analysis is important for disease monitoring and in idualized treatment. But it is laborious and technically demanding. We aimed to develop and validate an effective model to predict EA with multidimensional assessment (MDA). The asthma patients who underwent a successful sputum induction cytological analysis were consecutively recruited from March 2014 to January 2021. The variables assessed by MDA were screened by least absolute shrinkage and selection operator (LASSO) and logistic regression to develop a nomogram and an online web calculator. Validation was performed internally by a bootstrap s ling method and externally in the validation cohort. Diagnostic accuracy of the model in different asthma subgroups were also investigated. In total of 304 patients in the training cohort and 95 patients in the validation cohort were enrolled. Five variables were identified in the EA prediction model: gender, nasal polyp, blood eosinophils, blood basophils and FeNO. The C-index of the model was 0.86 (95% CI: 0.81-0.90) in the training cohort and 0.84 (95% CI: 0.72-0.89) in the validation cohort. The calibration curve showed good agreement between the prediction and actual observation. The decision curve analysis (DCA) also demonstrated that the EA prediction model was clinically beneficial. An online publicly available web calculator was constructed (asthmaresearcherlimin.shinyapps.io/DynNomapp/). We developed and validated a multivariable model based on MDA to help the diagnosis of EA, which has good diagnostic performance and clinical practicability. This practical tool may be a useful alternative for predicting EA in the clinic.
Publisher: Wiley
Date: 29-09-2021
DOI: 10.1111/RESP.14147
Abstract: Oral corticosteroids (OCS) are frequently used for asthma treatment. This medication is highly effective for both acute and chronic diseases, but evidence indicates that indiscriminate OCS use is common, posing a risk of serious side effects and irreversible harm. There is now an urgent need to introduce OCS stewardship approaches, akin to successful initiatives that optimized appropriate antibiotic usage. The aim of this TSANZ (Thoracic Society of Australia and New Zealand) position paper is to review current knowledge pertaining to OCS use in asthma and then delineate principles of OCS stewardship. Recent evidence indicates overuse and over‐reliance on OCS for asthma and that doses mg prednisolone‐equivalent cumulatively are likely to have serious side effects and adverse outcomes. Patient perspectives emphasize the detrimental impacts of OCS‐related side effects such as weight gain, insomnia, mood disturbances and skin changes. Improvements in asthma control and prevention of exacerbations can be achieved by improved inhaler technique, adherence to therapy, asthma education, smoking cessation, multidisciplinary review, optimized medications and other strategies. Recently, add‐on therapies including novel biological agents and macrolide antibiotics have demonstrated reductions in OCS requirements. Harm reduction may also be achieved through identification and mitigation of predictable adverse effects. OCS stewardship should entail greater awareness of appropriate indications for OCS prescription, risk–benefits of OCS medications, side effects, effective add‐on therapies and multidisciplinary review. If implemented, OCS stewardship can ensure that clinicians and patients with asthma are aware that OCS should not be used lightly, while providing reassurance that asthma can be controlled in most people without frequent use of OCS.
Publisher: Elsevier BV
Date: 04-2000
Abstract: The relationship between airway inflammation and asthma severity in corticosteroid-treated asthma is unclear. Our purpose was to characterize the inflammatory cell profile of the airway lumen and epithelium in corticosteroid-treated asthma and to relate these findings to clinical and physiologic markers of asthma severity. Adults (n = 20) with asthma received standardized high-dose inhaled corticosteroid therapy with beclomethasone 2000 microgram per day for 8 weeks. Airway responsiveness to methacholine and hypertonic (4.5%) saline solution was then assessed, followed by sputum induction and, 1 week later, bronchoscopy with bronchoalveolar lavage and bronchial brush biopsy to assess inflammatory cells. Clinical asthma severity was associated with airway hyperresponsiveness. Metachromatic cells were the main granulocyte present in bronchial brush biopsy specimens and correlated with airway responsiveness to saline solution (r = -0.75), methacholine (r = -0.74), peak flow variability (r = 0.59), and clinical asthma severity (r = 0.57). Eosinophils were the main granulocyte present in sputum and correlated with airway responsiveness to saline solution (r = -0.63) but not with other clinical markers of asthma severity. Bronchoalveolar lavage cell counts were not related to clinical asthma severity. In asthmatic patients treated with cortico-steroids, the dominant inflammatory effector cell in the epithelium is the metachromatic cell, and in sputum it is the eosinophil. These cells correlate with the degree of airway hyperresponsiveness. Clinical asthma severity correlates with airway responsiveness and epithelial metachromatic cells. Induced sputum eosinophils and airway responsiveness to hypertonic saline solution may be useful markers of airway inflammation for clinical practice.
Publisher: Elsevier BV
Date: 04-2003
Publisher: Cambridge University Press (CUP)
Date: 07-2009
DOI: 10.1017/S0007114508019880
Abstract: Prebiotics are food ingredients that improve health by modulating the colonic microbiota. The bifidogenic effect of the prebiotic inulin is well established however, it remains unclear which species of Bifidobacterium are stimulated in vivo and whether bacterial groups other than lactic acid bacteria are affected by inulin consumption. Changes in the faecal microbiota composition were examined by real-time PCR in twelve human volunteers after ingestion of inulin (10 g/d) for a 16-d period in comparison with a control period without any supplement intake. The prevalence of most bacterial groups examined did not change after inulin intake, although the low G+C % Gram-positive species Faecalibacterium prausnitzii exhibited a significant increase (10·3 % for control period v. 14·5 % during inulin intake, P = 0·019). The composition of the genus Bifidobacterium was studied in four of the volunteers by clone library analysis. Between three and five Bifidobacterium spp. were found in each volunteer. Bifidobacterium adolescentis and Bifidobacterium longum were present in all volunteers, and Bifidobacterium pseudocatenulatum , Bifidobacterium animalis , Bifidobacterium bifidum and Bifidobacterium dentium were also detected. Real-time PCR was employed to quantify the four most prevalent Bifidobacterium spp., B. adolescentis , B. longum , B. pseudocatenulatum and B. bifidum , in ten volunteers carrying detectable levels of bifidobacteria. B. adolescentis showed the strongest response to inulin consumption, increasing from 0·89 to 3·9 % of the total microbiota ( P = 0·001). B. bifidum was increased from 0·22 to 0·63 % ( P 0·001) for the five volunteers for whom this species was present.
Publisher: Wiley
Date: 06-2017
DOI: 10.1111/IMJ.13441
Abstract: Severe asthma is a complex heterogeneous disease that is refractory to standard treatment and is complicated by multiple comorbidities and risk factors. In mild to moderate asthma, the burden of disease can be minimised by inhaled corticosteroids, bronchodilators and self-management education. In severe asthma, however, management is more complex. When patients with asthma continue to experience symptoms and exacerbations despite optimal management, severe refractory asthma (SRA) should be suspected and confirmed, and other aetiologies ruled out. Once a diagnosis of SRA is established, patients should undergo a systematic and multidimensional assessment to identify inflammatory endotypes, risk factors and comorbidities, with targeted and in idualised management initiated. We describe a practical approach to assessment and management of patients with SRA.
Publisher: Wiley
Date: 06-2017
DOI: 10.1111/ALL.13185
Abstract: Sputum basophil numbers are increased in allergic asthmatics, but it is unclear what role airway basophils play in "TH2-low" asthma phenotypes. Using flow cytometry, we found that basophils were significantly increased in all asthmatics (n=26) compared with healthy controls (n=8) (P=0.007) with highest levels observed in eosinophilic asthma (EA) median 0.22%, IQR 0.11%-0.47% n=14) compared with non-EA (NEA) (0.06%, 0.00%-0.20% n=12 P<0.05). In asthmatics, basophils were positively correlated with sputum eosinophils (r=0.54 P<0.005) and inversely with sputum neutrophils (r=-0.46: P<0.05), but not with FEV
Publisher: Wiley
Date: 10-10-2017
DOI: 10.1111/JGH.13791
Abstract: A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D. Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool s le in which elastase concentration was measured by ELISA. A concentration of < 100 mcg/g stool represented severe and < 200 mcg/g mild to moderate PEI. Patients whose fecal elastase was < 200 mcg/g underwent testing for pancreatic pathology with an endoscopic ultrasound or abdominal CT. Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis. One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported.
Publisher: Elsevier BV
Date: 04-2022
DOI: 10.1016/J.JACI.2021.10.003
Abstract: Obesity is a risk factor for asthma, and obese asthmatic in iduals are more likely to have severe, steroid-insensitive disease. How obesity affects the pathogenesis and severity of asthma is poorly understood. Roles for increased inflammasome-mediated neutrophilic responses, type 2 immunity, and eosinophilic inflammation have been described. We investigated how obesity affects the pathogenesis and severity of asthma and identified effective therapies for obesity-associated disease. We assessed associations between body mass index and inflammasome responses with type 2 (T2) immune responses in the sputum of 25 subjects with asthma. Functional roles for NLR family, pyrin domain-containing (NLRP) 3 inflammasome and T2 cytokine responses in driving key features of disease were examined in experimental high-fat diet-induced obesity and asthma. Body mass index and inflammasome responses positively correlated with increased IL-5 and IL-13 expression as well as C-C chemokine receptor type 3 expression in the sputum of subjects with asthma. High-fat diet-induced obesity resulted in steroid-insensitive airway hyperresponsiveness in both the presence and absence of experimental asthma. High-fat diet-induced obesity was also associated with increased NLRP3 inflammasome responses and eosinophilic inflammation in airway tissue, but not lumen, in experimental asthma. Inhibition of NLRP3 inflammasome responses reduced steroid-insensitive airway hyperresponsiveness but had no effect on IL-5 or IL-13 responses in experimental asthma. Depletion of IL-5 and IL-13 reduced obesity-induced NLRP3 inflammasome responses and steroid-insensitive airway hyperresponsiveness in experimental asthma. We found a relationship between T2 cytokine and NLRP3 inflammasome responses in obesity-associated asthma, highlighting the potential utility of T2 cytokine-targeted biologics and inflammasome inhibitors.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JAIP.2019.02.042
Abstract: Severe asthma is complex and heterogeneous ad hoc outpatient assessment can be suboptimal. Systematic evaluation improves outcomes and is recommended by international guidelines. Electronic templates improve physician performance and clinical processes, and may be useful in severe asthma systematic evaluation. We developed the Severe Asthma Global Evaluation (SAGE) electronic platform to streamline this process, via Research Electronic Data Capture (REDCap). It incorporates: a questionnaire battery for patient completion before clinical consultation asthma and comorbidity modules a clinical summary page in an asthma management module a nurse educator module a structured panel discussion record and an automatically generated report incorporating all key data. SAGE incorporates 282 clinician input fields, with a typical consultation requiring completion of 169. To streamline the process SAGE contains 34 autocalculations and 20 decision support tools. It incorporates all 95 core variables of the International Severe Asthma Registry, with which it is directly compatible. SAGE improves symptom control and exacerbations in patients with difficult asthma. In conclusion, we developed and validated an electronic platform that facilitates a comprehensive but streamlined systematic evaluation of severe asthma that is available for free download via REDCap. Its use enhances management of patients with severe asthma and facilitates audit and international research collaboration.
Publisher: Informa UK Limited
Date: 05-05-2022
DOI: 10.1080/02770903.2022.2070763
Abstract: An imbalance in autonomic nervous system (ANS) activity may play a role in asthma, but it is unclear whether this is associated with specific pathophysiology. This study assessed ANS activity by measuring heart rate variability (HRV) in eosinophilic (EA) and non-eosinophilic asthma (NEA) and people without asthma. HRV, combined hypertonic saline challenge/sputum induction, exhaled nitric oxide (FeNO), skin prick tests to measure atopy, and spirometry tests were conducted in teenagers and young adults (14-21 years) with ( HRV parameters did not differ between asthmatics and non-asthmatics or EA and NEA. They were also not associated with markers of inflammation, lung function or atopy. However, increased absolute low frequency (LFµs ANS activity (as measured using HRV analysis) is not associated with pathophysiology or inflammatory phenotype in young asthmatics with generally well-controlled asthma. However, enhanced SNS activity can be detected in asthmatics with AHR or who use β-agonist medication.
Publisher: Elsevier BV
Date: 02-2007
Publisher: Elsevier BV
Date: 04-1991
DOI: 10.1016/0091-6749(91)90140-J
Abstract: Bijma et al. (2007a,b) presented a quantitative genetic theory of multilevel selection and showed how to estimate the relevant parameters using standard restricted maximum-likelihood (REML) methodology. Extending their results we develop a wider class of models that provide a more realistic framework for capturing the effects of interacting in iduals. These models also make use of standard REML techniques and include the original model as a special case.
Publisher: BMJ
Date: 06-03-2015
DOI: 10.1136/THORAXJNL-2014-206067
Abstract: Steroid-insensitive endotypes of asthma are an important clinical problem and effective therapies are required. They are associated with bacterial infection and non-eosinophilic inflammatory responses in the asthmatic lung. Macrolide therapy is effective in steroid-insensitive endotypes, such as non-eosinophilic asthma. However, whether the effects of macrolides are due to antimicrobial or anti-inflammatory mechanisms is not known. To determine and assess the efficacy of macrolide (ie, clarithromycin) and non-macrolide (ie, amoxicillin) antibiotic treatments in experimental models of infection-induced, severe, steroid-insensitive neutrophilic allergic airways disease (SSIAAD), compared with steroid-sensitive AAD and to delineate the antimicrobial and anti-inflammatory effects of macrolide therapy. We developed and used novel mouse models of Chlamydia and Haemophilus lung infection-induced SSIAAD. We used these models to investigate the effects of clarithromycin and amoxicillin treatment on immune responses and airways hyper-responsiveness (AHR) in Ova-induced, T helper lymphocyte (Th) 2 -associated steroid-sensitive AAD and infection-induced Th1/Th17-associated SSIAAD compared with dexamethasone treatment. Clarithromycin and amoxicillin had similar antimicrobial effects on infection. Amoxicillin did attenuate some features, but did not broadly suppress either form of AAD. It did restore steroid sensitivity in SSIAAD by reducing infection. In contrast, clarithromycin alone widely suppressed inflammation and AHR in both steroid-sensitive AAD and SSIAAD. This occurred through reductions in Th2 responses that drive steroid-sensitive eosinophilic AAD and tumour necrosis factor α and interleukin 17 responses that induce SSIAAD. Macrolides have broad anti-inflammatory effects in AAD that are likely independent of their antimicrobial effects. The specific responses that are suppressed are dependent upon the responses that dominate during AAD.
Publisher: Elsevier BV
Date: 2019
Publisher: Wiley
Date: 12-2004
DOI: 10.1111/J.1365-2222.2004.02130.X
Abstract: Allergic rhinitis (AR) and asthma often coexist and may represent two manifestations of the same disease recently named combined AR and asthma syndrome (CARAS). To review the common pathophysiology of combined AR and asthma and to investigate the efficacy of intranasal corticosteroids (INCS). Medline was used to identify articles relevant to mechanisms. A Cochrane systematic review was performed to assess the efficacy of INCS in CARAS. There is cross-talk, evidence of a common inflammatory response in both sites, linked by a systemic component. The efficacy of anti-inflammatory INCS on asthma outcomes was assessed in a systematic review of 12 randomized controlled trials involving 425 subjects. After INCS there were non-significant trends for improvement in asthma symptom score (standardized mean difference (SMD) of 0.61 P=0.07), forced expiratory volume in 1 s (SMD of 0.31 P=0.08), and morning peak expiratory flow (weighted mean difference of 36.51 P=0.06). There was no impact on methacholine airways responsiveness (SMD of -0.20 P=0.4). The review identified two promising new treatment options in united airway disease such as INCS as monotherapy in rhinitis and mild asthma, and a combined intranasal and intrabronchial corticosteroid (IBCS) deposition technique. Common mucosal inflammatory responses occur in CARAS. This systematic review shows trends for a benefit of INCS in CARAS, but recognizes that more research is needed. At this stage, the current best practice is to treat asthma conventionally with IBCS with or without beta(2)-agonist and to add INCS to improve specific rhinitis symptoms.
Publisher: American Thoracic Society
Date: 2001
DOI: 10.1164/AJRCCM.163.1.9807061
Abstract: Corticosteroids can have acute effects on airway function and methacholine airway responsiveness in asthma as early as 6 h after dosing, suggesting there may be an acute anti-inflammatory effect of inhaled corticosteroid in asthma. This study aimed to determine the effects of a single dose of inhaled budesonide on sputum eosinophils and mast cells in adults with asthma, and to examine whether the mechanism of clearance of eosinophils was by apoptosis. A randomized, double-blind, placebo-controlled, crossover study was conducted. At the screening visit, adults with stable asthma (n = 41) ceased inhaled corticosteroid therapy for 4 d and those with significant sputum eosinophilia (> or = 7%) were randomized (n = 26) to a single dose of budesonide 2,400 microg or placebo via Turbuhaler, on two separate study days. Symptoms and lung function were followed for 6 h, then sputum was induced and airway responsiveness to hypertonic saline determined. Sputum eosinophils (mean, SE) were significantly lower 6 h after budesonide (25%, 4.5), compared with placebo (37%, 6.2, p < 0.05). There was a 2.2-fold (95% CI 1.45 to 3.33) improvement in airway responsiveness with budesonide. No significant difference was seen on mast cells, apoptotic eosinophils, symptoms, or lung function. In conclusion, a single dose of inhaled corticosteroids has beneficial effects on airway inflammation and airway hyperresponsiveness as early as 6 h after dosing. This may be clinically useful as therapy during mild exacerbations of asthma.
Publisher: BMJ
Date: 02-2003
Abstract: The relationship between the clinical pattern of asthma and airway inflammation in childhood asthma is poorly characterised, yet underpins the treatment recommendations in current asthma guidelines. A study was undertaken to examine the relationship between airway inflammation and clinical asthma in children. Children with asthma (n=146) and healthy controls (C, n=37) were recruited from primary and specialist clinics. Sputum induction and hypertonic saline challenge were performed. As the frequency of asthma episodes in the past 12 months increased, there were significant increases in sputum eosinophils (median infrequent episodic (IE) 1.5%, frequent episodic (FE) 2.3%, persistent (P) 3.8%, control (C) 1.0% p=0.002), sputum eosinophil cationic protein (ECP) (IE 113 ng/ml, FE 220, P 375, C 139 p=0.003), and desquamated bronchial epithelial cells (IE 2.0%, FE 6.0%, P 5.0%, C 2.5% p=0.04). Treatment intensity was also associated with increased sputum eosinophils (p=0.005). The relationships between other severity markers (current symptoms, lung function) were less strong. Children with more frequent episodes of clinical asthma exhibit increasing airway inflammation that is characterised by sputum eosinophilia and bronchial epithelial desquamation. The results support clinical assessment by frequency of wheezing episodes over the past 12 months when determining anti-inflammatory treatment requirements, and indicate that current symptoms are determined by mechanisms in addition to sputum eosinophilia.
Publisher: Elsevier BV
Date: 02-2012
Publisher: Springer Science and Business Media LLC
Date: 20-06-2017
DOI: 10.1007/S11882-017-0719-9
Abstract: Obesity is a commonly reported comorbidity in asthma, particularly in severe asthma. Obese asthmatics are highly symptomatic with a poor quality of life, despite using high-dose inhaled corticosteroids. While the clinical manifestations have been documented, the aetiologies of obese-asthma remain unclear. Several potential mechanisms have been proposed, including poor diet quality, physical inactivity and consequent accrual of excess adipose tissue. Each of these factors independently activates inflammatory pathways, potentially exerting effects in the airways. Because the origins of obesity are multifactorial, it is now believed there are multiple obese-asthma phenotypes, with varied aetiologies and clinical consequences. In this review, we will describe the clinical implications of obesity in people with asthma, our current understanding of the mechanisms driving this association and describe recently proposed obese-asthma phenotypes. We will then discuss how asthma management is complicated by obesity, and provide graded recommendations for the management of obesity in this population.
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JRI.2014.09.051
Abstract: Pregnancy provides a unique challenge for maternal immunity, requiring the ability to tolerate the presence of a semi-allogeneic foetus, and yet still being capable of inducing an immune response against invading pathogens. To achieve this, numerous changes must occur in the activity and function of maternal immune cells throughout the course of pregnancy. Respiratory viruses take advantage of these changes, altering the sensitive balance of maternal immunity, leaving the mother with increased susceptibility to viral infections and increased disease severity. Influenza virus is one of the most common respiratory virus infections during pregnancy, leading to an increased risk of ICU hospitalisations, pneumonia, acute respiratory distress syndrome and even death. Whilst much research has been performed to understand the changes that must take place in maternal immunity during pregnancy, considerable work is still needed to fully comprehend this tremendous feat. To date, few studies have focused on the alterations that occur in maternal immunity during respiratory virus infections. This review highlights the role of dendritic cells (DCs) and CD8 T cells during pregnancy, and the changes that occur in these antiviral cells following influenza virus infections.
Publisher: Wiley
Date: 13-11-2002
DOI: 10.1046/J.1440-1754.2002.00043.X
Abstract: To compare mite allergen levels in carpeted sleeping accommodation in private dwellings and public places. The concentration of Dermatophagoides pteronyssinus Group 1 allergen in house dust was measured in mat-tresses and bedroom floors in 12 homes, 5 hotels, 11 child care centres and a university hall of residence. Indoor temperature and relative humidity were also measured. A questionnaire clarified details regarding the age of the building, age of the carpet, method and frequency of cleaning, frequency of room use and use of air-conditioning. Median allergen levels in mattresses and carpets in private homes (21.1 and 20.6 micro g/g dust, respectively) were significantly higher than in public places (2.5 and 3.1 micro g/g, respectively P < 0.0001). Mean relative humidity was significantly higher in private houses (68.5% 95% CI 67.2-69.3%) than in public places (56.4% 95% CI 52.7-60.1% P < 0.0001). Carpeted sleeping accommodation in public places has lower house dust mite allergen levels than private houses. Lower levels of relative humidity may be an important component of the explanation.
Publisher: Public Library of Science (PLoS)
Date: 16-06-2016
Publisher: Wiley
Date: 21-06-2013
DOI: 10.1111/RESP.12079
Abstract: Increased sputum neutrophilia has been observed in asthma, but also during normal ageing in asthmatics and non-asthmatics. It remains unclear what constitutes 'normal' neutrophil levels in different age groups. We assessed the relationship between age and airway neutrophils of 194 asthmatics and 243 non-asthmatics (age range: 6-80 years). Regression analyses were used to assess this relationship adjusted for confounders including asthma status, atopy, gender, smoking and current use of inhaled corticosteroids (ICS). Age-corrected reference values for different age groups were determined using the 95th percentile of non-asthmatic participants. Age was positively associated with sputum neutrophils in both asthmatic and non-asthmatic adults (0.46% neutrophil increase/year (95% confidence interval (CI) 0.18, 0.73) and 0.44%/year (0.25, 0.64, respectively), but no association was found in the 95th percentile of non-asthmatic counts for any given age group) were significantly more likely to be asthmatic (odds ratio = 2.5 95% CI: 1.3, 5.0), with the greatest effect observed in the older age group. Other factors that independently associated with increased sputum neutrophil levels included atopy in non-asthmatic adults, male gender and current use of ICS in asthmatic adults. Age-specific reference values for neutrophil percentage were under 20 years-76%, 20-40 years-62%, 40-60 years-63% and over 60 years-67%. Airway neutrophilia is related to age in adults, with a neutrophilic asthma phenotype present in older adults. The use of appropriate age-specific reference values is recommended for future studies aimed at elucidating the role of neutrophils in asthma.
Publisher: BMJ
Date: 16-03-2013
Publisher: Oxford University Press (OUP)
Date: 17-11-2010
Abstract: the diagnosis and management of obstructive airway diseases (OADs) such as asthma and chronic obstructive pulmonary disease (COPD) can be challenging in older people. to assess the clinical, functional, biological and behavioural characteristics relevant to the management of older people with OAD. a cross-sectional study was conducted in a tertiary teaching hospital. Older people (> 55 years) (n = 100) with an OAD underwent a multidimensional assessment (MDA) involving questionnaires, clinical assessments, physiological measurements and biomarkers. the assessment identified a mean (SD) of 11.3 (2.5) clinical management issues and 3.1 (1.8) comorbid conditions per participant. Common problems were: airways hyper-responsiveness (80%) airway inflammation (74%) activity limitation (74%) and systemic inflammation (60.5%). The number and type of issues were similar irrespective of a diagnosis of asthma or COPD (P = 0.2). The degree of health status impairment correlated significantly with the number of clinical management issues detected (r = 0.59 P < 0.0001). older people with OAD experience multiple clinical issues that adversely impact their health status. The number and type are similar irrespective of diagnosis. This MDA identifies significant clinical issues that may not be addressed in a diagnosis centred approach suggesting that a multidisciplinary approach is necessary when assessing and managing older people with OAD.
Publisher: Elsevier BV
Date: 08-2017
Publisher: MDPI AG
Date: 07-01-2016
DOI: 10.3390/NU8010030
Publisher: BMJ
Date: 07-2003
DOI: 10.1136/EBM.8.4.115
Publisher: Hindawi Limited
Date: 13-03-2018
DOI: 10.1155/2018/8387150
Abstract: Chronic obstructive pulmonary disease (COPD) is associated with irreversible persistent airflow limitation and enhanced inflammation. The episodes of acute exacerbation (AECOPD) largely depend on the colonized pathogens such as nontypeable Haemophilus influenzae (NTHi), one of the most commonly isolated bacteria. Regulatory T cells (Tregs) are critical in controlling inflammatory immune responses and maintaining tolerance however, their role in AECOPD is poorly understood. In this study, we hypothesized a regulatory role of Tregs, as NTHi participated in the progress of COPD. Immunological pathogenesis was investigated in a murine COPD model induced by cigarette smoke (CS). NTHi was administrated through intratracheal instillation for an acute exacerbation. Weight loss and lung function decline were observed in smoke-exposed mice. Mice in experimental groups exhibited serious inflammatory responses via histological and cytokine assessment. Expression levels of Tregs and Th17 cells with specific cytokines TGF- β 1 and IL-17 were detected to assess the balance of pro-/anti-inflammatory influence partially. Our findings suggested an anti-inflammatory activity of Tregs in CS-induced model. But this activity was suppressed after NTHi administration. Collectively, these data suggested that NTHi might play a necessary role in downregulating Foxp3 to impair the function of Tregs, helping development into AECOPD.
Publisher: Informa UK Limited
Date: 10-2017
DOI: 10.2147/COPD.S136256
Publisher: Elsevier BV
Date: 09-2007
Publisher: Informa UK Limited
Date: 31-01-2013
DOI: 10.3109/02770903.2012.757777
Abstract: To determine the relationship between psychosocial variables, future exacerbation risk during pregnancy, and perinatal outcomes. A secondary analysis of a randomized controlled trial of exhaled nitric oxide versus guideline-based treatment adjustment in pregnant women with asthma. Women were recruited between 12 and 20 weeks gestation and monitored for the remainder of the pregnancy. Psychosocial questionnaires including the Perceived Control of Asthma Questionnaire, the Brief Illness Perception Questionnaire, and the Six-Item Short-Form State Trait Anxiety Inventory were assessed at randomization. Exacerbations were defined as hospitalization, emergency visit, unscheduled doctor visit, or oral corticosteroid use for worsening asthma. Perinatal outcomes included preterm birth, small for gestational age, and cesarean section. Multiple logistic regressions were performed with predictor variables, including demographics and psychosocial and clinical variables. The 175 participants had a mean (SD) age = 28.5(5.4) years, forced expiratory volume in 1 second (FEV(1)%) predicted = 95.9(13.4), and asthma control score = 0.88(0.70). Greater perceived control of asthma reduced the odds of subsequent exacerbation (odds ratio (OR) [95%CI] 0.92 [0.85, 0.98], p = .016), cesarean without labor (0.84 [0.75, 0.94], p = .003), and preterm birth (0.84 [0.72, 0.97], p = .019), while increased anxiety increased the odds of subsequent exacerbation (1.05 [1.01, 1.08], p = .008). Women's perceptions of asthma control and their psychosocial state (anxiety) are related to future exacerbation risk, cesarean section, and preterm birth.
Publisher: Wiley
Date: 15-03-2023
DOI: 10.1111/RESP.14492
Abstract: People living with asthma, their carers, clinicians and policymakers are the end‐users of research and need research that address their in idual healthcare needs. We aimed to understand the research priorities of end‐users of asthma research. A national cross‐sectional mixed‐methods study was conducted. The study included an online survey that engaged patients, carers, healthcare professionals and policymakers to provide statements to free‐text questions about what they would like to see answered by research to improve living with asthma on a day‐to‐day basis. Responses where thematically analysed followed by three online priority setting consensus workshops. There were 593 respondents who provided 1446 text comments. Participants prioritized 10 asthma research themes which were: (1) asthma in children, (2) COVID 19 and asthma, (3) asthma care and self‐management, (4) diagnosis and medication, (5) managing asthma attacks, (6) causes, prevention and features of asthma, (7) mental health, (8) asthma and ageing, (9) severe asthma, (10) asthma and other health conditions. Each theme comprises specific research questions. This project successfully established 10 priority research themes for asthma, reflecting the collective voice of the end‐users of this research. These novel data can be used to address the documented mismatch in research prioritization between the research community and the end‐users of research.
Publisher: BMJ
Date: 11-09-2021
DOI: 10.1136/THORAXJNL-2020-215979
Abstract: The significance of endoplasmic reticulum (ER) stress in asthma is unclear. Here, we demonstrate that ER stress and the unfolded protein response (UPR) are related to disease severity and inflammatory phenotype. Induced sputum (n=47), bronchial lavage (n=23) and endobronchial biopsies (n=40) were collected from participants with asthma with varying disease severity, inflammatory phenotypes and from healthy controls. Markers for ER stress and UPR were assessed. These markers were also assessed in established eosinophilic and neutrophilic murine models of asthma. Our results demonstrate increased ER stress and UPR pathways in asthma and these are related to clinical severity and inflammatory phenotypes. Genes associated with ER protein chaperone ( BiP, CANX, CALR ), ER-associated protein degradation ( EDEM1, DERL1) and ER stress-induced apoptosis ( DDIT3, PPP1R15A ) were dysregulated in participants with asthma and are associated with impaired lung function (forced expiratory volume in 1 s) and active eosinophilic and neutrophilic inflammation. ER stress genes also displayed a significant correlation with classic Th2 (interleukin-4, IL-4/13) genes, Th17 (IL-17F/CXCL1) genes, proinflammatory (IL-1b, tumour necrosis factor α, IL-8) genes and inflammasome activation (NLRP3) in sputum from asthmatic participants. Mice with allergic airway disease (AAD) and severe steroid insensitive AAD also showed increased ER stress signalling in their lungs. Heightened ER stress is associated with severe eosinophilic and neutrophilic inflammation in asthma and may play a crucial role in the pathogenesis of asthma.
Publisher: Elsevier BV
Date: 2019
Publisher: Springer Science and Business Media LLC
Date: 08-12-2022
DOI: 10.1186/S12884-022-05231-8
Abstract: Little is known about the physical and mental health impact of exposure to landscape fire smoke in women with asthma. This study examined the health impacts and information-seeking behaviours of women with asthma exposed to the 2019/2020 Australian fires, including women who were pregnant. Women with asthma were recruited from the Breathing for Life Trial in Australia. Following the landscape fire exposure period, self-reported data were collected regarding symptoms (respiratory and non-respiratory), asthma exacerbations, wellbeing, quality of life, information seeking, and landscape fire smoke exposure mitigation strategies. Participants’ primary residential location and fixed site monitoring was used to geolocate and estimate exposure to landscape fire-related fine Particulate Matter (PM 2.5 ). The survey was completed by 81 pregnant, 70 breastfeeding and 232 non-pregnant and non-breastfeeding women with asthma. Participants had a median daily average of 17 μg/m 3 PM 2.5 and 105 μg/m 3 peak PM 2.5 exposure over the fire period (October 2019 to February 2020). Over 80% of participants reported non-respiratory and respiratory symptoms during the fire period and 41% reported persistent symptoms. Over 82% reported asthma symptoms and exacerbations of asthma during the fire period. Half the participants sought advice from a health professional for their symptoms. Most (97%) kept windows/doors shut when inside and 94% stayed indoors to minimise exposure to landscape fire smoke. Over two in five (43%) participants reported that their capacity to participate in usual activities was reduced due to prolonged smoke exposure during the fire period. Participants reported greater anxiety during the fire period than after the fire period (mean (SD) = 53(13) versus 39 (13) p 0.001). Two in five (38%) pregnant participants reported having concerns about the effect of fire events on their pregnancy. Prolonged landscape fire smoke exposure during the 2019/2020 Australian fire period had a significant impact on the health and wellbeing of women with asthma, including pregnant women with asthma. This was despite most women taking actions to minimise exposure to landscape fire smoke. Effective and consistent public health messaging is needed during landscape fire events to guard the health of women with asthma.
Publisher: MDPI AG
Date: 16-06-2022
Abstract: Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily in idualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%) wheeze/whistling chest (53%) and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.
Publisher: Informa UK Limited
Date: 07-2021
DOI: 10.2147/COPD.S305380
Publisher: Springer Science and Business Media LLC
Date: 2010
Publisher: American Thoracic Society
Date: 15-08-2005
Publisher: Elsevier BV
Date: 11-2009
Publisher: Springer Science and Business Media LLC
Date: 09-06-2010
DOI: 10.1038/EJCN.2010.68
Abstract: Preservation of lung health with aging is an important health issue in the general population, as loss of lung function with aging can lead to the development of obstructive lung disease and is a predictor of all-cause and cardiovascular mortality. Inflammation is increasingly linked to loss of lung function and evidence suggests that consumption of dietary fat exacerbates inflammation. We aimed to determine the association between dietary fat intake and lung function in older people. Participants from the Hunter community study, a population-based cohort, were recruited during 2004 and 2005. Participants received a clinical assessment, including spirometry, and provided a blood s le. Diets were analyzed using food-frequency questionnaires. Plasma interleukin (IL)-6 and C-reactive protein was measured by Enzyme-Linked immunosorbent assay. Using backward stepwise linear regression, %energy from dietary fat, age and plasma IL-6 were considered as negative predictors of forced expiratory volume in one second (FEV(1)) in men. Also in men, % energy intake from dietary fat, age, body mass index and IL-6 were negative predictors of %predicted forced vital capacity (FVC). Smoking and age were negative predictors of FEV(1)/FVC. In women, plasma IL-6 and age were negative predictors of %FVC, whereas obesity was positively associated with FEV(1)/FVC. An increased proportion of fat in the diet is associated with the reduced lung function in older men. Dietary-fat induced innate immune activation and IL-6 release may contribute to this effect. Dietary interventions involving fat restriction should be further investigated as means of preserving lung function with aging.
Publisher: Wiley
Date: 12-10-2021
DOI: 10.1111/RESP.14167
Abstract: Caring for people with severe asthma and chronic obstructive pulmonary disease (COPD) can impair the quality of life (QoL) of the carer. We aimed to describe the QoL and needs of severe asthma and COPD carers. Carers of severe asthma ( n = 89) and COPD ( n = 48) completed an online cross‐sectional survey assessing QoL and carer support needs using the Short Form Health Survey 12v2 (SF‐12), the Hospital Anxiety and Depression Scale (HADS) and Carers Support Needs Assessment Tool (CSNAT) questionnaires. Carers of people with severe asthma and COPD were similar in age (mean ± SD 57.78 ± 14.09 vs. 56.93 ± 12.91) and gender (65% female vs. 66%) however, they differed in caring duration (proportion caring for years: 65% vs. 33%, p 0.002). QoL was impaired in both groups, but there were no significant differences between severe asthma and COPD carers in either of the SF‐12 component scores. The HADS scores revealed no difference between groups. Compared to severe asthma carers, COPD carers had significantly greater needs for: ‘having time for self’ (33% vs. 13%, p = 0.006), ‘equipment to help care for relative’ (33% vs. 13%, p = 0.006), ‘practical help in the home’ (35% vs. 18%, p = 0.006) and ‘getting a break from caring overnight’ (21% vs. 6%, p = 0.023). QoL is impaired in carers of people with severe asthma to a similar degree of COPD carers and other debilitating diseases like cancer. These novel data highlight the support needs of severe asthma carers and identifies areas where tailored support is needed to reduce their substantial carer burden.
Publisher: American Thoracic Society
Date: 15-06-2011
Publisher: American Thoracic Society
Date: 10-2001
DOI: 10.1164/AJRCCM.164.7.2103015
Abstract: Induced sputum using hypertonic saline (HS) is a useful research tool to study airway inflammation (AI). HS provocation testing can also be used to measure airway hyperresponsiveness (AHR). A combined HS challenge and sputum induction procedure has been developed to permit assessment of AI and AHR in a single test. The aim of this study is to report the success and tolerability of sputum induction alone, and in combination with a HS bronchial provocation challenge. Sputum induction alone was performed with beta2-agonist pretreatment. In the combined challenge, no beta2-agonist pretreatment was used. A high-output ultrasonic nebulizer with valve box and tubing were used to deliver 4.5% saline in doubling time periods from 0.5 s to 4 min. Outcomes assessed were completion of the test protocol, adequacy of sputum s les, decrease in FEV1, and adverse effects during the procedure. Fifty-three children who underwent a sputum induction alone, and 182 children who underwent a combined sputum induction and bronchial provocation using HS. Sputum induction alone was well tolerated, with 98% of children completing the procedure and only 4% experiencing a significant (> 15%) fall in FEV1. An adequate s le of sputum was obtained in 92% of children. The combined challenge was completed by 90% of children. A distressing cough occurred in 13% of children and irritation of the mucosa in 1% of children. In the combined challenge an adequate s le of sputum was obtained in significantly fewer children than with sputum induction alone (70% versus 92%, p < 0.05). Sputum cellular changes reflected the shorter nebulization time with sputum induction alone. We conclude that induction of sputum using HS after pretreatment with bronchodilator is well tolerated with a high success rate in children. Combining the HS challenge with sputum induction provides additional information and is a useful means of comparing AHR and AI simultaneously, but at the expense of having a reduced success rate in obtaining an adequate s le of sputum, as well as increased side effects.
Publisher: Wiley
Date: 07-08-2003
DOI: 10.1046/J.1440-1843.2003.00488.X
Abstract: Changes in health-related quality of life (HRQoL) were evaluated in adults with severe asthma following inhaled corticosteroid treatment with high-dose beclomethasone dipropionate or budesonide (BDP/BUD) and compared with fluticasone propionate taken at approximately half the dose of BDP/BUD. HRQoL was assessed as part of an open, multicentre, randomized, parallel-group study in Australia evaluating the safety and efficacy of switching to fluticasone propionate (FP) 1000-2000 micro g/day (n = 67) compared with remaining on BDP/BUD >/=1750 micro g/day (n = 66) for 6 months. Patients completed two HRQoL questionnaires, the Asthma Quality of Life Questionnaire (AQLQ) and the Medical Outcomes Study Short Form-36 (SF-36), at baseline and at weeks 12 and 24. A change in AQLQ score of >/=0.5 was considered to be clinically meaningful. There were significant improvements in HRQoL with FP on four of the eight dimensions on the SF-36 (i.e. physical functioning, general health, role-emotional, and mental health), while there were no significant improvements in HRQoL in the BDP/BUD group. Overall, patients in the FP group experienced significantly greater improvement (P < 0.001) in AQLQ scores at weeks 12 and 24 compared with the BDP/BUD group. On the in idual domains of the AQLQ, there were significant treatment differences (P < 0.01) in favour of FP in three of the four domains (activity limitations [0.92], symptoms [0.73], and emotional function [1.02]). Mean differences between groups for overall score and these three domains were also clinically meaningful. Patients with severe asthma who received FP (at approximately half the dose of BDP/BUD) experienced statistically significant, as well as clinically meaningful, improvements in their HRQoL.
Publisher: European Respiratory Society
Date: 06-2019
Publisher: Elsevier BV
Date: 07-2000
Abstract: The prevalence of asthma varies widely throughout the world. We now believe that asthma is due to airway inflammation caused by an imbalance of the T-lymphocytes in the airway. The atopy that drives asthma is due to a predominance of Th2 lymphocytes in the airway. This paper links the prevalence of asthma inversely to the prevalence of tuberculosis and enteric infection. We will argue that the reason we observe such marked variations in the prevalence of asthma around the world is the fact that in the developing world there is a survival advantage in the fetal immune response to mature from Th2 to Th1 lymphocyte predominant. A Th1 response is required to combat infectious diseases such as typhoid and tuberculosis. Data from the World Health Organization confirms that these two infectious diseases occur very rarely in those communities where the asthma is high. It may be that the clean and infection-free environment of Australia and New Zealand is responsible for the region of Oceania having the dubious honor of having the highest prevalence of asthma in the world.
Publisher: Elsevier BV
Date: 03-2011
DOI: 10.1016/J.CCM.2010.10.001
Abstract: Worldwide the prevalence of asthma among pregnant women is on the rise, and pregnancy leads to a worsening of asthma for many women. This article examines the changes in asthma that may occur during pregnancy, with particular reference to asthma exacerbations. Asthma affects not only the mother but the baby as well, with potential complications including low birth weight, preterm delivery, perinatal mortality, and preecl sia. Barriers to effective asthma management and opportunities for optimized care and treatment are discussed, and a summary of the clinical guidelines for the management of asthma during pregnancy is presented.
Publisher: European Respiratory Society (ERS)
Date: 30-09-2011
Publisher: Informa UK Limited
Date: 12-2005
DOI: 10.1080/07315724.2005.10719490
Abstract: Elevated oxidative stress and impaired antioxidant defences are increasingly recognised features of asthma. Carotenoids are potent dietary antioxidants that may protect against asthma by reducing oxidative damage. This study aimed firstly, to characterise circulating and airway levels of carotenoids in asthma compared to healthy controls, in relation to dietary intake. Secondly, the study aimed to test whether airway lycopene defences can be improved using oral supplements. Induced sputum and peripheral blood s les were collected from subjects with asthma (n = 15) and healthy controls (n = 16). Dietary carotenoid intakes were estimated using the 24-hour recall method and analysed using a modified version of the Foodworks 210 Nutrient Calculation Software. Another group of healthy controls (n = 9) were supplemented with 20 mg/day lycopene for 4 weeks. Carotenoids (beta-carotene, lycopene, alpha-carotene, beta-cryptoxanthin, lutein/zeaxanthin) were measured by HPLC. Despite similar dietary intake, whole blood levels of total carotenoids, lycopene, lutein, beta-cryptoxanthin, alpha-carotene and beta-carotene were significantly lower in asthma than controls. However, there were no differences in plasma or sputum carotenoid levels. Induced sputum carotenoid levels were significantly lower than plasma and whole blood levels, but correlated strongly with plasma levels (r = 0.798, p < 0.001). Although there were no overall increases in either plasma or sputum lycopene levels following supplementation, changes in airway lycopene levels correlated with changes in plasma levels (r = 0.908, p < 0.002). Whole blood, but not plasma or sputum, carotenoid levels are deficient in asthma. Plasma carotenoid levels reflect airway carotenoid levels and when plasma levels are improved using oral supplements this is reflected in the airways.
Publisher: Wiley
Date: 12-1994
DOI: 10.1111/J.1440-1754.1994.TB00719.X
Abstract: The development of educational packages on health-related topics has become common in school curricula. This paper describes an integrated health and education input in the development of an educational package about asthma for Year 8 high school students. Ownership and educational relevance of the package (ensuring its appropriateness for inclusion within the Personal Development/Health/Physical Education curriculum) was achieved by collaboration between teachers with an understanding of the principles of curriculum design and health professionals with content knowledge about asthma. The model used for the production of the package about asthma could be extended to other health topics.
Publisher: BMJ
Date: 13-07-2010
Abstract: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. Pregnant women with mild asthma (n=52), moderate-severe asthma (n=71) and without asthma (n=51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p=0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r=-0.286, p=0.017) and, despite a decrease in placental GR mRNA (p=0.003), placental GRalpha protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or post-translational modifications.
Publisher: Wiley
Date: 03-2001
DOI: 10.1046/J.1440-1843.2001.00289.X
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) is a condition that results from a hypersensitivity reaction to the fungus Aspergillus fumigatus. The purpose of the present review is to examine the pathogenesis of this condition and the evidence for treatments available. Allergic bronchopulmonary aspergillosis is characterized by an intense airway inflammation with eosinophils and the formation of mucus plugs. Clinically, there are periods of exacerbation and remission that may lead to proximal bronchiectasis and fibrotic lung disease. New evidence confirms the role of intense airway inflammation with eosinophils, but also suggests a role for interleukin (IL)-8/neutrophil-mediated inflammation in this process, and the potential deficiency of anti-inflammatory cytokines such as reduced IL-10. Treatment for ABPA has so far focused on corticosteroids to suppress eosinophilic airway inflammation. An expanding knowledge of the pathology of ABPA also suggests other therapies may be of potential benefit, particularly the use of azole antifungal agents. Allergic bronchopulmonary aspergillosis is itself an important complication of asthma and cystic fibrosis. A greater understanding of the condition is required to improve management and well-designed clinical trials need to be carried out to critically assess new and current treatments. In addition, the information gained from the studies of its pathogenesis has the potential to benefit our understanding of the disease processes in asthma and bronchiectasis.
Publisher: BMJ
Date: 25-02-2021
DOI: 10.1136/THORAXJNL-2020-215526
Abstract: Asthma in pregnancy is associated with respiratory diseases in the offspring. To investigate if maternal asthma is associated with lung function in early life. Data on lung function measured at 5–6 weeks of age were combined from two large birth cohorts: the Bern Infant Lung Development (BILD) and the Australian Breathing for Life Trial (BLT) birth cohorts conducted at three study sites (Bern, Switzerland Newcastle and Sydney, Australia). The main outcome variable was time to reach peak tidal expiratory flow as a percentage of total expiratory time(tPTEF:tE%). Bayesian linear hierarchical regression analyses controlling for study site as random effect were performed to estimate the effect of maternal asthma on the main outcome, adjusting for sex, birth order, breast feeding, weight gain and gestational age. In separate adjusted Bayesian models an interaction between maternal asthma and sex was investigated by including an interaction term. All 406 BLT infants were born to mothers with asthma in pregnancy, while 193 of the 213 (91%) BILD infants were born to mothers without asthma. A significant interaction between maternal asthma and male sex was negatively associated with tPTEF:tE% (intercept 37.5 estimate: –3.5 95% credible interval –6.8 to –0.1). Comparing the model posterior probabilities provided decisive evidence in favour of an interaction between maternal asthma and male sex (Bayes factor 33.5). Maternal asthma is associated with lower lung function in male babies, which may have lifelong implications on their lung function trajectories and future risk of wheezing and asthma.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.JACI.2018.09.033
Abstract: Mepolizumab has demonstrated favorable safety and efficacy profiles in placebo-controlled trials of 12 months' duration or less however, long-term data are lacking. We sought to evaluate the long-term safety and efficacy of mepolizumab in patients with severe eosinophilic asthma (SEA). COLUMBA (Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects, NCT01691859) was an open-label extension study in patients with SEA previously enrolled in DREAM (Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma, NCT01000506). Patients received 100 mg of subcutaneous mepolizumab every 4 weeks plus standard of care until a protocol-defined stopping criterion was met. Safety end points included frequency of adverse events (AEs), serious AEs, and AEs of special interest. Efficacy end points included annualized exacerbation rates, changes from baseline in Asthma Control Questionnaire 5 scores, and blood eosinophil counts. Immunogenicity was also assessed. Overall, 347 patients were enrolled for an average of 3.5 years (maximum, 4.5 years total exposure, 1201 patient-years). On-treatment AEs were reported in 94% of patients (exposure-adjusted rate, 3688 events/1000 patient-years). The most frequently reported on-treatment AEs were respiratory tract infection, headache, bronchitis, and asthma worsening. Seventy-nine (23%) patients experienced 1 or more on-treatment serious AEs there were 6 deaths, none of which were assessed as related to mepolizumab. For patients with 156 weeks or greater enrollment, the exacerbation rate was 0.74 events/y (weeks 0-156), a 56% reduction from the off-treatment period between DREAM and COLUMBA. For all patients, at the first postbaseline assessment, the mean Asthma Control Questionnaire 5 score was reduced by 0.47 points, and blood eosinophil counts were reduced by 78%, with similar improvements maintained throughout the study. The immunogenicity profile (8% anti-drug antibodies) was consistent with previous studies. These data support the long-term safety and efficacy of mepolizumab in patients with SEA.
Publisher: European Respiratory Society (ERS)
Date: 02-2004
DOI: 10.1183/09031936.03.00081403
Abstract: A nonfatal pneumococcal lung infection model was required to investigate immune responses during recovery, and the interaction of other diseases subsequent to infection. A murine model of nonfatal pneumococcal lung infection was developed and the effect of genetic background on susceptibility was determined in BALB/c and C57BL/6 mice. Bacteria colonised the lungs and mice developed mild clinical illness with pathophysiology similar to human bronchopneumonia. Recovery was associated with immune cell influx, which cleared bacteria but induced tissue damage characteristic of pneumococcal bronchopneumonia. After clearance, immune cell populations returned to normal and tissues appeared less inflamed. Although bacterial exposure and clearance were similar, the extent of immune cell influx and tissue damage differed significantly. Larger numbers of neutrophils and lymphocytes entered lung tissue and the affected area was greater in BALB/c compared with C57BL/6 mice. An inflammatory basis for differences was determined with greater levels of phagocytosis and oxidative burst observed in BALB/c mice. C57BL/6 mice cleared the low inoculum with a reduced immune response however, C57BL/6 mice are more susceptible to larger inocula, which overwhelms the immune system. These different susceptibilities result from a greater inflammatory response in BALB/c compared with C57BL/6 mice.
Publisher: Informa UK Limited
Date: 12-2021
DOI: 10.2147/JAA.S328104
Publisher: Springer Science and Business Media LLC
Date: 07-06-2021
DOI: 10.1186/S12931-021-01746-4
Abstract: Comorbidities can complicate the management of severe asthma therefore, the presence of comorbid conditions or traits often need to be considered when considering treatment options for patients with severe asthma. The aim of this analysis is to investigate the efficacy of mepolizumab in patients with severe eosinophilic asthma and comorbidities. This was a post hoc analysis (GSK ID:209140) of data from the Phase IIb/III studies DREAM, MENSA, SIRIUS, and MUSCA. Patients aged ≥ 12 years with severe eosinophilic asthma were randomized to: mepolizumab 750, 250, or 75 mg intravenously or placebo (DREAM) mepolizumab 75 mg intravenously or 100 mg subcutaneously or placebo (MENSA) or mepolizumab 100 mg subcutaneously or placebo (SIRIUS and MUSCA) every 4 weeks for 24 weeks in SIRIUS and MUSCA, 32 weeks in MENSA or 52 weeks in DREAM. In this analysis the primary endpoint was the annual rate of clinically significant exacerbations secondary endpoints were Asthma Control Questionnaire-5 score, St George’s Respiratory Questionnaire total score, and pre-bronchodilator forced expiratory volume in 1 s at study end. Subgroups were based on comorbidities at baseline. Overall, 1878 patients received placebo (n = 689) or mepolizumab (n = 1189). Across all comorbidity subgroups mepolizumab reduced the rate of clinically significant exacerbations by 44–68% versus placebo, improved Asthma Control Questionnaire-5 score by 0.27–0.59 points, and improved St George’s Respiratory Questionnaire total score by 5.0–11.6 points. Pre-bronchodilator forced expiratory volume in 1 s was improved by 27.1–286.9 mL in all but one comorbidity subgroup, the diabetes mellitus subgroup. Mepolizumab reduces exacerbations, and improves asthma control, health-related quality of life, and lung function in patients with severe eosinophilic asthma despite comorbid conditions, including upper respiratory conditions, psychopathologies, cardiovascular conditions, gastroesophageal reflux disease, diabetes mellitus, and obesity. Trial registration : clinicaltrials.gov/ DREAM, MEA112997/NCT01000506 MENSA, MEA115588/NCT01691521 SIRIUS, MEA115575/NCT01842607 MUSCA, 200862/NCT02281318.
Publisher: Wiley
Date: 30-10-2008
Publisher: Informa UK Limited
Date: 26-10-2017
DOI: 10.1080/02770903.2017.1318914
Abstract: Asthma is often suboptimally controlled, in part due to patients' disease knowledge. Understanding patients' knowledge, prior to education may help in in idualizing content. However, there are no well validated or internationally relevant patient asthma knowledge questionnaires available. To translate and validate the rigorously validated Questionnaire de connaissances sur l'asthme destiné aux patients adultes (QCA-PA) based on key points related to asthma knowledge and self-management accordingly to the Global Initiative for Asthma report. Based on Vallerand's methodology, a preliminary version of the "Patient-completed Asthma Knowledge Questionnaire" (PAKQ) was back-translated and evaluated by an expert committee. A s le of 20 in iduals with asthma pretested the questionnaire, after which 62 adults were recruited. Sociodemographic data were collected and the PAKQ together with a comparator questionnaire (Consumer Questionnaire (CQ)) were completed. Fourteen days after the first visit, participants returned to recomplete both questionnaires half were randomly selected to receive a one-on-one asthma education session and again completed both questionnaires immediately after education, and at 10 days follow-up. The PAKQ showed good internal consistency (KR-20 = 0.77). Moderate correlation with CQ (r = 0.596, p = 0.01) attested to its concurrent validity. Confirmatory factor analyses confirmed a single factor structure. A repeated measures ANOVA showed its reproducibility (n = 21:F The PAKQ is a valid asthma knowledge questionnaire which is based on international asthma recommendations and could help healthcare professionals in in idualizing educational interventions for people with asthma.
Publisher: European Respiratory Society (ERS)
Date: 03-09-2015
DOI: 10.1183/09031936.00080514
Abstract: Obese asthma is characterised by infiltration of adipose tissue by activated macrophages and mast cells. The aim of this study was to examine the age and sex effects of immunometabolism in obese asthma. Obese and non-obese asthmatic children and adults underwent spirometry, body composition assessment by dual energy X-ray absorptiometry and measurement of serum soluble CD163 (sCD163), tryptase, C-reactive protein (CRP) and other adipocytokines. Plasma CRP (p .01) and leptin (p .01) were elevated in obese asthmatic adults, and sCD163 (p=0.003) was elevated in obese asthmatic children. We observed significantly higher sCD163 in obese female children compared to obese female adults and male children, and higher CRP in obese female adults compared to obese male children and adults. Serum tryptase concentrations were not significantly different across age groups. sCD163 positively correlated with the proportion of android fat in obese female children (r=0.70, p=0.003) and obese female adults (r=0.65, p=0.003). In obese female children, sCD163 was inversely associated with forced expiratory volume in 1 s % predicted (r=−0.55, p=0.02) and was positively associated with the Asthma Control Questionnaire (r=0.57, p=0.02). Obese children with asthma have sex-specific macrophage activation, which may contribute to worse asthma control and lung function. The heterogeneous systemic inflammatory profile across age and sex suggests the existence of sub-phenotypes in obese asthma at the molecular level.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.IAC.2022.04.007
Abstract: Much interest has been given to the asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) in the past 2 decades, but the condition is still ill-defined. There is general agreement that a patient with longstanding asthma who develops fixed airflow obstruction after years of smoking has ACO although defining asthma in the face of COPD can be challenging. Many features of asthma are also found in patients with COPD without indicating an overlap and no consensus exists on which characteristics should be included in the definition of ACO. Nevertheless, some guidance has been issued to help clinicians and researchers to make a diagnosis of ACO and these will be reviewed here.
Publisher: American Thoracic Society
Date: 12-2003
Publisher: American Thoracic Society
Date: 12-2013
Publisher: Springer Science and Business Media LLC
Date: 11-12-2012
DOI: 10.1007/S40266-012-0042-Z
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are common obstructive airway diseases, especially among older people. These conditions are associated with a significant and increasing disease burden. The diagnosis and management of asthma and COPD in older populations are complex, and consequently clinicians are faced with many therapeutic and diagnostic challenges. Both aging and obstructive airway diseases are associated with complex co-morbidities and these coexisting illnesses confound management. Moreover, the age-related physiological changes that occur in the lungs may lead to airflow limitation, and this may be difficult to distinguish from an active disease state. In practice, management of asthma and COPD is informed by disease-specific clinical practice guidelines however, most older people with these conditions are excluded from clinical trials that are designed to inform practice, creating major evidence gaps. Furthermore, seldom do clinical practice guidelines consider the complexities of management in older populations. The problems experienced by older people are complex and multifactorial and our approach to management must reflect these challenges. Opportunities exist to improve the management and outcomes for older people with obstructive airway disease and there is an urgent need for clinical trials to test management approaches in this population current research must consider the challenges and evidence gaps that exist.
Publisher: The American Association of Immunologists
Date: 15-10-2013
Abstract: The induction of regulatory T cells (Tregs) to suppress aberrant inflammation and immunity has potential as a therapeutic strategy for asthma. Recently, we identified key immunoregulatory components of Streptococcus pneumoniae, type 3 polysaccharide and pneumolysoid (T+P), which suppress allergic airways disease (AAD) in mouse models of asthma. To elucidate the mechanisms of suppression, we have now performed a thorough examination of the role of Tregs. BALB/c mice were sensitized to OVA (day 0) i.p. and challenged intranasal (12–15 d later) to induce AAD. T+P was administered intratracheally at the time of sensitization in three doses (0, 12, and 24 h). T+P treatment induced an early (36 h–4 d) expansion of Tregs in the mediastinal lymph nodes, and later (12–16 d) increases in these cells in the lungs, compared with untreated allergic controls. Anti-CD25 treatment showed that Treg-priming events involving CD25, CCR7, IL-2, and TGF-β were required for the suppression of AAD. During AAD, T+P-induced Tregs in the lungs displayed a highly suppressive phenotype and had an increased functional capacity. T+P also blocked the induction of IL-6 to prevent the Th17 response, attenuated the expression of the costimulatory molecule CD86 on myeloid dendritic cells (DCs), and reduced the number of DCs carrying OVA in the lung and mediastinal lymph nodes. Therefore, bacterial components (T+P) drive the differentiation of highly suppressive Tregs, which suppress the Th2 response, prevent the Th17 response and disable the DC response resulting in the effective suppression of AAD.
