Peter Sly

Global strategy for the diagnosis and management of asthma in children 5 years and younger

Publisher: Wiley

Date: 20-10-2010

DOI: 10.1002/PPUL.21321

Abstract: Asthma is the most common chronic disease of childhood and the leading cause of childhood morbidity from chronic disease as measured by school absences, emergency department visits, and hospitalisation. During the past two decades, many scientific advances have improved our understanding of asthma and our ability to manage and control it effectively. However, in children 5 years and younger, the clinical symptoms of asthma are variable and non-specific. Furthermore, neither airflow limitation nor airway inflammation, the main pathologic hallmarks of the condition, can be assessed routinely in this age group. For this reason, to aid in the diagnosis of asthma in young children, a symptoms-only descriptive approach that includes the definition of various wheezing phenotypes has been recommended. In 1993, the Global Initiative for Asthma (GINA) was implemented to develop a network of in iduals, organizations, and public health officials to disseminate information about the care of patients with asthma while at the same time assuring a mechanism to incorporate the results of scientific investigations into asthma care. Since then, GINA has developed and regularly revised a Global Strategy for Asthma Management and Prevention. Publications based on the Global Strategy for Asthma Management and Prevention have been translated into many different languages to promote international collaboration and dissemination of information. In this report, Global Strategy for Asthma Management and Prevention in Children 5 Years and Younger, an effort has been made to present the special challenges that must be taken into account in managing asthma in children during the first 5 years of life, including difficulties with diagnosis, the efficacy and safety of drugs and drug delivery systems, and the lack of data on new therapies. Approaches to these issues will vary among populations in the world based on socioeconomic conditions, genetic ersity, cultural beliefs, and differences in healthcare access and delivery. Patients in this age group are often managed by pediatricians and general practitioners routinely faced with a wide variety of issues related to childhood diseases.

Guest Editorial

Publisher: Elsevier BV

Date: 09-2008

DOI: 10.1016/J.PRRV.2008.05.001

Managing Asthma in Pregnancy (MAP) trial: FENO levels and childhood asthma

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.

A worldwide charter for all children with asthma

Publisher: Wiley

Date: 06-03-2020

DOI: 10.1002/PPUL.24713

Home Recording of Peak Expiratory Flow Rates and Perception of Asthma

Publisher: American Medical Association (AMA)

Date: 05-1985

DOI: 10.1001/ARCHPEDI.1985.02140070053032

Abstract: Fourteen asthmatic children, aged 7.9 to 18.0 years (mean, 11.3 years), recorded peak expiratory flow rates three times a day at home for four weeks in an attempt to improve perception of their airway obstruction. Pulmonary function tests were performed and a subjective severity score was recorded before and after this period. The accuracy of the parents' perceptions of their child's airway obstruction was also assessed. These children were unable to accurately predict their degree of airway obstruction, and no improvement in prediction was seen following the learning period. Parents' perceptions of the child's airway obstruction were also inaccurate. Recording of peak expiratory flow rate at home did not improve the child's perception of his asthma. Rational management of troublesome asthma requires the use of an inexpensive peak flowmeter to provide continual objective measurements of lung function.

Boosting airway T-regulatory cells by gastrointestinal stimulation as a strategy for asthma control

Publisher: Elsevier BV

Date: 2011

DOI: 10.1038/MI.2010.43

Abstract: The hallmark of atopic asthma is transient airways hyperresponsiveness (AHR) preceded by aeroallergen-induced Th-cell activation. This is preceded by upregulation of CD86 on resident airway dendritic cells (DCs) that normally lack competence in T-cell triggering. Moreover, AHR duration is controlled via T-regulatory (Treg) cells, which can attenuate CD86 upregulation on DC. We show that airway mucosal Treg/DC interaction represents an accessible therapeutic target for asthma control. Notably, baseline airway Treg activity in sensitized rats can be boosted by microbe-derived stimulation of the gut, resulting in enhanced capacity to control CD86 expression on airway DC triggered by aeroallergen and accelerated resolution of AHR.

Higher exhaled nitric oxide at 6 weeks of age is associated with less bronchiolitis and wheeze in the first 12 months of age

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.

Oxidation contributes to low glutathione in the airways of children with cystic fibrosis

Publisher: European Respiratory Society (ERS)

Date: 23-03-2014

DOI: 10.1183/09031936.00170213

Abstract: Glutathione is an important antioxidant in the lungs but its concentration is low in the airways of patients with cystic fibrosis. Whether this deficit occurs from an early age or how oxidative stress contributes to lowering glutathione is unknown. We measured glutathione, its oxidation products, myeloperoxidase, and biomarkers of hypochlorous acid in bronchoalveolar lavage from children with cystic fibrosis and disease controls using mass spectrometry and immunological techniques. The concentration of glutathione was lower in bronchoalveolar lavage from children with cystic fibrosis, whereas glutathione sulfonamide, a specific oxidation product of hypochlorous acid, was higher. Oxidised glutathione and glutathione sulfonamide correlated with myeloperoxidase and a biomarker of hypochlorous acid. The percentage of glutathione attached to proteins was higher in children with cystic fibrosis than controls. Pulmonary infections in cystic fibrosis resulted in lower levels of glutathione but higher levels of oxidised glutathione and glutathione sulfonamide in bronchoalveolar lavage. The concentration of glutathione is low in the airways of patients with cystic fibrosis from an early age. Increased oxidation of glutathione by hypochlorous acid and its attachment to proteins contribute to this deficiency. Therapies targeted against myeloperoxidase may boost antioxidant defence and slow the onset and progression of lung disease in cystic fibrosis.

Acquisition and eradication of P. aeruginosa in young children with cystic fibrosis

Publisher: European Respiratory Society (ERS)

Date: 17-09-2202

DOI: 10.1183/09031936.00043108

Abstract: When do infants and young children with cystic fibrosis acquire infection with Pseudomonas aeruginosa? Can this be eradicated when first detected? Children <6 yrs of age participated in an annual bronchoalveolar lavage (BAL)-based microbiological surveillance programme in Perth, Australia. When P. aeruginosa was detected, an eradication programme using combination treatment with i.v., oral and nebulised antibiotics was undertaken. Repeat BAL was performed 3 months following treatment, to assess eradication success. P. aeruginosa was detected in 33 (28.4%) children median (range) age at detection was 30.5 (3.3-71.4) months. P. aeruginosa was mucoid at detection in six (18.2%) out of 33 patients and associated with respiratory symptoms in 16 (48.5%) out of 33 children. In total, 26 children underwent eradication therapy, with P. aeruginosa eradicated in 20 (77%) out of 26 following one eradication cycle and in three (total 88%) additional children following a second cycle. Eradication was associated with a significant decrease in neutrophil elastase and interleukin-1beta in BAL fluid 12 months post eradication. Eradication of Pseudomonas aeruginosa infection is achievable in young children with cystic fibrosis for up to 5 yrs using combination i.v., oral and nebulised antibiotic therapy and is associated with reduced pulmonary inflammation 12 months post eradication.

Household size, T regulatory cell development, and early allergic disease: a birth cohort study

Publisher: Wiley

Date: 06-2022

DOI: 10.1111/PAI.13810

Abstract: Children born to larger households have less allergic disease. T regulatory cell (Treg) development may be a relevant mechanism, but this has not been studied longitudinally. We aim to (i) describe how prenatal and postnatal environmental factors are associated with Treg development and (ii) investigate whether serial Treg measures predict allergic outcomes at 1 year of age. A birth cohort ( n = 1074) with information on prenatal and postnatal early life factors. Both naïve Treg (nTreg) and activated Treg (aTreg) cell populations (as a proportion of CD4 + T cells) were available in 463 infants at birth (cord blood), 600 at 6 months, and 675 at 12 months. 191 infants had serial measures. Measures of allergic status at 12 months were polysensitization (sensitization to 2 or more allergens), clinically proven food allergy, atopic eczema, and atopic wheeze. Infants born to larger households (3 or more residents) had higher longitudinal nTreg proportions over the first postnatal year with a mean difference (MD) of 0.67 (95% CI 0.30–1.04)%. Higher nTreg proportions at birth were associated with a reduced risk of infant allergic outcomes. Childcare attendance and breastfeeding were associated with higher longitudinal nTreg proportions (MD 0.48 (95% CI 0.08–0.80)%. Multiple prenatal and postnatal microbial factors are associated with nTreg and aTreg development. Larger household size was associated with higher nTreg at birth which in turn was associated with reduced allergic sensitization and disease at 12 months of age.

Respiratory viral infections in children with asthma: do they matter and can we prevent them?

Publisher: Springer Science and Business Media LLC

Date: 13-09-2012

DOI: 10.1186/1471-2431-12-147

Abstract: Asthma is a major public health problem with a huge social and economic burden affecting 300 million people worldwide. Viral respiratory infections are the major cause of acute asthma exacerbations and may contribute to asthma inception in high risk young children with susceptible genetic background. Acute exacerbations are associated with decreased lung growth or accelerated loss of lung function and, as such, add substantially to both the cost and morbidity associated with asthma. While the importance of preventing viral infection is well established, preventive strategies have not been well explored. Good personal hygiene, hand-washing and avoidance of cigarette smoke are likely to reduce respiratory viral infections. Eating a healthy balanced diet, active probiotic supplements and bacterial-derived products, such as OM-85, may reduce recurrent infections in susceptible children. There are no practical anti-viral therapies currently available that are suitable for widespread use. Hand hygiene is the best measure to prevent the common cold. A healthy balanced diet, active probiotic supplements and immunostimulant OM-85 may reduce recurrent infections in asthmatic children.

Th2-Associated Local Reactions to the Acellular Diphtheria-Tetanus-Pertussis Vaccine in 4- to 6-Year-Old Children

Publisher: American Society for Microbiology

Date: 12-2005

DOI: 10.1128/IAI.73.12.8130-8135.2005

Abstract: Acellular vaccines against diphtheria-tetanus-pertussis (acellular pertussis) (DTaP) are being progressively introduced into vaccination programs worldwide, with the aim of reducing T-helper 1 (Th1)-associated reactogenicity associated with the cellular diphtheria-tetanus-pertussis (whole-cell pertussis) (DTwP) vaccine. The DTaP vaccine has an improved safety profile in infants, but little information is available concerning the nature of the ensuing immunological memory in older children and how this may affect the reactogenicity of DTaP booster doses. We have addressed this question in the present study by assessing polyclonal and vaccine antigen-specific humoral and cellular immune responses to boosting with DTaP in 4- to 6-year-old children primed during infancy with DTaP ( n = 30) or DTwP ( n = 16) and by correlating these parameters, in particular cytokine responses, with expression of local side effects at the injection site. Large local reactions (≥50-mm diameter) 24 to 72 h after receiving the DTaP booster occurred in 43% of exclusively DTaP-primed children, in contrast to 6% of children primed with DTwP. These reactions were associated with vigorous T helper 2 (Th2)-polarized memory responses to vaccine antigen exemplified by interleukin 5 (IL-5), IL-6, and IL-13 production and log-scale boosting of tetanus-specific immunoglobulin E and occurred most frequently among children who are intrinsically “high Th2 responders” as detected by in vitro responsiveness to polyclonal mitogen. Our findings suggest that priming during infancy with DTaP promotes stable, boostable Th2-polarized immunity against vaccine antigens, which in a significant subset of children is subsequently associated with local reactions at the booster site. The time course of these reactions suggests that the underlying mechanism involves reactivation of Th2-polarized cellular immune memory.

Altered stability of pulmonary surfactant in SP-C-deficient mice

Publisher: Proceedings of the National Academy of Sciences

Date: 08-05-2001

DOI: 10.1073/PNAS.101500298

Abstract: The surfactant protein C (SP-C) gene encodes an extremely hydrophobic, 4-kDa peptide produced by alveolar epithelial cells in the lung. To discern the role of SP-C in lung function, SP-C-deficient (−/−) mice were produced. The SP-C (−/−) mice were viable at birth and grew normally to adulthood without apparent pulmonary abnormalities. SP-C mRNA was not detected in the lungs of SP-C (−/−) mice, nor was mature SP-C protein detected by Western blot of alveolar lavage from SP-C (−/−) mice. The levels of the other surfactant proteins (A, B, D) in alveolar lavage were comparable to those in wild-type mice. Surfactant pool sizes, surfactant synthesis, and lung morphology were similar in SP-C (−/−) and SP-C (+/+) mice. Lamellar bodies were present in SP-C (−/−) type II cells, and tubular myelin was present in the alveolar lumen. Lung mechanics studies demonstrated abnormalities in lung hysteresivity (a term used to reflect the mechanical coupling between energy dissipative forces and tissue-elastic properties) at low, positive-end, expiratory pressures. The stability of captive bubbles with surfactant from the SP-C (−/−) mice was decreased significantly, indicating that SP-C plays a role in the stabilization of surfactant at low lung volumes, a condition that may accompany respiratory distress syndrome in infants and adults.

Breast is best for preventing asthma and allergies—or is it?

Publisher: Elsevier BV

Date: 09-2002

DOI: 10.1016/S0140-6736(02)11068-3

Inflammatory Responses to Individual Microorganisms in the Lungs of Children With Cystic Fibrosis

Publisher: Oxford University Press (OUP)

Date: 15-08-2011

DOI: 10.1093/CID/CIR399

Abstract: We hypothesized that the inflammatory response in the lungs of children with cystic fibrosis (CF) would vary with the type of infecting organism, being greatest with Pseudomonas aeruginosa and Staphylococcus aureus. A microbiological surveillance program based on annual bronchoalveolar lavage (BAL) collected fluid for culture and assessment of inflammation was conducted. Primary analyses compared inflammation in s les that grew a single organism with uninfected s les in cross-sectional and longitudinal analyses. Results were available for 653 s les from 215 children with CF aged 24 days to 7 years. A single agent was associated with pulmonary infection (≥10(5) cfu/mL) in 67 BAL s les, with P. aeruginosa (n = 25), S. aureus (n = 17), and Aspergillus species (n = 19) being the most common. These microorganisms were associated with increased levels of inflammation, with P. aeruginosa being the most proinflammatory. Mixed oral flora (MOF) alone was isolated from 165 BAL s les from 112 patients, with 97 of these s les having a bacterial density ≥10(5) cfu/mL, and was associated with increased pulmonary inflammation (P < .001). For patients with current, but not past, infections there was an association with a greater inflammatory response, compared with those who were never infected (P < .05). However, previous infection with S. aureus was associated with a greater inflammatory response in subsequent BAL. Pulmonary infection with P. aeruginosa, S. aureus, or Aspergillus species and growth of MOF was associated with significant inflammatory responses in young children with CF. Our data support the use of specific surveillance and eradication programs for these organisms. The inflammatory response to MOF requires additional investigation.

A Review of Pulmonary Function Testing in Children

Publisher: Informa UK Limited

Date: 1990

DOI: 10.3109/02770909009073314

Abstract: Early infection with murine cytomegalovirus (MCMV) induces circulating levels of interleukin (IL)-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF). Studies presented here further characterize these responses by defining kinetics and extending evaluation to include IL-1, IL-6, and glucocorticoids. IL-12 p40, IFN-gamma, TNF, IL-1alpha, and IL-6 were shown to be increased, but IL-1beta was undetectable, in serum of MCMV-infected mice. The IL-12 p40, IFN-gamma, TNF, and IL-6 responses were dramatic with peak levels reaching >150-10,000 pg/ml at 32-40 h after infection and rapidly declining thereafter. Glucocorticoid induction, peaking at 36 h and reaching 30-fold increases above control values, accompanied the cytokine responses. Mice with cytokine deficiencies or neutralized cytokine function demonstrated that IL-6 was the pivotal mediator of the glucocorticoid response, with IL-1 contributing to IL-6 production. The IL-6 requirement appeared to be specific for virus-type stimuli as the synthetic analogue of viral nucleic acid, polyinosinic-polycytidylic acid, also induced IL-6-dependent glucocorticoid release, but treatments with the bacterial product lipopolysaccharide and a non-immune physical restraint stressor elicited IL-6-independent responses. Collectively, the results identify IL-6 as a primary mediator of glucocorticoid induction, and elucidate specific pathways of interactions between immune and neuroendocrine systems during viral infection.

High tidal volume ventilation does not exacerbate acid-induced lung injury in infant rats

Publisher: Elsevier BV

Date: 10-2013

DOI: 10.1016/J.RESP.2013.07.013

Abstract: The impact of mechanical ventilation with high V(T)-low PEEP in infant rats with preinjured lungs is unknown. After tracheal instillation of saline or acid, two week old rats were ventilated with V(T) 7 mL/kg and PEEP 5 cm H₂O or V(T) 21 mL/kg and PEEP 1cm H₂O for 4 h. Airway resistance and the coefficient of tissue elastance, measured via low-frequency forced-oscillation technique, and quasi-static pressure-volume curves deteriorated less with high V(T)-low PEEP when compared with low V(T)-high PEEP. IL-6 concentration in bronchoalveolar lavage fluid (BALF) did not differ between all ventilated groups. Moreover, differences in BALF protein concentration and histological lung injury scores were independent of applied ventilation strategies. In contrast to experimental studies with adult rats, short-term mechanical ventilation with high V(T)-low PEEP is not deleterious when compared to low V(T)-high PEEP in both healthy and pre-injured infant rat lungs. Our results call for caution when extrapolating data from adult studies and highlight the need for age-specific animal models.

Elucidation of Pathways Driving Asthma Pathogenesis: Development of a Systems-Level Analytic Strategy

Publisher: Frontiers Media SA

Date: 23-09-2014

DOI: 10.3389/FIMMU.2014.00447

Site of inflammation influences site of hyperresponsiveness in experimental asthma

Publisher: Elsevier BV

Date: 12-2003

DOI: 10.1016/J.RESP.2003.09.003

Abstract: Our recently developed murine asthma model is capable of inducing airway-specific chronic inflammatory changes and remodeling, features of human asthma commonly missing in conventional animal models. To validate this model by site-specific physiological evaluation of hyperresponsiveness. Non-sensitized and sensitized mice received either short-term uncontrolled or long-term controlled low-level exposures to aerosolized ovalbumin (OVA). Respiratory impedance (Zrs) was measured in response to increasing doses of methacholine (Mch). The constant-phase model was fitted to Zrs spectra to determine the specific site of hyperresponsiveness. Sensitized acutely exposed mice had significantly increased tissue d ing (G), tissue elastance (H) and hysteresivity (eta) in response to Mch, but no significant increase in airway resistance (Raw), indicating tissue-specific hyperresponsiveness. In contrast, sensitized chronically exposed mice had significantly elevated Raw at all concentrations of Mch but no increases in G, H or eta indicating airway-specific hyperresponsiveness. Chronic inhalational exposure of sensitized mice to low-mass concentrations of OVA induces airway-specific hyperresponsiveness.

Lung Function in African Infants in the Drakenstein Child Health Study. Impact of Lower Respiratory Tract Illness

Publisher: American Thoracic Society

Date: 15-01-2017

DOI: 10.1164/RCCM.201601-0188OC

Assessment and validation of bronchodilation using the interrupter technique in preschool children

Publisher: Wiley

Date: 17-05-2010

DOI: 10.1002/PPUL.21210

Abstract: To determine and validate a cut-off value for bronchodilation using the interrupter resistance (Rint) in preschool children. Rint was measured in 60 healthy children (age range 2.7-6.4 years) before and after salbutamol inhalation (200 microg). Four potential methods for assessing BDR were evaluated: percent change from baseline, percent change of predicted values, absolute change in Rint, and change in Z-score. These cut-off values, determined as the fifth percentile of the healthy group, were applied to children referred for the assessment of recurrent wheezing, classified on the basis of acute symptoms and/or abnormal chest examination into symptomatic (n = 60, age range 2.9-6.1 years) and asymptomatic (n = 60, age range 2.5-5.7 years) groups. The cut-off values for bronchodilation calculated in healthy children were: -32% baseline -33% predicted -0.26 kPa L(-1) sec and -1.25 Z-scores. Assessing BDR in children with a history of wheezing by either a decrease in absolute Rint or a decrease in Z-score gave sensitivity, specificity, negative predictive value, and positive predictive value all >80% for detecting children with current respiratory symptoms. Both a decrease in Rint > or =0.26 kPa L(-1) sec and a decrease in Z-score of > or =1.25 are appropriate for assessing BDR in preschool children with a history of recurrent wheezing. As Z-score is a more general solution, we recommend using a change in Z-score to determine BDR in preschool children. Further longitudinal studies will be required to determine the clinical utility of measuring BDR in managing lung disease in such children.

Immunotherapy — anergy, deviation or suppression?

Publisher: Wiley

Date: 08-1998

DOI: 10.1046/J.1365-2222.1998.00323.X

Development of a novel angiotensin converting enzyme 2 stimulator with broad implications in SARS-CoV2 infection and type 1 diabetes

Publisher: Research Square Platform LLC

Date: 05-04-2023

DOI: 10.21203/RS.3.RS-2642181/V1

Abstract: Angiotensin-converting enzyme 2 (ACE2) is protective in cardiovascular disease, lung injury and diabetes yet paradoxically underlies our susceptibility to SARs-CoV2 infection and the fatal heart and lung disease it can induce. Furthermore, diabetic patients have chronic, systemic inflammation and altered ACE2 expression resulting in increased risk of severe COVID-19 and the associated mortality. A drug that could increase ACE2 activity and inhibit cellular uptake of severe acute respiratory syndrome coronavirus 2 (SARs-CoV2), thus decrease infection, would be of high relevance to cardiovascular disease, diabetes and SARs-CoV2 infection. While the need for such a drug lead was highlighted over a decade ago receiving over 600 citations, 1 to date, no such drugs are available. 2 Here, we report the development of a novel ACE2 stimulator, designated ‘2A’(international PCT filed), which is a 10 amino acid peptide derived from a snake venom, and demonstrate its in vitro and in vivo efficacy against SARs-CoV2 infection and associated lung inflammation. Peptide 2A also provides remarkable protection against glycaemic dysregulation, weight loss and disease severity in a mouse model of type 1 diabetes. No untoward effects of 2A were observed in these pre-clinical models suggesting its strong clinical translation potential.

Small macrophages are present in early childhood respiratory disease

Publisher: Elsevier BV

Date: 05-2012

DOI: 10.1016/J.JCF.2011.11.008

Abstract: Recently, an established "small macrophage" phenotype has been observed in the sputum of patients with CF and COPD. However, little is known about the prevalence of this phenotype in the airways of young children. Since respiratory inflammation begins early in CF, we hypothesised that these small macrophages would be increased in paediatric CF bronchoalveolar lavage (BAL). Macrophage populations in CF and disease control BAL were assessed by multicolour flow cytometry. BAL inflammatory indices were collected as part of the AREST-CF programme. Small macrophages were present in CF (n=35, mean 36±12% of BAL macrophages) but not significantly different to the respiratory disease controls (n=7, mean 40±21%). Number of small macrophages correlated significantly with number of BAL neutrophils (r=0.44, p<0.01) but not infection or IL-8. In paediatric patients small macrophages are not unique to CF, but their establishment as the dominant phenotype in adults may be due to chronicity of inflammation and infection.

Determinants of early-life lung function in African infants

Publisher: BMJ

Date: 17-11-2017

DOI: 10.1136/THORAXJNL-2015-207401

Sublingual immunotherapy for allergic respiratory disease

Publisher: Elsevier BV

Date: 02-1998

DOI: 10.1016/S0140-6736(05)78425-7

Abstract: Little research has been reported on evaluating the safety of the fixation construct in cervical kyphosis correction. In this study, we proposed a principal-strain criterion to evaluate the safety of the fixation construct and validated the modeling method against a retrospective case of anterior cervical discectomy fusion (ACDF). From C2 to T2 vertebra bodies, fixation instruments were reconstructed and positioned as per postoperative computed tomography (CT) scans. Head weight (HW) and various moments estimated from isometric strength data were imposed onto the C2. The postoperative stability of non-surgical segments, deformations surrounding the screw trajectories, and contact slipping on zygapophysial joints were analyzed. The model was validated against the reality that the patient had a good fusion and deformity correction. The ACDF restricted the range of motions (ROMs) of cervical segments and lent stability to vertebra fusion, no failure was found in the finite element (FE) model of cervical vertebrae. The deformation surrounding the screw trajectories were concentrated to the lateral sides of trajectories, recommending that the shape of the anterior cervical plate conforming to the curvature of the vertebra and screws fully inserted into vertebrae reduced the deformation concentration around the screw trajectories.

The role of the neonatal intensive care nurse in decision‐making: Advocacy, involvement in ethical decisions and communication

Publisher: Wiley

Date: 25-04-2005

DOI: 10.1111/J.1440-172X.2005.00512.X

Support for 2 variants of eczema

Publisher: Elsevier BV

Date: 11-2005

DOI: 10.1016/J.JACI.2005.06.038

Abstract: Studies investigating the natural history and risk factors for eczema have historically considered eczema as a single entity, without regard for the in idual's atopic status. The association between atopy and eczema is complex, and as many as (2/3) of patients with eczema are not atopic. To investigate the risk factors for eczema in relation to the child's atopic status in a cohort of high-risk children. A prospective birth cohort of 263 children was followed for 5 years and closely examined for eczema. Antenatal and postnatal data on environmental exposures were collected by interview. Skin prick test to define atopic status was performed at 6 months and 2 and 5 years of age. Of the subjects, 66.1% had eczema in the first 5 years, and the majority (85.5%) reported onset of rash in the first year. A third of those with eczema were not atopic (nonatopic/intrinsic eczema). Children with atopic eczema (extrinsic eczema) were more likely to be male, to have been breast-fed longer, and to have a history of food allergies, allergic rhinitis, and current wheeze. Nonatopic eczema was more common in girls, and an association was found with early daycare attendance. This study supports the presence of 2 variants of eczema: atopic eczema occurring early in childhood and nonatopic eczema with early daycare attendance. It is likely that environmental factors have a different effect on these 2 variants of eczema, and future studies should thus consider eczema as 2 variants in determining the effect of attributable risks.

Penh is not a measure of airway resistance!

Publisher: European Respiratory Society (ERS)

Date: 10-2007

DOI: 10.1183/09031936.00091307

Effect of misoprostol on fat malabsorption in cystic fibrosis.

Publisher: BMJ

Date: 09-1988

DOI: 10.1136/ADC.63.9.1081

Abstract: Misoprostol, a synthetic prostaglandin that is known to reduce gastric acid production and stimulate duodenal bicarbonate production, was evaluated in 22 patients with cystic fibrosis. In those patients who had greater than 10% fat malabsorption while taking pancrease the addition of misoprostol significantly reduced the degree of fat malabsorption.

Contribution of nasal pathways to low frequency respiratory impedance in infants

Publisher: BMJ

Date: 05-2002

DOI: 10.1136/THORAX.57.5.396

Abstract: In infants the impedance of the nasal pathways (Zn) is a significant proportion of the total respiratory impedance (Zrs). In 11 infants Zrs was partitioned into Zn and lower respiratory system impedance (Zlrs) using a nasal catheter. A low frequency oscillatory signal (0.5-20 Hz) was applied during a pause in breathing to obtain the impedance spectra. A model of the respiratory system containing an airway and tissue compartment was then fitted to Zrs and Zlrs. The airway compartment consisted of a frequency independent resistance (R) and inertance (I), while the tissue compartment was described by coefficients of tissue d ing (G) and elastance (H). Zrs could be reliably partitioned into Zn and Zlrs. The nasal pathway acted as a purely resistive-inertive impedance and contributed approximately half of the airway resistance (mean (SE) 44.6 (4.9)%) and most of the respiratory system inertance (71.7 (3.5)%). In studies investigating changes in airway resistance in nasally breathing infants, the separation of nasal and lower respiratory system mechanics will increase the sensitivity of the tests.

Value of serology in predicting Pseudomonas aeruginosa infection in young children with cystic fibrosis

Publisher: BMJ

Date: 10-2010

DOI: 10.1136/THX.2009.132845

Abstract: Early detection of Pseudomonas aeruginosa is essential for successful eradication. The accuracy of serum antibodies against specific and multiple P aeruginosa antigens at predicting lower airway infection in young children with cystic fibrosis (CF) was investigated. A commercial P aeruginosa multiple antigen (MAg) ELISA and an in-house exotoxin A (ExoA) ELISA were compared in two populations: a discovery population of 76 children (0.1-7.1 years) undergoing annual bronchoalveolar lavage (BAL)-based microbiological surveillance and a test population of 55 children (0.1-5.6 years) participating in the Australasian CF Bronchoalveolar Lavage Trial. In the discovery population, P aeruginosa was cultured from BAL fluid (≥10(5) colony-forming units (cfu)/ml) in 15/76 (19.7%) children (median age 1.88 years). Positive MAg and ExoA serological results were found in 38 (50.0%) and 30 (39.5%) children, respectively. Positive (PPV) and negative (NPV) predictive values for serology at diagnosing P aeruginosa infection (≥10(5) cfu/ml) were 0.14 and 0.99 respectively (MAg assay) and 0.11 and 0.98 (ExoA assay). In the test population, P aeruginosa was cultured from BAL fluid (≥10(5) cfu/ml) in 16/55 (29.1%) children (median age 1.86 years) and from oropharyngeal swabs in 32/36 (88.9%). Positive MAg and ExoA serology was detected in 19 (34.5%) and 33 (60.0%) children, respectively. The PPV and NPV of serology were 0.26 and 0.94 respectively (MAg assay) and 0.19 and 0.98 (ExoA assay) and were marginally higher for oropharyngeal cultures. Measuring serum antibody responses against P aeruginosa is of limited value for detecting early P aeruginosa infection in young children with CF.