Publisher: Elsevier BV
Date: 06-2020
Publisher: MDPI AG
Date: 17-02-2020
DOI: 10.3390/NU12020507
Abstract: The prevalence of obesity in asthmatic children is high and is associated with worse clinical outcomes. We have previously reported that weight loss leads to improvements in lung function and asthma control in obese asthmatic children. The objectives of this secondary analysis were to examine: (1) changes in diet quality and (2) associations between the baseline subject characteristics and the degree of weight loss following the intervention. Twenty-eight obese asthmatic children, aged 8–17 years, completed a 10-week diet-induced weight loss intervention. Dietary intake, nutritional biomarkers, anthropometry, lung function, asthma control, and clinical outcomes were analysed before and after the intervention. Following the intervention, the body mass index (BMI) z-score decreased (Δ = 0.18 ± 0.04 p 0.001), %energy from protein increased (Δ = 4.3 ± 0.9% p = 0.002), and sugar intake decreased (Δ = 23.2 ± 9.3 g p= 0.025). Baseline lung function and physical activity level were inversely associated with Δ% fat mass. The ΔBMI z-score was negatively associated with physical activity duration at baseline. Dietary intervention is effective in achieving acute weight loss in obese asthmatic children, with significant improvements in diet quality and body composition. Lower lung function and physical engagement at baseline were associated with lesser weight loss, highlighting that subjects with these attributes may require greater support to achieve weight loss goals.
Publisher: Therapeutic Guidelines Limited
Date: 08-2001
Publisher: Allergy, Asthma, and Immunology Association of Thailand
Date: 02-07-2014
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.PUPT.2015.06.007
Abstract: Chronic cough is regarded as a challenging clinical problem due to its frequency and often limited therapeutic options. Chronic cough that remains refractory to usual medical treatment causes significant quality of life impairment. Recent developments in the treatment of cough include the use of speech pathology and pharmacotherapy with gabapentin. Relevant randomised control trials, reviews and case reports were identified through a PubMed and SCOPUS search of English-language literature referring to these concepts over the last eight years. The effectiveness of neuromodulating medications such as gabapentin and pregabalin in the treatment of cough has been supported primarily through case series, case reports, prospective reviews and a double blind randomised controlled trial. Gabapentin results in a reduction in cough frequency and cough severity. It improves cough related quality of life. The effect is greatest in patients with features of central reflex sensitisation such as laryngeal paraesthesia, hypertussia and allotussia. These symptoms can be measured using the Newcastle Laryngeal Hypersensitivity Questionnaire. Side effects of gabapentin include somnolence and dizziness. Recent additions in the treatment of chronic cough have been significant as they consider cough to have a unifying diagnosis of cough hypersensitivity with or without the presence of a neuropathic basis. Effective treatments for refractory chronic cough that target these areas include behavioural treatment such as speech pathology and pharmaceutical treatment with neuromodulating medications such as gabapentin.
Publisher: European Respiratory Society
Date: 06-2019
Publisher: American Thoracic Society
Date: 03-2000
DOI: 10.1164/AJRCCM.161.3.9809071
Abstract: Although airway inflammation is recognized as a key feature of asthma, the characteristics of airway inflammation in children with acute severe asthma are not well defined. The aim of this study was to describe the characteristics of airway inflammation in children with an acute exacerbation of asthma using sputum cell counts and fluid-phase measurements and to examine the changes in these parameters upon resolution of the exacerbation. Children (n = 38) presenting to the Emergency Department with acute asthma underwent successful sputum induction using ultrasonically nebulized normal saline (n = 22), or expectorated sputum spontaneously (n = 16). Sputum induction was repeated at least 2 wk later when the children had recovered (n = 28). Sputum portions were selected, dispersed and total and differential cell counts performed. Neutrophil elastase and EG2-positive eosinophils were assessed and fluid-phase eosinophil cationic protein (ECP), myeloperoxidase (MPO), interleukin-8 (IL-8), and IL-5 were measured. During the acute exacerbation the median (range) total cell count was 8.4 x 10(6)/ml (0.5 to 190.3), and fell significantly at resolution to 1.3 x 10(6)/ml (p < 0.01). The inflammatory cell infiltrate was mixed and included eosinophils (0.8 x 10(6)/ml), neutrophils (3.3 x 10(6)/ml), and mast cells. EG2(+) cells were high and correlated with the degree of airflow obstruction (r = -0.5, p = 0.02). They decreased significantly at resolution as did supernatant ECP (1,078 versus 272 ng/ml), suggesting that eosinophils were activated during the exacerbation. MPO was 220 ng/ ml at exacerbation and fell significantly to 1 ng/ml at resolution. Levels of IL-8 and IL-5 were elevated during the acute exacerbation and IL-8 concentrations decreased at resolution. In conclusion, airway inflammation can be studied in children with acute asthma by sputum induction. Airway inflammation is present during an acute exacerbation of asthma, and is characterized by infiltration and activation of both eosinophils and neutrophils. The heterogeneity of airway inflammation in acute asthma may influence response to corticosteroid therapy.
Publisher: Elsevier BV
Date: 07-2012
Abstract: The role of systemic inflammation in asthma is unclear. The aim of this study was to compare systemic inflammation in subjects with stable asthma, categorized by airway inflammatory phenotype, with healthy control subjects. Adults with stable asthma (n = 152) and healthy control subjects (n = 83) underwent hypertonic saline challenge and sputum induction. Differential leukocyte counts were performed on selected sputum. Plasma high-sensitivity C-reactive protein (CRP), IL-6, and tumor necrosis factor-α levels and sputum IL-8 and neutrophil elastase levels were determined by enzyme-linked immunosorbent assay. Sputum IL-8 receptor α (IL-8RA) and IL-8 receptor β (IL-8RB) messenger RNA expression were determined by real-time polymerase chain reaction. Subjects with asthma were classified as having nonneutrophilic asthma or neutrophilic asthma. The asthma (neutrophilic) group had increased systemic inflammation compared with the asthma (nonneutrophilic) and healthy control groups, with median (interquartile range) CRP levels of 5.0 (1.6-9.2), 1.8 (0.9-5.3), and 1.8 (0.8-4.1) mg/L (P = .011), respectively, and IL-6 levels of 2.1 (1.5-3.1), 1.4 (1.0-2.1), and 1.1 (0.8-1.5) pg/mL (P < .001), respectively. The proportion of subjects with elevated CRP and IL-6 levels was also higher in the asthma (neutrophilic) group. Sputum IL-8 and neutrophil elastase protein and IL-8RA and IL-8RB gene expression were significantly increased in the asthma (neutrophilic) group. In multiple regression analysis of subjects with asthma, sex, BMI, statin use, and percent sputum neutrophils were significant predictors of log(10)CRP. Sex, BMI, and %FEV(1) were significant predictors of log(10)IL-6. Systemic inflammation is increased in patients with asthma with neutrophilic airway inflammation and associated with worse clinical outcomes. Systemic inflammation may contribute to the pathophysiology of neutrophilic asthma.
Publisher: American Thoracic Society
Date: 08-2017
Publisher: Wiley
Date: 25-10-2014
DOI: 10.1002/PPUL.22930
Abstract: Asthma is a complex disease that involves both genetic factors and environmental exposures. Aberrant epigenetic modifications, such as DNA methylation, may be important in asthma development. Fetal exposure to maternal asthma during critical periods of in utero development may lead to epigenetic alterations that predispose infants to a greater risk of developing asthma themselves. We investigated alterations in the DNA methylation profile of peripheral blood from infants exposed to maternal asthma during pregnancy. Peripheral blood was collected from 12-month-old infants born to women with (n = 25) and without (n = 15) doctor diagnosed asthma during pregnancy. Genomic DNA was extracted, bisulfite converted, and hybridized to Infinium Methylation 27 arrays (Illumina), containing over27,000 CpGs from 14,495 genes. CpG loci in only autosomal genes were classified as differentially methylated at the 99% level (P 22 and delta beta >0.06). There were 70 CpG loci, corresponding to 67 genes that were significantly differentially methylated. Twelve CpG loci (11 genes) showed greater than 10% comparative difference in DNA methylation, including hyper-methylated loci of FAM181A, MRI1, PIWIL1, CHFR, DEFA1, MRPL28, AURKA, and hypo-methylated loci of NALP1L5, MAP8KIP3, ACAT2, and PM20D1 in maternal asthma. Methylation of MAPK8IP3 was significantly negatively correlated with maternal blood eosinophils (r = -0.38 P = 0.022), maternal eNO (r = -0.44 P = 0.005), and maternal serum total IgE (r = -0.39, P = 0.015). Methylation of AURKA negatively correlated with maternal hemoglobin (r = -0.43 P = 0.008), infants height (r = -0.51 P < 0.001) and weight (r = -0.36 P = 0.021). Methylation of PM20D1 was lower in infants born to mothers with asthma on inhaled corticosteroid treatment. Methylation of PM20D1 was lower and MRI1 was higher in infants born to atopic mothers without asthma. In an Australian study population, exposure to maternal asthma during pregnancy is associated with differential methylation profiles of infants' peripheral blood DNA, which may act as risk factors for future asthma development.
Publisher: AMPCo
Date: 07-2018
DOI: 10.5694/MJA18.00477
Publisher: Wiley
Date: 03-08-2017
DOI: 10.1111/RESP.13134
Abstract: The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies experimental/outcome studies and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 21-06-2013
DOI: 10.1111/CEA.12115
Abstract: Obesity is highly prevalent in asthmatic children and associated with worse clinical outcomes. Energy restriction to induce weight loss in asthmatic children has not been investigated in a randomized controlled trial (RCT). To assess if (1) weight loss can be achieved in obese asthmatic children using a dietary intervention and (2) changes in asthma outcomes occur following diet-induced weight loss. In a 10-week pilot RCT, obese asthmatic children, aged 8-17 years, were randomized to a wait-list control (WLC) (n = 15) or dietary-intervention group (DIG) (n = 13). Lung function, Asthma Control Questionnaire (ACQ) score, and sputum and systemic inflammation were assessed at baseline and post-intervention. (Australian New Zealand Clinical Trials Registry: ACTRN12610000955011). Body mass index (BMI) z-score reduced significantly in the DIG vs. the WLC (-0.2 [-0.4, -0.1] vs. 0.0 [-0.1, 0.0], P = 0.014). Expiratory reserve volume (ERV) increased significantly within the DIG, but not compared to the WLC (0.7 [0.0, 1.0] L vs. 0.3 [0.0, 0.8] L, P = 0.355). ACQ improved significantly in the DIG, compared to the WLC (-0.4 [-0.7, 0.0] vs. 0.1 [0.0, 0.6], P = 0.004). Airway and systemic inflammation did not change within the DIG. In comparison, C-Reactive Protein (CRP) increased significantly in the WLC (-0.4 [-0.5, 0.4] vs. 0.7 [-0.1, 1.9], P = 0.037). Change (∆) in BMI z-score correlated with ∆CRP (r = 0.47, P = 0.012) and ∆exhaled nitric oxide (eNO) (r = 0.46, P = 0.034), and ∆ACQ was associated with ∆CRP (r = 0.43, P = 0.029). Dietary intervention can induce acute weight loss in obese asthmatic children with subsequent improvements in static lung function and asthma control. Systemic and airway inflammation did not change following weight loss. However, changes in BMI z-score were associated with changes in airway and systemic inflammation and this requires further investigation in a larger RCT. This is the first weight loss RCT conducted in obese asthmatic children. Diet-induced weight loss can achieve significant improvements in clinical outcomes for obese children with asthma.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.JVOICE.2017.03.020
Abstract: Talking is a significant trigger for cough in patients with chronic cough however, the stimulus required to trigger cough has not been quantified. The aim of this study was to examine the effect of a vocal loading task on phonation and cough behavior in patients with chronic cough and identify change following therapy. This is a prospective observational study. This study involved 33 patients with chronic cough. Participants were assessed with the lingWAVES Vocal Loading Test protocol before and after intervention for chronic cough. At baseline, almost 40% of patients had impaired vocal function and were unable to complete the vocal loading test. This improved following therapy, with 94% of patients being able to complete the test at follow-up. There was difficulty maintaining phonation, with 60% of the task unvoiced at baseline. This improved following therapy. The vocal loading test triggered coughing in 58% of patients however, this improved following intervention. Acoustic measures during the vocal loading test did not change following therapy. Phonation is an important trigger for cough. Patients with chronic cough demonstrated impaired performance on tests of vocal loading. Most parameters improved following therapy.
Publisher: Wiley
Date: 08-1994
DOI: 10.1111/J.1440-1754.1994.TB00652.X
Abstract: Under-reporting of asthma and inappropriate management at school can h er a child's academic progress. The aim of this study was to assess asthma reporting and crisis management, following implementation of a Primary School Asthma Programme. The intervention covered 12 primary schools with 5093 students in an area of high unemployment with a large proportion of the community from a non-English background. The programme included School Asthma First Aid Kits, training workshops for school staff and in idual Crisis Management Plans for students with asthma. Registration of students with asthma at school increased from 6.2% before the intervention in 1989 to 12.7% in 1992. School Asthma Crisis Plans were completed appropriately by the child's doctor and parents and returned by 68% of the students with asthma. Teachers' asthma knowledge and confidence with the management of acute asthma at school improved following asthma education workshops. It was concluded that asthma reporting and acute crisis management of asthma at school can be achieved by a programme undertaken by school medical services.
Publisher: Wiley
Date: 26-03-2013
Abstract: There is conflicting literature on the effect of maternal asthma on congenital malformations and neonatal outcomes. This review and meta-analysis sought to determine if maternal asthma is associated with an increased risk of adverse neonatal outcomes. We searched electronic databases for: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between 1975 and March 2012 reporting at least one perinatal outcome of interest (congenital malformations, neonatal complications, perinatal mortality). In all, 21 studies met inclusion criteria in pregnant women with and without asthma. Further analysis was conducted on 16 studies where asthmatic women were stratified by exacerbation history, corticosteroid use, bronchodilator use or asthma severity. Maternal asthma was associated with a significantly increased risk of congenital malformations (relative risk [RR] 1.11, 95% confidence interval [95% CI] 1.02-1.21, I(2) = 59.5%), cleft lip with or without cleft palate (RR 1.30, 95% CI 1.01-1.68, I(2) = 65.6%), neonatal death (RR 1.49, 95% CI 1.11-2.00, I(2) = 0%), and neonatal hospitalisation (RR 1.50, 95% CI 1.03-2.20, I(2) = 64.5%). There was no significant effect of asthma on major malformations (RR 1.31, 95% CI 0.57-3.02, I(2) = 70.9%) or stillbirth (RR 1.06, 95% CI 0.9-1.25, I(2) = 35%). Exacerbations and use of bronchodilators and inhaled corticosteroids were not associated with congenital malformation risk. Despite limitations related to the observational nature of the primary studies, this review demonstrates a small increased risk of neonatal complications among pregnant women with asthma. Further investigations into mechanisms and potential preventive interventions to improve infant outcomes are required.
Publisher: Hindawi Limited
Date: 2016
DOI: 10.1155/2016/2180417
Abstract: Inflammation is a complex biological response to detrimental stimuli and can be a double-edged sword. Inflammation plays a protective role in removing pathogenic factors, but dysregulated inflammation is associated with several major fatal diseases such as asthma, cancer, and cardiovascular diseases. Asthma is a complex heterogenous disease caused by genetic and environmental factors. TLRs are the primary proteins associated with the innate and adaptive immune responses to these fatal factors and play an important role in recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), which initiates the downstream immune response. Due to the complex TLRs cascade and nowadays unsuccessful control in asthma, new studies are focused on TLRs and other potential targets in TLR cascade to minimize airway inflammation.
Publisher: International Union Against Tuberculosis and Lung Disease
Date: 11-2014
Abstract: Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease, are responsible for a large global disease burden. The recognition of airway disease phenotypes is important for the application of new therapies targeted at specific underlying biological mechanisms. Biomarkers are indicators of biological or pathogenic processes that are objectively measured. In airway disease, biomarkers will ideally provide predictive information regarding diagnosis, disease mechanisms, phenotypes, treatment responses and prognosis or future risk. Non-invasive biomarkers that aid phenotyping are crucial to the development of targeted and more efficacious treatment, leading to personalised approaches to airway disease management. Sputum and peripheral blood eosinophils and fractional exhaled nitric oxide (FeNO) are current ex les of potential biomarkers. However, recent advances in technology have demonstrated the role for airway transcriptomics in biomarker discovery. This perspective piece discusses the need for biomarkers in airway disease, the use of eosinophil counts and FeNO as biomarkers, the use of transcriptomics for biomarker discovery, and the application of biomarkers in clinical and research settings. A combined approach incorporating clinical information with biological markers such as eosinophils, FeNO and inflammatory gene markers is likely to have the most success in predicting patient outcomes.
Publisher: BMJ
Date: 03-2020
DOI: 10.1136/BMJOPEN-2019-032877
Abstract: Severe asthma imposes a significant burden on in iduals, families and the healthcare system. New treatment and management approaches are emerging as effective options for severe asthma. Translating new knowledge to multidisciplinary healthcare professionals is a priority. We developed ‘The Severe Asthma Toolkit’ (toolkit.severeasthma.org.au ) to increase awareness of severe asthma, provide evidence-based resources and support decisionmaking by healthcare providers. Roundtable discussions and a survey of Australians clinicians were conducted to determine clinician preferences, format and content for a severe asthma resource. A reference group from stakeholder and consumer bodies and severe asthma experts provided advice and feedback. A multidisciplinary team of international experts was engaged to develop content. Written content was based on up-to-date literature. Peer and editorial review were performed to finalise content and inform web design. Website design focused on user experience, navigation, engagement, interactivity and tailoring of content for a clinical audience. A web-based resource was developed. Roundtable discussions and a needs assessment survey identified the need for dedicated severe asthma management resources to support skills training. The end-product, which launched 26 March 2018, includes an overview of severe asthma, diagnosis and assessment, management, medications, comorbidities, living with severe asthma, establishing a clinic, paediatrics/adolescents and clinical resources. Analytics indicate access by users worldwide (32 169 users from 169 countries). User survey results (n=394) confirm access by the target audience (72% health professionals), who agreed the toolkit increased their knowledge (73%) and confidence in managing severe asthma (66%), and 75% are likely to use the resource in clinic. The Severe Asthma Toolkit is a unique, evidence-based internet resource to support healthcare professionals providing optimal care for people with severe asthma. It is a comprehensive, accessible and independent resource developed by leading severe asthma experts to improve clinician knowledge and skills in severe asthma management.
Publisher: Wiley
Date: 11-2001
DOI: 10.1046/J.1365-2222.2001.01230.X
Abstract: Sputum induction is a safe and effective technique to study airway inflammation in stable asthma. However, it has the potential to induce bronchospasm and the safety and efficacy of the technique in acute asthma has not been determined. The objective of this study was to evaluate the safety and efficacy of a protocol to induce sputum using isotonic saline in adults with acute exacerbations of asthma. Adults (n = 47) presenting to the emergency room with acute asthma and an FEV1 > 1.0 L underwent supervised sputum induction with 0.9% saline delivered by an ultrasonic nebuliser. Induction was ceased if there was a fall of 20% or greater from baseline FEV1. Subjects had moderate to severe exacerbations of acute asthma. An adequate sputum s le was obtained in 87% of subjects. Four subjects ceased induction because of symptom distress. There was a fall > or = 20% in 28% of subjects. Bronchoconstriction was successfully reversed by salbutamol in all subjects. Predictors of significant bronchoconstriction were older age, use of ingested corticosteroids, and a requirement for high-dose nebulized salbutamol for the exacerbation. Maintenance long-acting beta2-agonist therapy protected against bronchoconstriction during sputum induction. Sputum induction in acute asthma using isotonic saline is highly efficacious in obtaining an adequate sputum s le. There is the potential for significant bronchoconstriction to occur but this can be managed safely with minimal discomfort to subjects.
Publisher: Wiley
Date: 23-10-2000
Publisher: Wiley
Date: 04-08-2022
DOI: 10.1111/RESP.14341
Abstract: See related article
Publisher: Informa UK Limited
Date: 2003
Abstract: Animal studies have shown elevated surfactant production in response to lung injury. In human airways, the contribution of surfactant to the airway epithelial barrier and importance of eosinophilic inflammation is increasingly appreciated. The relationship between blood and sputum inflammatory indices of childhood asthma to surfactant levels is unknown. In this study we hypothesized that the degree of inflammation influences the level of dipalmitoyl phosphatidycholine (DPPC) in airways of children with asthma. Sixteen children with asthma (ages 5.5-16 years) underwent venipuncture, skin prick test, spirometry, hypertonic saline challenge, and induced sputum during a nonacute phase. Sputum (sp) and blood (se) markers of inflammation (eosinophils, neutrophils, eosinophilic cationic protein [ECP]), were related to sputum DPPC levels and several markers of asthma severity (airway hyperresponsiveness, quality of life, FEV1). On multiple regression, sp-DPPC significantly correlated to sp-ECP (r=0.53, P=0.0048). Se-ECP, se-Eo, sp-eosinophils, sp-neutrophils, se-neutrophils, and inhaled steroids dose did not significantly influence sp-DPPC. Exposure to smoke did not influence inflammatory markers. FEV1 and quality of life data did not relate to any blood or sputum variable. A significant association between AHR and se-eosinophils, but not between AHR and se-ECP, sp-eosinophils, or sp-ECP was found. Elevated DPPC levels occur in the presence of chronic eosinophilic inflammation in airways of children with stable asthma. Whether this represents an inherent lung mechanism for epithelial protection remains to be elucidated.
Publisher: Elsevier BV
Date: 10-2015
Publisher: The American Association of Immunologists
Date: 05-2016
Abstract: Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)–induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV. Dexamethasone treatment completely inhibited all features of allergic disease, including AHR and eosinophil infiltration, in uninfected OVA-sensitized/challenged mice. Conversely, dexamethasone treatment following RSV-induced exacerbation only partially suppressed AHR and failed to d en macrophage and neutrophil infiltration or inflammatory cytokine production (TNF-α, MCP-1, and KC). This mimics clinical observations in patients with exacerbations, which is associated with increased neutrophils and often poorly responds to corticosteroid therapy. Interestingly, we also observed increased TNF-α levels in sputum s les from patients with neutrophilic asthma. Although RSV-induced exacerbation was resistant to steroid treatment, inhibition of TNF-α and MCP-1 function or depletion of macrophages suppressed features of disease, including AHR and macrophage and neutrophil infiltration. Our findings highlight critical roles for macrophages and inflammatory cytokines (including TNF-α and MCP-1) in viral-induced exacerbation of asthma and suggest examination of these pathways as novel therapeutic approaches for disease management.
Publisher: Oceanside Publications Inc.
Date: 05-2022
DOI: 10.2500/AAP.2022.43.220022
Abstract: Background: Cough is often the most prominent and intractable symptom reported by patients with asthma, but few studies have explored the characteristics of patients with asthma and with chronic cough (CC) in a real-world setting. Methods: In a prospective cohort study, patients ages ≥ 18 years with stable asthma were consecutively recruited at the West China Hospital, Sichuan University. The patients were classified as having asthma with CC (the CC group) or asthma with non-CC (the non-CC group) after 3 months of optimized asthma therapy according to standard guidelines. Multidimensional assessment was performed at baseline, followed by a 12-month follow-up to assess asthma exacerbations. Results: Of 323 patients with asthma, 127 patients were assigned to the CC group and 196 patients were assigned to the non-CC group. The participants with CC were older and had more airflow obstruction worse asthma control and quality of life increased airway inflammation upper respiratory tract infection as a trigger and more comorbidities, such as psychological dysfunction, rhinitis, chronic obstructive pulmonary disease, and bronchiectasis. They reported greater work productivity loss and daily activity impairment, and increased moderate-to-severe exacerbations. Conclusion: The participants with asthma and with CC had a significant disease burden, with increased exacerbations, health-care utilization, and impaired work productivity and daily activity. These observations indicated potential clinical implications in patients with asthma and with CC, and call for more attention to this aspect of asthma.
Publisher: Wiley
Date: 18-02-2019
DOI: 10.1111/J.1440-1843.2007.01047.X
Abstract: There is an urgent need to define new treatment strategies for severe persistent asthma. Using a severe asthma clinic model, it is possible to systematically assess diagnosis, self-management skills, and treatment efficacy. The addition of single-patient trials of therapy is useful to detect in idual responders to drugs where use is limited because of access, cost, or toxicity. Omalizumab is effective in severe asthma, however access is restricted by cost and availability. We conducted single patient efficacy trials of omalizumab in 12 subjects with severe refractory asthma. There were 2 definite and 6 partial responders. Patients with difficult/therapy resistant or refractory asthma can respond to omalizumab, and this response can be detected in in idual patients using a single patient controlled trial conducted in the setting of a severe asthma clinic.
Publisher: American Thoracic Society
Date: 09-2005
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.JACI.2018.04.037
Abstract: Both obesity and high dietary fat intake activate the nucleotide oligomerization domain-like receptor protein 3 (NLRP3) inflammasome. We aimed to examine NLRP3 inflammasome activity in the airways of obese asthmatic patients after macronutrient overload and in immune cells challenged by inflammasome triggers. Study 1 was a cross-sectional observational study of nonobese (n = 51) and obese (n = 76) asthmatic adults. Study 2 was a randomized, crossover, acute feeding study in 23 asthmatic adults (n = 12 nonobese and n = 11 obese subjects). Subjects consumed 3 isocaloric meals on 3 separate occasions (ie, saturated fatty acid, n-6 polyunsaturated fatty acid, and carbohydrate) and were assessed at 0 and 4 hours. For Studies 1 and 2, airway inflammation was measured based on sputum differential cell counts, IL-1β protein levels (ELISA), and sputum cell gene expression (Nanostring nCounter). In Study 3 peripheral blood neutrophils and monocytes were isolated by using Ficoll density gradient and magnetic bead separation and incubated with or without palmitic acid, LPS, or TNF-α for 24 hours, and IL-1β release was measured (ELISA). In Study 1 NLRP3 and nucleotide oligomerization domain 1 (NOD1) gene expression was upregulated, and sputum IL-1β protein levels were greater in obese versus nonobese asthmatic patients. In Study 2 the saturated fatty acid meal led to increases in sputum neutrophil percentages and sputum cell gene expression of Toll-like receptor 4 (TLR4) and NLRP3 at 4 hours in nonobese asthmatic patients. In Study 3 neutrophils and monocytes released IL-1β when challenged with a combination of palmitic acid and LPS or TNF-α. The NLRP3 inflammasome is a potential therapeutic target in asthmatic patients. Behavioral interventions that reduce fatty acid exposure, such as weight loss and dietary saturated fat restriction, warrant further exploration.
Publisher: Hindawi Limited
Date: 2013
DOI: 10.1155/2013/462934
Publisher: American Thoracic Society
Date: 08-2019
Publisher: The American Association of Immunologists
Date: 10-2010
Abstract: Inflammation and airway hyperresponsiveness (AHR) are hallmark features of asthma and often correlate with the severity of clinical disease. Although these features of asthma can be effectively managed with glucocorticoid therapy, a subgroup of patients, typically with severe asthma, remains refractory to therapy. The mechanisms leading to steroid resistance in severe asthmatics are poorly understood but may be related to the activation of innate host defense pathways. Previously, we have shown that IFN-γ–producing cells and LPS, two factors that are associated with severe asthma, induce steroid-resistant AHR in a mouse model. We now demonstrate that cooperative signaling induced by IFN-γ and LPS results in the production of IL-27 by mouse pulmonary macrophages. IL-27 and IFN-γ uniquely cooperate to induce glucocorticoid-resistant AHR through a previously unknown MyD88-dependent mechanism in pulmonary macrophages. Importantly, integrated signaling by IL-27/IFN-γ inhibits glucocorticoid-induced translocation of the glucocorticoid receptor to the nucleus of macrophages. Furthermore, expression of both IL-27 and IFN-γ was increased in the induced sputum of steroid-refractory asthmatics. These results suggest that a potential mechanism for steroid resistance in asthma is the activation of MyD88-dependent pathways in macrophages that are triggered by IL-27 and IFN-γ, and that manipulation of these pathways may be a therapeutic target.
Publisher: Wiley
Date: 04-2014
DOI: 10.1111/RESP.12278
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 05-07-2022
DOI: 10.1097/CM9.0000000000002050
Abstract: Although existing mycological tests (bronchoalveolar lavage [BAL] galactomannan [GM], serum GM, serum (1,3)-β-D-glucan [BDG], and fungal culture) are widely used for diagnosing invasive pulmonary aspergillosis (IPA) in non-hematological patients with respiratory diseases, their clinical utility in this large population is actually unclear. We aimed to resolve this clinical uncertainty by evaluating the diagnostic accuracy and utility of existing tests and explore the efficacy of novel sputum-based Aspergillus assays. Existing tests were assessed in a prospective and consecutive cohort of patients with respiratory diseases in West China Hospital between 2016 and 2019 while novel sputum assays (especially sputum GM and Aspergillus -specific lateral-flow device [LFD]) in a case-controlled subcohort. IPA was defined according to the modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Sensitivity and specificity were computed for each test and receiver operating characteristic (ROC) curve analysis was performed. The entire cohort included 3530 admissions (proven robable IPA = 66, no IPA = 3464) and the subcohort included 127 admissions (proven robable IPA = 38, no IPA = 89). Sensitivity of BAL GM (≥1.0 optical density index [ODI]: 86% [24/28]) was substantially higher than that of serum GM (≥0.5 ODI: 38% [39/102]) ( χ 2 = 19.83, P 0.001), serum BDG (≥70 pg/mL: 33% [31/95]) ( χ 2 = 24.65, P 0.001), and fungal culture (33% [84/253]) ( χ 2 = 29.38, P 0.001). Specificity varied between BAL GM (≥1.0 ODI: 94% [377/402]), serum GM (≥0.5 ODI: 95% [2130/2248]), BDG (89% [1878/2106]), and culture (98% [4936/5055]). Sputum GM (≥2.0 ODI) had similar sensitivity (84% [32/38]) (Fisher's exact P = 1.000) to and slightly lower specificity (87% [77/89]) ( χ 2 = 5.52, P = 0.019) than BAL GM (≥1.0 ODI). Area under the ROC curve values were comparable between sputum GM (0.883 [0.812–0.953]) and BAL GM (0.901 [0.824–0.977]) ( P = 0.734). Sputum LFD had similar specificity (91% [81/89]) ( χ 2 = 0.89, P = 0.345) to and lower sensitivity (63% [24/38]) ( χ 2 = 4.14, P = 0.042) than BAL GM (≥1.0 ODI), but significantly higher sensitivity than serum GM (≥0.5 ODI) ( χ 2 = 6.95, P = 0.008), BDG ( χ 2 = 10.43, P = 0.001), and fungal culture ( χ 2 = 12.70, P 0.001). Serum GM, serum BDG, and fungal culture lack sufficient sensitivity for diagnosing IPA in respiratory patients. Sputum GM and LFD assays hold promise as rapid, sensitive, and non-invasive alternatives to the BAL GM test.
Publisher: Wiley
Date: 05-01-2018
DOI: 10.1111/RESP.13249
Publisher: S. Karger AG
Date: 2021
DOI: 10.1159/000510793
Abstract: b i Background: /i /b Reducing asthma exacerbations is a major target of current clinical guidelines, but identifying features of exacerbation-prone asthma (EPA) using multidimensional assessment (MDA) is lacking. b i Objective: /i /b To systemically explore the clinical and inflammatory features of adults with EPA in a Chinese population. b i Methods: /i /b We designed a cross-sectional study using the Severe Asthma Web-based Database from the Australasian Severe Asthma Network (ASAN). Eligible Chinese adults with asthma ( i n /i = 546) were assessed using MDA. We stratified patients based on exacerbation frequency: none, few (1 or 2), and exacerbation prone (≥3). Univariate and multivariable negative binomial regression analyses were performed to investigate features associated with the frequency of exacerbations. b i Results: /i /b Of 546 participants, 61.9% had no exacerbations ( i n /i = 338), 29.6% had few exacerbations ( i n /i = 162), and 8.4% were exacerbation prone ( i n /i = 46) within the preceding year. EPA patients were characterized by elevated blood and sputum eosinophils but less atopy, with more controller therapies but worse asthma control and quality of life (all i /i & #x3c 0.05). In multivariable models, blood and sputum eosinophils (adjusted rate ratio = 2.23, 95% confidence interval = [1.26, 3.84] and 1.67 [1.27, 2.21], respectively), FEV sub /sub (0.90 [0.84, 0.96]), bronchodilator responsiveness (1.16 [1.05, 1.27]), COPD (2.22 [1.41, 3.51]), bronchiectasis (2.87 [1.69, 4.89]), anxiety (2.56 [1.10, 5.95]), and depression (1.94 [1.20, 3.13]) were found. Further, upper respiratory tract infection (1.83 [1.32, 2.54]) and food allergy (1.67 [1.23, 2.25]) were at high risk of asthma symptom triggers. b i Conclusion: /i /b EPA is a clinically recognizable phenotype associated with several recognizable traits that could be addressed by targeted treatment.
Publisher: Hindawi Limited
Date: 2017
DOI: 10.1155/2017/8539294
Abstract: Viral infection is a common trigger for acute exacerbations of chronic obstructive pulmonary disease (AECOPD). The aim of this study is to investigate the expression of cytokines in AECOPD. Patients with AECOPD requiring hospitalization were recruited. Meanwhile healthy volunteers of similar age that accepted routine check-ups and showed no clinical symptoms of inflammatory diseases were also recruited. Induced sputum and serum were collected. Induced sputum of participants was processed and tested for thirteen viruses and bacteria. Forty cytokines were assayed in serum using the Quantibody Human Inflammation Array 3 (Ray Biotech, Inc.). The most common virus detected in virus positive AECOPD (VP) was influenza A (16%). No virus was found in controls. Circulating levels of IL-6, TNF- α , and MCP-1 were elevated in VP and coinfection subjects ( p 0.05 ), while the levels of 37 other cytokines showed no difference, compared with virus negative groups and controls ( p 0.05 ). Additionally, VP patients were less likely to have received influenza vaccination. VP patients had a systemic inflammation response involving IL-6, TNF- α , and MCP-1 which may be due to virus-induced activation of macrophages. There are important opportunities for further investigating AECOPD mechanisms and for the development of better strategies in the management and prevention of virus-related AECOPD.
Publisher: MDPI AG
Date: 29-09-2020
DOI: 10.3390/NU12102978
Abstract: Low 25-hydroxyvitamin D (25(OH)D) levels are common in pregnancy and associated with adverse maternal/neonatal outcomes. In pregnant women with asthma, this study examined the association of lifestyle- and asthma-related factors on 25(OH)D levels and maternal/neonatal outcomes by vitamin D status. Serum 25(OH)D was measured at 16 and 35 weeks gestation in women with asthma (n = 103). Body mass index (BMI), gestational weight gain (GWG), smoking status, inhaled corticosteroid (ICS) use, asthma control, airway inflammation, and exacerbations, and maternal/neonatal outcomes were collected. Baseline and change (Δ) in 25(OH)D were modelled separately using backward stepwise regression, adjusted for season and ethnicity. Maternal/neonatal outcomes were compared between low (25(OH)D 75 nmol/L at both time points) and high (≥75 nmol/L at one or both time points) vitamin D status. Fifty-six percent of women had low vitamin D status. Obesity was significantly associated with lower baseline 25(OH)D (Adj-R2 = 0.126, p = 0.008) ICS and airway inflammation were not. Excess GWG and season of baseline s le collection were significantly associated with Δ25(OH)D (Adj-R2 = 0.405, p 0.0001) asthma-related variables were excluded (p 0.2). Preecl sia was more common in the low (8.6%) vs. high (0%) vitamin D group (p 0.05). Obesity and excess GWG may be associated with gestational 25(OH)D levels, highlighting the importance of antenatal weight management.
Publisher: Elsevier BV
Date: 03-1998
DOI: 10.1016/S0091-6749(98)70242-8
Abstract: To describe a case of chronic myelogenous leukemia (CML) with retinal leukemic infiltration identified by optical coherence tomography (OCT) and OCT angiography (OCTA). Case report. A 64-year-old man presented with bilateral painless blurred vision as well as three weeks of fatigue, unintentional weight loss, and complete hearing loss. Dilated fundus exam of both eyes showed peripheral intraretinal hemorrhages with white centers, vascular tortuosity, and peripheral non-perfusion. No macular lesions were identified by slit l exam, fundus photography, fundus autofluorescence, or fluorescein angiography. OCT through the macula revealed multiple hyperreflective lesions throughout the inner retinal layers. Some of these lesions showed intrinsic flow by OCTA, but many lesions did not. The bone marrow biopsy confirmed CML, and these intraretinal lesions were deemed to be leukemic infiltrates. The patient regained vision after systemic chemotherapy with resolution of the retinal infiltrates over time. Primary leukemic retinal involvement can be challenging to diagnose, especially when the macula appears normal clinically. OCT and OCTA are useful imaging modalities for the detection of retinal leukemic infiltration. Completing a thorough review of systems and initiating an urgent, systemic work-up are warranted in cases of retinal infiltration.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.JAIP.2021.08.028
Abstract: Pulmonary comorbidities can increase disease severity and health care costs associated with asthma management. Vocal cord dysfunction/inducible laryngeal obstruction is a common comorbidity that results from intermittent laryngeal obstruction. Patients describe distinct episodes of dyspnea that do not respond to bronchodilators. Inspiratory stridor is common. The gold standard diagnostic testing strategy is continuous laryngoscopy performed during exercise or irritant challenges. Dysfunctional breathing (DB) is an overarching term that describes conditions with a chronic change in the pattern of breathing that results in pulmonary and extrapulmonary symptoms. The prevalence of DB in asthma is up to 30%, and breathing retraining can improve symptoms and quality of life in people with DB and asthma. Asthma-chronic obstructive pulmonary disease overlap (ACO) refers to both asthmatics who develop fixed airflow obstruction after a history of exposure to smoke or biomass and patients with chronic obstructive pulmonary disease who have "asthmatic features" such as a large bronchodilator response, elevated levels of serum IgE, or peripheral eosinophil counts ≥300 per μL. Triple inhaler therapy with inhaled corticosteroid/long-acting beta-agonist/long-acting muscarinic should be considered in people with ACO and severe symptoms or frequent exacerbations. The clinical expression of bronchiectasis involves persistent mucus hypersecretion, recurrent exacerbations of infective bronchitis, incompletely reversible airflow obstruction, and lung fibrosis and can occur in up to 30% of adults with longstanding asthma. The treatable traits strategy is a useful model of care to manage the complexity and heterogeneity of asthma with pulmonary comorbidity.
Publisher: Wiley
Date: 21-08-2014
DOI: 10.1111/CEA.12345
Abstract: In asthma, the airway inflammatory phenotype influences clinical characteristics and treatment response. Although induced sputum is the gold standard test for phenotyping asthma, a more accessible method is needed for clinical practice. To investigate whether white blood cell counts and/or their derived ratios can predict sputum eosinophils or neutrophils in uncontrolled asthma. This cross-sectional study evaluated 164 treated but uncontrolled asthmatic patients with sputum induction and blood collection. Receiver-operating characteristic (ROC) curves were used to assess the relationship between blood and sputum parameters. There was a significant positive relationship between blood eosinophil parameters and the percentage of sputum eosinophil count. A weak but significant correlation was found between sputum neutrophil percentage and blood neutrophil percentage (r = 0.219, P = 0.005). ROC curve analysis identified that blood eosinophil percentage count was the best predictor for eosinophilic asthma, with an area under the curve (AUC) of 0.907 (P < 0.001). The optimum cut-point for blood eosinophil percentage was 2.7%, and this yielded a sensitivity of 92.2% and a specificity of 75.8%. The absolute blood eosinophil count was also highly predictive with an AUC of 0.898 (P < 0.0001) at a blood eosinophil cut-off of 0.26 × 10(9) /L. The blood eosinophil/lymphocyte ratio (ELR) and eosinophil/neutrophil ratio (ENR) were increased in eosinophilic asthma, and the neutrophil/lymphocyte ratio (NLR) was increased in neutrophilic asthma. Neutrophilic asthma could also be detected by blood neutrophil percentages and NLR, but with less accuracy. Blood eosinophil counts and derived ratios (ELR and ENR) can accurately predict eosinophilic asthma in patients with persistent uncontrolled asthma despite treatment. Blood neutrophil parameters are poor surrogates for the proportion of sputum neutrophils. Blood counts may be a useful aid in the monitoring of uncontrolled asthma.
Publisher: Elsevier BV
Date: 09-2008
DOI: 10.1016/J.JVOICE.2007.01.001
Abstract: Voice problems have been reported to occur in association with chronic cough (CC) and can interfere with quality of life. Voice symptoms can improve following behavioral intervention for CC that persists despite medical management however, formal measures of voice changes have not been reported. The aim of this study was to measure the changes in perceptual, acoustic, and electroglottographic voice characteristics after a SPEech Pathology Intervention Program for CHronic Cough (SPEICH-C) compared to a Healthy Lifestyle Education intervention program (HLE control). Eighty-two participants with CC that was refractory to medical management were randomly allocated to receive either the SPEICH-C or an HLE control. Participants in the SPEICH-C group demonstrated a significant reduction in perceptual ratings of breathy, rough, strain, and glottal fry qualities (P<0.001) in comparison to the HLE control group. There was a significant improvement between pre- and postintervention maximum phonation time, jitter, and harmonic-to-noise ratio values in the SPEICH-C group however, the magnitude of change was not significantly different between groups. There was no significant change in fundamental frequency, standard deviation of fundamental frequency, phonation range, or closed phase of vocal fold vibration after intervention for either group. These results demonstrated that SPEICH-C can improve perceptual aspects of voice quality suggesting that dysphonia may be a fundamental characteristic of CC.
Publisher: Wiley
Date: 22-02-2014
DOI: 10.1111/CEA.12223
Abstract: Severe asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which the mechanisms are not fully understood. A disintegrin and metalloproteinase domain 8 (ADAM8) is an enzyme expressed on most leucocytes and may be important for facilitating leucocyte migration in respiratory disease. To investigate ADAM8 mRNA and protein expression in asthma and COPD and its relationship between asthma severity and inflammatory phenotypes. Induced sputum was collected from 113 subjects with asthma (severe n = 31, uncontrolled n = 39 and controlled n = 35), 20 subjects with COPD and 21 healthy controls. Sputum ADAM8 mRNA expression was measured by qPCR, and soluble ADAM8 (sADAM8) protein was measured in the sputum supernatant by validated ELISA. ADAM8 mRNA correlated with ADAM8 protein levels (r = 0.27, P < 0.01). ADAM8 mRNA (P = 0.004) and sADAM8 protein (P = 0.014) levels were significantly higher in both asthma and COPD compared with healthy controls. ADAM8 mRNA (P = 0.035) and sADAM8 protein (P = 0.002) levels were significantly higher in severe asthma compared with controlled asthma. Total inflammatory cell count (P < 0.01) and neutrophils (P < 0.01) were also elevated in severe asthmatic sputum. Although ADAM8 mRNA was significantly higher in eosinophilic and neutrophilic asthma (P < 0.001), sADAM8 did not differ between asthma inflammatory phenotypes. ADAM8 expression positively correlated with sputum total cell count and sputum neutrophils. ADAM8 expression is increased in both severe asthma and COPD and associated with sputum total cell count and neutrophils. ADAM8 may facilitate neutrophil migration to the airways in severe asthma and COPD.
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.ANAI.2017.07.016
Abstract: Asthma is a heterogeneous airway disease, so it is crucial to clearly identify clinical phenotypes to achieve better asthma management. To identify and prospectively validate asthma clusters in a Chinese population. Two hundred eighty-four patients were consecutively recruited and 18 sociodemographic and clinical variables were collected. Hierarchical cluster analysis was performed by the Ward method followed by k-means cluster analysis. Then, a prospective 12-month cohort study was used to validate the identified clusters. Five clusters were successfully identified. Clusters 1 (n = 71) and 3 (n = 81) were mild asthma phenotypes with slight airway obstruction and low exacerbation risk, but with a sex differential. Cluster 2 (n = 65) described an "allergic" phenotype, cluster 4 (n = 33) featured a "fixed airflow limitation" phenotype with smoking, and cluster 5 (n = 34) was a "low socioeconomic status" phenotype. Patients in clusters 2, 4, and 5 had distinctly lower socioeconomic status and more psychological symptoms. Cluster 2 had a significantly increased risk of exacerbations (risk ratio [RR] 1.13, 95% confidence interval [CI] 1.03-1.25), unplanned visits for asthma (RR 1.98, 95% CI 1.07-3.66), and emergency visits for asthma (RR 7.17, 95% CI 1.26-40.80). Cluster 4 had an increased risk of unplanned visits (RR 2.22, 95% CI 1.02-4.81), and cluster 5 had increased emergency visits (RR 12.72, 95% CI 1.95-69.78). Kaplan-Meier analysis confirmed that cluster grouping was predictive of time to the first asthma exacerbation, unplanned visit, emergency visit, and hospital admission (P < .0001 for all comparisons). We identified 3 clinical clusters as "allergic asthma," "fixed airflow limitation," and "low socioeconomic status" phenotypes that are at high risk of severe asthma exacerbations and that have management implications for clinical practice in developing countries.
Publisher: Springer Science and Business Media LLC
Date: 14-08-2020
DOI: 10.1186/S12874-020-01065-0
Abstract: Severe asthma exerts a disproportionately heavy burden on patients and health care. Due to the heterogeneity of the severe asthma population, many patients need to be evaluated to understand the clinical features and outcomes of severe asthma in order to facilitate personalised and targeted care. The International Severe Asthma Registry (ISAR) is a multi-country registry project initiated to aid in this endeavour. ISAR is a multi-disciplinary initiative benefitting from the combined experience of the ISAR Steering Committee (ISC comprising 47 clinicians and researchers across 29 countries, who have a special interest and/or experience in severe asthma management or establishment and maintenance of severe asthma registries) in collaboration with scientists and experts in database management and communication. Patients (≥18 years old) receiving treatment according to the 2018 definitions of the Global Initiative for Asthma (GINA) Step 5 or uncontrolled on GINA Step 4 treatment will be included. Data will be collected on a core set of 95 variables identified using the Delphi method. Participating registries will agree to provide access to and share standardised anonymous patient-level data with ISAR. ISAR is a registered data source on the European Network of Centres for Pharmacoepidemiology and Pharmacovigilance. ISAR’s collaborators include Optimum Patient Care, the Respiratory Effectiveness Group (REG) and AstraZeneca. ISAR is overseen by the ISC, REG, the Anonymised Data Ethics & Protocol Transparency Committee and the ISAR operational committee, ensuring the conduct of ethical, clinically relevant research that brings value to all key stakeholders. ISAR aims to offer a rich source of real-life data for scientific research to understand and improve disease burden, treatment patterns and patient outcomes in severe asthma. Furthermore, the registry will provide an international platform for research collaboration in respiratory medicine, with the overarching aim of improving primary and secondary care of adults with severe asthma globally.
Publisher: Elsevier BV
Date: 02-2018
Publisher: Elsevier BV
Date: 07-2022
Publisher: Wiley
Date: 22-07-2002
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/10715760701767307
Abstract: Antioxidant-rich diets are associated with reduced asthma prevalence. However, direct evidence that altering intake of antioxidant-rich foods affects asthma is lacking. The objective was to investigate changes in asthma and airway inflammation resulting from a low antioxidant diet and subsequent use of lycopene-rich treatments. Asthmatic adults (n=32) consumed a low antioxidant diet for 10 days, then commenced a randomized, cross-over trial involving 3 x 7 day treatment arms (placebo, tomato extract (45 mg lycopene/day) and tomato juice (45 mg lycopene/day)). With consumption of a low antioxidant diet, plasma carotenoid concentrations decreased, Asthma Control Score worsened, %FEV(1) and %FVC decreased and %sputum neutrophils increased. Treatment with both tomato juice and extract reduced airway neutrophil influx. Treatment with tomato extract also reduced sputum neutrophil elastase activity. In conclusion, dietary antioxidant consumption modifies clinical asthma outcomes. Changing dietary antioxidant intake may be contributing to rising asthma prevalence. Lycopene-rich supplements should be further investigated as a therapeutic intervention.
Publisher: BMJ
Date: 28-04-2009
Publisher: Elsevier BV
Date: 08-2011
Abstract: Despite the commonality of cough and its burden, there are no published data on the relationship between atopy or sex on objectively measured cough frequency or subjective cough scores in children. In 202 children with and without cough, we determined the effect of sex and atopy on validated cough outcome measurements (cough receptor sensitivity [CRS], objective cough counts, and cough scores). We hypothesized that in contrast to adult data, sex does not influence cough outcome measures, and atopy is not a determinant of these cough measurements. We combined data from four previous studies. Atopy (skin prick test), the concentration of capsaicin causing two and five or more coughs (C2 and C5, respectively), objectively measured cough frequency, and cough scores were determined and their relationship explored. The children's (93 girls, 109 boys) mean age was 10.6 years (SD 2.9), and 56% had atopy. In multivariate analysis, CRS was influenced by age (C2 coefficient, 5.9 P = .034 C5 coefficient, 29.1 P = .0001). Atopy and sex did not significantly influence any of the cough outcomes (cough counts, C2, C5, cough score) in control subjects and children with cough. Atopy does not influence important cough outcome measures in children with and without chronic cough. However, age, but not sex, influences CRS in children. Unlike adult data, sex does not affect objective counts or cough score in children with and without chronic cough. Studies on cough in children should be age matched, but matching for atopic status and sex is less important.
Publisher: Bioscientifica
Date: 07-2005
DOI: 10.1677/JOE.1.06030
Abstract: Females have a significantly greater life expectancy than males, which in part may be due to the cardio-protective effects of the female sex hormone, estrogen, on vascular function. However, the sex-specific mechanisms contributing to these differences are complex and not fully understood. Previously we have reported that corticotropin-releasing hormone (CRH) has potent dilator effects in the female skin circulation via mast cell degranulation. Furthermore the dilator response to CRH was more enhanced in females than in age-matched males, suggesting that estrogens may be involved. In this study we examined whether CRH-induced dilation and endothelial cell-dependent dilation in the skin circulation of pre-menopausal females were associated with changes in estrogen during the menstrual cycle. CRH-induced dilation (1 nM) was enhanced in the presence of high circulating concentrations of estrogen and a positive correlation was identified between CRH-induced dilation and plasma estrogen concentrations. Endothelial cell-dependent dilation was examined using acetylcholine. Acetylcholine-induced dilation (1 nM) was not correlated with circulating concentrations of estrogen. These data suggest the variation in CRH-induced dilation in the skin microvasculature during the menstrual cycle may be due to estrogenic effects on mast cell function and not due to direct changes in endothelial cell function.
Publisher: Wiley
Date: 08-1998
DOI: 10.1002/(SICI)1099-0496(199808)26:2<97::AID-PPUL4>3.0.CO;2-E
Abstract: Recombinant human deoxyribonuclease (rhDNase) has been shown to reduce sputum viscoelasticity and to improve lung function in patients with cystic fibrosis (CF). The aim of this study was to determine whether airway inflammation would decrease after administration of rhDNase. Twenty patients with CF and chronic suppurative lung disease inhaled 2.5 mg of rhDNase daily for 1 month. Before and after the 1-month trial, lung function was measured and sputum was obtained, either after spontaneous expectoration or after sputum induction with hypertonic saline. Sputum total cell and differential counts were measured using techniques previously described. The mean age of the patients was 16.8 years (range, 6.7-27.5). After 1 month of rhDNase, mean FEV1 increased from a baseline of 62.3% predicted to 70.8% (P= 0.02, paired t test) and FVC increased from 74.4% to 83.9% predicted (P=0.007). No significant differences were found in sputum cytology before or after rhDNase (median total cell counts 16.0 x 10(6)/ml vs. 19.3 x 10(6)/ml, P=0.68). Thirteen patients had a 10% or greater increase in FEV1 after rhDNase (responders). Initial lung function was less in responders than in nonresponders (53.5% vs. 78.6%, P=0.007). There was no significant change in total cell count and neutrophil count after rhDNase in either responders or nonresponders. We conclude that airway inflammation, as measured by total cell counts in sputum, was a prominent feature in cystic fibrosis, and neutrophils were the dominant inflammatory cells. Although the administration of rhDNase resulted in significant improvements in FEV1, there was no evidence of accompanying changes in airway inflammation.
Publisher: BMJ
Date: 10-1995
DOI: 10.1136/ADC.73.4.321
Abstract: Adolescents with asthma, their peers, and their teachers were studied in order to establish the level of knowledge concerning asthma and its management, their attitudes towards asthma, and the degree quality of life impairment due to asthma. A community survey was conducted among year 8 high school students (n = 4161) and their teachers (n = 1104). There was a good response rate to the questionnaires from students (93%) and teachers (61%). Twenty three per cent of students had asthma and this caused mild to moderate quality of life impairment, particularly with strenuous exercise. Asthma was provoked by passive smoke exposure in 30% of asthmatic students and up to 51% of students avoided situations because of asthma triggers. Asthma knowledge was low in teachers (mean score 14.90 out of a possible 31), students without asthma (11.25) and students with asthma (14.50). Specific knowledge on the prevention and treatment of exercise induced asthma was poor. There was a moderate degree of tolerance towards asthma among all three groups. Most considered internal locus of control as important, although students without asthma also considered chance to be a determinant of outcomes for people with asthma. Asthma is a common cause of quality of life impairment among year 8 high school students. Although specific knowledge on asthma is low, students and teachers hold favourable attitudes towards asthma. There are opportunities to intervene and improve asthma management among adolescents.
Publisher: Elsevier BV
Date: 06-2005
Publisher: Springer Science and Business Media LLC
Date: 02-2003
DOI: 10.1007/BF03256635
Publisher: Springer Netherlands
Date: 2010
Publisher: Oxford University Press (OUP)
Date: 08-2005
DOI: 10.1093/AJE/KWI184
Abstract: A number of studies have investigated two common polymorphisms in the beta(2)-adrenoceptor gene, Arg/Gly16 and Gln/Glu27, in relation to asthma susceptibility. The authors performed a meta-analysis of each polymorphism, as well as haplotype analysis, for adult and pediatric populations separately, using published data, supplemented by additional data requested from the original authors. In idual analysis detected no effect of Arg/Gly16 in adults but did suggest a recessive protective effect of Gly16 for children, with an odds ratio of 0.71 (95% confidence interval (CI): 0.53, 0.96) compared with the other genotypes. Results for Gln/Glu27 in adults seem to indicate that heterozygotes are at decreased risk of asthma than either homozygote (odds ratio = 0.73, 95% CI: 0.62, 0.87), although the studies are heterogeneous in children, the Glu/Glu genotype has a decreased risk of asthma (odds ratio = 0.60, 95% CI: 0.35, 0.99) compared with the other genotypes. Despite the proximity of these two polymorphic sites, the linkage disequilibrium coefficient of 0.41 was not high (p < 0.001). Haplotype analysis suggests that there may be an interaction between the two sites, with a lower risk of asthma associated with the Glu27 allele (compared with Gln27), and that this risk is modified by the allele at position 16.
Publisher: Elsevier BV
Date: 2008
Publisher: Wiley
Date: 21-06-2013
DOI: 10.1111/RESP.12068
Abstract: Severe asthma exacerbations during pregnancy are a common complication leading to poor health outcomes for both the mother and the baby. Asthma exacerbations are caused most frequently by respiratory viruses. A balance between antiviral and inflammatory immune responses is critical during pregnancy the balance may be altered by asthma and respiratory virus infection. Peripheral blood mononuclear cells (PBMCs) were isolated from (i) non-pregnant healthy controls, (ii) pregnant non-asthmatics, (iii) post-partum non-asthmatics, (iv) non-pregnant asthmatics (v) pregnant asthmatics, and (vi) post-partum asthmatics. Cells were cultured in vitro with the mitogen phytohaemagglutinin or with a strain of the 2009 pandemic swine influenza. Interferon (IFN)-γ, interleukin (IL)-10 and IL-17 protein were measured from culture supernatant. Neutrophil counts were obtained in s les from pregnant and post-partum women. Following the phytohaemagglutinin stimulation of PBMCs, pregnant asthmatics had significantly higher IL-17 and significantly lower IFN-γ responses compared with healthy non-pregnant women. Following infection with influenza, a significant reduction was also observed in IFN-γ and IL-10 production from PBMC of pregnant asthmatics. The IL-17 response to phytohaemagglutinin correlated with the neutrophil percentage. Differences in IFN-γ, IL-10 and IL-17 were found to persist for at least 6 months post-partum. A reduction in antiviral and regulatory immunity with increased inflammation during pregnancy occurs in PBMC from pregnant women with asthma. This novel information may relate to the increased susceptibility and disease severity to respiratory virus infections observed during pregnancy.
Publisher: Elsevier BV
Date: 03-2004
Publisher: S. Karger AG
Date: 11-09-2013
DOI: 10.1159/000352053
Abstract: b i Background: /i /b The progression of obstructive airway diseases (OADs) including asthma, chronic obstructive pulmonary disease (COPD) and asthma-COPD overlap syndrome in older adults is not well understood. b i Objective: /i /b To examine the prognosis of OADs and to identify potential determinants for longitudinal changes in clinical outcomes. b i Methods: /i /b We consecutively recruited 99 older adults ( years) with OADs who underwent a multidimensional assessment at baseline and 4 years which involved spirometry, 6-min walk distance (6MWD), assessments of health status (Saint George's Respiratory Questionnaire, SGRQ), comorbidity, and serum and sputum biomarkers. All-cause mortality and respiratory hospitalisation during the follow-up period were recorded. Clinical outcomes were compared between basal and final visits, and changes in clinical outcomes were compared among asthma, COPD and asthma-COPD overlap groups. Associations between clinical parameters, biomarkers and prognosis were examined. b i Results: /i /b After a median follow-up of 4.2 years, outcome data were available for 75 (75.8%) patients. There were 16 (16.2%) deaths. The BODE index predicted all-cause mortality in older people with OADs. While spirometry, 6MWD and SGRQ deteriorated significantly over the 4 years, there was significant heterogeneity in the longitudinal changes in these clinical outcomes. Participants with COPD had a significant decline in FEV sub /sub (p = 0.003), SGRQ (p = 0.030) and 6MWD [decline of 75.5 (93.4) m, p = 0.024]. The change in 6MWD was lower in the asthma-COPD overlap group. Airflow reversibility was associated with a reduced decline in 6MWD. b i Conclusion: /i /b COPD patients had a poor prognosis compared with asthma and asthma-COPD overlap patients. The BODE index is a useful prognostic indicator in older adults with OADs. Both airway disease diagnosis and BODE index warrant specific attention in clinical practice.
Publisher: American College of Physicians
Date: 10-1995
DOI: 10.7326/0003-4819-123-7-199510010-00002
Abstract: To compare the action points in published asthma management plans with those derived from quality-control analysis of peak expiratory flow recordings. Longitudinal observational study. An ambulatory asthma education and management program in a tertiary care hospital. 35 adults with asthma and exacerbation of asthma. Peak expiratory flow diaries and symptom recordings. Asthma action points from published asthma management guidelines had poor operating characteristics. The success rate was 35% when the action point was a peak expiratory flow rate less than 60% of the patient's best peak flow. The success rate improved to 88% when the action point was a peak expiratory flow rate less than 80% of the patient's best peak flow. Published action points had a high failure rate. Peak flow decreased to below the published action points during a stable period of asthma in 7% to 51% of patients studied. Action points defined using quality-control analysis did significantly better. A peak flow value less than 3 standard deviations below the patient's mean peak flow detected 84% of exacerbations and had a low failure rate (19%). Other quality-control tests had sensitivities of 91% and 71%. Quality-control action points could detect exacerbations up to 4.5 days earlier than conventional methods. In idualized action points can be derived for patients with asthma by applying quality-control analysis to peak flow recordings. These action points are more sensitive in detecting exacerbations of asthma and have fewer false-positive results. Action plans developed in this manner should be more useful for the early detection of deteriorating asthma.
Publisher: European Respiratory Society (ERS)
Date: 12-2021
DOI: 10.1183/20734735.0118-2021
Abstract: COPD is complex and heterogeneous with respect to its aetiology, clinical presentation, phenotypes and biological mechanisms. Despite this, COPD is still diagnosed and treated according to simple clinical measures, including airflow limitation, symptoms and exacerbation frequency, leading to failure to recognise the disease's heterogeneity and/or to provide targeted interventions. COPD continues to have a very large burden of disease with suboptimal outcomes for people with the disease, including frequent hospitalisation with exacerbations, rapid lung function decline, multimorbidity and death from respiratory failure. In light of this, there have been increasing calls for a renewed taxonomy with better characterisation of COPD phenotypes and endotypes. This would allow the unravelling of COPD's complexity and heterogeneity, the implementation of targeted interventions and improved patient outcomes. The treatable traits strategy is a proposed vehicle for the implementation of precision medicine in chronic airway diseases. In this review, in addition to summarising the key knowledge on the heterogeneity of COPD, we refer to the existing evidence pertaining to the treatable traits strategy as applied in COPD and discuss implementation in different settings.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2006
DOI: 10.1097/01.MCP.0000199808.64882.12
Abstract: This review examines the commencement of maintenance pharmacotherapy for asthma: inhaled corticosteroids alone or in combination with long-acting beta2 agonists. A systematic review of randomized controlled trials has examined the starting dose of inhaled corticosteroids (high, moderate, low) and the dose regimen (step down versus constant) in asthma. There was no significant difference in key asthma outcomes for step down compared with a constant inhaled corticosteroid dose. There was no significant difference between high or moderate dose inhaled corticosteroid groups (n=11) for morning peak expiratory flow, symptoms and rescue medication use. There may be a benefit from high-dose inhaled corticosteroids for airway hyperresponsiveness. There was a significant improvement in peak expiratory flow and nocturnal symptoms in favour of a moderate inhaled corticosteroid dose compared with low-dose treatment. Long-acting beta2 agonists combined with inhaled corticosteroids as initial asthma therapy has been examined in a systematic review of nine randomized controlled trials. Inhaled corticosteroids combined with long-acting beta2 agonists led to significant improvements in forced expiratory volume in 1 s, morning peak expiratory flow, symptom score and symptom-free days but no difference in exacerbations requiring oral corticosteroids. A randomized controlled trial of patients with uncontrolled asthma found a benefit of escalating doses of salmeterol/fluticasone compared with fluticasone on asthma control. Initial inhaled corticosteroid therapy should begin with a constant, moderate dose. Initial therapy with long-acting beta2 agonist and inhaled corticosteroids achieves superior improvement in symptoms and lung function, and at a quicker rate than inhaled corticosteroids alone. There is no benefit in terms of reduced exacerbations unless an escalating inhaled corticosteroid dose strategy is used.
Publisher: The Endocrine Society
Date: 04-2002
DOI: 10.1210/JC.87.4.1660
Publisher: Springer Science and Business Media LLC
Date: 22-10-2021
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.RESINV.2015.02.004
Abstract: Patients with chronic obstructive pulmonary diseases (COPD) often experience comorbid conditions. The most common comorbidities that have been associated with COPD include cardiovascular diseases, lung cancer, metabolic disorder, osteoporosis, anxiety and depression, skeletal muscle dysfunction, cachexia, gastrointestinal diseases, and other respiratory conditions. Not only are comorbidities common but they also considerably influence disease prognosis and patients׳ health status, and are associated with poor clinical outcomes. However, perusal of literature indicates that little has been done so far to effectively assess, manage, and treat comorbidities in patients with COPD. The aim of this review is to comprehensively narrate the comorbid conditions that often coexist with COPD, along with their reported prevalence and their significant impacts in the disease management of COPD. A perspective on integrated disease management approaches for COPD is also discussed.
Publisher: BMJ
Date: 08-08-2017
Publisher: Elsevier BV
Date: 10-2021
Publisher: Wiley
Date: 20-03-2011
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JAIP.2019.03.050
Abstract: People with chronic cough can experience significant quality-of-life impairment. New concepts based around cough reflex hypersensitivity are leading to improved management strategies and showing promise in relieving the distress from persistent cough. The clinical cough assessment seeks to classify patients on the basis of symptom duration, and to identify and manage exposures and diseases that activate the afferent limb of the cough reflex. Cough hypersensitivity is also addressed by managing laryngeal dysfunction with speech pathology therapy and managing central cough reflex sensitization with neuromodulators. There are prospects for novel therapies based around several new treatment targets.
Publisher: Scientific and Practical Reviewed Journal Pulmonology
Date: 10-06-2021
DOI: 10.18093/0869-0189-2021-31-3-272-295
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including metaanalyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force’s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: • suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes • suggest using a blood eosinophil cut-point ≥150 μL −1 to guide anti-IL-5 initiation in adult patients with severe asthma • suggest considering specific eosinophil (≥260 μL −1 ) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy • suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4 – 5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies • suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype • suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
Publisher: Wiley
Date: 10-2020
DOI: 10.1111/AJO.13061
Abstract: The use of fractional exhaled nitric oxide (FeNO)-based asthma management during pregnancy can significantly reduce asthma exacerbations in non-smoking pregnant women. The feasibility of implementing this strategy into antenatal care has not been explored. To examine the feasibility of implementing FeNO-based asthma management into antenatal clinics in New South Wales (NSW) Australia. Semi-structured face-to-face interviews with video elicitation were conducted with healthcare professionals (HCPs) providing antenatal care in one of two hospital-based antenatal clinics in NSW, Australia. The video shown demonstrated the use of the FeNO instrument and other aspects of the management strategy, in antenatal care. Interviews were recorded, transcribed and analysed using qualitative content analysis. A total of 20 interviews were conducted with 15 midwives, four obstetricians, and one general practitioner. Two main themes and ten sub-themes arose: Getting a number (sub-themes: engaging, technically easy, objective, predictive, reassuring) and Resourcing (sub-themes: time and timing, systems, staff, education and cost). Comments included: 'It's easy, fast and effective' and 'the main barrier is time'. All HCPs felt capable of facilitating the FeNO-based management strategy, with appropriate education, and were willing to undertake this strategy, saying: '…it would be perfectly acceptable for a midwife or doctor to do it' also, 'they don't necessarily need to see a physician, it's something that midwives would take on generally…'. Participants in this study considered FeNO-based asthma management for pregnant women to be a feasible addition to antenatal care following appropriate provision of resources and education.
Publisher: Wiley
Date: 19-09-2019
DOI: 10.1111/RESP.13389
Abstract: A new taxonomic and management approach, termed treatable traits, has been proposed for airway diseases including severe asthma. This study examined whether treatable traits could be identified using registry data and whether particular treatable traits were associated with future exacerbation risk. The Australasian Severe Asthma Web-Based Database (SAWD) enrolled 434 participants with severe asthma and a comparison group of 102 participants with non-severe asthma. Published treatable traits were mapped to registry data fields and their prevalence was described. Participants were characterized at baseline and every 6 months for 24 months. In SAWD, 24 treatable traits were identified in three domains: pulmonary, extrapulmonary and behavioural/risk factors. Patients with severe asthma expressed more pulmonary and extrapulmonary treatable traits than non-severe asthma. Allergic sensitization, upper-airway disease, airflow limitation, eosinophilic inflammation and frequent exacerbations were common in severe asthma. Ten traits predicted exacerbation risk among the strongest were being prone to exacerbations, depression, inhaler device polypharmacy, vocal cord dysfunction and obstructive sleep apnoea. Treatable traits can be assessed using a severe asthma registry. In severe asthma, patients express more treatable traits than non-severe asthma. Traits may be associated with future asthma exacerbation risk demonstrating the clinical utility of assessing treatable traits.
Publisher: Elsevier BV
Date: 08-2020
Publisher: BMJ
Date: 13-09-2012
DOI: 10.1136/THORAXJNL-2011-200708
Abstract: Acute respiratory tract infections are common ailments to all in iduals and the human rhinoviruses (HRVs) cause most of these infections. Pregnant women have increased susceptibility and disease severity to viral infections like influenza and HRVs, as do asthmatics. Successful pregnancy requires immunological modulation to permit fetal tolerance. To determine whether pregnant women have reduced innate antiviral interferon (IFN) responses to HRV infection compared with non-pregnant women. An in vitro culture system was used, where peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of 54 women, including 10 stable asthmatics who were pregnant and 10 who were not pregnant, 10 non-asthmatic women who were pregnant, 10 who were ≥6 months post partum and 10 who were not pregnant. S les were also collected from four exacerbating pregnant asthmatics. PBMCs were cultured with HRV43 and HRV1B. The antiviral proteins IFNα and IFNλ were measured from culture supernatants by ELISA. Compared with healthy non-pregnant women, pregnant women had significantly reduced innate IFN responses to HRV infection (p<0.02), persisting ≥6 months post partum (p≤0.02). Pregnant asthmatics had significantly reduced IFNλ responses compared with healthy non-pregnant women (p≤0.034), while during current asthma exacerbations a decrease in IFNα (p≤0.023) and IFNλ (p=0.007) was observed. Induction by a TLR7 agonist induced a similar pattern of decreased innate IFNs during pregnancy as observed when HRV was the inducing agent. Reduced antiviral IFNs during pregnancy and asthma provide an important mechanism for increased susceptibility, morbidity and mortality in pregnant women with respiratory viral infection.
Publisher: Elsevier BV
Date: 2018
Publisher: Elsevier BV
Date: 02-2022
Publisher: Wiley
Date: 16-09-2016
DOI: 10.1111/RESP.14596
Publisher: Wiley
Date: 26-12-2014
DOI: 10.1111/CEA.12323
Publisher: Informa UK Limited
Date: 05-01-2019
DOI: 10.1080/14767058.2017.1419176
Abstract: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma, and whether higher vitamin D levels are associated with fewer adverse respiratory outcomes in their infants. Pregnant women with asthma, recruited from John Hunter Hospital Newcastle Australia (latitude 33°S), had serum total 25-hydroxyvitamin-D (25(OH)D) measured at 16 and 35 weeks gestation. Infant respiratory outcomes were collected at 12 months by parent-report questionnaire. Mother-infant dyads were grouped by serum 25(OH)D during pregnancy: 25(OH)D < 75 nmol/L (at both time-points) versus 25(OH)D ≥ 75 nmol/L (at one or both time-points). In 52 pregnant women with asthma, mean serum 25(OH)D levels were 61 (range 26-110) nmol/L at 16 weeks, and 65 (range 32-116) nmol/L at 35 weeks, gestation. Thirty-one (60%) women had 25(OH)D < 75 nmol/L at both time-points 21 (40%) had 25(OH)D ≥ 75 nmol/L at one or both time-points. Maternal 25(OH)D < 75 nmol/L during pregnancy was associated with a higher proportion of infants with "wheeze ever" at 12 months, compared with 25(OH)D ≥ 75 nmol/L (71 versus 43%, p = .04). Infant acute-care presentations (45 versus 13%, p = .02) and oral corticosteroid use (26 versus 4%, p = .03) due to "asthma/wheezing" were higher in the maternal group with 25(OH)D < 75 nmol/L, versus ≥75 nmol/L. Most pregnant women with asthma had low vitamin D status, which persisted across gestation. Low maternal vitamin D status was associated with greater risk of adverse respiratory outcomes in their infants, a group at high risk of developing childhood asthma.
Publisher: MDPI AG
Date: 18-12-2020
DOI: 10.3390/NU12123872
Abstract: Measurement of vitamin D status has significant use in clinical and research settings, including during pregnancy. We aimed to assess the agreement of total 25-hydroxyvitamin D (25(OH)D) concentration, and its three analytes (25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2) and Epi-25-hydroxyvitamin D3 (Epi-25(OH)D3)), in plasma and serum s les collected during pregnancy, and to examine the proportion of women who change vitamin D status category based on s le type. Matching s les were collected from n = 114 non-fasting women between 12–25 weeks gestation in a clinical trial in Newcastle, Australia. S les were analysed by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to quantify total 25(OH)D and its analytes and examined using Bland-Altman plots, Pearson correlation (r), intraclass correlation coefficient and Cohen’s Kappa test. Serum total 25(OH)D ranged from 33.8–169.8 nmol/L and plasma ranged from 28.6–211.2 nmol/L. There was a significant difference for total 25(OH)D based on s le type (measurement bias 7.63 nmol/L for serum vs plasma (95% Confidence Interval (CI) 5.36, 9.90, p ≤ 0.001). The mean difference between serum and plasma concentrations was statistically significant for 25(OH)D3 (7.38 nmol/L 95% CI 5.28, 9.48, p ≤ 0.001) and Epi-25(OH)D3 (0.39 nmol/L 95% CI 0.14, 0.64, p = 0.014). Of 114 participants, 28% were classified as vitamin D deficient ( nmol/L) or insufficient ( nmol/L) based on plasma s le and 36% based on serum s le. Nineteen (16.7%) participants changed vitamin D status category based on s le type. 25-hydroxyvitamin D quantification using LC-MS/MS methodology differed significantly between serum and plasma, yielding a higher value in plasma this influenced vitamin D status based on accepted cut-points, which may have implications in clinical and research settings.
Publisher: American Thoracic Society
Date: 02-2019
Abstract: The inflammatory response during allergen-induced asthma was assessed using serial measures of peripheral blood eosinophils (Eo), basophils (B), and Eo/B progenitor cells (Eo/B-CFU). A group of 14 stable asthmatic in iduals (beta 2-agonists only as needed) had inhalation provocation tests with allergen (18 tests in total) and with diluent. Serial blood s les were taken before and 1 and 24 h after the tests methylcellulose cultures for Eo/B-CFU and granulocyte-macrophage (GM-CFU) were scored at 14 days. Circulating Eo, B, and Eo/B-CFU were increased at 24 h after allergen inhalation when this resulted in increased histamine airway responsiveness (n = 13). In the 5 subjects with isolated early asthmatic responses the Eo, B, and Eo/B-CFU counts did not change. There was no change in the GM-CFU after allergen. The ratio change in circulating Eo/B-CFU was negatively correlated with baseline histamine airway responsiveness (r = -0.8, p less than 0.05). Four subjects who had an isolated early response and no blood changes to one allergen developed an increase in histamine airway responsiveness and an increase in Eo, B, and Eo/B progenitors after inhalation of a second different allergen. The results indicate that in subjects with an allergen-induced increase in histamine airway responsiveness, an inflammatory response occurs that includes an increase in the number of Eo/B progenitors. This response, possibly mediated by Eo/B growth and differentiation factors, could lead to the accumulation of these cells in the airway and contribute to the airways inflammation present in asthma.
Publisher: Elsevier BV
Date: 03-1988
DOI: 10.1016/0041-3879(88)90041-4
Abstract: Two cases are described in which the diagnosis of pulmonary tuberculosis was suspected on both clinical and radiological grounds. Sputum smear and culture were negative for acid fast bacilli. Consequently a bronchoscopy and bronchial washings from the affected lobe were undertaken. While this procedure achieved a positive diagnosis of pulmonary tuberculosis, it also resulted in a significant extension of the disease.
Publisher: European Respiratory Society (ERS)
Date: 04-2003
DOI: 10.1183/09031936.03.00001803
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus, causing severe asthma that may progress to bronchiectasis. Sputum neutrophilia can occur in association with sputum eosinophilia and correlates with the degree of bronchiectasis. The mechanisms of sputum neutrophilia in ABPA are not known. The aim of this study was to investigate the role of the chemokine interleukin (IL)-8 in sputum neutrophilia in ABPA. Induced sputum was obtained from subjects with ABPA (n=29), and compared to nonsensitised asthma (n=9) and healthy controls (n=21). Semiquantitative polymerase chain reaction was used to assess IL-8 gene expression in induced sputum and IL-8 protein was measured by enzyme-linked immunosorbent assay. Sputum IL-8 protein was significantly higher in ABPA compared to asthma and controls. IL-8 messenger ribonucleic acid/glyceraldehyde-3-phosphate dehydrogenase ratio was elevated in ABPA compared to asthma and controls. Sputum IL-8 correlated with sputum neutrophils, matrix metalloproteinase-9 levels and forced expiratory volume in one second. Interleukin-8 gene expression and protein release were increased in allergic bronchopulmonary aspergillosis and correlated with airway neutrophilia and airway obstruction. The interleukin-8-mediated neutrophil influx in allergic bronchopulmonary aspergillosis may induce lung damage via release of matrix metalloproteinase-9, potentially leading to bronchiectasis.
Publisher: Wiley
Date: 04-2006
Publisher: Wiley
Date: 15-09-2023
DOI: 10.1111/RESP.14593
Publisher: European Respiratory Society (ERS)
Date: 07-2022
DOI: 10.1183/13993003.00298-2022
Abstract: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide ( F ENO )-based asthma management improves perinatal outcomes compared to usual care. The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6–12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). Pregnant women with current asthma were recruited 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention OR 1.21, 95% CI 0.94–1.56 p=0.15), preterm birth (OR 1.14, 95% CI 0.78–1.68), SGA (OR 1.06, 95% CI 0.78–1.68), perinatal mortality (OR 3.62, 95% CI 0.80–16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89–1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69–2.05). F ENO -guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.
A Sputum 6 Gene Expression Signature Predicts Inflammatory Phenotypes and Future Exacerbations of COPD
Publisher: Informa UK Limited
Date: 07-2020
DOI: 10.2147/COPD.S245519
Publisher: Informa UK Limited
Date: 31-05-2020
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.RMED.2010.04.003
Abstract: Asthma guidelines recommend reducing inhaled corticosteroids (ICS) to the minimum effective dose, but the timing of long-acting beta(2)-agonist (LABA) withdrawal is unclear. Recent FDA guidelines recommend LABA withdrawal once asthma is well-controlled. This 13-month double-blind study of patients taking high-dose combination therapy investigated the effect of discontinuation of LABA before ICS down-titration. Adults using salmeterol/fluticasone combination (SFC) 50/500 microg bd were randomized to SFC 50/500 microg bd or fluticasone propionate (FP) 500 microg bd, with subsequent ICS down-titration 8-weekly using a clinical algorithm. The primary outcome was mean daily FP dose, including ICS for exacerbations. 82 subjects were randomized. Asthma was well-controlled at baseline, with mean FEV(1) 84.8% predicted and Asthma Control Questionnaire (ACQ) score 0.9. There was no significant difference in mean daily FP dose (SFC: 721 microg, FP:816 microg, p = 0.3), but final dose was lower with SFC (534 microg cf. 724 microg, p = 0.005). ICS dose was reduced by >or=80% in 41% SFC and 15% FP patients. Ambulatory lung function was significantly higher with SFC, but there were no differences between groups in rescue beta(2)-agonist use, clinic spirometry, airway responsiveness, ACQ, sputum eosinophils or FeNO. Baseline airway responsiveness, and pre-reduction blood eosinophils, were significant predictors of mean daily FP dose and dose reduction failure respectively. Many patients prescribed high-dose combination therapy may be over-treated. Substantial reductions in dose can be achieved with a clinical algorithm, reaching lower FP doses with SFC than FP without losing asthma control or increasing disease activity. This study was commenced before mandatory registration of clinical trials.
Publisher: BMJ
Date: 03-2001
Abstract: A systematic literature review was conducted to assess the effect of treating reflux oesophagitis on asthma outcomes. Randomised controlled trials of reflux oesophagitis treatment in adults or children that reported asthma health outcomes were included and assessed in accordance with the standard Cochrane systematic review process. Patients were typically adults with asthma and concurrent symptomatic gastro-oesophageal reflux who received interventions that included pharmacological therapy, conservative management, and surgery. The following outcome measures were assessed: lung function, peak expiratory flow, asthma symptoms, asthma medications, and nocturnal asthma. From 22 potentially relevant published and unpublished randomised controlled trials, 12 were included. Treatment duration ranged from 1 week to 6 months. Eight trials reported that treatment improved at least one asthma outcome, but these outcomes differed between trials. Overall, treatment of reflux oesophagitis did not consistently improve forced expiratory volume in one second (FEV(1)), peak expiratory flow rate, asthma symptoms, nocturnal asthma symptoms, or use of asthma medications in asthmatic subjects. Significant improvement in wheeze was reported in two studies. The published literature does not consistently support treatment of reflux oesophagitis as a means of controlling asthma. Further large randomised controlled trials in subjects with a demonstrated temporal relationship between gastro-oesophageal reflux and asthma are needed. These trials should be conducted over at least 6 months to allow adequate time to observe a treatment effect.
Publisher: American Thoracic Society
Date: 11-2016
Publisher: Wiley
Date: 07-06-2022
DOI: 10.1111/RESP.14302
Abstract: Severe asthma (SA) is a heterogeneous disease. Transcriptomic analysis contributes to the understanding of pathogenesis necessary for developing new therapies. We sought to identify and validate mechanistic pathways of SA across two independent cohorts. Transcriptomic profiles from U‐BIOPRED and Australian NOVocastrian Asthma cohorts were examined and grouped into SA, mild/moderate asthma (MMA) and healthy controls (HCs). Differentially expressed genes (DEGs), canonical pathways and gene sets were identified as central to SA mechanisms if they were significant across both cohorts in either endobronchial biopsies or induced sputum. Thirty‐six DEGs and four pathways were shared across cohorts linking to tissue remodelling/repair in biopsies of SA patients, including SUMOylation, NRF2 pathway and oxidative stress pathways. MMA presented a similar profile to HCs. Induced sputum demonstrated IL18R1 as a shared DEG in SA compared with healthy subjects. We identified enrichment of gene sets related to corticosteroid treatment immune‐related mechanisms activation of CD4 + T cells, mast cells and IL18R1 and airway remodelling in SA. Our results identified differentially expressed pathways that highlight the role of CD4 + T cells, mast cells and pathways linked to ongoing airway remodelling, such as IL18R1, SUMOylation and NRF2 pathways, as likely active mechanisms in the pathogenesis of SA.
Publisher: Wiley
Date: 21-07-2003
Publisher: Elsevier BV
Date: 07-2021
Publisher: BMJ
Date: 14-07-2001
Publisher: Wiley
Date: 24-11-2020
DOI: 10.1002/PPUL.25165
Publisher: European Respiratory Society (ERS)
Date: 07-03-2019
DOI: 10.1183/13993003.02058-2018
Abstract: “Treatable traits” have been proposed as a new paradigm for the management of airway diseases, particularly complex disease, which aims to apply personalised medicine to each in idual to improve outcomes. Moving new treatment approaches from concepts to practice is challenging, but necessary. In an effort to accelerate progress in research and practice relating to the treatable traits approach, the Treatable Traits Down Under International Workshop was convened in Melbourne, Australia in May 2018. Here, we report the key concepts and research questions that emerged in discussions during the meeting. We propose a programme of research that involves gaining international consensus on candidate traits, recognising the prevalence of traits, and identifying a potential hierarchy of traits based on their clinical impact and responsiveness to treatment. We also reflect on research methods and designs that can generate new knowledge related to efficacy of the treatable traits approach and consider multidisciplinary models of care that may aid its implementation into practice.
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/IMJ.13166
Abstract: Severe asthma is a high impact disease. Omalizumab targets the allergic inflammatory pathway however, effectiveness data in a population with significant comorbidities are limited. To describe severe allergic asthma, omalizumab treatment outcomes and predictors of response among the Australian Xolair Registry participants. A web-based post-marketing surveillance registry was established to characterise the use, effectiveness and adverse effects of omalizumab (Xolair) for severe allergic asthma. Participants (n = 192) (mean age 51 years, 118 female) with severe allergic asthma from 21 clinics in Australia were assessed, and 180 received omalizumab therapy. They had poor asthma control (Asthma Control Questionnaire, ACQ-5, mean score 3.56) and significant quality of life impairment (Asthma-related Quality of Life Questionnaire score 3.57), and 52% were using daily oral corticosteroid (OCS). Overall, 95% had one or more comorbidities (rhinitis 48%, obesity 45%, cardiovascular disease 23%). The omalizumab responder rate, assessed by an improvement of at least 0.5 in ACQ-5, was high at 83%. OCS use was significantly reduced. The response in participants with comorbid obesity and cardiovascular disease was similar to those without these conditions. Baseline ACQ-5 ≥ 2.0 (P = 0.002) and older age (P = 0.05) predicted the magnitude of change in ACQ-5 in response to omalizumab. Drug-related adverse events included anaphylactoid reactions (n = 4), headache (n = 2) and chest pains (n = 1). Australian patients with severe allergic asthma report a high disease burden and have extensive comorbidity. Symptomatic response to omalizumab was high despite significant comorbid disease. Omalizumab is an effective targeted therapy for severe allergic asthma with comorbidity in a real-life setting.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.JAIP.2017.09.022
Abstract: Physical inactivity and sedentary time are distinct behaviors that may be more prevalent in severe asthma, contributing to poor disease outcomes. Physical activity and sedentary time in severe asthma however have not been extensively examined. We aimed to objectively measure physical activity and sedentary time in people with severe asthma compared with age-matched control participants, describing the associations of these behaviors with clinical and biological outcomes. We hypothesized that people with severe asthma would be less active and more sedentary. In addition, more activity and less sedentary time would be associated with better clinical outcomes and markers of systemic and airway inflammation in people with severe asthma. Adults with severe asthma (n = 61) and sex- and age-matched controls (n = 61) underwent measurement of lung function, exercise capacity, asthma control, health status, and airway and systemic inflammation. Physical activity and sedentary time were measured using an accelerometer. The severe asthma and control groups were matched in terms of age and sex (32 [53%] females in each group). In iduals with severe asthma accumulated less minutes per day in moderate and higher intensity activity, median (IQR) 21.9 (12.9-36.0) versus 41.7 (29.5-65.2) (P < .0001) and accumulated 2,232 fewer steps per day (P = .0002). However, they engaged in more light-intensity physical activity. No differences were found for sedentary time. In a multivariate regression model, steps per day were strongly and independently associated with better exercise capacity in participants with severe asthma (coefficient, 0.0169 95% CI, 0.008-0.025 P < .001). People with severe asthma perform less moderate and vigorous activity than do controls. Higher levels of activity and lower levels of sedentary time are associated with better exercise capacity, asthma control, and lower levels of systemic inflammation.
Publisher: European Respiratory Society (ERS)
Date: 30-07-2020
DOI: 10.1183/13993003.00240-2020
Abstract: Asthma is a heterogeneous and complex disease, and the description of asthma phenotypes based on extrapulmonary treatable traits has not been previously reported. to identify and characterise clusters based on clinical, functional, anthropometrical, and psychological characteristics in participants with moderate-to-severe asthma. This is a cross-sectional multicentre study involving centres from Brazil and Australia. Participants (N=296) with moderate-to-severe asthma were consecutively recruited. Physical activity and sedentary time, clinical asthma control, anthropometric data, pulmonary function, psychological, and health-status were evaluated. Participants were classified by hierarchical cluster analysis and the clusters compared using ANOVA, Kruskal-Wallis, and Chi-square tests. Multiple logistic and linear regression models were performed to evaluate the association between variables. We identified four clusters: (1)controlled asthma who were physically active, (2)uncontrolled asthma who were physically inactive and more sedentary, (3)uncontrolled asthma with low physical activity, who were also obese and experienced anxiety and/or depression symptoms (4)very uncontrolled asthma, who were physically inactive, more sedentary, obese and experienced anxiety and/or depression symptoms. Higher levels of sedentary time, female sex, and anxiety symptoms were associated with increased odds of exacerbation risk while being more active showed a protective factor for hospitalisation. Asthma control was associated with sex, the occurrence of exacerbation, physical activity, and health-status. Traits such as physical inactivity, obesity, and symptoms of anxiety and/or depression were associated with worse asthma outcomes, and closely and inextricably with asthma control. This cluster analysis supports the importance of assessing extrapulmonary traits to improve personalised management and outcomes for people with moderate and severe asthma.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.RMED.2011.10.007
Abstract: Post infectious chronic cough is a disabling illness. In 2009 an influenza pandemic occurred due to a novel strain of H1N1 influenza. Prolonged symptoms such as chronic cough remaining after the infection has cleared have not been examined. This study sought to investigate the prevalence, characteristics and mechanism of chronic cough following laboratory-confirmed H1N1 2009 influenza. Out of 836 eligible patients who had been tested by PCR assay for H1N1, 136 responders participated. Nineteen underwent detailed clinical investigation of cough, and airway function using symptom questionnaires, hypertonic saline challenge, and cough monitoring. Post H1N1 chronic cough was reported by 43%, and chronic cough after non-H1N1 infection was present in 36% of participants. In the participants who progressed to testing objectively measured cough frequency was 3 times greater there was a 9-fold increase in cough reflex sensitivity and greater quality of life impairment in the participants with postinfectious chronic cough following H1N1 infection than for the participants with no cough following H1N1 infection and for the healthy controls. This study reports the first evaluation of chronic cough following H1N1 infection. Patients that develop chronic cough after H1N1 infection display increased cough reflex sensitivity up to 220 days after confirmed infection. There is an absence of associated risk factors and less impairment in quality of life compared to those patients normally seen in a specialist cough clinic. The associated mechanism was found to be cough reflex hypersensitivity. This clinical trial has been registered with the Australian New Zealand Clinical Trials Register, ACTRN12610000540011.
Publisher: Elsevier BV
Date: 09-2008
Publisher: MDPI AG
Date: 20-10-2017
DOI: 10.3390/NU9101147
Publisher: Wiley
Date: 25-07-2011
DOI: 10.1111/J.1440-1843.2011.02012.X
Abstract: Severe asthma affects 5-20% of the asthma population but is discordantly responsible for the major burden of illness and impairment to quality of life. Patients with severe asthma continue to experience ongoing symptoms despite maximal therapy. A severe asthma service provides a systematic approach to the management of the disease and aids in confirming the correct diagnosis, managing comorbid conditions that may mimic or aggravate asthma, and provides the environment to optimize treatment and asthma self-management skills and education. A severe asthma service is also the ideal environment for trialling add-on therapies and hence can improve patient outcomes and clinical practice. Within such a service there are many opportunities for training and research. In this article we describe the purpose of a severe asthma clinic, the necessary components of a service including staffing and facilities and the processes for trialling additional therapies used in the management of severe asthma.
Publisher: BMJ
Date: 04-12-2018
Publisher: Informa UK Limited
Date: 2009
DOI: 10.1080/01902140902777490
Abstract: Neutrophilic inflammation is a key effector arm of the innate immune response. Neutrophils may contribute significantly to airway inflammation in certain asthma subtypes. The objective of this study is to investigate the innate immune responses of isolated airway and circulating neutrophils in asthma. Participants with asthma (n = 17) and healthy volunteers (n = 11) underwent induced sputum and blood collection. Neutrophils were isolated from dispersed selected sputum and blood granulocytes using magnetic cell separation. Neutrophils were cultured with or without lipopolysaccharide (100 ng/mL) for 24 hours. Innate immune mediators were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Airway neutrophils from participants with asthma spontaneously released lower levels of interleukin (IL)-8, IL-1beta and tumor necrosis factor-alpha proteins, and had lower levels of cytokine gene expression compared to healthy controls. Toll-like receptor 4 (TLR4) gene expression was significantly decreased in airway neutrophils from participants with asthma compared to healthy volunteers. Resting and lipopolysaccharide (LPS)-stimulated circulating neutrophils had lower levels of TLR2 and IL-1beta gene expression in asthma, but were otherwise similar to healthy controls. No differences were seen for matrix metalloproteinase (MMP)-9 release in asthma. Innate immune responses of airway neutrophil cells are impaired in asthmatic subjects on prophylactic therapy and may impact on susceptibility to, and severity of, airway infections.
Publisher: Wiley
Date: 03-2000
DOI: 10.1046/J.1440-1843.2000.00226.X
Abstract: To evaluate induced sputum eosinophils in asthma and chronic cough. This was an analytical, cross-sectional study set in an ambulatory respiratory clinic. Subjects (n=75) referred for evaluation of symptomatic asthma or episodic respiratory symptoms had a clinical assessment, spirometry, hypertonic saline challenge and induced sputum. Two diagnostic groups were identified. The first group comprised subjects with symptomatic asthma and variable airway obstruction (VAO) (n=32). The second group included subjects with episodic respiratory symptoms and no VAO (n=43). The prevalence of eosinophilic bronchitis (eosinophils >2.75%) was greatest in asthma (n=14, 44%), compared to the episodic respiratory symptoms group (n=9, 21%, P = 0.02). Clinical variables did not predict increased eosinophils (P > 0.05). Sputum eosinophils were highest in asthmatics not using inhaled corticosteroids (6.5% vs 0.5%, P = 0.02). Sputum neutrophils were higher in subjects using inhaled corticosteroid (53% vs 25%, P = 0.04). Airway inflammation with eosinophilia was common among patients presenting to a respiratory clinic, especially those with asthma who were not using inhaled corticosteroids. Induced sputum also identified eosinophilic bronchitis in those without asthma. It was not possible to detect the presence or absence of airway eosinophilia by routine clinical assessment. The results in this study imply that the assessment of induced sputum eosinophils may be a useful guide to therapy, especially in the assessment of persistent symptoms in asthmatics on corticosteroids, and in the assessment of non-asthmatic subjects with symptoms.
Publisher: Elsevier BV
Date: 03-2016
Abstract: Chronic refractory cough (CRC) is a difficult problem to treat. Speech pathology treatment (SPT) improves symptoms but resolution is incomplete. Centrally acting neuromodulators also improve cough symptoms, but not cough reflex sensitivity, and the effect is short-lived. We hypothesized that combined SPT and centrally acting neuromodulators would have a superior outcome than SPT alone. Our goal was to determine whether combined pregabalin and SPT is more effective than SPT alone. Randomized placebo controlled trial. Forty patients with CRC were randomly assigned to receive either combined SPT and pregabalin 300 mg daily or combined SPT and placebo. Outcome measures were collected at baseline, end of treatment, and 4 weeks after the end of treatment. Primary outcome measures were cough frequency using the Leicester Cough Monitor, cough severity using a visual analog scale (coughVAS), and cough-related quality of life (QOL) using the Leicester Cough Questionnaire (LCQ). Cough severity, cough frequency, and cough QOL improved in both groups. The degree of improvement in LCQ and coughVAS was greater with combined SPT and pregabalin than SPT alone the mean difference in LCQ was 3.5, 95%CI of difference 1.1 to 5.8 the mean difference in coughVAS was 25.1, 95% CI of difference 10.6 to 39.6. There was no significant difference in improvement in cough frequency between groups. There was no deterioration in symptoms once pregabalin was withdrawn. Median capsaicin cough sensitivity improved from 15.7 to 47.5 μM with combined SPT and pregabalin and from 3.92 to 15.7 μM with SPT alone. Combined SPT and pregabalin reduces symptoms and improves QOL compared with SPT alone in patients with CRC.
Publisher: American Thoracic Society
Date: 07-1997
DOI: 10.1164/AJRCCM.156.1.9605044
Abstract: We tested the hypothesis that hyperresponsiveness of the upper airway (UAHR) is present in patients with chronic cough of erse etiology. We determined the frequency of bronchial hyperresponsiveness (BHR), hyperresponsiveness of the upper airway, sputum eosinophilia, pulmonary aspiration, and psychological symptoms in adults with chronic cough. Consecutive adults (n = 30) presenting to a tertiary referral clinic with chronic cough were compared with a group of 20 asymptomatic adults. Measurements included histamine provocation testing with measurement of flow volume curves to determine inspiratory and expiratory airflow obstruction hypertonic saline induced sputum for analysis of eosinophils, mast cells and lipid-laden macrophages and a validated psychological symptom questionnaire. Symptomatic rhinitis and gastroesophageal reflux were common causes of chronic cough. BHR occurred in seven patients (23%) and in no control subjects (p 0.05). Eosinophils were present in the sputum of more patients with cough than control subjects (50% versus 19% p < 0.05). High degrees of eosinophilia were present in six patients with cough, including three without BHR. No subject had significant lipid-laden macrophages. There was greater somatization in patients with chronic cough ten subjects scored in the clinically significant range (p < 0.05). Abnormalities in one or more of these tests were 7.67-fold (95% CI 1.83-34.52) more likely to occur in cough patients than control subjects. We conclude that chronic cough is a nonspecific symptom that is associated with several apparently unrelated mechanisms. These include UAHR, somatization, BHR, and eosinophilic bronchitis. UAHR cannot be implicated as a single unifying mechanism. These findings emphasize the need to systematically evaluate several different causes of cough in patients who present with chronic cough.
Publisher: European Respiratory Society (ERS)
Date: 2018
DOI: 10.1183/23120541.00130-2017
Abstract: Protracted bacterial bronchitis (PBB) in young children is characterised by prolonged wet cough, prominent airway interleukin (IL)-1β expression and infection, often with nontypeable Haemophilus influenzae (NTHi). The mechanisms responsible for IL-1-driven inflammation in PBB are poorly understood. We hypothesised that the inflammation in PBB involves the NLRP3 and/or AIM2 inflammasome/IL-1β axis. Lung macrophages obtained from bronchoalveolar lavage (BAL), peripheral blood mononuclear cells (PBMCs), blood monocytes and monocyte-derived macrophages from patients with PBB and age-matched healthy controls were cultured in control medium or exposed to live NTHi. In healthy adult PBMCs, CD14 + monocytes contributed to 95% of total IL-1β-producing cells upon NTHi stimulation. Stimulation of PBB PBMCs with NTHi significantly increased IL-1β expression (p .001), but decreased NLRC4 expression (p .01). NTHi induced IL-1β secretion in PBMCs from both healthy controls and patients with recurrent PBB. This was inhibited by Z-YVAD-FMK (a caspase-1 selective inhibitor) and by MCC950 (a NLRP3 selective inhibitor). In PBB BAL macrophages inflammasome complexes were visualised as fluorescence specks of NLRP3 or AIM2 colocalised with cleaved caspase-1 and cleaved IL-1β. NTHi stimulation induced formation of specks of cleaved IL-1β, NLRP3 and AIM2 in PBMCs, blood monocytes and monocyte-derived macrophages. We conclude that both the NLRP3 and AIM2 inflammasomes probably drive the IL-1β-dominated inflammation in PBB.
Publisher: Springer Science and Business Media LLC
Date: 12-12-2022
DOI: 10.1186/S12931-022-02266-5
Abstract: Anxiety and depression are comorbidities of severe asthma. However, clinical characteristics associated with coexisting severe asthma and anxiety/depression are poorly understood. The study objective is to determine clinical characteristics associated with anxiety and depressive symptoms in severe asthma. Severe asthma participants (N = 140) underwent a multidimensional assessment. Categorization of symptoms of anxiety and depression were based on HADS scale sub-scores and ided into four groups ( 8 on both subscales ≥ 8 on one subscale ≥ 8 on both subscales). Clinical characteristics were compared between subgroups. Multivariate logistic regression determined associations of clinical characteristics and anxiety and/or depressive symptoms in people with severe asthma. Participants were (mean ± SD) 59.3 ± 14.7 years old, and 62% female. There were 74 (53%) severe asthma participants without symptoms of anxiety/depression, 11 (7%) with symptoms of anxiety, 37 (26%) with symptoms of depression and 18 (13%) with symptoms of anxiety and depression. Quality of life impairment was greater in participants with symptoms of depression (4.4 ± 1.2) and combined symptoms of anxiety and depression (4.4 ± 1.1). Asthma control was worse in those with symptoms of depression (2.9 ± 1.1) and combined anxiety and depression (2.6 ± 1.0). In multivariate models, dysfunctional breathing was associated with symptoms of anxiety (OR = 1.24 [1.01, 1.53]). Dyspnoea was associated with symptoms of depression (OR = 1.90 [1.10, 3.25]). Dysfunctional breathing (OR 1.16 [1.04, 1.23]) and obesity (OR 1.17 [1.00, 1.35]) were associated with combined symptoms of anxiety and depression. People with severe asthma and anxiety and/or depressive symptoms have poorer QoL and asthma control. Dyspnoea, dysfunctional breathing and obesity are associated with these symptoms. These key clinical characteristics should be targeted in severe asthma management.
Publisher: Wiley
Date: 31-05-2022
DOI: 10.1111/IMJ.15216
Abstract: Low‐dose long‐term azithromycin is recommended in clinical practice guidelines for obstructive airway diseases (OAD) however, an optimal therapeutic regimen is not yet established. To understand the patterns of azithromycin use in OAD, characterise the patients who received it and evaluate its safety and efficacy using real‐world data. We audited 91 patients who had received azithromycin for at least 4 weeks for the management of asthma, chronic obstructive pulmonary disease (COPD) or non‐cystic fibrosis bronchiectasis. The mean age was 65 ± 18 years, 60% were female and 48% were ex‐smokers. The majority had asthma (75%), either alone (50%) or in combination with COPD (12%) or bronchiectasis (13%). Most (64%) reported cough or sputum at baseline. The most common treatment regimen was azithromycin 250 mg daily (73%) for more than 1 year (57%), with only seven adverse events. There was a significant reduction in the proportions of patients requiring emergency department visits (48% vs 32% P 0.001) and hospital admissions (35% vs 31% P 0.001) after starting azithromycin. In 88% of cases, physicians favoured the use of azithromycin. Physicians are currently using low‐dose azithromycin for a long duration of more than 1 year for the management of OAD. The typical case definition is an older non‐smoking adult with persistent asthma, often in combination with another OAD and presenting with bothersome cough or sputum. Azithromycin was well tolerated and led to reduced healthcare utilisation. Further research is required to establish an optimal dosage regimen of azithromycin in OAD.
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 2023
DOI: 10.1016/J.JAIP.2022.09.034
Abstract: Optimizing asthma diagnosis is an essential part of global strategies to reduce the excessive illness burden from asthma. New understanding about how to address the complexity and heterogeneity of the different forms of asthma means that asthma diagnosis now requires a compound diagnostic approach and label. Eliciting the typical symptoms and abnormal physiology of variable airflow limitation permits the recognition of asthma, and the identification of further features, such as eosinophilic or type 2 inflammation, allows a compound diagnostic label of eosinophilic asthma. This conveys key information about future exacerbation risk and likely treatment responsiveness. Treatable traits are a useful way to implement this new approach to diagnosis. Targeted assessment is used to inform a specific treatment plan in a pragmatic and iterative process.
Publisher: Wiley
Date: 19-10-2017
DOI: 10.1111/RESP.13200
Publisher: Wiley
Date: 26-10-2008
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/407271
Abstract: Background . Innate immune antimicrobial peptides, including β -defensin-1, promote the chemotaxis and activation of several immune cells. The role of β -defensin-1 in asthma and chronic obstructive pulmonary disease (COPD) remains unclear. Methods . Induced sputum was collected from healthy controls and in iduals with asthma or COPD. β -defensin-1 protein in sputum supernatant was quantified by ELISA. Biomarker potential was examined using receiver operating characteristic curves. β -defensin-1 release from primary bronchial epithelial cells (pBECs) was investigated in culture with and without cigarette smoke extract (CSE). Results . Airway β -defensin-1 protein was elevated in COPD participants compared to asthma participants and healthy controls. Inflammatory phenotype had no effect on β -defensin-1 levels in asthma or COPD. β -defensin-1 protein was significantly higher in severe asthma compared to controlled and uncontrolled asthma. β -defensin-1 protein could predict the presence of COPD from both healthy controls and asthma patients. Exposure of pBECs to CSE decreased β -defensin-1 production in healthy controls however in pBECs from COPD participants the level of β -defensin-1 remanied unchanged. Conclusions . Elevated β -defensin-1 protein is a feature of COPD and severe asthma regardless of inflammatory phenotype. β -defensin-1 production is dysregulated in the epithelium of patients with COPD and may be an effective biomarker and potential therapeutic target.
Publisher: European Respiratory Society (ERS)
Date: 23-06-2022
DOI: 10.1183/23120541.00215-2022
Abstract: Chronic airway diseases including asthma and COPD are prevalent and high-burden conditions with the majority of patients successfully managed in the primary care setting. However, for some patients with more complex disease such as difficult-to-treat or severe asthma, or complex COPD, tertiary care is required. This review provides an overview of the successful tertiary care multidisciplinary respiratory service that operates in Newcastle, New South Wales, Australia, which has been integrated into the tertiary care outpatient clinics for almost three decades. The service is multifaceted in terms of the clinical care it provides it includes an “Inpatient Service”, “Asthma Management Service”, “Difficult Airways Clinic”, “Drug Administration Clinic”, “Rapid Access Clinic” and “Pulmonary Rehabilitation”, and has an integrated research programme. The core of the multidisciplinary approach to airway diseases is a person-centred model of care, the “Treatable Traits” approach. The staffing of this service comprises consultant physicians, respiratory advanced trainees, respiratory scientists, physiotherapists, speech pathologists, nurse specialists and a nurse consultant. Patients that present to this service undergo an initial assessment and clinical review by team members, synthesis of relevant data, and development of a diagnosis and management plan. Based on this clinical review, specific interventions are determined according to the traits identified. Over time the service has evolved to accommodate the increasing numbers of patients requiring access to the Difficult Airways Clinic assessment and therapies. This has been facilitated by partnering with the Centres of Excellence in Severe Asthma and Treatable Traits to develop educational and practice management tools.
Publisher: Wiley
Date: 13-03-2018
DOI: 10.1111/CEA.13112
Abstract: Obstructive airways diseases (OAD) represent a huge burden of illness world-wide, and in spite of the development of effective therapies, significant morbidity and mortality related to asthma and COPD still remains. Over the past decade, our understanding of OAD has improved vastly, and novel treatments have evolved. This evolution is the result of successful translational research, which has connected clinical presentations of OAD and underlying disease mechanisms, thereby enabling the development of targeted treatments. The next challenge of translational research will be to position these novel treatments for OAD for optimal clinical use. At the same time, there is great potential in these treatments providing even better insights into disease mechanisms in OAD by studying the effects of blocking in idual immunological pathways. To optimize this potential, there is a need to ensure that translational aspects are added to randomized clinical trials, as well as real-world studies, but also to use other trial designs such as platform studies, which allow for simultaneous assessment of different interventions. Furthermore, demonstrating clinical impact, that is research translation, is an increasingly important component of successful translational research. This review outlines concepts of translational research, exemplifying how translational research has moved management of obstructive airways diseases into the next century, with the introduction of targeted, in idualized therapy. Furthermore, the review describes how these therapies may be used as research tools to further our understanding of disease mechanisms in OAD, through translational, mechanistic studies. We underline the current need for implementing basic immunological concepts into clinical care in order to optimize the use of novel targeted treatments and to further the clinical understanding of disease mechanisms. Finally, potential barriers to adoption of novel targeted therapies into routine practice and how these may be overcome are described.
Publisher: Wiley
Date: 09-09-2019
DOI: 10.1111/CEA.13474
Abstract: Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users. We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N = 45 Aim 2, N = 13 and Aim 3, N = 5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%) 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%). The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.
Publisher: Hogrefe Publishing Group
Date: 03-2004
Publisher: European Respiratory Society (ERS)
Date: 07-2018
Publisher: MDPI AG
Date: 10-09-2013
DOI: 10.3390/NU5093506
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/17549500801932089
Abstract: Sensory function may be important in the pathogenesis of Chronic Cough (CC) and Paradoxical Vocal Fold Movement (PVFM). This paper aims to explore sensory issues related to the pathogenesis, classification, assessment and management of these conditions. Sensory disruption of the vagus nerve can occur through neural plasticity whereby a change occurs in the way a central neuron reacts to an incoming stimulus. Such disruption can be demonstrated through assessment of cough reflex sensitivity and extrathoracic airway hyperresponsiveness both of which may be increased in CC and PVFM. In addition, sensory function may be determined by measuring the laryngeal adductor reflex, however this phenomenon is yet to be explored in CC and PVFM. The similarity in sensory dysfunction between CC and PVFM provides support for a link between the two conditions. There are also similarities in underlying medical conditions and symptom profiles between CC/PVFM and voice disorders such as muscle tension dysphonia. Although coughing and throat clearing may be contributing factors in the development and maintenance of voice disorders, they may occur in response to extrathoracic airway hyperresponsiveness. Dysphonia can occur in CC/PVFM and may improve following behavioural treatment of CC.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 04-2012
Publisher: Wiley
Date: 16-08-2006
DOI: 10.1002/JSFA.2604
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/219374
Abstract: Background . Respiratory infections are a major cause of asthma exacerbations where neutrophilic inflammation dominates and is associated with steroid refractory asthma. Structural airway cells in asthma differ from nonasthmatics however it is unknown if neutrophils differ. We investigated neutrophil immune responses in patients who have good ( A G o o d ) and suboptimal ( A S u b o p t ) asthma symptom control. Methods . Peripheral blood neutrophils from A G o o d (ACQ 0.75, n = 11 ), A S u b o p t (ACQ 0.75, n = 7 ), and healthy controls (HC) ( n = 9 ) were stimulated with bacterial (LPS (1 μ g/mL), fMLF (100 nM)), and viral (imiquimod (3 μ g/mL), R848 (1.5 μ g/mL), and poly I:C (10 μ g/mL)) surrogates or live rhinovirus (RV) 16 (MOI1). Cell-free supernatant was collected after 1 h for neutrophil elastase (NE) and matrix metalloproteinase- (MMP-) 9 measurements or after 24 h for CXCL8 release. Results . Constitutive NE was enhanced in A G o o d neutrophils compared to HC. fMLF stimulated neutrophils from A S u b o p t but not A G o o d produced 50% of HC levels. fMLF induced MMP-9 was impaired in A S u b o p t and A G o o d compared to HC. fMLF stimulated CXCL8 but not MMP-9 was positively correlated with FEV 1 and FEV 1 /FVC. A S u b o p t and A G o o d responded similarly to other stimuli. Conclusions . Circulating neutrophils are different in asthma however, this is likely to be related to airflow limitation rather than asthma control.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Wiley
Date: 06-1989
DOI: 10.1111/J.1445-5994.1989.TB00263.X
Abstract: Bronchoalveolar lavage is a safe and simple technique for s ling the inflammatory cells of the lung. However, while its use in the evaluation of pulmonary pathogenic mechanisms is both well accepted and described, its clinical utility is more controversial. Marked variation in results may occur through variation in the lavage procedure. Standardisation of the lavage technique and laboratory processing of the specimen are essential for reliable results. This review examines the current clinical role of bronchoalveolar lavage in the assessment of patients with diffuse lung diseases, and immunocompromised patients with pulmonary infiltrates. In this latter category, for patients with Acquired Immunodeficiency Syndrome, lavage is of equal efficacy to lung biopsy and can establish the cause of pulmonary infiltrates in over 90% of cases. Bronchoalveolar lavage can detect abnormalities in patients with diffuse lung diseases prior to the development of irreversible fibrosis. Lavage features have been described for sarcoidosis, cryptogenic fibrosing alveolitis, extrinsic allergic alveolitis, connective tissue diseases, and asbestosis. In cryptogenic fibrosing alveolitis lavage data may be used to indicate a subsequent deterioration in the patient's condition, or predict a favourable response to therapy.
Publisher: BMJ
Date: 02-2002
Abstract: Airway inflammation with eosinophils is now reported to occur not only in asthma but in other airway diseases such as cough variant asthma, chronic cough, atopic cough, episodic symptoms without asthma, allergic rhinitis, and COPD. Although the prevalence of eosinophilic bronchitis (EB) is less than in asthma, the causes, mechanisms and treatment of EB in these conditions appears to be similar to asthma where allergen induced IL-5 secretion and symptoms are readily responsive to inhaled corticosteroids. The prognosis of EB without asthma is not known but it may be a precursor for asthma and, if so, recognition of this syndrome may permit effective treatment and reduction in the rising prevalence of asthma. Induced sputum analysis allows recognition of EB in clinical practice. The place of the asthma treatment paradigm with early and sustained corticosteroid treatment needs to be defined in EB without asthma. Airway wall remodelling can occur in rhinitis, COPD, and cough variant asthma with EB. The mechanisms and long term implications of this complication in EB without asthma need to be clarified.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2014
Publisher: Wiley
Date: 23-03-2018
DOI: 10.1111/CEA.13109
Abstract: Adipose tissue-derived inflammation is linked to obesity-related comorbidities. This study aimed to quantify and immuno-phenotype adipose tissue macrophages (ATMs) from obese asthmatics and obese non-asthmatics and to examine associations between adipose tissue, systemic and airway inflammation. Visceral (VAT) adipose tissue and subcutaneous (SAT) adipose tissue were collected from obese adults undergoing bariatric surgery and processed to obtain the stromovascular fraction. Pro-inflammatory (M1) and anti-inflammatory (M2) macrophages were quantified by flow cytometry. Cytospins of induced sputum were stained for differential cell counts. Plasma C-reactive protein (CRP) and CD163 were measured by ELISA. VAT contained a higher number of ATMs compared to SAT. A higher percentage of M1 ATMs was observed in VAT of obese asthmatics compared to obese non-asthmatics. The M1:M2 ratio in VAT was negatively associated with FEV Visceral inflammation with increased pro-inflammatory macrophages (M1) occurs in obese asthma and may be a determinant of systemic inflammation and asthma severity.
Publisher: Wiley
Date: 10-07-2022
DOI: 10.1111/RESP.14323
Abstract: Exercise capacity is associated with health‐related quality of life and symptom control in severe asthma. Thus, interventions targeting exercise capacity are likely to be beneficial. However, clinical and biological factors impacting exercise capacity in severe asthma are sparsely investigated. We aimed to describe the association of selected clinical and biological factors with 6‐min walk distance (6MWD) in adults with severe asthma and investigate the impact of sex on these outcomes. A cross‐sectional study in adults with severe asthma was conducted. Exercise capacity was measured by 6‐min walk test, and association between 6MWD and predictors were evaluated using multiple linear regression. A total of 137 patients (females, 85 median age, 59 years) were recruited. Overall, asthma control (−15.2 m, 95% CI −22.6 to −7.7 p = 0.0001) and BMI (−3.2 m, 95% CI −5.1 to −1.3 p = 0.001) were significantly associated with exercise capacity (adjusted variance, adj. R 2 = 0.425). In females, 5‐item Asthma Control Questionnaire (ACQ‐5 p = 0.005) and BMI ( p 0.001) were significantly associated with 6MWD (adj. R 2 = 0.423). In males, a 0.5‐point increase in ACQ‐5 was associated with a decrease in 6MWD by 10.2 m (95% CI −22.8 to 2.4 p = 0.11), but no clinical nor biological factors reached statistical significance (adj. R 2 = 0.393). Asthma symptoms and BMI were associated with exercise capacity in the overall population. Optimizing these factors may enhance the ability of patients to improve their exercise capacity and gain the associated positive health outcomes, but further studies are warranted.
Publisher: European Respiratory Society (ERS)
Date: 06-2017
DOI: 10.1183/13993003.00180-2017
Abstract: Biomarkers that predict responses to oral corticosteroids (OCS) facilitate patient selection for asthma treatment. We hypothesised that asthma patients would respond differently to OCS therapy, with biomarkers and inflammometry predicting response. Adults with stable asthma underwent a randomised controlled cross-over trial of 50 mg prednisolone daily for 10 days (n=55). A six-gene expression biomarker signature ( CLC , CPA3 , DNASE1L3 , IL1B , ALPL and CXCR2 ) in induced sputum, and eosinophils in blood and sputum were assessed and predictors of response were investigated (changes in forced expiratory volume in 1 s (ΔFEV 1 ), six-item Asthma Control Questionnaire score (ΔACQ6) or exhaled nitric oxide fraction (Δ F eNO )). At baseline, responders to OCS (n=25) had upregulated mast cell CPA3 gene expression, poorer lung function, and higher sputum and blood eosinophils. Following treatment, CLC and CPA3 gene expression was reduced, whereas DNASE1L3, IL1B, ALPL and CXCR2 expression remained unchanged. Receiver operating characteristic (ROC) analysis showed the six-gene expression biomarker signature as a better predictor of clinically significant responses to OCS than blood and sputum eosinophils. The six-gene expression signature including eosinophil and Th2 related mast cell biomarkers showed greater precision in predicting OCS response in stable asthma. Thus, a novel sputum gene expression signature highlights an additional role of mast cells in asthma, and could be a useful measurement to guide OCS therapy in asthma.