Preoperative pulmonary hemodynamics determines changes in airway and tissue mechanics following surgical repair of congenital heart diseases

Publisher: Wiley

Date: 28-10-2004

DOI: 10.1002/PPUL.20117

Abstract: To characterize the effect of changes in pulmonary hemodynamics on airway and tissue mechanics, forced oscillatory input impedance of the respiratory system (Zrs) was measured between 0.4-12 Hz in two groups of children undergoing surgical repair of congenital heart disease (CHD) immediately before sternotomy and after chest closure during short apneic intervals. Children with lesions associated with high pulmonary blood flow and/or pressure (septal defects HP group, n = 12) and children with hypoperfused lungs (tetralogy of Fallot LP group, n = 12) were included in the study. Airway resistance (Raw), and coefficients of respiratory tissue d ing (G) and elastance (H), were estimated from Zrs by model-fitting. A postoperative reduction in pulmonary blood flow and/or pressure in the HP group resulted in an immediate decrease in Raw of 29 +/- 9 (SE)% (P < 0.05), whereas children in the LP group had increases in Raw (24 +/- 17%, no significance) after surgery. No significant change was observed in G in either the HP (6.4 +/- 13%) or LP (27 +/- 23%) group, while H increased in children of both the HP (23 +/- 8%, P < 0.05) and LP (36 +/- 7%, P < 0.01) groups. These results suggest that the preoperative pulmonary hemodynamic condition determines changes in airway mechanics: surgical repair of CHD leads to an improvement in airway function only in children with congested lungs. The adverse effects of surgery, mechanical ventilation, and/or cardiopulmonary bypass may be responsible for the increased stiffness of the respiratory system observed in both groups of children.

Hyperresponsiveness to inhaled but not intravenous methacholine during acute respiratory syncytial virus infection in mice

Publisher: Springer Science and Business Media LLC

Date: 12-2005

DOI: 10.1186/1465-9921-6-142

Abstract: To characterise the acute physiological and inflammatory changes induced by low-dose RSV infection in mice. BALB/c mice were infected as adults (8 wk) or weanlings (3 wk) with 1 × 10 5 pfu of RSV A2 or vehicle (intranasal, 30 μl). Inflammation, cytokines and inflammatory markers in bronchoalveolar lavage fluid (BALF) and airway and tissue responses to inhaled methacholine (MCh 0.001 – 30 mg/ml) were measured 5, 7, 10 and 21 days post infection. Responsiveness to iv MCh (6 – 96 μg/min/kg) in vivo and to electrical field stimulation (EFS) and MCh in vitro were measured at 7 d. Epithelial permeability was measured by Evans Blue dye leakage into BALF at 7 d. Respiratory mechanics were measured using low frequency forced oscillation in tracheostomised and ventilated (450 bpm, f lexiVent) mice. Low frequency impedance spectra were calculated (0.5 – 20 Hz) and a model, consisting of an airway compartment [airway resistance (Raw) and inertance (Iaw)] and a constant-phase tissue compartment [coefficients of tissue d ing (G) and elastance (H)] was fitted to the data. Inflammation in adult mouse BALF peaked at 7 d (RSV 15.6 (4.7 SE) vs. control 3.7 (0.7) × 10 4 cells/ml p 0.001), resolving by 21 d, with no increase in weanlings at any timepoint. RSV-infected mice were hyperresponsive to aerosolised MCh at 5 and 7 d (PC 200 Raw adults: RSV 0.02 (0.005) vs. control 1.1 (0.41) mg/ml p = 0.003) (PC 200 Raw weanlings: RSV 0.19 (0.12) vs. control 10.2 (6.0) mg/ml MCh p = 0.001). Increased responsiveness to aerosolised MCh was matched by elevated levels of cysLT at 5 d and elevated VEGF and PGE 2 at 7 d in BALF from both adult and weanling mice. Responsiveness was not increased in response to iv MCh in vivo or EFS or MCh challenge in vitro. Increased epithelial permeability was not detected at 7 d. Infection with 1 × 10 5 pfu RSV induced extreme hyperresponsiveness to aerosolised MCh during the acute phase of infection in adult and weanling mice. The route-specificity of hyperresponsiveness suggests that epithelial mechanisms were important in determining the physiological effects. Inflammatory changes were dissociated from physiological changes, particularly in weanling mice.

Lung Disease at Diagnosis in Infants with Cystic Fibrosis Detected by Newborn Screening

Publisher: American Thoracic Society

Date: 15-07-2009

DOI: 10.1164/RCCM.200901-0069OC

Bacterial colonization dynamics associated with respiratory syncytial virus during early childhood

Publisher: Wiley

Date: 16-03-2020

DOI: 10.1002/PPUL.24715

Commentaries on Viewpoint: Standards for quantitative assessment of lung structure

Publisher: American Physiological Society

Date: 09-2010

DOI: 10.1152/JAPPLPHYSIOL.00678.2010

Rangos de referencia en niños preescolares mexicanos con el empleo de la técnica de oscilación forzada

Publisher: Elsevier BV

Date: 08-2013

DOI: 10.1016/J.ARBRES.2013.01.014

Abstract: Recently, multi-ethnic reference ranges for spirometry have been created for use worldwide. In comparison, forced oscillation technique (FOT) reference values are limited to specific equipment and study populations, with current FOT reference ranges created in a Caucasian population. We aimed to develop FOT reference ranges for preschool-aged Mexican children and to compare these with current FOT reference ranges. Respiratory resistance (Rrs) and reactance (Xrs) was measured in healthy Mexican children three to five years of age using commercial FOT equipment. The relationship between height and Rrs and Xrs was determined using regression analyses, taking into account age, weight, sex, and exposure to tobacco smoke. Reference equations were calculated for the Mexican children and Z-scores determined for Rrs and Xrs at 6 and 8Hz. A paired t-test assessed the difference in Z-scores between the Australian reference values and those created for the Mexican cohort. FOT was successfully measured in 584 children. Height was a significant predictor of Rrs and Xrs at 6 and 8Hz (P<.05). Z-scores calculated using the Australian reference equations overestimated lung function in Mexican children for both Rrs and Xrs at 6 and 8Hz (P<.001). The development of FOT reference ranges specific to Mexican preschool-aged children will allow for the correct interpretation of FOT measurements. This study also showed that current FOT reference ranges overestimate lung function in Mexican children. Highlighting, the importance of using ethnic appropriate reference ranges for interpreting lung function.

Exposure to 4% SF6 during multiple breath washout affects subsequent infant tidal breathing analysis

Publisher: Wiley

Date: 20-01-2022

DOI: 10.1002/PPUL.25820

Airway, but not serum or urinary, levels of YKL-40 reflect inflammation in early cystic fibrosis lung disease

Publisher: Springer Science and Business Media LLC

Date: 27-02-2014

DOI: 10.1186/1471-2466-14-28

Lung Function, Airway Inflammation, and Polycyclic Aromatic Hydrocarbons Exposure in Mexican Schoolchildren

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-2014

DOI: 10.1097/JOM.0000000000000111

New Leadership for Reviews on Environmental Health

Publisher: Walter de Gruyter GmbH

Date: 2012

DOI: 10.1515/REVEH-2012-0041

Febrile respiratory illnesses in infancy and atopy are risk factors for persistent asthma and wheeze

Publisher: European Respiratory Society (ERS)

Date: 15-09-2011

DOI: 10.1183/09031936.00193310

Abstract: Severe viral respiratory illnesses and atopy are risk factors for childhood wheezing and asthma. The aim of this study was to explore associations between severe respiratory infections and atopy in early childhood with wheeze and asthma persisting into later childhood. 147 children at high atopic risk were followed from birth to age 10 yrs. Data on all respiratory infections occurring in infancy were collected prospectively and viral aetiology ascertained. Atopy was measured by skin prick tests at 6 months, and 2 and 5 yrs. History of wheeze and doctor-diagnosed eczema and asthma was collected regularly until 10 yrs of age. At 10 yrs, 60% of the cohort was atopic, 25.9% had current eczema, 18.4% current asthma and 20.4% persistent wheeze. 35.8% experienced at least one lower respiratory infection (LRI) associated with fever and/or wheeze in first year of life. Children who had wheezy or, in particular, febrile LRI in infancy and were atopic by 2 yrs, were significantly more likely to have persistent wheeze (RR 3.51, 95% CI 1.83-6.70 p<0.001) and current asthma (RR 4.92, 95% CI 2.59-9.36 p<0.001) at 10 yrs. Severe viral respiratory infections in infancy and early atopy are risk factors for persistent wheeze and asthma. The strongest marker of the asthmatogenic potential of early life infections was concurrent fever. The occurrence of fever during respiratory illnesses is an important marker of risk for wheeze and asthma later in childhood, suggesting it should be measured in prospective studies of asthma aetiology.

Childhood atopy and mental health: a prospective, longitudinal investigation

Publisher: Cambridge University Press (CUP)

Date: 20-10-2016

DOI: 10.1017/S0033291716001896

Abstract: Prior studies have suggested a relationship between atopy and mental health, although methodological barriers have limited the generalizability of these findings. The objective of this study was to investigate the relationship between early-life atopy and vulnerability to mental health problems among youth in the community. Data were drawn from the Raine Study ( N = 2868), a population-based birth cohort study in Western Australia. Logistic regression and generalized estimating equations were used to examine the relationship between atopy at ages 1–5 years [using parent report and objective biological confirmation (sera IgE)], and the range of internalizing and externalizing mental health problems at ages 5–17 years. Atopy appears to be associated with increased vulnerability to affective and anxiety problems, compared to youth without atopy. These associations remained significant after adjusting for a range of potential confounders. No relationship was evident between atopy and attention deficit hyperactivity disorder or externalizing problems. Findings are the first linking atopy (measured by both parent report and objective verification) with increased vulnerability to affective and anxiety problems. Therefore, replication is required. If replicated, future research aimed at understanding the possible biological and/or social and environmental pathways underlying these links is needed. Such information could shed light on shared pathways that could lead to more effective treatments for both atopy and internalizing mental health problems.

Impact of lung disease on respiratory impedance in young children with cystic fibrosis

Publisher: European Respiratory Society (ERS)

Date: 24-09-2015

DOI: 10.1183/13993003.00156-2015

Abstract: This study aimed to evaluate the ability of the forced oscillation technique (FOT) to detect underlying lung disease in preschool children with cystic fibrosis (CF) diagnosed following newborn screening. 184 children (aged 3–6 years) with CF underwent lung function testing on 422 occasions using the FOT to assess respiratory resistance and reactance at the time of their annual bronchoalveolar lavage collection and chest computed tomography scan. We examined associations between FOT outcomes and the presence and progression of respiratory inflammation, infection and structural lung disease. Children with CF who had pronounced respiratory disease, including free neutrophil elastase activity, infection with pro-inflammatory pathogens and structural lung abnormalities had similar FOT outcomes to those children without detectable lung disease. In addition, the progression of lung disease over 1 year was not associated with worsening FOT outcomes. We conclude that the forced oscillation technique is relatively insensitive to detect underlying lung disease in preschool children with CF. However, FOT may still be of value in improving our understanding of the physiological changes associated with early CF lung disease.

Early detection of infection with Pseudomonas aeruginosa in cystic fibrosis: The Holy Grail or an achievable goal?

Publisher: Elsevier BV

Date: 09-2014

DOI: 10.1016/J.JCF.2014.08.001

Antigen-Specific Responses to Diphtheria-Tetanus-Acellular Pertussis Vaccine in Human Infants Are Initially Th2 Polarized

Publisher: American Society for Microbiology

Date: 07-2000

DOI: 10.1128/IAI.68.7.3873-3877.2000

Abstract: Immune responses to exogenous antigens in infant experimental animals display various degrees of Th2 polarization. Preliminary evidence from small human studies suggest a similar age-dependent response pattern to vaccines, but detailed investigations on vaccine immunity during infancy have not yet been undertaken. We report below the results of a comprehensive prospective study on responses to the tetanus component of the diphtheria, tetanus, acellular pertussis (DTaP) vaccine in a cohort of 55 healthy children, employing peripheral blood mononuclear cells (PBMC) collected at the 2-, 4-, and 6-month vaccinations and at 12 months. Antigen-specific production of interleukin-4 (IL-4), IL-5, IL-6, IL-9, IL-10, IL-13, and gamma interferon (IFN-γ) was determined at each s le point, in parallel with polyclonal (phytohemagglutinin PHA-induced) cytokine responses. Our results indicate early and persistent Th2 responses to the vaccine, in contrast to a more delayed and transient pattern of IFN-γ production. This initial disparity between the Th1 and Th2 components of the vaccine response was mirrored by patterns of polyclonally induced cytokine production, suggesting that the delayed maturation of the Th1 component of the vaccine response during infancy is secondary to developmental processes occurring within the overall Th cell system.

A screening tool to identify risk for bronchiectasis progression in children with cystic fibrosis

Publisher: Wiley

Date: 12-10-2022

DOI: 10.1002/PPUL.25712

Abstract: The marked heterogeneity in cystic fibrosis (CF) disease complicates the selection of those most likely to benefit from existing or emergent treatments. We aimed to predict the progression of bronchiectasis in preschool children with CF. Using data collected up to 3 years of age, in the Australian Respiratory Early Surveillance Team for CF cohort study, clinical information, chest computed tomography (CT) scores, and biomarkers from bronchoalveolar lavage were assessed in a multivariable linear regression model as predictors for CT bronchiectasis at age 5–6. Follow‐up at 5–6 years was available in 171 children. Bronchiectasis prevalence at 5–6 was 134/171 (78%) and median bronchiectasis score was 3 (range 0–12). The internally validated multivariate model retained eight independent predictors accounting for 37% (adjusted R 2 ) of the variance in bronchiectasis score. The strongest predictors of future bronchiectasis were: pancreatic insufficiency, repeated intravenous treatment courses, recurrent lower respiratory infections in the first 3 years of life, and lower airway inflammation. Dichotomizing the resulting prediction score at a bronchiectasis score of above the median resulted in a diagnostic odds ratio of 13 (95% confidence interval [CI], 6.3–27) with positive and negative predictive values of 80% (95% CI, 72%–86%) and 77% (95% CI, 69%–83%), respectively. Early assessment of bronchiectasis risk in children with CF is feasible with reasonable precision at a group level, which can assist in high‐risk patient selection for interventional trials. The unexplained variability in disease progression at in idual patient levels remains high, limiting the use of this model as a clinical prediction tool.

Objective assessment of lung disease in wheezy infants: The time has come

Publisher: Wiley

Date: 2006

DOI: 10.1002/PPUL.20386

Policy decisions on endocrine disruptors should be based on science across disciplines: a response to Dietrich et al.

Publisher: Oxford University Press (OUP)

Date: 12-2013

DOI: 10.1530/EJE-13-0763

Monocytes from children with clinically stable cystic fibrosis show enhanced expression of toll-like receptor 4

Publisher: Wiley

Date: 17-08-2010

DOI: 10.1002/PPUL.21230

Abstract: Lung disease in patients with cystic fibrosis (CF) is characterized by recurrent bacterial respiratory infections and intense airway inflammation. Pattern recognition receptors such as Toll-like receptor 2 (TLR2) and TLR4 identify bacterial pathogens and activate the innate immune response. We therefore hypothesized that increased expression of these receptors would be found on circulating immune cells from children with CF. A cohort of 66 young children (median age 3 years) with CF was studied and compared to both healthy controls (n = 14) and children without CF who were being investigated for recurrent respiratory infections (non-CF disease controls n = 17) of a similar age. Surface expression of TLR2 and TLR4 on peripheral blood monocytes was analyzed using flow cytometry. TLR4 expression was significantly higher in patients with CF compared to healthy controls (P = 0.017) and non-CF disease controls (P = 0.025) but did not vary according to the presence or absence of pulmonary infection with Gram-negative or Gram-positive bacteria (P = 0.387) in the CF group. In contrast, TLR2 expression was similar across all three study groups (P = 0.930). The increased surface expression of TLR4 seen in young children with CF appears to be related to having CF per se and not related to current pulmonary infection.

Specific patterns of responsiveness to microbial antigens staphylococcal enterotoxin B and purified protein derivative by cord blood mononuclear cells are predictive of risk for development of atopic

Publisher: Wiley

Date: 04-2003

DOI: 10.1046/J.1365-2222.2003.01627.X

Abstract: Mononuclear cells from children with active atopic dermatitis (AD) have been reported to be hyper-responsive to certain microbial stimuli, in particular staphylococcal enterotoxin B (SEB). However, it is not known whether this responsiveness is acquired during disease development, or is inherent. We investigated this question in a cohort of children at high risk of atopy followed prospectively from birth to age 3 years. We asked whether their cord blood mononuclear cell (CBMC) cytokine responses to SEB, to an unrelated microbial stimulus purified protein derivative (PPD), or to common allergens, were predictive of risk for subsequent AD development during infancy. Children at high risk of developing atopy were randomly selected from an ongoing prospective cohort. Cord blood was collected at birth. The children were seen at 6 months, 1, 2 and 3 years and examined for the development of AD. IFN-gamma, IL-5, IL-10 and IL-13 production by CBMC cultured in the presence of SEB, PPD, PHA, house dust mite (HDM) allergen, ovalbumin (OVA) and cat allergen was determined. SEB-induced IL-5 production by CBMC was elevated in children who developed AD at 6 months (P = 0.01) and 2 years (P = 0.009). PPD-induced IL-5 responses were also elevated in CBMC from children who developed AD at 6 months, 2 years and 3 years (P = 0.05, P = 0.06 and P = 0.06, respectively), as were PPD-induced IL-10 responses (P = 0.05 at 1 years, P = 0.007 at 2 years, P = 0.003 at 3 years) and corresponding IFN-gamma responses (P = 0.05 at 6 months, P = 0.003 at 2 years, P = 0.0004 at 3 years). Increased IL-10 responses to HDM allergen were also observed throughout the observation period in CBMC from children who developed AD. Children who develop infantile AD appear to have a predisposition to respond to SEB in a Th2-dominant manner involving selective stimulation of IL-5 production. The increased IL-10 and IFN-gamma induced in response to PPD by children with AD may point to additional intrinsic differences in responses to microbial stimuli between those at high vs. those at low risk for AD, which merit more detailed investigations.

Environmental exposures: an underrecognized contribution to noncommunicable diseases

Publisher: Walter de Gruyter GmbH

Date: 2013

DOI: 10.1515/REVEH-2012-0033

High tidal volume ventilation in infant mice

Publisher: Elsevier BV

Date: 06-2008

DOI: 10.1016/J.RESP.2008.04.010

Abstract: Infant mice were ventilated with either high tidal volume (V(T)) with zero end-expiratory pressure (HVZ), high V(T) with positive end-expiratory pressure (PEEP) (HVP), or low V(T) with PEEP. Thoracic gas volume (TGV) was determined plethysmographically and low-frequency forced oscillations were used to measure the input impedance of the respiratory system. Inflammatory cells, total protein, and cytokines in bronchoalveolar lavage fluid (BALF) and interleukin-6 (IL-6) in serum were measured as markers of pulmonary and systemic inflammatory response, respectively. Coefficients of tissue d ing and tissue elastance increased in all ventilated mice, with the largest rise seen in the HVZ group where TGV rapidly decreased. BALF protein levels increased in the HVP group, whereas serum IL-6 rose in the HVZ group. PEEP keeps the lungs open, but provides high volumes to the entire lungs and induces lung injury. Compared to studies in adult and non-neonatal rodents, infant mice demonstrate a different response to similar ventilation strategies underscoring the need for age-specific animal models.

Extending the simple linear regression model to account for correlated responses: An introduction to generalized estimating equations and multi-level mixed modelling

Publisher: Wiley

Date: 15-06-1998

DOI: 10.1002/(SICI)1097-0258(19980615)17:11<1261::AID-SIM846>3.0.CO;2-Z

Abstract: Much of the research in epidemiology and clinical science is based upon longitudinal designs which involve repeated measurements of a variable of interest in each of a series of in iduals. Such designs can be very powerful, both statistically and scientifically, because they enable one to study changes within in idual subjects over time or under varied conditions. However, this power arises because the repeated measurements tend to be correlated with one another, and this must be taken into proper account at the time of analysis or misleading conclusions may result. Recent advances in statistical theory and in software development mean that studies based upon such designs can now be analysed more easily, in a valid yet flexible manner, using a variety of approaches which include the use of generalized estimating equations, and mixed models which incorporate random effects. This paper provides a particularly simple illustration of the use of these two approaches, taking as a practical ex le the analysis of a study which examined the response of portable peak expiratory flow meters to changes in true peak expiratory flow in 12 children with asthma. The paper takes the reader through the relevant practicalities of model fitting, interpretation and criticism and demonstrates that, in a simple case such as this, analyses based upon these model-based approaches produce reassuringly similar inferences to standard analyses based upon more conventional methods.

Adolescent peer aggression and its association with mental health and substance use in an Australian cohort

Publisher: Wiley

Date: 12-11-2013

DOI: 10.1016/J.ADOLESCENCE.2013.10.006

Abstract: Prospective longitudinal birth cohort data was used to examine the association between peer aggression at 14 years and mental health and substance use at 17 years. A s le of 1590 participants from the Western Australian Pregnancy Cohort (Raine) study were ided into mutually exclusive categories (victims, perpetrators, victim‐perpetrators and uninvolved). Involvement in any type of peer aggression as a victim (10.1%), perpetrator (21.4%), or a victim‐perpetrator (8.7%) was reported by 40.2% of participants. After adjusting for confounding factors, those who were a victim of peer aggression had increased odds of later depression and internalising symptoms whilst perpetrators of peer aggression were found to be at increased risk of depression and harmful alcohol use. Victim‐perpetrators of peer aggression were more likely to have externalising behaviours at 17 years. These results show an independent temporal relationship between peer aggression and later mental health and substance use problems in adolescence.

Genes related to lung growth and mucociliary function are altered by in utero exposure to arsenic via drinking water

Publisher: Elsevier BV

Date: 08-2011

DOI: 10.1016/J.TOXLET.2011.05.641

Ecological burden of e-waste in Bangladesh: participant’s characteristics and methods of cross-sectional assessment to measure the exposure to e-waste and associated health outcomes (Preprint)

Publisher: JMIR Publications Inc.

Date: 02-06-2022

DOI: 10.2196/PREPRINTS.38201

Abstract: lectronic waste (e-waste) is a rapidly growing waste stream worldwide, and Bangladesh is a hub of e-waste handling. Informal e-waste recycling operations involve crude methods for dismantling, repairing, sorting, and recycling electronic goods with bare hands and without personal health protections. Direct inhalation or dermal exposure to toxicants during informal recycle is common. Evidence suggests that e-waste derived toxicants pollute the terrestrial ecosystem and have been linked with adverse health effects. However, e-waste recycling-related occupational health hazards have not been adequately explored in the context of Bangladesh. ur study aims to expand the current understanding of exposure to e-waste. This study will measure the metal concentrations in biological and environmental s les and evaluate the relationship between heavy metals and the biochemical systems of the e-waste workers. he study employs a cross-sectional study design consisting of an exposed and a non-exposed control site. The trained team collected information on in idual exposures, detailed work/medical history, and collected biological s les (blood, urine, and hair) from each subject. This study will measure heavy metal levels (lead, cadmium, and mercury) and biochemical parameters (hematological, hormonal, renal, and others) from biological s les with reported physical function as outcomes of interest. In addition, we also collected soil and dust s les from both exposed and non-exposed control sites to measure the health risk. All the environmental s les will be analyzed using inductively coupled plasma mass spectrometer (ICP-MS) to determine metal concentrations. he protocol has been approved by the Institutional Review Boards of the International Centre for Diarrheal Disease Research, Bangladesh (icddr,b) and the University of Queensland’s (UQ) Human Behavioural Ethics Committee. Informed written consent was obtained from all participants. We recruited 199 workers from the e-waste sites with at least 5 years of exposure and 104 control subjects with no industrial or e-waste exposure. S le analysis is estimated to be completed in 2022. lthough many studies have identified potential adverse health outcomes from exposure to e-waste, there is a lack of published epidemiologic research in Bangladesh. Research in this field is particularly pressing in the context of the current e-waste trend and the need to deepen understanding of exposures and outcomes.

Evaluation of a novel anterior nasal swab for the detection of SARS-CoV-2

Publisher: Elsevier BV

Date: 06-2023

DOI: 10.1016/J.JVIROMET.2023.114713

Omega-3 Fatty Acid Supplementation During Pregnancy and Respiratory Symptoms in Children

Publisher: Elsevier BV

Date: 08-2014

DOI: 10.1378/CHEST.13-1432

Prevention of bronchoconstriction in sensitized guinea pigs: efficacy of common prophylactic drugs

Publisher: Elsevier BV

Date: 07-2004

DOI: 10.1016/J.RESP.2004.04.013

Environmental Contributions to the Leading Causes of Disease Burden Among Australian Children

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 05-2013

DOI: 10.1097/MPG.0B013E3182848A23

After asthma: redefining airways diseases

Publisher: Elsevier BV

Date: 2018

DOI: 10.1016/S0140-6736(17)30879-6

Application of a shortened inhaled adenosine-5′-monophosphate challenge in young children using the forced oscillation technique

Publisher: Elsevier BV

Date: 07-2009

DOI: 10.1378/CHEST.08-2848

Abstract: Adenosine-5'-monophosphate (AMP) is an indirect challenge agent thought to reflect allergic airway inflammation. The forced oscillation technique (FOT) is ideal for use in young children and is suitable for inhaled challenge studies in patients who are in this age group. We assessed the agreement between a shortened and a standard AMP challenge and the repeatability of the shortened AMP challenge using FOT as a primary outcome variable. Eighteen children completed a shortened and a standard AMP challenge, and 20 children completed repeated shortened AMP challenges. The children inhaled nebulized AMP tidally for 2 min, following which the presence of wheeze and pulse oximetric saturation (Spo(2)) was recorded prior to FOT measurement. Testing continued until the maximum dose was reached or until wheeze, a decrease in Spo(2) to < 90%, or an increase in respiratory resistance at 8 Hz of 2.0 hPa/s/L or 30% was noted. Concordance was assessed as a binary response, and agreement in provocation concentrations (PCs) causing a response was assessed with intraclass correlations. There was a high degree of concordance between the shortened and standard AMP protocols (94%) and repeated shortened AMP protocols (100%). The mean log(10) PCs displayed a high degree of agreement for both AMP protocols, with intraclass correlation coefficients of 0.94 (95% confidence interval, 0.85 to 0.98) and 0.94 (95% confidence interval, 0.82 to 0.98), respectively. We demonstrated that a shortened AMP challenge that can be applied to young children is comparable to the standard AMP challenge and is highly repeatable. Further studies in young children to assess the clinical role of a shortened AMP challenge using FOT are required.

Interactions between RSV Infection, Asthma, and Atopy

Publisher: Rockefeller University Press

Date: 18-11-2002

DOI: 10.1084/JEM.20021572

The Maternal Diet, Gut Bacteria, and Bacterial Metabolites during Pregnancy Influence Offspring Asthma

Publisher: Frontiers Media SA

Date: 31-03-2017

DOI: 10.3389/FIMMU.2017.00365

Longitudinal effects of prenatal exposure to plastic‐derived chemicals and their metabolites on asthma and lung function from childhood into adulthood

Publisher: Wiley

Date: 02-10-2023

DOI: 10.1111/RESP.14386

Abstract: Environmental exposure to phthalates and bisphenol A (BPA), chemicals used in the production of plastics, may increase risk for asthma and allergies. However, little is known about the long‐term effects of early life exposure to these compounds. We investigated if prenatal exposure to these compounds was associated with asthma, allergy and lung function outcomes from early childhood into adulthood in a cohort study. Maternal serum s les collected from 846 pregnant women in the Raine Study were assayed for BPA and phthalate metabolites. The children of these women were followed up at 5, 13 and 22 years where spirometry and respiratory questionnaires were conducted to determine asthma and allergy status. Lung function trajectories were derived from longitudinal spirometry measurements. Multinomial logistic regression and weighted quantile sum regression was used to test associations of in idual and chemical mixtures with asthma phenotypes and lung function trajectories. Effects of prenatal BPA and phthalates on asthma phenotypes were seen in male offspring, where BPA was associated with increased risk for persistent asthma, while mono‐iso‐butyl phthalate and mono‐iso‐decyl phthalate was associated with increased risk for adult asthma. Prenatal BPA had no effect on lung function trajectories, but prenatal phthalate exposure was associated with improved lung function. Prenatal BPA exposure was associated with increased likelihood of persistent asthma in males, while prenatal phthalate exposure was associated with increased likelihood of adult asthma in males. Results suggest that prenatal exposure to prenatal BPA and phthalates affect asthma risk, particularly in males, however lung function was not adversely affected.

Antenatal retinoic acid does not alter alveolization or postnatal lung function in preterm sheep

Publisher: European Respiratory Society (ERS)

Date: 07-2000

DOI: 10.1034/J.1399-3003.2000.16A18.X

Abstract: Retinoic acid exposure has been shown to promote surfactant production in foetal rats and to promote alveolization in neonatal rats. It was hypothesized that antenatal retinoic acid treatment would promote alveolization and accelerate functional maturation in the lungs of late gestation preterm sheep. Foetuses received a single i.m. injection of all-trans retinoic acid (RA, 20 mg x kg(-1)) or vehicle control at 115 days gestation (term=150 days) and were delivered at 125 days gestation. To examine the longer term effects of RA on alveolization a second group of animals received RA or vehicle at 121 days gestation and were delivered at 146 days gestation. Liver retinol levels at time of delivery were 2-3-fold higher in both preterm and near-term RA treated animals, indicating a significant impact of RA treatment on retinol metabolism. Dynamic compliance, gas exchange, lung gas volume and saturated phosphatidylcholine pool size at 125 days were unaffected by antenatal RA treatment. Alveolar volume, wall thickness and number at 125 or 146 days were also unaffected by RA treatment. Retinoic acid, as administered in this study, does not appear to accelerate structural or functional maturation of the foetal sheep lung. Response to retinoic acid may be species dependent, highlighting a need for caution when interpreting results from animal based studies.

Numerical modeling of post-collisional carbonated alkaline magmatism

Publisher: Elsevier BV

Date: 09-2020

DOI: 10.1016/J.SESCI.2020.05.002

Development of allergen-specific T-cell memory in atopic and normal children

Publisher: Elsevier BV

Date: 1999

DOI: 10.1016/S0140-6736(98)05104-6

Rhinovirus exacerbates house-dust-mite induced lung disease in adult mice

Publisher: Public Library of Science (PLoS)

Date: 14-03-2014

DOI: 10.1371/JOURNAL.PONE.0092163

Pressure flow characteristics of the valve in spacer devices.