Publisher: Wiley
Date: 18-02-2019
DOI: 10.1111/CEA.13346
Abstract: Depressive symptoms worsen asthma outcomes however, the mechanism remains largely unexplored. This study aimed to determine whether depressive symptom-associated immune inflammation correlates with impaired bronchodilator response (BDR) and airway inflammatory phenotypes. Eligible adults with asthma (n = 198) underwent clinical assessment, sputum induction and blood s ling. Depressive symptoms were defined by scores on the depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Pre- and post-bronchodilator spirometry was performed for BDR. Airway inflammatory phenotypes were defined by sputum cell counts. CRP, IL-1β, IL-5, IL-6, IL-8, TNF-α, IFN-γ, CCL17 and CCL22 in serum and sputum were detected. Compared with the non-depressive group (n = 174), the depressive group (n = 24) exhibited impaired BDR (P = 0.032) and increased sputum neutrophils (P = 0.023), which correlated with the HADS-D scores (P = 0.027 and P = 0.029). Levels of IL-1β, TNF-α and IFN-γ in the serum and those of IL-1β and IFN-γ in the sputum were elevated in the depressive group compared to those in the non-depressive group (all P < 0.05). Multiple regression models indicated that TNF-α in the sputum and IL-1β, IL-6 and IFN-γ in both the serum and sputum were inversely associated with BDR TNF-α in the sputum and IL-1β in both the serum and sputum were positively correlated with sputum neutrophils. Mediation analyses revealed that IL-1β and TNF-α in the sputum and IL-1β in both the serum and sputum mediate the correlations of the HADS-D scores with BDR and sputum neutrophils, respectively. Asthma patients with depressive symptoms present worse asthma control, which is most likely explained by impaired BDR and neutrophilic airway inflammation. IL-1β and TNF-α, which are two key pro-inflammatory cytokines that mediate the correlation of depressive symptoms with impaired BDR and neutrophilic airway inflammation, may serve as targeted biomarkers in the neuropsychological phenotype of asthma however, this result needs to be further validated.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2021
DOI: 10.1186/S12890-021-01436-3
Abstract: Physical inactivity is common in severe asthma and associated with poor health outcomes. New approaches are needed to address physical inactivity in this group. To examine whether yoga and mindfulness improves health-related quality of life (HRQoL) compared with a minimal active control group and collect feasibility data to inform future studies. Over 12-weeks, adults with severe asthma were recruited. Participants were randomised 2:1 to parallel yoga or control groups. All participants received an activity tracker. The yoga group received tailored group classes twice a week for 16-weeks with a qualified yoga instructor. The control group set activity goals with a research officer and received eight progress calls. Outcomes were assessed at 16-weeks. Primary outcome was St George’s Respiratory Questionnaire (SGRQ). Secondary outcomes included asthma control, physical activity, breathlessness, and inflammation. Face-to-face qualitative interviews were conducted to determine acceptability. There were 15 participants randomised to yoga (mean 67 years 60% female) and 9 to control (68 years 56% female). Planned comparisons indicated the yoga group had greater SGRQ improvement than the control group. There was little change in secondary outcomes. Moderate-vigorous activity increased substantially in the control group. Participants found the intervention acceptable key barriers and facilitators were social connection, the setting, addressing breathing and asthma symptoms, changing their mindset, and the intersection of different elements. A yoga and mindfulness intervention was feasible, acceptable to patients and improved HRQoL. The findings will inform design of much needed future research into physical activity interventions for severe asthma. World Health Organization International Clinical Trials Registry Platform The study was registered under the Australian New Zealand Clinical Trials Registry (ANZCTR) on the 26th of November 2018, Trial ID ACTRN12618001914257.
Publisher: Elsevier BV
Date: 2009
DOI: 10.1016/J.PLIPRES.2008.10.001
Abstract: Local airway inflammation in chronic respiratory disease is well described. Recently it has been recognised that chronic obstructive respiratory disease, asthma and obstructive sleep apnoea, all involve a systemic inflammatory component. Overspill of airway inflammation, as well as direct metabolic effects, are potential contributors to systemic inflammation. This review will discuss the role of certain types of fatty acids in promoting systemic inflammation, via the innate immune response. Fatty acids are necessary as the key energy source in the body. However, they can be detrimental if present in excess. Various features of respiratory disease lead to altered lipid metabolism, and notably an increase in circulating levels of non-esterified fatty acids (NEFA). Dietary intake, obesity, hypoxia and smoking, will be discussed as factors promoting an increase in circulating NEFA. While n-3 polyunsaturated and monounsaturated fatty acids may be non-(or anti-)inflammatory, saturated and n-6 polyunsaturated fatty acids have been shown to stimulate the innate immune response. Thus, increased circulating NEFA may be directly contributing to systemic inflammation, thereby increasing susceptibility of in iduals to chronic inflammatory diseases, including respiratory disease, cardiovascular disease and diabetes. Finally, the review will discuss how the recognition of NEFA as important inflammatory stimulants in respiratory disease, leads to the possibility that pathways involved in lipid metabolism may provide therapeutic targets.
Publisher: Wiley
Date: 11-2022
DOI: 10.1111/PAI.13872
Publisher: Wiley
Date: 12-2009
Publisher: Wiley
Date: 21-01-2002
Publisher: Elsevier BV
Date: 09-2006
DOI: 10.1016/J.JVOICE.2005.08.001
Abstract: Chronic cough (CC) and paradoxical vocal fold movement (PVFM) are debilitating conditions. PVFM has been given many labels, including vocal cord dysfunction, Munchausen's stridor, functional inspiratory stridor, nonorganic functional or psychogenic upper airway obstruction, factitious asthma, psychogenic stridor, emotional laryngeal wheezing, and episodic laryngeal dyskinesia. Although CC and PVFM have been considered separate entities in many reports, there is preliminary support for the notion that there may be an underlying link between these two conditions. Speech pathologists have become increasingly involved in the treatment of these patients and therefore need to understand the theoretical background of these disorders, the pathophysiological links between the two, and the impact of voice disorders on these populations. The aim of this article is to review the current literature on CC and PVFM from a speech pathology perspective to provide a model for defining and conceptualizing the disorders and to provide a framework for management and future research.
Publisher: Wiley
Date: 02-03-2021
DOI: 10.1111/ALL.14768
Abstract: The AMAZES randomized controlled trial demonstrated that long‐term low‐dose azithromycin treatment reduces exacerbations of poorly controlled asthma, but the therapeutic mechanisms remain unclear. Dysregulation of the inflammatory tumour necrosis factor (TNF) pathway is implicated in asthma and could be suppressed by azithromycin. We aimed to determine the inflammatory and clinical associations of soluble TNF signalling proteins (TNF receptors [TNFR] 1 and 2, TNF) in sputum and serum, and to test the effect of 48 weeks of azithromycin vs placebo on TNF markers. Sputum supernatant and serum TNFR1, TNFR2 (n = 142 75 azithromycin‐treated, 67 placebo‐treated) and TNF (n = 48 22 azithromycin‐treated, 26 placebo‐treated) were measured by ELISA in an AMAZES trial sub‐population at baseline and end of treatment. Baseline levels were compared between sputum inflammatory phenotypes, severe/non‐severe asthma and frequent/non‐frequent exacerbators. Effect of azithromycin on markers was tested using linear mixed models. Baseline sputum TNFR1 and TNFR2 were significantly increased in neutrophilic vs non‐neutrophilic asthma phenotypes, while serum markers did not differ. Sputum TNFR1 and TNFR2 were increased in severe asthma and correlated with poorer lung function, worse asthma control and increasing age. Serum TNFR1 was also increased in severe asthma. Sputum and serum TNFR2 were increased in frequent exacerbators. Azithromycin treatment significantly reduced sputum TNFR2 and TNF relative to placebo, specifically in non‐eosinophilic participants. We demonstrate dysregulation of TNF markers, particularly in the airways, that relates to clinically important phenotypes of asthma including neutrophilic and severe asthma. Suppression of dysregulated TNF signalling by azithromycin could contribute to its therapeutic mechanism.
Publisher: Springer Science and Business Media LLC
Date: 17-05-2016
Publisher: Informa UK Limited
Date: 2008
DOI: 10.1080/02770900802207279
Abstract: The prevalence of asthma is higher in women than men of reproductive age and almost half of all hospitalisations for asthma in women occur during the perimenstrual phase of the cycle. The mechanisms of premenstrual asthma (PMA) are unknown and a definition of PMA has not been clearly presented in the literature. The objective of this study was to determine the prevalence of PMA using a variety of definitions, to investigate the cycle-to-cycle variation in PMA, the effects of oral contraceptive use and the relationship between PMA and premenstrual symptoms. Premenopausal women with asthma (n = 28) were prospectively followed for at least 12 weeks over 2-4 consecutive menstrual cycles. Asthma symptoms, beta(2)-agonist and inhaled corticosteroid use and morning and evening peak expiratory flow were recorded daily. The following types of PMA definitions were investigated: self-reported PMA, increased symptoms, increased medication use, decreased peak flow or a combination of changes in symptoms, medication and peak flow. Changes of more than 20%, for at least 2 consecutive days of the luteal phase (last 14 days of the cycle prior to menstruation) compared to the early follicular phase average (first 7 days after menstruation) were considered PMA. Using a composite definition where subjects experienced increased symptoms and medication use with or without a change in peak flow, 16 subjects were classified as having PMA (57%), while 12 did not have PMA. Only 4 subjects (25%) had PMA in every cycle examined. Fifty-five percent of subjects who used oral contraceptives had PMA, while 59% of subjects who did not use oral contraceptives had PMA. Women who were defined PMA using the composite definition were more likely than those without PMA to experience a 20% decrease in peak flow during the luteal phase. There was no relationship between asthma symptoms and premenstrual symptoms on day 1 of the menstrual cycle in women with PMA. PMA resulting in increased symptoms and medication use occurred in 57% of subjects studied for 2-4 menstrual cycles. The use of oral contraceptives is not protective and further work is required to elucidate the mechanisms of PMA.
Publisher: European Respiratory Society (ERS)
Date: 2008
DOI: 10.1183/09031936.00138707
Abstract: Asthma is a serious health problem throughout the world. During the past two decades, many scientific advances have improved our understanding of asthma and ability to manage and control it effectively. However, recommendations for asthma care need to be adapted to local conditions, resources and services. Since it was formed in 1993, the Global Initiative for Asthma, a network of in iduals, organisations and public health officials, has played a leading role in disseminating information about the care of patients with asthma based on a process of continuous review of published scientific investigations. A comprehensive workshop report entitled "A Global Strategy for Asthma Management and Prevention", first published in 1995, has been widely adopted, translated and reproduced, and forms the basis for many national guidelines. The 2006 report contains important new themes. First, it asserts that "it is reasonable to expect that in most patients with asthma, control of the disease can and should be achieved and maintained," and recommends a change in approach to asthma management, with asthma control, rather than asthma severity, being the focus of treatment decisions. The importance of the patient-care giver partnership and guided self-management, along with setting goals for treatment, are also emphasised.
Publisher: Elsevier BV
Date: 09-2011
Publisher: American Thoracic Society
Date: 15-03-2011
Publisher: Wiley
Date: 21-03-2013
DOI: 10.1111/RESP.12015
Abstract: Dietary intake is an important modifiable risk factor for asthma and may be related to disease severity and inflammation, through the effects of intake of anti-oxidant-rich foods and pro-inflammatory nutrients. This study aimed to examine dietary intake in asthma in relation to asthma severity, lung function, inhaled corticosteroid use, leptin levels and inflammation. Food frequency questionnaires, spirometry and hypertonic saline challenge were completed by 137 stable asthmatics and 65 healthy controls. Plasma leptin was analysed by immunoassay. Induced sputum differential cell counts were determined. Subjects with severe persistent asthma consumed more fat and less fibre as compared with healthy controls (odds ratio 1.04 (95% confidence interval: 1.01-1.07), P = 0.014) (odds ratio 0.94 (95% confidence interval: 0.90-0.99), P = 0.018). Among asthmatics, higher fat and lower fibre intakes were associated with lower forced expiratory volume in 1 s and airway eosinophilia. Leptin levels were increased in both male and female asthmatics as compared with healthy controls. No association existed among asthmatics between corticosteroid use and dietary intake. It was found that asthmatics within the subgroup of severe persistent asthma have a different pattern of dietary intake as compared with healthy controls, which was associated with lower lung function and increased airway inflammation.
Publisher: Wiley
Date: 30-07-2023
DOI: 10.1111/RESP.14556
Abstract: The landscape of asthma has considerably changed in the last decade. Effective medications and inhaler devices have been developed and integrated into the asthma pharmacopoeia, but unfortunately, the proportion of uncontrolled patients remains unacceptably high. This is now recognized to be mainly due to the inappropriate use of medications or inhaler devices, heterogeneity of the disease or other factors contributing to the disease. Currently, inhaled corticosteroids (ICS), with or without long‐acting beta agonists (LABA), are the cornerstone of asthma management, and recently international guidelines recognized the importance of combination inhaler therapy (ICS/LABA) even in mild asthma. In future, ultra‐long‐acting personalized medications and smart inhalers will complement combination inhaler therapy in order to effectively addresses issues such as adherence, inhaler technique and polypharmacy (both of drugs and devices). Asthma is now acknowledged as a multifaceted cluster of disorders and the treatment model has evolved from one‐size‐fits‐all to precision medicine approaches such as treatable traits (TTs, defined as measurable and treatable clinically important factors) which encourages the quality use of medications and identification and management of all underlying behavioural and biological treatable risk factors. TT requires research and validation in a clinical context and the implementation strategies and efficacy in various settings (primary/secondary/tertiary care, low‐middle income countries) and populations (mild/moderate/severe asthma) are currently evolving. Combination inhaler therapy and the TTs approach are complementary treatment approaches. This review examines the current status of personalized medicine and combination inhaler therapy, and describes futuristic views for these two strategies.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.JVOICE.2010.07.009
Abstract: The aims of this study were to examine cough triggers in in iduals with chronic cough (CC), identify sensory symptoms consistent with central reflex sensitization (paresthesia and allotussia), and interpret this information in relation to sensory laryngeal neuropathy. Prospective observational study. Patients (n=53) with CC that was refractory to medical management based on the anatomic diagnostic protocol completed questionnaires regarding cough triggers, anxiety and depression, and factors contributing to laryngeal irritation such as vocal hygiene and laryngopharyngeal reflux. An abnormal sensation in the laryngeal area (laryngeal paresthesia) was present in 94% of people with refractory CC. Nontussive stimuli including phonation were frequent triggers for cough (allotussia), occurring in 71% of participants. Although tussive stimuli were significantly more potent than nontussive stimuli (P=0.005), the relative clinical importance was not statistically different (P=0.072). Most participants with refractory cough had poor vocal hygiene. The sensory symptom changes that accompany CC suggest central reflex sensitization and include laryngeal paresthesia and allotussia. The results are consistent with cough as a sensory neuropathic disorder.
Publisher: BMJ
Date: 07-2002
Abstract: There is increasing evidence that inflammatory mechanisms other than eosinophilic inflammation may be involved in producing the final common pathway of enhanced bronchial reactivity and reversible airflow obstruction that characterises asthma. A review of the literature has shown that, at most, only 50% of asthma cases are attributable to eosinophilic airway inflammation. It is hypothesised that a major proportion of asthma is based on neutrophilic airway inflammation, possibly triggered by environmental exposure to bacterial endotoxin, particulate air pollution, and ozone, as well as viral infections. If there are indeed two (or more) subtypes of asthma, and if non-eosinophilic (neutrophil mediated) asthma is relatively common, this would have major consequences for the treatment and prevention of asthma since most treatment and prevention strategies are now almost entirely focused on allergic/eosinophilic asthma and allergen avoidance measures, respectively. It is therefore important to study the aetiology of asthma further, including the underlying inflammatory profiles.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.JAIP.2018.02.027
Abstract: Physical inactivity and high sedentary time are associated with adverse health outcomes in several diseases. However, their impact in asthma is less clear. We aimed to synthesize the literature characterizing physical activity and sedentary time in adults with asthma, to estimate activity levels using meta-analysis, and to evaluate associations between physical activity and sedentary time and the clinical and physiological characteristics of asthma. Articles written in English and addressing the measurement of physical activity or sedentary time in adults ≥18 years old with asthma were identified using 4 electronic databases. Meta-analysis was used to estimate steps/day in applicable studies. There were 42 studies that met the inclusion criteria. Physical activity in asthma was lower compared with controls. The pooled mean (95% confidence interval) steps/day for people with asthma was 8390 (7361, 9419). Physical activity tended to be lower in females compared with males, and in older people with asthma compared with their younger counterparts. Higher levels of physical activity were associated with better measures of lung function, disease control, health status, and health care use. Measures of sedentary time were scarce, and indicated a similar engagement in this behavior between participants with asthma and controls. High sedentary time was associated with higher health care use, and poorer lung function, asthma control, and exercise capacity. People with asthma engage in lower levels of physical activity compared with controls. Higher levels of physical activity may positively impact on asthma clinical outcomes. Sedentary time should be more widely assessed.
Publisher: Elsevier BV
Date: 11-2000
Publisher: Wiley
Date: 06-08-2019
DOI: 10.1111/CEA.13452
Abstract: Dysfunction of the bronchial epithelium plays an important role in asthma however, its measurement is challenging. Columnar epithelial cells are often quantified, yet rarely analysed, in induced sputum studies. We aimed to test whether sputum columnar epithelial cell proportion and count are altered in asthma, and whether they are associated with clinical and inflammatory variables. We aimed to test whether sputum-based measures could provide a relatively non-invasive means through which to monitor airway epithelial activation status. We examined the relationship of sputum columnar epithelial cells with clinical and inflammatory variables of asthma in a large retrospective cross-sectional cohort (901 participants with asthma and 138 healthy controls). In further studies, we used flow cytometry, microarray, qPCR and ELISA to characterize sputum columnar epithelial cells and their products. Multivariate analysis and generation of 90th centile cut-offs (≥11% or ≥18.1 × 10 Sputum columnar epithelial cells are related to important clinical and inflammatory variables in asthma. Measurement of epithelial biomarkers in sputum s les could allow non-invasive assessment of altered bronchial epithelium status in asthma.
Publisher: Wiley
Date: 05-2016
DOI: 10.1111/IMJ.13056
Abstract: Studies have suggested a diagnostic role for faecal calprotectin (FC) in patients with gastroenterological disorders. To investigate Australian gastroenterologists' (GE) views on FC use and to elicit factors that affect physicians' choices. Electronic surveys were sent out to 405 consultants and 34 registrars in Australia. Respondents who answered 50% response 73% reported using FC in their clinical practice. Factors cited by non-users in restricting their FC use included cost (24%), availability (47%) and familiarity (18%). Even among users, 69% cited funding as a major deciding factor 98 and 86% of FC users believed that the test is a reliable method of differentiating between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) and assessing for mucosal healing in IBD respectively. Of non-users, 78 and 58%, respectively, would use FC to differentiate IBD from IBS and assess for mucosal healing in IBD, if FC testing was Medical Benefits Schedule (MBS) listed. Both users (79%) and non-users (68%) reported that use of FC to defer or avoid colonoscopies was likely if the test was MBS funded. Australian GE endorse the use of FC to discriminate between IBD and IBS, to check for mucosal healing in IBD and to reduce colonoscopy rates. Absence of MBS funding is an important factor contributing to the lack of usage of FC, in addition to the lack of familiarity with FC testing and availability.
Publisher: Wiley
Date: 06-2016
DOI: 10.5694/MJA16.00357
Abstract: Coal workers' pneumoconiosis (CWP) is an untreatable but preventable lung disease arising from chronic inhalation of coal dust. Recent reports of CWP in Queensland, along with international data, suggest that there is a resurgence in pneumoconiosis. The prevalence of CWP varies considerably between countries. In Australia, there is no mandatory reporting system and no national data on the prevalence of CWP. The symptoms and manifestations of CWP vary depending on the composition of the inhaled dust, duration of exposure, stage of disease and host-related factors. CWP may develop into progressive massive fibrosis (PMF), which can be fatal. Radiological assessment should be performed according to evidence-based standards using the ILO (International Labour Office) International Classification of Radiographs of Pneumoconioses. As preventing exposure to coal dust prevents CWP, it is important to implement and enforce appropriate standards limiting exposure. In Australia, these standards currently vary between states and are not in keeping with international understanding of the levels of coal dust that cause disease. Longitudinal screening programs are crucial for monitoring the health of coal workers to identify in iduals with early-stage disease and prevent progression from mild disease to PMF. We recommend: standardisation of coal dust exposure limits, with harmonisation to international regulations implementation of a national screening program for at-risk workers, with use of standardised questionnaires, imaging and lung function testing development of appropriate training materials to assist general practitioners in identifying pneumoconiosis and a system of mandatory reporting of CWP to a centralised occupational lung disease register.
Publisher: Public Library of Science (PLoS)
Date: 29-12-2022
DOI: 10.1371/JOURNAL.PONE.0279338
Abstract: Currently there is no consistent and widely accepted approach to the diagnosis of vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO). Harmonised diagnostic methods are vital to enable optimal diagnosis, advance management and enable research. We aim to obtain consensus on how expert clinicians recognise and diagnose VCD/ILO. Two-round modified Delphi, with workshop validation. Institutional Board Review was obtained from the Monash Health Human Research Ethics Committee. The dissemination plan is for presentation and publication. Registered at Australia and New Zealand Clinical Trials Registry ACTRN12621001520820p.
Publisher: Wiley
Date: 12-01-2010
Publisher: Wiley
Date: 11-1990
DOI: 10.1111/J.1365-2222.1990.TB02705.X
Abstract: Circulating eosinophils, basophils and eosinophil/basophil (Eo/B) progenitors were examined in 12 patients at the time of an exacerbation of asthma accompanied by sputum eosinophilia and after resolution of the exacerbation with inhaled corticosteroid treatment. Differential counts were performed and peripheral blood non-adherent mononuclear cells were cultured for 14 days in methyl-cellulose to determine the number of Eo/B and granulocyte-macrophage (GM) colonies without knowledge of the clinical conditions or findings. With resolution of the asthma exacerbation on beclomethasone therapy, there were significant falls in circulating eosinophils, basophils and Eo/B colonies whereas GM colonies were unchanged. To elucidate whether the observed changes could be due to systemic absorption or local action of inhaled corticosteroid, seven subjects with allergic rhinitis and no current evidence of lower airway inflammation (no symptoms of asthma and normal methacholine airway responsiveness) received 14 days' treatment with the same dose of inhaled beclomethasone or of placebo in a double-blind randomized cross-over study. No significant changes in airway function or in circulating cell counts were observed. The results suggest reduced production of eosinophils and basophils after the resolution of an exacerbation of asthma. This effect may be due to reduced levels of airway-derived eosinophil-basophil growth and differentiation factors.
Publisher: Informa UK Limited
Date: 11-08-2014
DOI: 10.4161/EPI.33066
Publisher: Elsevier BV
Date: 03-2012
Publisher: Informa UK Limited
Date: 24-08-2015
DOI: 10.3109/02770903.2015.1038833
Abstract: To investigate the relationship between asthma control and psychosocial outcomes in pregnant women with asthma. Secondary analysis (N = 221) of a randomized controlled trial of treatment adjustments, based on fractional exhaled nitric oxide versus clinical guideline-based algorithms. Psychosocial variables included generic and asthma-specific quality of life (SF12, AQLQ-M), illness perceptions (BIPQ), perceived control (PCAQ), perceived risk of side effects (PRSE) and anxiety (STAI-6). Asthma control was defined as controlled (Asthma Control Questionnaire (ACQ7) ≤1.5 at randomization and end of study), improved (ACQ7 > 1.5 at randomization and ≤1.5 at end of study) and unimproved (ACQ7 >1.5 at end of study). Regression models were fitted for each psychosocial measure at the end of the study, with adjustment for baseline values and smoking status, with predictor variable asthma control. Women with unimproved asthma had poorer physical (SF12, p = 0.012) and asthma-specific quality of life across all domains (AQLQ-M, p ≤ 0.012) compared to women with controlled asthma. They believed that they had less control over their asthma (PCAQ total p = 0.014), had more symptoms and that their illness had a greater effect on their emotions and their lives in general (BIPQ identity, consequences, concern, emotional response p ≤ 0.015). Women with improved asthma control had significantly lower AQLQ-M breathlessness (p = 0.048) and lower total scores (p = 0.04) than women with controlled asthma. Pregnant women who are not able to get control of their asthma symptoms may experience worse quality of life and are likely to have more negative perceptions about their condition.
Publisher: Wiley
Date: 18-07-2007
Publisher: Wiley
Date: 12-1996
DOI: 10.1002/(SICI)1099-0496(199612)22:6<402::AID-PPUL9>3.0.CO;2-K
Abstract: Supplementation with vitamin D has the potential to both reduce and increase risk of falling, and parathyroid hormone (PTH) may contribute to fall risk. To assess the associations of intra-trial mean circulating levels of 25-hydroxyvitamin D [25(OH)D] and PTH on incident falls in healthy older adults. Observational within a clinical trial. The Bone Metabolism Laboratory at the USDA Nutrition Center at Tufts University. 410 men and women age ≥65 years who participated in the 3-year Boston STOP IT trial to determine the effect of supplementation with 700 IU of vitamin D3 plus calcium on incident falls (secondary endpoint). Intra-trial exposures of 25(OH)D and PTH were calculated as the mean of biannual measures up to and including the first fall. Incidence of first fall. Intra-trial mean 25(OH)D was significantly associated with risk of falling in a U-shaped pattern the range associated with minimal risk of falling was approximately 20 to 40 ng/mL. PTH was not significantly associated with risk of falling. The findings highlight the importance of maintaining the circulating 25(OH)D level between 20 and 40 ng/mL, the range that is also recommended for bone health. At PTH levels within the normal range, there was no detectible independent association of PTH with fall risk.
Publisher: Wiley
Date: 04-05-2020
DOI: 10.1111/CEA.13609
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.CHEST.2015.10.066
Abstract: Children with recurrent protracted bacterial bronchitis (PBB) and bronchiectasis share common features, and PBB is likely a forerunner to bronchiectasis. Both diseases are associated with neutrophilic inflammation and frequent isolation of potentially pathogenic microorganisms, including nontypeable Haemophilus influenzae (NTHi), from the lower airway. Defective alveolar macrophage phagocytosis of apoptotic bronchial epithelial cells (efferocytosis), as found in other chronic lung diseases, may also contribute to tissue damage and neutrophil persistence. Thus, in children with bronchiectasis or PBB and in control subjects, we quantified the phagocytosis of airway apoptotic cells and NTHi by alveolar macrophages and related the phagocytic capacity to clinical and airway inflammation. Children with bronchiectasis (n = 55) or PBB (n = 13) and control subjects (n = 13) were recruited. Alveolar macrophage phagocytosis, efferocytosis, and expression of phagocytic scavenger receptors were assessed by flow cytometry. Bronchoalveolar lavage fluid interleukin (IL) 1β was measured by enzyme-linked immunosorbent assay. For children with PBB or bronchiectasis, macrophage phagocytic capacity was significantly lower than for control subjects (P = .003 and P < .001 for efferocytosis and P = .041 and P = .004 for phagocytosis of NTHi PBB and bronchiectasis, respectively) median phagocytosis of NTHi for the groups was as follows: bronchiectasis, 13.7% (interquartile range [IQR], 11%-16%) PBB, 16% (IQR, 11%-16%) control subjects, 19.0% (IQR, 13%-21%) and median efferocytosis for the groups was as follows: bronchiectasis, 14.1% (IQR, 10%-16%) PBB, 16.2% (IQR, 14%-17%) control subjects, 18.1% (IQR, 16%-21%). Mannose receptor expression was significantly reduced in the bronchiectasis group (P = .019), and IL-1β increased in both bronchiectasis and PBB groups vs control subjects. A reduced alveolar macrophage phagocytic host response to apoptotic cells or NTHi may contribute to neutrophilic inflammation and NTHi colonization in both PBB and bronchiectasis. Whether this mechanism also contributes to the progression of PBB to bronchiectasis remains unknown.
Publisher: European Respiratory Society (ERS)
Date: 07-11-2020
DOI: 10.1183/13993003.01208-2019
Abstract: This European Respiratory Society/Thoracic Society of Australia and New Zealand statement outlines a review of the literature and expert opinion concerning the management of reproduction and pregnancy in women with airways diseases: asthma, cystic fibrosis (CF) and non-CF bronchiectasis. Many women with these diseases are now living into reproductive age, with some developing moderate-to-severe impairment of lung function in early adulthood. The statement covers aspects of fertility, management during pregnancy, effects of drugs, issues during delivery and the post-partum period, and patients’ views about family planning, pregnancy and parenthood. The statement summarises current knowledge and proposes topics for future research, but does not make specific clinical recommendations.
Publisher: The American Association of Immunologists
Date: 05-2012
Abstract: Asthma is an allergic airways disease (AAD) caused by dysregulated immune responses and characterized by eosinophilic inflammation, mucus hypersecretion, and airway hyperresponsiveness (AHR). NKT cells have been shown to contribute to AHR in some mouse models. Conversely, regulatory T cells (Tregs) control aberrant immune responses and maintain homeostasis. Recent evidence suggests that Streptococcus pneumoniae induces Tregs that have potential to be harnessed therapeutically for asthma. In this study, mouse models of AAD were used to identify the S. pneumoniae components that have suppressive properties, and the mechanisms underlying suppression were investigated. We tested the suppressive capacity of type-3-polysaccharide (T3P), isolated cell walls, pneumolysoid (Ply) and CpG. When coadministered, T3P + Ply suppressed the development of: eosinophilic inflammation, Th2 cytokine release, mucus hypersecretion, and AHR. Importantly, T3P + Ply also attenuated features of AAD when administered during established disease. We show that NKT cells contributed to the development of AAD and also were suppressed by T3P + Ply treatment. Furthermore, adoptive transfer of NKT cells induced AHR, which also could be reversed by T3P + Ply. T3P + Ply-induced Tregs were essential for the suppression of NKT cells and AAD, which was demonstrated by Treg depletion. Collectively, our results show that the S. pneumoniae components T3P + Ply suppress AAD through the induction of Tregs that blocked the activity of NKT cells. These data suggest that S. pneumoniae components may have potential as a therapeutic strategy for the suppression of allergic asthma through the induction of Tregs and suppression of NKT cells.
Publisher: Elsevier BV
Date: 12-2004
Publisher: AME Publishing Company
Date: 05-2017
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.JACI.2009.10.018
Abstract: Asthma typically originates in early-life, and the impact of infection during immunologic maturation is a critical factor in disease pathogenesis. The progression of aberrant T(H)2 cell responses and disease development has been attributed to a lack of infections. However, exposure to specific pathogens such as Chlamydia may alter immunologic programming and predispose to asthma. To investigate the effects of chlamydial infection at different ages on allergic airways disease in later life. Neonatal, infant, or adult BALB/c mice were infected and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Hallmark features of allergic airways disease were compared with uninfected allergic and nonallergic controls. Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Notably early-life infection increased mucus-secreting cell numbers, IL-13 expression, and airway hyperresponsiveness. Neonatal infection attenuated eosinophil influx and ovalbumin-specific T(H)2 cytokine release and numbers of activated myeloid dendritic cells (DCs) in lymph nodes. By contrast, infant infection augmented features of allergic inflammation with increased airway eosinophils, T(H)2 cytokine, and DC responses. Both neonatal and infant infection increased systemic DC-induced IL-13 release from CD4(+) T cells. The timing of infection had significant effects on lung structure because neonatal but not infant or adult infection induced increases in alveolar diameter. Early-life respiratory chlamydial infections modulate immune responses, alter lung function and structure, and enhance the severity of allergic airways disease in later life.
Publisher: European Respiratory Society (ERS)
Date: 2002
DOI: 10.1183/09031936.02.00226302
Abstract: Acute exacerbations of asthma are frequently caused by viral infections, but the inflammatory mechanisms in virus-induced asthma are poorly understood. The aim of the present study was to determine whether viral infection in acute asthma was associated with increased sputum neutrophil degranulation and increased cellular lysis and whether these changes are related to clinical severity. Adults (n=49) presenting to the emergency department with acute asthma were examined for infection by means of sputum direct-fluorescence antigen detection, sputum culture, and sputum polymerase chain reaction for Mycoplasma, Chlamydia and Legionella pneumophila, and all common respiratory viruses. Subjects infected with one of these agents were classed as having an infective exacerbation. Spirometry and sputum induction were performed on presentation and 4-5 weeks later. Thirty-seven subjects (76%) had virus infection and acute asthma. Those with virus infection had increased sputum neutrophils (p<0.05) and increased neutrophil elastase (p<0.05), this was related to increased elevated sputum lactate dehydrogenase (LDH). Subjects with noninfective asthma had an increase in the proportion of sputum eosinophils. Both groups had elevated sputum eosinophil cationic protein (ECP) concentrations. Higher levels of sputum LDH and ECP were associated with a longer hospital stay. Virus infection and acute asthma is associated with neutrophilic inflammation, cell lysis and more severe clinical disease.
Publisher: Informa UK Limited
Date: 16-09-2021
Publisher: Wiley
Date: 23-12-2016
DOI: 10.1111/CEA.12634
Abstract: Non-eosinophilic asthma (NEA) is a distinct, often corticosteroid-resistant inflammatory asthma phenotype. NK and NKT-like cells are effector lymphocytes that we have shown, like CD28null T cells, to be relatively resistant to steroids and major sources of pro-inflammatory/cytotoxic mediators. We hypothesized that these cells and mediators would be increased in peripheral blood in NEA. Adults with severe asthma and variable airflow obstruction, poorly controlled despite maintenance therapy with inhaled glucocorticosteroids and long-acting bronchodilators, were recruited. Blood was assessed in those with eosinophilic asthma (n = 12), NEA (n = 25) and healthy non-smoking controls (n = 30). We applied flow cytometry to measure T, CD28null, NK and NKT-like cells and their expression of granzyme B, perforin, and killer inhibitory/activating receptors CD94(Kp43), CD158b and CD107A. Intracellular pro-inflammatory cytokine production (IFN-γ and TNF-α) was assessed in 18 controls and 10 patients with asthma/group. In NEA, there was increased expression of granzyme B by CD8+ T cells vs. There was increased expression of granzyme B and CD158 and decreased CD94 on NK cells, vs. healthy controls and those with eosinophilic asthma. IFN-γ production by NK cells and TNF-α production by NKT-like cells in NEA were significantly increased vs. In both eosinophilic and NEA phenotypes, there were significant increases in CD4+28null T cells (72% and 81% increases, respectively, vs. controls) and their expression of pro-inflammatory cytokines. Significant correlations were noted between blood CD4+28null T cells and neutrophil numbers in induced sputum, and between corticosteroid dose and blood NKT-like cells, and their production of granzyme B and TNF-α and NK IFN-γ. In poorly controlled asthma, altered expression of cytotoxic ro-inflammatory mediators can be seen on a variety of lymphocyte subsets in the peripheral blood these changes are most apparent in NEA. Whether this pattern of expression is a marker of treatment responsiveness and future risk of exacerbations remains to be determined.
Publisher: Wiley
Date: 28-03-2022
DOI: 10.5694/MJA2.51464
Publisher: Wiley
Date: 11-04-2023
DOI: 10.1111/RESP.14505
Publisher: Informa UK Limited
Date: 2005
Abstract: Exhaled nitric oxide (eNO) is a potential tool in epidemiological studies of asthma. It was hypothesized that in a cross-sectional survey of asthma in adolescent children, eNO may contribute to the detection of this disease. A cohort of Australian school children in two educational years (n = 107, aged 14.7 +/- 2.3 years, 42.9% female) were surveyed in terms of exhaled nitric oxide (eNO), which was compared with other indicators of asthma: asthma symptoms, atopy [skin prick tests (SPT)], hypertonic saline bronchial reactivity, sputum inflammatory cells and eosinophilic cationic protein. Significant positive correlations were found with eNO and number of positive skin prick tests (p = 0.001 n = 98), symptoms (p = 0.05 n = 107), sputum eosinophils (p = 0.025 n = 83), and sputum eosinophilic cationic protein (p = 0.009 n = 83). There was no significant relationship with airway hyperresponsiveness (p = 0.3 n = 15). eNO had a negative predictive value for asthma of 83%, and a positive predictive value of 54%, which is comparable with most current tests for diagnosing asthma. eNO appears to be a useful indicator of atopy and airway inflammation, but in this population it was not closely related to airway hyperresponsiveness.
Publisher: Wiley
Date: 07-10-2008
DOI: 10.1002/PPUL.20906
Abstract: Protracted bacterial bronchitis (PBB) is a common cause of paediatric chronic moist cough. PBB is defined as the presence of isolated chronic moist cough which resolves with antibiotic therapy within 2 weeks and an absence of pointers suggesting alternative diagnoses. Our aim was to describe the clinical profile and examine the airway cellularity and likely promoters of neutrophilic inflammation in the bronchoalveolar lavage (BAL) of children with PBB compared with chronic cough due to other causes and controls. We explored the innate immune signaling receptors, toll-like receptors (TLR)-2 and TLR-4, as well as relevant effector molecules. A cross-sectional comparison was made of 100 children median age 2.58 years (with either PBB, coughing due to another cause or no cough controls) who underwent flexible bronchoscopy with lavage. BAL was evaluated for airway cytology, microbiology, inflammatory mediators interleukin 8 (IL-8) and active matrix metalloproteinase 9 (MMP-9) and TLR-2 and TLR-4 messenger RNA (mRNA) expression. Children with PBB had marked airway neutrophilia and increased median cytokine levels when compared to those with cough that resolved naturally and no cough controls: IL-8 0.67 versus 0.07 and 0.06 ng/ml (P < 0.005) and active MMP-9 7.25 versus 1.35 and 0.38 ng/ml (P < 0.005). The values for TLR-2 and TLR-4 mRNA expression were significantly elevated in children with PBB when compared to the control group. PBB is a paediatric condition which presents with chronic moist cough and its airway profile is characterized by intense neutrophilic airway inflammation with marked inflammatory mediator response and evidence of innate immune activation.
Publisher: Wiley
Date: 19-07-2004
Publisher: Wiley
Date: 04-03-2021
DOI: 10.1111/ALL.14741
Abstract: Airway and systemic eosinophilia are important treatable traits in both severe asthma and COPD. The molecular basis of eosinophilia in COPD is poorly understood but could involve type 2 cytokines (IL5, IL13) and prostaglandin D 2 (PGD 2 ). This study included non‐obstructive airways disease (OAD) controls ( n = 19), a COPD cohort ( n = 96) and a severe asthma cohort ( n = 84). Demographics, exacerbation history, disease impact (SGRQ) and spirometry were assessed. Participants were categorized as eosinophilic using either sputum eosinophil proportion (≥3%) or blood eosinophil count (≥300/μL). Sputum type 2 inflammatory measures included PGD 2 by ELISA and gene expression (qPCR) of IL5 , IL13 and the haematopoietic PGD 2 synthase ( HPGDS ). Type 2 markers did not differ across groups except HPGDS mRNA which was highest in non‐OAD controls and lowest in COPD. IL5 and IL13 mRNA and PGD 2 levels were significantly increased in eosinophilic vs non‐eosinophilic severe asthma but did not differ between eosinophilic COPD and eosinophilic severe asthma or non‐eosinophilic COPD. HPGDS expression was higher in eosinophilic severe asthma compared with eosinophilic COPD. Results were similar using sputum or blood eosinophil cut‐offs. Sputum IL5 and IL13 were highly intercorrelated in severe asthma ( r = 0.907, p 0.001) and COPD ( r = 0.824, p 0.001), were moderately correlated with sputum eosinophils in severe asthma ( IL5 r = 0.440, p 0.001 IL13 r = 0.428, p 0.001) and were weakly correlated in COPD ( IL5 r = 0.245, p 0.05 IL13 r = 0.317, p 0.05). Molecular markers of type 2 airway inflammation do not differ between eosinophilic asthma and eosinophilic COPD however, the relationship between eosinophilia and type 2 airway markers appears weaker in COPD than in severe asthma.
Publisher: Wiley
Date: 28-01-2016
DOI: 10.1111/JGH.13078
Abstract: Dietary restrictions contribute to the unpleasantness of bowel preparation for colonoscopy. We compare the effectiveness and tolerability of a low residue diet of white-colored foods ("White Diet") with a clear-fluid diet the day prior to colonoscopy in an endoscopist-blinded randomized non-inferiority trial. Adults undergoing outpatient colonoscopy were randomized with stratification by procedure timing to a White Diet or clear-fluid diet. All received a 2-L polyethylene glycol lavage solution with ascorbate, sodium sulfate, and electrolytes, the day-before for morning and as a split-dose for afternoon procedures. The primary end-point was successful bowel preparation (A or B on the Harefield Cleansing Scale). Regimen tolerance/acceptance was assessed by questionnaire. An intention-to-treat analysis with a predefined non-inferiority margin of 15% was used to compare efficacy. A total of 226 patients (average age 52 years, 51% male) were randomized (111 clear diet, 115 White Diet). Bowel preparation was successful in 91% on the clear-fluid diet vs 84.4% on the White Diet, difference being -6.6% (lower one sided 95% CI -13.8%), with no difference according to diet. The split-dose regimen (in 55%) had a higher success rate than day-before regimen (96% vs 80%, p < 0.001). The White Diet was preferred with less hunger and interference with daily activities (p < 0.001). Procedural/withdrawal time and polyp/adenoma detection were similar between groups. The White Diet was preferred and better tolerated by patients without detriment to the success of bowel preparation or colonoscopy performance, especially with the split-dose regimen.
Publisher: S. Karger AG
Date: 08-10-2009
DOI: 10.1159/000245899
Abstract: i Background: /i The assessment of eosinophilic airway inflammation using induced sputum identifies a corticosteroid-responsive subtype that can be used to guide anti-inflammatory therapy. The stability of airway inflammation in asthma over time is not known, yet this information is crucial to inflammation-based patient management. i Objective: /i The aim of this study was to determine the reproducibility of non-eosinophilic asthma. i Methods: /i Participants with stable asthma (n = 26) underwent a sputum induction each month for 5 months. Sputum was dispersed and differential cell counts were performed. The reproducibility of inflammatory subtype with different eosinophil cut points (starting at 1% eosinophils) was examined and the minimum number of visits required to determine inflammatory subtype was calculated. i Results: /i One hundred and twenty- two sputum s les were obtained (success 94%). All cut points greater than 2% eosinophils were reproducible and a 3% cut point resulted in the highest agreement with a κ statistic of 0.538. Specificity and sensitivity were high for determining inflammatory subtype after 1 or 3 sputum s les. i Conclusions: /i A cut point of 3% eosinophils should be used to distinguish eosinophilic from non-eosinophilic airway inflammation in asthma. This allows a single sputum s le to be used to reliably determine the presence of eosinophilia.
Publisher: Elsevier BV
Date: 09-2011
DOI: 10.1016/J.PRRV.2011.01.009
Abstract: Asthma and obesity have been increasing in prevalence internationally among children. Evidence points to an association between these chronic morbidities, suggesting the development of an 'obese asthma' phenotype in childhood. This review summarises the evidence that the proinflammatory environment created by excess adiposity may provide a mechanism leading to obese asthma in children and adolescents. Weight loss studies conducted in children without asthma have demonstrated a reduction in systemic inflammation. However, the impact of weight loss in the obese paediatric population with asthma has not been investigated. The paucity of information highlights the need for high quality randomised controlled trials of weight loss in this population that include assessment of systemic and airway inflammation, and clinical asthma outcomes. This will lead to refinements in management approaches for these patients.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JAIP.2019.04.012
Abstract: Terminology used to define clinical cough is based on features such as duration, underlying causes, and associated characteristics such as whether the cough is "dry" or "productive." Terms such as "refractory chronic cough," "unexplained chronic cough," and "idiopathic cough" are commonly used to describe a cough that persists despite extensive investigation and therapeutic trials. The use of these terms, sometimes interchangeably, has led to a degree of confusion and with the emergence of the new clinical and mechanisitic concept associated with cough, "cough hypersensitivity syndrome," there is a need for some clarity in the nomenclature used to describe this condition.
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.VACCINE.2007.09.034
Abstract: Asthma is a common inflammatory disease of the airways. Current therapies alleviate symptoms but do not treat the disease. We aim to develop effective immunomodulatory therapies (IMTs) for asthma that target the underlying causes of disease based on Streptococcus pneumoniae (Spn). The effect of Spn IMT on the development of asthma [allergic airways disease (AAD)] was determined in mice. Killed Spn was administered before, during or after ovalbumin sensitization, and the subsequent development of AAD was assessed. IMT attenuated T cell cytokine production, goblet cell hyperplasia, airways hyperresponsiveness (AHR), and eosinophil numbers in the blood, bronchoalveolar lavage fluid and peribronchial tissue. This indicates the potential of Spn as an IMT for asthma.
Publisher: American Thoracic Society
Date: 07-1993
Abstract: Mast cell mediators are known to contribute to the pathogenesis of asthma. There is some disagreement concerning the numbers of mast cells in asthmatic mucosa. In this study a standardized bronchial brush technique was developed and used to assess intraepithelial mast cells and other inflammatory cells in allergic and nonallergic asthmatic and nonasthmatic subjects. A total of 10 nonasthmatic (5 allergic) and 13 asthmatic (8 allergic) subjects with stable controlled asthma treated with beta-agonist only were assessed by history, spirometry, allergy prick tests, and methacholine airway responsiveness. During fiberoptic bronchoscopy, bronchoalveolar lavage (BAL) was performed from the middle lobe and standardized bronchial brushings were taken from the lingula and left lower lobe bronchi. Quantitative cell counts were performed blind to the clinical characteristics of the subjects. The average total cell recovery from the brushings was 1.04 (SEM 0.09) x 10(6) ml, with a cell viability of 64% (5.3%). Reproducible total cell and mast cell counts were obtained from brushings taken from two lobar bronchi (ICC 0.86). Mast cells were significantly elevated in asthmatic compared with nonasthmatic subjects (1.5 +/- 0.34 versus 0.15 +/- 0.06%). Allergic asthmatic subjects had the greatest numbers of mast cells (1.86 +/- 0.48%) however, the numbers present in brushings from nonallergic asthmatic subjects were also increased (1.03 +/- 0.45%). The mast cells had the staining characteristics of mucosal mast cells, with formalin-blockable metachromatic staining and positive staining for tryptase. Both asthmatic groups also had elevated BAL eosinophils, and neutrophils were elevated in nonallergic asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: American Thoracic Society
Date: 03-2005
Publisher: Wiley
Date: 27-07-1998
Publisher: European Respiratory Society (ERS)
Date: 24-09-2010
DOI: 10.1183/09031936.00027409
Abstract: Asthma is characterised into eosinophilic and non-eosinophilic phenotypes based on inflammatory cell patterns in airway secretions. Neutrophils are important in innate immunity, and are increased in the airways in non-eosinophilic asthma. The present study investigated the activity of neutrophils in asthma phenotypes. Participants with eosinophilic (n = 8) and non-eosinophilic asthma (n = 9) and healthy controls (n = 11) underwent sputum induction and blood collection. Neutrophils were isolated and cultured with or without lipopolysaccharide. Cytokines were measured by ELISA, and gene expression was analysed using a gene expression microarray and quantitative PCR. In non-eosinophilic asthma, blood neutrophils released significantly higher levels of interleukin-8 at rest. Cytokine gene expression and sputum neutrophil protein production did not differ between asthma subtypes. Microarrays demonstrated closely related expression profiles from participants with non-eosinophilic asthma that were significantly distinct from those in eosinophilic asthma. A total of 317 genes were significantly altered in resting neutrophils from participants with non-eosinophilic asthma versus eosinophilic asthma, including genes related to cell motility and regulation of apoptosis. Non-eosinophilic and eosinophilic asthma are associated with specific gene expression profiles, providing further evidence that these phenotypes of asthma involve different molecular mechanisms of disease pathogenesis at the systemic level. The mechanisms of non-eosinophilic asthma may involve enhancement of blood neutrophil chemotaxis and survival.
Publisher: Wiley
Date: 16-04-2015
DOI: 10.1111/CEA.12505
Abstract: Oral corticosteroids (OCS) are an efficacious treatment for asthma exacerbations, yet risk of adverse effects may decrease patient adherence to therapy. In particular, changes in appetite and dietary intake, which lead to weight gain and changes in body composition, are considered undesirable. To determine whether 10-day OCS therapy in adults with asthma causes changes in leptin, appetite, dietary intake, body weight and body composition. Double-blinded, placebo-controlled randomized cross-over trial of 10 days prednisolone (50 mg) in adults with stable asthma (n = 55) (ACTRN12611000562976). Pre- and post-assessment included spirometry, body weight, body composition measured by dual-energy X-ray absorptiometry and bioelectrical impedance analysis, appetite measured using a validated visual analogue scale (VAS) and dietary intake assessed using 4-day food records. Leptin was measured as a biomarker of appetite and eosinophils as an adherence biomarker. Outcomes were analysed by generalized linear mixed models. Subject adherence was confirmed by a significant decrease in blood eosinophils (× 10(9) /L) following prednisolone compared to placebo [Coef. -0.29, 95% CI: (-0.39, -0.19) P < 0.001]. There was no difference in serum leptin (ng/mL) [Coef. 0.13, 95% CI: (-3.47, 3.72) P = 0.945] or appetite measured by VAS (mm) [Coef. -4.93, 95% CI: (-13.64, 3.79) P = 0.267] following prednisolone vs. placebo. There was no difference in dietary intake (kJ/day) [Coef. 255, 95% CI: (-380, 891) P = 0.431], body weight (kg) [Coef. -0.38, 95% CI: (-0.81, 0.05) P = 0.083] or body fat (%) [Coef. -0.31, 95% CI: (-0.81, 0.20) P = 0.230]. Symptoms including sleep and gastrointestinal disturbance were reported significantly more often during prednisolone vs. placebo. Short-term OCS in stable asthma did not induce significant changes in appetite, dietary intake, body weight or composition, although other adverse effects may require medical management. This evidence may assist in increasing medication adherence of asthmatics prescribed OCS for exacerbations.
Publisher: Springer Science and Business Media LLC
Date: 14-10-2007
DOI: 10.1038/NM1660
Abstract: The role of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in immune responses mediated by T-helper 2 (T(H)2) lymphocytes is unknown. Here we characterize the development of allergic airway disease in TRAIL-deficient (Tnfsf10(-/-)) mice and in mice exposed to short interfering RNA targeting TRAIL. We show that TRAIL is abundantly expressed in the airway epithelium of allergic mice and that inhibition of signaling impairs production of the chemokine CCL20 and homing of myeloid dendritic cells and T cells expressing CCR6 and CD4 to the airways. Attenuated homing limits T(H)2 cytokine release, inflammation, airway hyperreactivity and expression of the transcriptional activator STAT6. Activation of STAT6 by interleukin-13 restores airway hyperreactivity in Tnfsf10(-/-) mice. Recombinant TRAIL induces pathognomic features of asthma and stimulates the production of CCL20 in primary human bronchial epithelium cells. TRAIL is also increased in sputum of asthmatics. The function of TRAIL in the airway epithelium identifies this molecule as a target for the treatment of asthma.
Publisher: European Respiratory Society (ERS)
Date: 26-07-2022
DOI: 10.1183/13993003.00546-2022
Abstract: Physical inactivity is common in asthma and is recognised as an important modifiable risk for poor clinical outcomes such as impaired asthma control and health-related quality of life (HRQoL). Despite evidence supporting the role of physical activity in reducing the risk of these outcomes, little is known about optimal interventions for increasing physical activity in those with severe disease. This systematic review and meta-analysis evaluates the effectiveness of interventions in increasing physical activity in severe asthma. MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, PubMed, Informit, SPORTDiscus and Cochrane databases were searched up to September 2021 for physical activity-based intervention studies that assessed physical activity outcomes ( e.g. steps per day, time spent undertaking physical activity) in adults with severe asthma. Data on asthma-related ( e.g. asthma control) and health-related outcomes ( e.g. HRQoL) were assessed as secondary outcomes. The revised Cochrane Risk of Bias tool was used to assess risk of bias. Random-effects meta-analyses synthesised data where possible. Four randomised controlled trials (all 12 weeks in duration) including 176 adults with moderate-to-severe asthma were included. An increase in physical activity was reported with a moderate-vigorous intensity aerobic and resistance training intervention (steps per day and time spent undertaking physical activity), and an unsupervised pedometer-based intervention (steps per day). Meta-analyses showed that physical activity interventions had an overall positive effect on steps per day (mean difference (MD) 1588, 95% CI 399–2778 p = 0.009, I 2 =23), asthma control (MD −0.65, 95% CI −0.95–−0.35 p .0001, I 2 =0%) and HRQoL (MD 0.56, 95% CI 0.10–1.01 p = 0.02, I 2 =16%) compared to control. While there is some evidence supporting the effectiveness of interventions in improving physical activity in adults with severe asthma, higher-quality, large-scale studies of longer duration are needed to determine the optimal intervention.
Publisher: Wiley
Date: 27-05-2016
DOI: 10.1111/CEA.12742
Abstract: Adipokines, such as resistin and adiponectin, modify inflammation and may contribute to increased asthma risk and severity in obese people. To examine plasma resistin and resistin:adiponectin ratio (i) in asthmatics compared to healthy controls, (ii) according to asthma severity, obesity and gender (iii) following weight loss in obese asthmatics. In a cross-sectional observational study of asthmatic adults (n = 96) and healthy controls (n = 46), plasma resistin and adiponectin were measured. In a separate intervention study, obese asthmatic adults (n = 27) completed a 10-week weight loss intervention and plasma resistin and adiponectin concentrations were analysed. Plasma resistin and resistin:adiponectin ratio were higher in asthma compared to controls and were higher again in subjects with a severe vs. mild-to-moderate asthma pattern. Amongst asthmatic subjects, resistin was not modified by gender or obesity, while adiponectin was lower in males and obese subjects. As a result, resistin:adiponectin ratio was higher in obese males, non-obese males and obese females, compared to non-obese females. In a logistic regression model, plasma resistin concentration was a predictor of asthma risk. In a multiple linear regression model, plasma resistin:adiponectin ratio was a negative predictor of FEV1 in asthma. Following weight loss, neither resistin, adiponectin nor resistin:adiponectin ratio was changed. However, the change (∆) in %body fat was associated with ∆ resistin:adiponectin ratio. Post-intervention ∆ resistin was negatively correlated with both ∆FRC and ∆RV. This study demonstrates that resistin and resistin:adiponectin ratio are higher in asthma and are higher again in subjects who have more severe disease. Resistin:adiponectin ratio is highest in obese male asthmatics. As resistin is a predictor of asthma risk and resistin:adiponectin is a predictor of FEV1 in asthma, these adipokines may be contributing to the obese asthma phenotype, thus providing a potential therapeutic target for obese asthma.
Publisher: BMJ
Date: 12-2006
Publisher: Canadian Science Publishing
Date: 05-2017
Abstract: Due to gastrointestinal tract adaptability, the study aimed to determine the impact of gut-training protocol over 2 weeks on gastrointestinal status, blood glucose availability, fuel kinetics, and running performance. Endurance runners (n = 25) performed a gut-challenge trial (GC1), consisting of 2 h running exercise at 60% V̇O 2max whilst consuming gel-discs containing 30 g carbohydrates (2:1 glucose/fructose, 10% w/v) every 20 min and a 1 h distance test. Participants were then randomly assigned to a carbohydrate gel-disc (CHO-S), carbohydrate food (CHO-F), or placebo (PLA) gut-training group for 2 weeks of repetitive gut-challenge intervention. Participants then repeated a second gut-challenge trial (GC2). Gastrointestinal symptoms reduced in GC2 on CHO-S (60% p = 0.008) and CHO-F (63% p = 0.046) reductions were greater than PLA (p 0.05). H 2 peak was lower in GC2 on CHO-S (mean (CI): 6 (4–8) ppm) compared with CHO-F (9 (6–12) ppm) and PLA (12 (2–21) ppm) (trial × time: p 0.001). Blood glucose concentration was higher in GC2 on CHO-S (7.2 (6.3–8.1) mmol·L −1 ) compared with CHO-F (6.1 (5.7–6.5) mmol·L −1 ) and PLA (6.2 (4.9–7.5) mmol·L −1 ) (trial × time: p = 0.015). No difference in oxidation rates, plasma I-FABP, and cortisol concentrations were observed between groups and trials. Distance test improved on CHO-S (5.2%) and CHO-F (4.3%) in GC2, but not on PLA (–2.1%) (trial × time: p = 0.009). Two weeks of gut-training with CHO-S and CHO-F improved gastrointestinal symptoms and running performance compared with PLA. CHO-S also reduced malabsorption and increased blood glucose availability during endurance running compared with PLA.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2002
DOI: 10.1097/00130832-200206000-00002
Abstract: Monitoring asthma outcomes is an essential step to the successful implementation of national asthma guidelines. Symptoms, airflow obstruction and exacerbations can be monitored by patients with asthma and by physicians. Patients who practise self-monitoring in conjunction with use of a written action plan and regular medical review have significantly fewer hospitalizations, emergency room visits and lost time from work. Additional monitoring tools are under evaluation, and these include measures of airway responsiveness, airway inflammation, and Internet-based monitoring systems.
Publisher: Elsevier BV
Date: 07-2021
Publisher: Elsevier BV
Date: 03-2023
Publisher: BMJ
Date: 1992
DOI: 10.1136/THX.47.1.25
Abstract: Airway inflammation is considered to be important in asthma but is relatively inaccessible to study. Less invasive methods of obtaining sputum from patients unable to produce it spontaneously should provide a useful investigational tool in asthma. A method to induce sputum with inhaled hypertonic saline was modified for use in 17 asthmatic patients and 17 normal subjects who could not produce sputum spontaneously. The success rate and safety of the method, the reproducibility of cell counts, and differences in cell counts between the asthmatic and normal groups were examined. Hypertonic saline solution 3-5% was inhaled for up to 30 minutes after inhalation of salbutamol. Subjects were asked to expectorate sputum every five minutes. The quality of the s le was scored on the volume of plugs and the extent of salivary contamination. Plugs from the lower respiratory tract were selected for a total cell count and for differential cell counts of eosinophils and metachromatic cells (mast cells and basophils) in direct smears. Adequate s les from the lower respiratory tract were obtained in 76% of first attempts. The mean fall in the forced expiratory volume in one second (FEV1) during inhalation of saline was 5.3% and the maximum fall 20%. Eosinophil and metachromatic cell counts were reproducible (reliability coefficient 0.8 and 0.7 respectively). When compared with sputum from normal subjects sputum from asthmatic patients contained a significantly higher proportion of eosinophils (mean 18.5% (SE 3.8%) v 1.9% (0.6%)) and metachromatic cells (0.50% (0.18%) v 0.039% (0.014%)). In the asthmatic group the differential eosinophil count correlated with the baseline FEV1. Induced sputum is capable of detecting differences in cell counts between normal and asthmatic subjects and merits further development as a potential means of assessing airway inflammation in asthma.
Publisher: Wiley
Date: 25-07-2013
DOI: 10.1111/RESP.12103
Abstract: Diseases associated with laryngeal dysfunction include chronic refractory cough (CRC), paradoxical vocal fold movement (PVFM), muscle tension dysphonia (MTD) and globus pharyngeus. We hypothesized the presence of a common sensory laryngeal dysfunction, the 'laryngeal hypersensitivity' syndrome, in these conditions. The aim of the study was to compare symptoms and sensory function in patients with CRC, PVFM, MTD and globus. The 103 participants included healthy controls (n = 13) and four case groups: CRC (n = 33), PVFM (n = 28), globus pharyngeus (n = 11) and MTD (n = 18). Participants completed self-report questionnaires: Symptom Frequency and Severity Scale, Voice Handicap Index and the Laryngeal Paraesthesia Questionnaire and quantitative sensory testing: capsaicin cough reflex sensitivity, hypertonic saline challenge, the timed swallow test, acoustic voice testing, cough frequency monitor and a voice stress test. All case groups reported a high-symptom burden in comparison to controls. The case groups showed a similar pattern of symptoms, with impairment in each of the cough, respiration, vocal and upper airway symptom domains. Objective testing revealed significant sensory impairment in the case groups compared to controls and also showed an overlap in sensory dysfunction between the four case groups. Furthermore, there was cross-sensory stimulation of symptoms whereby stimulation of a particular response resulted in symptoms in another domain. These discrete clinical laryngeal syndromes display considerable overlap in their clinical features and a common sensory dysfunction, supporting the 'laryngeal hypersensitivity' hypothesis. Reconceptualizing functional laryngeal disorders as a form of laryngeal hypersensitivity syndrome provides an alternative approach to management of these perplexing conditions.