Publisher: BMJ

Date: 09-1989

DOI: 10.1136/ADC.64.9.1305

Abstract: The valve system in the mouth piece of two spacer devices was analysed. Pressures required to open and close the non-rebreathing valve were very low (less than 0.1 kPa). Inspiratory flow requirements were within physiological limits for infants' normal tidal breathing. Expiratory flow requirements varied significantly, and the flow required to prevent rebreathing from the chamber may exceed the physiological flow limits for normal tidal breathing.

Prenatal adverse life events increase the risk for atopic diseases in children, which is enhanced in the absence of a maternal atopic predisposition

Publisher: Elsevier BV

Date: 07-2014

DOI: 10.1016/J.JACI.2014.01.033

Abstract: There is evidence to suggest an association between prenatal maternal stress and the development of asthma or other atopic diseases in offspring. Yet, insights on the lasting effect of multiple, common prenatal stressors are rare, and the effects of prenatal timing are poorly understood. Further, it remains elusive if prenatal life events modify the risk for atopic diseases in the context of a parental predisposition to atopy. We tested whether women's experiences of common, adverse life events during the first or second half of pregnancy predicted the risk of developing atopic diseases in their children and whether a reported parental atopic disease moderated this association. We calculated the odds of a child developing asthma, eczema, and/or allergic rhinitis at ages 6 or 14 years, depending on maternal prenatal exposure to negative life events in a s le of 1587 children from the Western Australian Pregnancy Cohort (Raine) Study by using multivariable logistic regression. We observed that the likelihood of asthma and eczema at age 14 years was significantly increased in children of mothers who had experienced adverse life events during the second half of gestation (1 life event: adjusted odds ratio for asthma, 2.08 [95% CI, 1.22-3.54]). A stronger increase in the odds to develop asthma upon prenatal life events was present in children of mothers without asthma compared with mothers with asthma. Maternal adverse life events during the second half of gestation are linked to an increased risk for the development of atopic disorders, asthma, and eczema, in the case of asthma, particularly in the absence of a maternal asthma.

Early identification of atopy in the prediction of persistent asthma in children

Publisher: Elsevier BV

Date: 09-2008

DOI: 10.1016/S0140-6736(08)61451-8

Influence of inertance on respiratory mechanics measurements in mechanically ventilated puppies

Publisher: Wiley

Date: 08-1999

DOI: 10.1002/(SICI)1099-0496(199908)28:2<130::AID-PPUL9>3.0.CO;2-X

Abstract: The complete equation of motion for a single compartment model (SCM) includes an inertance term to describe pressure changes in phase with acceleration, as well as terms for resistance and elastance. Inertance has traditionally been excluded from the model when measuring respiratory mechanics at conventional ventilatory frequencies in mature respiratory systems. However, this omission has been questioned recently for measurements of respiratory mechanics in intubated infants where higher ventilation frequencies and smaller tracheal tubes are the norm. We investigated 1) the significance of inertance in an immature respiratory system during mechanical ventilation, and 2) the effect of omitting it from the model on estimates of respiratory mechanics. Six anesthetised, paralysed and mechanically ventilated puppies (2.6-3.9 kg) were studied. A SCM, including an inertance term was fitted to measurements of flow and airway opening (P(AO)) or transpulmonary (P(TP)) pressure using multiple linear regression to estimate respiratory system and lung resistance (R(RS), R(L)), elastance (E(RS), E(L)) and inertance (I(RS), I(L)) respectively, at various ventilation frequencies (0.2-2 Hz). Data obtained at each ventilation frequency were also fitted with a similar model without the inertance term. Inertance contributed significantly to the model at frequencies greater than approximately 0.3-0.5 Hz (20-30 breaths per minute), with I(RS) dominated by the lung. The importance of including the inertance term in the model increased as ventilation frequency increased. Exclusion of inertance from the model led to underestimation of E(RS) and E(L), but no errors in estimates of R(RS) or R(L). The errors increased with ventilation frequency to approximately 10-20% for E(RS) and approximately 10-40% for E(L) at 2 Hz. While inertance contributed significantly to the SCM at ventilation frequencies typically required to maintain normal gas exchange in puppies, the errors from excluding this term were small: <3% for E(RS) and <9% for E(L).

From the Cradle to the Grave: The Early-Life Origins of Chronic Obstructive Pulmonary Disease

Publisher: American Thoracic Society

Date: 2016

DOI: 10.1164/RCCM.201509-1801ED

Clinical investigation of respiratory system admittance in preschool children

Publisher: Wiley

Date: 09-08-2012

DOI: 10.1002/PPUL.21515

Abstract: The upper airway shunt attenuates measurements of respiratory system impedance (Zrs), with greater impact in young children. Changes in respiratory system admittance, Ars (or Zrs(-1)), are theoretically independent of the shunt. This study compared the ability of Ars, to standard oscillatory outcomes, to determine respiratory disease and differentiate responses to inhaled bronchial challenges in the clinical setting. The forced oscillation technique (FOT) was used to establish reference equations for Ars in healthy preschool children, compare the change in Ars to standard oscillatory outcomes during bronchial challenge with inhaled adenosine-5'-monophosphate (AMP) and to inhaled bronchodilator in healthy children and those with respiratory disease. Children with respiratory disease had lower baseline Ars than healthy children (P < 0.05). However, there was no improved ability for Ars to differentiate between bronchodilator responses in healthy and disease populations. In contrast, the response to inhaled AMP occurred at a lower concentration, [25 (3.12-400) mg ml(-1) median (10th-90th centile)], as measured by Ars when compared to respiratory system resistance [225 (6.25-400) mg ml(-1) P = 0.016]. This study supports the use of Ars during inhaled challenges, but not in response to bronchodilation.

Interaction Between Adaptive and Innate Immune Pathways in the Pathogenesis of Atopic Asthma

Publisher: Elsevier BV

Date: 05-2011

DOI: 10.1378/CHEST.10-2397

Abstract: Atopic asthma is the most common form of asthma, particularly during childhood, and in many cases it persists into adult life. Although atopy is clearly a risk factor for development of this disease, only a small subset of subjects sensitized to aeroallergens express persistent symptoms, suggesting that additional pathogenic mechanisms are involved. Recent studies have implicated respiratory viral infections as key cofactors in asthma development in atopic patients. In relation to initial expression of the asthma phenotype in early childhood, it has been shown that although both atopic sensitization and early severe lower respiratory tract infections can operate as independent asthma risk factors, the persistence of asthma is most frequent among children who experience both insults, suggesting that the relevant inflammatory pathways interact to maximally drive disease pathogenesis. Importantly, it has been established that both these factors must be operative contemporaneously for these interactions to occur (ie, the interactions are likely to be direct). Recent studies on viral-induced asthma exacerbations in atopic children have provided a plausible mechanism for these interactions. Notably, it has been demonstrated that signals triggered during the innate immune response to the virus can lead to the release of large numbers of migrating high-affinity IgE receptor-bearing bone marrow-derived precursors of mucosal dendritic cells into the blood. The subsequent trafficking of these cells to the infected airway mucosa where dendritic cell turnover is very high provides a potential mechanism for recruitment of underlying aeroallergen-specific T-helper 2 immunity into the already inflamed milieu in the infected airway mucosa.

Lung function in African infants: A pilot study

Publisher: Wiley

Date: 11-12-2015

DOI: 10.1002/PPUL.22965

Policy Decisions on Endocrine Disruptors Should Be Based on Science across Disciplines: A Response to Dietrich et al.

Publisher: S. Karger AG

Date: 2013

DOI: 10.1159/000355668

Reciprocal patterns of allergen‐induced GATA‐3 expression in peripheral blood mononuclear cells from atopics vs. non‐atopics

Publisher: Wiley

Date: 2002

DOI: 10.1046/J.0022-0477.2001.01288.X

Abstract: T helper (Th)2 cytokines are considered to play a central role in the induction and expression of allergic disease. However, the relative importance of in idual cytokines is unclear, and overall disease pathogenesis appears to involve the coordinate activities of a range of Th2 cytokines acting in sequence or in parallel. The present study examines an alternative approach to the study of cytokine gene function in atopy, focusing instead upon T cell transcription factors (TFs) which play a role in the regulation of multiple cytokine genes. To investigate the allergen-induced expression of the TF GATA-3 and c-Maf in peripheral blood mononuclear cells (PBMCs) and in cytokine-driven Th polarization. PBMC from house dust mite (HDM)-atopic and non-atopics were stimulated in vitro with allergen or anti-CD3/IL-2. TF expression was analysed by semiquantitative RT-PCR and major findings were validated by real-time PCR. Cell separations were performed to analyse the contribution of CD45RO+ cells. CD4+ cord blood cells were Th1 or Th2 polarized in vitro by exogenous cytokines and TF expression analysed by Northern blot and real-time PCR. Results We demonstrate for the first time that during differentiation of CD4+ CD45RA+ naïve human T cells towards Th2 commitment, and during allergen-specific reactivation of peripheral CD4+ CD45RO+ Th2 memory cells in established atopics, expression of the Th2-associated TF GATA-3 is rapidly up-regulated, whereas T cells from non-atopics display equally rapid GATA-3 down-regulation under identical conditions of allergen stimulation. These findings identify Th2-associated TFs as key determinants of the atopic phenotype, suggesting their unique potential as therapeutic targets for disease control.

Children’s Health in Latin America: The Influence of Environmental Exposures

Publisher: Environmental Health Perspectives

Date: 03-2015

DOI: 10.1289/EHP.1408292

Height and weight fail to detect early signs of malnutrition in children with cystic fibrosis

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-2001

DOI: 10.1097/00005176-200109000-00017

Abstract: Many children with cystic fibrosis grow poorly and are malnourished. This study was undertaken to determine whether extensive anthropometry could detect early signs of malnutrition in prepubertal children with cystic fibrosis to prevent deficits in height and weight. Height, weight, six skin folds (triceps, subscapular, supraspinale, abdominal, front thigh, and medial calf) and five girths (arm relaxed, forearm, chest, thigh, and calf) were measured in a cross-sectional study of children aged 6 to 11 years with cystic fibrosis. The children with cystic fibrosis were shorter and lighter for their age and gender than those in the reference groups. The mean weight and height z scores for the girls with cystic fibrosis were lower than those for the boys, significantly so for z weight ( P < 0.05). Although, the mean percent ideal body weight value of 98.6% suggested that the children with cystic fibrosis were adequately nourished, most of the measures of muscularity and adiposity of the children with cystic fibrosis were significantly lower than those of the reference group ( P < 0.05). The z scores of the anthropometric measures revealed that the deficit in muscularity of the children with cystic fibrosis was relatively much greater than the deficit in adiposity. The percent ideal body weight index does not seem to be an adequate measure of nutritional status in children with cystic fibrosis. Anthropometric assessments should include skin-fold and circumference measurements of numerous sites on the upper and lower body, the trunk, and the limbs to detect deterioration in nutritional status early. Early detection of deficits in nutritional status may result in the adverse effects of malnutrition on height and weight, and possibly clinical status, being prevented.

Association Between Socioeconomic Status and the Development of Asthma: Analyses of Income Trajectories

Publisher: American Public Health Association

Date: 03-2010

DOI: 10.2105/AJPH.2008.150771

Abstract: Objectives. Using data on 2868 children born in the Western Australian Pregnancy Cohort (Raine) Study, we examined the association between changes in family socioeconomic status and childhood asthma. Methods. We determined the likelihood (odds ratio) of a child having asthma at ages 6 and 14 years for 4 family-income trajectories (chronic low, increasing, decreasing, and never low) over the child's lifetime. The trajectories were created from longitudinal latent-class models. Results. We found a 2-fold increased risk of asthma at age 14 years among children who had lived in a low-income family since birth, especially for girls. Asthma was less likely to occur in children born to single parents income rose over time in many of these families. Compared with children in chronic low-income families, children in households with increasing incomes had a 60% lower risk of asthma. Single-point measures of low income were not found to be associated with asthma. Conclusions. Chronic exposure to a low-income environment from birth was associated with the development of persistent asthma. There was also a protective effect against asthma among those children whose families had moved out of poverty.

Postnatal lung function in preterm lambs: Effects of a single exposure to betamethasome and thyroid hormones

Publisher: Elsevier BV

Date: 03-1995

DOI: 10.1016/0002-9378(95)90014-4

Abstract: We determined the effect of a single direct fetal injection of corticosteroid and thyroid hormones on postnatal pulmonary function in preterm lambs. Initially fetal sheep (126 days' gestation) randomly received saline solution, betamethasone (Celestone Soluspan, 0.5 mg/kg), betamethasone plus triiodothyronine (5 micrograms/kg), or betamethasone plus thyroxine (15 micrograms/kg) as a single injection. Forty-eight hours later (128 days' gestation) the fetuses were delivered and ventilated for 50 minutes. In a second protocol fetuses were delivered at 128 days' gestation, after only 24 hours of hormone exposure. Betamethasone treatment improved compliance nearly twofold after 24 or 48 hours of exposure. Efficiency of ventilation also improved after steroid therapy this effect was augmented 48 hours after thyroxine exposure (but not triiodothyronine). No thyroxine effect was noted after 24 hours of exposure. Maximal lung volume increased by 80% after steroid treatment and doubled in response to combination betamethasone and thyroxine therapy. Alveolar pool sizes of saturated phosphatidylcholine and surfactant protein A were comparable for all groups exposed for 48 hours. A single fetal exposure to betamethasone improves postnatal pulmonary function after 24 or 48 hours. Addition of thyroxine (but not triiodothyronine) augments this effect at 48 hours.

Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk for persistent airways hyper-responsiveness in experimental asthma

Publisher: Elsevier BV

Date: 05-2012

DOI: 10.1038/MI.2012.13

Abstract: A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial aeroallergens. We investigated underlying mechanisms in sensitized rats focusing on a strain expressing the high-allergen-responder phenotype characteristic of human atopic asthmatics, and find that their high susceptibility to aeroallergen-induced persistent AHR is associated with deficiencies in the immunoregulatory and mucosal trafficking properties of inducible T-regulatory cells (iTregs). Counterintuitively, AHR susceptibility was inversely related to aeroallergen exposure level, high exposures conferring protection. We demonstrate that underlying this AHR-susceptible phenotype is reduced capacity of airway mucosal dendritic cells (AMDCs) for allergen s ling in vivo this defect is microenvironmentally acquired, as allergen uptake by these cells in vitro is normal. Moreover, intranasal transfer of in vitro aeroallergen-loaded AMDC from naïve animals into AHR-susceptible animals during prolonged aerosol challenge markedly boosts subsequent accumulation of iTregs in the airway mucosa and rapidly resolves their chronic AHR, suggesting that compromised antigen surveillance by AMDC resulting in defective functional programming of iTreg may be causally related to AHR susceptibility.

Management of tuberculosis in children

Publisher: Wiley

Date: 12-2000

DOI: 10.1046/J.1440-1754.2000.00565.X

Abstract: This paper provides specific guidelines on the management of tuberculosis infection and disease, covering general principles, recommended drug regimens and discuss the evidence to support these. It also covers use of corticosteroids, intermittent therapy, directly observed therapy and an approach to the management of a patient with drug-resistant tuberculosis.

Policy Decisions on Endocrine Disruptors Should Be Based on Science Across Disciplines: A Response to Dietrich et al.

Publisher: The Endocrine Society

Date: 11-2013

DOI: 10.1210/EN.2013-1854

Bidirectional Interactions between Antigen-bearing Respiratory Tract Dendritic Cells (DCs) and T Cells Precede the Late Phase Reaction in Experimental Asthma

Publisher: Rockefeller University Press

Date: 30-06-2003

DOI: 10.1084/JEM.20021328

Abstract: The airway mucosal response to allergen in asthma involves influx of activated T helper type 2 cells and eosinophils, transient airflow obstruction, and airways hyperresponsiveness (AHR). The mechanism(s) underlying transient T cell activation during this inflammatory response is unclear. We present evidence that this response is regulated via bidirectional interactions between airway mucosal dendritic cells (AMDC) and T memory cells. After aerosol challenge, resident AMDC acquire antigen and rapidly mature into potent antigen-presenting cells (APCs) after cognate interactions with T memory cells. This process is restricted to dendritic cells (DCs) in the mucosae of the conducting airways, and is not seen in peripheral lung. Within 24 h, antigen-bearing mature DCs disappear from the airway wall, leaving in their wake activated interleukin 2R+ T cells and AHR. Antigen-bearing activated DCs appear in regional lymph nodes at 24 h, suggesting onward migration from the airway. Transient up-regulation of CD86 on AMDC accompanies this process, which can be reproduced by coculture of resting AMDC with T memory cells plus antigen. The APC activity of AMDC can be partially inhibited by anti-CD86, suggesting that CD86 may play an active role in this process and/or is a surrogate for other relevant costimulators. These findings provide a plausible model for local T cell activation at the lesional site in asthma, and for the transient nature of this inflammatory response.

High Tidal Volume Ventilation Is Not Deleterious in Infant Rats Exposed to Severe Hemorrhage

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 10-2010

DOI: 10.1097/TA.0B013E3181D7503C

Persistent activation of interlinked type 2 airway epithelial gene networks in sputum-derived cells from aeroallergen-sensitized symptomatic asthmatics

Publisher: Springer Science and Business Media LLC

Date: 24-01-2018

DOI: 10.1038/S41598-018-19837-6

Abstract: Atopic asthma is a persistent disease characterized by intermittent wheeze and progressive loss of lung function. The disease is thought to be driven primarily by chronic aeroallergen-induced type 2-associated inflammation. However, the vast majority of atopics do not develop asthma despite ongoing aeroallergen exposure, suggesting additional mechanisms operate in conjunction with type 2 immunity to drive asthma pathogenesis. We employed RNA-Seq profiling of sputum-derived cells to identify gene networks operative at baseline in house dust mite-sensitized (HDM S ) subjects with/without wheezing history that are characteristic of the ongoing asthmatic state. The expression of type 2 effectors (IL-5, IL-13) was equivalent in both cohorts of subjects. However, in HDM S -wheezers they were associated with upregulation of two coexpression modules comprising multiple type 2- and epithelial-associated genes. The first module was interlinked by the hubs EGFR, ERBB2, CDH1 and IL-13. The second module was associated with CDHR3 and mucociliary clearance genes. Our findings provide new insight into the molecular mechanisms operative at baseline in the airway mucosa in atopic asthmatics undergoing natural aeroallergen exposure, and suggest that susceptibility to asthma amongst these subjects involves complex interactions between type 2- and epithelial-associated gene networks, which are not operative in equivalently sensitized/exposed atopic non-asthmatics.

Using imprecise probabilities to address the questions of inference and decision in randomized clinical trials

Publisher: Wiley

Date: 05-2002

DOI: 10.1046/J.1365-2753.2002.00358.X

Abstract: Randomized controlled clinical trials play an important role in the development of new medical therapies. There is, however, an ethical issue surrounding the use of randomized treatment allocation when the patient is suffering from a life threatening condition and requires immediate treatment. Such patients can only benefit from the treatment they actually receive and not from the alternative therapy, even if it ultimately proves to be superior. We discuss a novel new way to analyse data from such clinical trials based on the use of the recently developed theory of imprecise probabilities. This work draws an explicit distinction between the related but nevertheless distinct questions of inference and decision in clinical trials. The traditional question of scientific interest asks 'Which treatment offers the greater chance of success?' and is the primary reason for conducting the clinical trial. The question of decision concerns the welfare of the patients in the clinical trial, asking whether the accumulated evidence favours one treatment over the other to such an extent that the next patient should decline randomization and instead express a preference for one treatment. Consideration of the decision question within the framework of imprecise probabilities leads to a mathematical definition of equipoise and a method for governing the randomization protocol of a clinical trial. This paper describes in detail the protocol for the conduct of clinical trials based on this new method of analysis, which is illustrated in a retrospective analysis of data from a clinical trial comparing the anti-emetic drugs ondansetron and droperidol in the treatment of postoperative nausea and vomiting. The proposed methodology is compared quantitatively using computer simulation studies with conventional clinical trial designs and is shown to maintain high statistical power with reduced s le sizes, at the expense of a high type I error rate that we argue is irrelevant in some specific circumstances. Particular emphasis is placed on describing the type of medical conditions and treatment comparisons where the new methodology is expected to provide the greatest benefit.

Pulmonary Function in a Hospital Population of Asthmatic Children

Publisher: Informa UK Limited

Date: 1991

DOI: 10.3109/02770909109073384

Abstract: Traditionally, assessment of control of pediatric asthma has relied on symptoms reported by the child and his or her family, and on clinical examination at office visits. A survey of the pulmonary function of 100 clinically stable asthmatic children, recruited from the outpatient clinics of the Royal Children's Hospital, Melbourne, Australia for a clinical drug trial was performed. Correlation of baseline pulmonary function with symptom scores recorded at home and home monitoring of peak expiratory flow variability (PEFV) found that a third of these clinically stable asthmatic children had an abnormal FEV1 and half had an abnormal FEF25-75 however, there was no correlation between symptom scores and FEV1 or PEFV. Objective measurements of pulmonary function are needed to ensure good asthma control. Home monitoring of peak expiratory flow can provide a valuable aid for the management of pediatric asthma.

Protecting the human fetus against effects of bisphenol A

Publisher: Elsevier BV

Date: 10-2013

DOI: 10.1016/S2213-8587(13)70105-0

Intrusion of Magmatic Bodies Into the Continental Crust

Publisher: American Geophysical Union (AGU)

Date: 03-2018

DOI: 10.1002/2017TC004738

Raised serum IgE associated with reduced responsiveness to DPT vaccination during infancy

Publisher: Elsevier BV

Date: 05-1998

DOI: 10.1016/S0140-6736(05)78871-1

Abstract: Previous studies examined the impact of parenting on adolescents' mobile phone addiction tendencies. However, relatively few studies examined the potential mechanism underlying such a relationship. Thus, the present study further explored the mediation effect of self-control and the moderating effect of future time perspective between parenting and mobile phone addiction tendencies of Chinese adolescents. A s le of 1,349 Chinese adolescents (

Th2 cytokines in the asthma late-phase response

Publisher: Elsevier BV

Date: 10-2007

DOI: 10.1016/S0140-6736(07)61587-6

Interpretation of urinary 8-oxo-7,8-dihydro-2′-deoxyguanosine is adversely affected by methodological inaccuracies when using a commercial ELISA

Publisher: Elsevier BV

Date: 06-2010

DOI: 10.1016/J.FREERADBIOMED.2010.02.017

Abstract: The DNA lesion 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a urinary marker of oxidative stress, is produced from reactions of reactive oxygen species with host DNA 2'-deoxyribonucleotides. The current gold-standard assessment is by complex chromatographic methods using HPLC or LC-MS/MS. Several studies have reported that commercial 8-oxodG ELISA kits correlate sufficiently with chromatographic techniques to be an easier alternative for laboratories without access to gold-standard techniques. However, the assumption that significant correlation translates into a similar ability to differentiate disease categories or treatment groups is yet to be tested. Using LC-MS/MS and two variants of a commercial ELISA, we measured urinary 8-oxodG and creatinine concentrations in young children with cystic fibrosis, a disease associated with oxidative stress, and age-matched controls. We show that, despite significant correlation, both ELISAs overestimate the levels of 8-oxodG, and neither ELISA accurately depicted the difference in group means that was observed by gold-standard LC-MS/MS. The implications of these findings for study outcomes add further support for chromatographic techniques, despite their cost and complexity, to remain the gold standard in urinary 8-oxodG assessment.

Monitoring of lung volume recruitment and derecruitment using oscillatory mechanics during high-frequency oscillatory ventilation in the preterm lamb

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 03-2004

DOI: 10.1097/01.PCC.0000113263.93347.F1

Abstract: To determine whether the low-frequency forced oscillation technique (LFOT) can track changes in lung mechanics resulting from prophylactic intratracheal surfactant and a volume recruitment-derecruitment maneuver during high-frequency oscillatory ventilation (HFOV) and how this relates to the d ing of the tracheal pressure waveform (P(tr)). Interventional laboratory study. Rural animal research facility in Western Australia. Sedated newborn preterm lambs. Two separate studies were performed. Study 1 involved a volume recruitment-derecruitment maneuver during HFOV using stepwise changes (4 cm H(2)O) in mean airway opening pressure (P(ao), n = 5). Study 2 involved instillation of 4 mL/kg fetal lung fluid (n = 5) or exogenous surfactant (n = 8) at birth and subsequent intermittent mandatory ventilation for 40 mins. Arterial blood gases were recorded every 10 mins and ventilation was appropriately adjusted to achieve moderate hypercarbia (Paco(2), 50-60 mm Hg). Lung mechanics were measured using LFOT 10 mins following each adjustment in P(ao) in parallel with measurements of P(tr) and tidal volume (study 1) or after 40 mins (study 2). Both the recruitment-derecruitment maneuver and prophylactic surfactant administration achieved similar improvements (decrease) in tissue impedance (Z(ti)). The coefficient of tissue resistance (G) decreased more than the coefficient of tissue elastance (H), consistent with improved homogeneity of the lung tissue compartment as lung volume was recruited. Minimum Z(ti) coincided with minimum tracheal pressure litude (DeltaP(tr)) on the deflation limb of the volume recruitment-derecruitment maneuver during HFOV. There was a linear relationship between DeltaP(tr) and H. In the preterm lamb, the LFOT can successfully detect changes in lung mechanics resulting from volume recruitment maneuvers during both HFOV and ventilation at conventional rates and may provide information on ventilation inhomogeneity. Minimization of Z(ti) is crucial to d ing of P(tr) and may limit potential barotrauma to proximal alveolar units during establishment of HFOV.

Effect of valve closure time on the determination of respiratory resistance by flow interruption

Publisher: Springer Science and Business Media LLC

Date: 03-1987

DOI: 10.1007/BF02442841

Abstract: DR (dietary restriction), or reduced food intake without malnutrition, is associated with extended longevity, improved metabolic fitness and increased stress resistance in a wide range of organisms. DR is often referred to as calorie restriction, implying that reduced energy intake is responsible for its widespread and evolutionarily conserved benefits. However, recent data indicate dietary amino acid restriction as a key mediator of DR benefits. In fruitflies, an imbalance in essential amino acid intake is thought to underlie longevity benefits of DR. In mammals, reduced dietary protein or essential amino acid intake can extend longevity, improve metabolic fitness and increase stress resistance. In the present paper we review two evolutionarily conserved signal transduction pathways responsible for sensing amino acid levels. The eIF2α (eukaryotic initiation factor 2α) kinase GCN2 (general amino acid control non-derepressible 2) senses the absence of one or more amino acids by virtue of direct binding to uncharged cognate tRNAs. The presence of certain amino acids, such as leucine, permits activation of the master growth regulating kinase TOR (target of rapamycin). These two signal transduction pathways react to amino acid deprivation by inhibiting general protein translation while at the same time increasing translation of specific mRNAs involved in restoring homoeostasis. Together, these pathways may contribute to the regulation of longevity, metabolic fitness and stress resistance.

General method for describing and extrapolating monotonic transients and its application to respiratory mechanics

Publisher: Springer Science and Business Media LLC

Date: 03-1987

DOI: 10.1007/BF02442840

Abstract: Dairy and meat consumption may impact breast cancer risk through modification of hormones (e.g., estrogen), through specific nutrients (e.g., vitamin D), or through products formed in processing/cooking (e.g., heterocyclic amines). Results relating meat and dairy intake to breast cancer risk have been conflicting. Thus, we examined the risk of breast cancer in relation to intake of dairy and meat in a large prospective cohort study. In the Black Women's Health Study, 1,268 incident breast cancer cases were identified among 52,062 women during 12 years of follow-up. Multivariable (MV) relative risks (RRs) and 95 % confidence intervals (CIs) were calculated using Cox proportional hazards models. Null associations were observed for total milk (MV RR = 1.05, 95 % CI 0.74-1.46 comparing ≥1,000-0 g/week) and total meat (MV RR = 1.04, 95 % CI 0.85-1.28 comparing ≥1,000 < 400 g/week) intake and risk of breast cancer. Associations with intakes of specific types of dairy, specific types of meat, and dietary calcium and vitamin D were also null. The associations were not modified by reproductive (e.g., parity) or lifestyle factors (e.g., smoking). Associations with estrogen receptor (ER) positive (+), ER negative (-), progesterone receptor (PR) +, PR-, ER+/PR+, and ER-/PR- breast cancer were generally null. This analysis of African-American women provides little support for associations of dairy and meat intake with breast cancer risk.

Phase 2 Evaluation of Parainfluenza Type 3 Cold Passage Mutant 45 Live Attenuated Vaccine in Healthy Children 6–18 Months Old

Publisher: Oxford University Press (OUP)

Date: 02-2004

DOI: 10.1086/381184

Abstract: A phase 2 evaluation of live attenuated parainfluenza type 3 (PIV3)-cold passage mutant 45 (cp45) vaccine was conducted in 380 children 6-18 months old 226 children (59%) were seronegative for PIV3. Of the 226 seronegative children, 114 received PIV3-cp45 vaccine, and 112 received placebo. No significant difference in the occurrence of adverse events (i.e., runny nose, cough, or temperature > or =38 degrees C) was noted during the 14 days after vaccination. There was no difference between groups in the occurrence of acute otitis media or serous otitis media. Paired serum s les were available for 109 of the seronegative vaccine recipients and for 110 of the seronegative placebo recipients 84% of seronegative vaccine recipients developed a > or =4-fold increase in antibody titers. The geometric mean antibody titer after vaccination was 1 : 25 in the vaccine group and <1 : 4 in the placebo group. PIV3-cp45 vaccine was safe and immunogenic in seronegative children and should be evaluated for efficacy in a phase 3 field trial.