Publisher: Elsevier BV
Date: 04-2019
DOI: 10.1016/J.CHEST.2019.01.002
Abstract: Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. BAL was prospectively collected from 28 children with PBB (median age, 1.7 years range, 0.6-7.4) and 8 control patients (median age, 1.9 years range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation. Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P = .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more erse microbiota including Prevotella species. Alpha ersity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha ersity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.
Publisher: Informa UK Limited
Date: 18-11-2009
DOI: 10.3109/10715760903362576
Abstract: Potential bacterial pathogens are found in the airways in several diseases that are associated with neutrophilic inflammation. The aim of this study was to characterize subjects with stable asthma, with no symptoms of respiratory infection, to assess whether key potentially pathogenic bacteria were present in significant quantities in the airways and to correlate this with the pattern of airway inflammation and oxidative stress. Subjects with stable asthma (n = 115) and healthy controls (n = 8) underwent clinical assessment, including hypertonic saline challenge combined with sputum induction. A significant load of potentially pathogenic bacteria (> 10(6) cfu/mL) was cultured from the sputum of 17 (15%) subjects with stable asthma and was associated with higher total cell counts, proportion and number of neutrophils, sputum IL-8 and 8-isoprostane concentrations. The role of bacteria in potentiating neutrophilic asthma warrants further investigation. Therapies such as antibiotic and antioxidant treatment may be most effective in this sub-group of patients.
Publisher: Elsevier BV
Date: 02-0008
DOI: 10.1016/J.RMED.2015.12.003
Abstract: An overlap between obesity and asthma exists, and inflammatory cells in adipose tissue could drive the development of asthma. Comparison of adipose tissue gene expression among Inuit living in Greenland to those in Denmark provides an opportunity to assess how changes in adipose tissue inflammation can be modified by migration and diet. To examine mast cell and inflammatory markers in adipose tissue and the association with asthma. Two Inuit populations were recruited, one living in Greenland and another in Denmark. All underwent adipose subcutaneous biopsy, followed by clinical assessment of asthma, and measurement of AHR. Adipose tissue biopsies were homogenised, RNA extracted, and PCR was performed to determine the relative gene expression of mast cell (tryptase, chymase, CPA3) and inflammatory markers (IL-6, IL-1β, and CD163). Of the 1059 Greenlandic Inuit participants, 556 were living in Greenland and 6.4% had asthma. Asthma was increased in Denmark (9%) compared to Greenland (3.6%, p < 0.0001) and associated with increased adipose tissue IL-6 gene expression and increased BMI. There was no association between asthma and adipose tissue mast cell gene expression. Pro-inflammatory gene expression (IL-6, IL-1β) was higher in those living in Denmark, and with increasing BMI and dietary changes. The anti-inflammatory (M2) macrophage marker, CD163, was higher in Greenland-dwelling Inuit (p < 0.01). No association was found between gene expression of mast cell markers in adipose tissue and asthma. Among Greenlandic Inuit, adipose tissue inflammation is also increased in those who migrate to Denmark, possibly as a result of dietary changes.
Publisher: American College of Physicians
Date: 15-08-1988
DOI: 10.7326/0003-4819-109-4-288
Abstract: Radiation pneumonitis occurs 6 to 12 weeks after thoracic irradiation, and is thought to be due to direct radiation-induced lung injury. Four patients who developed pneumonitis after unilateral thoracic irradiation for carcinoma of the breast were studied with bronchoalveolar lavage, gallium scan of the lung, and respiratory function tests. On the irradiated side of the chest, all four patients showed an increase in total cells recovered from the lavage fluid and a marked increase in the percentage of lymphocytes. When results for the unirradiated lung were compared with results for the irradiated lung, there was a comparable increase in total cells and percentage of lymphocytes. Gallium scans showed increases for both irradiated and unirradiated lungs. Prompt improvement was seen after corticosteroid therapy in all patients. The fact that abnormal findings occur equally in irradiated and unirradiated lung is inconsistent with simple direct radiation-induced injury and suggests an immunologically mediated mechanism such as a hypersensitivity pneumonitis.
Publisher: Wiley
Date: 2006
DOI: 10.1111/J.1440-1843.2006.00784.X
Abstract: The authors sought to investigate the detection of non-eosinophilic asthma using induced sputum. Although this is an important subtype of clinical asthma, its recognition is not standardized. Adult non-smokers with asthma and healthy controls underwent sputum induction and hypertonic saline challenge. Non-eosinophilic asthma was defined as symptomatic asthma with normal sputum eosinophil counts. The normal range for sputum eosinophil count was determined using the 95th percentile from the healthy control group as a cut-off point. The recognition of non-eosinophilic asthma using eosinophil proportion was in agreement with a definition based on absolute eosinophil count (kappa 0.67). Non-eosinophilic asthma was a stable subtype over both the short term (4 weeks) and longer term (5 years, kappa 0.77). Airway inflammation in asthma could be categorized into four inflammatory subtypes based on sputum eosinophil and neutrophil proportions. These subtypes were neutrophilic asthma, eosinophilic asthma, mixed granulocytic asthma and paucigranulocytic asthma. Subjects with increased neutrophils (neutrophilic asthma and mixed granulocytic asthma) were older and had an increased total cell count and cell viability compared with other subtypes. Induced sputum eosinophil proportion is a good discriminator for eosinophilic asthma, providing a reproducible definition of a homogenous group. The remaining non-eosinophilic subjects are heterogeneous and can be further classified based on the presence of neutrophils. These inflammatory subtypes have important implications for the investigation and characterization of airway inflammation in asthma.
Publisher: BMJ
Date: 04-2002
DOI: 10.1136/ADC.86.4.270
Abstract: Prospective data on the temporal relation between cough, asthma symptoms, and airway inflammation in childhood asthma is unavailable. Using several clinical (diary, quality of life), lung function (FEV(1), FEV(1) variability, airway hyperresponsiveness), cough (diary, cough receptor sensitivity (CRS)), and inflammatory markers (sputum interleukin 8, eosinophilic cationic protein (ECP), myeloperoxidase and serum ECP) of asthma severity, we prospectively described the course of these markers in children with asthma during a non-acute, acute, and resolution phase. A total of 21 children with asthma underwent these baseline tests 11 were retested during days 1, 3, 7, and 28 of an exacerbation. Asthma exacerbations were characterised by increased asthma and cough symptoms and eosinophilic inflammation. Sputum ECP showed the largest increase and peaked later than clinical scores. Asthma scores consistently related to cough score only early in the exacerbation. Neither CRS nor cough scores related to any inflammatory marker. In mild asthma exacerbations, eosinophilic inflammation is dominant. In asthmatic children who cough as a dominant symptom, cough heralds the onset of an exacerbation and increased eosinophilic inflammation, but cough scores and CRS do not reflect eosinophilic airway inflammation.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.CHEST.2019.10.051
Abstract: Regional and/or national severe asthma registries provide valuable country-specific information. However, they are often limited in scope within the broader definitions of severe asthma, have insufficient statistical power to answer many research questions, lack intraoperability to share lessons learned, and have fundamental differences in data collected, making cross comparisons difficult. What is missing is a worldwide registry which brings all severe asthma data together in a cohesive way, under a single umbrella, based on standardized data collection protocols, permitting data to be shared seamlessly. The International Severe Asthma Registry (ISAR isaregistries.org/) is the first global adult severe asthma registry. It is a joint initiative where national registries (both newly created and preexisting) retain ownership of their own data but open their borders and share data with ISAR for ethically approved research purposes. Its strength comes from collection of patient-level, anonymous, longitudinal, real-life, standardized, high-quality data (using a core set of variables) from countries across the world, combined with organizational structure, database experience, inclusivity/openness, and clinical, academic, and database expertise. This gives ISAR sufficient statistical power to answer important research questions, sufficient data standardization to compare across countries and regions, and the structure and expertise necessary to ensure its continuance and the scientific integrity and clinical applicability of its research. ISAR offers a unique opportunity to implement existing knowledge, generate new knowledge, and identify the unknown, therefore promoting new research. The aim of this commentary is to fully describe how ISAR may improve our understanding of severe asthma.
Publisher: Cambridge University Press (CUP)
Date: 29-10-2009
DOI: 10.1017/S0007114509992376
Abstract: Dietary antioxidants are important in protecting against oxidative stress. We have previously demonstrated that circulating dietary antioxidant levels are reduced in asthma. The present study examined the variation in dietary antioxidant levels in asthma, according to airway responsiveness, asthma control and clinical asthma pattern. Peripheral blood was collected from forty-one subjects with stable, persistent asthma. Airway responsiveness was assessed by hypertonic saline challenge. Asthma control was assessed using the Asthma Control Questionnaire. Clinical asthma pattern was determined using Global Initiative for Asthma (GINA) criteria. Whole-blood carotenoids (β-carotene, lycopene, α-carotene, β-cryptoxanthin, lutein/zeaxanthin) and tocopherols (α-, δ-, γ-tocopherol) were measured by HPLC. Plasma antioxidant potential (AOP) was determined by colorimetric assay (OxisResearch, Portland, OR, USA). Asthmatic subjects with airway hyper-responsiveness (AHR) had reduced levels of β-carotene and α-tocopherol compared with those without AHR. Subjects with uncontrolled asthma had low levels of AOP compared with those with controlled or partly controlled asthma. Subjects with a severe persistent clinical asthma pattern had reduced levels of α-tocopherol compared with those with a mild to moderate asthma pattern. We conclude that asthmatic subjects with AHR, uncontrolled asthma and a severe asthma pattern have impaired antioxidant defences and are thus most susceptible to the damaging effects of oxidative stress. This highlights the potential role for antioxidant supplementation in these subjects.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.CHEST.2019.10.053
Abstract: Clinical characteristics of the international population with severe asthma are unknown. Intercountry comparisons are hindered by variable data collection within regional and national severe asthma registries. We aimed to describe demographic and clinical characteristics of patients treated in severe asthma services in the United States, Europe, and the Asia-Pacific region. The International Severe Asthma Registry retrospectively and prospectively collected data in patients with severe asthma (≥ 18 years old), receiving Global Initiative for Asthma (GINA) Step 5 treatment or with severe asthma remaining uncontrolled at GINA Step 4. Baseline demographic and clinical data were collected from the United States, United Kingdom, South Korea, Italy, and the Severe Asthma Web-based Database registry (including Australia, Singapore, and New Zealand) from December 2014 to December 2017. We included 4,990 patients. Mean (SD) age was 55.0 (15.9) years, and mean (SD) age at asthma onset was 30.7 (17.7) years. Patients were predominantly female (59.3%) and white (72.6%), had never smoked (60.5%), and were overweight or obese (70.4%) 34.9% were at GINA Step 5 and 57.2% had poorly controlled disease. A total of 51.1% of patients were receiving regular intermittent oral corticosteroids, and 25.4% were receiving biologics (72.6% for those at GINA Step 5). Mean (SD) exacerbation rate was 1.7 (2.7) per year. Intercountry variation was observed in clinical characteristics, prescribed treatments, and biomarker profiles. Using a common data set and definitions, this study describes severe asthma characteristics of a large patient cohort included in multiple severe asthma registries and identifies country differences. Whether these are related to underlying epidemiological factors, environmental factors, phenotypes, asthma management systems, treatment access, and/or cultural factors requires further study.
Publisher: Informa UK Limited
Date: 22-10-2013
DOI: 10.3109/14767058.2013.847080
Abstract: To investigate if maternal asthma is associated with an increased risk of maternal and placental complications in pregnancy. Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). Cohort studies published between January 1975 and March 2012 were considered for inclusion. Forty publications met the inclusion criteria, reporting at least one maternal or placental complication in pregnant women with and without asthma. Relative risk (RR) with 95% confidence intervals (CIs) was calculated. Maternal asthma was associated with a significantly increased risk of cesarean section (RR = 1.31, 95%CI = [1.22-1.39]), gestational diabetes (RR = 1.39, 95%CI = [1.17-1.66]), hemorrhage (antepartum: RR = 1.25, 95%CI = [1.10-1.42] postpartum: RR = 1.29, 95%CI = [1.18-1.41]), placenta previa (RR = 1.23, 95%CI = [1.07-1.40]), placental abruption (RR = 1.29, 95%CI = [1.14-1.47]) and premature rupture of membranes (RR = 1.21, 95%CI = 1.07-1.37). Moderate to severe asthma significantly increased the risk of cesarean section (RR = 1.19, 95%CI = [1.09-1.31]) and gestational diabetes (RR = 1.19, 95%CI = [1.06-1.33]) compared to mild asthma. Bronchodilator use was associated with a significantly lowered risk of gestational diabetes (RR = 0.64, 95%CI = [0.57-0.72]). Pregnant women with asthma are at increased risk of maternal and placental complications, and women with moderate/severe asthma may be at particular risk. Further studies are required to elucidate whether adequate control of asthma during pregnancy reduces these risks.
Publisher: The Korean Academy of Asthma, Allergy and Clinical Immunology and The Korean Academy of Pediatric Al
Date: 2014
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.CLNU.2007.12.002
Abstract: Antioxidant status is disturbed in asthma. Measurement of both oxidized and reduced forms of antioxidants provides important information regarding the oxidant/antioxidant balance. The aim of this study was to investigate the clinical relevance of key antioxidants (alpha-tocopherol and glutathione) in asthma, by measuring the oxidized and reduced forms, in the airways (induced sputum) and systemically (peripheral blood). This cross-sectional study examines stable asthmatics (n=44) and healthy controls (n=31) recruited through John Hunter Hospital, NSW, Australia. We collected peripheral blood and induced sputum during hypertonic saline challenge. Alpha-tocopherol and alpha-tocopherol quinone were measured by HPLC. Total glutathione and glutathione disulfide were determined by a colorimetric assay. Plasma alpha-tocopherol was low in asthma versus controls. Subjects with asthma had higher levels of whole blood alpha-tocopherol quinone and %alpha-tocopherol quinone than controls and %alpha-tocopherol quinone correlated with asthma control (p=0.009). Sputum supernatant levels of total, reduced and oxidized glutathione were elevated in asthma versus controls. Oxidized glutathione in sputum supernatant negatively correlated with FEV(1)/FVC% (p=0.029). In asthma, both systemic and airway antioxidant defences are disturbed. Oxidized forms of alpha-tocopherol and glutathione are associated with clinical asthma outcomes, and should be further investigated as a tool for monitoring asthma.
Publisher: Wiley
Date: 23-12-2014
DOI: 10.1111/RESP.12213
Abstract: The non-eosinophilic phenotype of asthma (NEA) is associated with chronic airway inflammation and airway neutrophilia. An accumulation of apoptotic airway epithelial cells, if not efficiently cleared by efferocytosis, can undergo secondary necrosis, with the potential for inflammation of surrounding tissues. Apoptosis may occur via the T cell granzyme B pathway. The role of granzyme B in NEA is not known. The aim of this study was to investigate production of granzyme B and its inhibitor proteinase inhibitor (PI)-9 by T cells from induced sputum and compare expression between eosinophilic, NEA and healthy controls. We investigated T cell intracellular granzyme B and its inhibitor, PI-9, in sputum from healthy control subjects (n = 10), and patients with NEA (n = 22) or eosinophilic asthma (EA) (n = 15) using flow cytometry. Granzyme B expression and the ratio of granzyme B to PI-9 positive cells were highest in those with NEA for both CD3+ and CD4+ T cells. The expression of granzyme B was not statistically different between patients with NEA and EA however, the ratio of granzyme B to PI-9 positive cells for CD3+ T cells was significantly higher in those with NEA compared with EA. Induced sputum provides a non-invasive tool for investigating T cell cytotoxic mediators in the various asthma subtypes. Granzyme B expression is increased in NEA and the contribution of granzyme B to chronic inflammation requires further study.
Publisher: Wiley
Date: 27-03-2019
DOI: 10.1111/RESP.13545
Publisher: Elsevier BV
Date: 04-1995
Abstract: Asthma management guidelines emphasize increased autonomy for asthmatics through patient education and patient-initiated action plans. The aim of this study was to examine autonomy, as reflected in the preferences of asthmatic subjects for decision making and their preferences for information seeking. The results were related to quality of life in asthma. One hundred twenty-three adults with asthma. Questionnaire-based cross-sectional analytic survey. Eighty-five subjects were recruited from community pharmacies at the point of sale of albuterol inhalers for asthma and compared with 38 subjects recently hospitalized for acute severe asthma. Asthma-related quality of life, autonomy preferences questionnaire. The subjects in both groups had a mild-to-moderate quality of life impairment in all domains that was greater in the posthospitalization group (p < 0.05). Both groups expressed strong preferences for information concerning their condition (92se 0.8, 91se 1.1, out of a possible 100). Subjects did not prefer to make decisions alone about the management of asthma exacerbations (51.0se 1.2, 52.5 se2.0, out of a possible 100). As the severity of the asthma exacerbation increased, the desire to make decisions decreased (p < 0.05). Older subjects expressed less desire for decision making than younger subjects. Self-management autonomy was not correlated with quality of life in asthma. We conclude that while asthmatics have strong desires to be informed about their illness, they do not wish to be the prime decision makers during an exacerbation. These findings have implications for the success of self-management programs and action plans.
Publisher: European Respiratory Society (ERS)
Date: 04-2020
DOI: 10.1183/23120541.00270-2019
Abstract: We aimed to assess adherence to the Australian national guideline (COPD-X) against audited practice, and to document the outcomes of patients hospitalised with an acute exacerbation of chronic obstructive pulmonary disease (COPD) at discharge and 28 days after. A prospective clinical audit of COPD hospital admission from five tertiary care hospitals in five states of Australia was conducted. Post-discharge follow-up was conducted via telephone to assess for readmission and health status. There were 207 admissions for acute exacerbation (171 patients mean 70.2 years old 50.3% males). Readmission rates at 28 days were 25.4%, with one (0.6%) death during admission and eight (6.1%) post-discharge within 28 days. Concordance to the COPD-X guidance was variable 22.7% performed spirometry, 81.1% had blood gases collected when forced expiratory volume in 1 s was L, 99.5% had chest radiography performed, 95.1% were prescribed systemic corticosteroids and 95% were prescribed antibiotic therapy. There were 89.1% given oxygen therapy and 92.6% when arterial oxygen tension was mmHg 65.6% were given ventilatory assistance when pH was .35. Only 32.4% were referred to pulmonary rehabilitation but 76.8% had general practitioner follow-up arranged. When compared against clinical practice guidelines, we found important gaps in management of patients admitted with COPD throughout tertiary care centres in Australia. Strategies to improve guideline uptake are needed to optimise care.
Publisher: Wiley
Date: 28-01-2016
DOI: 10.1111/CEA.12609
Abstract: Airway hyperresponsiveness (AHR) to inhaled mannitol is associated with indirect markers of mast cell activation and eosinophilic airway inflammation. It is unknown how AHR to mannitol relates to mast cell phenotype, mast cell function and measures of eosinophilic inflammation in airway tissue. We compared the number and phenotype of mast cells, mRNA expression of mast cell-associated genes and number of eosinophils in airway tissue of subjects with asthma and healthy controls in relation to AHR to mannitol. Airway hyperresponsiveness to inhaled mannitol was measured in 23 non-smoking, corticosteroid-free asthmatic in iduals and 10 healthy controls. Mast cells and eosinophils were identified in mucosal biopsies from all participants. Mast cells were ided into phenotypes based on the presence of chymase. mRNA expression of mast cell-associated genes was measured by real-time PCR. The proportion of submucosal MCTC was higher in asthmatic in iduals with AHR to mannitol compared with asthmatic in iduals without AHR (median: 40.3% vs. 18.7%, P = 0.03). Increased submucosal MCTC numbers were associated with increased levels of mRNA for thymic stromal lymphopoietin (TSLP) and CPA3 in asthmatics. Reactivity to mannitol correlated significantly with eosinophils in submucosa (r(s): 0.56, P = 0.01). Airway hyperresponsiveness to inhaled mannitol is associated with an altered submucosal mast cell profile in asthmatic in iduals. This mast cell profile is associated with increased levels of TSLP and CPA3. The degree of AHR to mannitol is correlated with the degree of eosinophilic inflammation in the airway submucosa.
Publisher: Informa UK Limited
Date: 02-2017
DOI: 10.2147/COPD.S119443
Publisher: Elsevier
Date: 2008
Publisher: Wiley
Date: 2021
DOI: 10.1111/CEA.13811
Abstract: Monocytes and macrophages are critical innate immune cells of the airways. Despite their differing functions, few clinical studies discriminate between them and little is known about their regulation in asthma. We aimed to distinguish and quantify macrophages, monocytes and monocyte subsets in induced sputum and blood and examine their relationship with inflammatory and clinical features of asthma. We applied flow cytometry to distinguish macrophages, monocytes and subsets in sputum and blood (n = 53 45 asthma, 8 non‐asthma) and a second asthma sputum cohort (n = 26). Monocyte subsets were identified by surface CD14/CD16 (CD14 ++ CD16 − classical, CD14 + CD16 + intermediate and CD14 + CD16 ++ non‐classical monocytes). Surface CD206, a marker of monocyte tissue differentiation, was measured in sputum. Relationship to airway inflammatory phenotype (neutrophilic n = 9, eosinophilic n = 14, paucigranulocytic n = 22) and asthma severity (severe n = 12, non‐severe n = 33) was assessed. Flow cytometry‐ and microscope‐quantified sputum differential cell proportions were significantly correlated. Sputum macrophage number was reduced ( p = .036), while classical monocyte proportion was increased in asthma vs non‐asthma ( p = .032). Sputum classical monocyte number was significantly higher in neutrophilic vs paucigranulocytic asthma ( p = .013). CD206 − monocyte proportion and number were increased in neutrophilic vs eosinophilic asthma ( p .001, p = .013). Increased sputum classical and CD206 − monocyte numbers in neutrophilic asthma were confirmed in the second cohort. Blood monocytes did not vary with airway inflammatory phenotype, but blood classical monocyte proportion and number were increased in severe vs non‐severe asthma ( p = .022, p = .011). Flow cytometry allowed distinction of sputum macrophages, monocytes and subsets, revealing compartment‐specific dysregulation of monocytes in asthma. We observed an increase in classical and CD206 − monocytes in sputum in neutrophilic asthma, suggesting co‐recruitment of monocytes and neutrophils to the airways in asthma. Our data suggest further investigation of how airway monocyte dysregulation impacts on asthma‐related disease activity is merited.
Publisher: Mary Ann Liebert Inc
Date: 10-2009
Abstract: Depletion of antioxidants through consumption of a low antioxidant diet has been reported to increase neutrophilic airway inflammation and worsen symptoms of asthma. Using a nutrigenomics approach, this study explores the mechanisms of airway neutrophilic inflammation due to depletion of dietary antioxidants. Induced sputum s les were collected at baseline and after participants consumed a low antioxidant diet for 14 days. Genome-wide gene expression profiles were generated from sputum RNA s les from participants with a >10% change in sputum neutrophils using Illumina Humanref-8 expression microarrays. There were 104 genes differentially expressed following the dietary change. Upregulated genes were involved in the innate immune response and included the innate immune receptors TLR2, IL1R2, CD93, the signaling molecules IRAK2, IRAK3, and neutrophil proteases MMP25 and CPD. Downregulated genes included those involved in endogenous antioxidant defenses (GSTA1, GSTA2) and protease inhibition (SLPI, SERPINB3). Altered expression of five genes (TLR2, IRAK2, IL1R2, C20orf114, and SERPINB3) was confirmed using real-time polymerase chain reaction (PCR). These observations suggest that depletion of dietary antioxidants in asthma may result in upregulation of genes involved in the innate immune response. A diet low in antioxidants may be contributing to the development of neutrophilic asthma through activation of the innate immune response.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.JACI.2013.12.1091
Abstract: Airway inflammation is associated with asthma exacerbation risk, treatment response, and disease mechanisms. This study aimed to identify and validate a sputum gene expression signature that discriminates asthma inflammatory phenotypes. An asthma phenotype biomarker discovery study generated gene expression profiles from induced sputum of 47 asthmatic patients. A clinical validation study (n = 59 asthmatic patients) confirmed differential expression of key genes. A 6-gene signature was identified and evaluated for reproducibility (n = 30 asthmatic patients and n = 20 control subjects) and prediction of inhaled corticosteroid (ICS) response (n = 71 asthmatic patients). Receiver operating characteristic curves were calculated, and area under the curve (AUC) values were reported. From 277 differentially expressed genes between asthma inflammatory phenotypes, we identified 23 genes that showed highly significant differential expression in both the discovery and validation populations. A signature of 6 genes, including Charcot-Leydon crystal protein (CLC) carboxypeptidase A3 (CPA3) deoxyribonuclease I-like 3 (DNASE1L3) IL-1β (IL1B) alkaline phosphatase, tissue-nonspecific isozyme (ALPL) and chemokine (C-X-C motif) receptor 2 (CXCR2), was reproducible and could significantly (P 12% change in FEV1 AUC, 91.5%). ICS treatment reduced the expression of CLC, CPA3, and DNASE1L3 in patients with eosinophilic asthma. A sputum gene expression signature of 6 biomarkers reproducibly and significantly discriminates inflammatory phenotypes of asthma and predicts ICS treatment response. This signature has the potential to become a useful diagnostic tool to assist in the clinical diagnosis and management of asthma.
Publisher: Wiley
Date: 11-2019
DOI: 10.1111/RESP.13428
Abstract: Physical activity (PA) in obstructive airway diseases (OAD) is likely to be impaired but this has not been extensively studied outside of chronic obstructive pulmonary disease (COPD). We describe PA levels in severe asthma and bronchiectasis compared to moderate-severe COPD and to controls, and tested the cross-sectional associations of PA (steps/day) with shared disease characteristics in the OAD group. Adults with OAD (severe asthma = 62, COPD = 67, bronchiectasis = 60) and controls (n = 63) underwent a multidimensional assessment, including device-measured PA levels. The OAD group included 189 participants (58.7% females), with median (interquartile range) age of 67 (58-72) years and mean forced expiratory volume in the first second (FEV PA impairment is common in OAD. The activity level was associated with shared characteristics of these diseases. Interventions to improve PA should be multifactorial and consider the level of impairment and the associated characteristics.
Publisher: Wiley
Date: 23-05-2023
DOI: 10.1111/RESP.14518
Abstract: Vocal cord dysfunction/inducible laryngeal obstruction (VCD/ILO), is a common condition characterized by breathlessness associated with inappropriate laryngeal narrowing. Important questions remain unresolved, and to improve collaboration and harmonization in the field, we convened an international Roundtable conference on VCD/ILO in Melbourne, Australia. The aims were to delineate a consistent approach to VCD/ILO diagnosis, appraise disease pathogenesis, outline current management and model(s) of care and identify key research questions. This report summarizes discussions, frames key questions and details recommendations. Participants discussed clinical, research and conceptual advances in the context of recent evidence. The condition presents in a heterogenous manner, and diagnosis is often delayed. Definitive diagnosis of VCD/ILO conventionally utilizes laryngoscopy demonstrating inspiratory vocal fold narrowing %. Computed tomography of the larynx is a new technology with potential for swift diagnosis that requires validation in clinical pathways. Disease pathogenesis and multimorbidity interactions are complex reflecting a multi‐factorial, complex condition, with no single overarching disease mechanism. Currently there is no evidence‐based standard of care since randomized trials for treatment are non‐existent. Recent multidisciplinary models of care need to be clearly articulated and prospectively investigated. Patient impact and healthcare utilization can be formidable but have largely escaped inquiry and patient perspectives have not been explored. Roundtable participants expressed optimism as collective understanding of this complex condition evolves. The Melbourne VCD/ILO Roundtable 2022 identified clear priorities and future directions for this impactful condition.
Publisher: Wiley
Date: 06-04-2016
DOI: 10.1111/ALL.12891
Abstract: Both systemic inflammation and sex hormones have been proposed as potential mediators of the obese-asthma phenotype. The aim of this study was to examine the associations between sex hormones, oral contraceptive pill (OCP) use, systemic inflammation and airway inflammation in adults with asthma. Obese (n = 39) and nonobese (n = 42) females and obese (n = 24) and nonobese (n = 25) males with asthma were recruited. Females were further categorized as reproductive-aged ( 50 years old n = 45). Thirteen (36.1%) reproductive-aged females were using the OCP. Participants had induced sputum cell counts measured and blood analysed for sex hormones and inflammatory markers. Obese reproductive-aged females had higher sputum %neutrophils than nonobese reproductive-aged females (45.4 ± 24.3% vs 27.5 ± 17.5%, P = 0.016) however, there was no difference in sputum neutrophils in obese compared with nonobese males (P = 0.620) or older females (P = 0.087). Multiple linear regression analysis found testosterone and OCP use to be negative predictors of sputum %neutrophils, while C-reactive protein and IL-6 were positive predictors of sputum %neutrophils. BMI and age were not significant predictors in the multivariate model. Reproductive-aged females using the OCP had significantly lower sputum %neutrophils than those not using the OCP (23.2 ± 12.6% vs 42.1 ± 23.8%, P = 0.015). This study suggests that sex hormones and systemic inflammation may be mediating the obese-asthma phenotype. The observation that OCP use was associated with lower sputum %neutrophils in reproductive-aged females warrants further investigation.
Publisher: Georg Thieme Verlag KG
Date: 04-2017
Abstract: One in 10 pregnant women worldwide has asthma and of these, 10% will have a severe exacerbation requiring oral corticosteroids (OCSs) in pregnancy. This review of recent publications in the field will describe the effects of exacerbation on maternal and neonatal health, the use of asthma medications during pregnancy, and will suggest novel management approaches for asthma in pregnancy. Pregnancy results in unpredictable changes in the disease therefore, regular monitoring of symptoms is recommended. Uncontrolled asthma is frequently described in cohorts of pregnant women with asthma, and some recent studies show associations with adverse perinatal outcomes, as previously demonstrated with exacerbations. Guidelines for the management of asthma recommend the continued use of inhaled corticosteroids (ICSs) in pregnancy, with budesonide having a particularly good safety profile. Recent data suggest small effects of asthma and/or asthma medication use on congenital malformations however, there is less data available on the safety of ICS/long-acting β agonist combinations, which are increasingly used for maintenance treatment. Novel management strategies are needed to address the complex needs of pregnant women with asthma. These include medication nonadherence and the presence of numerous comorbidities which can affect asthma, such as rhinitis, cigarette smoking, obesity, and mental health issues. Inflammation-based management has been shown to be effective in reducing exacerbations in pregnancy and may also improve perinatal outcomes. The involvement of a multidisciplinary team and the assessment of comorbidities have potential to improve the health of mothers and their offspring.
Publisher: MDPI AG
Date: 13-07-2021
Abstract: Due to climate change, bushfires are becoming a more frequent and more severe phenomenon which contributes to poor health effects associated with air pollution. In pregnancy, environmental exposures can have lifelong consequences for the fetus, but little is known about these consequences in the context of bushfire smoke exposure. In this review we summarise the current knowledge in this area, and propose a potential mechanism linking bushfire smoke exposure in utero to poor perinatal and respiratory outcomes in the offspring. Bushfire smoke exposure is associated with poor pregnancy outcomes including reduced birth weight and an increased risk of prematurity. Some publications have outlined the adverse health effects on young children, particularly in relation to emergency department presentations and hospital admissions for respiratory problems, but there are no studies in children who were exposed to bushfire smoke in utero. Prenatal stress is likely to occur as a result of catastrophic bushfire events, and stress is known to be associated with poor perinatal and respiratory outcomes. Changes to DNA methylation are potential epigenetic mechanisms linking both smoke particulate exposure and prenatal stress to poor childhood respiratory health outcomes. More research is needed in large pregnancy cohorts exposed to bushfire events to explore this further, and to design appropriate mitigation interventions, in this area of global public health importance.
Publisher: Elsevier BV
Date: 11-2017
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.JPEDS.2012.03.049
Abstract: To determine bronchoalveolar lavage (BAL) levels of 3 innate immunity components (human β-defensin-2 [hBD2], mannose-binding lectin [MBL], and surfactant protein-A [SP-A]), the relationship with airway neutrophilia and infection, and cytokine production of stimulated BAL cells in children with current protracted bacterial bronchitis (PBB), children with resolved PBB (PBB well), and controls. BAL of 102 children (mean age 2.8 years) fulfilling predefined criteria of current PBB (n = 61), PBB well (n = 20), and controls (n = 21) was cultured (quantitative bacteriology) and viruses examined by polymerase chain reaction. hBD2, MBL, and SP-A were measured, and cytokine production by lipopolysaccharide-stimulated BAL cells was determined. Median hBD2 and MBL levels were significantly higher in the current PBB group (hBD2 = 164.4, IQR 0-435.5 pg/mL MBL = 1.7, 0.4-4 ng/mL) than in the PBB well group (hBD2 = 0, IQR 0-85.2 MBL = 0.6, IQR 0.03-2.9) and controls (hBD2 = 3.6, IQR 0-126 MBL = 0.4, IQR 0.02-79). hBD2 was significantly higher in children with airway infection (n = 54 median 76.9, IQR 0-397.3) compared with those without (n = 48 0, IQR 0-236.3), P= .04. SP-A levels and cytokine production of stimulated BAL cells were similar between groups. In children's airways, hBD2, but not MBL and SP-A, relates to inflammation and infection. In children with PBB, mechanisms involving airway hBD2 and MBL are augmented. These pulmonary innate immunity components and the ability of BAL cells to respond to stimuli are unlikely to be deficient.
Publisher: European Respiratory Society (ERS)
Date: 04-2005
DOI: 10.1183/09031936.05.00085704
Abstract: Asthma is becoming increasingly prevalent worldwide. Numerous historical and prospective cohort studies have investigated the effects of maternal asthma on pregnancy outcome however, the data has been conflicting and many studies have not used standard classifications for asthma severity. Overall, the literature suggests that asthmatic females are more at risk of low birth weight neonates, pre-term delivery and complications such as pre-ecl sia, especially in the absence of actively managed asthma treated with inhaled corticosteroids. Pregnancy with a female foetus may particularly increase the risk of these outcomes. In addition, pregnancy has an effect on the course of asthma. The risk of an exacerbation requiring medical intervention may be as high as 50% in females with severe asthma and this may further increase the risk of poor outcomes, particularly low birth weight and pre-term delivery. The mechanisms responsible for changes in asthma with pregnancy, or alterations in pregnancy outcomes due to asthma have not been thoroughly explored. Maternal inflammatory pathways may contribute to reduced foetal growth through alterations in placental function. Asthma treatment, by reducing maternal inflammation and preventing exacerbations, is safe for use in pregnant females and contributes to improved outcomes for both mother and foetus.
Publisher: Elsevier BV
Date: 12-2000
Abstract: Interleukin 10 (IL-10) is an anti-inflammatory, immunomodulatory cytokine that regulates mucosal inflammation. This study evaluated the safety, tolerance, and efficacy of recombinant human IL-10 (rhuIL-10) for mild to moderately active Crohn's disease. We conducted a 24-week multicenter, prospective, randomized, double-blind, placebo-controlled, and sequential-escalating-dose study. Ninety-five patients with Crohn's Disease Activity Index of 200-350, not presently undergoing corticosteroid, mesalamine, or immunosuppressive therapy, were treated with subcutaneous rhuIL-10 (1, 5, 10, or 20 microg/kg) or placebo once daily for 28 consecutive days. Patients were followed up for 20 weeks after treatment. Evaluation of safety and tolerance was the first objective, and efficacy was the second objective. Adverse effects were dose-related, mild-to-moderate in severity, and reversible. Asymptomatic and reversible anemia and thrombocytopenia were observed at higher doses. No withdrawal or delayed adverse effects were evident during 20 weeks of follow-up. At the end of treatment (day 29), intent-to-treat analysis showed that 23.5% (confidence interval [CI], 6.8%-49.9%) of patients receiving 5 micro/kg rhuIL-10 experienced clinical remission and endoscopic improvement 0% (CI, 0%-14.8%) of patients in the placebo group did. Higher doses of recombinant human IL-10 were less effective than 5 microg/kg. No rhuIL-10 serum accumulation and no antibody against IL-10 were detected after 4 weeks. Subcutaneous rhuIL-10 administered daily for 28 days to patients with mild to moderately active Crohn's disease is safe, well-tolerated, and shows clinical and endoscopic improvement.
Publisher: Wiley
Date: 16-09-2015
DOI: 10.1111/RESP.12642
Abstract: Chronic obstructive pulmonary disease (COPD) frequently coexists with other conditions often known as comorbidities. The prevalence of most of the common comorbid conditions that accompany COPD has been widely reported. It is also recognized that comorbidities have significant health and economic consequences. Nevertheless, there is scant research examining how comorbidities should be assessed and managed in the context of COPD. Also, the underlying mechanisms linking COPD with its comorbidities are still not fully understood. Owing to these knowledge gaps, current disease-specific approaches provide clinicians with little guidance in terms of managing comorbid conditions in the clinical care of multi-diseased COPD patients. This review discusses the concepts of comorbidity and multi-morbidity in COPD in relation to the overall clinical outcome of COPD management. It also summarizes some of the currently available clinical scores used to measure comorbid conditions and their prognostic abilities. Furthermore, recent developments in the proposed mechanisms linking COPD with its comorbidities are discussed.
Publisher: Wiley
Date: 24-12-2013
DOI: 10.1111/J.1365-2222.2012.04075.X
Abstract: Many patients with non-eosinophilic asthma have increased numbers of neutrophils in the airways. The explanation for this chronic inflammation remains unclear, but may result from an impaired ability of alveolar macrophages to phagocytose apoptotic cells (a process termed 'efferocytosis'), as we have shown in chronic obstructive pulmonary disease (COPD). To examine induced sputum as a non-invasive technique to characterize efferocytosis in chronic lung diseases and to compare efferocytosis in patients with non-eosinophilic asthma, eosinophilic asthma and COPD. Participants with stable asthma (20 with eosinophilic and 30 with non-eosinophilic) and COPD (n = 11) underwent clinical assessment including allergy skin tests, saline challenge and sputum induction. Sputum cells were dispersed using dithiothreitol and resuspended in culture medium. Efferocytosis of apoptotic bronchial epithelial cells by sputum-derived macrophages was determined using flow cytometry. There were no significant differences in efferocytosis between paired sputum and bronchoalveolar lavage macrophages from three subjects. Efferocytosis was significantly impaired in patients with non-eosinophilic asthma [mean (SD) 0.95 (0.24)] compared with eosinophilic asthma [1.17 (0.19)] and to a similar degree as patients with COPD [1.04 (0.16)]. Sputum neutrophils were significantly higher in patients with COPD and non-eosinophilic asthma compared with eosinophilic asthma. Induced sputum provides a reliable and non-invasive method for studying macrophage efferocytosis in chronic lung disease. Macrophage efferocytosis is impaired in non-eosinophilic asthma to a similar degree as that in COPD and may explain the persistent airway neutrophilia and chronic inflammation that characterizes this asthma subtype.
Publisher: Elsevier BV
Date: 11-2017
DOI: 10.1016/J.RMED.2017.10.019
Abstract: Treatment with mepolizumab, a humanized monoclonal antibody to interleukin-5, reduces the rate of asthma exacerbations and the requirement for systemic glucocorticoids while maintaining asthma control. Treatment decisions are guided by predictors of response, including blood eosinophil thresholds in patients with frequent exacerbations despite intensive anti-inflammatory and controller treatment. Identification of additional predictors of response could aid treatment decisions. We investigated genetic associations that may predict response to mepolizumab-treatment. In this post hoc analysis of DREAM and MENSA, association of genetic markers was tested in patients with severe asthma treated with mepolizumab who provided consent for pharmacogenetic research. Association was tested in a tiered approach with alpha spend differing for candidate genetic markers selected for prior history of association with relevant traits or pathways and in a genome-wide analyses (p < 4.7 × 10 No genetic marker was significantly associated with the primary endpoint, clinically significant exacerbation rate. One genetic marker was associated with time to first clinically significant exacerbation, but this association was driven by the DREAM data and was not supported in additional sensitivity analyses by treatment regimen/dose. No genetic effect on mepolizumab-treatment response was identified in this population on intensive asthma treatment, with history of frequent exacerbations and pre-selected for airway eosinophilia.
Publisher: Public Library of Science (PLoS)
Date: 07-06-2022
DOI: 10.1371/JOURNAL.PONE.0269038
Abstract: Whilst multidimensional assessment enables the detection of treatable traits in severe asthma and has the potential to improve patient outcomes, healthcare disparities exist, and little is known about the factors influencing optimal management in severe asthma. This study aimed to explore perceived barriers, and enablers to implementing personalised care in severe asthma, from the healthcare professionals’ perspective. A descriptive, qualitative study involving a single focus group (n = 7) and semi-structured interviews (n = 33) with multidisciplinary healthcare professionals involved in severe asthma care was conducted. A hybrid thematic and content analysis was undertaken to identify themes, which were then deductively mapped to the Theoretical Domains Framework (TDF). Overall, three emergent themes were identified: (1) Barriers- (2) Enablers- to optimal management (3) Desired model of care. Across all TDF domains, 6 constructs influenced development and implementation of optimal care: (1) belief about consequences, (2) environmental context and resources, (3) belief about capabilities, (4) social rofessional role and identity, (5) goals and (6) knowledge. Implementation of personalised care in severe asthma is complex and non-linear. The use of a theory-based approach effectively demonstrated how a variety of behaviours could be targeted to optimise and promote personalised care in different clinical setting.
Publisher: Public Library of Science (PLoS)
Date: 31-05-2013
Publisher: BMJ
Date: 06-05-2015
DOI: 10.1136/THORAXJNL-2014-206740
Abstract: The overlap between asthma and COPD is increasingly recognised. This review examines the new insights, treatment and remaining knowledge gaps for asthma-COPD overlap. A systematic literature review of cluster analyses of asthma and COPD was performed. Articles from 2009 to the present dealing with prevalence, morbidity and treatment of asthma-COPD overlap were identified and reviewed. Asthma-COPD overlap was consistently recognised in studies using a variety of different study designs and s ling. The prevalence was approximately 20% in patients with obstructive airways diseases. Asthma-COPD overlap was associated with increased morbidity and possibly an increased mortality and comorbidity. There was evidence of a heterogeneous pattern of airway inflammation that included eosinophilic (in adult asthma), neutrophilic or mixed patterns (in severe asthma and COPD). Systemic inflammation was present in asthma-COPD overlap and resembled that of COPD. Within asthma-COPD overlap, there is evidence of different subgroups, and recognition using bronchodilator responsiveness has not been successful. Guidelines generally recommend a serial approach to assessment, with treatment recommendations dominated by an asthma paradigm. Research is needed into key clinical features that impact outcome, mechanisms and treatment approaches in asthma-COPD overlap. Identifying and treating disease components by multidimensional assessment shows promise. Asthma-COPD overlap has drawn attention to the significant heterogeneity that exists within obstructive airway diseases. It should be replaced by novel approaches that identify and manage the components of this heterogeneity, such as multidimensional assessment and treatment. Future research is needed to test these novel and personalised approaches.
Publisher: European Respiratory Society (ERS)
Date: 05-2017
Publisher: European Respiratory Society (ERS)
Date: 11-06-2021
DOI: 10.1183/23120541.00131-2021
Abstract: Dysregulation of tumour necrosis factor-α (TNF-α) signalling is implicated in neutrophilic asthma. TNF-α signalling involves membrane-bound and soluble ligand (TNF-α) and receptors (TNFRs) however, little is known about how these proteins are altered in asthma. We hypothesised that intercompartment-, immune cell- and/or asthma inflammatory phenotype-dependent regulation could relate to TNF dysregulation in neutrophilic asthma. Measurements were made in 45 adults with asthma (36 non-neutrophilic, 9 neutrophilic) and 8 non-asthma controls. Soluble TNF-α, TNF receptor 1 (TNFR1) and TNFR2 were quantified in plasma and sputum supernatant by ELISA, and membrane-bound TNF-α/TNFR1/TNFR2 measured on eosinophils, neutrophils, monocytes, and macrophages in blood and sputum by flow cytometry. Marker expression was compared between inflammatory phenotypes and compartments, and relationship of membrane-bound and soluble TNF markers and immune cell numbers tested by correlation. Soluble sputum TNFR1 and TNFR2 were increased in neutrophilic versus non-neutrophilic asthma (p=0.010 and p=0.029). Membrane-bound TNF-α expression was upregulated on sputum versus blood monocytes, while TNFR1 and TNFR2 levels were reduced on airway versus blood monocytes and neutrophils. Soluble TNFR1 and TNFR2 in sputum significantly correlated with the number of airway monocytes (p=0.016, r=0.358 and p=0.029, r=0.327). Our results imply that increased sputum soluble TNF receptor levels observed in neutrophilic asthma relate to the increased recruitment of monocytes and neutrophils into the airways and their subsequent receptor shedding. Monocytes also increase TNF-α ligand expression in the airways. These results suggest an important contribution of airway monocytes to the altered inflammatory milieu in neutrophilic asthma.
Publisher: BMJ
Date: 09-1989
DOI: 10.1136/THX.44.9.693
Abstract: The reproducibility of sputum cell counts was examined and the cell counts in patients with asthma were compared with those in patients with chronic bronchitis. Three groups of subjects were studied. Sputum from eight patients with chronic asthma and with sputum production were studied to determine the reproducibility of sputum cell counts. The findings in 10 non-smokers with asthma uncomplicated by other airway disease examined at the time of an exacerbation with sputum (group 2) were compared with those from eight smokers with chronic cough and sputum but no features of asthma (group 3). Sputum plugs were selected by microscopy to ensure their origin from the lower respiratory tract. A total cell count was performed on a trypsinised suspension, and differential and metachromatic cell counts were performed on undiluted plugs. The within specimen and test-retest reproducibility of these measurements was high (reliability coefficient, R, = 0.99 and 0.89). The sputum of the asthmatic patients was characterised by eosinophilia (69%, range 46-92%) and the presence of formaldehyde blockable metachromatic cells (1.5%, range 0.6-2.8%). In comparison, the sputum of the patients with chronic bronchitis had few eosinophils (0.5%) or metachromatic cells (0.14%) the dominant cell type was the macrophage (83%). It is concluded that sputum cell counts are reproducible in the short term, the inflammation of asthma is characterised by eosinophilia and metachromatic cells in sputum, and sputum may provide a useful source of cells for investigating the cellular characteristics of airway inflammation.
Publisher: Springer Science and Business Media LLC
Date: 24-01-2015
Publisher: BMJ
Date: 12-2007
Publisher: Wiley
Date: 16-12-2020
DOI: 10.1111/RESP.13735
Publisher: Wiley
Date: 15-04-2009
Publisher: Wiley
Date: 19-07-2004
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.JACI.2017.03.044
Abstract: Asthma pathophysiology and treatment responsiveness are predicted by inflammatory phenotype. However, the relationship between airway microbiology and asthma phenotype is poorly understood. We aimed to characterize the airway microbiota in patients with symptomatic stable asthma and relate composition to airway inflammatory phenotype and other phenotypic characteristics. The microbial composition of induced sputum specimens collected from adult patients screened for a multicenter randomized controlled trial was determined by using 16S rRNA gene sequencing. Inflammatory phenotypes were defined by sputum neutrophil and eosinophil cell proportions. Microbiota were defined by using α- and β- ersity measures, and interphenotype differences were identified by using similarity of percentages, network analysis, and taxon fold change. Phenotypic predictors of airway microbiology were identified by using multivariate linear regression. Microbiota composition was determined in 167 participants and classified as eosinophilic (n = 84), neutrophilic (n = 14), paucigranulocytic (n = 60), or mixed neutrophilic-eosinophilic (n = 9) asthma phenotypes. Airway microbiology was significantly less erse (P = .022) and more dissimilar (P = .005) in neutrophilic compared with eosinophilic participants. Sputum neutrophil proportions, but not eosinophil proportions, correlated significantly with these ersity measures (α- ersity: Spearman r = -0.374, P < .001 β- ersity: r = 0.238, P = .002). Interphenotype differences were characterized by a greater frequency of pathogenic taxa at high relative abundance and reduced Streptococcus, Gemella, and Porphyromonas taxa relative abundance in patients with neutrophilic asthma. Multivariate regression confirmed that sputum neutrophil proportion was the strongest predictor of microbiota composition. Neutrophilic asthma is associated with airway microbiology that is significantly different from that seen in patients with other inflammatory phenotypes, particularly eosinophilic asthma. Differences in microbiota composition might influence the response to antimicrobial and steroid therapies and the risk of lung infection.
Publisher: American Thoracic Society
Date: 09-2019
Publisher: Springer Science and Business Media LLC
Date: 13-03-2012
DOI: 10.1007/S11325-012-0687-1
Abstract: Sleep disturbance is reported to be more prevalent in children and adolescents with asthma than those without. However, this has not been described adequately using objective measures. The aim of this study was to objectively characterise sleep disturbance in asthmatic and non-asthmatic children and adolescents. A retrospective analysis of polysomnography recordings from children aged 5-17 years old, with (n = 113) and without asthma (n = 104), referred for a sleep study over the period 2005-2010 at the Paediatric Sleep Unit, John Hunter Children's Hospital in Newcastle, NSW Australia, was carried out. Polysomnographic recordings were analysed to compare sleep quality and quantity between asthmatic and non-asthmatic children. Sleep latency was significantly longer in asthmatic children compared to controls. However, this result was significant for females only (46.2 (5.6) vs 33.2 (2.7) min, p < 0.05). Male asthmatics had significantly shorter sleep duration (425.9 (5.4) vs 441.8 (5.4) min, p < 0.05) than male controls. Sleep disturbance exists in children with asthma and manifests differently in males and females. Further investigation into the clinical implication of increased sleep latency and reduced sleep duration upon daytime functioning and lifestyle behaviours in children and adolescents with asthma is warranted.
Publisher: Elsevier BV
Date: 05-2002
Abstract: In childhood asthma, cough is a major symptom in some but not in others. There is only limited data on the frequency, severity and prevalence of cough in children with classical asthma. Studies have largely shown no relationship between cough frequency and cough receptor sensitivity with various asthma severity indices. However relating cough severity with asthma severity is limited by various methodological and sensitivity issues, and these are presented in this paper. Mild asthma exacerbations in a group of children with cough as a dominant symptom were characterised by an increase in cough severity (daytime cough scores) and eosinophilic inflammation but not neutrophilic inflammation. However neither cough receptor sensitivity or cough scores related to airway IL-8, eosinophil cationic protein, myeloperoxidase or serum eosinophil cationic protein, and, asthma scores consistently related to cough score only early in the asthma exacerbation phase.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Wiley
Date: 09-2014
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.PHARMTHERA.2009.06.004
Abstract: Obstructive airway diseases such as asthma and chronic obstructive pulmonary disease (COPD) are major global health issues. Although considered as distinct diseases, airway inflammation is a key underlying pathophysiological process in asthma, COPD and bronchiectasis. Persistent neutrophilic airway inflammation (neutrophilic bronchitis) occurs with innate immune activation and is a feature of each of these airway diseases. Little is known about the mechanisms leading to neutrophilic bronchitis and few treatments are effective in reducing neutrophil accumulation in the airways. There is a similar pattern of inflammatory mediator release and toll like receptor 2 expression in asthma, COPD and bronchiectasis. We propose the existence of an active lification mechanism, an effector arm of the innate immune system, involving toll like receptor 2, operating in persistent neutrophilic bronchitis. Neutrophil persistence in the airways can occur through a number of mechanisms such as impaired apoptosis, efferocytosis and mucus hypersecretion, all of which are impaired in airways disease. Impairment of neutrophil clearance results in a reduced ability to respond to bacterial infection. Persistent activation of airway neutrophils may result in the persistent activation of the innate immune system resulting in further airway insult. Current therapies are limited for the treatment of neutrophilic bronchitis possible treatments being investigated include theophylline, statins, antagonists of pro-inflammatory cytokines and macrolide antibiotics. Macrolides have shown great promise in their ability to reduce airway inflammation, and can reduce airway neutrophils, levels of CXCL8 and neutrophil proteases in the airways. Studies also show improvements in quality of life and exacerbation rates in airways diseases.
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.JVOICE.2005.12.008
Abstract: Chronic cough (CC) and paradoxical vocal fold movement (PVFM) share several common features however, there has been no systematic comparison of these two conditions. The aims of this study were to contrast and compare the symptom profiles of CC and PVFM, to clarify the relationship between the two conditions, and to explore how symptom characteristics could be used to design an in idualized treatment program. Participants included 55 people with a combination of PVFM and CC that was refractory to medical treatment, 8 people with PVFM alone, 56 people with CC alone, 25 people with voice disorders, and 27 normal controls. Symptoms and descriptive features of CC, PVFM, and voice disorders were assessed via structured case history interview, symptom frequency, and severity ratings, ratings of activity limitation, and anxiety/depression ratings. Results indicated consistent overlap in the symptom profile between people with CC and those presenting with a combination of CC and PVFM. Participants with PVFM without cough and those with voice disorders overlapped with the participants with CC on some dimensions however, there were still some significant differences between them. These data suggest that CC and PVFM are related and manifestations of a common underlying condition but that voice disorders are a discrete entity. Most participants had normal ratings on screening for anxiety and depression. Results indicated that there were no consistent psychiatric symptoms in any of the groups studied, and they do not support the label of psychogenic cough for CC that is refractory to medical treatment. Characteristics of CC such as nature and timing of the cough provide important information for developing behavioral treatment programs for in idual patients who have exhausted medical options. A template has been provided that is a practical method of designing an integrated behavioral treatment program based on those in idual patient characteristics.
Publisher: Wiley
Date: 16-09-2009
Publisher: Informa UK Limited
Date: 14-11-2022
DOI: 10.1080/02770903.2021.1993246
Abstract: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, in iduals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control. This cohort survey-based study included mothers with ( n = 157) and without ( n = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index - Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire. Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control. This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and s ling bias, levels of parenting stress in asthmatic mothers may be underreported in our s le.
Publisher: Wiley
Date: 2021
DOI: 10.1002/CTI2.1296
Abstract: Offspring born to mothers with asthma in pregnancy are known to have lower lung function which tracks with age. Human group 2 innate lymphoid cells (ILC2) accumulate in foetal lungs, at 10‐fold higher levels compared to adult lungs. However, there are no data on foetal ILC2 numbers and the association with respiratory health outcomes such as lung function in early life. We aimed to investigate cord blood immune cell populations from babies born to mothers with asthma in pregnancy. Cord blood from babies born to asthmatic mothers was collected, and cells were stained in whole cord blood. Analyses were done using traditional gating approaches and computational methodologies (t‐distributed stochastic neighbour embedding and PhenoGraph algorithms). At 6 weeks of age, the time to peak tidal expiratory flow as a percentage of total expiratory flow time (tPTEF/tE%) was determined as well as Lung Clearance Index (LCI), during quiet natural sleep. Of 110 eligible infants (March 2017 to November 2019), 91 were successfully immunophenotyped (82.7%). Lung function was attempted in 61 infants (67.0%), and 43 of those infants (70.5% of attempted) had technically acceptable tPTEF/tE% measurements. Thirty‐four infants (55.7% of attempted) had acceptable LCI measurements. Foetal ILC2 numbers with increased expression of chemoattractant receptor‐homologous molecule (CRTh2), characterised by two distinct analysis methodologies, were associated with poorer infant lung function at 6 weeks of age.” Foetal immune responses may be a surrogate variable for or directly influence lung function outcomes in early life.
Publisher: European Respiratory Society (ERS)
Date: 09-2008
DOI: 10.1183/09031936.00155307
Abstract: Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.
Publisher: S. Karger AG
Date: 2007
DOI: 10.1159/000104464
Abstract: Voice problems have been reported in chronic cough (CC) and paradoxical vocal fold movement (PVFM), however, there is a lack of a systematic description of voice characteristics in these conditions. This study examined the perceptual voice characteristics of 56 in iduals with CC, 8 with PVFM and 55 with both CC and PVFM, compared to 25 people with muscle tension dysphonia (MTD) and 27 healthy controls. There was a high prevalence of abnormal voice quality in the CC and PVFM groups compared with healthy controls. More than one third of participants with CC and PVFM demonstrated strained, rough and/or breathy voices to a moderate or severe degree. The perceptual features in CC and PVFM were similar to those in MTD with greater severity evident in MTD. Possible mechanisms for abnormalities in voice quality include the presence of muscle tension and the frequency of coughing. These results have implications for the identification and management of voice disorders in CC and PVFM and suggest that clinicians should be alert to the incidence of voice abnormalities in these populations.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Wiley
Date: 19-05-2021
DOI: 10.1111/RESP.13841
Publisher: Wiley
Date: 02-2021
DOI: 10.1002/RCR2.717
Publisher: Elsevier BV
Date: 11-2004
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.JACI.2012.08.023
Abstract: Currently, the cornerstone of asthma management is the achievement and maintenance of optimal asthma control, but the diagnostic performances of the Asthma Control Test (ACT) and Asthma Control Questionnaire (ACQ) have not been evaluated systematically. We explored the diagnostic performances of and statistically compared the ACT and ACQ. Studies that examined the accuracy of the ACT, ACQ, or both in the assessment of asthma control were found by searching PubMed, CENTRAL, Web of Science, Ovid, and Embase. Summary estimates of sensitivity, specificity, and diagnostic odds ratios for the different levels of asthma control were determined by using bivariate random-effects models and hierarchical summary receiver operating characteristic models. Twenty-one studies with 11,141 subjects assessed with the ACT and 12,483 assessed with the ACQ were identified. The ACT had good diagnostic accuracy for assessment of controlled and not well-controlled asthma, and the ACQ (ACQ-7 and ACQ-6) had good diagnostic accuracy for assessment of not well-controlled asthma at prespecified cutoff points. The ACT and ACQ had significant differences in the assessment of controlled and not well-controlled asthma after adjusting for potential factors (P = .001 and P = .015). For assessment of uncontrolled asthma, the ACT had poor accuracy, with a hierarchical summary receiver operating characteristic area under the curve of 0.69, and the cutoff point for the ACQ has not been established. The ACT is preferable to the ACQ in clinical practice, and the ACQ requires further cross-validation. Moreover, neither the ACT nor the ACQ is useful for the assessment of uncontrolled asthma.
Publisher: Wiley
Date: 17-08-2016
DOI: 10.1111/RESP.12870
Publisher: BMJ
Date: 11-2004
DOI: 10.1136/EBM.9.6.178
Publisher: BMJ
Date: 22-10-2015
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.JACI.2011.01.036
Abstract: Dietary fat activates systemic innate immune responses, but the effect on airway responses is unknown. To examine effects of a high-fat versus low-fat meal on systemic and airway inflammation in asthma. Nonobese subjects with asthma were randomized to consume a high-fat (n = 19 48% [49 g] fat) or low-fat (n = 18 15% [3 g] fat) meal. Fourteen obese patients with asthma and 21 healthy controls also consumed a high-fat meal. Another group of patients with asthma consumed a high-trans (n = 5 5.2 g trans fat) or nontrans (n = 5, <0.3 g trans fat) fatty acid meal. Lung function was measured at baseline (prebronchodilator) and 2, 3, and 4 hours after bronchodilator. Airway inflammation was assessed by using induced sputum cell counts and Toll-like receptor 4 mRNA expression by real-time PCR. Systemic inflammation was measured by ELISA quantification of plasma TNF-α, high-sensitivity C-reactive protein, and IL-6 concentrations. In patients with asthma, at 4 hours postmeal, increases in sputum % neutrophils and Toll-like receptor 4 mRNA expression were higher and increases in FEV(1)/forced vital capacity (FVC) were lower in the high-fat versus low-fat groups. Changes in plasma fatty acids correlated with changes in sputum % neutrophils and were negatively associated with changes in % FEV(1), % FVC, and FEV(1)/FVC. After the high-trans fatty acid meal, sputum % neutrophils were significantly higher than after the nontrans meal. A high-fat meal augments neutrophilic airway inflammation, with the effect dependent on the type of fat consumed. A high-fat meal also suppresses bronchodilator recovery in asthma. Modifying dietary fat intake may be useful in asthma.
Publisher: Informa UK Limited
Date: 10-12-2016
Publisher: Elsevier BV
Date: 08-2019
Publisher: BMJ
Date: 09-05-2014
Publisher: Elsevier BV
Date: 09-2012
Abstract: Antioxidant-rich diets are associated with reduced asthma prevalence in epidemiologic studies. We previously showed that short-term manipulation of antioxidant defenses leads to changes in asthma outcomes. The objective was to investigate the effects of a high-antioxidant diet compared with those of a low-antioxidant diet, with or without lycopene supplementation, in asthma. Asthmatic adults (n = 137) were randomly assigned to a high-antioxidant diet (5 servings of vegetables and 2 servings of fruit daily n = 46) or a low-antioxidant diet (≤2 servings of vegetables and 1 serving of fruit daily n = 91) for 14 d and then commenced a parallel, randomized, controlled supplementation trial. Subjects who consumed the high-antioxidant diet received placebo. Subjects who consumed the low-antioxidant diet received placebo or tomato extract (45 mg lycopene/d). The intervention continued until week 14 or until an exacerbation occurred. After 14 d, subjects consuming the low-antioxidant diet had a lower percentage predicted forced expiratory volume in 1 s and percentage predicted forced vital capacity than did those consuming the high-antioxidant diet. Subjects in the low-antioxidant diet group had increased plasma C-reactive protein at week 14. At the end of the trial, time to exacerbation was greater in the high-antioxidant than in the low-antioxidant diet group, and the low-antioxidant diet group was 2.26 (95% CI: 1.04, 4.91 P = 0.039) times as likely to exacerbate. Of the subjects in the low-antioxidant diet group, no difference in airway or systemic inflammation or clinical outcomes was observed between the groups that consumed the tomato extract and those who consumed placebo. Modifying the dietary intake of carotenoids alters clinical asthma outcomes. Improvements were evident only after increased fruit and vegetable intake, which suggests that whole-food interventions are most effective. This trial was registered at www.actr.org.au as ACTRN012606000286549.
Publisher: Public Library of Science (PLoS)
Date: 06-10-2011
Publisher: Wiley
Date: 20-03-2013
DOI: 10.1111/CRJ.12017
Abstract: Outcome assessment is an important part of the management of airways disease, yet older adults may have difficulty with the burden of testing. This study evaluated the patient perception of tests used for the assessment of airways disease in older people. Older adults (>55 years) with obstructive airway disease and healthy controls (N = 56) underwent inhaler technique assessment, skin allergy testing, venepuncture, fractional exhaled nitric oxide (FENO) and gas diffusion measurement, exercise testing, sputum induction, and questionnaire assessment. They then completed an assessment burden questionnaire across five domains: difficulty, discomfort, pain, symptoms and test duration. Test perception was generally favourable. Induced sputum had the greatest test burden perceived as being more difficult (mean 0.83, P = 0.001), associated with more discomfort (mean 1.3, P < 0.001), more painful (0.46, P = 0.019), longer test duration (0.84, P < 0.001) and worsening symptoms (0.55, P = 0.001) than the questionnaires. FENO had a more favourable assessment but was assessed to be difficult to perform. Inhaler technique received the most favourable assessment. Older adults hold favourable perceptions to a range of tests that they might encounter in the course of their care for airway disease. The newer tests of sputum induction and FENO have some observed difficulties, in particular sputum induction. The results of this study can inform current practice by including details of the test and its associated adverse effects when conducting the test, as well as providing clear explanations of the utility of tests and how the results might aid in patient care.
Publisher: BMJ
Date: 14-12-2015
DOI: 10.1136/BMJ.H5590
Abstract: Chronic refractory cough (CRC) is defined as a cough that persists despite guideline based treatment. It is seen in 20-46% of patients presenting to specialist cough clinics and it has a substantial impact on quality of life and healthcare utilization. Several terms have been used to describe this condition, including the recently introduced term cough hypersensitivity syndrome. Key symptoms include a dry irritated cough localized around the laryngeal region. Symptoms are not restricted to cough and can include globus, dyspnea, and dysphonia. Chronic refractory cough has factors in common with laryngeal hypersensitivity syndromes and chronic pain syndromes, and these similarities help to shed light on the pathophysiology of the condition. Its pathophysiology is complex and includes cough reflex sensitivity, central sensitization, peripheral sensitization, and paradoxical vocal fold movement. Chronic refractory cough often occurs after a viral infection. The diagnosis is made once the main diseases that cause chronic cough have been excluded (or treated) and cough remains refractory to medical treatment. Several treatments have been developed over the past decade. These include speech pathology interventions using techniques adapted from the treatment of hyperfunctional voice disorders, as well as the use of centrally acting neuromodulators such as gabapentin and pregabalin. Potential new treatments in development also show promise.
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.ANAI.2022.04.020
Abstract: T2-low asthma is an often severe asthma subtype with limited treatment options and biologic therapeutics are lacking. Several monoclonal antibodies (mAbs) targeting non-T2 cytokines were previously reported to be ineffective in asthma. These trials often investigated heterogeneous asthma populations and negative outcomes could be related to unsuitable study cohorts. More tailored approaches in selecting participants based on specific biomarkers have been beneficial in treating severe T2-high asthma. Similarly, mAbs previously deemed ineffective bear the potential to be useful when administered to the correct target population. Here, we review in idual clinical trials conducted between 2005 and 2021 and assess the suitability of the selected cohorts, whether study end points were met, and whether outcome measures were appropriate to investigate the effectiveness of the respective drug. We discuss potential target groups within the T2-low asthma population and suggest biomarkers that may predict a treatment response. Furthermore, we assess whether biomarker-guided approaches or subgroup analyses were associated with more positive study outcomes. The mAbs directed against alarmins intervene early in the inflammatory cascade and are the first mAbs found to have efficacy in T2-low asthma. Several randomized controlled trials performed predefined subgroup analyses that included T2-low asthma. Subgroup analyses were associated with positive outcomes and were able to reveal a stronger response in at least 1 subgroup. A better understanding of T2-low subgroups and specific biomarkers is necessary to identify the most responsive target population for a given mAb.
Publisher: Oxford University Press (OUP)
Date: 15-07-2013
Abstract: Pregnant women are a high-risk group during influenza pandemics. In this study we determined whether plasmacytoid dendritic cells (pDCs) and CD8 T cells from pregnant women display altered activity following in vitro infection with 2009 pandemic swine influenza (H1N1/09). Peripheral blood mononuclear cells (PBMCs) were isolated from pregnant (n = 26) and nonpregnant (n = 28) women. DC subtypes were enumerated from PBMCs. PBMCs were infected with H1N1/09 and CD86, human leukocyte antigen-DR (HLA-DR), and programmed death ligand 1/2 (PDL1/2) measured on pDCs. PD receptor 1 (PD1) was measured on CD8 T cells. Interferon-alpha (IFN-α), interleukin-2 (IL-2), tumor necrosis factor-alpha (TNFα), and IFN-gamma were measured from culture supernatant. pDC (ie, CD303(+)/CD1c(-) PBMCs) percentages were lower in pregnant compared with nonpregnant women (P < .05). Following H1N1/09 infection, pDCs from pregnant women showed higher expression of CD86 (P < .01), HLA-DR (P < .001), and PDL1 (P < .001) compared with nonpregnant women. Expression of PD1 on CD8 T cells was higher during pregnancy (P < .05). Following H1N1/09 infection, PBMCs from pregnant women displayed reduced IFN-α (P < .01), IL-2 (P < .01), and IFN-γ (P < .01) compared with nonpregnant women. Blocking PDL1 during H1N1/09 infection increased these cytokines during pregnancy (P < .05). Altered maternal cellular antiviral activity is implicated in the increased morbidity during pregnancy following influenza pandemics.
Publisher: European Respiratory Society (ERS)
Date: 10-2002
DOI: 10.1183/09031936.02.00192002
Abstract: Infection with Chlamydia pneumoniae can trigger acute asthma and is associated with severe chronic asthma. The aim of the present study was to examine the relationship between airway inflammation and serological response to C. pneumoniae in acute severe asthma. Subjects (n=54) were recruited within 4 h of presentation to the emergency department with an acute exacerbation of asthma. Clinical history taking, sputum induction (0.9% saline), spirometry and acute and convalescent serology for C. pneumoniae immunoglobulins A and G were performed. At presentation, 47% of subjects had antibodies directed against C. pneumoniae, and 38% (20) demonstrated an increase in C. pneumoniae antibody levels, with 15 demonstrating a rise in immunoglobulin A concentration. C. pneumoniae responders exhibited significantly higher sputum neutrophil levels (4.6 x 10(6) cells x mL(-1)) compared to nonresponders (1.2 x 10(6) cells x mL(-1), p=0.02) and elevated sputum eosinophil cationic protein concentration (3,981 versus 1,122 ng x mL(-1), p=0.02). An acute antibody response to Chlamydia pneumoniae is common in exacerbations of asthma. The serological features suggest that Chlamydia pneumoniae reactivation may trigger neutrophilic airway inflammation in acute asthma.
Publisher: Springer Science and Business Media LLC
Date: 27-05-2015
DOI: 10.1038/EJCN.2015.85
Abstract: Preservation of lung health requires understanding the modifiable risk factors of airflow limitation. This study investigates the association between diet and lung function in a population of Greenland Inuit residing in the Arctic (Greenland) or Western Europe (Denmark). Two unselected Inuit populations were recruited, one living in Greenland (Urban (Nuuk) n=358 Rural (Uummannaq) n=207) and the other in Denmark (n=539). Lung function was measured using spirometry and diet by a food frequency questionnaire. Factors associated with airflow limitation were assessed using multiple linear regression models. The dietary composition differed significantly in the two regions, with higher whale, seal and wild meat intake and lower fruit and vegetable intake in the Arctic regions compared with Denmark. Consumption of vegetables (P=0.004) and whale and/or seal (P<0.0001) was significantly and positively associated with FEV1, as well as with FVC (vegetables: P=0.001, whale and/or seal: P=0.002). Regular fruit intake was included in the statistical models however, it did not reach statistical significance (FEV1: P=0.053 FVC: P=0.055). High dietary intake of vegetables as well as intake of arctic marine mammals had independent positive associations with lung function in this cohort of Greenlandic Inuit. These findings suggest an additive role of dietary intake of antioxidants and unsaturated fatty acids in lung health, which warrants prospective evaluation.
Publisher: Wiley
Date: 19-04-2004
Publisher: Springer Science and Business Media LLC
Date: 03-2004
Publisher: Elsevier BV
Date: 11-2012
Publisher: BMJ
Date: 12-2004
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JAIP.2019.06.033
Abstract: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wheeze in offspring. In this secondary analysis of a randomized controlled trial, we investigated the influence of maternal body mass index, gestational weight gain (GWG), and fractional exhaled nitric oxide (F A total of 220 women were randomized to asthma treatment adjustment according to symptoms (control group), or F F The benefits of F
Publisher: Elsevier BV
Date: 06-1989
DOI: 10.1016/S0140-6736(89)92801-8
Abstract: Sputum cell-counts were studied in 7 non-smokers with corticosteroid-responsive chronic cough productive of sputum and 8 smokers with a clinical diagnosis of chronic bronchitis, all of whom had normal lung function tests and methacholine airway responsiveness, and in 10 non-smokers with asthma, examined during an exacerbation. Sputum from asthmatic patients and subjects with corticosteroid-responsive cough contained eosinophils and metachromatic cells. Macrophages were by far the dominant cell type in sputum from subjects with chronic bronchitis. Airway inflammation with eosinophils and metachromatic cells is not always accompanied by increased airway responsiveness, and current definitions of obstructive airways disease may need to be revised.
Publisher: Wiley
Date: 03-11-2015
DOI: 10.1111/RESP.12423
Abstract: While weight loss has been shown to reduce obesity-related comorbidity, many weight loss treatments fail. Factors that enhance weight loss success are unknown, particularly in those with asthma. The aim of the study was to identify patient characteristics that predict weight loss success in adults with asthma. Baseline and change in asthma characteristics and eating behaviours were investigated for relationships with weight loss and fat loss using multiple linear regression, in 38 overweight and obese adults with asthma randomized to dietary, exercise or combined interventions targeting weight loss for 10 weeks. Mean ± standard deviation weight loss was 6.6 ± 5.1 kg. Greater %weight loss and %fat loss was achieved in those with poorer asthma-related quality of life at baseline ((rs = 0.398, P = 0.015) and (rs = 0.455, P = 0.005) respectively), with 1.7% greater absolute weight loss at week 10 corresponding to each one unit reduction in the asthma-related quality of life score at baseline. Furthermore, a lower baseline forced expiratory volume in 1 s/forced vital capacity correlated with greater weight loss (rs = 0.398, P = 0.015). Male sex was associated with a 3.6 kg greater weight loss (P = 0.087). Reducing emotional eating during the programme was associated with greater weight loss in women (rs = 0.576, P = 0.010). This study demonstrates that in iduals with more severe asthma at baseline are more successful in achieving weight loss, which could be a consequence of greater motivation and could be used as a motivational tool within the clinical setting. Gender tailoring of weight loss programmes may be useful to enhance weight loss success. Future studies are urgently needed to establish predictors of long-term weight loss maintenance in those with asthma.
Publisher: Wiley
Date: 22-07-2016
DOI: 10.1111/CEA.12774
Abstract: Omalizumab (Xolair) dosing in severe allergic asthma is based on serum IgE and bodyweight. In Australia, patients eligible for omalizumab but exceeding recommended ranges for IgE (30-1500 IU/mL) and bodyweight (30-150 kg) may still receive a ceiling dose of 750 mg/4 weeks. About 62% of patients receiving government-subsidized omalizumab are enrolled in the Australian Xolair Registry (AXR). To determine whether AXR participants above the recommended dosing ranges benefit from omalizumab and to compare their response to within-range participants. Data were stratified according to dose range status (above-range or within-range). Further sub-analyses were conducted according to the reason for being above the dosing range (IgE only vs. IgE and weight). Data for 179 participants were analysed. About 55 (31%) were above recommended dosing criteria other characteristics were similar to within-range participants. Above-range participants had higher baseline IgE [812 (IQR 632, 1747) IU/mL vs. 209 (IQR 134, 306) IU/mL] and received higher doses of omalizumab [750 (IQR 650, 750) mg] compared to within-range participants [450 (IQR, 300, 600) mg]. At 6 months, improvements in Juniper 5-item Asthma Control Questionnaire (ACQ-5, 3.61 down to 2.01 for above-range, 3.47 down to 1.93 for within-range, P < 0.0001 for both) and Asthma Quality of Life Questionnaire (AQLQ mean score (3.22 up to 4.41 for above-range, 3.71 up to 4.88 for within-range, P < 0.0001) were observed in both groups. Forced expiratory volume in one second (FEV Patients with severe allergic asthma above recommended dosing criteria for omalizumab have significantly improved symptom control, quality of life and lung function to a similar degree to within-range participants, achieved without dose escalation above 750 mg.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Wiley
Date: 03-2002
DOI: 10.1046/J.1440-1746.2002.02640.X
Abstract: Microscopic colitis is an umbrella term used to include two idiopathic inflammatory bowel disorders that present with chronic watery diarrhea, normal endoscopic findings and characteristic inflammatory changes on histology. Collagenous colitis and lymphocytic colitis are distinguished by the presence of a thickened subepithelial collagen table. It is likely that they are a spectrum of one disease, but this is yet to be proven. The majority of cases tend to undergo spontaneous remission within a few years of onset, and their clinical course is benign, with no increase in risk of colorectal cancer. Sufficient evidence exists to suggest that microscopic colitis occurs as a response to one or more luminal antigens. A variety of medications have been reported in the treatment of this condition, but only colloidal bismuth and budesonide have thus far been shown to be effective in randomized controlled trials.
Publisher: Elsevier BV
Date: 03-2022
Publisher: AMPCo
Date: 22-06-2020
DOI: 10.5694/MJA2.50674
Publisher: BMJ
Date: 03-2007
Publisher: Wiley
Date: 25-07-2011
DOI: 10.1111/J.1440-1843.2011.01965.X
Abstract: Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) strains are primarily associated with skin and soft tissue infections however, they are increasingly causing more invasive infections including severe community-acquired pneumonia. The objective of this study was to describe the clinico-pathological characteristics of community-acquired MRSA pneumonia. A retrospective analysis of case records from January 2002 to August 2008 was performed on patients admitted with community-acquired MRSA pneumonia to two large teaching hospitals. Sixteen patients with community-acquired MRSA pneumonia were identified. Their age ranged from 11 months to 86 years (median age 30 years). Duration of symptoms before hospital presentation ranged from one to 21 days. Most patients had productive cough, fever and dyspnoea. The most common radiological presentation included multilobar consolidation (8/16), necrotizing consolidation (7/16) and empyema (5/16). Seven patients required intensive care support four required ionotropic support and five required mechanical ventilation for a mean duration of 53 h and 6.6 days, respectively. Six patients underwent surgery (VATS or open thoracotomy). There was a mean delay of approximately 69 h (range 18 h to 11 days) after presentation before appropriate MRSA antimicrobial treatment was initiated. Three patients died of complications from pneumonia, all within 72 h of presentation. Among survivors, the average length of hospital stay was 23.8 days (range 10-49 days). Majority of survivors were left with mild residual radiological changes. Community-acquired MRSA pneumonia is increasing and should be suspected in patients with severe community-acquired pneumonia. There was a delay in initiation of appropriate antimicrobial treatment that could have lead to increased morbidity.
Publisher: European Respiratory Society (ERS)
Date: 23-12-2016
DOI: 10.1183/13993003.01098-2015
Abstract: Mast cells are a resident inflammatory cell of the airways, involved in both the innate and adaptive immune response. The relationship between mast cells and inflammatory phenotypes and treatment response of asthma is not clear. Clinical characteristics of subjects with stable asthma (n=55), inflammatory cell counts and gene expression microarrays in induced sputum were analysed. Sputum mast cell subtypes were determined by molecular phenotyping based on expression of mast cell biomarkers (tryptase ( TPSAB1 ), chymase ( CMA1 ) and carboxypeptidase A3 ( CPA3 )). Effects of mast cell subtypes on steroid response were observed in a prospective cohort study (n=50). MC T (n=18) and MC T/CPA3 (mRNA expression of TPSAB1 and CPA3 n=29) subtypes were identified, as well as a group without mast cell gene expression (n=8). The MC T/CPA3 subtype had elevated exhaled nitric oxide fraction, sputum eosinophils, bronchial sensitivity and reactivity, and poorer asthma control. This was accompanied by upregulation of 13 genes. Multivariable logistic regression identified CPA3 (OR 1.21, p=0.004) rather than TPSAB1 (OR 0.92, p=0.502) as a determinant of eosinophilic asthma. The MC T/CPA3 subtype had a better clinical response and reduced signature gene expression with corticosteroid treatment. Sputum mast cell subtypes of asthma can be defined by a molecular phenotyping approach. The MC T/CPA3 subtype demonstrated increased bronchial sensitivity and reactivity, and signature gene expression, which was associated with airway eosinophilia and greater corticosteroid responsiveness.
Publisher: European Respiratory Society (ERS)
Date: 10-2017
DOI: 10.1183/23120541.00025-2017
Abstract: Protracted bacterial bronchitis (PBB) in young children is a common cause of prolonged wet cough and may be a precursor to bronchiectasis in some children. Although PBB and bronchiectasis are both characterised by neutrophilic airway inflammation and a prominent interleukin (IL)-1β signature, the contribution of the IL-1β pathway to host defence is not clear. This study aimed to compare systemic immune responses against common pathogens in children with PBB, bronchiectasis and control children and to determine the importance of the IL-1β pathway. Non-typeable Haemophilus influenzae (NTHi) stimulation of peripheral blood mononuclear cells (PBMCs) from control subjects (n=20), those with recurrent PBB (n=20) and bronchiectasis (n=20) induced high concentrations of IL-1β, IL-6, interferon (IFN)-γ and IL-10. Blocking with an IL-1 receptor antagonist (IL-1Ra) modified the cellular response to pathogens, inhibiting cytokine synthesis by NTHi-stimulated PBMCs and rhinovirus-stimulated PBMCs (in a separate PBB cohort). Inhibition of IFN-γ production by IL-1Ra was observed across multiple cell types, including CD3 + T cells and CD56 + NK cells. Our findings highlight the extent to which IL-1β regulates the cellular immune response against two common respiratory pathogens. While blocking the IL-1β pathway has the potential to reduce inflammation, this may come at the cost of protective immunity against NTHi and rhinovirus.
Publisher: Wiley
Date: 02-1995
DOI: 10.1111/J.1365-2222.1995.TB01017.X
Abstract: The purpose of this study was to examine airway responsiveness, sputum cells and the effects of inhaled corticosteroid in the chronic cough syndrome associated with eosinophilic bronchitis. We studied nine consecutive referrals with chronic cough, sputum with > 10% eosinophils, normal spirometry, and normal methacholine airway responsiveness. Clinical assessment, sputum analysis, allergy skin tests and a methacholine inhalation test were performed at the first visit. Peak expiratory flow (PEF) was measured twice daily for 1 week followed by an adenosine monophosphate (AMP) inhalation test. Subjects were then treated with inhaled beclomethasone 0.4 mg twice daily for 7 days. Sputum analysis and measurement of methacholine responsiveness were then repeated. Excessive airway narrowing to methacholine was not present in any of the subjects. A methacholine plateau response was present in five subjects. Hyperresponsiveness to AMP was absent in six of the nine subjects, and PEF variability was not increased for eight subjects. Corticosteroid therapy led to a reduction in sputum eosinophil counts from 40.1 (SD 21.4)% to 4.0 (4.5)% but there was no significant change in metachromatic cell counts (0.8 SD 0.5% vs 0.6 SD 0.6%) or total cell counts. Methacholine responsiveness improved within the normal range in the three subjects in whom it could be determined. Chronic cough associated with eosinophilic airway inflammation can occur in the absence of variable airflow obstruction (asthma) and can improve after treatment with inhaled corticosteroid. This treatment can reduce the level of methacholine responsiveness within the normal range and reduces sputum eosinophils but not mast cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Publisher: European Respiratory Society (ERS)
Date: 31-01-2016
DOI: 10.1183/13993003.01359-2015
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms ( i.e. endotypes), and present similar clinical, functional, imaging and/or biological features that can be observed ( i.e. phenotypes) which require in idualised treatment. Precision medicine is defined as “treatments targeted to the needs of in idual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations”. In this Perspective, we propose a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular.
Publisher: Wiley
Date: 24-01-2007
Publisher: American Thoracic Society
Date: 15-09-2007
Publisher: Wiley
Date: 18-10-2007
DOI: 10.1111/J.1365-2222.2007.02839.X
Abstract: Eosinophilic airway inflammation is a key pathophysiological feature of asthma that can predict treatment response. However, the prognostic value of sputum eosinophilia is not established. The aim of this study was to determine the influence of induced sputum eosinophilia on the prognosis of childhood asthma. A cohort of children with asthma was evaluated by induced sputum analysis at inception and classified as having either eosinophilic asthma (EA) (sputum eosinophils >2.5%) or non-eosinophilic asthma (NEA). After a mean follow-up period of 5 years, eligible subjects (n=83) were contacted and 69 subjects (33 EA, 36 NEA) evaluated. The children had a mean age of 15.9 years, and 61% were male. Children with EA reported more wheeze during the follow-up period (27% vs. 6% wheezed most years P<0.0001), increased night waking during the past 12 months (28% vs. 3% reported weekly waking P=0.01), and greater impairment of quality of life due to asthma (P=0.04). Subsequent beta2-agonist use was increased in children with EA (P=0.02), although there was no difference in corticosteroid use. In EA, subsequent forced expiratory volume in 1 s/forced vital capacity was lower (79% vs. 86% P=0.01) and grass pollen allergy was more prevalent (77% vs. 27% P=0.006). In children, eosinophilic airway inflammation is associated with deteriorating asthma over time. This is consistent with the hypothesis that airway inflammation has an adverse impact on the prognosis of childhood asthma, and suggests a role for monitoring inflammation in asthma management.
Publisher: BMJ
Date: 23-07-2011
Abstract: The well-characterised airway inflammatory phenotypes of asthma include eosinophilic, neutrophilic, mixed eosinophilic/neutrophilic and paucigranulocytic asthma, identified based on the proportion of sputum granulocytes. Systemic inflammation is now recognised as an important part of some airway diseases, but the involvement of systemic inflammation in the pathogenesis of airway inflammatory phenotypes of asthma remains unknown. Induced sputum s les and peripheral blood were collected from participants with asthma (n=36). Airway inflammatory cell counts were performed from induced sputum and inflammatory phenotype assigned based on the airway eosinophil and neutrophil cut-offs of 3% and 61%, respectively. RNA was extracted from whole blood and gene expression profiles were generated (Illumina Humanref-8 V3) and analysed using GeneSpring GX11. There were six genes classified as differentially expressed between the four asthma phenotypes, including the α-defensins (DEFA) 1, 1B, 3 and 4 and neutrophil proteases cathepsin G (CTSG) and elastase (ELA2). Systemic expression of DEFA1,1B,3,4,CTSG and ELA2 was significantly higher in the neutrophilic asthma (NA) phenotype. Microarray results of the α-defensins and neutrophil proteases were successfully validated using real-time PCR. Plasma elastase was significantly increased in people with neutrophilic airway inflammation. There is systemic upregulation of α-defensin and neutrophil protease expression in NA, which may represent proinflammatory effects on the bone marrow and the release of immature neutrophils into the circulation. This demonstrates a systemic inflammatory component in NA that further differentiates this from other asthma phenotypes and indicates different mechanisms in NA.
Publisher: European Respiratory Society
Date: 06-2019
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.JAIP.2018.04.015
Abstract: Chronic refractory cough (CRC), a phenotype of cough hypersensitivity syndrome (CHS), is a disabling problem. Laryngeal dysfunction may be important in CRC and CHS because laryngeal symptoms are common however, the role of laryngeal dysfunction in CHS has not been systematically examined. To determine the nature of laryngeal dysfunction in patients with CRC and compare with the related laryngeal conditions of vocal cord dysfunction (VCD) and muscle tension dysphonia (MTD). A cross-sectional analytic design was used. We recruited 69 participants including healthy controls and patients with CRC, VCD, and MTD who were referred for behavioral speech interventions. Participants underwent a comprehensive assessment of laryngeal function during breathing, phonation, and swallowing. Cough frequency was high in patients with CRC (10.2 coughs/h) and VCD (16.5 coughs/h), but low in healthy controls (1.5 coughs/h) (P < .001). Patients with CRC, VCD, and MTD had impaired voice-related quality of life (vs controls, P < .05) and laryngeal hypersensitivity (vs controls, P < .05). Most voice assessment measures (3 out of 4) were significantly impaired in the CRC group compared with controls and were similar to the VCD and MTD groups. Paradoxical vocal fold movement during respiration was present in 47% of the patients with CRC at rest and in 67% after odor challenge. Mediolateral laryngeal constriction during phonation was present in 45% of the participants with CRC, 93% of the participants with VCD (P < .001 vs CC), and 64% of the participants with MTD. Laryngeal dysfunction is common in CRC and CHS and may contribute to CHS mechanisms. Assessment and treatment of laryngeal dysfunction using speech pathology interventions are likely to be beneficial in CHS.
Publisher: John Wiley & Sons, Ltd
Date: 21-01-2009
Publisher: Wiley
Date: 13-12-2014
DOI: 10.1111/PAI.12156
Publisher: Wiley
Date: 06-12-2020
DOI: 10.1111/RESP.13749
Abstract: Severe asthma is responsible for a disproportionate burden of illness and healthcare costs spent on asthma. This study analyses sputum transcriptomics to investigate the mechanisms and novel treatment targets of severe asthma. Induced sputum s les were collected in a cross-sectional study from participants with severe asthma (n = 12, defined as per GINA criteria), non-severe uncontrolled (n = 21) and controlled asthma (n = 21) and healthy controls (n = 15). Sputum RNA was extracted and transcriptomic profiles were generated (Illumina HumanRef-8 V2) and analysed (GeneSpring). Sputum protein lysates were analysed for p38 activation in a validation study (n = 24 asthma, n = 8 healthy) by western blotting. There were 2166 genes differentially expressed between the four groups. In severe asthma, the expression of 1875, 1308 and 563 genes was altered compared to healthy controls, controlled and uncontrolled asthma, respectively. Of the 1875 genes significantly different to healthy controls, 123 were >2-fold change from which four networks were identified. Thirty genes (>2-fold change) were significantly different in severe asthma compared to both controlled asthma and healthy controls. There was enrichment of genes in the p38 signalling pathway that were associated with severe asthma. Phosphorylation of p38 was increased in a subset of severe asthma s les, correlating with neutrophilic airway inflammation. Severe asthma is associated with substantial differences in sputum gene expression that underlie unique cellular mechanisms. The p38 signalling pathway may be important in the pathogenesis of severe asthma, and future investigations into p38 inhibition are warranted as a 'non-Th2' therapeutic option.
Publisher: European Respiratory Society (ERS)
Date: 12-09-2019
DOI: 10.1183/13993003.01381-2019
Abstract: Preventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and in idual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma. We completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes. Three studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated. Maintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.
Publisher: Wiley
Date: 20-06-2019
DOI: 10.1111/RESP.13626
Publisher: American Thoracic Society
Date: 15-08-2001
DOI: 10.1164/AJRCCM.164.4.2009119
Abstract: Asthma during pregnancy is associated with low-birthweight neonates at term but the mechanisms that cause this outcome are presently unknown. Changes in placental vascular function resulting from asthma or its treatment could contribute to altered fetal growth. We have prospectively followed women with asthma and a control group of women without asthma during their pregnancies, classified them based on asthma severity and glucocorticoid intake, and monitored fetal development and placental blood flow using Doppler ultrasound at 18 and 30 wk gestation. The placentae from these women were collected after delivery and vascular responses to dilator and constrictor agonists assessed using an in vitro placental perfusion method. At 18 wk gestation, umbilical artery flow velocity waveforms were significantly reduced in the moderate and severe asthmatic groups and in those women using high-dose inhaled glucocorticoid for the treatment of their asthma (ANOVA, p 0.05). Corticotropin-releasing hormone (CRH), a potent vasodilator that acts via the nitric oxide pathway, caused a dose-dependent vasodilatory response in all placentae in vitro. However, CRH-induced dilation was significantly reduced in moderate and severe asthmatics (ANOVA, p < 0.05). Vasoconstrictor responses to potassium chloride and prostaglandin F(2alpha) were reduced in placentae from moderate and severe asthmatic women (ANOVA, p < 0.05). These studies demonstrate significant differences in placental vascular function in pregnancies complicated by asthma, which may relate directly to the asthma or be a consequence of the associated glucocorticoid treatment. These changes in vascular function in asthmatic pregnancies may contribute to the low-birthweight outcome observed in this condition.
Publisher: Wiley
Date: 10-1999
DOI: 10.1002/(SICI)1099-0496(199910)28:4<261::AID-PPUL5>3.0.CO;2-I
Abstract: The aim of this study was to examine the relationship between sputum cell counts and clinical variables in children with an acute exacerbation of asthma. Sputum was successfully obtained from 37 of 42 children presenting to the Emergency Department with acute asthma, using ultrasonically nebulized normal saline (n = 19) or spontaneous expectoration (n = 18). Sputum portions were selected and dispersed, and total and differential cell counts were performed. Sputum supernatant was assessed for eosinophil cationic protein (ECP), interleukin (IL)-5, and IL-8. The exacerbations were of 3 inflammatory cell patterns: eosinophilic (n = 16 or 43% of total), combined eosinophilic/neutrophilic (E/N n = 13.3 or 35% of total), or noneosinophilic (n = 8 or 22% of total). IL-5 was highest in eosinophilic exacerbations. Combined E/N exacerbations had increased mast cells (77%) and higher sputum ECP levels than eosinophilic exacerbations: 2,146 ng/mL vs. 666 ng/mL (P = 0.04). The speed of onset of the exacerbation was not related to the inflammatory cell profile. Logistic regression identified maintenance asthma treatment (odds ratio (OR), 5.9 95% confidence interval (CI), 1.3-26.8) and lung function during the acute episode (OR, 4.0 95% CI, 1.7-93) as significantly associated with the intensity of sputum eosinophilia. Eosinophils were lowest in children who received maintenance treatment with oral corticosteroids compared to those with no background asthma preventer therapy (P = 0.001). In conclusion, we identified three distinct patterns of airway inflammation in children with acute asthma they included increased eosinophils, combined eosinophilic-neutrophilic infiltration, and a noneosinophilic pattern. Eosinophil degranulation was greatest with the combined eosinophilic/neutrophilic pattern of airway inflammation. Sputum eosinophils were associated with clinical severity, and background asthma therapy, but not with outcome, nor with speed of onset of exacerbations. These different inflammatory cell profiles imply different etiological agents and may require differing treatment strategies.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JACI.2018.12.1020
Abstract: Improved diagnostic tools for predicting future exacerbation frequency in asthmatic patients are required. A sputum gene expression signature of 6 biomarkers (6-gene signature [6GS], including Charcot-Leyden crystal galectin [CLC] carboxypeptidase 3 [CPA3] deoxyribonuclease 1-like 3 [DNASE1L3] alkaline phosphatase, liver/bone/kidney [ALPL] CXCR2 and IL1B) predicts inflammatory and treatment response phenotypes in patients with stable asthma. Recently, we demonstrated that azithromycin (AZM) add-on treatment in patients with uncontrolled moderate-to-severe asthma significantly reduced asthma exacerbations (AMAZES clinical trial). We sought to test whether the 6GS predicts future exacerbation and inflammatory phenotypes in a subpopulation of AMAZES and to test the effect of AZM therapy on 6GS expression and prognostic capacity. One hundred forty-two patients (73 placebo-treated and 69 AZM-treated patients) had sputum stored for quantitative PCR of 6GS markers at baseline and after 48 weeks of treatment. Logistic regression and receiver operating characteristic and area under the curve (AUC) determination were performed on baseline measures, and in an exploratory analysis the predictive value of the 6GS was compared with conventional biomarkers for exacerbation and inflammatory phenotypes. The 6GS significantly predicted all future exacerbation phenotypes tested. Calculated AUCs for the 6GS were significantly greater than AUCs for peripheral blood eosinophil counts, sputum neutrophil counts, and combined sputum eosinophil and neutrophil counts. 6GS AUCs were also numerically but not significantly greater than those for fractional exhaled nitric oxide values and sputum eosinophil counts. AZM treatment altered neither 6GS expression nor the predictive capacity of the 6GS for future exacerbation phenotypes. The 6GS was a significant predictor of airway inflammatory phenotype in this population. We demonstrate that a sputum gene signature can predict future exacerbation phenotypes of asthma, with the greatest biomarker performance in identifying those who would experience frequent severe exacerbations. AZM therapy did not modify 6GS expression or biomarker performance, suggesting the therapeutic action of AZM is independent of 6GS-related inflammatory pathways.
Publisher: Informa Healthcare
Date: 24-04-2009
DOI: 10.1517/14712590902916999
Abstract: Asthma is a common global health problem. Environmental exposures such as bacteria may protect against asthma development. This review aims to examine the possible protective role of pneumococcal infection and vaccination in asthma. A review of known experimental biology and human epidemiology relating to asthma and pneumococcal infection was performed. Pneumococcal infection can modulate components of allergic airways disease such as airways hyperresponsiveness and airway eosinophilia. Exposure to killed pneumococcus can reproduce these effects and the mechanism may involve control by T regulatory cells. Pneumococcal immunoregulatory therapy is a potentially important approach to asthma management that requires further evaluation in well-designed research studies.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.JAIP.2021.10.017
Abstract: Chronic cough and vocal cord dysfunction are manifestations of laryngeal hypersensitivity syndrome. The aim of the study was to determine the clinical utility of functional transnasal laryngoscopy in patients with laryngeal hypersensitivity syndromes. This study was a prospective observational cross-sectional study design of 71 participants with laryngeal hypersensitivity syndrome referred for functional transnasal laryngoscopy. Participants had a clinical assessment with a speech pathologist after which a provisional diagnosis of chronic cough, suspected vocal cord dysfunction, suspected muscle tension dysphonia, or a combination was made. A laryngoscopy with provocation was performed and the diagnosis revised after which the provisional and revised diagnoses were compared. The diagnosis changed in 67% of participants after laryngoscopy. Vocal cord dysfunction was diagnosed in an additional 17 cases when not expected clinically but discounted when suspected clinically in 12 participants. Muscle tension dysphonia was diagnosed in an additional 31 cases when not suspected clinically and not confirmed when suspected in 2. This study demonstrated that conditions such as muscle tension dysphonia and vocal cord dysfunction cannot be diagnosed based on symptoms alone. In addition to diagnostic accuracy, functional laryngoscopy enhances treatment planning and provides immediate feedback regarding laryngeal movement during respiration and phonation.
Publisher: MDPI AG
Date: 25-02-2017
Publisher: BMJ
Date: 24-09-2013
Publisher: Wiley
Date: 10-02-2012
Publisher: Wiley
Date: 09-2000
DOI: 10.1007/S11745-000-0607-X
Abstract: Oxidlative stress is believed to play an important role in the pathophysiology of asthma. Recently discovered F2-isoprostanes, of which 8-iso-PGF2alpha is the most well-known isomer, have emerged as the most reliable marker of in vivo oxidative stress. The aim of this study was to examine 8-iso-PGF2alpha as a biomarker of oxidative stress in mild asthma in relation to endogenous and dietary antioxidant protection. Total (free and esterified) plasma 8-iso-PGF2alpha, plasma dietary antioxidants (vitamins E and C, Beta-carotene, Zn, and Se), and erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase) were measured in 15 mild asthmatics and 15 age-and sex-matched controls. Total plasma 8-iso-PGF2alpha levels [median (quartile 1 - quartile 3)] were significantly increased in the asthmatics [213 pg/mL (122-455) vs. 139 pg/mL (109-174), P= 0.042]. The 8-iso PGF2alpha levels were found to be associated with clinical asthma severity (P = 0.044) and inhaled corticosteroid use (P = 0.027) in asthmatics. No differences were observed in the plasma dietary antioxidant vitamins. The asthmatics had significantly lower plasma levels of Zn (P = 0.027) and Se (P = 0.006). Plasma Se correlated negatively with 8-iso-PGF2alpha (r = -0.725, P= 0.002). No differences between the groups were observed for glutathione peroxidase or superoxide dismutase, however, superoxide dismutase activity was negatively associated with asthma severity (P = 0.042). In conclusion, oxidative stress is increased in mildly asthmatics, as reflected by increased plasma levels of 8-iso-PGF2alpha and a deficiency in plasma Zn and Se. The isoprostane 8-iso-PGF2alpha may provide a useful tool in intervention studies aimed at improving clinical status in asthma.
Publisher: Wiley
Date: 12-03-2009
DOI: 10.1111/J.1365-2222.2009.03226.X
Abstract: Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improved selection of active treatment(s) based on in idual response, and improved titration of treatment using markers that are better related to treatment outcomes. To review the methodological and design features of noninvasive marker studies in asthma. Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO). FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this. Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy.
Publisher: BMJ
Date: 07-2004
DOI: 10.1136/EBM.9.4.115
Publisher: Elsevier BV
Date: 09-2010
Abstract: The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FeNO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FeNO to usual clinical guideline management including spirometry however, significant design issues may exist. Overall, FeNO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FeNO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FeNO. Monitoring FeNO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases.
Publisher: Informa UK Limited
Date: 08-06-2019
DOI: 10.1080/02770903.2018.1471709
Abstract: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time. Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment. At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication and was significantly reduced following education. There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.
Publisher: Hogrefe Publishing Group
Date: 09-2004
Publisher: Wiley
Date: 23-04-2012
Publisher: Informa UK Limited
Date: 25-03-2016
DOI: 10.1586/17476348.2016.1165096
Abstract: Severe asthma is recognised as an important and emerging area of unmet need in asthma. The assessment of severe asthma should include three steps (1) determining the diagnosis of asthma, including verification that the disease is severe asthma, (2) assessing comorbidities and contributing factors that will impact on clinical severity, as well as (3) assessing asthma phenotypes. These steps recognize the importance of heterogeneity in asthma as a key factor that determines the disease course and increasingly the choice of successful therapy. This assessment should be undertaken systematically and is best done by an expert multidisciplinary team. Here, we will outline the important aspects that should be included in the clinical assessment of the patient in the severe asthma clinic, including diagnosis, clinical history, the assessment of important comorbidities and the key investigations needed to support them.
Publisher: European Respiratory Society (ERS)
Date: 16-08-2012
DOI: 10.1183/09031936.00195111
Abstract: This systematic review and meta-analysis sought to investigate whether asthma exacerbations, oral corticosteroid use or asthma severity are associated with prematurity and intrauterine growth restriction. Cohort studies published between 1975 and March 11, 2012 were considered for inclusion. 138 publications were identified for possible inclusion, and nine papers met the inclusion criteria, by reporting perinatal outcomes of interest (low birth weight, <2500 g), pre-term birth (<37 weeks gestation unless otherwise stated) and small for gestational age (<10th percentile for gestational age and sex) in groups of asthmatic patients stratified by history of exacerbations, oral corticosteroid use or asthma severity. Maternal asthma exacerbations and oral corticosteroid use had a significant effect on outcomes, including low birth weight (RR 3.02, 95% CI 1.87-4.89 and RR 1.41, 95% CI 1.04-1.93, respectively) and pre-term delivery (RR 1.54, 95% CI 0.89-2.69 and RR 1.51, 95% CI 1.15-1.98, respectively). Moderate-to-severe asthma during pregnancy was associated with an increased risk of small for gestational age (RR 1.24, 95% CI 1.15-1.35) and low birth weight (RR 1.15, 95% CI 1.05-1.26) infants. These data suggest that asthma exacerbations, oral corticosteroid use or asthma severity defined as moderate-to-severe may be associated with pre-term delivery, low birth weight, and small for gestational age infants. Further studies on the effect of maternal asthma control on perinatal outcomes are warranted.
Publisher: Wiley
Date: 09-1998
DOI: 10.1046/J.1365-2222.1998.00331.X
Abstract: Induced sputum is a useful way to monitor airway inflammation in asthma, but cell counts are time-consuming and labour intensive. The aim of this study was to evaluate a novel processing method using eosinophil cationic protein (ECP) as a biochemical marker of sputum eosinophil number and activation in subjects with asthma and other airway diseases. Sputum was dispersed with dithiothreitol and centrifuged to yield cell free supernatant and a cell pellet. The pellet was treated with a cellular lysis buffer to release cell-associated ECP. ECP was measured in sputum supernatant and in the lysed cell pellet and was compared with sputum eosinophil counts in 31 adults with asthma, chronic obstructive airway disease (COAD), bronchiectasis and healthy controls. The ratio of supernatant to pellet ECP was evaluated as an index of eosinophil degranulation. The effect of sputum processing reagents and storage time on ECP measurement was also evaluated. ECP measured in the cell pellet lysate correlated closely with sputum absolute eosinophil counts across a range of subject groups (r = 0.72, P = 0.004). Sputum eosinophil counts were less well correlated with supernatant ECP levels (r = 0.54, P < 0.05). Incubation with dithiothreitol or lysis buffer did not influence ECP measurement and sputum ECP levels were stable over a 6-9 month period. Sputum supernatant and pellet lysate ECP concentrations were increased in stable asthma, asthma exacerbations and COAD/bronchiectasis (P < 0.05). The ratio of supernatant to pellet ECP was used as an index of eosinophil degranulation and found to be elevated in asthma exacerbations, COAD and bronchiectasis, but not in stable asthma. The measurement of ECP in the sputum cell pellet provides a reliable and efficient estimate of sputum eosinophil counts which can potentially be used in clinical trials and epidemiological surveys. The ECP ratio may be a useful marker of eosinophil activation, and was increased in asthma exacerbation and COAD. The increased ECP in COAD reflects a non-selective accumulation of eosinophils in this condition.
Publisher: European Respiratory Society (ERS)
Date: 31-03-2014
Publisher: European Respiratory Society (ERS)
Date: 10-2017
DOI: 10.1183/13993003.01655-2017
Abstract: On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often overlap and that both require in idualised assessment and treatment. This paper summarises the presentations and discussions that took place during the seminar. Specifically, we discussed the need for a new taxonomy of human diseases, the role of different players in this scenario (exposome, genes, endotypes, phenotypes, biomarkers and treatable traits) and a number of unanswered key questions in the field. We also addressed how to deploy airway precision medicine in clinical practice today, both in primary and specialised care. Finally, we debated the type of research needed to move the field forward.
Publisher: Elsevier BV
Date: 03-2005
DOI: 10.1016/J.CCCN.2004.11.002
Abstract: Cystic fibrosis (CF) is the most commonly occurring lethal autosomal recessive disorder. The gene defect causes defective sodium and chloride transport across epithelial cells of the respiratory, hepatobiliary, gastrointestinal and reproductive tracts, resulting in thick mucus secretions. In the respiratory tract, mucus traps bacteria, causing repeated lung infections, progressive bronchiectasis and eventual death due to respiratory failure. In the gastrointestinal tract, mucus prevents pancreatic enzymes reaching the gut, leading to nutrient malabsorption. Careful nutritional management has a dramatic effect on growth and survival rates in CF. Appropriate nutritional support includes pancreatic enzyme replacement therapy, a high-fat/high-energy diet and essential nutrient supplementation, specifically fat-soluble vitamins and essential fatty acids (EFA). Long-term studies are required to examine the effects of nutritional interventions on key clinical outcomes in CF, such as the rate of decline of lung function. The use of circulating markers to assess the influence of nutritional therapy allows short-term intervention studies to predict the potential for clinical improvements. This article provides an overview of the biomarkers useful in the prediction of the efficacy of nutritional therapy on improvements in quality and quantity of life in CF.
Publisher: Wiley
Date: 12-08-2015
DOI: 10.1111/RESP.12602
Abstract: Severe or therapy-resistant asthma represents a major problem, and despite advanced treatment, many patients require oral corticosteroids (OCS). We aimed to determine if patients with severe asthma and elevated peripheral blood eosinophils (PBE) could have treatment with OCS adjusted using an algorithm that controlled PBE (<0.2 × 10(9) /L). In 11 patients, the OCS dose was adjusted to suppress PBE, leading to a reduced exacerbation frequency and improvement in asthma symptoms with an overall lower OCS dose.
Publisher: Elsevier BV
Date: 07-2017
DOI: 10.1016/J.JAIP.2017.03.040
Abstract: Obesity is a risk factor for exacerbations of asthma, but the mechanisms of this effect in pregnancy are unknown. This study determined the influence of maternal body mass index, gestational weight gain, eosinophilic inflammation, and systemic macrophage activation on the risk of exacerbations during pregnancy. Women with asthma (n = 164) participated in the study. Body mass index recorded at baseline (17 weeks gestation) was categorized as healthy weight (18.5-24.9 kg/m Exacerbations occurred in a higher proportion of overweight (51.1%) and obese (48.4%) women compared with healthy weight women (25% P = .026). Excess weight gain during pregnancy was not associated with exacerbation risk. Macrophage activation (elevated serum soluble CD-163) was associated with exacerbations requiring oral corticosteroids (P = .043), whereas high peripheral blood eosinophils or fractional exhaled nitric oxide were not associated with exacerbation or oral corticosteroid use. Being overweight or obese confers a greater risk of asthma exacerbation during pregnancy, and may be due to systemic macrophage activation.
Publisher: BMJ
Date: 03-03-2012
DOI: 10.1136/THORAXJNL-2011-200160
Abstract: 20-30% of patients with asthma have neutrophilic airway inflammation and reduced responsiveness to steroid therapy. They often have chronic airway bacterial colonisation and Haemophilus influenzae is one of the most commonly isolated bacteria. The relationship between chronic airway colonisation and the development of steroid-resistant neutrophilic asthma is unclear. To investigate the relationship between H influenzae respiratory infection and neutrophilic asthma using mouse models of infection and ovalbumin (OVA)-induced allergic airways disease. BALB/c mice were intratracheally infected with H influenzae (day 10), intraperitoneally sensitised (day 0) and intranasally challenged (day 12-15) with OVA. Treatment groups were administered dexamethasone intranasally during OVA challenge. Infection, allergic airways disease, steroid sensitivity and immune responses were assessed (days 11, 16 and 21). The combination of H influenzae infection and allergic airways disease resulted in chronic lung infection that was detected on days 11, 16 and 21 (21, 26 and 31 days after infection). Neutrophilic allergic airways disease and T helper 17 cell development were induced, which did not require active infection. Importantly, all features of neutrophilic allergic airways disease were steroid resistant. Toll-like receptor 4 expression and activation of phagocytes was reduced, but most significantly the influx and/or development of phagocytosing neutrophils and macrophages into the airways was inhibited. The combination of infection and allergic airways disease promotes bacterial persistence, leading to the development of a phenotype similar to steroid-resistant neutrophilic asthma and which may result from dysfunction in innate immune cells. This indicates that targeting bacterial infection in steroid-resistant asthma may have therapeutic benefit.
Publisher: European Respiratory Society (ERS)
Date: 12-2000
DOI: 10.1034/J.1399-3003.2000.16F13.X
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity reaction to the fungus Aspergillus fumigatus that may progress to bronchiectasis. The aim of the present study was to characterize airway inflammation in patients with clinically stable ABPA and asthma, and to correlate this with bronchiectasis severity. Subjects with ABPA and central bronchiectasis (ABPA-CB n=16) and ABPA with serological evidence alone (ABPA-S n=10) were studied. Comparison groups were A. fumigatus-sensitized asthma (n=19), non-A. fumigatus-sensitized asthma (n=15) and healthy controls (n=8). Hypertonic saline challenge, sputum induction and high-resolution computed tomography (HRCT) of the chest were performed. Sputum eosinophil numbers were markedly elevated in ABPA-CB (median 8.4%) compared to ABPA-S (2.4%), A. fumigatus-sensitized asthma (1.8%), asthma (1.8%) and controls (0.3%) (p<0.01) sputum eosinophil cationic protein levels were higher in ABPA-CB (median 13,706 ng.mL(-1)), compared to ABPA-S (1,633.5 ng.mL(-1)), A. fumigatus-sensitized asthma (1,550.7 ng.mL(-1)), asthma (309.2 ng.mL(-1)), and controls (110 ng.mL(-1)) (p<0.001). ABPA-CB also showed increased sputum neutrophil number (median 60.3%) compared to the other groups (controls 29.3%) (p=0.01). The severity of bronchiectasis on HRCT correlated with sputum neutrophil (r=0.6) and eosinophil number (r=0.5) but not serum immunoglobulin-E levels. In conclusion, clinically stable allergic bronchopulmonary aspergillosis with bronchiectasis is characterized by an intense heterogenous inflammatory infiltrate consisting of eosinophils and neutrophils, which correlates closely with the severity of bronchiectasis on high-resolution computed tomography. Sputum analysis may be useful in monitoring the course of allergic bronchopulmonary aspergillosis.
Publisher: European Respiratory Society (ERS)
Date: 22-07-2021
DOI: 10.1183/23120541.00319-2021
Abstract: Objective quantification of cough is rarely utilised outside of research settings and the role of cough frequency monitoring in clinical practice has not been established. This study examined the clinical utility of cough frequency monitoring in an outpatient clinical setting. The study involved a retrospective review of cough monitor data. Participants included 174 patients referred for treatment of cough and upper airway symptoms (103 chronic cough 50 inducible laryngeal obstruction 21 severe asthma) and 15 controls. Measures, taken prior to treatment, included 24-h ambulatory cough frequency using the Leicester Cough Monitor, the Leicester Cough Questionnaire and Laryngeal Hypersensitivity Questionnaire. Post-treatment data were available for 50 participants. Feasibility and clinical utility were also reported. Analysis time per recording was up to 10 min. 75% of participants could use the monitors correctly, and most (93%) recordings were interpretable. The geometric mean cough frequency in patients was 10.1±2.9 (mean± sd ) compared to 2.4±2.0 for healthy controls (p=0.003). There was no significant difference in cough frequency between clinical groups (p=0.080). Cough frequency decreased significantly following treatment (p .001). There was a moderate correlation between cough frequency and both cough quality of life and laryngeal hypersensitivity. Cough frequency monitoring was responsive to therapy and able to discriminate differences in cough frequency between diseases. While ambulatory cough frequency monitoring remains a research tool, it provides useful clinical data that can assist in patient management. Logistical issues may preclude use in some clinical settings, and additional time needs to be allocated to the process.
Publisher: Elsevier BV
Date: 05-2018
Publisher: Elsevier BV
Date: 10-2014
Abstract: Protracted bacterial bronchitis (PBB) is a common and treatable cause of chronic wet cough in children in which the mechanisms are not understood. This study investigates the IL-1 pathway and a neutrophil gene expression signature in PBB. BAL was collected from children in an experimental cohort (n = 21, PBB n = 33, control subjects), and a second validation cohort (n = 36, PBB n = 11, control subjects). IL-1β, IL-1 receptor antagonist (IL-1RA), and α-defensins 1-3 were assayed by enzyme-linked immunosorbent assay, western blot, and quantitative real-time polymerase chain reaction, together with selected IL-1 pathway members and neutrophil-related molecules. In the experimental cohort, children with symptomatic PBB had significantly higher levels of IL-1β and α-defensin gene and protein expression. Expression of the neutrophil chemokine receptor C-X-C motif receptor 2 was also higher in PBB. IL-1RA protein was higher, however, the IL-1RA:IL-1β ratio was lower in children with PBB than control subjects. In the validation cohort, protein and gene expression of IL-1β and α-defensins 1-3 were confirmed higher, as was gene expression of IL-1 pathway members and C-X-C motif receptor 2. IL-1β and α-defensin 1-3 levels lowered when PBB was treated and resolved. In children with recurrent PBB, gene expression of the IL-1β signaling molecules pellino-1 and IL-1 receptor-associated kinase 2 was significantly higher. IL-1β protein levels correlated with BAL neutrophilia and the duration and severity of cough symptoms. IL-1β and α-defensin 1-3 levels were highly correlated. PBB is characterized by increased IL-1β pathway activation. IL-1β and related mediators were associated with BAL neutrophils, cough symptoms, and disease recurrence, providing insight into PBB pathogenesis.
Publisher: Elsevier BV
Date: 08-2021
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.JAIP.2018.08.016
Abstract: The lack of centralized data on severe asthma has resulted in a scarcity of information about the disease and its management. The development of a common data collection tool for the International Severe Asthma Registry (ISAR) will enable standardized data collection, subsequently enabling data interoperability. To create a standardized list of variables for the first international registry for severe asthma via expert consensus. A modified Delphi process was used to reach consensus on a minimum set of variables to capture in ISAR: the core variables. The Delphi panel brought together 27 international experts in the field of severe asthma research. The process consisted of 3 iterative rounds. In each round, all Delphi panel members were issued an electronic ISAR Delphi workbook to complete and return to the ISAR Delphi administrator. Workbooks and result summaries were anonymously distributed by the Delphi administrator to all panel members at subsequent rounds. Finalization of the core variable list was facilitated by 2 face-to-face meetings. Of the initial 747 selected variables, the Delphi panel reached a consensus on 95. The chosen variables will allow severe asthma to be assessed against patient demographics and medical history, patient-reported outcomes, diagnostic information, and clinical characteristics. Physician-reported outcomes such as nonadherence and information about treatment and management strategies will also be recorded. This is the first global attempt to generate an ISAR using a common set of core variables to ensure that data collected across all participating countries are standardized.
Publisher: Wiley
Date: 23-02-2018
DOI: 10.1111/JHN.12546
Abstract: The low FODMAP (fermentable, oligo-, di-, mono-saccharides and polyols) diet is an effective strategy to improve symptoms of irritable bowel syndrome. However, combining the low FODMAP diet with another dietary restriction such as vegetarianism/veganism is challenging. Greater knowledge about the FODMAP composition of plant-based foods and food processing practices common to vegetarian/vegan eating patterns would assist in the implementation of the diet in this patient population. The present study aimed to quantify the FODMAP content of plant-based foods common in vegetarian/vegan diets and to investigate whether food processing can impact FODMAP levels. Total FODMAP content was quantified in 35 foods, including fructose-in-excess-of-glucose, lactose, sorbitol, mannitol, galacto-oligosaccharide and total fructan, using high-performance-liquid-chromatography and enzymatic assays. The effects of cooking, sprouting, pickling, fermentation, activation and canning on FODMAP content were assessed. The Monash University criteria to classify foods as low FODMAP was used. Of the 35 foods, 20 were classified as low FODMAP, including canned coconut milk (0.24 g serve The present study provides a greater FODMAP composition knowledge of plant-based foods that can now be applied to the dietetic management of vegetarians/vegans requiring a low FODMAP diet. Food processing lowered the FODMAP content of foods, thereby increasing options for patients following a low FODMAP diet.