Bronchiectasis in Infants and Preschool Children Diagnosed with Cystic Fibrosis after Newborn Screening

Publisher: Elsevier BV

Date: 11-2009

DOI: 10.1016/J.JPEDS.2009.05.005

Abstract: To determine the prevalence of bronchiectasis in young children with cystic fibrosis (CF) diagnosed after newborn screening (NBS) and the relationship of bronchiectasis to pulmonary inflammation and infection. Children were diagnosed with CF after NBS. Computed tomography and bronchoalveolar lavage were performed with anesthesia (n = 96). Scans were analyzed for the presence and extent of abnormalities. The prevalence of bronchiectasis was 22% and increased with age (P = .001). Factors associated with bronchiectasis included absolute neutrophil count (P = .03), neutrophil elastase concentration (P = .001), and Pseudomonas aeruginosa infection (P = .03). Pulmonary abnormalities are common in infants and young children with CF and relate to neutrophilic inflammation and infection with P. aeruginosa. Current models of care for infants with CF fail to prevent respiratory sequelae. Bronchiectasis is a clinically relevant endpoint that could be used for intervention trials that commence soon after CF is diagnosed after NBS.

Defective Respiratory Tract Immune Surveillance in Asthma

Publisher: Elsevier BV

Date: 02-2014

DOI: 10.1378/CHEST.13-1341

Abstract: The relative importance of respiratory viral infections vs inhalant allergy in asthma pathogenesis is the subject of ongoing debate. Emerging data from long-term prospective birth cohorts are bringing increasing clarity to this issue, in particular through the demonstration that while both of these factors can contribute independently to asthma initiation and progression, their effects are strongest when they act in synergy to drive cycles of episodic airways inflammation. An important question is whether susceptibility to infection and allergic sensitization in children with asthma arises from common or shared defect(s). We argue here that susceptibility to recurrent respiratory viral infections, failure to generate protective immunologic tolerance to aeroallergens, and ultimately the synergistic interactions between inflammatory pathways triggered by concomitant responses to these agents all result primarily from functional deficiencies within the cells responsible for local surveillance for antigens impinging on airway surfaces: the respiratory mucosal dendritic cell (DC) network. The effects of these defects in DCs from children wtih asthma are accentuated by parallel attenuation of innate immune functions in adjacent airway epithelial cells that reduce their resistance to the upper respiratory viral infections, which are the harbingers of subsequent inflammatory events at asthma lesion site(s) in the lower airways. An important common factor underpinning the innate immune functions of these unrelated cell types is use of an overlapping series of pattern recognition receptors (exemplified by the Toll-like receptor family), and variations in the highly polymorphic genes encoding these receptors and related molecules in downstream signaling pathways appear likely contributors to these shared defects. Findings implicating recurrent respiratory infections in adult-onset asthma, much of which is nonatopic, suggest a similar role for deficient immune surveillance in this phenotype of the disease.

How children with asthma breathe: have we been overlooking a problem?

Publisher: European Respiratory Society (ERS)

Date: 30-04-2013

DOI: 10.1183/09031936.00204412

Standards for infant respiratory function testing:what(ever) next?

Publisher: European Respiratory Society (ERS)

Date: 10-2000

DOI: 10.1034/J.1399-3003.2000.16D01.X

Prevention of Methacholine-induced Changes in Respiratory Mechanics in Piglets

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 09-1997

DOI: 10.1097/00000542-199709000-00019

Abstract: Sevoflurane is a new volatile anesthetic agent that may be a useful alternative to halothane for anesthesia in children. However, there is insufficient information about its effects on respiratory mechanics, particularly in the presence of constrictor stimuli. Eighteen piglets had anesthesia induced and maintained with either pentobarbital (control: n = 8), 1 minimum alveolar concentration (MAC) sevoflurane (sevo: n = 5), or 1 MAC halothane (halo: n = 5). Pressure, flow, and volume were measured at the airway opening and used to calculate lung compliance (C(L)) and resistance (R(L)). Resistance was partitioned into airway (Raw) and parenchymal (Vti) components using alveolar pressure. Methacholine was infused intravenously in a dose sufficient (15 microg x kg(-1) x h(-1)) to approximately double R(L). The increase in R(L) seen in the control group was almost entirely due to an increase in Vti. Sevoflurane and halothane prevented the increase in R(L) and Vti (both P & 0.02) and the decrease in C(L) (both P & 0.02). Sevoflurane and halothane can prevent methacholine-induced changes in lung function.

Maternal asthma is associated with reduced lung function in male infants in a combined analysis of the BLT and BILD cohorts

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.

Cystic fibrosis pathogens survive for extended periods within cough-generated droplet nuclei.

Publisher: BMJ

Date: 07-04-2018

DOI: 10.1136/THORAXJNL-2018-211567

Abstract: The airborne route is a potential pathway in the person-to-person transmission of bacterial strains among cystic fibrosis (CF) populations. In this cross-sectional study, we investigate the physical properties and survival of common non- Pseudomonas aeruginosa CF pathogens generated during coughing. We conclude that Gram-negative bacteria and Staphylococcus aureus are aerosolised during coughing, can travel up to 4 m and remain viable within droplet nuclei for up to 45 min. These results suggest that airborne person-to-person transmission is plausible for the CF pathogens we measured.

Virus infection and allergy in the development of asthma

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-2012

DOI: 10.1097/ACI.0B013E3283520166

Exacerbation of chronic cigarette-smoke induced lung disease by rhinovirus in mice

Publisher: Elsevier BV

Date: 04-2022

DOI: 10.1016/J.RESP.2022.103846

Abstract: A significant proportion of chronic obstructive pulmonary disease exacerbations are strongly associated with rhinovirus infection (HRV). In this study, we combined long-term cigarette smoke exposure with HRV infection in a mouse model. Our aim was to better understand the effects of HRV infection on such exacerbations, using a realistic method for generating a COPD-like phenotype. After 12-weeks of cigarette smoke exposure, adult female BALB/c mice were infected with HRV-1A and three days later we assessed a range of outcomes including lung volume and function, collected lung tissue for measurement of viral titre, bronchoalveolar lavage for assessment of pulmonary inflammation and levels of key mediators, and fixed lungs for stereological structural analyses. Cigarette smoke exposure alone significantly increased total cells and macrophages, and reduced MIP-2 in bronchoalveolar lavage. HRV-1A infection alone increased neutrophilic inflammation, IP-10 and total protein in lavage and also increased specific airway resistance measured at functional residual capacity. Cigarette smoke and HRV-1A together impacted various lung structural parameters including increasing stereological lung volume. Our results show that long-term cigarette smoke exposure and HRV-1A infection both in idually impact respiratory outcomes and combine to alter aspects of lung structure in a mouse model, thus providing insight into the development of future mechanistic studies and appropriate interventions in human disease.

Risk factors for bronchiectasis in children with cystic fibrosis

Publisher: Massachusetts Medical Society

Date: 23-05-2013

DOI: 10.1056/NEJMOA1301725

Changes in urinary glutathione sulfonamide (GSA) levels between admission and discharge of patients with cystic fibrosis

Publisher: Cold Spring Harbor Laboratory

Date: 25-10-2023

DOI: 10.1101/2023.10.24.23297497

Original article: Predictors of response to bronchial allergen challenge in 5‐ to 6‐year‐old atopic children

Publisher: Wiley

Date: 12-03-2007

DOI: 10.1111/J.1398-9995.2007.01329.X

Abstract: The relationship between atopy and bronchial allergy in young children is not completely understood. To examine the association between response to bronchial allergen challenge, immune markers of atopy and other clinical characteristics in 5- to 6-year-old children. Children with positive skin test (SPT) to aeroallergen, together with a proportion of SPT negative children (as controls), were recruited from a birth cohort of 198 children at high risk of developing atopic disease and underwent allergen challenge. Thirty-seven children (26 atopic and 11 SPT negative), median age 74.5 months, were challenged: 31 with house dust mite and six with grass allergen. Only atopic children responded to challenge: n = 12/26 (46%). Wheal size [odds ratio (OR) 2.5 (1.2-5.3), P = 0.01], allergen-specific immunoglobulin E (IgE) [OR 3.4 (1.23-9.61), P = 0.02], total IgE [OR 8.6 (1.1-68.7), P = 0.04], current wheeze [OR 12 (1.7-81.7), P = 0.006] and persistent eczema [OR 11.0 (1.7-68.3), P = 0.006] emerged as the strongest independent predictors of response to allergen challenge. Prediction of response to allergen challenge was significantly improved when immune markers of atopy, and in particular wheal size, were combined with clinical characteristics. The relationship between atopy and bronchial allergy is quantitative at this age. There may be potential to create more powerful indicators of the presence of respiratory allergy in young children when immunological markers of atopy are considered quantitatively and when combined with clinical history of coexistent allergic disease.

Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy

Publisher: BMJ

Date: 07-05-2014

DOI: 10.1136/THORAXJNL-2013-204908

Access to highly specialized growth substrates and production of epithelial immunomodulatory metabolites determine survival of Haemophilus influenzae in human airway epithelial cells

Publisher: Public Library of Science (PLoS)

Date: 27-01-2022

DOI: 10.1371/JOURNAL.PPAT.1010209

Abstract: Haemophilus influenzae (Hi) infections are associated with recurring acute exacerbations of chronic respiratory diseases in children and adults including otitis media, pneumonia, chronic obstructive pulmonary disease and asthma. Here, we show that persistence and recurrence of Hi infections are closely linked to Hi metabolic properties, where preferred growth substrates are aligned to the metabolome of human airway epithelial surfaces and include lactate, pentoses, and nucleosides, but not glucose that is typically used for studies of Hi growth in vitro . Enzymatic and physiological investigations revealed that utilization of lactate, the preferred Hi carbon source, required the LldD L-lactate dehydrogenase (conservation: 98.8% of strains), but not the two redox-balancing D-lactate dehydrogenases Dld and LdhA. Utilization of preferred substrates was directly linked to Hi infection and persistence. When unable to utilize L-lactate or forced to rely on salvaged guanine, Hi showed reduced extra- and intra-cellular persistence in a murine model of lung infection and in primary normal human nasal epithelia, with up to 3000-fold attenuation observed in competitive infections. In contrast, D-lactate dehydrogenase mutants only showed a very slight reduction compared to the wild-type strain. Interestingly, acetate, the major Hi metabolic end-product, had anti-inflammatory effects on cultured human tissue cells in the presence of live but not heat-killed Hi, suggesting that metabolic endproducts also influence HI-host interactions. Our work provides significant new insights into the critical role of metabolism for Hi persistence in contact with host cells and reveals for the first time the immunomodulatory potential of Hi metabolites.

Consequences of bullying victimization in childhood and adolescence: A systematic review and meta-analysis

Publisher: Baishideng Publishing Group Inc.

Date: 2017

DOI: 10.5498/WJP.V7.I1.60

Polybrominated diphenyl ether flame retardant concentrations in faeces from young children in Queensland, Australia and associations with environmental and behavioural factors

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1016/J.ENVRES.2017.07.022

Abstract: The aim of our study was to investigate children's exposure to the flame retardants polybrominated diphenyl ethers (PBDEs) by analysing faecal content, a non-invasive matrix, as well as responses to an exposure-assessment questionnaire. A convenience s le of 61 parents with children (aged >3 months to 80% s les above the limit of detection (LOD). BDE-47 (0.23ng/g dw) and BDE-153 (0.03ng/g dw) were each detected above the LOD in approximately 60% of s les. Age was associated with BDE-47 (-7%/month) and BDE-153 (-12%/month) concentrations in faeces, but not BDE-209. Other variables associated with PBDE concentrations included features of the home (carpet, pets) and behaviour (hand-to-mouth, removing shoes, using a car sunshade, frequency of walks outdoors). However, given the small s le size of this study additional research is required to confirm these findings. In this study we demonstrated that faeces may be a viable alternative to monitor human exposure to PBDEs, but further validation studies are required.

Plasmacytoid dendritic cells during infancy are inversely associated with childhood respiratory tract infections and wheezing

Publisher: Elsevier BV

Date: 10-2009

DOI: 10.1016/J.JACI.2009.07.009

Abstract: It has been proposed that immune dysfunction during early childhood plays an important role in asthma pathogenesis. However, it is not known specifically whether changes in dendritic cells (DCs) during infancy antedate the development of respiratory tract infections, asthma, and related clinical phenotypes. We sought to assess the association between the level of blood DCs during the first year and the subsequent development of respiratory tract infections, wheezing, and allergic sensitization. A community-based cohort of children with a family history of atopy was followed to age 5 years. Children were monitored intensively for respiratory tract infections. History of wheeze and asthma was collected annually, atopy was documented at 5 years, and flow cytometry was used to identify DC subsets in blood s les collected when children were well. Levels of plasmacytoid DCs (pDCs) during infancy were inversely correlated with symptoms of lower respiratory tract infections, parent-reported wheezing, and the cumulative rate of physician-diagnosed asthma up to age 5 years. These relationships were independent of atopy, as determined by allergy skin test results and total and specific IgE levels. In contrast, levels of myeloid DCs were not associated with respiratory tract infections, asthma, or wheezing but were associated with total IgE levels at age 5 years. In children with a family history of atopy, relative deficiency of circulating pDCs during infancy appears to be a risk factor for more frequent and more severe respiratory tract infections, wheezing, and a diagnosis of asthma. Infants with higher numbers of pDCs are protected against these outcomes.

Pollution, climate change, and childhood asthma in Australia

Publisher: AMPCo

Date: 04-2018

DOI: 10.5694/MJA17.01145

Accumulation mode particles and LPS exposure induce TLR-4 dependent and independent inflammatory responses in the lung

Publisher: Springer Science and Business Media LLC

Date: 22-01-2018

DOI: 10.1186/S12931-017-0701-Z

The Impact of Oral Premedication with Midazolam on Respiratory Function in Children

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 06-2009

DOI: 10.1213/ANE.0B013E3181A324C3

Abstract: Premedication with midazolam is commonly used in children to reduce anxiety and improve cooperation before anesthesia. However, it has the potential to alter respiratory function because of its muscle relaxant properties. We assessed functional residual capacity (FRC), ventilation homogeneity, using a lung clearance index (LCI), and respiratory mechanics in children awake and 20 min after oral premedication with midazolam (0.3 mg/kg). FRC and LCI were measured using a SF(6) multibreath washout technique while respiratory resistance and elastance were extracted from the input impedance obtained by forced oscillation technique in 18 children (3-8 yr) before and after oral premedication with midazolam. Premedication led to a small (6.5%) but statistically significant decrease in group mean FRC from 25.0 (SD 1.4) to 23.4 (1.9) mL/kg and an associated increase in LCI by 7.8% from 6.4 (0.4) to 6.9 (0.4), indicating increased ventilation inhomogeneities. Furthermore, midazolam resulted in a statistically significant increase in respiratory resistance by 7.4% from 3.38 (0.6) to 3.62 (0.6) cm H(2)O s/L (P < 0.001) and in respiratory elastance by 9.2% from 48.8 to 52.9 cm H(2)O s/L (P < 0.001). The changes in FRC, LCI, resistance and elastance were significantly correlated (P < 0.001). In children with normal lungs, premedication with a relatively small-dose of midazolam led to mild changes in respiratory variables shortly after its administration. However, the anesthesiologist should be aware that using midazolam in children at high risk of respiratory complications under anesthesia might lead to a greater decrease in respiratory function.

Airway resistance: synonyms, surrogates, and precision

Publisher: American Physiological Society

Date: 03-2011

DOI: 10.1152/AJPLUNG.00410.2010

Lung Function, Bronchial Responsiveness, and Asthma in a Community Cohort of 6-Year-Old Children

Publisher: American Thoracic Society

Date: 04-2004

DOI: 10.1164/RCCM.200304-556OC

Chest MRI in patients with cystic fibrosis: a radiation-free method Response

Publisher: BMJ

Date: 16-10-2013

DOI: 10.1136/THORAXJNL-2012-202670

Elemental carbon exposure and lung function in schoolchildren from Mexico City

Publisher: European Respiratory Society (ERS)

Date: 10-02-2011

DOI: 10.1183/09031936.00111410

Abstract: Though exposure to air pollution has a detrimental effect on respiratory health, few studies have examined the association between elemental carbon exposure and lung function among schoolchildren. The aim of the present study was to present the association between short-term elemental carbon exposure and lung function in schoolchildren from Mexico City. 55 asthmatic and 40 non-asthmatic children were followed for an average of 22 weeks. A spirometry test was performed every 15 days during follow-up. Portable air s lers collected particulate matter onto Teflon filters. Gravimetric analysis was conducted and elemental carbon was quantified using transmission densitometry. The association between the main variables was analysed using linear mixed effects models. The mean ± sd of elemental carbon light absorption was 92.7 ± 54.7 Mm(-1). An increase of one interquartile range in the 24-h average of elemental carbon (100.93 Mm(-1)) was associated with a significant negative impact on forced expiratory volume in 1 s (FEV(1)) (-62.0 (95% CI -123.3- -1.2) mL) and forced expiratory flow at 25-75% of forced vital capacity (FVC) (FEF(25-75%)) (-111 (95% CI -228.3- -4.1) mL) among asthmatic children, equal to 3.3% and 5.5%, respectively and on FEV(1) (-95.0 (95% CI -182.3- -8.5) mL) and FVC (-105.0 (95% CI -197.0- -13.7) mL) among non-asthmatic children. Exposure to elemental carbon resulted in an important negative effect on lung function in atopic schoolchildren, regardless of asthma status.

New and future developments of therapy for asthma in children

Publisher: European Respiratory Society

Date: 06-2012

DOI: 10.1183/1025448X.10018310

Environmental effects on pulmonary mechanics and the response to inhaled methacholine

Publisher: Wiley

Date: 05-1998

DOI: 10.1002/(SICI)1099-0496(199805)25:5<332::AID-PPUL7>3.0.CO;2-K

Abstract: To investigate the role of environmental exposure from birth on airway and lung parenchymal responsiveness to inhaled methacholine (Mch), three litters of puppies (n = 14) were studied when 8-10 weeks of age. Two litters, one mongrel (n = 7) and one foxhound-beagle cross (n = 3), were born and raised in a clean animal house environment (clean mongrels and clean cross, respectively). Another litter of mongrels was born (n = 4) and raised in an external environment (external mongrels), exposed to normal rural environmental contaminants. Animals were studied open-chested with alveolar capsules used to partition mechanics into airway and parenchymal components. Lung mechanics were measured after abrupt flow interruptions. The animals born and raised in the external environment were significantly more responsive to inhaled Mch than those born and raised in the clean environment. This finding was true for both airway and parenchymal responsiveness. The group mean effective dose of Mch that produced a doubling of airway resistance (ED200Raw) for the external mongrel group was 4.40 mg/ml compared with 19.44 mg/ml for the clean mongrel group and 16.34 mg/ml for the clean cross group (P < 0.02). The group mean effective dose of Mch that produced a doubling of pressure difference in airways after the initial rapid rise in airway pressure (ED200Pdif) for the external mongrel group was 0.79 mg/ml compared with 3.90 mg/ml for the clean mongrel group and 10.78 mg/ml for the clean cross group (P < 0.01). Generalized linear modeling analysis showed that both "environment" and "breed" were significant factors in determining ED200Pdif, but only "environment" significantly influenced ED200Raw. In summary, the present study has demonstrated that the environment in which an animal is born and raised can influence lung mechanics and responsiveness to methacholine. This finding is particularly true for the lung parenchyma.

Defining healthy' in preschool-aged children for forced oscillation technique reference equations

Publisher: Wiley

Date: 05-10-2018

DOI: 10.1111/RESP.13186

Abstract: Selecting 'healthy' preschool-aged children for reference ranges may not be straightforward. Relaxing inclusion criteria for normative data does not affect spirometry z-scores. We therefore investigated the effect of similarly relaxing inclusion criteria in preschoolers on reference ranges for respiratory impedance (Zrs) using a modified forced oscillation technique (FOT). The International Study of Asthma and Allergies in Childhood questionnaire classified 585 children into a healthy and five mutually exclusive groups. Zrs was measured between 4 and 26 Hz and resistance (R) and compliance (C) obtained by model fitting. Prediction models were determined using mixed effect models and z-scores compared between healthy children and the five groups. Zrs data were obtained for 494 participants (4.30 ± 0.7 years) on 587 occasions. Comparison of the Zrs z-scores between the healthy children and the health groups found significant differences in children with asthma, current wheeze and respiratory symptoms, but not in children born preterm or with early-life wheeze. Adding these two groups to the healthy dataset had no significant effect on the distribution of z-scores and increased the size of the dataset by 22.3%. Our data suggest that preschool-aged children born preterm or with early-life wheeze can be included in FOT reference equations, while those with asthma, current wheeze and respiratory symptoms within 4 weeks of testing should be excluded. This more inclusive approach results in more robust FOT reference ranges.

Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis

Publisher: Elsevier BV

Date: 15-11-2010

DOI: 10.1016/J.FREERADBIOMED.2010.07.010

Abstract: We aimed to determine whether myeloperoxidase (MPO) is the main peroxidase present in the airways of children with cystic fibrosis (CF) and to assess which oxidants it produces and whether they are associated with clinical features of CF. Children with CF (n=54) and without CF (n=16) underwent bronchoscopy and bronchoalveolar lavage (BAL) for assessment of pulmonary infection and inflammation. BAL fluid was analyzed for MPO, halogenated tyrosines as markers of hypohalous acids, thiocyanate, and protein carbonyls. MPO was the only peroxidase detected in BAL s les from children with CF and its concentration was markedly higher than in controls. Levels of 3-chlorotyrosine and 3-bromotyrosine in proteins were higher in the CF group. They correlated with neutrophils and MPO. The concentration of thiocyanate in BAL s les was below 1μM. Protein carbonyl levels correlated with MPO and halogenated tyrosines in patients with CF. Levels of MPO and halogenated tyrosines were higher in children with infections, especially Pseudomonas aeruginosa, and in the presence of respiratory symptoms. They also correlated with the Kanga clinical score. Our findings suggest that MPO produces hypobromous acid as well as hypochlorous acid in the airways of children with CF and that these oxidants are involved in the early pathogenesis of CF.

Role of innate immunity in the development of allergy and asthma

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 04-2011

DOI: 10.1097/ACI.0B013E32834487C6

Genetic polymorphism of KIR2DL4 (CD158d), a putative NK cell receptor for HLA-G, does not influence susceptibility to asthma

Publisher: Wiley

Date: 23-08-2013

DOI: 10.1111/TAN.12185

Abstract: Human leukocyte antigen (HLA)-G is upregulated on the bronchial epithelium of asthma patients and genetic polymorphism affecting expression of HLA-G has been reported to influence susceptibility to asthma. As the NK cell receptor KIR2DL4 has been reported to induce interferon gamma (IFNγ) secretion when ligated with HLA-G, we postulated that the 9A/10A genetic polymorphism of KIR2DL4 which influences receptor structure may influence susceptibility to asthma. KIR2DL4 genotypes were determined in two cohorts of children (n = 219 and n = 1356) in whom total serum IgE, allergen-specific IgE, atopy, bronchial reactivity and asthma symptoms had been studied between birth and 14 years. No reproducible associations with KIR2DL4 genotype were identified, leading us to conclude that the KIR2DL4 9A/10A polymorphism has no influence on susceptibility to asthma.

Modification of Acute and Late-Phase Allergic Responses to Ovalbumin with Lipopolysaccharide

Publisher: S. Karger AG

Date: 2002

DOI: 10.1159/000065881

Abstract: i Background: /i We have previously shown that lipopolysaccharide (LPS) exposure in sensitised animals 18 h after ovalbumin (OVA) challenge inhibits OVA-induced airway hyper-responsiveness (AHR). In the present study, we investigated the effect of LPS on OVA-induced acute and late-phase allergic responses in sensitised rats when challenged with OVA. i Methods: /i Rats were sensitised with OVA and 11 days later challenged with 1% OVA in the presence or absence of LPS (0.5–50 µg/ml) given in the same nebulizer. Acute responses to OVA were measured each minute for 30 min after challenge. In a separate group of animals, late-phase responses to OVA were determined at 24 h. At the end of each study, Evans blue dye was injected and animals sacrificed 30 min later. Bronchoalveolar lavage was obtained to monitor inflammatory cell migration and microvascular leakage. i Results: /i OVA challenge in sensitised animals produced an acute response with changes in lung mechanics peaking 10.0 ± 0.9 min after OVA and returning to baseline within 30 min. This was followed 24 h later by increased responses to methacholine chloride (MCh), inflammatory cell influx and increased Evans blue leakage into the lungs. Presence of 5 or 50 µg/ml LPS in the nebulizer during OVA challenge altered the kinetics of the acute-phase response, with an immediate decrease in lung function (time to peak decreased from 10.3 ± 1.2 to 1.8 ± 0.2 and 2.2 ± 0.3 min, respectively: p 0.001, n = 6) and a dose-dependent attenuation of late-phase AHR, cellular influx (n = 5, p 0.001) and Evans blue leakage (n = 5, p 0.001) at 24 h. i Conclusions: /i In summary, co-administration of OVA with LPS modifies both the acute and late-phase responses to the allergen, inducing an earlier acute change in lung function and a dose-dependent inhibition of late-phase responses to the allergen.

Increased susceptibility of airway epithelial cells from ataxia-telangiectasia to S. pneumoniae infection due to oxidative damage and impaired innate immunity

Publisher: Springer Science and Business Media LLC

Date: 22-02-2019

DOI: 10.1038/S41598-019-38901-3

Abstract: Respiratory disease is a major cause of morbidity and mortality in patients with ataxia-telangiectasia (A-T) who are prone to recurrent sinopulmonary infections, bronchiectasis, pulmonary fibrosis, and pulmonary failure. Upper airway infections are common in patients and S. pneumoniae is associated with these infections. We demonstrate here that the upper airway microbiome in patients with A-T is different from that to healthy controls, with S. pneumoniae detected largely in patients only. Patient-specific airway epithelial cells and differentiated air-liquid interface cultures derived from these were hypersensitive to infection which was at least in part due to oxidative damage since it was partially reversed by catalase. We also observed increased levels of the pro-inflammatory cytokines IL-8 and TNF-α (inflammasome-independent) and a decreased level of the inflammasome-dependent cytokine IL-β in patient cells. Further investigation revealed that the ASC-Caspase 1 signalling pathway was defective in A-T airway epithelial cells. These data suggest that the heightened susceptibility of these cells to S. pneumoniae infection is due to both increased oxidative damage and a defect in inflammasome activation, and has implications for lung disease in these patients.

Factors predisposing to abnormal pulmonary function after adenovirus type 7 pneumonia.

Publisher: BMJ

Date: 10-1984

DOI: 10.1136/ADC.59.10.935

Abstract: Adenoviruses are well known causes of respiratory illness in children. Long term sequelae reported with types 3, 7, and 21 include bronchiolitis obliterans, bronchiectasis, and the hyperlucent lung or McLeod syndrome. Twenty children admitted to hospital with adenovirus type 7 pneumonia between 1960 and 1978 were studied and compared with 20 controls admitted during the same period with adenovirus type 7 upper respiratory tract infections. Sixty five per cent of the pneumonia group had developed evidence of airways obstruction compared with 10% of controls. Young age at the time of pneumonia and a 'measles-like' illness before its onset increase the chance of developing long term pulmonary function abnormalities. Sex and family history of smoking or atopy do not influence outcome.

Time to get serious about the detection and monitoring of early lung disease in cystic fibrosis

Publisher: BMJ

Date: 29-04-2021

DOI: 10.1136/THORAXJNL-2020-216085

Abstract: Structural and functional defects within the lungs of children with cystic fibrosis (CF) are detectable soon after birth and progress throughout preschool years often without overt clinical signs or symptoms. By school age, most children have structural changes such as bronchiectasis or gas trapping/hypoperfusion and lung function abnormalities that persist into later life. Despite improved survival, gains in forced expiratory volume in one second (FEV 1 ) achieved across successive birth cohorts during childhood have plateaued, and rates of FEV 1 decline in adolescence and adulthood have not slowed. This suggests that interventions aimed at preventing lung disease should be targeted to mild disease and commence in early life. Spirometry-based classifications of ‘normal’ (FEV 1 ≥90% predicted) and ‘mild lung disease’ (FEV 1 70%–89% predicted) are inappropriate, given the failure of spirometry to detect significant structural or functional abnormalities shown by more sensitive imaging and lung function techniques. The state and readiness of two imaging (CT and MRI) and two functional (multiple breath washout and oscillometry) tools for the detection and monitoring of early lung disease in children and adults with CF are discussed in this article. Prospective research programmes and technological advances in these techniques mean that well-designed interventional trials in early lung disease, particularly in young children and infants, are possible. Age appropriate, randomised controlled trials are critical to determine the safety, efficacy and best use of new therapies in young children. Regulatory bodies continue to approve medications in young children based on safety data alone and extrapolation of efficacy results from older age groups. Harnessing the complementary information from structural and functional tools, with measures of inflammation and infection, will significantly advance our understanding of early CF lung disease pathophysiology and responses to therapy. Defining clinical utility for these novel techniques will require effective collaboration across multiple disciplines to address important remaining research questions. Future impact on existing management burden for patients with CF and their family must be considered, assessed and minimised. To address the possible role of these techniques in early lung disease, a meeting of international leaders and experts in the field was convened in August 2019 at the Australiasian Cystic Fibrosis Conference. The meeting entitiled ‘Shaping imaging and functional testing for early disease detection of lung disease in Cystic Fibrosis’, was attended by representatives across the range of disciplines involved in modern CF care. This document summarises the proceedings, key priorities and important research questions highlighted.

Cockroach sensitivity in Norway: a previously unidentified problem?

Publisher: Wiley

Date: 17-05-2002

DOI: 10.1034/J.1398-9995.2002.13305.X

Abstract: Little is known about cockroach sensitization in Scandinavia, whereas cockroaches are implicated in allergic diseases throughout large parts of the world. In association with the Genetics of Asthma International Network (GAIN) study, we report sensitization to cockroaches and possible association with IgE-mediated diseases in Norway. 100 Norwegian families (426 subjects) of 7-35-year-old sibling-pairs with asthma and their parents underwent questionnaire/interview (medical and exposure history), skin prick test (SPT) to common local inhalant allergens and German cockroach, and IgE specific to mites, mosquito, shrimp and cockroach. Cockroach sensitization was defined as positive if there was a positive (> or = 3 mm) skin prick test and/or presence of IgE antibody of class 2 or more. Thirty-one subjects (7.5%) were sensitized (five monosensitized) to cockroach (27 by skin prick test and seven by IgE antibody, all with additional inhalant allergy). Co-sensitization was most common to grass (in 61%), cat (48%), dog (48%) and mites (42%). Reported allergic diseases in cockroach-sensitized subjects were asthma and rhinitis (n = 10), asthma only (n = 9), rhinitis only (n = 2) and neither asthma nor rhinitis (n = 10). Since cockroach sensitization was relatively frequent in Norwegian atopic families, albeit with unclear clinical implications, we suggest that cockroach allergy should be considered in atopic subjects with respiratory disease.