Publisher: European Respiratory Society (ERS)
Date: 05-2004
DOI: 10.1183/09031936.04.00043104A
Abstract: Excessive salivary contamination of induced sputum s les prevents the satisfactory examination of lower airway inflammation. The effects of salivary contamination on different sputum fluid phase measures and the levels of salivary contamination preventing analysis are not defined. The present study sought to examine this by investigating the effect of increasing salivary contamination on induced sputum s les. Sputum and saliva s les from subjects with asthma and healthy controls were collected, and treated with dithiothreitol (DTT). Saliva was then added to aliquots of dispersed sputum in increasing proportions (0% to 100%). The effect of increasing saliva contamination was assessed on sputum total cell count, viability, differential cell count and fluid phase levels of interleukin (IL)-8, eosinophil cationic protein (ECP) and total protein. The addition of saliva to induced sputum reduced total cell counts and absolute cell counts but did not change the differential cell count. Levels of fluid phase ECP and IL-8 were significantly reduced with increased salivary contamination. There was a progressive reduction in ECP and IL-8, which reached significance at 70% and 80% saliva contamination, respectively. IL-8 levels corrected for total protein showed no change with increasing saliva concentrations. Induced sputum differential cell counts expressed as the proportion of nonsquamous cells are robust measures that are not influenced by salivary contamination. Studies reporting total and absolute cell counts and fluid phase mediator levels require control for squamous contamination.
Publisher: European Respiratory Society (ERS)
Date: 30-09-2013
Publisher: SAGE Publications
Date: 05-2007
Abstract: Chronic cough (CC) can be refractory to medical treatment and newer strategies are required for these patients. Behaviour modification therapies are a potential approach for management of cough that does not respond to medical management. Behaviour modification therapy for CC involves an in idually tailored programme teaching in iduals to increase control over cough symptoms and includes education, specific strategies to suppress the cough, vocal hygiene training and psychoeducational counselling. Several case series have described speech pathology treatment for CC and a recent randomized control trial has demonstrated a significant improvement in symptoms. Possible mechanisms for this improvement include reduced cough reflex sensitivity, increased voluntary control of the cough and reduced stimulation of cough receptors. Respiratory retraining used by physiotherapists may also have potential for use in CC. The validity of psychological therapeutic approaches to CC rests on concepts of CC as a disorder with a psychogenic component, and the ability of cognitive therapies to modify the cough pathway. This work outlines current literature into behavioural management of CC and suggests new directions for practice and research in adults with this condition. Chronic Respiratory Disease 2007 4: 89—97
Publisher: MDPI AG
Date: 10-01-2017
DOI: 10.3390/NU9010057
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2019
Publisher: BMJ
Date: 13-07-2010
Abstract: Smoking and severe asthma exacerbations in pregnancy are risk factors for low birth weight babies. No studies have assessed the clinical implications of smoking on asthma exacerbations in pregnancy. Pregnant women with current asthma (n=80) were prospectively assessed at clinic visits (18, 30, 36 weeks), during exacerbations and with fortnightly phone calls. The asthma control questionnaire was administered at each contact and exacerbations classified as severe (requiring medical intervention) or mild (self-managed). Medications, self-management skills, smoking history, fractional exhaled nitric oxide (FENO), exhaled carbon monoxide (ECO) and lung function were assessed. Pregnant women without asthma (controls, n=46) were assessed prospectively at clinic visits. Women with asthma were more likely to smoke (34% current smokers) than women without asthma (15% current smokers). In women with asthma, the median (IQR) exacerbation rate during pregnancy was 2.0 (1.0-3.0) in current smokers, 2.0 (1.0-3.0) in ex-smokers and 1.5 (1.0-2.0) in never smokers. The asthma control score during exacerbations was higher in current smokers (median (IQR) 2.17 (1.17-2.7)) compared with never smokers (1.17 (0.8-2.17), p=0.056). An adjusted linear regression model found that smoking was significantly associated with higher asthma control score during exacerbation (P=0.04). birth weights were lower among children of smokers than non-smokers (p=0.023 control group, p=0.086 asthma group). During pregnancy, asthma exacerbations are more common and more severe in current smokers than never smokers. The risk of effects of maternal asthma on the fetus may be greater among smokers.
Publisher: Elsevier BV
Date: 04-2018
Publisher: Springer Science and Business Media LLC
Date: 20-11-2019
DOI: 10.1186/S12931-019-1225-5
Abstract: Respiratory virus-induced asthma exacerbations occur frequently during pregnancy and are associated with adverse outcomes for mother and child. Primary nasal epithelial cells (pNECs) provide a useful method to study immune responses in pregnancy. pNECs were obtained by nasal brushings from pregnant and non-pregnant women with and without asthma. pNECS were infected in vitro with major group Rhinovirus 43 (RV43) and seasonal influenza (H3N2). Following infection, pNECs showed measurable quantities of interferon (IFN)-λ, IL-1β, IL-8, IP-10 and MIP1-α. pNECs provide a safe and effective method for studying respiratory epithelial cell responses during pregnancy.
Publisher: Springer Science and Business Media LLC
Date: 07-2005
DOI: 10.1016/J.JSGI.2005.01.024
Abstract: We conducted a comparative proteomic analysis of placental and umbilical cord blood proteins using surface-enhanced laser desorption ionization-time of flight mass spectrometry (SELDI-TOF MS) to examine the associations among asthma, fetal gender, and protein profiles. Placental tissue and umbilical vein plasma were collected from 10 healthy and 20 asthmatic women. Placental proteins were extracted using phosphate-buffered saline containing protease inhibitors. S les were applied to the surfaces of strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using a Ciphergen Protein Biology System IIc (Freemont, CA), and differences in in idual peak intensities between groups were determined. Fourteen placental peaks were significantly different between asthmatic and non-asthmatic women (seven more highly expressed and seven less highly expressed). Ten umbilical cord blood peak differences were identified, with four peaks more highly expressed and six peaks less highly expressed in asthmatics. Four placental and three umbilical cord blood proteins differed significantly between male and female fetuses. Two placental and five umbilical cord blood peaks were specifically increased in a subgroup of s les collected from asthmatic women who did not use inhaled glucocorticoids and were pregnant with a female fetus, a group previously found to have altered placental function. This study demonstrates the abilities of the SELDI technique as a tool for protein profiling in tissue or plasma. Further work to positively identify the candidate peptides found in this study may provide a greater understanding of the placental mechanisms leading to alterations in fetal growth in patients with bronchial asthma.
Publisher: Wiley
Date: 22-11-2007
Publisher: Elsevier BV
Date: 08-2009
DOI: 10.1016/J.JNUTBIO.2008.06.001
Abstract: Rhinovirus infection results in increased release of inflammatory mediators from airway epithelial cells in asthma. As an antioxidant, lycopene offers protection from adverse effects of inflammation. The aim of this study was to find an appropriate method of lycopene enrichment of airway epithelial cells and to determine the effects of lycopene enrichment on the inflammatory response of cells infected by rhinovirus or exposed to lipopolysaccharide. Lycopene enrichment of airway epithelial cells using solubilisation in tetrahydrofuran versus incorporation in liposomes was compared. After determining that solubilisation of lycopene in tetrahydrofuran was the most suitable method of lycopene supplementation, airway epithelial cells (Calu-3) were incubated with lycopene (dissolved in tetrahydrofuran) for 24 h, followed by rhinovirus infection or lipopolysaccharide exposure for 48 h. The release of interleukin-6, interleukin-8 and interferon-gamma induced protein-10 (IP-10) and their messenger RNA levels were measured using enzyme linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. Viral replication was measured by tissue culture infective dose of 50% assay. Lycopene concentration of cells and media were analysed using high-performance liquid chromatography. Preincubation of airway epithelial cells with lycopene (dissolved in tetrahydrofuran) delivered lycopene into the cells and resulted in a 24% reduction in interleukin-6 after rhinovirus-1B infection, 31% reduction in IP-10 after rhinovirus-43 infection and 85% reduction in rhinovirus-1B replication. Lycopene also decreased the release of IL-6 and IP-10 following exposure to lipopolysaccharide. We conclude that lycopene has a potential role in suppressing rhinovirus induced airway inflammation.
Publisher: MDPI AG
Date: 06-12-2022
DOI: 10.3390/JCM11237241
Abstract: Background: Skeletal muscle mass (SMM) has been suggested to be associated with multiple health-related outcomes. However, the potential influence of SMM on asthma has not been largely explored. Objective: To study the association between SMM and clinical features of asthma, including asthma control and exacerbation, and to construct a model based on SMM to predict the risk of asthma exacerbation (AEx). Methods: In this prospective cohort study, we consecutively recruited patients with asthma (n = 334), classified as the SMM Normal group (n = 223), SMM Low group (n = 88), and SMM High group (n = 23). We investigated the association between SMM and clinical asthma characteristics and explored the association between SMM and asthma control and AEx within a 12-month follow-up period. Based on SMM, an exacerbation prediction model was developed, and the overall performance was externally validated in an independent cohort (n = 157). Results: Compared with the SMM Normal group, SMM Low group exhibited more airway obstruction and worse asthma control, while SMM High group had a reduced eosinophil percentage in induced sputum. Furthermore, SMM Low group was at a significantly increased risk of moderate-to-severe exacerbation compared with the SMM Normal group (relative risk adjusted 2.02 [95% confidence interval (CI), 1.35–2.68] p = 0.002). In addition, a model involving SMM was developed which predicted AEx (area under the curve: 0.750, 95% CI: 0.691–0.810). Conclusions: Low SMM was an independent risk factor for future AEx. Furthermore, a model involving SMM for predicting the risk of AEx in patients with asthma indicated that assessment of SMM has potential clinical implications for asthma management.
Publisher: BMJ
Date: 02-2004
DOI: 10.1136/THORAX.2003.011858
Abstract: Written action plans for asthma facilitate the early detection and treatment of an asthma exacerbation. Several versions of action plans have been published but the key components have not been determined. A study was undertaken to determine the impact of in idual components of written action plans on asthma health outcomes. Randomised controlled trials (n=26) that evaluated asthma action plans as part of asthma self-management education were identified. Action plans were classified as being in idualised and complete if they specified when and how to increase treatment (n=17), and as incomplete (n=4) or non-specific (n=5) if they did not include these instructions. For in idualised complete written action plans the use of 2-4 action points and the use of both inhaled (ICS) and oral (OCS) corticosteroid consistently improved asthma outcomes. Action points based on personal best peak expiratory flow (PEF) consistently improved health outcomes while those based on percentage predicted PEF did not. The efficacy of incomplete action plans was inconclusive because of insufficient data. Non-specific action plans led to improvements in knowledge and symptoms. In idualised written action plans based on personal best PEF, using 2-4 action points, and recommending both ICS and OCS for treatment of exacerbations consistently improve asthma health outcomes. Other variations appear less beneficial or require further study. These observations provide a guide to the types of variations possible with written action plans, and strongly support the use of in idualised complete written action plans.
Publisher: Wiley
Date: 30-11-2017
DOI: 10.1111/RESP.12957
Abstract: Asthma is a chronic respiratory disease characterized by respiratory symptoms, airway inflammation, airway obstruction and airway hyper-responsiveness. Asthma is common and directly affects 10% of Australians, 1-5% of adults in Asia and 300 million people worldwide. It is a heterogeneous disorder with many clinical, molecular, biological and pathophysiological phenotypes. Current management strategies successfully treat the majority of patients with asthma who have access to them. However, there is a subset of an estimated 5-10% of patients with asthma who have severe disease and are disproportionately impacted by symptoms, exacerbations and overall illness burden. The care required for this relatively small proportion of patients is also significant and has a major impact on the healthcare system. A number of new therapies that hold promise for severe asthma are currently in clinical trials or are entering the Australian and international market. However, recognition of severe asthma in clinical practice is variable, and there is little consensus on the best models of care or how to integrate emerging and often costly therapies into current practice. In this article, we report on roundtable discussions held with severe asthma experts from around Australia, and make recommendations about approaches for better patient diagnosis and assessment. We assess current models of care for patient management and discuss how approaches may be optimized to improve patient outcomes. Finally, we propose mechanisms to assess new therapies and how to best integrate these approaches into future treatment.
Publisher: European Respiratory Society (ERS)
Date: 03-2005
Publisher: Wiley
Date: 04-12-2016
DOI: 10.1002/PPUL.23351
Publisher: American Thoracic Society
Date: 15-09-2016
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.CHEST.2019.06.012
Abstract: Neutrophil extracellular traps (NETs) are extrusions of intracellular DNA and attached granular material that enable bacterial killing. NETs are increasingly recognized for their role in the pathogenesis of respiratory disease. NETs are composed of a complex mix of intracellularly derived material that neutrophils organize within the cytoplasm and then expel in a nondirected manner in the vicinity of invading organisms. Combined, these trap and destroy multiple genera of microbes including bacteria, fungi, viruses, and protozoans, limiting infection especially where phagocytosis is not possible. At first, NET formation was thought to be a terminal event for neutrophils however, it is now apparent that some neutrophils survive this process, becoming anuclear, and may drive ongoing tissue damage. NETs are now known to be directly cytotoxic to lung epithelium and endothelium, and their excessive production is seen in pneumonia and acute lung injury as well as several chronic diseases, including COPD, asthma, and cystic fibrosis. NETs also appear to play a role in both tumor defense and dissemination, depending on the local microenvironment and the specific tumor subtype. It is becoming increasingly apparent that NET formation can exert a positive or negative influence on multiple respiratory pathologies and that simply globally reducing or increasing NET formation is unlikely to be a therapeutic success. Rather, as our understanding grows, it is likely that targeted NET up- or downregulation along with destruction or protection of already formed NETs may become an additional point of intervention for respiratory physicians.
Publisher: Wiley
Date: 30-11-2017
DOI: 10.1111/RESP.12956
Publisher: Informa UK Limited
Date: 04-2001
DOI: 10.1080/07315724.2001.10719028
Abstract: To examine oxidative stress in CF by measuring 8-iso-PGF2alpha and antioxidant defenses, in relation to dietary intake, immune function and clinical status. We measured total plasma concentrations of 8-iso-PGF2alpha and dietary antioxidants (vitamin E, vitamin C, beta-carotene), erythrocyte antioxidant enzyme activities (glutathione peroxidase and superoxide dismutase), lung function and dietary intake in 21 CF subjects and 21 healthy age- and gender-matched controls. Total plasma 8-iso-PGF2alpha concentration (median [quartile 1-quartile 3]) was significantly higher in CF subjects compared to controls (214 pg/mL (155-331) vs. 135 pg/mL (101-168), p = 0.001). Neutrophil, monocyte and total white cell counts were elevated in the CF group and these correlated with 8-iso-PGF2alpha concentration. Despite similar dietary intake, lower plasma antioxidant concentrations were observed in the CF group (vitamin E, p < 0.001, vitamin C, p = 0.004, beta-carotene, p = 0.001). 8-iso-PGF2alpha correlated negatively with plasma vitamin E, C and beta-carotene concentrations. Oxidative stress is increased in CF patients, despite normal dietary antioxidant intake. The immune response appears to be a key factor causing oxidative stress. Antioxidant intervention aimed at reducing oxidative stress in CF needs to be assessed.
Publisher: AMPCo
Date: 02-2017
DOI: 10.5694/MJA16.00731
Abstract: Targeted therapy has emerged as a highly effective treatment approach for chronic respiratory diseases. Many of these conditions have dismal outcomes however, targeted therapy shows great results for the subgroup who respond. This represents a new way to approach these conditions and offers great promise as a future treatment direction. In severe eosinophilic asthma, therapy that targets the interleukin-5 pathway with monoclonal antibodies leads to a 50% reduction in asthma exacerbations in previously refractory disease. In cystic fibrosis, lung function improves with therapy that targets specific molecular abnormalities in the cystic fibrosis transmembrane conductance regulator to increase the probability that this chloride channel is open. In lung cancer, specifically adenocarcinoma with epidermal growth factor receptor (EGFR) mutation and overexpression of EGFR tyrosine kinase, therapy that inhibits EGFR tyrosine kinase gives better outcomes than conventional chemotherapy.
Publisher: Public Library of Science (PLoS)
Date: 31-03-2011
Publisher: Wiley
Date: 12-1987
DOI: 10.1111/J.1445-5994.1987.TB01254.X
Abstract: Between 1983 and 1985, 71 patients with the acquired immunodeficiency syndrome (AIDS) were evaluated. Pulmonary manifestations were present in 42 patients (59%). Pneumocystis carinii pneumonia (PCP) was the most common pulmonary manifestation, present in 32 patients (45%). Other pulmonary findings were cytomegalovirus pneumonia (one patient), Candida pneumonia (one patient), cryptococcal pneumonia (one patient), bacterial pneumonia (three patients), nonspecific pneumonitis (three patients), Kaposi's sarcoma (one patient), and non-Hodgkin's lymphoma (one patient). The presenting features of PCP were reviewed and in seven patients the chest X-ray and blood gases were normal at the time of diagnosis of PCP. Bronchoscopy was a safe and useful technique for obtaining specimens for diagnosis promptly, and a combination of s les obtained by bronchial washings/brushings and transbronchial biopsy was found to give a higher diagnostic yield than any single s le. Drug side-effects were common during therapy, requiring change of therapy in 16 patients. At one month after diagnosis 16% of patients with PCP had died. PCP is a common pulmonary manifestation in patients with AIDS which is treatable and has an initially favourable outcome.
Publisher: SAGE Publications
Date: 2019
Abstract: Acute exacerbations of chronic airway disease are common occurrences that cause a major burden of illness. Acute exacerbations are associated with impaired health status, increased lung function decline, hospitalization and increased risk of death. Exacerbation avoidance is a major priority. Despite this goal, exacerbations continue to occur and the need for effective models of care that optimize patient outcomes are urgently needed. ‘Treatable Traits’ is an approach to personalized medicine that has been proposed for the management of airway diseases. The treatable traits approach allows for the recognition of clinically important, identifiable and treatable disease characteristics, followed by targeted and in idualized treatment interventions to address each trait. We review the literature relating to treatable traits in airway diseases in particular, those traits that can predict exacerbations and approaches to management that aim to prevent exacerbations by using a treatable traits model of care. We propose this approach as a potentially useful model of care to both prevent and manage acute exacerbations.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2016
Publisher: Informa UK Limited
Date: 28-04-2011
DOI: 10.1517/14656566.2011.576249
Abstract: Chronic cough is responsible for a significant illness burden in the community. Refractory cough causes substantial quality-of-life impairment in people with this problem. Neuromodulators for sensory neuropathic cough and new compounds to block transient receptor potential (TRP) receptors hold promise for chronic cough and upper airway hypersensitivity. The authors examine current evidence on the new concepts of chronic cough that relate to the study of idiopathic/refractory cough, the role of central nervous system control of cough and the role of laryngeal irritability and sensory neuropathy in cough. Compounds in development to block TRP receptors, treatment for a neuropathic disorder with neuromodulators and cough suppression with opioids, especially codeine and morphine, are investigated. Relevant randomized control trials and case reports were identified through a PubMed search of English-language literature referring to these concepts. The concept that sensory neuropathic disorder may underlie some cases of chronic cough is useful in characterizing cough, understanding its mechanisms and guiding drug development.
Publisher: Georg Thieme Verlag KG
Date: 04-2006
Abstract: Allergic bronchopulmonary aspergillosis is an uncommon but serious respiratory condition characterized by chronic airway inflammation and airway damage resulting from persistent colonization by and sensitization to the fungus Aspergillus fumigatus. The immunopathogenesis of allergic bronchopulmonary aspergillosis involves several pathways. Aspergillus allergens stimulate an interleukin 5-mediated Th2 pathway responsible for the eosinophilic infiltrate, whereas aspergillus proteases promote epithelial activation and a potent chemokine response that induces neutrophilic airway inflammation. The resulting airway inflammation is intense, involves tissue damage and remodeling, and is linked with the severity of bronchiectasis. Treatment involves corticosteroids and antifungal therapy with oral azoles. Additional management seeks to monitor and control the other disease components of severe asthma, bronchiectasis, and disease exacerbations.
Publisher: Elsevier BV
Date: 05-2001
Abstract: To identify the characteristics of airway inflammation in persistent asthma and to examine the role of neutrophilic inflammation in noneosinophilic persistent asthma. Nonsmoking adults (n = 56) with persistent asthma and healthy control subjects (n = 8) underwent hypertonic saline solution challenge and sputum induction. Selected sputum portions were dispersed with dithiothreitol and assayed for total cell count, cellular differential, supernatant eosinophil cationic protein (ECP), myeloperoxidase, and interleukin (IL)-8. We identified two distinct inflammatory patterns. Typical eosinophilic inflammation occurred in 41% of subjects, whereas the remainder exhibited noneosinophilic asthma (59%). Both neutrophil percentage and absolute neutrophil counts were increased in subjects with noneosinophilic asthma (64%, 283 x 10(6)/mL) compared to eosinophilic asthma (14%, 41 x 10(6)/mL) and control subjects (34%, 49 x 10(6)/mL p = 0.0001). Myeloperoxidase was elevated in both noneosinophilic (280 ng/mL) and eosinophilic groups (254 ng/mL) compared with control subjects (82 ng/mL p = 0.002). Sputum IL-8 levels were highest in subjects with noneosinophilic asthma (45 ng/mL) compared to eosinophilic asthma (9.6 ng/mL) and control subjects (3.5 ng/mL p = 0.0001). Neutrophils correlated with IL-8 levels (r = 0.72). ECP was highest in subjects with eosinophilic asthma (2,685 ng/mL) compared with noneosinophilic asthma (1,081 ng/mL) and control subjects (110 ng/mL p = 0.0001). Induced-sputum analysis in persistent asthma identifies two different inflammatory patterns. The most common pattern is noneosinophilic, associated with a neutrophil influx and activation, which may be mediated by IL-8 secretion. There is heterogeneity of airway inflammation in persistent asthma, which indicates differing mechanisms and may impact on treatment responses.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 07-2019
Publisher: Elsevier BV
Date: 08-2018
Publisher: European Respiratory Society (ERS)
Date: 04-1998
DOI: 10.1183/09031936.98.11040848
Abstract: We aimed to describe induced sputum cell counts in healthy nonasthmatic children, and to compare these to children with controlled and uncontrolled asthma. Following clinical assessment and spirometry, ultrasonically nebulized hypertonic saline was used to induce sputum from children with asthma (n=50) and without asthma (n=72). Sputum was dispersed and cell counts performed to yield total and differential cell counts. Specific stains were used for eosinophil and mast cell counts. All of the children with asthma were receiving inhaled and/or oral corticosteroids. Current asthma control was assessed in terms of symptoms and lung function. Children were classified as controlled on inhaled corticosteroids (no current symptoms, normal lung function n=15), current symptomatic asthma (n=16) and asthma exacerbation (n=11). It was found that eosinophils comprised a median 0.3% (interquartile range (IQR): 0, 1.05) of cells in sputum from healthy children. Sputum eosinophils (4.3% (IQR: 15, 14.1) p=0.0005) and epithelial cells (14% (IQR: 6, 19.4) p=0.0005) were significantly higher in children with asthma than in nonasthmatic children. Children whose asthma was controlled, as well as those with symptoms, had more sputum eosinophils and epithelial cells than the nonasthmatics. Mast cells were found in the sputum of only four of the 42 children with asthma. This study demonstrates that eosinophilic airway inflammation and epithelial damage can occur in children with asthma. Airway inflammation persists even in those children who are receiving inhaled corticosteroids, have normal lung function and good symptomatic control of their disease.
Publisher: Wiley
Date: 12-10-2021
DOI: 10.1111/RESP.13950
Publisher: Wiley
Date: 09-02-2009
DOI: 10.1002/LARY.20114
Abstract: Laryngeal symptoms are increasingly recognized to occur in chronic persistent cough and may result from the sensory hyperresponsiveness that characterizes this condition. Apart from cough, the motor consequences of sensory activation have not been well described in chronic persistent cough. The efficacy of speech pathology treatment for chronic cough suggests that laryngeal dysfunction may be relevant in chronic persistent cough. This study investigated the relationship between cough reflex sensitivity and laryngeal dysfunction, which was assessed as paradoxical vocal cord movement (PVCM) and extrathoracic airway hyperresponsiveness, in patients with chronic cough. Cross-sectional case-control comparison of subjects with chronic cough and healthy controls. Adults with chronic persistent cough (n = 25) and healthy controls (n = 11) were assessed by cough-specific quality of life questionnaire, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity, and fibreoptic laryngoscopy to assess PVCM. Laryngeal dysfunction was present in many patients with chronic persistent cough. PVCM was present in 56% of subjects with chronic cough and accompanied by cough reflex hypersensitivity and impaired quality of life. Inspiratory airflows were reduced in cough with PVCM, and there was significant extrathoracic airway hyperresponsiveness. Laryngeal dysfunction is common in chronic cough, where it is manifest as paradoxical vocal cord movement and extrathoracic airway hyperresponsiveness. Laryngeal dysfunction in chronic cough is associated with reduced quality of life. Laryngeal hypersensitivity may be a common mechanism that can be effectively treated by speech language therapy.
Publisher: Informa UK Limited
Date: 07-05-2013
DOI: 10.3109/02770903.2013.790415
Abstract: The aim of this study was to explore older peoples' experiences of asthma or COPD with reference to their journey in the healthcare system. We recruited older patients with a confirmed diagnosis of asthma or COPD and invited them to participate in a qualitative interview. Interviews were conducted with 21 participants. A line-by-line analysis of the interviews was performed and they were coded for common themes. From the data, six main themes emerged, these were "limits to being", "being with or without a diagnosis", "not being heard or recognized", "expectation, fears, and hopes", "to medicate or not: the underuse, abuse, and misuse", and "needing to understand more". The findings of these interviews provide an important understanding of the behaviors and healthcare needs of older people with asthma and COPD. Older patients' adherence patterns, desire for person-centeredness, and involvement in shared decisions as well as desire for increased objective assessment are described. These findings provide an important understanding of the behaviors and healthcare needs of older people with asthma and COPD, an area that has not been well defined. The knowledge gained about older patients' desire for person--centeredness and involvement in shared decisions, as well as desire for increased objective assessment is essential in improving care.
Publisher: Wiley
Date: 11-01-2017
DOI: 10.1111/J.1365-2222.2009.03371.X
Abstract: Assessment of airway inflammation in asthma is becoming increasingly important, as the inflammatory phenotype underpins the treatment response. This study aimed to evaluate mannitol as a tool for assessing airway responsiveness and airway inflammation in asthma, compared with hypertonic saline. Fifty-five subjects with stable asthma completed a hypertonic (4.5%) saline challenge and a mannitol challenge at two separate visits, performed 48-72 h apart, in random order. Induced sputum was obtained from 49 (89%) subjects during the saline challenge and 42 (76%) subjects during the mannitol challenge (P>0.05). There was a significant correlation between the greatest percentage fall in forced expiratory volume in 1 s (FEV(1)) (r=0.6, P<0.0001), the dose-response slope (r=0.73), cumulative dose (r=0.55) and PD15 (r=0.46) for mannitol and hypertonic saline. The greatest percentage fall in FEV(1) to mannitol was less in non-eosinophilic asthma. There was a lower total cell count in mannitol vs. hypertonic-saline-induced sputum. However, sputum eosinophils and neutrophils were not significantly different. Using mannitol, a higher proportion of subjects were classified as having eosinophilic asthma. There were no differences in IL-8, neutrophil elastase or matrix-metalloproteinase 9 concentrations in sputum s les induced with mannitol or hypertonic saline. We conclude that mannitol can be used to induce good-quality sputum, useful for analysis of inflammatory mediators and for predicting the inflammatory phenotype in asthma.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.RMED.2019.06.010
Abstract: Severe asthma and bronchiectasis are heterogeneous diseases that contribute to disability beyond the pulmonary system. The magnitude of the impact that these extrapulmonary features has on health-related quality of life (HRQoL) is unknown. We analysed the cross-sectional relationships between HRQoL (St. George's Respiratory Questionnaire SGRQ) and extrapulmonary characteristics, including physical activity (steps/day), anxiety and depression, isometric leg strength, systemic inflammation, and several comorbidities in adults with severe asthma (n = 70) and bronchiectasis (n = 61). Participants with severe asthma and bronchiectasis had similar SGRQ total scores (mean scores 43.7 and 37.8 for severe asthma and bronchiectasis p > 0.05), and similar pulmonary and extrapulmonary characteristics. The associations between extrapulmonary variables and HRQoL did not differ according to diagnosis (all interactions p > 0.05). Greater anxiety and depressive symptoms, fewer steps/day and greater systemic inflammation were statistically associated with poorer HRQoL in both diseases (p < 0.05). Lower isometric leg strength in severe asthma, and greater Charlson Comorbidity Index in bronchiectasis were also associated with poorer HRQoL (p < 0.05). In the multivariable regression model performed in the combined disease groups, anxiety and depression, steps/day, systemic inflammation and isometric leg strength remained independently associated with HRQoL. Associations between extrapulmonary characteristics and SGRQ domains were stronger for the activity and impact domains, than symptoms. In severe asthma and bronchiectasis, extrapulmonary features including physical activity and leg strength have a significant impact on HRQoL, especially within the activity and impact domains. These features should be considered as part of the assessment of these conditions, and they may represent additional treatment targets to improve HRQoL.
Publisher: Wiley
Date: 23-04-2008
Publisher: Wiley
Date: 12-2004
DOI: 10.1002/PPUL.20095
Abstract: Our objective was to determine whether an asthma education program in schools would have 1) a direct impact on student knowledge and attitudes to asthma and quality of life of the students with asthma, 2) an indirect impact on teacher knowledge and attitudes to asthma and on school policies about asthma, and 3) a sustainable program after the resources to implement the research were withdrawn. Seventeen intervention and 15 control schools participated in a controlled trial. Baseline knowledge and attitudes were measured in year 8 students (ages 13-14 years) and their teachers together with quality of life in the students with asthma. A three-lesson package about asthma was delivered by teachers as part of the Personal Development/Health/Physical Education (PD/H/PE) curriculum. Follow-up questionnaires were administered to students and staff. Efforts to change school policies were documented. Five years after the intervention, PD/H/PE teachers were contacted to determine whether the program was still operating. Main outcome measures included asthma knowledge, attitudes, and quality of life. Questionnaires were returned by 4,161/4,475 of the year 8 students at baseline and by 3,443 at follow-up. In intervention schools, compared with control schools, students showed improved asthma knowledge (P < 0.0001), improvement in tolerance to asthma (P = 0.02), internal control (P = 0.03), and less tendency to believe in the role of chance in asthma control (P = 0.04). Students from intervention but not control schools showed significant improvements in overall quality of life (P = 0.003 vs. P = 0.82, respectively). Teachers from intervention schools showed significant increases in knowledge compared to control schools (P < 0.0001). Intervention schools were more likely to seek further health education about asthma (P < 0.01). Five years after the 35 schools involved in the development of the materials or the trial had been offered the Living With Asthma package, 25 (71%) were still teaching the program to most or all of their students. Fifty-nine of the 61 (97%) high schools in the Hunter Region now have the program. Management and distribution of the Living With Asthma program have been taken over by the Asthma Foundation of New South Wales. The package has been updated and is being offered to all high schools throughout New South Wales as part of the National Asthma-Friendly Schools Project. In conclusion, a teacher-led asthma education program in secondary school had direct and indirect beneficial outcomes and was sustained at a high level for 5 years in most schools in the Hunter Region, despite minimal ongoing maintenance and support from health workers.
Publisher: Elsevier BV
Date: 05-2003
Abstract: Allergic bronchopulmonary aspergillosis (ABPA) complicates chronic asthma and results from hypersensitivity to the fungus Aspergillus fumigatu s, causing an intense systemic immune response and progressive lung damage. We sought to determine whether treatment with the antifungal agent itraconazole reduced eosinophilic airway inflammation in subjects with ABPA. A randomized, double-blind, placebo-controlled trial was performed in stable subjects with ABPA (n = 29). Subjects received 400 mg of itraconazole per day (n = 15) or placebo (n = 14) for 16 weeks. All subjects were reviewed monthly with history, spirometry, and sputum induction to measure airway inflammation, serum total IgE and IgG levels to A fumigatu s, and blood eosinophil counts. By using regression analysis in a random-effects model, subjects receiving itraconazole had a decrease in sputum eosinophils of 35% per week, with no decrease seen in the placebo arm (P <.01). Sputum eosinophil cationic protein levels decreased with itraconazole treatment by 42% per week compared with 23% in the placebo group (P <.01). Itraconazole reduced systemic immune activation, leading to a decrease in serum IgE levels (310 IU/mL) compared with levels seen in the placebo group (increase of 18 IU/mL, P <.01) and a decrease in IgG levels to A fumigatu s (15.4 IU/mL) compared with levels seen in the placebo group (increase of 3.7 IU/mL, P =.03). There were fewer exacerbations requiring oral cortico-steroids in those treated with itraconazole compared with in the placebo group (P =.03). Itraconazole treatment of subjects with stable ABPA reduces eosinophilic airway inflammation, systemic immune activation, and exacerbations. These results imply that itraconazole is a potential adjunctive treatment for ABPA.
Publisher: Wiley
Date: 26-10-2019
DOI: 10.1111/RESP.13713
Abstract: The aim of this secondary analysis of a randomized controlled trial (RCT) of asthma management in pregnancy was to determine the treatment decision differences between a symptom control algorithm and a fractional exhaled nitric oxide (FENO)-guided algorithm, and whether the approach was effective in non-eosinophilic asthma (NEA). In this double-blind parallel group RCT, women with asthma were randomized prior to 22 weeks gestation to treatment adjustment according to a symptom control algorithm (control group), or a FENO-guided algorithm (inhaled corticosteroid (ICS) dose adjusted according to FENO with long-acting beta-agonist (LABA) added for uncontrolled symptoms). NEA was classified as baseline blood eosinophils <0.26 × 10 Among 220 non-smokers (n = 109 control, n = 111 FENO), 1006 treatment decisions were made, with significant group differences after the first and second algorithm applications. 53% of women had NEA. Treatment was better targeted to phenotype in the FENO group: ICS use increased in eosinophilic asthma (EA, 48-86%), while ICS/LABA increased in NEA (11-30%). Fewer women in the FENO group had exacerbations during pregnancy in NEA only (18.9% FENO vs 44% control, P = 0.006). The FENO algorithm was more effective in treating NEA, resulting in reduced exacerbations, compared to a symptom control algorithm. This was not the result of ICS overtreatment, since the benefits occurred at a lower median daily ICS dose. Two applications of the FENO-guided algorithm, one month apart, were sufficient to achieve beneficial effects in terms of asthma exacerbations, among pregnant women with asthma.
Publisher: Wiley
Date: 24-02-2016
DOI: 10.1111/RESP.12746
Abstract: Obesity is an established risk factor for poor health outcomes, but paradoxically in chronic obstructive pulmonary disease (COPD), it is associated with improved survival and lung function. A major evidence gap exisits to inform treatment recommendations for patients with COPD who are obese. We aimed to determine the effect of weight reduction involving a low-energy diet utilizing a partial meal replacement plan, coupled with resistance exercise training in obese COPD patients. In a proof of concept before-after clinical trial, obese (body mass index ≥30 kg/m(2) ) COPD patients received a 12 week weight reduction programme involving meal replacements, dietary counselling by a dietitian and resistance exercise training prescribed and supervised by a physiotherapist. Patients were reviewed face to face by the dietitian and physiotherapist every 2 weeks for counselling. Twenty-eight participants completed the intervention. Mean (standard deviation) body mass index was 36.3 kg/m(2) (4.6) at baseline and reduced by 2.4 kg/m(2) ((1.1) P < 0.0001) after the intervention. Importantly, skeletal muscle mass was maintained. Clinical outcomes improved with weight loss including exercise capacity, health status, dyspnea, strength and functional outcomes. There was also a significant reduction in the body mass index, obstruction, dyspnea and exercise score (BODE). Systemic inflammation measured by C-reactive protein however did not change. In obese COPD patients, dietary energy restriction coupled with resistance exercise training results in clinically significant improvements in body mass index, exercise tolerance and health status, whilst preserving skeletal muscle mass. This novel study provides a framework for development of guidelines for the management of obese COPD patients and in guiding future research.
Publisher: Baishideng Publishing Group Inc.
Date: 2014
Publisher: European Respiratory Society (ERS)
Date: 31-07-2012
Publisher: Informa UK Limited
Date: 17-11-2022
DOI: 10.1080/02770903.2020.1847934
Abstract: Guidelines for asthma management contain a consensus recommendation that inhaled corticosteroid (ICS) dose should not be stepped down in pregnancy. However, this is not consistent with consumer preferences and pharmacological principles to minimize medication exposure during pregnancy. We investigated exacerbations after changes to ICS and long acting beta agonist (LABA) therapy in pregnant women with asthma. Pregnant women ( ICS were used by 137 (62.3%) women at some time during pregnancy. ICS dose remained unchanged in 16 women (11.7%, 95% confidence interval [CI] 7-18%), increased in 37 women (27%, 95%CI 20-35%), decreased in 34 women (24.8%, 95%CI 18%-33%), or both increased and decreased in 50 women (36.5%, 95%CI 29-45%). Exacerbations occurred within 14 days of ICS step-down in 11 women (13%, 95%CI 7.5%-22%). This was not significantly different from exacerbations occurring within 14 days of step-up, in 7 women (8.1%, 95%CI 4%-16%, ICS step-down could be considered when eosinophilic inflammation or symptoms are low, and may be a useful management approach for women, doctors, and midwives wishing to minimize ICS exposure during pregnancy.
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.JVOICE.2018.12.002
Abstract: Speech pathology intervention is effective for chronic refractory cough (CRC). Speech pathology treatment for CRC includes therapy exercises to teach cough suppression and reduce laryngeal closure during respiration. The aim of this study was to evaluate the benefit of providing patients with supplemental pre-recorded videos of speech pathology exercises for chronic refractory cough (CRC) to assist with patients' independent practice. These videos were pre-made recordings of the treating speech pathologist demonstrating specific exercises for chronic cough suppression. This study was a prospective randomized controlled trial design. Participants included 18 adult patients attending a speech pathology outpatient clinic in a tertiary referral hospital for treatment of CRC. Participants were randomized to receive either standard speech pathology intervention (SPI) for CRC combined with supplemental pre-recorded videos for home practice or standard SPI alone. The primary outcome measure was a rating of accuracy during demonstration of the speech pathology exercises for cough suppression. This rating was assigned by the treating speech pathologist from session 2 onwards. The treating speech pathologist asked the patient to demonstrate the exercises they had been practising since the last speech pathology session. Secondary outcome measures included the Symptom Frequency and Severity Rating Scale, Leicester Cough Questionnaire, and Consensus Auditory Perceptual Evaluation of Voice. There was a significant pre- to post-treatment improvement in both groups however the degree of improvement was not significantly different between the two groups. The addition of supplemental pre-recorded videos of SPI for CRC did not lead to greater accuracy of therapy exercise practice or superior treatment outcomes than standard SPI alone. There are no interests to declare.
Publisher: European Respiratory Society (ERS)
Date: 10-2019
DOI: 10.1183/23120541.00056-2019
Abstract: Low-dose azithromycin is an effective therapy for persistent asthma however, its benefit in severe asthma is not defined. Participants with severe asthma were identified from the AMAZES randomised, placebo-controlled trial of long-term (48 weeks) low-dose azithromycin. Participants who met one of the following severe asthma definitions were included: 1) Global Initiative for Asthma step 4 treatment with poor asthma control (asthma control questionnaire score ≥0.75) 2) International Severe Asthma Registry definition 3) American Thoracic Society and European Respiratory Society severe asthma definitions. The rate of total exacerbations was calculated for each subgroup and efficacy of azithromycin compared with placebo. Asthma-related quality of life was assessed before and after treatment along with adverse effects. Azithromycin significantly reduced asthma exacerbations in each group. In patients meeting the American Thoracic Society and European Respiratory Society task force definition of severe asthma (n=211), the rate of exacerbations with treatment was 1.2 per person-year, which was significantly less than for placebo (2.01 per person-year), giving an incidence rate ratio (95% CI) of 0.63 (0.41, 0.96). The proportion of participants experiencing at least one asthma exacerbation was reduced by azithromycin from 64% to 49% (p=0.021). A similar beneficial treatment effect was seen in participants poorly controlled with Global Initiative for Asthma step 4 treatment and those with International Severe Asthma Registry-defined severe asthma. Azithromycin also significantly improved the quality of life in severe asthma (p .05). Treatment was well tolerated, with gastrointestinal symptoms being the main adverse effect. Long-term, low-dose azithromycin reduced asthma exacerbations and improved the quality of life in patients with severe asthma, regardless of how this was defined. These data support the addition of azithromycin as a treatment option for patients with severe asthma.
Publisher: Informa UK Limited
Date: 08-2019
DOI: 10.2147/JAA.S178927
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 25-01-2016
DOI: 10.1111/RESP.12730
Abstract: Neutrophil extracellular traps (NETs) are web-like structures comprising DNA and antimicrobial proteins, expelled from neutrophils during NETosis. Persistence of NETs can be pro-inflammatory, yet their role in respiratory disease remains unclear. This study aimed to investigate the presence of NETs in sputum from patients with asthma and COPD, and the relationship of NETs with inflammatory phenotype and disease severity. Induced sputum was collected from healthy controls, asthma and COPD patients. Extracellular DNA (eDNA) was quantified by PicoGreen. LL-37, α-defensins1-3, NE, IL-1β and CXCL8 were quantified by ELISA. PAD4 and NLRP3 gene expression was performed using qPCR. NETs were imaged in sputum smears using immunofluorescence microscopy. Sputum eDNA and NET neutrophil antimicrobial proteins were significantly elevated in asthma and COPD compared with healthy controls. Levels of eDNA and NET components were significantly higher in neutrophilic versus non-neutrophilic asthma and COPD. NETs were clearly visualized in sputum smears. PAD4 mRNA was upregulated in neutrophilic COPD. The level of eDNA was higher in severe asthma. High eDNA levels were associated with heightened innate immune responses, including elevated CXCL8 and IL-1β, and NLRP3 gene expression in both COPD and asthma. Antimicrobial proteins and eDNA were positively correlated with airway neutrophils, and negatively correlated with lung function and symptoms. NETs are present in the airways of subjects with asthma and COPD. Accumulation of excessive NETs was associated with activation of innate immune responses contributing to disease pathogenesis in chronic airway disease.
Publisher: BMJ
Date: 02-2006
Publisher: Elsevier BV
Date: 05-2021
DOI: 10.1016/J.RMED.2021.106367
Abstract: Sedentary time (ST) and light-intensity physical activity (LIPA) are movement behaviours associated with important health outcomes, but are not widely explored in respiratory diseases. We aimed to describe their volume and/or accumulation patterns in moderate-severe COPD, bronchiectasis and severe asthma using the accurate postural-based accelerometer activPAL, contrasting these values with a non-respiratory population. We also sought to test the cross-sectional associations of these behaviours with disease characteristics by diagnostic group, and as a combined label-free disease group. Adults with COPD (n = 64), bronchiectasis (n = 61), severe asthma (n = 27), and controls (n = 61) underwent cross-sectional measurements of volume and/or accumulation patterns of ST and LIPA. The prevalence and characteristics, and associations with exercise capacity, health-status, airflow-limitation, dyspnoea, systemic inflammation and exacerbations were analysed. ST volumes in COPD were higher than that of bronchiectasis and severe asthma. Values in bronchiectasis and severe asthma were similar to each other and controls (≈8.9 h/day). Their accumulation patterns were also significantly better than in COPD, but similar if not worse compared to controls. LIPA volumes in bronchiectasis and severe asthma were also higher than those of COPD (p < 0.05) and controls. In bronchiectasis and COPD, lower levels/better patterns of ST accumulation, as well as higher LIPA volume were associated with better clinical characteristics. These associations may be mediated by airflow limitation. The discordance between engagement in ST volume versus ST patterns highlights the importance of accounting for both these different yet complementary metrics. ST and LIPA are low-intensity activities associated with important clinical characteristics in people with chronic respiratory diseases. Not applicable.
Publisher: European Respiratory Society (ERS)
Date: 15-09-2012
DOI: 10.1183/09031936.00022011
Abstract: The receptor for advanced glycation end-products (RAGE) is a pattern-recognition receptor involved in the host response to injury, infection and inflammation. It is a membrane receptor, but also has soluble forms (sRAGE). Deficiencies in sRAGE are linked to heightened inflammation in various chronic conditions. We determined whether airway and systemic levels of sRAGE and the RAGE ligands HMGB1 (high-mobility group box-1) and serum amyloid A (SAA) are related to neutrophilic inflammation in asthma and chronic obstructive pulmonary disease (COPD). Bronchial lavage fluid from subjects with moderate-to-severe persistent asthma (n = 16) or COPD (n = 37), or from healthy controls (n = 18), was analysed for neutrophils, total sRAGE, endogenous secretory RAGE (esRAGE), HMGB1 and SAA. We also determined systemic levels of sRAGE in a separate group of asthmatic (n = 101) and COPD (n = 34) subjects. Subjects with neutrophilic asthma or COPD had undetectable levels of lung sRAGE, while levels of sRAGE in asthma/COPD without neutrophilia were similar to those in controls. Systemic sRAGE was significantly decreased in subjects with neutrophilic asthma or COPD compared with those without airway neutrophilia. There was significant positive correlation between total sRAGE and esRAGE in the lung and systemically. HMGB1 levels were similar in all subject groups, while SAA was below detectable levels. Neutrophilic airway inflammation in asthma and COPD is associated with reduced sRAGE.
Publisher: American Thoracic Society
Date: 15-01-2008
Publisher: Elsevier BV
Date: 09-2015
Abstract: The innate inflammatory pathways involved in the frequent exacerbator phenotypes of asthma and COPD are not well understood. This study aimed to investigate airway innate immune activation and systemic inflammation as predictors of exacerbations in asthma and COPD. In this prospective cohort study, baseline airway IL-1β, serum C-reactive protein, and IL-6 were assessed in 152 participants with stable asthma (n = 63) or COPD (n = 89) and were related to exacerbations over the following 12 months. Clinical characteristics and inflammatory biomarkers were compared between the frequent (two or more exacerbations in the follow-up) and infrequent exacerbators. The frequent exacerbation phenotype and exacerbation frequency were analyzed with multivariable modeling. The relationships among airway inflammation, systemic inflammation, and future exacerbations were examined using path analysis. Ninety-four participants experienced a total of 201 exacerbations, and 36.4% had two or more exacerbations. Serum IL-6 and sputum gene expression of IL-1β at baseline were higher in the frequent exacerbators with COPD. Significant pathways initiated by previous exacerbations were identified as occurring through activation of the IL-1β-systemic inflammatory axis leading to future exacerbations in COPD. Systemic inflammation was also associated with increased exacerbation risk in asthma. Airway IL-1β and systemic inflammation are associated with frequent exacerbations and may mediate a vicious cycle between previous and future exacerbations in COPD. Treatment strategies aimed at attenuating these inflammatory pathways to reduce COPD exacerbations deserve further investigation.
Publisher: Wiley
Date: 02-1990
DOI: 10.1111/J.1445-5994.1990.TB00368.X
Abstract: The aim of this study was to determine the degree and duration of hypoxaemia during bronchoalveolar lavage (BAL) and to examine the effect of supplemental oxygen on this response. Transcutaneous oxygen tension (PO2) was recorded continuously in 22 patients having bronchoscopy alone (Group 1), and during BAL in patients with a variety of connective tissue disorders. Thirty eight of these patients were breathing room air (Group 2) and 28 were given supplemental oxygen (Group 3). The mean fall in PO2 in Group 1 was 12 +/- 3 mmHg and the PO2 in these subjects rose promptly to the initial value once the bronchoscopy was finished. The mean falls in Groups 2 and 3 were 24 +/- 4 and 32 +/- 5 mmHg and the mean times taken for the PO2 values to return to baseline after the procedure were 47 +/- 9 and 53 +/- 10 minutes respectively. The PO2 fell to less than 60 mmHg in 76% of the patients in Group 2 but in only 25% of those in Group 3. It is recommended that supplemental oxygen be given to all patients having BAL during and for one hour after the procedure and that oxygenation be monitored continuously throughout the bronchoscopy. Arterial blood gases should be always measured prior to bronchoscopy and BAL. In those cases where it is not possible to maintain the PaO2 at 70 mmHg or more the procedure should be undertaken with great care and with due consideration of the risk of the hypoxaemia that may occur.
Publisher: Elsevier BV
Date: 02-2007
DOI: 10.1016/J.JACI.2006.10.043
Abstract: Combination therapy with long-acting beta-agonists (LABAs)/inhaled corticosteroids (ICSs) has become established as effective maintenance treatment for asthma. To compare and contrast the efficacy and safety of LABAs/ICSs against different maintenance ICS strategies in adults with asthma. Cochrane systematic reviews of randomized controlled trials (to April 2004) were identified that compared the addition of LABA to ICS against 3 inhaled corticosteroid strategies: (1) a similar dose (n = 4312 subjects), (2) a higher dose (n = 4951), and (3) a similar dose in steroid-naive subjects (n = 968). The outcomes evaluated were asthma exacerbations, asthma control, and adverse effects. Pediatric studies were excluded. The addition of LABA to ICSs significantly reduced the risk of exacerbations compared with a similar ICS dose, number needed to treat = 18. The effects of LABA/ICSs on exacerbations compared with the other maintenance inhaled corticosteroid strategies were not statistically significant. LABA added to inhaled corticosteroids led to significant improvements in asthma control compared with all 3 maintenance ICS strategies. There was an increased risk of tremor with LABA/ICSs that reached significance for initial therapy, number needed to harm = 21, and compared with higher ICS doses, number needed to harm = 74. Maintenance asthma therapy with LABA/ICSs has differential effects on asthma control and asthma exacerbations. The greatest benefit and least harm of LABAs comes when they are added to a similar ICS dose in adults with symptomatic asthma.
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.RMED.2008.12.013
Abstract: Neutrophilic asthma and COPD are obstructive airway diseases common in older age and have a characteristic airway inflammation with neutrophilic bronchitis. The structural differences between neutrophilic asthma and COPD have not been investigated. The aim of this study was to examine the airway and parenchymal abnormalities using high resolution computed tomographic (HRCT) scanning in participants with neutrophilic asthma, COPD and smoking controls. Participants (neutrophilic asthma (n=10), COPD (n=17) and smoking controls (n=8)) underwent clinical assessment and sputum induction. HRCT of the chest was performed and independently scored by a radiologist blinded to the subject group using a modified Bhalla scoring system. Participants were of a similar age and those with COPD had a similar degree of airflow obstruction to those with neutrophilic asthma. The pattern of radiographic abnormalities differed between groups. Abnormal bronchial wall thickening was significantly more common in neutrophilic asthma, compared to COPD or smoking controls. Emphysema was greatest in the COPD group, and not recorded as a feature of neutrophilic asthma. FEV(1)% predicted was negatively associated with bronchial wall thickening and consolidation while KCO% predicted was negatively associated with the total emphysema score. Bronchiectasis was minimal in all groups. The pattern of radiographic lung abnormality in neutrophilic asthma differs significantly from COPD, and resembles asthma. Neutrophilic asthma is a distinct inflammatory subtype of asthma with a different pathogenesis to COPD.
Publisher: Elsevier BV
Date: 10-2014
Publisher: Mary Ann Liebert Inc
Date: 04-2013
Abstract: Systemic inflammation is reported to be associated with neutrophilic airway inflammation in asthma, but mechanisms underlying this finding are not well understood. This study aimed to examine the molecular mechanisms of the airway neutrophilia that are associated with systemic inflammation in asthma. Fifty stable nonsmoking adults with asthma had plasma high sensitivity C-reactive protein (hsCRP) and interleukin 6 (IL-6) assayed. Subjects with an elevation of both hsCRP and IL-6 were grouped as asthmatics with systemic inflammation, and those with both hsCRP and IL-6 within the normal ranges were grouped as asthmatics without systemic inflammation. Clinical characteristics and sputum inflammatory cell counts were compared between the two groups. Gene expression profiles from sputum were analyzed and altered expression of four genes (CCL8, IL8RA, SELL, and PI3) was confirmed using quantitative PCR. Asthmatics with systemic inflammation (n=18, 36%) had a higher BMI, greater history of cigarette smoking, lower FVC% predicted, and increased sputum neutrophils compared to those without systemic inflammation (n=16, 32%). Microarray analysis identified 449 genes that were significantly altered in sputum between the two groups. Altered genes were involved in IL-1, TNF-α/nuclear factor-κB, and Kit receptor pathways, and were related to innate immune response, defense and inflammatory response, in particular neutrophilic inflammation. Systemic inflammation was associated with airway neutrophilia in asthma, and was related to a group of differentially expressed genes in the lung involving multiple cytokine pathways. Our findings suggest that targeting systemic inflammation might provide a novel therapeutic strategy for neutrophilic asthma.
Publisher: Wiley
Date: 18-01-2016
DOI: 10.1111/RESP.12734
Abstract: Chronic obstructive pulmonary disease (COPD) is characterized by progressive airflow limitation and inflammation. Airway bacterial colonization is increased in COPD however, the role of potentially pathogenic and non-pathogenic bacteria in the pathogenesis of disease is unclear. This study characterized the presence of bacteria in a well-characterized cohort of adults with COPD and healthy controls. Adults with COPD (n = 70) and healthy controls (n = 51) underwent clinical assessment and sputum induction. Sputum was dispersed, and total and differential cell counts were performed. Bacteria were cultured, identified and enumerated. Supernatants were assessed for neutrophil elastase (NE) and IL-1β. Common respiratory pathogens were also determined using real-time PCR. Participants with COPD had a typical neutrophilic inflammatory profile. The total load of bacteria was increased in COPD and was associated with poorer respiratory health status, as measured by the St George's Respiratory Questionnaire (Spearman's r = 0.336, P = 0.013). Significantly lower levels of culturable Bacillus species were identified compared with healthy controls. PCR analyses revealed increased rates of detection of potentially pathogenic bacteria with Haemophilus influenzae detection associated with higher sputum levels of NE and IL-1β, while Streptococcus pneumoniae was more common in male ex-smokers with emphysema and a deficit in diffusion capacity. Non-pathogenic and pathogenic bacteria were altered in the sputum of patients with COPD. These observations highlight the potential to identify treatment and management strategies that both target specific bacterial pathogens and restore the microbial balance, which may lead to reductions in inflammation and subsequent improvements in lung health.
Publisher: Springer Science and Business Media LLC
Date: 12-2013
Abstract: Galectins constitute an evolutionary conserved family that bind to β-galactosides. Increasing evidence shows that galectins are involved in many fundamental biological processes such as cellular communication, inflammation, differentiation and apoptosis. Changes in galectin-3 (Gal-3) expression are commonly seen in cancer and pre-cancerous conditions, and Gal-3 may be involved in the regulation of erse cancer cell activities that contribute to tumourigenesis, cancer progression and metastasis. In addition, Gal-3 is a pro-inflammatory regulator in rheumatoid arthritis. Gal-3 has been shown to be involved in many aspects in allergic inflammation, such as eosinophil recruitment, airway remodeling, development of a Th2 phenotype as well as increased expression of inflammatory mediators. In an in vivo model it was shown that bronchoalveolar lavage (BAL) fluid from ovalbumin-challenged mice contained significantly higher levels of Gal-3 compared to control mice. The molecular mechanisms of Gal-3 in human asthma have not been fully elucidated. This review will focus on what is known about the Gal-3 and its role in the pathophysiological mechanisms of asthma to evaluate the potential of Gal-3 as a biomarker and therapeutic target of asthma.
Publisher: Wiley
Date: 21-11-2013
Publisher: European Respiratory Society (ERS)
Date: 26-09-2019
DOI: 10.1183/13993003.00588-2019
Abstract: This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force's questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations: 1) suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes 2) suggest using a blood eosinophil cut-point ≥150 μL −1 to guide anti-IL-5 initiation in adult patients with severe asthma 3) suggest considering specific eosinophil (≥260 μL −1 ) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy 4) suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4–5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies 5) suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype and 6) suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels. These recommendations should be reconsidered as new evidence becomes available.
Publisher: American Thoracic Society
Date: 09-2016
Publisher: Springer Science and Business Media LLC
Date: 12-2014
Publisher: Wiley
Date: 05-1995
DOI: 10.1111/J.1365-2923.1995.TB02834.X
Abstract: The quality of medical education during internship is a cause for concern. This paper describes a structured educational programme for interns that was based around learning modules, clinical attachments and bedside teaching. The programme was incorporated into the term rotation of interns within an Area Health Service, and evaluated. Learning modules were timetabled by a Programme Coordinator and interns were reminded to attend. Clinical attachments were organized by the interns from a list of willing supervisors. Attendance at timetabled learning modules averaged 67%, which was greater than the 27% attendance at clinical attachments. Both sessions received high ratings for quality and clinical relevance. This structured education programme was based upon adult learning methods and was both feasible and well received by interns. Intern training programmes need to be programmed into the working week to ensure attendance, and modified following evaluation by interns. Such programmes should be considered by all hospitals to which interns are allocated.
Publisher: American Thoracic Society
Date: 07-2009
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.PUPT.2008.11.005
Abstract: Chronic cough may persist despite systematic evaluation and medical treatment of known associated diseases such as asthma, rhinitis, and gastro-esophageal reflux. These patients have refractory chronic cough and many exhibit laryngeal hypersensitivity that is manifest at both a sensory and motor level. Ex les of this are heightened sensitivity of the cough reflex to capsaicin, and laryngeal motor dysfunction with hoarse vocal quality and paradoxical vocal cord movement. Chronic cough that persists despite medical treatment may respond to speech pathology intervention. A multidimensional speech pathology treatment programme was designed based upon methods used to treat hyperfunctional voice disorders and paradoxical vocal fold movement. This included education, vocal hygiene training, cough suppression strategies and psychoeducational counseling. When tested in a single-blind, randomized, placebo-controlled trial involving 87 patients, participants in the treatment group demonstrated a significant reduction in cough, breathing, voice and upper airway symptoms following intervention, as well as improvements in auditory perceptual ratings of voice quality (breathy, rough, strain and glottal fry) and significant improvement in voice acoustic parameters (maximum phonation time, jitter and harmonic-to-noise ratio). Speech pathology intervention can be an effective way to treat refractory chronic cough.
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.CHEST.2021.07.026
Abstract: Neutrophil extracellular traps (NETs) increasingly are implicated in acute and chronic conditions involving multiple organ systems. Are NET concentrations higher in parapneumonic effusions compared with effusions of other origin and does this reflect the inflammatory nature of these effusions? Patients (N = 101) seeking hospital treatment for undifferentiated pleural effusion underwent pleural fluid classification based on cytologic analysis results, biochemical findings, microbiological characteristics, and clinical judgement. Concentrations of NET markers (extracellular DNA [eDNA], citrullinated histone H3 [citH3]), neutrophils (α-defensins), and inflammation (IL-1β)-related proteins were quantified by enzyme-linked immunosorbent assay. Differences between groups were analyzed using the Kruskal-Wallis one-way analysis of variance. Correlations used Spearman coefficient. Receiver operating characteristic (ROC) curves were calculated. Effusions were classified into four groups: parapneumonic (n = 18), malignant (n = 35), transudative (n = 22), and unclassifiable (n = 26). Concentrations of NETs markers were significantly higher in the parapneumonic group compared with malignant, transudative, and unclassifiable groups (median eDNA, 12.8 ng/mL vs 0.77 ng/mL, 0.44 ng/mL, and 0.86 ng/mL [P < .001] and median citH3, 127.1 ng/mL vs 0.44 ng/mL, 0.34 ng/mL, and 0.49 ng/mL [P < .001]). citH3 and eDNA were correlated highly with lactate dehydrogenase (LDH Spearman r = 0.66 and r = 0.73, respectively P < .001) and moderately negatively correlated with pH (r = -0.55 and r = -0.62, respectively P < .001). α-Defensins and IL-1β were higher in the parapneumonic group than in other groups (median α-defensins, 124.4 ng/mL vs 4.7 ng/mL,7 ng/mL, and 6.9 ng/mL [P < .001] and median IL-1β, 145 pg/mL vs 1.87 pg/mL, 1.39 pg/mL, and 2.6 pg/mL [P < .001]) and moderately correlated with LDH (r = 0.60 and r = 0.57 P < .001). ROC curves showed high sensitivity and specificity for NET markers for prediction of parapneumonic effusion. High levels of some NET-related mediators in parapneumonic effusions correlate with inflammation. Effusions of other causes do not show high levels of NETs. These results may have treatment implications because NETs may be an important contributor to the inflammation and viscosity of parapneumonic effusions and may help us to understand the therapeutic benefit of deoxyribonuclease in empyema.
Publisher: American Thoracic Society
Date: 07-2012
Publisher: European Respiratory Society (ERS)
Date: 10-1996
DOI: 10.1183/09031936.96.09102104
Abstract: The aims of this study were: to assess the safety of a sputum induction method using inhaled normal saline in children with acute asthma and to investigate changes in sputum cell counts between acute exacerbations of asthma and its resolution. Ultrasonically nebulized normal saline was used to induce sputum from children (n = 8) presenting with acute asthma within 1 h of arrival and again at least 14 days later, after resolution of the exacerbation. Children received pretreatment with bronchodilator, and peak expiratory flow (PEF) was monitored throughout the procedure. S les were analysed for total cell count, differential cell counts, and for eosinophils and neutrophils using specific immunochemical stains. Sputum induction was performed without adverse effect in each child with acute asthma. The mean fall in PEF from baseline during sputum induction was 5.3% during the acute attack and 3.4% at resolution. A shorter nebulization time was required to induce sputum in acute asthma than at follow-up (7.8 vs 13.9 min p = 0.04). During acute asthma, there was an intense cellular infiltrate (mean total cell count 34 x 10(6) cells.mL-1), which resolved after recovery (1.9 x 10(6) cells.mL-1) (p = 0.04). The infiltrate was heterogenous, comprising eosinophils (6.7 x 10(6) cells.mL-1), neutrophils (5.4 x 10(6) cells.mL-1) and mast cells (0.47 x 10(6) cells.mL-1). Resolution of the exacerbation was accompanied by a significant fall in eosinophils and neutrophils (p or = 0.04). Normal saline induction of sputum can be used to assess airway inflammation in acute asthma. Children with acute asthma have intense airway inflammation that is heterogeneous and involves neutrophils, eosinophils and mast cells.
Publisher: Wiley
Date: 06-04-2020
DOI: 10.1002/PPUL.24756
Publisher: European Respiratory Society (ERS)
Date: 14-03-2007
DOI: 10.1183/09031936.00150006
Abstract: Airway neuropeptides, in particular calcitonin gene-related peptide (CGRP), are likely to be important in the pathogenesis of chronic cough. The present authors evaluated the following: 1) the relationship between cough sensitivity and bronchoalveolar lavage (BAL) neuropeptides and 2) the effect of reflux oesophagitis (RO) on cough, cough sensitivity and BAL neuropeptides in children not selected for cough. It was hypothesised that CGRP would be increased in children with chronic cough and would relate to cough sensitivity. Capsaicin cough sensitivity was performed in children undergoing gastro-duodenal endoscopy. CGRP, substance P and neurokinin A were measured in BAL obtained nonbronchoscopically. Children were defined as "coughers" if chronic cough was present. Coughers (n = 21) had significantly reduced cough sensitivity but were just as likely as noncoughers (n = 19) to have RO. The median CGRP was significantly higher in coughers with oesophagitis than in noncoughers with oesophagitis. CGRP significantly negatively correlated to cough sensitivity in coughers but not in noncoughers. Elevated calcitonin gene-related peptide, but not substance P or neurokinin A, is only associated with chronic cough in children when oesophagitis coexists. Calcitonin gene-related peptide in bronchoalveolar lavage relates to cough sensitivity and is likely to be important in the pathophysiology of chronic cough.
Publisher: Elsevier BV
Date: 09-2008
Publisher: Springer Science and Business Media LLC
Date: 26-08-2015
Publisher: Elsevier BV
Date: 03-2021
Publisher: Elsevier BV
Date: 03-2021
Publisher: European Respiratory Society (ERS)
Date: 24-01-2013
DOI: 10.1183/09031936.00124912
Abstract: Obese asthma presents via altered airway and systemic inflammation in adults. This has not been comprehensively described in children. The aim of the present study was to compare airway and systemic inflammation in obese and nonobese asthmatic children and controls. In a cross-sectional study, children aged 8-17 years were assigned to one of four groups: obese asthma (OA, n=74) nonobese asthma (NOA, n=249) obese control (OC, n=9) nonobese control (NOC, n=29). Lung function, and both sputum and systemic inflammatory biomarkers were measured. Non-eosinophilic asthma was more prevalent among OA females (60.0%) versus OA males (30.8%). However, there were no differences in the percentage of eosinophils or neutrophils between OA and NOA. Leptin was higher in OC, but not OA, versus NOA and NOC, while adiponectin was reduced in OA versus NOC only. Expiratory reserve volume was reduced in OA, versus NOC. Residual volume (RV) and RV/total lung capacity were reduced in OC versus OA, and OC versus OA and NOA, respectively. Obesity was associated with significant lung restriction in children with and without asthma. Obesity was not associated with significantly altered airway or systemic inflammation in asthmatic children. However, the higher prevalence of non-eosinophilic asthma in female obese asthmatics, compared to males, warrants further investigation.
Publisher: BMJ
Date: 11-2021
DOI: 10.1136/BMJRESP-2021-000974
Abstract: Neural mechanisms may play an important role in non-eosinophilic asthma (NEA). This study compared airway sensory nerve reactivity, using capsaicin challenge, in eosinophilic asthma (EA) and NEA and non-asthmatics. Thirty-eight asthmatics and 19 non-asthmatics (aged 14–21 years) underwent combined hypertonic saline challenge/sputum induction, fractional exhaled nitric oxide, atopy and spirometry tests, followed by capsaicin challenge. EA and NEA were defined using a sputum eosinophil cut-point of 2.5%. Airway hyperreactivity was defined as a ≥15% drop in FEV 1 during saline challenge. Sensory nerve reactivity was defined as the lowest capsaicin concentration that evoked 5 (C5) coughs. Non-eosinophilic asthmatics (n=20) had heightened capsaicin sensitivity (lower C5) compared with non-asthmatics (n=19) (geometric mean C5: 58.3 µM, 95% CI 24.1 to 141.5 vs 193.6 µM, 82.2 to 456.0 p .05). NEA tended to also have greater capsaicin sensitivity than EA, with the difference in capsaicin sensitivity between NEA and EA being of similar magnitude (58.3 µM, 24.1 to 141.5 vs 191.0 µM, 70.9 to 514.0) to that observed between NEA and non-asthmatics however, this did not reach statistical significance (p=0.07). FEV 1 was significantly reduced from baseline following capsaicin inhalation in both asthmatics and non-asthmatics but no differences were found between subgroups. No associations with capsaicin sensitivity and atopy, sputum eosinophils, blood eosinophils, asthma control or treatment were observed. NEA, but not EA, showed enhanced capsaicin sensitivity compared with non-asthmatics. Sensory nerve reactivity may therefore play an important role in the pathophysiology of NEA.
Publisher: Wiley
Date: 28-09-2022
DOI: 10.1111/ALL.15087
Abstract: Neutrophilic asthma (NA) is a clinically important asthma phenotype, the cellular and molecular basis of which is not completely understood. Airway macrophages are long‐lived immune cells that exert important homeostatic and inflammatory functions which are dysregulated in asthma. Unique transcriptomic programmes reflect varied macrophage phenotypes in vitro. We aimed to determine whether airway macrophages are transcriptomically altered in NA. We performed RNASeq analysis on flow cytometry‐isolated sputum macrophages comparing NA ( n = 7) and non‐neutrophilic asthma (NNA, n = 13). qPCR validation of RNASeq results was performed (NA n = 13, NNA n = 23). Pathway analysis ( PANTHER , STRING ) of differentially expressed genes (DEGs) was performed. Gene set variation analysis (GSVA) was used to test for enrichment of NA macrophage transcriptomic signatures in whole sputum microarray (cohort 1 ‐ controls n = 16, NA n = 29, NNA n = 37 cohort 2 U‐BIOPRED ‐ controls n = 16, NA n = 47, NNA n = 57). Flow cytometry‐sorting significantly enriched sputum macrophages (99.4% post‐sort, 44.9% pre‐sort, p .05). RNASeq analysis confirmed macrophage purity and identified DEGs in NA macrophages. Selected DEGs ( SLAMF7 , DYSF , GPR183 , CSF3 , PI3 , CCR7 , all p .05 NA vs. NNA) were confirmed by qPCR. Pathway analysis of NA macrophage DEGs was consistent with responses to bacteria, contribution to neutrophil recruitment and increased expression of phagocytosis and efferocytosis factors. GSVA demonstrated neutrophilic macrophage gene signatures were significantly enriched in whole sputum microarray in NA vs. NNA and controls in both cohorts. We demonstrate a pathophysiologically relevant sputum macrophage transcriptomic programme in NA. The finding that there is transcriptional activation of inflammatory programmes in cell types other than neutrophils supports the concept of NA as a specific endotype.
Publisher: Elsevier BV
Date: 07-2000
Abstract: The monitoring of symptoms, airflow obstruction, and exacerbations is essential to asthma management. Patients who practice self-monitoring in conjunction with use of a written action plan and regular medical review have significantly fewer hospitalizations, emergency department visits, and lost time from work. Either symptom monitoring or peak expiratory flow monitoring is satisfactory, provided the results are interpreted with reference to the patient's own baseline asthma status. Regular monitoring by physicians also improves health outcomes for patients, provided the physician is systematic and monitors control, medications, and skills at regular intervals. Additional monitoring tools are under evaluation, and these include measures of airway responsiveness, airway inflammation, and Internet-based monitoring systems. Administrators need to monitor the quality and cost of care, as well as compliance with national management guidelines. Assessment of the hospitalization rate and regular audit may achieve these aims in the hospital setting. The best way to assess and monitor asthma in primary care remains an unresolved yet crucial issue because primary care physicians manage the vast burden of illness caused by asthma. Monitoring asthma outcomes is an essential step toward the successful implementation of national guidelines for the management of asthma.
Publisher: Informa UK Limited
Date: 07-2016
DOI: 10.2147/COPD.S100338
Publisher: Elsevier BV
Date: 09-2011
Publisher: Elsevier BV
Date: 1998
DOI: 10.1016/S1054-139X(97)00203-6
Abstract: [This corrects the article DOI: 10.1371/journal.pone.0203463.].
Publisher: Oxford University Press (OUP)
Date: 12-06-2012
Abstract: Pregnant women are considered to have a high risk for influenza virus infection, although little is known about the biological reasons for this risk. Antiviral immunity is critical during influenza virus infection, and understanding the changes that occur during pregnancy and the effect of vaccination is essential for improving health outcomes for mother and baby. Peripheral blood mononuclear cells (PBMCs) were isolated from 26 healthy, nonpregnant women and 28 healthy pregnant women and cultured with 2009 pandemic influenza A virus subtype H1N1 (H1N1/09). Protein concentrations of interferon α (IFN-α), IFN-λ, and IFN-γ were measured from culture supernatant. Messenger RNA expression of protein kinase R (PKR) and Toll-like receptors 3, 7, and 9 was also measured from cell lysates. PBMCs from pregnant women produced significantly less IFN-α (median level, 114.06 pg/mL [range, 51.48-394.9]) and IFN-λ (median level, 30.65 pg/mL [range, 0-260]), compared with PBMCs from nonpregnant women (median level, 800.38 pg/mL [range, 259-1458] and 479.87 pg/mL [257.1-1113], respectively P < .01). PKR expression was also significantly reduced in PBMCs from pregnant women (P < .05). Vaccination significantly improved innate and adaptive immunity in pregnancy (P < .01). PBMCs from nonvaccinated pregnant women have attenuated antiviral immunity following H1N1/09 stimulation, but vaccination improves this response. These novel findings help improve understanding of the increased susceptibility and disease severity to influenza virus infection during pregnancy and the importance of influenza vaccination.
Publisher: Public Library of Science (PLoS)
Date: 22-08-2014
Publisher: Springer Science and Business Media LLC
Date: 15-10-2013
DOI: 10.1038/PR.2013.181
Abstract: Whether body composition is associated with lung function in asthmatic children has not been investigated. This study aimed to primarily investigate whether BMI z-score and body composition were associated with respiratory function in asthmatic children. In a cross-sectional study, male (n = 27 mean age: 11.9 y (SD: 2.3)) and female (n = 21 mean age: 13.6 y (SD: 2.2)) asthmatic children underwent clinical assessment. BMI z-score was associated with forced expiratory volume in 1 s (FEV1 r = 0.458), forced vital capacity (FVC r = 0.477), and total lung capacity (TLC r = 0.451) in males only (P < 0.05). Total lean mass was associated with FEV1 (r = 0.655), FVC (r = 0.562), and TLC (r = 0.635) in males, as was thoracic lean mass (FEV1 (r = 0.573), FVC (r = 0.526), and TLC (r = 0.497) P < 0.05). TLC was associated with total (r = 0.522) and thoracic (r = 0.532) lean mass in females (P < 0.05). Fat mass was not associated with lung function in this group. Lean mass, not fat mass, is associated with lung function in children with asthma. The positive association between BMI z-score and respiratory function in male children is driven by lean mass. Although body weight can be easily monitored in the clinical setting, body composition can provide important information. Future research exploring lean mass and lung function associations could inform future interventions.
Publisher: Elsevier BV
Date: 11-1997
Abstract: CD36 is a transmembrane glycoprotein expressed on the surface of a number of cell types. The analysis of CD36 from platelets using immunoblotting, gel filtration, and native PAGE indicated the presence of high molecular complexes exceeding the Mr of monomeric CD36. Experiments using transfected COS-7 cells revealed these complexes were homodimers and -multimers of CD36. The multimers could be dissociated by treatment with a reducing agent, indicating they were formed by intermolecular cysteine-bridging. Mutagenesis of the cDNA for CD36 implicated the cysteines in the extracellular domain of the molecule. The potential physiological roles of CD36 multimerisation are discussed.
Publisher: Wiley
Date: 06-1999
DOI: 10.1046/J.1440-1754.1999.00358.X
Abstract: Asthma is common in Australian children, with a prevalence of 30%. Airway inflammation is an important determinant of asthma symptoms. Chemotherapy used for the treatment of many childhood cancers suppresses inflammation. The prevalence of asthma symptoms in children treated with chemotherapy is unknown. We therefore performed a survey of symptoms of asthma in children attending the oncology clinic at John Hunter Children's Hospital during the first 6 months of 1996. Fifty children aged 1-17 years were surveyed. Thirty-two of the children were in remission and had completed treatment with chemotherapy and 18 were currently undergoing treatment with chemotherapy. There was no significant difference in the prevalence of asthma in children before, during and after chemotherapy (26%, 22% and 34%), or in the prevalence of asthma in their siblings (28%). No child was classified as having persistent asthma while on chemotherapy and there was a significant reduction in the requirement for preventive asthma drugs 12% versus 0% (P = 0.03) being reported during chemotherapy. The prevalence of asthma in children who develop cancer is similar to their siblings and the same as the population as a whole. While asthma symptoms do not disappear completely during chemotherapy, the severity of asthma symptoms is less, with no need for asthma preventive treatment. The immunosuppressive side effects of the chemotherapy used in the treatment of childhood cancer appear to induce a remission in asthma symptoms. The ongoing requirement for bronchodilator therapy in patients whilst on chemotherapy suggests airway hyperreactivity persists in children while they are on chemotherapy. Prospective study of the airways of this group of patients promises to provide insights into the relationships between airway hyperreactivity, airway inflammation and asthma.
Publisher: MDPI AG
Date: 12-07-2021
Abstract: Air pollution exposure during pregnancy may be a risk factor for altered immune maturation in the offspring. We investigated the association between ambient air pollutants during pregnancy and cell populations in cord blood from babies born to mothers with asthma enrolled in the Breathing for Life Trial. For each patient (n = 91), daily mean ambient air pollutant levels were extracted during their entire pregnancy for sulfur dioxide (SO2), nitric oxide, nitrogen dioxide, carbon monoxide, ozone, particulate matter μm (PM10) or .5 μm (PM2.5), humidity, and temperature. Ninety-one cord blood s les were collected, stained, and assessed using fluorescence-activated cell sorting (FACS). Principal Component (PC) analyses of both air pollutants and cell types with linear regression were employed to define associations. Considering risk factors and correlations between PCs, only one PC from air pollutants and two from cell types were statistically significant. PCs from air pollutants were characterized by higher PM2.5 and lower SO2 levels. PCs from cell types were characterized by high numbers of CD8 T cells, low numbers of CD4 T cells, and by high numbers of plasmacytoid dendritic cells (pDC) and low numbers of myeloid DCs (mDCs). PM2.5 levels during pregnancy were significantly associated with high numbers of pDCs (p = 0.006), and SO2 with high numbers of CD8 T cells (p = 0.002) and low numbers of CD4 T cells (p = 0.011) and mDCs (p = 4.43 × 10−6) in cord blood. These data suggest that ambient SO2 and PM2.5 exposure are associated with shifts in cord blood cell types that are known to play significant roles in inflammatory respiratory disease in childhood.
Publisher: Frontiers Media SA
Date: 08-10-2002
DOI: 10.3389/FPSYG.2021.713804
Abstract: Maternal asthma in pregnancy is associated with an increased risk of adverse perinatal outcomes. Adverse perinatal outcomes may result in poorer infant developmental outcomes, such as temperament and sensory difficulties. This study aimed to (1) assess differences in temperament and sensory features between infants born to mothers with and without asthma and (2) investigate differences in these infant behaviours as a function of maternal asthma severity and asthma control. Mothers completed the Carey Temperament Scales and the Sensory Profile 2 at either 6 weeks, 6 months, or 12 months postpartum. Overall, we observed no significant differences between infants born to mothers with and without asthma in their temperament or sensory features scores in both domains fell within the normative range. More infants in the asthma group, however, were reported to be highly distractible. When compared with normative data, infants in both groups were reported to have poor predictability of biological functions and fewer infants engaged in low levels of sensory behaviours. Some infants were observed to experience difficulties with hyper-reactivity within several domains. Maternal asthma severity and control during pregnancy were not linked to significant differences between infant temperament and sensory features. The present findings indicate that infants born to mothers with asthma are not at an increased risk overall for temperament or sensory difficulties, compared to control infants. However, a subset of infants across both groups may be at risk for attention or sensory hyper-reactivity difficulties. Further research into the developmental outcomes of infants born to mothers with asthma is warranted.
Publisher: Elsevier BV
Date: 06-2021
Publisher: European Respiratory Society (ERS)
Date: 10-2018
DOI: 10.1183/23120541.00031-2018
Abstract: Long-term, low-dose azithromycin reduces exacerbation frequency in chronic obstructive pulmonary disease (COPD), yet the mechanism remains unclear. This study characterised genome-wide gene expression changes in patients with neutrophilic COPD following long-term, low-dose azithromycin treatment. Patients with neutrophilic COPD ( % or ×10 4 cells per mL sputum neutrophils) were randomised to receive either azithromycin or placebo for 12 weeks. Sputum and blood were obtained before and after 12 weeks of treatment. Gene expression was defined using microarrays. Networks were analysed using the Search Tool for the Retrieval of Interacting Gene database. In sputum, 403 genes were differentially expressed following azithromycin treatment (171 downregulated and 232 upregulated), and three following placebo treatment (one downregulated and two upregulated) compared to baseline (adjusted p .05 by paired t-test, fold-change .5). In blood, 138 genes were differentially expressed with azithromycin (121 downregulated and 17 upregulated), and zero with placebo compared to baseline (adjusted p .05 by paired t-test, fold-change .3). Network analysis revealed one key network in both sputum (14 genes) and blood (46 genes), involving interferon-stimulated genes, human leukocyte antigens and genes regulating T-cell responses. Long-term, low-dose azithromycin is associated with downregulation of genes regulating antigen presentation, interferon and T-cell responses, and numerous inflammatory pathways in the airways and blood of neutrophilic COPD patients.
Publisher: Springer Science and Business Media LLC
Date: 29-03-2011
Publisher: Wiley
Date: 17-01-2016
DOI: 10.1111/CEA.12702
Abstract: IL-33 represents a potential link between the airway epithelium and induction of a Th2-type inflammatory response in asthma. However, the association with markers of eosinophilic airway inflammation has not previously been reported in patients with steroid-free asthma. To describe the relationship between airway IL-33 and markers of eosinophilic airway inflammation, as well potential triggers of IL-33, in mild, steroid-free asthma. IL-33 mRNA expression and IL-33 immunoreactivity were measured in bronchial biopsies from patients with asthma untreated with inhaled steroids and healthy in iduals. Furthermore, fractional exhaled nitric oxide (FeNO) and eosinophils in sputum and BAL were measured, as well as airway hyperresponsiveness to mannitol and methacholine. Epithelial integrity was assessed by computerized image analysis on haematoxylin-stained sections, and TLR mRNA expression by PCR. A total of 23 patients with asthma and 10 healthy in iduals were examined (age: 24 years (20-40) females: 53%). The level of IL-33 mRNA expression was significantly higher in patients with asthma compared to healthy in iduals (Median (IQR) 1.12 (0.78) vs. 0.86, P = 0.04). There was a positive correlation between IL-33 mRNA expression and the level of FeNO (r = 0.56, P = 0.01), whereas there was no association with airway or blood eosinophils. IL-33 expression was unrelated to loss of epithelial integrity, but correlated with an increased expression of TLR2 and TLR4 (TLR2: r = 0.47, P = 0.04 TLR4: 0.68, P < 0.001), as well allergy to house dust mites (HDMs). In mild untreated asthma, the expression of IL-33 mRNA in bronchial mucosa is related to innate immune activation and allergic sensitization to HDM, rather than epithelial damage, and correlates with FeNO. These findings suggest that in mild allergic asthma, IL-33 may represent a link between innate immune activation and FeNO production.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2021
Publisher: Public Library of Science (PLoS)
Date: 19-03-0030
Publisher: Elsevier BV
Date: 02-2021
Publisher: BMJ
Date: 17-02-2012
Publisher: Elsevier BV
Date: 02-2021
Publisher: Elsevier BV
Date: 09-2003
DOI: 10.1016/S0954-6111(03)00134-3
Abstract: Education about asthma and self-management of asthma are now key recommendations of asthma management guidelines. A Cochrane systematic review of 12 RCTs found that limited education programmes that offer information about asthma but not self-management skills did not reduce hospitalisation rates or visits to the doctor for asthma. The positive outcomes from limited asthma education were a reduction in symptoms. Asthma self-management education which consists of information, self-monitoring, regular medical review, and a written action plan is effective and leads to a reduction in hospitalisation and ER visits for asthma, unscheduled doctors visits, days lost from work, episodes of nocturnal asthma, indirect costs and an improvement in quality of life. The effects were large enough to be of both clinical and statistical significance. While a structured asthma self-management programme is effective in a hospital setting, attempts to deliver these programmes in primary care have met with varying success.
Publisher: European Respiratory Society (ERS)
Date: 10-2021
DOI: 10.1183/23120541.00357-2021
Abstract: Lung diseases can complicate pregnancy, but little is known about the experiences of pregnancy among women living with such diseases. This survey aimed to understand the experiences of women with a lung condition before and during pregnancy, in childbirth and post-partum. The survey was translated into nine languages and hosted online between March and May 2018. This paper reports on 327 women who had asthma, cystic fibrosis (CF), lymphangioleiomyomatosis (LAM) and sarcoidosis as a sole or primary lung condition. Women with CF and LAM were most likely to report that their condition influenced their decision to have children. Those with CF and LAM who did become pregnant reported greater satisfaction with their healthcare during pregnancy and gave more consideration to factors such as location and type of birth they were also more concerned about the impact of the pregnancy on their health than women with other diseases. Women with sarcoidosis reported receiving conflicting advice as to both the impact of their condition on pregnancy and how becoming pregnant might impact their health. Women with asthma reported not always being able to access the information they needed from healthcare professionals. The results suggest that healthcare providers should be having dialogues with affected women early on, from before conception, throughout the pregnancy and after giving birth, and training should be provided to healthcare staff to equip them with the information they need to do this.
Publisher: European Respiratory Society (ERS)
Date: 28-01-2021
DOI: 10.1183/23120541.00812-2020
Abstract: Family carers and significant others play a fundamental role in the well-being of people with severe asthma. This study aimed to investigate the challenges faced by family carers/significant others of people with severe asthma, to understand if there is an unmet need and to explore coping strategies. Carers of people with severe asthma were invited to participate in a face-to-face or telephone interview. Semi-structured interviews were conducted until reaching data saturation of themes. The 20 interviews were recorded and transcribed, and analysis of data followed an inductive thematic approach. We report three overarching emergent themes: 1) “Caring role impacts”, which centred around the negative and positive impacts of caring on carers' well-being 2) “Unmet needs”, which encapsulated the support needs participants desired and were categorised into unmet information, biopsychosocial needs and carers' involvement in decision-making and 3) “Coping strategies”, which were central to the range of tools and positive approaches in dealing with caring demands. Caring for someone with severe asthma can be burdensome and may negatively affect the physical and psychosocial health of the carer. Various coping strategies are used to manage the demands of these caring roles. Carers of people with severe asthma expressed a need for informational, biopsychosocial and involvement in care decision-making support . Tailored support services that are sensitive to their needs may improve their quality of life and encourage healthcare providers to value and acknowledge the important contribution that carers make.
Publisher: Elsevier BV
Date: 07-2021
Publisher: European Respiratory Society
Date: 06-2019
Publisher: Elsevier
Date: 2022
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.CHEST.2015.12.018
Abstract: Asthma is a heterogeneous chronic inflammatory disease in which host defense against respiratory viruses such as human rhinovirus (HRV) may be abnormal. This is a matter of some controversy, with some investigators reporting reduced type I interferon (IFN) synthesis and others suggesting that type I IFN synthesis is relatively normal in asthma. The objective of this study was to examine the responsiveness of circulating mononuclear cells to HRV in a large cohort of participants with poorly controlled asthma and determine whether IFN-α and IFN-β synthesis varies across different inflammatory phenotypes. Eligible adults with asthma (n = 86) underwent clinical assessment, sputum induction, and blood s ling. Asthma inflammatory subtypes were defined by sputum cell count, and supernatant assessed for IL-1β. Peripheral blood mononuclear cells (PBMCs) were exposed to HRV serotype 1b, and IFN-α and IFN-β release was measured by enzyme-linked immunosorbent assay. Participants (mean age, 59 years atopy, 76%) had suboptimal asthma control (mean asthma control questionnaire 6, 1.7). In those with neutrophilic asthma (n = 12), HRV1b-stimulated PBMCs produced significantly less IFN-α than PBMCs from participants with eosinophilic (n = 35) and paucigranulocytic asthma (n = 35). Sputum neutrophil proportion and the dose of inhaled corticosteroids were independent predictors of reduced IFN-α production after HRV1b exposure. Antiviral type I IFN production is impaired in those with neutrophilic airway inflammation and in those prescribed high doses of inhaled corticosteroids. Our study is an important step toward identifying those with poorly controlled asthma who might respond best to inhaled IFN therapy during exacerbations.
Publisher: Wiley
Date: 18-10-2007
Publisher: BMJ
Date: 28-07-2009
Abstract: There is a need to re-evaluate the concept of asthma and chronic obstructive pulmonary disease (COPD) as separate conditions, and to consider situations when they may coexist, or when one condition may evolve into the other. Epidemiological studies show that in older people with obstructive airway disease, as many as half or more may have overlapping diagnoses of asthma and COPD (overlap syndrome). These people are typically excluded from current therapy trials, which limit the generalisability of these trials, and this presents a problem for evidence-based guidelines for obstructive airway diseases. Studying overlap syndrome may shed light on the mechanisms of COPD development. Overlap syndrome is recognised by the coexistence of increased variability of airflow in a patient with incompletely reversible airway obstruction. Patients typically have inflammatory features that resemble COPD, with increased airway neutrophilia, as well as features of airway wall remodelling. Overlap syndrome can develop when there is accelerated decline in lung function, or incomplete lung growth, or both. The risk factors for these events are shared, such that increasing age, bronchial hyper-responsiveness, tobacco smoke exposure, asthma and lower respiratory infections/exacerbations are significant risk factors for both incomplete lung growth and accelerated loss of lung function. Studying these events may offer new insights into the mechanisms and treatment of obstructive airway diseases.
Publisher: Wiley
Date: 02-2021
DOI: 10.1111/IMJ.14806
Publisher: European Respiratory Society (ERS)
Date: 11-2019
Publisher: European Respiratory Society (ERS)
Date: 02-2019
DOI: 10.1183/23120541.00146-2018
Abstract: Since 2014, the Global Initiative for Asthma (GINA) has stated that asthma control should be measured using four questions concerning diurnal and nocturnal symptoms, activity limitation, and rescue medication use. We assessed how asthma control by this definition correlates with airway inflammation and quality of life. 113 asthmatic subjects consecutively recruited from their routine clinical appointment underwent spirometry, sputum induction and answered the Standardised Asthma Quality of Life Questionnaire (AQLQ(S)) during a single visit. 43 (38.1%), 37 (32.7%) and 33 (29.2%) subjects had controlled asthma, partly controlled asthma and uncontrolled asthma, respectively. The majority of subjects with controlled asthma (67.4%) had paucigranulocytic sputum. Eosinophilic sputum was present in all levels of asthma control. Although most subjects with controlled asthma (58.1%) achieved an AQLQ(S) score ≥6 (minimal or no impairment), the remaining patients (41.9%) had moderate/some impairment (AQLQ(S) score and ≥3) due to activity impairment and environmental exposure. The present GINA definition of current symptom control reflects control of airway inflammation. However, quality of life impairment can be present even in these patients. Measuring quality of life may provide useful information when evaluating asthma control.
Publisher: Elsevier BV
Date: 11-1993
DOI: 10.1016/0140-6736(93)92399-E
Abstract: [This corrects the article DOI: 10.4300/JGME-D-19-00597.1.].
Publisher: S. Karger AG
Date: 2008
DOI: 10.1159/000136902
Abstract: i Objective: /i Chronic cough (CC) and paradoxical vocal fold movement (PVFM) may be associated with voice problems. Objective acoustic and electroglottographic (EGG) measures have the capacity to delineate these vocal characteristics. This study investigated acoustic and EGG voice features of CC and PVFM. i Patients and Methods: /i Acoustic and EGG findings were compared among 5 groups of participants. The first 3 groups, CC (n = 56), PVFM (n = 8) and combined CC-PVFM (n = 55), included in iduals with cough and respiratory symptoms that persisted despite medical treatment. Groups 4 and 5 included in iduals with muscle tension dysphonia (n = 25) and healthy controls (n = 27). i Results: /i Participants with CC/PVFM recorded reduced phonation times (p 0.001), greater jitter (p 0.001), reduced harmonic to noise ratio (p = 0.001), reduced phonation range (p = 0.007) and shorter closed phase of vocal fold vibration (p = 0.006) in comparison to healthy controls. Females with CC had reduced fundamental frequency in connected speech (p = 0.009). There was consistent overlap between the participants with CC and those with PVFM. Duration of closed phase and fundamental frequency were lower in the participants with CC and PVFM than in those with muscle tension dysphonia. i Conclusion: /i These results confirm abnormalities in acoustic and EGG voice features in CC and PVFM.
Publisher: Elsevier BV
Date: 2017
DOI: 10.1016/J.CHEST.2016.09.035
Abstract: Asthma and COPD are common airway diseases. In iduals with overlapping asthma and COPD experience increased health impairment and severe disease exacerbations. Efficacious treatment options are required for this population. Omalizumab (anti-IgE) therapy is effective in patients with severe persistent asthma, but limited data are available on efficacy in populations with overlapping asthma and COPD. Data from the Australian Xolair Registry were used to compare treatment responses in in iduals with asthma-COPD overlap with responses in patients with severe asthma alone. Participants were assessed at baseline and after 6 months of omalizumab treatment. We used several different definitions of asthma-COPD overlap. First, we compared participants with a previous physician diagnosis of COPD to participants with no COPD diagnosis. We then made comparisons based on baseline lung function, comparing participants with an FEV Omalizumab treatment markedly improved asthma control and health-related quality of life in all populations assessed based on the Asthma Control Questionnaire and Asthma Quality of Life Questionnaire scores. Omalizumab treatment did not improve lung function (FEV Our study suggests that omalizumab improves asthma control and health-related quality of life in in iduals with severe allergic asthma and overlapping COPD. These findings provide real-world efficacy data for this patient population and suggest that omalizumab is useful in the management of severe asthma with COPD overlap.
Publisher: Elsevier BV
Date: 04-2009
DOI: 10.1016/J.PUPT.2008.12.009
Abstract: Twelve distinguished scientists attended the workshop, heard three presentations, and took part in the discussions. Fontana first described his unpublished studies on cough in exercise and during hyperventilation with healthy subjects. Both activities depressed cough induced by inhalation of distilled water aerosol (fog). The possible mechanisms were discussed. Gibson then described the successful use of speech therapy to treat chronic cough, and discussed the possible mechanisms, centering on the role of the larynx and its neural control. A comparison was made with the ability of speech and laughter to precipitate cough. Widdicombe discussed the scanty literature on the effect of singing and playing wind instruments on cough, most of the evidence being anecdotal. In the discussion periods several matters for future study arose. It is usually not clear if the modulation of cough, its depression, enhancement or excitation, arose primarily at peripheral sites (reflexes from the airways), or at a cortical level, or both. Nor is it clear whether the same results would be obtained with provoked cough and with spontaneous cough. But all three aspects of 'behavioual' changes in cough sensitivity (exercise, speech and music) could be further explored, and current techniques should make this possible.
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.RMED.2021.106572
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airways diseases. Both are complex and heterogeneous. Traditionally, clinical guidelines have advocated a stepwise approach to pharmacotherapy of asthma and COPD, but there is increasing realization that both require a more personalized and precise management approach. To this end, a management strategy based on the so-called Treatable Traits has been proposed. Emerging evidence suggests that this model improves relevant outcomes in patients with chronic airway diseases but further research is needed to guide implementation. This review discusses the challenges, opportunities, and hurdles that its implementation will have to face.
Publisher: Wiley
Date: 08-1995
DOI: 10.1111/J.1445-5994.1995.TB01897.X
Abstract: Although spacer devices are frequently used for aerosol therapy in asthma, the commonly used spacers have undergone little controlled evaluation, and their relation to nebuliser therapy is unclear. The aims of this study were to compare three delivery methods (Breath-A-Tech spacer, Volumatic spacer and jet nebuliser) for the administration of salbutamol to reverse acute histamine induced airway narrowing in asthma (Study 1) and to assess asthma control during two weeks use of inhaled therapy via Volumatic or Breath-A-Tech spacer (Study 2). A randomised double-blind cross-over comparison was conducted. In Study 1, 27 adults with stable asthma who were currently using pressurised metered dose inhaler therapy attended for three study days. On each study day subjects inhaled doubling doses of histamine and were randomised to receive: (a) salbutamol 200 micrograms via Breath-A-Tech spacer and placebo 200 micrograms via Volumatic spacer (b) placebo two puffs via Breath-A-Tech spacer and salbutamol 200 micrograms via Volumatic spacer or (c) salbutamol 1 mg in 2 mL saline via jet nebuliser. FEV1 and FEF 25-75% were measured at two minute intervals for 20 minutes. In Study 2, subjects were randomised to use regular asthma medication by Volumatic or Breath-A-Tech spacers and recorded symptoms and peak expiratory flow (PEF) in a daily diary. Lung function improved from a baseline FEV1 of 51% predicted to 72% after salbutamol inhalation from each of the delivery systems. The spacers and nebulisers produced the same maximum improvement in FEV1, however, lung function improved more rapidly when salbutamol was delivered by spacer. There was no difference in asthma control comparing inhaler use via Breath-A-Tech with Volumatic spacer over two weeks use. Subject preference favoured the Breath-A-Tech spacer (72% vs 4%). The Volumatic and Breath-A-Tech spacer devices are effective delivery systems in asthma and may offer a more rapid response than jet nebulisation at a lower cost.
Publisher: Wiley
Date: 22-12-2015
DOI: 10.1111/RESP.12701
Abstract: Neutrophilic inflammation has been implicated in non-eosinophilic asthma (NEA) in adults, but little is known about NEA in children/adolescents. We assessed clinical and inflammatory characteristics of NEA in adolescent asthma. Airway inflammation, sputum endotoxin, airway hyper-reactivity, atopy and lung function were assessed in 77 adolescents with asthma and 68 without asthma (12-17 years). Asthma was identified on the basis of wheeze and asthma history. The proportion of NEA (sputum eosinophils <2.5%) was 54%. In this group, atopy, sputum neutrophil, eosinophil, eosinophil cationic protein (ECP), endotoxin, neutrophil elastase and IL-8 levels were not different from those without asthma. In contrast, eosinophilic asthma (EA) was associated with atopy and sputum ECP and IL-8. The majority of NEA had no evidence of inflammation only 14% had neutrophilia (≥61% neutrophils), compared with 11% of EA, and 15% of those without asthma. Small differences in FEV1 (NS) were found between EA and NEA, but symptom prevalence and severity was not different (63% of EA and 52% of NEA were classified moderate to severe). NEA is common in adolescent asthma and has similar clinical characteristics as EA. Neutrophils do not appear to play a role in NEA in adolescents, and underlying mechanisms may not involve airway inflammation.
Publisher: SAGE Publications
Date: 2006
DOI: 10.1191/1479972306CD090RA
Abstract: Asthma self-management education is a fundamental component of asthma management guidelines. Self-management education should include the provision of information, self-monitoring, regular medical review and the provision of a written asthma management plan. Implementing this form of management can be challenging, this paper reviews the evidence supporting self-management education, provides recommendations and tools for delivering asthma education and discusses the challenges and solutions to implementing these recommendations. We have discussed ways to improve communication, develop patient partnerships and tailor management to facilitate behavioural change, adherence and self-management. Health Professionals providing education and guiding self-management require training to acquire and maintain the skills necessary to deliver this form of education. Provision of this training is important and can be achieved through varied methods of achieving competence.
Publisher: American Thoracic Society
Date: 06-1996
DOI: 10.1164/AJRCCM.153.6.8665035
Abstract: In a birth cohort of 114 normal children, this study examined the hypothesis that a transient absence of salivary IgA in the first year of life was associated with an increased risk of developing atopy, asthma, or bronchial hyperreactivity (BHR) later in life. Episodes of transient absence of IgA in saliva, of less than 1 mo, occurred in 18% of the study population in the first year of life. The children were assessed at age 7.5 to 12 yr for the presence of atopy (skin prick test to inhaled allergens), asthma (wheeze in the previous 12 mo), and BHR (histamine provocation). The transient absence of salivary IgA in the first year of life was associated with an increased risk of BHR (adjusted odds ratio [Adj OR]: 11.6 95% confidence interval [CI]: 2.2 to 60.9) and a trend toward a lowered risk of atopy to inhaled allergens (raw OR: 0.35 CI: 0.11 to 1.11). There was no relationship between the transient absence of salivary IgA and a clinical diagnosis of asthma (Adj OR: 0.9 CI: 0.2 to 3.6). The inconsistency in the relationships between the transient absence of salivary IgA and atopy, asthma, and BHR supports the concept that atopy, wheeze, and bronchial hyperreactivity are independent clinical outcomes. One possible explanation for the relationships observed in this study is that the transient absence of IgA in saliva in the first year of life identifies a cohort with mucosal hypoimmunity. These subjects are thus less likely to develop atopy and less able to effectively respond to a mucosal infection. Presentation of a mucosal antigen in these subjects may subsequently be associated with an inappropriate inflammatory response, which conditions bronchial hyperreactivity, and which is independent of atopy.
Publisher: Wiley
Date: 2006
DOI: 10.1111/J.1440-1843.2006.00782.X
Abstract: The course of asthma may be altered during pregnancy with at least one-third of women experiencing a worsening of asthma and 20% having an exacerbation during pregnancy. This study used the novel proteomic technique, surface-enhanced laser desorption ionization-time of flight mass spectrometry to determine if the presence of asthma during pregnancy was associated with alterations in plasma proteins. Plasma collected from healthy (n = 23) and asthmatic (n = 27) pregnant women at 18 and 30 weeks gestation was applied to strong anion exchange (SAX2), weak cation exchange (WCX2) and immobilized metal affinity capture (IMAC-Cu(2+)) chips. Mass analysis was conducted using Ciphergen Protein Biology System IIc and significant differences in in idual peak intensities between groups determined. At 18 weeks gestation, 91 peaks were significantly different between pregnant women with and without asthma, representing 28% of the total peaks identified. At 30 weeks gestation, 51 peaks were significantly different. There were two peaks that were significantly different between groups at both 18 and 30 weeks gestation and expressed at a similar level at both time points. One was increased in asthmatics (MW = 6444 Da) whereas the other decreased in asthmatics compared with non-asthmatic women (MW = 1846 Da). This study demonstrated that there are differences in protein patterns between pregnant women with and without asthma. Other techniques are needed to define the molecular species and classify pathophysiological significance. Surface-enhanced laser desorption ionization-time of flight mass spectrometry has potential as a tool to monitor disease progression in situations such as pregnancy.
Publisher: European Respiratory Society (ERS)
Date: 17-10-2014
DOI: 10.1183/09031936.00105013
Abstract: Asthma is a heterogeneous inflammatory airways disorder where interleukin (IL)-1β is thought to be a key mediator, especially in the neutrophilic subtype of asthma. The generation of active IL-1β requires proteolytic cleavage typically mediated through the formation of a caspase-1-containing inflammasome. This study hypothesised that an IL-1β endotype associated with the nucleotide-binding domain, leucine-rich repeat-containing family protein (NLRP)3/apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC)/caspase-1 inflammasome is characteristic of patients with the neutrophilic subtype of asthma. Participants with asthma (n=85) and healthy controls (n=27) underwent clinical assessment, spirometry and sputum induction. Sputum was processed for differential cell count, gene expression and protein mediators. NLRP3 and caspase-1 expression was also determined by immunocytochemistry. Sputum macrophages were isolated (n=8) and gene expression of NLRP3 and IL-1β determined. There was significantly elevated gene expression of NLRP3, caspase-1, caspase-4, caspase-5 and IL-1β in participants with neutrophilic asthma. Protein levels of IL-1β were significantly higher in those with neutrophilic asthma and correlated with sputum IL-8 levels. Sputum macrophages, as well as sputum neutrophils in neutrophilic asthma, expressed NLRP3 and caspase-1 protein. NLRP3 inflammasome is upregulated in neutrophilic asthma and may regulate the inflammation process observed in this asthma phenotype through production of IL-1β.
Publisher: European Respiratory Society (ERS)
Date: 10-12-2015
Publisher: The American Association of Immunologists
Date: 15-04-2010
Abstract: Neutrophilic asthma is a prevalent, yet recently described phenotype of asthma. It is characterized by neutrophilic rather than eosinophilic airway inflammation and airways hyperresponsiveness (AHR) and may have an infectious origin. Chlamydial respiratory infections are associated with asthma, but how these Th1-inducing bacteria influence Th2-mediated asthma remains unknown. The effects of chlamydial infection on the development of asthma were investigated using a BALB/c mouse model of OVA-induced allergic airways disease (AAD). The effects of current and resolved Chlamydia muridarum infection during OVA sensitization on AAD were assessed and compared with uninfected and nonsensitized controls. Current, but not resolved, infection attenuated hallmark features of AAD: pulmonary eosinophil influx, T cell production of IL-5, mucus-secreting cell hyperplasia, and AHR. Current infection also induced robust OVA-driven neutrophilic inflammation and IFN-γ release from T cells. The phenotype of suppressed but persistent Th2 responses in association with enhanced neutrophilia is reminiscent of neutrophilic asthma. This phenotype was also characterized by increased pulmonary IL-12 and IL-17 expression and activation of APCs, as well as by reduced thymus- and activation-regulated chemokine. Inhibition of pulmonary neutrophil influx during infection blocked OVA-induced neutrophilic inflammation and T cell IFN-γ production and reversed the suppressive effects on mucus-secreting cell hyperplasia and AHR during AAD. These changes correlated with decreased IL-12 and IL-17 expression, increased thymus- and activation-regulated chemokine and altered APC activation. Blocking IFN-γ and IL-17 during OVA challenge had no effect. Thus, active chlamydial respiratory infection during sensitization enhances subsequent neutrophilic inflammation and Th1/Th17 responses during allergen exposure and may have a role in the pathogenesis of neutrophilic asthma.
Publisher: Wiley
Date: 12-2002
DOI: 10.1046/J.1365-2222.2002.01556.X
Abstract: Epidemics of acute asthma associated with thunderstorms occur intermittently worldwide, though airway inflammation during these acute episodes has not been characterized. The aim of this study was to characterize airway inflammation in thunderstorm asthma. Cases were recruited after presentation to the emergency room with acute asthma immediately following a thunderstorm (n = 6). They were compared to two control groups: a group of atopic asthmatics that had presented with acute asthma to the emergency room prior to the thunderstorm (n = 12), and a second group of corticosteroid naive asthmatics who presented to the emergency room in the prior 12 months (n = 6). Subjects had spirometry, sputum induction and allergy skin tests acutely and at review 4 weeks later. Thunderstorm (TS) cases were more likely to have a history of hay fever and grass pollen allergy, and less likely to be on inhaled corticosteroids (ICS) prior to presentation. Cases and control groups had a similar degree of moderate to severe acute airway obstruction (P = 1.0). TS cases had elevated sputum eosinophils (14.8% of total cell count) compared to controls (1%, 2.6%, P < 0.01). TS cases had higher sputum eosinophil cationic protein (ECP 11,686 ng/mL) compared to controls (1,883, 3,300, P = 0.02) acutely. TS cases had more cells positive for IL-5 (30%) compared to controls (1, 1.5%, P = 0.02). When adjusted for ICS use, TS cases had a risk ratio for elevated sputum eosinophils of 2.4 (1.23-4.69). Thunderstorm asthma is characterized by airway inflammation with IL-5-mediated sputum eosinophilia and eosinophil degranulation. These results are consistent with allergen exposure as the cause of the exacerbation, and are consistent with the thunderstorm-induced grass pollen deluge as the cause of epidemic asthma after thunderstorms.
Publisher: Wiley
Date: 22-11-2005
Publisher: MDPI AG
Date: 08-02-2021
Abstract: Fetal exposure to tobacco smoke is an adverse risk factor for newborns. A plausible mechanism of how this exposure may negatively impact long term health is differential methylation of deoxyribonucleic acid (DNAm) and its relation to birth weight. We examined whether self-reported gestational smoking status and maternal exhaled carbon monoxide (eCO) during early pregnancy were associated with methylation of cytosine by guanines (CpG) sites that themselves predicted birth weight. We focused first on CpGs associated with maternal smoking, and secondly, among these, on CpGs related to birth weight found in another cohort. Then in 94 newborns from the Breathing for Life Trial (BLT) DNAm levels in cord blood were determined using Infinium Methylation EPIC BeadChip measuring K CpGs. We regressed CpGs on eCO and tested via mediation analysis whether CpGs link eCO to birth weight. Nine smoking related CpG sites were significantly associated with birth weight. Among these nine CpGs the methylation of cg02264407 on the LMO7 gene was statistically significant and linked with eCO measurements. eCO greater than six ppm showed a 2.3% decrease in infant DNAm (p = 0.035) on the LMO7 gene. A 1% decrease in methylation at this site resulted in decreased birth weight by 44.8 g (p = 0.003). None of the nine CpGs tested was associated with self-reported smoking. This is the first study to report potential mediation of DNA methylation, linking eCO measurements during early pregnancy with birth weight.
Publisher: American Thoracic Society
Date: 15-10-2009
Publisher: BMJ
Date: 07-01-2021
DOI: 10.1136/THORAXJNL-2020-216331
Abstract: Add-on azithromycin (AZM) significantly reduces exacerbations in poorly controlled asthma irrespective of disease phenotype. In a predefined substudy of the original AMAZES protocol (500 mg, three times a week for 48 weeks), we report that AZM treatment reduces key sputum inflammatory proteins (interleukin (IL)-6, IL-1β and extracellular DNA), which is more evident in non-eosinophilic asthma (NEA). Moreover, AZM reduced Haemophilus influenzae load only in NEA. Our data support the anti-inflammatory effects of AZM in poorly controlled asthma. Prospective studies are required to identify patients that derive greatest benefit from AZM add-on therapy.
Publisher: European Respiratory Society (ERS)
Date: 09-2017
DOI: 10.1183/13993003.00196-2017
Abstract: Asthma is a chronic respiratory condition frequently associated with aberrant airway and systemic inflammation. Various inflammatory phenotypes in asthmatic airways have been described that relate to clinical phenotypes and impact on responses to conventional and novel asthma therapies. Macrophages are abundant immunocytes in the lung, capable of mounting erse responses required for homeostasis and defence against pathogens.Here, we summarise the clinical evidence regarding macrophage dysfunction in asthma. We also describe evidence supporting the role of macrophages as therapeutic targets in asthma. We conclude that macrophage dysfunction in asthma is highly prevalent and heterogeneous, and hypothesise that macrophages may play roles in promoting the discrete inflammatory phenotypes of asthma.These clinical findings, along with recent ground-breaking insights into the ontogeny, behavioural complexity and longevity of pulmonary macrophages, support continued research into the role of macrophages as disease modifiers, biomarkers and therapeutic targets in asthma.
Publisher: Elsevier BV
Date: 12-2014
Publisher: European Respiratory Society (ERS)
Date: 04-06-2010
DOI: 10.1183/09031936.00049510
Abstract: An inverse association exists between some bacterial infections and the prevalence of asthma. We investigated whether Streptococcus pneumoniae infection protects against asthma using mouse models of ovalbumin (OVA)-induced allergic airway disease (AAD). Mice were intratracheally infected or treated with killed S. pneumoniae before, during or after OVA sensitisation and subsequent challenge. The effects of S. pneumoniae on AAD were assessed. Infection or treatment with killed S. pneumoniae suppressed hallmark features of AAD, including antigen-specific T-helper cell (Th) type 2 cytokine and antibody responses, peripheral and pulmonary eosinophil accumulation, goblet cell hyperplasia, and airway hyperresponsiveness. The effect of infection on the development of specific features of AAD depended on the timing of infection relative to allergic sensitisation and challenge. Infection induced significant increases in regulatory T-cell (Treg) numbers in lymph nodes, which correlated with the degree of suppression of AAD. Tregs reduced T-cell proliferation and Th2 cytokine release. The suppressive effects of infection were reversed by anti-CD25 treatment. Respiratory infection or treatment with S. pneumoniae attenuates allergic immune responses and suppresses AAD. These effects may be mediated by S. pneumoniae-induced Tregs. This identifies the potential for the development of therapeutic agents for asthma from S. pneumoniae.
Publisher: CSIRO Publishing
Date: 2015
DOI: 10.1071/AN15277
Abstract: Advancement in technologies to identify and quantify bacterial species in the gastrointestinal tract has escalated interest in its microbiome worldwide. There is enormous interest in understanding the roles that bacterial species play in gastrointestinal health and overall wellbeing. What constitutes a ‘healthy gut microbiome’ includes: favourable fermentation-dependent characteristics such as butyrate supply to all regions, minimisation of putrefaction of proteins, and adequate laxation. The relative abundance of specific bacterial species with certain functional characteristics is also important and include: traditional prebiotic bacteria – Bifidobacteria strongly butyrate-producing – Clostridium coccoides and Faecalibacterium prausnitzi as well as a mucus-associated bacterium Akkermansia muciniphila. Manipulation of diet and dietary factors may be essential to favourably influence these fermentation-dependent parameters and select for growth of beneficial bacterial species. In this regard, this laboratory has identified indigestible oligosaccharides with prebiotic effects and now has an extensive database that quantifies indigestible oligosaccharides in a wide variety of foods including whole grains, cereals, legumes, seeds, nuts, fruits and vegetables. Future research in this area should consider the role of dietary components that best establish and maintain a ‘healthy gut microbiome’.
Publisher: Wiley
Date: 23-04-2008
Publisher: Informa UK Limited
Date: 05-1996
Publisher: Informa UK Limited
Date: 14-04-2016
DOI: 10.1586/17512433.2016.1172208
Abstract: Severe asthma is a complex multifactorial disease that requires specialist multidisciplinary input for optimal clinical outcomes. Following multidimensional assessment for optimisation of current therapy, self-management skills and comorbidities, all patients should be accurately phenotyped. Only after this assessment has been completed should new monoclonal antibody therapies be considered. In this review, we summarise the new antibody approaches targeting identified pathological pathways in severe refractory asthma.
Publisher: Wiley
Date: 03-12-2011
DOI: 10.1111/J.1365-2222.2010.03669.X
Abstract: The role of toll-like receptors (TLRs) and innate immune activation in clinical asthma exacerbations and their relationship to virus infection are unclear. This study aimed to characterize TLR expression and innate immune activity during virus infection in acute asthma. Subjects with acute asthma, stable asthma and healthy controls were recruited and underwent spirometry and sputum induction with isotonic saline. Selected sputum was dispersed with dithiothreitol and total and differential leucocyte counts were performed. Selected sputum was also used for quantitative real-time PCR for TLR2, TLR3, TLR4, IL-10 and IP-10mRNA expression. Sputum supernatant was used for the measurement of innate immune markers, including IL-8, matrix metalloproteinase-9 and neutrophil elastase activity. Viruses were detected using real-time and gel-based PCR. Sputum TLR2 mRNA expression was up-regulated in both acute and stable asthma compared with healthy controls and decreased 4-6 weeks after acute exacerbation. Sputum TLR2 mRNA expression was elevated in viral, compared with non-viral, acute asthma. Sputum TLR3 mRNA expression was similar in controls, stable and acute asthma. However, in acute asthma, subjects with virus-induced acute asthma had significantly higher sputum TLR3 mRNA expression. Induced sputum gene expression for IP-10 and IL-10 were increased in viral, compared with non-viral, acute asthma. In virus-induced acute asthma, levels of IP-10 and IL-10 mRNA expression were correlated with the mRNA expression of TLR2 and TLR3. Virus-induced acute asthma leads to specific induction of TLR2, TLR3, IP-10 and IL-10, suggesting that signalling via TLRs may play an important role in mediating airway inflammation, via both innate and adaptive pathways, in virus-induced exacerbations. These mediators may provide potential treatment targets for virus-induced asthma. They may also be useful in diagnosing the nature of acute asthma exacerbations and monitoring treatment responses, which would be useful in the clinical management of asthma exacerbations.
Publisher: Wiley
Date: 06-2002
DOI: 10.1046/J.1440-1843.2002.00380.X
Abstract: Interleukin (IL)-5 measurement in sputum s les has produced variable results that appear to be due to methodological problems. The aim of the present study was to investigate the effects of dithiothreitol (DTT), sputum protease inhibition and s le storage on IL-5 recovery in order to develop a method to accurately measure IL-5 in dispersed sputum supernatant. Measurement of IL-5 in sputum was performed in 22 subjects with airway disease. Interleukin-5 recovery was measured in s les spiked with recombinant human IL-5 using a commercial ELISA. A mix of four protease inhibitors (PI) was added to sputum processed using the selection method with dispersion using DTT and stored with and without inhibitors. The addition of PI to sputum resulted in a 24% increase in IL-5 recovery. Recovery was not further increased with the addition of a blocking protein. Storage of IL-5-spiked sputum gave significantly less recovery. The addition of PI to sputum processed with DTT had no effect on total cell count, viability or cell differential. Interleukin-5 recovery is increased by the addition of PI to s les processed using the selected portion method with DTT dispersion. A protease inhibitor cocktail should be added to sputum for IL-5 assay.
Publisher: European Respiratory Society (ERS)
Date: 03-2004
Publisher: SAGE Publications
Date: 18-06-2021
Abstract: Asthma and gestational diabetes mellitus are prevalent during pregnancy and associated with adverse perinatal outcomes. The risk of gestational diabetes mellitus is increased with asthma, and more severe asthma yet, the underlying mechanisms are unknown. This review examines existing literature to explore possible links. Asthma and gestational diabetes mellitus are associated with obesity, excess gestational weight gain, altered adipokine levels and low vitamin D levels yet, it’s unclear if these underpin the gestational diabetes mellitus–asthma association. Active antenatal asthma management reportedly mitigates asthma-associated gestational diabetes mellitus risk. However, mechanistic studies are lacking. Existing research suggests asthma management during pregnancy influences gestational diabetes mellitus risk this may have important implications for future antenatal strategies to improve maternal-fetal outcomes by addressing both conditions. Addressing shared risk factors, as part of antenatal care, may also improve outcomes. Finally, mechanistic studies, to establish the underlying pathophysiology linking asthma and gestational diabetes mellitus, could uncover new treatment approaches to optimise maternal and child health outcomes.
No related grants have been discovered for Peter Gibson.