Diurnal variation of peak expiratory flow rate in asthmatic children

Publisher: Wiley

Date: 05-1986

DOI: 10.1002/PPUL.1950020305

Abstract: A diurnal variation in peak expiratory flow rate (PEFR) has been described in normal and asthmatic adults. This variation has been apparent in data reported from children, but the rhythm has not been characterized. Sixty-eight asthmatic children recorded PEFR three times a day for 4 weeks at home. Data were analyzed using paired t-tests, cosinor analysis, and spectral analysis. Fifty subjects (73.5%) had significant diurnal variations in PEFR on paired t-tests. Mean litude, derived from cosinor analysis, was 22.6% (SD = 13.2%) of mean PEFR. The trough of the PEFR rhythm occurred at 0345 hours for the group. Spectral analysis confirmed that the major component of the variation in PEFR was due to a rhythm with a period of 24 hours. The litude of the diurnal variation was not related to the subjects' age, sex, or medications taken but was inversely related to mean lung function (expressed as percentage predicted).

In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice

Publisher: Environmental Health Perspectives

Date: 02-2013

DOI: 10.1289/EHP.1205590

The association between particulate air pollution and respiratory admissions among young children in Hanoi, Vietnam

Publisher: Elsevier BV

Date: 02-2017

DOI: 10.1016/J.SCITOTENV.2016.08.012

Abstract: While the effects of ambient air pollution on health have been studied extensively in many developed countries, few studies have been conducted in Vietnam, where the population is exposed to high levels of airborne particulate matter. The aim of our study was to examine the short-term effects of PM

Early life rhinovirus infection exacerbates house-dust-mite induced lung disease more severely in female mice

Publisher: Informa UK Limited

Date: 02-01-2016

DOI: 10.3109/01902148.2015.1131346

Abstract: Recent studies have employed animal models to investigate links between rhinovirus infection and allergic airways disease, however, most do not involve early life infection, and none consider the effects of sex on responses. Here, we infected male and female mice with human rhinovirus 1B (or control) on day 7 of life. Mice were then subjected to 7 weeks of exposure to house-dust-mite prior to assessment of bronchoalveolar inflammation, serum antibodies, lung function, and responsiveness to methacholine. There were significant differences in responses between males and females in most outcomes. In males, chronic house-dust-mite exposure increased bronchoalveolar inflammation, house-dust-mite specific IgG1 and responsiveness of the lung parenchyma, however, there was no additional impact of rhinovirus infection. Conversely, in females, there were additive and synergistic effects of rhinovirus infection and house-dust-mite exposure on neutrophilia, airway resistance, and responsiveness of the lung parenchyma. We conclude that early life rhinovirus infection influences the development of house-dust-mite induced lung disease in female, but not male mice.

Airway dynamics in COPD patients by within-breath impedance tracking: effects of continuous positive airway pressure

Publisher: European Respiratory Society (ERS)

Date: 02-2017

DOI: 10.1183/13993003.01270-2016

Abstract: Tracking of the within-breath changes of respiratory mechanics using the forced oscillation technique may provide outcomes that characterise the dynamic behaviour of the airways during normal breathing. We measured respiratory resistance ( R rs ) and reactance ( X rs ) at 8 Hz in 55 chronic obstructive pulmonary disease (COPD) patients and 20 healthy controls, and evaluated R rs and X rs as functions of gas flow ( V ′) and volume ( V ) during normal breathing cycles. In 12 COPD patients, additional measurements were made at continuous positive airway pressure (CPAP) levels of 4, 8, 14 and 20 hPa. The R rs and X rs versus V ′ and V relationships displayed a variety of loop patterns, allowing characterisation of physiological and pathological processes. The main outcomes emerging from the within-breath analysis were the X rs versus V loop area (AXV) quantifying expiratory flow limitation, and the tidal change in X rs during inspiration (Δ X I ) reflecting alteration in lung inhomogeneity in COPD. With increasing CPAP, AXV and Δ X I approached the normal ranges, although with a large variability between in iduals, whereas mean R rs remained unchanged. Within-breath tracking of R rs and X rs allows an improved assessment of expiratory flow limitation and functional inhomogeneity in COPD thereby it may help identify the physiological phenotypes of COPD and determine the optimal level of respiratory support.

Detecting early lung disease in cystic fibrosis: are current techniques sufficient?

Publisher: BMJ

Date: 12-2004

DOI: 10.1136/THX.2004.025924

Face Masks and Cough Etiquette Reduce the Cough Aerosol Concentration of Pseudomonas aeruginosa in People with Cystic Fibrosis

Publisher: American Thoracic Society

Date: 02-2017

DOI: 10.1164/RCCM.201707-1457OC

Home environment and indoor air pollution exposure in an African birth cohort study

Publisher: Elsevier BV

Date: 12-1970

DOI: 10.1016/J.SCITOTENV.2015.06.136

Abstract: Household indoor air pollution (IAP) is a global health problem and a risk factor for childhood respiratory disease the leading cause of mortality in African children. This study aimed to describe the home environment and measure IAP in the Drakenstein Child Health Study (DCHS), an African birth cohort. An antenatal home visit to assess the home environment and measure IAP (particulate matter, sulphur dioxide, nitrogen dioxide, carbon monoxide and volatile organic compounds (VOCs)) was done on pregnant women enrolled to the DCHS, in a low-socioeconomic, peri-urban South African community. Urine cotinine measured maternal tobacco smoking and exposure. Dwellings were categorised according to 6 household dimensions. Univariate and multivariate analysis explored associations between home environment, seasons and IAP levels measured. 633 home visits were completed, with IAP measured in 90% of homes. Almost a third of participants were of the lowest socio-economic status and the majority of homes (65%) lacked 2 or more of the dwelling category dimensions. Most households had electricity (92%), however, fossil fuels were still used for cooking (19%) and heating (15%) in homes. Antenatal maternal smoking prevalence was 31% 44% had passive smoke exposure. Of IAP measured, benzene (VOC) was significantly above ambient standards with median 5.6 μg/m3 (IQR 2.6-17.1). There were significant associations between the use of fossil fuels for cooking and increased benzene [OR 3.4 (95% CI 2.1-5.4)], carbon monoxide [OR 2.9 (95% CI 1.7-5.0)] and nitrogen dioxide [OR 18.6 (95% CI 3.9-88.9)] levels. A significant seasonal association was found with higher IAP levels in winter. In this low-socioeconomic African community, multiple environmental factors and pollutants, with the potential to affect child health, were identified. Measurement of IAP in a resource-limited setting is feasible. Recognising and quantifying these risk factors is important in effecting public health policy changes.

Incentive device improves spacer technique but not clinical outcome in preschool children with asthma

Publisher: Wiley

Date: 11-2012

DOI: 10.1111/J.1440-1754.2011.02190.X

Editorial introductions

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 10-2006

DOI: 10.1097/01.ALL.0000244787.21165.9E

Loss of ATM in Airway Epithelial Cells Is Associated with Susceptibility to Oxidative Stress

Publisher: American Thoracic Society

Date: 08-2017

DOI: 10.1164/RCCM.201611-2210LE

Oxidation of calprotectin by hypochlorous acid prevents chelation of essential metal ions and allows bacterial growth: Relevance to infections in cystic fibrosis

Publisher: Elsevier BV

Date: 09-2015

DOI: 10.1016/J.FREERADBIOMED.2015.05.022

Abstract: Calprotectin provides nutritional immunity by sequestering manganese and zinc ions. It is abundant in the lungs of patients with cystic fibrosis but fails to prevent their recurrent infections. Calprotectin is a major protein of neutrophils and composed of two monomers, S100A8 and S100A9. We show that the ability of calprotectin to limit growth of Staphylococcus aureus and Pseudomonas aeruginosa is exquisitely sensitive to oxidation by hypochlorous acid. The N-terminal cysteine residue on S100A9 was highly susceptible to oxidation which resulted in cross-linking of the protein monomers. The N-terminal methionine of S100A8 was also readily oxidized by hypochlorous acid, forming both the methionine sulfoxide and the unique product dehydromethionine. Isolated human neutrophils formed these modifications on calprotectin when their myeloperoxidase generated hypochlorous acid. Up to 90% of the N-terminal amine on S100A8 in bronchoalveolar lavage fluid from young children with cystic fibrosis was oxidized. Oxidized calprotectin was higher in children with cystic fibrosis compared to disease controls, and further elevated in those patients with infections. Our data suggest that oxidative stress associated with inflammation in cystic fibrosis will stop metal sequestration by calprotectin. Consequently, strategies aimed at blocking extracellular myeloperoxidase activity should enable calprotectin to provide nutritional immunity within the airways.

The effect of a proximal compliance on interrupter measurements of resistance

Publisher: Elsevier BV

Date: 12-1987

DOI: 10.1016/0034-5687(87)90012-0

Abstract: The interrupter method for measuring respiratory system resistance involves rapidly interrupting flow at the airway opening while measuring the pressure just distal to the site of interruption. In general, the pressure signal obtained exhibits an initial rapid change (delta Pinit) accompanied by rapid d ed oscillations, followed by a further slow change to a steady-state plateau level. Delta Pinit is thought to principally reflect the resistance of the pulmonary airways Raw. We have developed a computer model capable of simulating the main features observed in an interrupter pressure signal. We show that the distinct phases in the pressure signal can be obscured by the existence of a compliant compartment between the airways and the occluding valve (e.g. the cheeks and pharynx) when Raw is increased. Our results suggest that supporting the cheeks may enable one to estimate Raw with the interrupter technique in the presence of mild to moderate bronchoconstriction, but that with severe bronchoconstriction (Raw increased 10-fold above normal) it may not be possible.

Relationship of asthma, atopy, and bronchial responsiveness to serum eosinophil cationic proteins in early childhood

Publisher: Elsevier BV

Date: 11-2004

DOI: 10.1016/J.JACI.2004.07.051

Abstract: The relationship between atopy, asthma, and eosinophilic inflammation is less clear in early childhood than later in life. We sought to determine the relationships between asthma, atopy, and serum eosinophil cationic protein (ECP), a biomarker of eosinophil activation, in 6-year-old children. Serum ECP levels were available from 968 six-year-old children who were part of a longitudinal birth cohort being assessed for asthma and atopy. Detailed clinical history and examination, lung function testing, methacholine challenge, and skin prick testing to 4 common allergens were undertaken. Subgroups of the children were compared by using t tests, ANOVA, chi 2 tests, and regression analysis. One hundred ninety-one (19.7%) children had current asthma, with 114 (59.7%) of these being atopic. The mean serum ECP level for the entire group was 18.0 mug/L (range, 2.0-146.0 mug/L), with no difference between male and female patients. Serum ECP was higher in atopic children (20.5 +/- 18.4), those with asthma (22.4 +/- 19.6), and those with asthma and atopy (26.6 +/- 22.4 all P < .001 compared with children with no asthma or atopy [16.1 +/- 15.9]). Serum ECP levels were highest in children with severe asthma ( P < .001), especially in those with concurrent atopy. Severity of atopy, judged on the basis of wheal size or derived variables combining wheal size and the number of positive skin tests, was a major determinant of serum ECP. Heightened methacholine responsiveness was not associated with increased serum ECP levels. The higher serum ECP levels seen in 6-year-old children with current asthma and more severe atopy suggest that atopy and eosinophilic inflammation are important in driving this clinical phenotype and that this might represent asthma that persists.

Primary Prevention of Allergic Sensitisation

Publisher: Springer Science and Business Media LLC

Date: 1999

DOI: 10.2165/00063030-199912010-00002

Abstract: Allergic diseases, particularly allergic asthma, are among the most frequent disorders seen in paediatric practice and clinic. Epidemiological data as well as recent immunological studies have largely contributed to the identification of risk factors eventually leading to the clinical manifestation of allergy. Various strategies of primary prevention are being developed and most of them include avoidance of identified or presumed risk factors. Another promising field of research investigates pharmacological approaches in the prevention of allergy, and drugs have been identified which interfere with the pathophysiological pathways. It seems likely that they may play an important role in future primary prevention strategies especially targeting infants at high risk.

Formation of Calprotectin-Derived Peptides in the Airways of Children with Cystic Fibrosis

Publisher: The American Association of Immunologists

Date: 15-02-2022

DOI: 10.4049/JIMMUNOL.2001017

Abstract: Calprotectin is released by activated neutrophils along with myeloperoxidase (MPO) and proteases. It plays numerous roles in inflammation and infection, and is used as an inflammatory biomarker. However, calprotectin is readily oxidized by MPO-derived hypohalous acids to form covalent dimers of its S100A8 and S100A9 subunits. The dimers are susceptible to degradation by proteases. We show that detection of human calprotectin by ELISA declines markedly because of its oxidation by hypochlorous acid and subsequent degradation. Also, proteolysis liberates specific peptides from oxidized calprotectin that is present at inflammatory sites. We identified six calprotectin-derived peptides by mass spectrometry and detected them in the bronchoalveolar lavage fluid of children with cystic fibrosis (CF). We assessed the peptides as biomarkers of neutrophilic inflammation and infection. The content of the calprotectin peptide ILVI was related to calprotectin (r = 0.72, p = 0.01, n = 10). Four of the peptides were correlated with the concentration of MPO (r & 0.7, p ≤ 0.01, n = 21), while three were higher (p & 0.05) in neutrophil elastase–positive (n = 14) than –negative s les (n = 7). Also, five of the peptides were higher (p & 0.05) in the bronchoalveolar lavage fluid from children with CF with infections (n = 21) than from non-CF children without infections (n = 6). The specific peptides liberated from calprotectin will signal uncontrolled activity of proteases and MPO during inflammation. They may prove useful in tracking inflammation in respiratory diseases dominated by neutrophils, including coronavirus disease 2019.

Severe winter asthma exacerbations can be prevented by omalizumab, but there is no carryover effect

Publisher: Elsevier BV

Date: 02-2017

DOI: 10.1016/J.JACI.2016.07.035

Factors Influencing I:E Ratio during High Frequency Oscillation

Publisher: Springer Science and Business Media LLC

Date: 04-1999

DOI: 10.1203/00006450-199904020-01875

Providing Feedback on Adherence Increases Use of Preventive Medication by Asthmatic Children

Publisher: Informa UK Limited

Date: 19-02-2010

DOI: 10.3109/02770900903483840

Abstract: This study investigates the impact of measuring adherence and providing feedback on medication usage by children with unstable asthma. Adherence was measured using an electronic monitoring device. Subjects were randomized to either being told of their adherence during review consultations or for their adherence to remain undisclosed to their parents and treating physician. Subjects were reviewed monthly for 4 months. Twenty-six children aged between 6 and 14 years were recruited. Adherence was significantly higher in the intervention group (79% versus 58%, p <.01). There were significant improvements in clinical measures of disease control compared with baseline in both groups. The change in forced expiratory volume in 1 s (FEV(1)) (% predicted) was greater in those subjects receiving feedback (13.8% versus 9.8%). However, lung function values were lower in the intervention group at baseline and the relative improvement failed to reach statistical significance. Measuring adherence and providing feedback increases the use of preventive medication. A larger study is required to explore implications for disease control.

Environmental Impacts on Infectious Disease: A Literature View of Epidemiological Evidence

Publisher: Ubiquity Press, Ltd.

Date: 2022

DOI: 10.5334/AOGH.3670

Structural controls on proterozoic nickel and gold mineral systems identified from geodynamic modelling and geophysical interpretation, east Kimberley, Western Australia

Publisher: Elsevier BV

Date: 04-2018

DOI: 10.1016/J.OREGEOREV.2018.03.010

Mortality and morbidity in populations in the vicinity of coal mining: a systematic review

Publisher: Springer Science and Business Media LLC

Date: 11-06-2018

DOI: 10.1186/S12889-018-5505-7

Reprint of: Policy decisions on endocrine disruptors should be based on science across disciplines: A response to Dietrich et al.

Publisher: Elsevier BV

Date: 02-2014

DOI: 10.1016/J.YHBEH.2013.09.001

Is home monitoring of lung function worthwhile for children with asthma?

Publisher: BMJ

Date: 11-2001

DOI: 10.1136/EWJM.175.5.344

CD14 C-159T and early infection with Pseudomonas aeruginosa in children with cystic fibrosis

Publisher: Springer Science and Business Media LLC

Date: 23-06-2005

DOI: 10.1186/1465-9921-6-63

Health impacts of climate change and biosecurity in the Asian Pacific region

Publisher: Walter de Gruyter GmbH

Date: 2011

DOI: 10.1515/REVEH.2011.002

Abstract: Our climate is changing as a result of human activity, and such changes have the potential to have a significant impact on human health. The basic requirements for health--clean air, safe drinking water, sufficient food and secure shelter--are all vulnerable to climate change. Low-income developing countries are especially vulnerable no country, however, is totally immune. In Australia, we are already seeing evidence of the health effects of climate change with an increase in temperature-related food poisoning events and an increase in mosquito-borne infections, including Ross River virus and Dengue fever. In the Asian Pacific region the issues identified as most pressing vary from country to country, but a common theme is a lack of public understanding and education and lack of capacity for implementing mitigation strategies. Strategies addressing the health impacts of climate change must incorporate the principles of social justice and equity within the region.

Environmental exposures in the era of climate change

Publisher: Walter de Gruyter GmbH

Date: 2011

DOI: 10.1515/REVEH.2011.001

Novel spacer device does not improve adherence in childhood asthma

Publisher: Wiley

Date: 26-06-2007

DOI: 10.1002/PPUL.20647

Abstract: The Funhaler (FH) is a novel spacer device (holding chamber) that has been designed to improve adherence and aerosol delivery in young asthmatic children using a metered dose inhaler. A pilot study reported a 38% increase in parent-reported adherence over 2 weeks compared with the child's normal spacer. The aim of this study was to investigate whether the FH would be associated with superior adherence in the medium term (3 months) using an objective assessment. Forty-seven children aged 18 months to 7 years were randomised to a FH or control small volume spacer. Participants were reviewed monthly for 3 months. Adherence was measured using an electronic monitoring device (Smartinhaler). Disease control was based on symptom scores and exacerbation rates. Twenty-six children were randomised to the FH and 21 to the control spacer. Three children withdrew (FH = 2). Median adherence each month for the 3 months was 74%, 54%, and 46% for the FH and 70%, 73%, and 54% for the control spacer. The difference in adherence was not statistically significant (P = 0.47, 0.37, and 0.23, respectively). There was also no significant difference in exacerbation rates or symptom scores. Seven of the FHs broke during the study. The FH was preferred by 21/24 parents randomised to the FH compared with their child's normal spacer. Despite the FH being popular with children and parents its use was not associated with improved adherence or disease control.

Clarithromycin therapy for patients with Cystic Fibrosis: A randomized controlled trial

Publisher: Wiley

Date: 20-01-2012

DOI: 10.1002/PPUL.21613

Abstract: The clinically significant actions of oral azithromycin in modifying progressive cystic fibrosis (CF) lung disease have been well documented. In vitro and clinical data suggests that clarithromycin has immunomodulatory properties similar to other 14-member macrolides, however two previously reported short term, open label trials of clairthromycin in small numbers of patients with CF failed to show significant benefits in modifying lung function or inflammation. We performed an international double blind, cross-over trial in which 63 subjects with CF were studied while receiving either placeo or 500 mg oral clarithromycin twice daily for 5 months, with a 1-month wash-out. The primary efficacy end point was the change in lung function (FEV(1) and FVC) during the clarithromycin treatment period compared to placebo treatment. Secondary efficacy end points included quality of life, number of pulmonary exacerbations, height and weight, sputum inflammatory mediator content, sputum transportability and surface properties, bacterial flora, nasal potential difference, and breath condensate. No significant difference in either the primary efficacy end point or any secondary end point was seen during the period of clarithromycin treatment compared to those seen during placebo administration. We conclude that clarithromycin is not effective in treating CF lung disease.

Histo-blood group antigens and rotavirus vaccine virus shedding in Australian infants

Publisher: Elsevier BV

Date: 12-2022

DOI: 10.1016/J.PATHOL.2022.04.006

Abstract: Rotavirus vaccine performance varies between high and low income countries. One possible explanation is inherited histo-blood group antigens (HBGAs) the expression of which differs between populations. HBGAs are polymorphic glycans on mucosal surfaces. Their presence indicates the secretor phenotype, while their absence identifies a non-secretor status. HBGAs can act as rotavirus receptors and might influence live-attenuated rotavirus vaccine virus replication and shedding. Studies in low and middle income countries of the human rotavirus vaccine Rotarix (RV1), suggest HBGA secretor phenotype is important for vaccine immunogenicity. We investigated in a high income country the association between HBGA phenotype (secretor and Lewis) and the bovine-human reassortment vaccine RotaTeq (RV5) vaccine shedding in the stools of infants following each vaccine dose. Eighty-two infants from an Australian birth cohort provided saliva and weekly stool s les after RV5 vaccination doses. Lewis and secretor HBGA phenotyping was identified from saliva s les and confirmed by genotyping. Vaccine virus strains were detected by real-time polymerase chain reaction assays. No significant association between secretor status and vaccine virus shedding was identified. The proportion of infants who shed rotavirus following the first RV5 dose for secretor and non-secretor infants was 57/64 (89%) and 17/18 (94%), respectively, decreasing to 24/64 (33%) and 9/18 (50%) after the second dose and 26/64 (42%) and 8/18 (44%) following the third vaccine dose, respectively. Similarly, no significant differences were observed in vaccine virus shedding by Lewis, or combined Lewis and secretor status, after each vaccine dose. We found HBGAs were not associated with RV5 vaccine virus shedding in Australian infants.

Non‐atopic intrinsic asthma and the ‘family tree’ of chronic respiratory disease syndromes

Publisher: Wiley

Date: 11-05-2009

DOI: 10.1111/J.1365-2222.2009.03258.X

Abstract: We present a scheme below in which the most common forms of inflammatory diseases of the respiratory tract, notably atopic and non-atopic asthma and COPD, are depicted as separate offshoots from a common 'at-risk' pathway underpinned by genotypes related to aberrations in control of host defence and tissue repair mechanisms. We propose that entrance into this pathway is initially programmed by environmental experience during infancy and early childhood, in particular by severe lower respiratory tract infection, and that further progression towards expression of specific disease phenotype(s) is determined by the nature, timing and frequency of additional environmental insults subsequently encountered. At the one extreme, early sensitization of at-risk subjects to aeroallergens can potentially drive rapid progression towards expression of the atopic asthmatic phenotype under the dual onslaught of inflammatory responses to allergens athogens. At the opposite end of the spectrum the drip-feed effects of occasional infections on respiratory function(s) are lified over a longer time frame by inflammation resulting from exposure to tobacco smoke and/or related chemical pollutants. Non-atopic asthma is envisaged to fit between these two extremes, being driven essentially by the downstream effects of respiratory infections alone in at-risk subjects. An important common factor in all three disease phenotypes is that acute exacerbations are typically driven by infections, the host responses to which display a characteristic T-helper type 2-like footprint, which in our view points to underlying genotype(s) which result in unbalanced host responses to respiratory pathogens.

Using mathematical transmission modelling to investigate drivers of respiratory syncytial virus seasonality in children in the Philippines

Publisher: Public Library of Science (PLoS)

Date: 27-02-2014

DOI: 10.1371/JOURNAL.PONE.0090094

Carbon dioxide as a proxy for orogenic gold source

Publisher: Elsevier BV

Date: 12-2020

DOI: 10.1016/J.OREGEOREV.2020.103829

Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: How can we delineate causal effects?

Publisher: Elsevier BV

Date: 07-2016

DOI: 10.1016/J.NEURO.2016.05.011

Abstract: Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research ex le: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures.

Early-life respiratory viral infections, atopic sensitization, and risk of subsequent development of persistent asthma

Publisher: Elsevier BV

Date: 05-2007

DOI: 10.1016/J.JACI.2006.12.669

Developmental changes in airway and tissue mechanics in mice

Publisher: American Physiological Society

Date: 07-2005

DOI: 10.1152/JAPPLPHYSIOL.01111.2004

Abstract: Most studies using mice to model human lung diseases are carried out in adults, although there is emerging interest in the effects of allergen, bacterial, and viral exposure early in life. This study aims to characterize lung function in BALB/c mice from infancy (2 wk) through to adulthood (8 wk). The low-frequency forced oscillation technique was used to obtain impedance data, partitioned into components representing airway resistance, tissue d ing, tissue elastance, and hysteresivity (tissue d ing/tissue elastance). Measurements were made at end-expiratory pause (transrespiratory system pressure = 2 cmH 2 O) and during relaxed slow expiration from 20 to 0 cmH 2 O. Airway resistance decreased with age from 0.63 cmH 2 O·ml −1 ·s at 2 wk to 0.24 cmH 2 O·ml −1 ·s at 8 wk ( P 0.001). Both tissue d ing and tissue elastance decreased with age ( P 0.001) from 2 to 5 wk, then plateaued through to 8 wk ( P 0.001). This pattern was seen both in measurements taken at end-expiratory pause and during expiration. There were no age-related changes seen in hysteresivity when measured at end-expiratory pause, but the pattern of volume dependence did differ with the age of the mice. These changes in respiratory mechanics parallel the reported structural changes of the murine lung from the postnatal period into adulthood.

Protective mechanical ventilation does not exacerbate lung function impairment or lung inflammation following influenza A infection

Publisher: American Physiological Society

Date: 11-2009

DOI: 10.1152/JAPPLPHYSIOL.00393.2009

Abstract: The degree to which mechanical ventilation induces ventilator-associated lung injury is dependent on the initial acute lung injury (ALI). Viral-induced ALI is poorly studied, and this study aimed to determine whether ALI induced by a clinically relevant infection is exacerbated by protective mechanical ventilation. Adult female BALB/c mice were inoculated with 10 4.5 plaque-forming units of influenza A/Mem/1/71 in 50 μl of medium or medium alone. This study used a protective ventilation strategy, whereby mice were anesthetized, tracheostomized, and mechanically ventilated for 2 h. Lung mechanics were measured periodically throughout the ventilation period using a modification of the forced oscillation technique to obtain measures of airway resistance and coefficients of tissue d ing and tissue elastance. Thoracic gas volume was measured and used to obtain specific airway resistance, tissue d ing, and tissue elastance. At the end of the ventilation period, a bronchoalveolar lavage s le was collected to measure inflammatory cells, macrophage inflammatory protein-2, IL-6, TNF-α, and protein leak. Influenza infection caused significant increases in inflammatory cells, protein leak, and deterioration in lung mechanics that were not exacerbated by mechanical ventilation, in contrast to previous studies using bacterial and mouse-specific viral infection. This study highlighted the importance of type and severity of lung injury in determining outcome following mechanical ventilation.

Impact of adolescent peer aggression on later educational and employment outcomes in an Australian cohort

Publisher: Wiley

Date: 04-06-2015

DOI: 10.1016/J.ADOLESCENCE.2015.05.007

Abstract: This study used prospective birth cohort data to analyse the relationship between peer aggression at 14 years of age and educational and employment outcomes at 17 years ( N = 1091) and 20 years ( N = 1003). Participants from the Western Australian Pregnancy Cohort (Raine) study were ided into mutually exclusive categories of peer aggression. Involvement in peer aggression was reported by 40.2% (10.1% victims 21.4% perpetrators 8.7% victim–perpetrators) of participants. Participants involved in any form of peer aggression were less likely to complete secondary school. Perpetrators and victim–perpetrators of peer aggression were more likely to be in the ‘No Education, Employment or Training’ group at 20 years of age. This association was explained by non‐completion of secondary school. These findings demonstrate a robust association between involvement in peer aggression and non‐completion of secondary school, which in turn was associated with an increased risk of poor educational and employment outcomes in early adulthood.

Plethysmographic estimation of thoracic gas volume in apneic mice

Publisher: American Physiological Society

Date: 08-2006

DOI: 10.1152/JAPPLPHYSIOL.00011.2006

Abstract: Electrical stimulation of intercostal muscles was employed to measure thoracic gas volume (TGV) during airway occlusion in the absence of respiratory effort at different levels of lung inflation. In 15 tracheostomized and mechanically ventilated CBA/Ca mice, the value of TGV obtained from the spontaneous breathing effort available in the early phase of the experiments (TGVsp) was compared with those resulting from muscle stimulation (TGVst) at transrespiratory pressures of 0, 10, and 20 cmH 2 O. A very strong correlation ( r 2 = 0.97) was found, although with a systematically (∼16%) higher estimation of TGVst relative to TGVsp, attributable to the different durations of the stimulated (∼50 ms) and spontaneous (∼200 ms) contractions. Measurements of TGVst before and after injections of 0.2, 0.4, and 0.6 ml of nitrogen into the lungs in six mice resulted in good agreement between the change in TGVst and the injected volume ( r 2 = 0.98). In four mice, TGVsp and TGVst were compared at end expiration with air or a helium-oxygen mixture to confirm the validity of isothermal compression in the alveolar gas. The TGVst values measured at zero transrespiratory pressure in all CBA/Ca mice [0.29 ± 0.05 (SD) ml] and in C57BL/6 ( N = 6 0.34 ± 0.08 ml) and BALB/c ( N = 6 0.28 ± 0.06 ml) mice were in agreement with functional residual capacity values from previous studies in which different techniques were used. This method is particularly useful when TGV is to be determined in the absence of breathing activity, when it must be known at any level of lung inflation or under non-steady-state conditions, such as during pharmaceutical interventions.

Children's Environmental Health Indicators in Context of the Sustainable Development Goals for Small Island Developing States.

Publisher: MDPI AG

Date: 03-07-2018

DOI: 10.3390/IJERPH15071404

Children's Environmental Health Indicators for Pacific Island Countries.

Publisher: MDPI AG

Date: 03-07-2018

DOI: 10.3390/IJERPH15071403

Prenatal determinants of cord blood total immunoglobulin E levels in Mexican newborns

Publisher: Oceanside Publications Inc.

Date: 09-2013

DOI: 10.2500/AAP.2013.34.3688

Paediatric origins of adult lung disease: Introduction

Publisher: BMJ

Date: 07-2000

DOI: 10.1136/THORAX.55.7.585

Role of Respiratory Viruses in Acute Upper and Lower Respiratory Tract Illness in the First Year of Life

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 08-2006

DOI: 10.1097/01.INF.0000226912.88900.A3

Partitioning of Airway and Parenchymal Mechanics in Unsedated Newborn Infants

Publisher: Springer Science and Business Media LLC

Date: 12-2005

DOI: 10.1203/01.PDR.0000185273.86320.13

Abstract: The recent trend toward development of noninvasive methods that can accurately evaluate the lung periphery has particular relevance for the predominantly parenchymal nature of neonatal respiratory disease. Concerns regarding the safety of sedating newborn (especially preterm) infants have also stimulated a drive toward measurements obtained during natural sleep. This study aimed to adapt existing methodology for the low-frequency forced oscillation technique to obtain partitioned measurements of airway and parenchymal mechanics during unsedated, quiet sleep in newborn infants without a history of previous respiratory disease. A face mask was positioned over the infant's mouth and nose and a brief (4-5 s) breathing pause was induced by evoking the Hering-Breuer reflex via end-inspiratory occlusion at raised lung volume (airway opening occluded at 2 kPa). Airway opening pressure and flow were measured while a pseudorandom noise (2-14 Hz) was applied to the airway. Acceptable pulmonary impedance data were collected in 11 of the 12 infants studied (34.1-42.6 wk postmenstrual age, 1.9-3.9 kg body weight) on 17 (total of 20) occasions. Airway parameters (resistance and inertance) and respiratory tissue parameters were calculated from the resultant impedance spectra. Tissue resistance and tissue elastance decreased with increasing body length albeit at different rates such that hysteresivity (tissue resistance/tissue elastance) also decreased. There was a trend toward reduction in airway resistance with increasing length. Measurements of lung function are feasible in the unsedated newborn infant using low-frequency forced oscillations and confirm the important contribution of tissue resistance to lung mechanics in the developing lung.

Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Publisher: Springer Science and Business Media LLC

Date: 06-02-2017

DOI: 10.1038/NG.3787

Validation of the GLI-2012 spirometry reference equations in Argentinian children

Publisher: Wiley

Date: 19-12-2018

DOI: 10.1002/PPUL.23923

Abstract: The Global Lung Function Initiative (GLI) has produced spirometry reference equations for use in different ethnic groups. Previous reports have shown that the GLI equations do not adequately describe lung function in all populations and that adopting the new equations into clinical practice can increase the number of patients considered to have abnormal lung function. Therefore, before adopting these equations into local practice it is necessary to establish how well the equations represent the local population. The present study was conducted to determine how well the GLI spirometry reference equations represented the young children in Argentina, a population not included in the GLI dataset. Spirometry was measured in 2072 healthy children (50.9% males) aged 3.0-12.4 years (mean 6.64 ± SD 1.39), with a height range of 93.0-158.5 cm and weight range from 13.1 to 54.7 kg. We used the GLI "Caucasian" and "other/mixed" race equations to create Z-scores. The Z-scores predicted by the Caucasian GLI equations did not differ from zero and fitted the data well. Z-scores calculated using "other/mixed race" fit less well. Using the GLI definition of low lung function (Z-score <1.65) 6.8% of our healthy population had abnormal FVC, 4.9% had abnormal FEV1, 5.9 % had abnormal FEV0.75, and 3.9% had abnormal FEF We recommend the use of the GLI-2012 Caucasian equations for spirometry undertaken in Argentinian children.

Peri-operative adverse respiratory events in children

Publisher: Wiley

Date: 25-11-2015

DOI: 10.1111/ANAE.12946

Abstract: Three quarters of all critical incidents and a third of all peri-operative cardiac arrests in paediatric anaesthesia are caused by adverse respiratory events. We screened for risk factors from children's and their families' histories, and assessed the usefulness of common markers of allergic sensitisation of the airway as surrogates for airway inflammation and increased risk for adverse respiratory events. One hundred children aged up to 16 years with two or more risk factors undergoing elective surgery were included in the study. Eosinophil counts, IgE level, specific IgE for D. pteronyssinus, cat epithelia and Gx2 (grass pollen) were measured for each child and adverse respiratory events (bronchospasm, laryngospasm, oxygen desaturation < 95%, severe persistent coughing, airway obstruction and postoperative stridor) were recorded. Twenty-one patients had an adverse respiratory event but allergic markers were poor predictors. Binary logistic regression showed a lack of predictive value of the eosinophil range and adverse respiratory events (p = 0.249). Receiver operating characteristic (ROC) curves for the presence of adverse respiratory events vs level of specific IgE antibody (to Gx2 (AUC 0.614), cat epithelia (0.564) and D. pteronyssinus (0.520)) demonstrated poor predictive values. However, the presence of risk factors was strongly associated with adverse respiratory events (p < 0.001) and a ROC-curve analysis indicated a fair capacity to predict adverse respiratory events (AUC 0.788). There was a significant difference (p = 0.001) between the presence of adverse respiratory events in patients with more than four (p = 0.006), compared with less than four (p = 0.001), risk factors. We conclude that while risk factors taken from the child's (or family) history proved good predictors of adverse respiratory events, immunological markers of allergic sensitisation demonstrated low predictive values. Pre-operative identification of children at high risk for an adverse respiratory event should rely on clinical, rather than immunological, assessment.

Heterogeneity in Diphtheria‐Tetanus–Acellular Pertussis Vaccine–Specific Cellular Immunity during Infancy: Relationship to Variations in the Kinetics of Postnatal Maturation of Systemic Th1 Function

Publisher: Oxford University Press (OUP)

Date: 07-2001

DOI: 10.1086/320996

Abstract: Cellular immunity to vaccines is highly variable during infancy. This study addressed the hypothesis that these responses are governed by the pace of maturational changes in adaptive immune competence, in particular, cellular functions that underlie the postnatal transition from Th2 to Th1 "bias." Tetanus-specific cytokine responses were tracked in peripheral blood mononuclear cells collected from infants at months 2, 4, 6, 12, and 18. These were compared with polyclonal responses. Results show that the Th2 component of the vaccine response develops rapidly and remains stable, unlike interferon (IFN)-gamma production, which also is initiated early but commonly declines after the final priming dose at 6 months. However, between 12 and 18 months, the IFN-gamma component of the vaccine-specific response has a spontaneous resurgence that coincides with a parallel increase in overall IFN-gamma production capacity. The Th2 component of vaccine-specific responses was more prominent in children with atopic family history.

Preservation of Lung Function in Cystic Fibrosis: Are Macrolides the Answer?

Publisher: American Thoracic Society

Date: 11-2018

DOI: 10.1164/RCCM.201806-1103ED

The allergic sensitization in infants with atopic eczema from different countries

Publisher: Wiley

Date: 21-01-2009

DOI: 10.1111/J.1398-9995.2008.01779.X

Abstract: No study has compared allergic sensitization patterns in infants with atopic eczema from different countries. The aim of this study was to investigate the patterns of allergic sensitization in a cohort of infants with atopic eczema participating in a multicentre, international study. Two thousand one hundred and eighty-four infants (mean age 17.6 months) with atopic eczema from allergic families were screened in 94 centres in 12 countries to participate in a randomized trial for the early prevention of asthma. Clinical history, Severity Scoring of Atopic Dermatitis Index, measurements for total serum IgE and specific IgE antibodies to eight food and inhalant allergens were entered into a database before randomization to treatment. A history of type of feeding in the first weeks of life and exposure to animals was recorded. A total of 52.9% of the infants had raised total IgE, and 55.5% were sensitized to at least one allergen. There was a wide difference in the total IgE values and in the sensitization rates to foods and aeroallergens among infants from different countries. The highest prevalence rates of allergen-sensitized infants were found in Australia (83%), the UK (79%) and Italy (76%). Infants from Belgium and Poland consistently had the lowest sensitization rates. In each country, a characteristic pattern of sensitization was found for aeroallergens (house dust mite > cat > grass pollen > Alternaria), but not for food allergens. In infants with atopic eczema, there is a wide variation in the pattern of allergic sensitization between countries, and data from one country are not necessarily generalizable to other countries.

Reference values of interrupter respiratory resistance in healthy preschool white children

Publisher: BMJ

Date: 09-2001

DOI: 10.1136/THORAX.56.9.691

Abstract: Interrupter respiratory resistance (Rint) is reported to be useful in evaluating lung function in poorly collaborating patients. However, no reference values are available from large s les of preschool children using the standard interrupter method. The aim of this study was to define reference Rint values in a population of healthy preschool children. Rint was assessed without supporting the cheeks in children with no history of wheeze from six kindergartens. To evaluate the effects of upper airway compliance on Rint in healthy children, an additional group of preschool children with either no history of wheeze or no respiratory symptoms at the time of testing underwent Rint measurements in our lung function laboratory with and without supporting the cheeks. Short term (about 1 minute apart) and long term (mean 2.5 months apart) repeatability of Rint measurements (2 SDs of the mean paired difference between measurements) was also assessed in children referred for cough or wheeze. A total of 284 healthy white children (age range 3.0-6.4 years) were evaluated. Mean inspiratory and expiratory Rint (RintI and RintE) did not differ significantly in boys and girls. Age, height, and weight showed a significant inverse correlation with both RintI and RintE in the univariate analysis with linear regression. Multiple regression with age, height, and weight as the independent variables showed that all three variables were significantly and independently correlated with RintI, whereas only height was significantly and independently correlated with RintE. Supporting the cheeks had no significant effect on RintI (n=29, median 0.673 v 0.660 kPa/l.s, p=0.098) or RintE (n=39, median 0.702 v 0.713 kPa/l.s, p=0.126). Short term repeatability was 0.202 kPa/l.s for RintI (n=50) and 0.242 kPa/l.s for RintE (n=69). Long term repeatability was 0.208 kPa/l.s for RintE (n=26). We have reported reference Rint values in preschool white children and have demonstrated the usefulness of this technique in assessing lung function in this age group.

Rhinovirus bronchiolitis, maternal asthma, and the development of asthma and lung function impairments

Publisher: Wiley

Date: 24-11-2020

DOI: 10.1002/PPUL.25165

Absence of cholinergic airway tone in normal BALB/c mice

Publisher: Elsevier BV

Date: 05-2008

DOI: 10.1016/J.RESP.2008.01.009

Abstract: Basal airway smooth muscle (ASM) tone has not been demonstrated in mice in vivo. To determine whether basal ASM tone is present in mouse airways we measured respiratory system impedance (Zrs) before and after either atropine or bilateral vagotomy. Zrs was measured using forced oscillations delivered via a wave-tube during slow ( approximately 35s) inflation-deflation maneuvers between transrespiratory pressures (Prs) of 0 and 20 cm H2O. A constant-phase tissue model was applied to the Zrs to calculate airway resistance (R aw), tissue d ing (G) and elastance (H). Thoracic gas volume (TGV) was determined plethysmographically at Prs=0 cm H2O and by integration of the inspiratory flow. The relationship between conductance (G aw=1/R aw) and TGV during inflation was also examined. Neither atropine nor vagotomy produced any change in R aw, H, eta (=G/H), TGV or the slope of G aw vs. TGV that was different to that observed in the relevant control groups. These data show that BALB/c mice do not have cholinergic ASM tone in vivo.

Author Correction: Increased susceptibility of airway epithelial cells from ataxia-telangiectasia to S. pneumoniae infection due to oxidative damage and impaired innate immunity

Publisher: Springer Science and Business Media LLC

Date: 24-07-2020

DOI: 10.1038/S41598-020-69649-W

Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Research and Innovation Opportunities to Improve Epidemiological Knowledge and Control of Environmentally Driven Zoonoses

Publisher: Ubiquity Press, Ltd.

Date: 2022

DOI: 10.5334/AOGH.3770

DUODENAL PH IN CYSTIC-FIBROSIS AND ITS RELATIONSHIP TO FAT MALABSORPTION

Publisher: Springer Science and Business Media LLC

Date: 10-1990

DOI: 10.1007/BF01536423

Abstract: Classically, the polymeric immunoglobulin receptor and its ligand, IgA, are thought to be sorted from basolateral early endosomes into transcytotic vesicles that directly fuse with the apical plasma membrane. In contrast, we have found that in MDCK cells IgA is delivered from basolateral endosomes to apical endosomes and only then to the apical cell surface. When internalized from the basolateral surface of MDCK cells IgA is found to accumulate under the apical plasma membrane in a compartment that is accessible to two apically added membrane markers: anti-secretory component Fab fragments, and avidin internalized from the biotinylated apical pole of the cell. This accumulation occurs in the presence of apical trypsin, which prevents internalization of the ligand from the apical cell surface. Using a modification of the diaminobenzidine density-shift assay, we estimate that approximately 80% of basolaterally internalized IgA resides in the apical endosomal compartment. In addition, approximately 50% of basolaterally internalized transferrin, a basolateral recycling protein, has access to this apical endosomal compartment and is efficiently recycled back to the basolateral surface. Microtubules are required for the organization of the apical endosomal compartment and it is dispersed in nocodazole-treated cells. Moreover, this compartment is largely inaccessible to fluid-phase markers added to either pole of the cell, and therefore seems analogous to the recycling endosome described in nonpolarized cells. We propose a model in which transcytosis is not a specialized pathway that uses unique transcytotic vesicles, but rather combines portions of pathways used by non-transcytosing molecules.

Characterizing well-differentiated culture of primary human nasal epithelial cells for use in wound healing assays.

Publisher: Elsevier BV

Date: 11-2018

DOI: 10.1038/S41374-018-0100-1

Abstract: The nasal epithelium is the initial contact between the external environment and the respiratory tract and how it responds to noxious stimuli and repairs epithelial damage is important. Growing airway epithelial cells in culture at air-liquid interface allows for a physiologically relevant model of the human upper airways. The aim of the present study was to characterize human primary nasal epithelial cells grown at the air-liquid interface and establish a model for use in wound healing assays. This study determined the time required for full differentiation of nasal epithelial cells in an air-liquid interface culture to be at least 7 weeks using the standardized B-ALI media. Also, a model was established that studied the response to wounding and the effect of EGFR inhibition on this process. Nasal epithelial cultures from healthy subjects were differentiated at air-liquid interface and manually wounded. Wounds were monitored over time to complete closure using a time lapse imaging microscope with cultures identified to have a rate of wound healing above 2.5%/h independent of initial wound size. EGFR inhibition caused the rate of wound healing to drop a significant 4.6%/h with there being no closure of the wound after 48 h. The robust model established in this study will be essential for studying factors influencing wound healing, including host disease status and environmental exposures in the future.

Progression of early structural lung disease in young children with cystic fibrosis assessed using CT

Publisher: BMJ

Date: 26-12-2012

DOI: 10.1136/THORAXJNL-2011-200912

Abstract: Cross-sectional studies implicate neutrophilic inflammation and pulmonary infection as risk factors for early structural lung disease in infants and young children with cystic fibrosis (CF). However, the longitudinal progression in a newborn screened population has not been investigated. To determine whether early CF structural lung disease persists and progresses over 1 year and to identify factors associated with radiological persistence and progression. 143 children aged 0.2-6.5 years with CF from a newborn screened population contributed 444 limited slice annual chest CT scans for analysis that were scored for bronchiectasis and air trapping and analysed as paired scans 1 year apart. Logistic and linear regression models, using generalised estimating equations to account for multiple measures, determined associations between persistence and progression over 1 year and age, sex, severe cystic fibrosis transmembrane regulator (CFTR) genotype, pancreatic sufficiency, current respiratory symptoms, and neutrophilic inflammation and infection measured by bronchoalveolar lavage. Once detected, bronchiectasis persisted in 98/133 paired scans (74%) and air trapping in 178/220 (81%). The extent of bronchiectasis increased in 139/227 (63%) of paired scans and air trapping in 121/264 (47%). Radiological progression of bronchiectasis and air trapping was associated with severe CFTR genotype, worsening neutrophilic inflammation and pulmonary infection. CT-detected structural lung disease identified in infants and young children with CF persists and progresses over 1 year in most cases, with deteriorating structural lung disease associated with worsening inflammation and pulmonary infection. Early intervention is required to prevent or arrest the progression of structural lung disease in young children with CF.

Drug development strategies for asthma: in search of a new paradigm

Publisher: Springer Science and Business Media LLC

Date: 07-2004

DOI: 10.1038/NI0704-695

Broadband frequency dependence of respiratory impedance in rats

Publisher: American Physiological Society

Date: 10-2005

DOI: 10.1152/JAPPLPHYSIOL.00383.2005

Abstract: Past studies in humans and other species have revealed the presence of resonances and antiresonances, i.e., minima and maxima in respiratory system impedance (Zrs), at frequencies much higher than those commonly employed in clinical applications of the forced oscillation technique (FOT). To help understand the mechanisms behind the first occurrence of antiresonance in the Zrs spectrum, the frequency response of the rat was studied by using FOT at both low and high frequencies. We measured Zrs in both Wistar and PVG/c rats using the wave tube technique, with a FOT signal ranging from 2 to 900 Hz. We then compared the high-frequency parameters, i.e., the first antiresonant frequency (far,1) and the resistive part of Zrs at that frequency [Rrs(far,1)], with parameters obtained by fitting a modified constant-phase model to low-frequency Zrs spectra. The far,1 was 570 ± 43 (SD) Hz and 456 ± 16 Hz in Wistar and PVG/c rats, respectively, and it did not shift with respiratory gases of different densities (air, heliox, and a mixture of SF 6 ). The far,1 and Rrs(far,1) were relatively independent of methacholine-induced bronchoconstriction but changed significantly with increasing transrespiratory pressures up to 20 cmH 2 O, in the same way as airway resistance but independently of changes to tissue parameters. These results suggest that, unlike the human situation, the first antiresonance in the rat is not primarily dependent on the acoustic dimensions of the respiratory system and can be explained by interactions between compliances and inertances localized to the airways, but this most likely does not include airway wall compliance.

Childhood pneumonia: A neglected, climate-sensitive disease?

Publisher: Elsevier BV

Date: 11-2010

DOI: 10.1016/S0140-6736(10)62141-1

Cord blood hemopoietic progenitor profiles predict acute respiratory symptoms in infancy

Publisher: Wiley

Date: 24-01-2008

DOI: 10.1111/J.1399-3038.2007.00615.X

The transient value of classifying preschool wheeze into episodic viral wheeze and multiple trigger wheeze

Publisher: Wiley

Date: 08-12-2009

DOI: 10.1111/J.1651-2227.2009.01508.X

Abstract: A recently proposed method for classifying preschool wheeze is to describe it as either episodic (viral) wheeze or multiple trigger wheeze. In research studies, phenotype is generally determined by retrospective questionnaire. To determine whether recently proposed phenotypes of preschool wheeze are stable over time. In all, 132 two to six-year-old children with doctor diagnosed asthma on maintenance inhaled corticosteroids were classified as having episodic (viral) wheeze or multiple trigger wheeze at a screening visit and then followed up at three-monthly intervals for a year. At each follow-up visit, standardized questionnaires were used to determine whether the subjects wheezed only with, or also in the absence of colds. Stability of the phenotypes was assessed at the end of the study. Phenotype as determined by retrospective parental report at the start of the study was not predictive of phenotype during the study year. Phenotypic classification remained the same in 45.9% of children and altered in 54.1% of children. When children with preschool wheeze are classified into episodic (viral) wheeze or multiple trigger wheeze based on retrospective questionnaire, the classification is likely to change significantly within a 1-year period.

Laser monitoring of chest wall displacement

Publisher: European Respiratory Society (ERS)

Date: 08-1997

DOI: 10.1183/09031936.97.10081865

Abstract: We developed a prototype laser monitor, consisting of a single laser sensor, to observe chest wall displacement during respiration. With this monitor, respiratory waveforms are expressed as an anterioposterior motion of the chest wall. The purpose of this study was to examine the characteristics and performance of this prototype. Performance was assessed: 1) under static conditions 2) using a lung model ventilated in both conventional and high frequency oscillation (HFOV) modes and 3) during spontaneous breathing in normal adults. In vitro, the monitor performed well both under static conditions and during mechanical ventilation. Reliable "respiratory" wave forms, with no frequency-dependent change in the relationship between displacement and volume, were produced during both conventional ventilation and HFOV at 15 Hz. In vivo, abdominal displacement, measured in the midline, was linearly correlated with the tidal volume signal integrated from flow. The waveforms produced by the monitor were adequate for monitoring respiration and for calculating respiratory timing variables. While a single laser sensor is unlikely to be sufficient for monitoring respiration in spontaneously breathing subjects, the performance of the prototype monitor was sufficiently impressive to encourage further development and further study of this type of truly noninvasive respiratory monitor.

Impact of prenatal and early life environmental exposures on normal human development

Publisher: Elsevier BV

Date: 12-2021

DOI: 10.1016/J.PRRV.2021.05.007

Susceptibility of Children to Environmental Pollutants

Publisher: Wiley

Date: 10-2008

DOI: 10.1196/ANNALS.1454.017

Abstract: Children are more vulnerable to adverse environmental exposures. The unique ways in which they interact with their environment and their dynamic developmental physiology mean that they generally receive a higher dose of toxicant for a given level of environmental exposure. In addition, children are frequently more likely to suffer adverse health outcomes from exposures. The developmental stage of the child during which the exposure occurs has a major influence on the consequences of the exposure. For ex le, exposures during organogenesis may result in permanent structural changes, whereas exposures once organogenesis is complete are more likely to result in functional consequences. The immune, respiratory, and central nervous systems are immature at birth and have a prolonged period of postnatal maturation. Thus, these organ systems are vulnerable to postnatal exposures.

Differing patterns of mechanical response to direct fetal hormone treatment

Publisher: Elsevier BV

Date: 03-1996

DOI: 10.1016/0034-5687(95)00095-X

Abstract: A single combined intramuscular dose of betamethasone and l-thyroxine (T4) or placebo was injected into the shoulder of fetal lambs 48 hours prior to delivery at days 121 (n = 14), 128 (n = 25) or 135 (n = 20) of gestation. Respiratory mechanics were calculated using multiple linear regression analysis. Both respiratory system resistance (RRS) and elastance (ERS) decreased approximately 4 fold between gestational days 121 (D121) and 135 (D135). Both variables were also reduced by hormone treatment. Reduction in ERS was due to a reduction in both lung (EL) and chest wall (EW) components. In absolute terms EW decreased with gestational age however, EW as a proportion of total elastance (% EW) increased. Inclusion of a volume-dependent elastance term in the multiple linear regression model enabled us to separate total elastance into volume-independent (E1) and volume-dependent (E2V) components. E1 decreased almost 8-fold compared with only a 2.5-fold fall in E2V between D121 and D135. %E2, the proportion of ERS which is volume-dependent and which provides an index of overventilation, doubled over this time period. Hormone treatment affected E1 and E2V components equally hence %E2 was not altered. Both excised lung volume and end expiratory alveolar volume increased with gestational age and with treatment. The response to treatment was qualitatively similar at each of the gestational ages examined, however, for all mechanics variables, except resistance and E1, the magnitude of response to treatment was significantly smaller in D135 animals compared with other age groups.

Tectonics and melting in intra-continental settings

Publisher: Elsevier BV

Date: 2015

DOI: 10.1016/J.GR.2013.09.021

Mineral systems prospectivity modelling for gold and nickel in the Halls Creek Orogen, Western Australia

Publisher: Elsevier BV

Date: 12-2020

DOI: 10.1016/J.OREGEOREV.2020.103809

Concentrations of organophosphate flame retardants and plasticizers in urine from young children in Queensland, Australia and associations with environmental and behavioural factors

Publisher: Elsevier BV

Date: 07-2018

DOI: 10.1016/J.ENVRES.2018.02.040

Abstract: In recent years, the production and usage volumes of organophosphate flame retardants (OPFRs) has increased substantially. Certain OPFRs are suspected reproductive toxins, carcinogenic, and neurotoxic. Insufficient information is available on human exposure pathways to these chemicals, particularly in Australia. We aim to assess the association between OPFR concentrations in the urine of children to environmental and behavioural risk factors. Concentrations of eight OPFRs and eleven metabolites were measured in the urine of 51 children, aged 3-29 months, in Southeast Queensland, Australia and compared to their behavioural and environmental risk factor data obtained by an online questionnaire. Of the 11 OPFR metabolites analysed, 55% were frequently detected in the majority (> 80%) of s les. The most frequently detected metabolite was bis(1,3-dichloroisopropyl) phosphate (BDCIPP) (detected in 100% of s les), followed by 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate (BCIPHIPP) (96%), diphenyl phosphate (DPHP) (94%) and bis(1-chloroisopropyl) phosphate (BCIPP) (86%). In multivariable modelling, age was positively associated with concentrations of bis(2-butoxyethyl) phosphate (BBOEP) and negatively associated with concentrations of BCIPP and BCIPHIPP. Other non-age related factors, including vacuuming frequency, hand-washing frequency and presence and number of some electrical appliances in the home were also associated with concentrations of OPFR metabolites.

Early Lung Disease in Infants and Preschool Children with Cystic Fibrosis. What Have We Learned and What Should We Do about It?

Publisher: American Thoracic Society

Date: 15-06-2017

DOI: 10.1164/RCCM.201606-1107CI

An official American Thoracic Society/European Respiratory Society statement: Pulmonary function testing in preschool children

Publisher: American Thoracic Society

Date: 15-06-2007

DOI: 10.1164/RCCM.200605-642ST

Methacholine responsiveness in infants assessed with low frequency forced oscillation and forced expiration techniques

Publisher: BMJ

Date: 2001

DOI: 10.1136/THORAX.56.1.42

Abstract: The contribution of the pulmonary tissues to the mechanical behaviour of the respiratory system is well recognised. This study was undertaken to detect airway and lung tissue responses to inhaled methacholine (Mch) using the low frequency forced oscillation technique (LFOT). The respiratory system impedance (Zrs, 0.5-20 Hz) was determined in 17 asymptomatic infants. A model containing airway resistance (Raw) and inertance (Iaw) and a constant phase tissue d ing (G) and elastance (H) was fitted to Zrs data. Tissue hysteresivity (eta) was calculated as eta=G/H. The raised volume rapid thoracic compression technique (RVRTC) was used to generate forced expiratory volume in 0.5 seconds (FEV(0.5)). Lung function was determined at baseline and following inhaled Mch in doubling doses (0.25-16 mg/ml) until the maximal dose was reached or a fall of 15% in FEV(0.5) was achieved (PC(15)FEV(0.5)). The response to Mch was defined in terms of the concentration of Mch provoking a change in lung function parameters of more than two standard deviation units (threshold concentration). At PC(15)FEV(0.5) a response in Raw, Iaw, G, and eta, but not H, was detected (mean (SE) 61.28 (12.22)%, 95.43 (34.31)%, 46.28 (22.36)%, 44.26 (25.83)%, and -6.48 (4.94)%, respectively). No significant differences were found between threshold concentrations of LFOT parameters and FEV(0.5). Inhaled Mch alters both airway and respiratory tissue mechanics in infants.

The bimodal quasi-static and dynamic elastance of the murine lung

Publisher: American Physiological Society

Date: 08-2008

DOI: 10.1152/JAPPLPHYSIOL.90328.2008

Abstract: The double sigmoidal nature of the mouse pressure-volume (PV) curve is well recognized but largely ignored. This study systematically examined the effect of inflating the mouse lung to 40 cm H 2 O transrespiratory pressure (P rs ) in vivo. Adult BALB/c mice were anesthetized, tracheostomized, and mechanically ventilated. Thoracic gas volume was calculated using plethysmography and electrical stimulation of the intercostal muscles. Lung mechanics were tracked during inflation-deflation maneuvers using a modification of the forced oscillation technique. Inflation beyond 20 cm H 2 O caused a shift in subsequent PV curves with an increase in slope of the inflation limb and an increase in lung volume at 20 cm H 2 O. There was an overall decrease in tissue elastance and a fundamental change in its volume dependence. This apparent “softening” of the lung could be recovered by partial degassing of the lung or applying a negative transrespiratory pressure such that lung volume decreased below functional residual capacity. Allowing the lung to spontaneously recover revealed that the lung required ∼1 h of mechanical ventilation to return to the original state. We propose a number of possible mechanisms for these observations and suggest that they are most likely explained by the unfolding of alveolar septa and the subsequent redistribution of the fluid lining the alveoli at high transrespiratory pressure.

Health effects of exposure to e-waste

Publisher: Elsevier BV

Date: 08-2013

DOI: 10.1016/S2214-109X(13)70020-2

Nanoparticles and Children's Lungs: is there a need for caution?

Publisher: Elsevier BV

Date: 06-2012

DOI: 10.1016/J.PRRV.2011.07.005

Intestinal helminth infestation is associated with increased bronchial responsiveness in children

Publisher: Wiley

Date: 07-2008

DOI: 10.1002/PPUL.20833

Abstract: Non-atopic asthma is the predominant phenotype in non-affluent parts of Latin America. We recently reported that infestation with Ascaris lumbricoides increased the risk of non-atopic asthma in less affluent areas of Brazil but the mechanism is unclear. The present study was conducted to determine whether helminth infestation is associated with heightened bronchial responsiveness (BHR), a common finding in asthma. A random s le of 50 asthmatic and 50 non-asthmatic controls (mean age 10.1 years) were selected from a larger cohort (n = 1,011) without knowledge of their helminth infestation status. Three stool s les were collected from each child on different days and each s le was analyzed by the Kato-Katz method for quantitative determination of helminth eggs. Bronchial provocation tests were performed with inhaled 4.5% hypertonic saline using the ISAAC Phase II standardized protocol. There was no difference between the prevalence of positive BHR in the asthmatics (20.4%) compared with the controls (14.6%) (P = 1.0). Helminth infestation was detected in 24.0% of children, with A. lumbricoides being the most common. Children with high load infestation (>or=100 eggs/g) were five times more likely to have BHR than children with low load or no infestation. Despite the small s le size the results of the present study suggest that the link between high load helminth infestation and non-atopic asthma may be mediated via heightened bronchial responsiveness, possibly due to an inflammatory response to the pulmonary phase of the helminth life cycle.

Applied Clinical Respiratory Physiology

Publisher: Elsevier

Date: 2008

DOI: 10.1016/B978-032304048-8.50011-6

Unintentional mortality associated with paracetamol and codeine preparations, with and without doxylamine, in Australia.

Publisher: Elsevier BV

Date: 2018

DOI: 10.1016/J.FORSCIINT.2017.11.026

Abstract: Misuse of paracetamol, codeine and doxylamine combination analgesics may lead to addiction and mortality. This study aimed to (1) identify unintentional deaths in Australia associated with use of combination analgesic products containing paracetamol, codeine and doxylamine (2) describe cases characteristics, including demographics and additional medication use and (3) identify common factors associated with misuse and mortality of these medicines in Australia. This retrospective case series analysed National Coronial Information System data to identify cases of unintentional death attributable to paracetamol, codeine and doxylamine products between 2002 and 2012. Three Eastern Australian states: New South Wales, Queensland, Victoria, comprising a population of approximately 18.6 million people. 441 unintentional deaths attributed to paracetamol/codeine products were identified doxylamine was detected in 102 cases (23%). Overall unintentional death rates rose from 0.9-per-million in 2002 to 3.6-per-million in 2009, declining to 1.9-per-million in 2012. Median age at time of death was 48, half of all cases occurred between 35-54 years of age, and 57% were female. Concomitant medication use was detected in 79% of cases, including benzodiazepines, other opioids, psychiatric medications, alcohol and illicit drugs. Behaviours consistent with drug misuse including doctor harmacy shopping, excessive dosages and extended use, were identified in 24% of cases. This study identified 441 deaths associated with codeine-combination analgesic products across three Australian states with an average of 40 deaths per year. Death commonly involved multiple substance use and abuse behaviours indicative of misuse and dependence.

Enhancement of vaccine-specific cellular immunity in infants by passively acquired maternal antibody

Publisher: Elsevier BV

Date: 09-2004

DOI: 10.1016/J.VACCINE.2004.03.052

Update in Asthma 2017

Publisher: American Thoracic Society

Date: 05-2018

DOI: 10.1164/RCCM.201801-0002UP

Effects of maternal smoking during pregnancy and a family history of asthma on respiratory function in newborn infants

Publisher: Elsevier BV

Date: 10-1996

DOI: 10.1016/S0140-6736(96)04446-7

Abstract: Infants of mothers who smoke have reduced respiratory function and are more likely to develop wheezing. Little evidence is available on the effect of in-utero cigarette-smoke exposure as opposed to postnatal exposure to environmental tobacco smoke. We used a previously validated non-invasive method to measure the time to peak tidal expiratory flow (tPTEF) as a proportion of expiratory time (tE) in newborn infants soon after birth to examine the effects of a family history of asthma and in-utero cigarette-smoke exposure on the infants' respiratory function. We collected respiratory-function data from 500 healthy infants of mothers taking part in the Western Australia Pregnancy Cohort Study. During behaviourally defined quiet sleep, measurements were obtained a median of 58 h (range 26-159) after the infants were born. We used uncalibrated inductance plethysmography. The uncalibrated volume signal was differentiated to flow and used to calculate respiratory rate, total inspiratory time, tE, and tPTEF. Mothers answered questionnaires on demographic, medical, and pregnancy characteristics, including smoking history. Serum cotinine measurements were available to validate self-reported smoking history in a subset of mothers (238). Data suitable for analysis were obtained from 461 infants. In multivariate regression analysis, lower values of tPTEF/tE were independently associated with respiratory rate (beta coefficient per 10 breaths/min 0.018 [SE 0.005], p < 0.01), age (beta coefficient per 10 h -0.008 [0.003], p 10 cigarettes daily beta coefficient -0.049 [0.022], p < 0.05), maternal hypertension during pregnancy (-0.037 [0.015], p < 0.02), and a family history of asthma (-0.028[0.014], p < 0.05). In-utero smoke exposure, a family history of asthma, and maternal hypertension during pregnancy are associated with reduced respiratory function after birth. We speculate that these factors adversely affect lung development in utero.

Physiological and inflammatory responses in an anthropomorphically relevant model of acute diesel exhaust particle exposure are sex and dose-dependent

Publisher: Informa UK Limited

Date: 29-11-2011

DOI: 10.3109/08958378.2011.625454

Abstract: Diesel exhaust particles (DEP) are an important contributor to suspended particulate matter (PM) in urban areas. While epidemiological evidence exists for a sex-influenced dose-response relationship between acute PM exposure and respiratory health, similar data are lacking for DEP. Further, experimental evidence showing deleterious effects on respiratory health due to acute DEP exposure is sparse. To establish and characterize a mouse model of acute DEP exposure, comparing male and female mice and assessing the kinetics of the elemental carbon content of alveolar macrophages (AMs) to relate our model to human exposure. Adult BALB/c mice were intranasally inoculated with 0 (control), 10, 30 or 100 µg DEP in saline. Bronchoalveolar lavage cellular inflammation and cytokine levels were assessed 3, 6, 12, 24, 48 and 168 hours post exposure. Elemental carbon uptake by AMs was additionally assessed at 336 and 672 hours post DEP exposure. Thoracic gas volume and lung mechanics were measured 6 and 24 hours post exposure. DEP resulted in dose-dependent cellular inflammation and cytokine production in both sexes. Males and females responded differently with females having more severe and prolonged neutrophilia, monocyte chemoattractant protein-1 and developing greater abnormalities in lung function. The sexual dimorphism in response was not related to the capacity of AMs to phagocytise DEP. Our mouse model of acute diesel exhaust particle exposure shows a dose dependency and sexual dimorphism in response. Quantification of elemental carbon in AMs allows for comparison of the results of our study with human studies.

HMGB1 amplifies ILC2-induced type-2 inflammation and airway smooth muscle remodelling

Publisher: Public Library of Science (PLoS)

Date: 13-07-2020

DOI: 10.1371/JOURNAL.PPAT.1008651

Policy decisions on endocrine disruptors should be based on science across disciplines: a response to Dietrichet al.

Publisher: Wiley

Date: 24-10-2013

DOI: 10.1111/J.2047-2927.2013.00151.X

Reprint of: Policy decisions on endocrine disruptors should be based on science across disciplines: A response to Dietrich, et al.

Publisher: Elsevier BV

Date: 2014

DOI: 10.1016/J.YFRNE.2013.09.003

Nonatopic asthma is associated with helminth infections and bronchiolitis in poor children

Publisher: European Respiratory Society (ERS)

Date: 03-2007

DOI: 10.1183/09031936.00127606

Abstract: Asthma is common in urban centres in Latin America, but atopic asthma may not be the main phenotype among children. Helminth infections are highly prevalent in poor populations, and it was hypothesised that they attenuate allergic asthma, whereas other factors are related to the expression of a nonatopic wheeze/asthma phenotype. A total of 1,982 children from Southern Brazil with a mean+/-sd age of 10.1+/-0.76 yrs completed asthma questionnaires, and 1,011 were evaluated for intestinal parasites and atopy using skin-prick tests (SPTs). Wheeze in the previous 12 months was reported by 25.6%, and 9.3% showed current asthma 13% were SPT-positive and 19.1% were positive for any helminths. Most children with either wheeze or asthma were SPT-negative however, severe wheeze was more prevalent among the atopic minority. Helminth infections were inversely associated with positive SPT results. Bronchiolitis before the age of 2 yrs was the major independent risk factor for asthma at age 10 yrs high-load Ascaris infection, a family history of asthma and positive SPT results were also asthma risk factors. Most asthma and wheeze are of the nonatopic phenotype, suggesting that some helminths may exert an attenuating effect on the expression of the atopic portion of the disease, whereas viral bronchiolitis predisposes more specifically to recurrent airway symptoms.

Exploring urinary biomarkers to assess oxidative DNA damage resulting from BTEX exposure in street children

Publisher: Elsevier BV

Date: 2022

DOI: 10.1016/J.ENVRES.2021.111725

Abstract: Children are highly susceptible to environmental contaminants as their physiology and some metabolic pathways differ from adults. The present cross-sectional study aimed to assess whether exposure to benzene, toluene, ethylbenzene, o,p-xylene, and m-xylene (BTEX) affects oxidative DNA damage in street children using a biomonitoring approach. Thirty-five boys (7-13 years of age), exposed by working at a busy intersection, and 25 unexposed boys of similar age and living in the neighborhood near the busy intersection were recruited. Urinary un-metabolized BTEX levels were quantified by a headspace gas chromatography-mass spectrometry (GC-MS). Urinary malonaldehyde (MDA) was measured with spectrophotometry. Sociodemographic and lifestyle conditions information was collected by interviews using administered questionnaires. Exposed subjects provided urine before (BE) and after work exposure (AE), while unexposed boys gave a single morning s le. Urinary BTEX concentrations in BE s les were similar to unexposed. Concentrations in AE s les were 2.36-fold higher than observed in BE s les (p < 0.05) and higher than those in the unexposed group (p < 0.05). In addition, urinary MDA levels in AE s les were 3.2 and 3.07-times higher than in BE s les and in the unexposed group (p < 0.05). Environmental tobacco smoke (ETS) increased urinary BTEX and MDA levels in both groups. Our findings confirm that street children working at busy intersections are significantly exposed to BTEX, which is associated with oxidative stress. Implementing protective measures is crucial to reduce exposure and to improve health outcomes in this group.

Impact of postnatal glucocorticoids on early lung development

Publisher: American Physiological Society

Date: 03-2005

DOI: 10.1152/JAPPLPHYSIOL.00486.2004

Abstract: Inhaled glucocorticoid treatment during the first 2 yr of life is controversial because this is a period of major structural remodeling of the lung. Rabbits received aerosolized budesonide (Bud 250 μg/ml) or injected dexamethasone (Dex 0.05 mg·ml −1 ·kg −1 ) between 1 and 5 wk of age. Treatment with Bud caused specific growth retardation of the lung. Dex but not Bud affected the mechanical properties of the lung parenchyma, when corrected for lung volume. Small peripheral airway walls in both glucocorticoid groups were thinner and had fewer alveolar attachment points with greater distance between attachments than controls, but collagen content was not affected by glucocorticoids. Dex led to reduced body weight, lung volume, alveolar number, and surface area. The alveolar size and number and elastin content, when related to lung volume, was not affected by Bud, suggesting normal structural development but inhibition of total growth. Arterial wall thickness and diameter were affected by Bud. This study demonstrates that developing lungs are sensitive to inhaled glucocorticoids. As such, the use of glucocorticoids in young infants and children should be monitored with caution and only the lowest doses that yield significant clinical improvement should be used.

The importance of the local environment in the transmission of respiratory syncytial virus

Publisher: Elsevier BV

Date: 09-2014

DOI: 10.1016/J.SCITOTENV.2014.06.021

Abstract: The role of the environment in the spread of respiratory infections is poorly understood, and consequently probably underappreciated. To improve our understanding of the environmental drivers of respiratory syncytial virus (RSV) transmission, we examined RSV seasonality in two settings with unusual seasonal patterns: The Gambia (where RSV epidemics occur at different times of the year) and Southeast Florida (where RSV seasonality differs from the rest of mainland USA). We used published data to correlate the seasonality of RSV with rainfall and child nutrition in the Gambia, and with rainfall and temperature in Florida. In the Gambia, RSV incidence was more strongly and more consistently correlated with child nutrition (r = -0.73 [95%CI -0.90 to -0.38]) than with rainfall (r = 0.37 [95%CI 0.20 to 0.52]). In Southeast Florida RSV incidence was strongly correlated with rainfall two months previously (r = 0.65 [95%CI 0.40 to 0.81]) compared to North Florida where RSV incidence was strongly correlated with temperature (r = -0.75 [95%CI -0.87 to -0.56]). We propose that nutrition is the dominant environmental driver of RSV seasonality in the Gambia, while rainfall is the dominant driver of RSV seasonality in Southeast Florida. This reinforces the importance of an ecological scale understanding of disease transmission: only with such an evidence base can setting-specific recommendations be made for public health interventions that are targeted for maximum efficacy.

Cystic Fibrosis Survival Gap Closing between the United States and Canada. Don’t Leave Anyone Behind!

Publisher: American Thoracic Society

Date: 15-03-2018

DOI: 10.1164/RCCM.201711-2201ED

Parental smoking impairs vaccine responses in children with atopic genotypes

Publisher: Elsevier BV

Date: 02-2007

DOI: 10.1016/J.JACI.2006.09.018

Abstract: Gene-environment interactions play central roles in controlling postnatal maturation of immune function, but their effects on infant vaccine responses are unknown. Genetic variants associated with atopy and the environmental factor of exposure to parental smoking (PS) of tobacco independently alter immune responses. We sought to investigate the hypothesis that genetic variants associated with atopy and their interaction with PS influence infant vaccine responsiveness. In 200 infants with parental atopic history, relationships were sought between polymorphisms in the IL-4, IL-4 receptor alpha (IL-4Ralpha), and IL-13 genes PS and immune responses to diphtheria/tetanus vaccination. Analyses stratified by PS unmasked negative associations between atopic alleles of these genes and vaccine outcomes. The most consistent involved the IL-4Ralpha 551 QR/QQ genotypes, which were associated with reduced IgG levels (P = .02) and T-cell responses (IFN-gamma, P = .002 IL-10, P = .01 1L-13, P = .01 IL-5, P = .06) to tetanus toxoid and parallel reductions in polyclonal T-cell responses and innate immune responses in PS-exposed infants. PS potentiates suppressive effects of variants in immune response genes in children. These effects are not observed in the absence of this exposure. Ultimately, this finding might have implications for infant vaccination in countries with high smoking rates. It might also have broader implications in relation to environmental toxicology because it demonstrates specific mechanisms through which the developing immune system might be differentially sensitive to low-level toxicant exposures. PS interacts with genes associated with atopy to impair vaccine responses. These interactions might have vaccine design and public health implications.

Pooling of bronchoalveolar lavage in children with cystic fibrosis does not adversely affect the microbiological yield or sensitivity in detecting pulmonary inflammation

Publisher: Elsevier BV

Date: 05-2018

DOI: 10.1016/J.JCF.2017.10.016

Abstract: Bronchoalveolar lavage (BAL) is a potentially useful outcome measure for clinical trials in children with CF but its use is limited by variations in approach internationally. We sought to determine if pooling adversely affected the diagnostic properties of BAL. Children undergoing bronchoscopy for clinical reasons were included. A multi-step study protocol ensured BAL was collected and analysed both separately and as a pooled fluid. Eighty-five children (53 CF, 32 control) were recruited. There was a high level of concordance between pooled and non-pooled s les in terms of organism identification (76%). There was good agreement (Bland Altman) between the two methods in terms of detection of inflammation independent of centre, microbiological concordance or disease status. Bi-directional variability in IL-8 levels between pooled and non-pooled s les was seen. Free neutrophil elastase (NE) was detected in 4 cases in pooled lavage when absent in non-pooled lavage. Levels of interleukin-8 (IL-8) were similar between the two groups with pooled s les showing a greater spread of values. Pooling of BAL in children does not negatively impact on either the detection of pulmonary infection or inflammation or the observed relationship between infection and inflammation. Intra-patient variability in BAL IL-8 levels suggests regional differences in inflammation.

Pediatric lung function testing during a pandemic: An international perspective

Publisher: Elsevier BV

Date: 11-2020

DOI: 10.1016/J.PRRV.2020.10.001

Children's environmental health: an under-recognised area in paediatric health care

Publisher: Springer Science and Business Media LLC

Date: 06-02-2009

DOI: 10.1186/1471-2431-9-10

Abstract: The knowledge that the environment in which we live, grow and play, can have negative or positive impacts on our health and development is not new. However the recognition that adverse environments can significantly and specifically affect the growth and development of a child from early intrauterine life through to adolescence, as well as impact their health later in adulthood, is relatively recent and has not fully reached health care providers involved in paediatric care. Over the past 15 years, world declarations and statements on children's rights, sustainable development, chemical safety and most recently climate change, have succeeded in cultivating a global focus on children's health and their right to a healthy environment. Many international calls for research in the area, have also been able to identify patterns of environmental diseases in children, assess children's exposures to many environmental toxicants, identify developmental periods of vulnerability, and quantify the cost benefits to public health systems and beyond, of addressing environmentally related diseases in children. Transferring this information to front-line health care providers and increasing their awareness about the global burden of disease attributed to the environment and children's especial vulnerability to environmental threats is the salient aim of this commentary.

Ultrastructural examination of bronchial specimens from children with moderate asthma

Publisher: BMJ

Date: 02-2003

DOI: 10.1136/THORAX.58.2.187

Nasal wash as an alternative to bronchoalveolar lavage in detecting early pulmonary inflammation in children with cystic fibrosis

Publisher: Wiley

Date: 03-2005

DOI: 10.1111/J.1440-1843.2005.00649.X

Abstract: The aim of this study was to determine whether nasal inflammation reflects pulmonary inflammation in young children with cystic fibrosis (CF), as assessed by inflammatory markers in nasal wash (NW) and bronchoalveolar lavage (BAL), respectively. CF patients younger than 6 years of age who were to undergo bronchoscopy for routine BAL from May 2000 to October 2001 were recruited for this study. NW was collected immediately after the patient was sedated for bronchoscopy. Total cell counts (TCC), differential cell counts and interleukin (IL)-8 levels (enzyme-linked immunosorbent assay) were assessed in NW and BAL. In total, 19 children with CF (mean age, 1.9 years SD, 1.7 years) were included in the study. There was a significant relationship between IL-8 and the percentages of neutrophils in NW (r (2) = 0.76 P < 0.001) and in BAL fluid (r 2 = 0.62 P = 0.006). Similarly, IL-8 concentrations in the NW correlated with those in the BAL (r 2 = 0.48 P = 0.036) and neutrophil percentages in NW correlated significantly with those in BAL (r 2 = 0.7 P = 0.004). When measured under 'ideal' conditions, nasal IL-8 reflects lower airway levels and may reflect the inflammatory stimulus that results in neutrophilic inflammation. These data encourage further assessment of nasal wash under clinically appropriate conditions to determine its utility for assessing inflammation in young children with CF.

Inhalant allergen-specific T-cell reactivity is detectable in close to 100% of atopic and normal individuals: Covert responses are unmasked by serum-free medium

Publisher: Wiley

Date: 07-1995

DOI: 10.1111/J.1365-2222.1995.TB01111.X

Abstract: It is widely held that in vitro T cell responses to allergens are more prominent in atopic than in normal in iduals, though this conclusion is based upon culture techniques which fail to detect proliferative responses in a significant minority of atopics and many normals. Study allergen-specific proliferative responses of T cells cultured in serum-free medium (SFM). Examine associations between atopic status, age and T cell reactivity. Initially, peripheral blood mononuclear cells were stimulated with allergens or antigens in SFM, and compared with cells cultured in RPMI + 10% fetal calf serum or human AB serum. Subsequently, T cell reactivity was studied in 34 adults (20-49 years), 27 children (2-13 years), and 19 infants (< or = 10 weeks) using SFM alone. Compared with serum-supplemented medium, SFM enhanced net T cell proliferation, both in bulk culture and when cloning at limiting dilution. In many subjects, SFM unmasked T cell reactivity to allergens which was not otherwise evident, and lowered the threshold allergen levels required for in vitro T cell triggering. For most allergens, T cell proliferative responses did not differ between adults who had specific IgE, and those who did not. The most vigorous responses observed were to ubiquitous inhalant allergens, which stimulated T cells from close to 100% of adults and children, and over 60% of infants. In contrast, responses to the 'vaccine' antigen tetanus toxoid were completely absent in the latter age group, but present in the majority of adults and children. These findings suggest that the extent of active T cell recognition of environmental allergens has been hitherto underestimated, and further that these responses may frequently be initiated in very early life. Additionally, these findings reinforce the notion that qualitative (as opposed to quantitative) variations in specific T cell reactivity ultimately determine allergen responder phenotype.

Developmental physiology: lung function during growth and development from birth to old age

Publisher: European Respiratory Society Journals Ltd

Date: 03-2010

DOI: 10.1183/1025448X.00011109

Meta-analysis identifies seven susceptibility loci involved in the atopic march

Publisher: Springer Science and Business Media LLC

Date: 06-11-2015

DOI: 10.1038/NCOMMS9804

Abstract: Eczema often precedes the development of asthma in a disease course called the ‘atopic march’. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27 P= 2.1 × 10 −8 ) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58 P= 5.3 × 10 −9 ). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema.

Developmental factors associated with risk for atopic disease: implications for vaccine strategies in early childhood

Publisher: Elsevier BV

Date: 28-07-2003

DOI: 10.1016/S0264-410X(03)00345-1

Abstract: There is growing interest in the potential interactions between infant vaccination and risk for development of atopic disease. The aspect of this issue which has dominated this debate concerns suggestions that infant vaccination may stimulate allergic sensitisation. These suggestions derive from retrospective epidemiological analyses and will remain speculative unless they can be confirmed in prospective studies, particularly as conflicting findings have been reported. However, there is a potentially more important issue surfacing in this debate, which entails the converse situation, i.e. that genetic risk for atopy influences capacity to respond to vaccination during infancy. Support for the latter possibility comes from recent studies on the role of developmental factors which determine immune competence during infancy, and attendant risk for inflammatory and infectious diseases. The relevant findings are reviewed briefly below.

Short term variability in urinary bisphenol A in Australian children

Publisher: Elsevier BV

Date: 07-2014

DOI: 10.1016/J.ENVINT.2014.03.027

Abstract: Used frequently in food contact materials, bisphenol A (BPA) has been studied extensively in recent years, and ubiquitous exposure in the general population has been demonstrated worldwide. Characterizing within- and between-in idual variability of BPA concentrations is important for characterizing exposure in biomonitoring studies, and this has been investigated previously in adults, but not in children. The aim of this study was to characterize the short-term variability of BPA in spot urine s les in young children. Children aged ≥2-<4 years (n=25) were recruited from an existing cohort in Queensland, Australia, and donated four spot urine s les each over a two day period. S les were analysed for total BPA using isotope dilution online solid phase extraction-liquid chromatography-tandem mass spectrometry, and concentrations ranged from 0.53 to 74.5 ng/ml, with geometric mean and standard deviation of 2.70 ng/ml and 2.94 ng/ml, respectively. Sex and time of s le collection were not significant predictors of BPA concentration. The between-in idual variability was approximately equal to the within-in idual variability (ICC=0.51), and this ICC is somewhat higher than previously reported literature values. This may be the result of physiological or behavioural differences between children and adults or of the relatively short exposure window assessed. Using a bootstrapping methodology, a single s le resulted in correct tertile classification approximately 70% of the time. This study suggests that single spot s les obtained from young children provide a reliable characterization of absolute and relative exposure over the short time window studied, but this may not hold true over longer timeframes.

Antibiotic use in the first year of life and risk of atopic disease in early childhood

Publisher: Wiley

Date: 19-11-2023

DOI: 10.1111/J.1365-2222.2008.03138.X

Abstract: Reduced post-natal microbial stimulation resulting from improvements in public health measures, smaller family size, and through increased antibiotic use has been postulated to account for the increasing prevalence of atopic diseases seen predominantly in developed countries. To investigate use of antibiotics in the first year of life and subsequent development of atopic disease in early childhood. A prospective birth cohort of 198 children at high atopic risk was recruited prenatally and followed for 5 years. Illnesses and antibiotic use were ascertained through daily diaries, and diagnoses of asthma and hayfever were collected by questionnaire interviews. The children were examined regularly for eczema, and atopic status was defined by skin prick tests and serum total IgE. The effect of antibiotic use on subsequent atopic disease was examined using logistic regression with propensity score adjustment. 54.0% (107/198) of children received at least one course of antibiotics, mainly for acute respiratory illnesses (ARI). Thirty-three percent (329/984) of the ARI involved the lower respiratory tract (LRI). Twenty-three percent (222/984) of ARI were treated with antibiotics, with LRI significantly more likely to receive antibiotics. Antibiotic use was associated with asthma (unadjusted odds ratio 2.3 95% confidence interval 1.2-4.5 P=0.01) but this association was reduced after propensity score adjustment. No associations were found between antibiotic use and eczema, current wheeze, current asthma, atopic asthma, allergic rhinoconjunctivitis or atopy. Although this was a small study, systematic and careful monitoring of ARI, antibiotic use, and asthma and atopic diseases did not indicate that receipt of antibiotics early in life led to subsequent asthma or atopy at 5 years.

Event-Based Consensus Tracking for Nonlinear Multi-Agent Systems under Semi-Markov Jump Topology

Publisher: Institute of Electrical and Electronics Engineers (IEEE)

Date: 2021

DOI: 10.1109/ACCESS.2021.3116253

γδ T cells provide a breath of fresh air for asthma research

Publisher: Springer Science and Business Media LLC

Date: 10-1999

DOI: 10.1038/13447

Abstract: gammadelta T cells downregulate airways responsiveness to allergen challenge, possibly by controlling the 'repair' response of the airway epithelium to alphabeta T cell-mediated damage (pages 1150-1156).

Directed neutrophil migration to IL-8 is increased in cystic fibrosis: a study of the effect of erythromycin

Publisher: BMJ

Date: 1

DOI: 10.1136/THORAX.56.1.62

Abstract: The aim of this study was to compare neutrophil migration in cystic fibrosis (CF) and non-CF populations and to investigate the effect of erythromycin on directed migration of neutrophils (PMNs) in CF. PMNs were isolated and their migratory capacity in response to interleukin-8 (IL-8) or f-Met-Leu-Phe (fMLP) in the presence or absence of erythromycin (1-100 microg/ml) was assessed. CF derived PMNs showed significantly increased migration to IL-8 but not to fMLP compared with non-CF PMNs. Erythromycin had no significant effect on migration responses to IL-8 and in vitro exposure of PMNs to erythromycin had no effect. CF derived PMNs show higher migratory responsiveness to IL-8 but not to fMLP, suggesting that CF PMNs may be "primed" to IL-8 which is significantly increased in CF serum compared with non-CF serum. Treatment with erythromycin had no significant effect on PMN migration in vitro.

Prevention of allergic respiratory disease in infants: current aspects and future perspectives

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 12-2007

DOI: 10.1097/ACI.0B013E3282F14A17

A Network Modeling Approach to Analysis of the Th2 Memory Responses Underlying Human Atopic Disease

Publisher: The American Association of Immunologists

Date: 15-05-2009

DOI: 10.4049/JIMMUNOL.0804125

Abstract: Complex cellular functions within immunoinflammatory cascades are conducted by networks of interacting genes. In this study, we employed a network modeling approach to dissect and interpret global gene expression patterns in allergen-induced Th cell responses that underpin human atopic disease. We demonstrate that a subnet of interconnected genes enriched for Th2 and regulatory T cell-associated signatures plus many novel genes is hardwired into the atopic response and is a hallmark of atopy at the systems level. We show that activation of this subnet is stabilized via hyperconnected “hub” genes, the selective disruption of which can collapse the entire network in a comprehensive fashion. Finally, we investigated gene expression in different Th cell subsets and show that regulatory T cell- and Th2-associated signatures partition at different stages of Th memory cell differentiation. Moreover, we demonstrate the parallel presence of a core element of the Th2-associated gene signature in bystander naive cells, which can be reproduced by rIL-4. These findings indicate that network analysis provides significant additional insight into atopic mechanisms beyond that achievable with conventional microarray analyses, predicting functional interactions between novel genes and previously recognized members of the allergic cascade. This approach provides novel opportunities for design of therapeutic strategies that target entire networks of genes rather than in idual effector molecules.

Differences in the antibody response to a mucosal bacterial antigen between allergic and non-allergic subjectsSmoke-free legislation reduces exposure in children

Publisher: BMJ

Date: 03-2008

DOI: 10.1136/THX.2006.069492

Abstract: The immune response to bacterial antigens on mucosal surfaces may be modified in in iduals allergic to aeroallergens due to a maturational or genetic difference or from the interaction between inhaled allergens and bacteria at the mucosa. Plasma from children and adults allergic (n = 97) and non-allergic (n = 54) to aeroallergens were initially tested for IgG1 (Th1) and IgG4 (Th2) reactivity to P6, a conserved outer membrane protein of Haemophilus influenzae. IgE binding was measured for some allergic donors. The development of the antibody responses to P6 was subsequently examined in the plasma from 35 children aged 1, 2 and 5 years taken from a prospective birth cohort. IgG4 antibodies to P6 were more readily detected in allergic subjects than in non-allergic subjects (p<0.001), with a strong bias to the male gender. Some allergic subjects (35%) also had IgE antibody (1-10 ng/ml) that was not associated with IgG4 or gender. In the cohort study of infants, subjects who developed skin prick test positivity to mite allergens by 5 years of age had an 85% reduction in the IgG1 anti-P6 antibody at year 2 (p<0.05) and, unlike skin test negative infants, this group had IgG4 anti-P6 antibodies at 5 years of age. The antibodies of subjects allergic to a bacterial antigen included IgE and IgG4 (particularly for males) compared with the almost exclusive IgG1 response of non-allergic subjects. The IgG1 responses of 2-year-old children who became skin test positive was markedly reduced and P6-specific IgG4 became detectable at 5 years of age.

Bullying in children and adolescents: A modifiable risk factor for mental illness

Publisher: SAGE Publications

Date: 06-12-2013

DOI: 10.1177/0004867413508456

Plasmacytoid dendritic cells protect from viral bronchiolitis and asthma through semaphorin 4a–mediated T reg expansion

Publisher: Rockefeller University Press

Date: 22-12-2017

DOI: 10.1084/JEM.20170298

Abstract: Respiratory syncytial virus–bronchiolitis is a major independent risk factor for subsequent asthma, but the causal mechanisms remain obscure. We identified that transient plasmacytoid dendritic cell (pDC) depletion during primary Pneumovirus infection alone predisposed to severe bronchiolitis in early life and subsequent asthma in later life after reinfection. pDC depletion ablated interferon production and increased viral load however, the heightened immunopathology and susceptibility to subsequent asthma stemmed from a failure to expand functional neuropilin-1+ regulatory T (T reg) cells in the absence of pDC-derived semaphorin 4a (Sema4a). In adult mice, pDC depletion predisposed to severe bronchiolitis only after antibiotic treatment. Consistent with a protective role for the microbiome, treatment of pDC-depleted neonates with the microbial-derived metabolite propionate promoted Sema4a-dependent T reg cell expansion, ameliorating both diseases. In children with viral bronchiolitis, nasal propionate levels were decreased and correlated with an IL-6high/IL-10low microenvironment. We highlight a common but age-related Sema4a-mediated pathway by which pDCs and microbial colonization induce T reg cell expansion to protect against severe bronchiolitis and subsequent asthma.

Volume Dependence of High-Frequency Respiratory Mechanics in Healthy Adults

Publisher: Springer Science and Business Media LLC

Date: 18-10-2007

DOI: 10.1007/S10439-007-9391-X

Abstract: Respiratory system input impedance (Zrs) at low to medium frequencies below 100 Hz, and study of its volume dependence, have been used extensively to quantify airway and tissue mechanics. Zrs at high oscillation frequencies including the first antiresonant frequency (far,1) may contain important information about airway mechanics. Changes in high-frequency Zrs with lung volume have not been studied. The volume-dependent behavior of high-frequency Zrs, specifically far,1 and respiratory system resistance at first antiresonance (Rrs(far,1)), was characterized in 16 healthy adults. Zrs was measured with a forced oscillation signal (5-302.5 Hz) through a wavetube setup. To track Zrs, subjects performed slow deep inspiratory and expiratory maneuvers over 30-s measurements, during which average impedance was calculated over 0.4-s intervals, with successive overlapping estimates every 0.156 s. Flow was measured using a pneumotachometer and integrated to obtain volume. Transpulmonary pressure dependence (Ptp) of Zrs was separately determined in five subjects. Both far,1 and Rrs(far,1) decreased with increasing lung volume and Ptp, consistent with an increase in airway caliber and decreased airway wall compliance as volume increased. These characterizations provide insight into airway mechanics, and are furthermore a necessary first step toward determining whether volume dependence of the first antiresonance is altered in disease.

Tracking of airway and tissue mechanics during TLC maneuvers in mice

Publisher: American Physiological Society

Date: 10-2003

DOI: 10.1152/JAPPLPHYSIOL.00104.2003

Abstract: A tracking impedance estimation technique was developed to follow the changes in total respiratory impedance (Zrs) during slow total lung capacity maneuvers in six anesthetized and mechanically ventilated BALB/c mice. Zrs was measured with the wave-tube technique and pseudorandom forced oscillations at nine frequencies between 4 and 38 Hz during inflation from a transrespiratory pressure of 0-20 cmH 2 O and subsequent deflation, each lasting for ∼20 s. Zrs was averaged for 0.125 s and fitted by a model featuring airway resistance (Raw) and inertance, and tissue d ing and elastance ( H). Lower airway conductance (Glaw) was linearly related to volume above functional residual capacity (V) between 0 and 75-95% maximum V, with a mean slope of dGlaw/dV = 13.6 ± 4.6 cmH 2 O -1 · s -1 . The interdependence of Raw and H was characterized by two distinct and closely linear relationships for the low- and high-volume regions, separated at ∼40% maximum V. Comparison of Raw with the highest-frequency resistance of the total respiratory system revealed a marked volume-dependent contribution of tissue resistance to total respiratory system resistance, resulting in the overestimation of Raw by 19 ± 8 and 163 ± 40% at functional residual capacity and total lung capacity, respectively, whereas the lowest frequency reactance was proportional to H these findings indicate that single-frequency resistance values may become inappropriate as surrogates of Raw when tissue impedance is changing.

The influence of age on aerosol deposition in children with cystic fibrosis

Publisher: European Respiratory Society (ERS)

Date: 12-1994

DOI: 10.1183/09031936.94.07122185

Abstract: Nebulized aerosols are commonly used to deliver drugs for the treatment of respiratory disease in children, but there are inadequate data on the dose of drug depositing in the lungs in this age group, and the effect of age on this dose. We therefore aimed to quantify total and regional deposition of nebulized aerosol in children of widely differing age. Twelve infants (median age 0.8 yrs, range 0.3-1.4 yrs) who were asleep, and eight older children (median age 10.8 yrs, range 6.3-18.0 yrs) with cystic fibrosis were studied. Radiolabelled normal saline aerosol was generated by a Turret nebulizer, with a driving flow of 9 l.min-1. All subjects inhaled aerosol via the nasal route, whilst the older children undertook a second study with inhalation via the oral route. Following aerosol inhalation, planar and single-photon emission computed tomography (SPECT) scans were obtained. For the nasal route, total lung deposition was lower in infants (median 1.3%, range 0.3-1.6%) than in older children (median 2.7%, range 1.6-4.4%). For the older children inhaling via the nasal or oral route, there was no influence of age on lung, upper respiratory tract, or the sum of upper respiratory tract and lung deposition. We conclude that the dose of a nasally inspired aerosol reaching the lungs of infants who are asleep is approximately half that for older children, when the nebulizer is operating at 9 l.min-1. Age does not affect deposition of nasally or orally inspired aerosols in older children.

Human Metapneumovirus Impairs Apoptosis of Nasal Epithelial Cells in Asthma via HSP70

Publisher: S. Karger AG

Date: 11-10-2017

DOI: 10.1159/000449101

Abstract: Asthmatics are highly susceptible to respiratory viral infections, possibly due to impaired innate immunity. However, the exact mechanisms of susceptibility are likely to differ amongst viruses. Therefore, we infected primary nasal epithelial cells (NECs) from adults with mild-to-moderate asthma, with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV) in vitro and investigated the antiviral response. NECs from these asthmatics supported elevated hMPV but not RSV infection, compared to non-asthmatic controls. This correlated with reduced apoptosis and reduced activation of caspase-9 and caspase-3/7 in response to hMPV, but not RSV. The expression of heat shock protein 70 (HSP70), a known inhibitor of caspase activation and subsequent apoptosis, was lified in response to hMPV infection. Chemical inhibition of HSP70 function restored caspase activation and reduced hMPV infection in NECs from asthmatic subjects. There was no impairment in the production of IFN by NECs from asthmatics in response to either hMPV or RSV, demonstrating that increased infection of asthmatic airway cells by hMPV is IFN-independent. This study demonstrates, for the first time, a mechanism for elevated hMPV infection in airway epithelial cells from adult asthmatics and identifies HSP70 as a potential target for antiviral and asthma therapies.

Longitudinal Cohort Studies on Child Health in South East Asia

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 2011

DOI: 10.1097/01.EDE.0000392232.53047.7A

Uniform symbols, abbreviations, and units in pediatric pulmonary function testing

Publisher: Wiley

Date: 07-1997

DOI: 10.1002/(SICI)1099-0496(199707)24:1<2::AID-PPUL2>3.0.CO;2-S

Abstract: Use of New Psychoactive Substances (NPS) has posed a global threat to public health and the security of the population. As of December 2019, the NPS items identified in total have outnumbered by three to one the controlled substances listed in the 1961 and 1971 UN Drug Conventions. However, most of these NPS have not been scheduled by the United Nations because of their easy modification on the chemical structures to shun control. Currently, the scheduling and control of NPS is mostly at the national level and a rational scheduling of NPS by objective assessments is essential but often lacking. To rationally schedule NPS, the NPS misuse situation was firstly estimated with the Taiwanese Substance Misuse Monitoring and Reporting Systems (SMMRS) from 2006 through 2019. Then, the assessment of drug-related harms with an expert Delphi procedure for drug scheduling was performed. The epidemiological analysis revealed that among 37 substances commonly misused in Taiwan, heroin posed the highest risk, followed by (meth) hetamine and ketamine. Of note, misuse of NPS, such as ketamine, synthetic cannabinoids (JWHs, AM-2201, XJR-11), synthetic cathinones (MDPV, bk-MDMA, 4 -MMCetc.), phenethylamines (PMMA, FMA, 2C-B, 2C-E etc.), piperazines (BZP, TFMPP) and tryptamines (5-MeO-DIPT) has been on the rise. Though perceived drug-related harms differed among experts with different professional backgrounds, the differences were not significant. Four dimensions of drug-related harms- addiction, misuse, social harm and physical harm- integrated from Nutt's model and scheduling criteria of Taiwan's Statute for the Prevention and Control of Illicit Drugs (SPCID), were further ided into 11 indicators and applied to assess harms of the 37 substances. Among the 11 indicators that corresponded to the four dimensions, 7 had significant prediction capabilities. Additionally, prevalence of misuse nationally was an important predictor of harm assessment. These indicators of harm assessment of drug misuse can help develop a proper scheduling system for the management of controlled/illicit drugs. In conclusions, drug scheduling is the first step toward proper management of drug use problems. Facing the threats of NPS, it is imperative to implement a rational and effective scheduling system for appropriate management. This study provides a mechanism to scrutinize, and improve, the current evaluation process for NPS scheduling.

Variability in preterm lamb lung mechanics after intra-amniotic endotoxin is associated with changes in surfactant pool size and morphometry

Publisher: American Physiological Society

Date: 11-2004

DOI: 10.1152/AJPLUNG.00158.2004

Abstract: Antenatal exposure to intra-amniotic (IA) endotoxin initiates a complex series of events, including an inflammatory cascade, increased surfactant production, and alterations to lung structure. Using the low frequency forced oscillation technique as a sensitive tool for measurement of respiratory impedance, we aimed to determine which factors contributed most to measured changes in lung mechanics. Respiratory impedance data obtained from sedated preterm lambs exposed to either IA injection with saline or 20 mg of endotoxin 1, 2, 4, and 15 days before delivery at 125 days gestation were studied, and association with indexes of standard lung morphometry, inflammatory response, and alveolar surfactant-saturated phosphatidylcholine (Sat PC) pool size was demonstrated. Reduction in tissue impedance with increasing interval between exposure and delivery was evident as early as 4 days after IA endotoxin injection, coinciding with resolution of inflammatory reaction, increased alveolar surfactant pools, and contribution of alveolar ducts to the parenchymal fraction, and a later decrease in the tissue component of the parenchymal fraction. Decreases in tissue d ing (resistance) were more marked than decreases in tissue elastance. Log alveolar Sat PC accounted for most variability in tissue d ing (88.9%) and tissue elastance (73.4%), whereas tissue fraction contributed 2 and 6.4%, respectively. The alveolar Sat PC pool size was the sole factor contributing to change in tissue hysteresivity. No changes were observed in airway resistance. Despite the complex cascade of events initiated by antenatal endotoxin exposure, variability in lung tissue mechanics is associated primarily with changes in alveolar Sat PC pool and lung morphology.

Respiratory function in healthy young children using forced oscillations

Publisher: BMJ

Date: 06-2007

DOI: 10.1136/THX.2006.067835

Gene Expression Imputation Across Multiple Tissue Types Provides Insight Into the Genetic Architecture of Frontotemporal Dementia and Its Clinical Subtypes

Publisher: Elsevier BV

Date: 04-2021

DOI: 10.1016/J.BIOPSYCH.2020.12.023

Early life origins of chronic non-communicable diseases: Towards the future

Publisher: Elsevier BV

Date: 12-2021

DOI: 10.1016/J.PRRV.2021.06.001

Monitoring asthma in children

Publisher: European Respiratory Society (ERS)

Date: 05-03-2015

DOI: 10.1183/09031936.00088814

Abstract: The goal of asthma treatment is to obtain clinical control and reduce future risks to the patient. To reach this goal in children with asthma, ongoing monitoring is essential. While all components of asthma, such as symptoms, lung function, bronchial hyperresponsiveness and inflammation, may exist in various combinations in different in iduals, to date there is limited evidence on how to integrate these for optimal monitoring of children with asthma. The aims of this ERS Task Force were to describe the current practise and give an overview of the best available evidence on how to monitor children with asthma. 22 clinical and research experts reviewed the literature. A modified Delphi method and four Task Force meetings were used to reach a consensus. This statement summarises the literature on monitoring children with asthma. Available tools for monitoring children with asthma, such as clinical tools, lung function, bronchial responsiveness and inflammatory markers, are described as are the ways in which they may be used in children with asthma. Management-related issues, comorbidities and environmental factors are summarised. Despite considerable interest in monitoring asthma in children, for many aspects of monitoring asthma in children there is a substantial lack of evidence.

Sunshine, rainfall, humidity and child pneumonia in the tropics: Time-series analyses

Publisher: Cambridge University Press (CUP)

Date: 13-08-2013

DOI: 10.1017/S0950268812001379

Abstract: Few studies have formally examined the relationship between meteorological factors and the incidence of child pneumonia in the tropics, despite the fact that most child pneumonia deaths occur there. We examined the association between four meteorological exposures (rainy days, sunshine, relative humidity, temperature) and the incidence of clinical pneumonia in young children in the Philippines using three time-series methods: correlation of seasonal patterns, distributed lag regression, and case-crossover. Lack of sunshine was most strongly associated with pneumonia in both lagged regression [overall relative risk over the following 60 days for a 1-h increase in sunshine per day was 0·67 (95% confidence interval (CI) 0·51–0·87)] and case-crossover analysis [odds ratio for a 1-h increase in mean daily sunshine 8–14 days earlier was 0·95 (95% CI 0·91–1·00)]. This association is well known in temperate settings but has not been noted previously in the tropics. Further research to assess causality is needed.

Guest editorial: susceptibility of children to pollutants

Publisher: Elsevier BV

Date: 12-2007

DOI: 10.1016/J.PRRV.2007.07.011

Frequent nocturnal awakening in early life is associated with nonatopic asthma in children

Publisher: European Respiratory Society (ERS)

Date: 30-11-2009

DOI: 10.1183/09031936.00040509

Abstract: Sleep deprivation has become a common phenomenon of the Western world and is associated with a variety of medical problems in children. This retrospective longitudinal analysis of a community-based birth cohort was undertaken to determine whether frequent nocturnal awakening during early life was associated with the development of childhood asthma. 2,398 children born to mothers recruited from the antenatal clinics of a single hospital in Perth, Australia during 1989-1991 were followed up at years 1, 2, 3, 6, 8, 10 and 14. Parent-completed questionnaires were analysed. The odds ratio for asthma at age 6 and 14 yrs in children with frequent nocturnal awakening during the first 3 yrs after birth was determined from multiple logistic regression. Following adjustment for asthma risk factors, co-sleeping and family stress, persistent nocturnal awakening was associated with nonatopic asthma at age 6 and 14 yrs (at age 14 yrs: OR 2.18, 95% CI 1.15-4.13) but not with atopic asthma. We found an increased risk of nonatopic asthma in children following frequent nocturnal awakening during the first 3 yrs of life. These hypothesis-generating data suggest the need for further systematic study of the effects of disordered sleep in early life on the development of asthma.

Regulation of T-helper cell responses to inhalant allergen during early childhood

Publisher: Wiley

Date: 09-1999

DOI: 10.1046/J.1365-2222.1999.00654.X

Abstract: Recent evidence suggests that preschool children manifest patterns of allergen-specific skin prick test (SPT) reactivity and in vitro T-cell cytokine production which are similar to that of either atopic or nonatopic adults. However, published studies on this age group involve small s le sizes and a restricted number of cytokines, usually in response to polyclonal stimuli. To elucidate the relationship between in vivo and in vitro immune responses to a major inhalant allergen house dust mite (HDM) in preschoolers. Peripheral blood mononuclear cells (PBMCs) from matched groups of HDM-SPT+ and SPT- 6-year-olds (n = 30 and 29, respectively) tested for PBMC responses to HDM, and cytokine production measured at both the protein and mRNA levels. Immunoglobulin (Ig) E and IgG subclass antibody titres were determined in serum. Interrelationships between in vitro and in vivo HDM responses were examined via multivariate analyses. SPT reactivity to HDM was associated with in vitro production by putative T cells of interleukin (IL) -4, IL-5, IL-9, IL-10, IL-13 and low level IFNgamma, and with production in vivo of IgE and (all) IgG subclass antibodies HDM responses in the SPT- group were restricted mainly to IL-10 and IFNgamma and very low levels of IL-4 IL-6 production from non-T-cell sources was common. The cytokine most associated with positive SPT responses was IL-9 SPT weal diameter correlated positively with IL-4, IL-5 and IL-13 and negatively with IL-10. Detailed analysis of cytokine responses in this very young age group have the potential to uncover subtle relationships between in vivo and in vitro allergen reactivity which may be less clear in adults, in whom T-cell response patterns are modified via chronic stimulation. The present findings which suggest potentially important roles for IL-9 and IL-10 in the early phase of allergic disease, may be one such ex le.

Linking lung function and inflammatory responses in ventilator-induced lung injury

Publisher: American Physiological Society

Date: 2011

DOI: 10.1152/AJPLUNG.00158.2010

Abstract: Despite decades of research, the mechanisms of ventilator-induced lung injury are poorly understood. We used strain-dependent responses to mechanical ventilation in mice to identify associations between mechanical and inflammatory responses in the lung. BALB/c, C57BL/6, and 129/Sv mice were ventilated using a protective [low tidal volume and moderate positive end-expiratory pressure (PEEP) and recruitment maneuvers] or injurious (high tidal volume and zero PEEP) ventilation strategy. Lung mechanics and lung volume were monitored using the forced oscillation technique and plethysmography, respectively. Inflammation was assessed by measuring numbers of inflammatory cells, cytokine (IL-6, IL-1β, and TNF-α) levels, and protein content of the BAL. Principal components factor analysis was used to identify independent associations between lung function and inflammation. Mechanical and inflammatory responses in the lung were dependent on ventilation strategy and mouse strain. Three factors were identified linking 1) pulmonary edema, protein leak, and macrophages, 2) atelectasis, IL-6, and TNF-α, and 3) IL-1β and neutrophils, which were independent of responses in lung mechanics. This approach has allowed us to identify specific inflammatory responses that are independently associated with overstretch of the lung parenchyma and loss of lung volume. These data provide critical insight into the mechanical responses in the lung that drive local inflammation in ventilator-induced lung injury and the basis for future mechanistic studies in this field.

Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

Publisher: American Physiological Society

Date: 12-2014

DOI: 10.1152/PHYSIOLGENOMICS.00061.2014

Abstract: Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18–22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 ( IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group ( n = 131) and the control group ( n = 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants ( P = 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers ( P = 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers ( P = 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development.

Effects of long‐term oral treatment with leflunomide on allergic sensitization, lymphocyte activation, and airway inflammation in a rat model of asthma

Publisher: Wiley

Date: 06-1998

DOI: 10.1046/J.1365-2222.1998.00309.X

Abstract: Short-term treatment with leflunomide is effective in suppressing antigen-specific antibody production and allergen-induced bronchoconstriction after sensitization. This agent may thus have a role in future primary prevention strategies in allergic disease. The current study aimed to determine whether long-term oral treatment with leflunomide prevents allergic sensitization permanently. After sensitization with ovalbumin, six groups of rats (n = 31) were treated daily with leflunomide or diluent for up to 30 days. Ovalbumin-specific IgE and IgG were determined weekly for at least 2 weeks after cessation of treatment. T lymphocytes from another 21 animals were stimulated ex vivo with ovalbumin or concanavalin A. Ovalbumin-specific IgE and IgG were lower during treatment with leflunomide compared with controls (P < 0.002) but increased after the cessation of treatment. Antigen-specific T-cell proliferation was decreased in cells obtained from leflunomide treated animals (P < 0.05), but not when stimulated with concanavalin A. Eosinophil (P < 0.0001) and neutrophil (P < 0.02) numbers in bronchoalveolar lavage 24 h after allergen challenge were lower in the leflunomide treated animals. Leflunomide prevents antigen-specific immunoglobulin production after sensitization during treatment, inhibits allergen-induced airway inflammation and diminishes antigen-specific T lymphocyte proliferation.

Lung Function in Cooperative Subjects

Publisher: Elsevier

Date: 2008

DOI: 10.1016/B978-032304048-8.50017-7

Leflunomide, a novel immunomodulating agent, prevents the development of allergic sensitization in an animal model of allergic asthma

Publisher: Wiley

Date: 03-1998

DOI: 10.1046/J.1365-2222.1998.00240.X

Abstract: Leflunomide is a new anti-inflammatory and immunomodulating agent which is showing promise in several immune disorders, especially rheumatoid arthritis. Its activity profile suggests it may be of use in modulating allergic sensitization. To investigate the effectiveness of leflunomide in preventing the development of allergic sensitization. Fifty-three brown Norway rats were sensitized by intraperitoneal injection of ovalbumin and adjuvant (ricin) on day 0. To determine the ability of leflunomide to inhibit primary allergic sensitization six rats were treated with A77 1726, the active metabolite of leflunomide, from day 0 through day 5, six were treated from day 5 through day 10, and nine rats acted as controls. On day 14, ovalbumin-specific serum antibody levels and the magnitude of the early-phase airway response (EAR) after inhalation allergen challenge were assessed. To determine the ability of acute topical treatment with leflunomide to inhibit mast cell degranulation, three groups of five animals received either vehicle, 100 microg A77 1726, or 1000 g A77 1726 60 min prior to aerosol allergen challenge. To determine the effects of leflunomide treatment in vivo on mast cell function in vitro, mast cells were obtained by bronchoalveolar lavage from 17 rats (nine treated with leflunomide and eight controls). Allergen-specific and non-specific degranulation (48/80 induced) were studied. In the leflunomide treated rats both ovalbumin-specific IgE and IgG levels were significantly reduced, and the increases in lung resistance and lung elastance were essentially abolished, compared to those of the control group. Non significant differences were found in any of the parameters between the two leflunomide treated groups. Topical pre-treatment with leflunomide did not prevent the allergen-induced EAR. Treatment with leflunomide in vivo prevented allergen-induced mast cell degranulation in vitro because the mast cells lacked IgE on their surface. Non allergen-specific degranulation was normal and allergen-induced degranulation could be restored by passive sensitization. These data suggests that leflunomide can prevent primary allergic sensitization and prevent allergen-induced EAR by inhibiting production of allergen-specific IgE antibodies. Further studies in atopic conditions are warranted.

The developing respiratory tract and its specific needs in regard to ultrafine particulate matter exposure

Publisher: Elsevier BV

Date: 06-2012

DOI: 10.1016/J.PRRV.2011.08.002

Abstract: Nanoparticles have unique physico-chemical properties compared to larger particles that have the potential to provide promising new possibilities for biomedical applications. Considerable research is currently exploring these potentials of nanotechnology. In contrast, airborne particles as components of indoor air, ambient air pollution associated with traffic-related pollution, industry, power plants, and other combustion sources have the potential to harm children's health. However, a similar research effort into the potential health effects of exposure to nanoparticles is lacking. Children differ markedly from adults in their developmental biology rendering young children the most vulnerable group with regard to potentially harmful effects induced by particulate exposure. This review discusses the differences between children and adults in regard to nanoparticle exposure highlighting the uniqueness and vulnerability of children.

CFTR-dependent defect in alternatively-activated macrophages in cystic fibrosis

Publisher: Elsevier BV

Date: 07-2017

DOI: 10.1016/J.JCF.2017.03.011

Abstract: The role of the macrophages in cystic fibrosis (CF) lung disease has been poorly studied. We hypothesized that alternatively activated M2 macrophages are abnormal in CF lung disease. Blood s les were collected from adults (n=13) children (n=27) with CF on admission for acute pulmonary exacerbation and when clinically stable. Monocytes were differentiated into macrophages and polarized into classical (M1) and alternatively-activated (M2) phenotypes, function determined ex-vivo and compared with healthy controls. In the absence of functional cystic fibrosis trans-membrane conductance regulator (CFTR), either naturally in patients with CF or induced with CFTR inhibitors, monocyte-derived macrophages do not respond to IL-13/IL-4, fail to polarize into M2s associated with a post-transcriptional failure to produce and express IL-13Rα1 on the macrophage surface Polarization to the M1 phenotype was unaffected. CFTR-dependent imbalance of macrophage phenotypes and functions could contribute to the exaggerated inflammatory response seen in CF lung disease.

The Effect of Nedocromil Sodium on Histamine Responsiveness in Clinically Stable Asthmatic Children

Publisher: Informa UK Limited

Date: 1993

DOI: 10.3109/02770909309056742

Abstract: A double-blind, randomized, placebo-controlled, parallel-group study was undertaken in 120 clinically stable asthmatic children (aged 6-19 years) to determine the ability of 8 weeks of treatment with nedocromil sodium (4 mg, three times a day) to reduce the level of histamine responsiveness. Despite the subjects being clinically stable and reporting few asthma symptoms, approximately one-third had abnormal pulmonary function on enrollment into the study. Statistically significant increases in pulmonary function were seen in the group treated with nedocromil sodium but not in the control group (p = 0.01). Furthermore, 52% of the in iduals with abnormal pulmonary function returned to normal following treatment with nedocromil sodium compared to 11% of those with abnormal pulmonary function who received placebo. However, there were no differences in the level of histamine responsiveness between the two treatment groups at baseline or after 4 or 8 weeks of treatment with nedocromil sodium or placebo. These data suggest that the level of histamine responsiveness is not intimately related to the level of asthma control in children.

Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic children

Publisher: Elsevier BV

Date: 06-2000

DOI: 10.1067/MAI.2000.105804

Abstract: Recent findings suggest that a hallmark of the atopic phenotype is reduced capacity to respond to vaccine antigens, as well as to environmental allergens, during infancy. This deficiency, which is most marked for the cytokine IFN-gamma, appears transient but can result in a long-lasting imbalance within T helper cell (T(H)) memory responses to allergens. Indirect evidence suggests that parallel effects may occur within immunologic memory responses against vaccine antigens in atopic children. Our purpose was to compare vaccine antigen-specific T(H) memory responses in atopic and nonatopic children. We analyzed specific serum IgG and cytokine responses to pertactin and tetanus antigens as well as to mitogen (PHA) and house dust mite (HDM) allergen in 25 HDM-sensitized atopic and 25 nonatopic 6-year-old children who were vaccinated and boosted with diphtheria-tetanus-pertussis (DTP) vaccine. PBMCs from the atopic subjects produced higher levels of T(H)1 and T(H)2 cytokines to HDM allergen and PHA. Vaccine antibody titers were normal in the atopic subjects vaccine-specific T(H)2 responses were rarely detectable, yet T(H)1 (IFN-gamma) responses, in particular against tetanus, were frequent and higher in the atopic subjects (121.5 [SE 64.3] vs 8.0 [3.5] pg/mL culture fluid, P =.04). Corresponding pertactin responses were comparable in both groups. At the completion of the full primer-booster DTP vaccination regimen, levels of vaccine-specific immunity in atopic 6-year-old children are at least equivalent to their nonatopic counterparts, indicating that the transient atopy-associated deficiency in T(H)1 function in childhood can be successfully overcome by appropriate vaccination and boosting regimens.

Predicting which children have asthma: Are we any closer to finding the Holy Grail?

Publisher: Wiley

Date: 18-03-2019

DOI: 10.1111/RESP.13529

The pattern of methacholine responsiveness in mice is dependent on antigen challenge dose

Publisher: Springer Science and Business Media LLC

Date: 23-09-2004

DOI: 10.1186/1465-9921-5-15

Review Series: What goes around, comes around: childhood influences on later lung health?: Relationship between environmental exposures in children and adult lung disease: The case for outdoor exposur

Publisher: SAGE Publications

Date: 09-10-2009

DOI: 10.1177/1479972309345929

Abstract: There is a growing understanding that chronic respiratory diseases in adults have their origins in early life. Adverse environmental exposures occurring in vulnerable periods during lung growth and development in the fetal period and in early childhood that alter lung structure and limit the growth in lung function may have lifelong consequences. Evidence is increasing that exposure to the ambient environment, including air pollutants, persistent toxic substances, water pollutants and respiratory viral infections, can inhibit lung function growth and predispose to chronic non-malignant lung diseases. These exposures generally interact with a genetic predisposition, and gene—environment interactions and epigenetic phenomena are attracting considerable study. An understanding of how ambient exposures impact on normal lung growth and development will aid in understanding of how chronic respiratory diseases of adults develop and may lead to new preventative strategies.

Neonatal genetics of gene expression reveal potential origins of autoimmune and allergic disease risk

Publisher: Springer Science and Business Media LLC

Date: 28-07-2020

DOI: 10.1038/S41467-020-17477-X

Abstract: Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4 + T cells from cord blood s les, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis -eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis -eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively. We identified cis regulatory factors acting as mediators of trans effects. There is extensive colocalisation between condition-specific neonatal cis -eQTLs and variants associated with immune-mediated diseases, in particular CTSH had widespread colocalisation across diseases. Mendelian randomisation shows causal neonatal gene expression effects on disease risk for BTN3A2 , HLA-C and others. Our study elucidates the genetics of gene expression in neonatal immune cells, and aetiological origins of autoimmune and allergic diseases.

Persistent organic pollutants in infants and toddlers: Relationship between concentrations in matched plasma and faecal samples

Publisher: Elsevier BV

Date: 10-2017

DOI: 10.1016/J.ENVINT.2017.06.019

Children’s Environmental Health in South and Southeast Asia: Networking for Better Child Health Outcomes

Publisher: Ubiquity Press, Ltd.

Date: 2019

DOI: 10.5334/AOGH.2403

Anti-inflammatory effects of lenabasum, a cannabinoid receptor type 2 agonist, on macrophages from cystic fibrosis

Publisher: Elsevier BV

Date: 09-2020

DOI: 10.1016/J.JCF.2020.03.015

Respiratory impedance in healthy unsedated South African infants: Effects of maternal smoking

Publisher: Wiley

Date: 11-01-2015

DOI: 10.1111/RESP.12463

Value of eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid for predicting lung function impairment in anaesthetised, asthmatic children*

Publisher: Wiley

Date: 07-11-2006

DOI: 10.1111/J.1365-2044.2006.04859.X

Abstract: Bronchial hyperactivity, a key feature of active asthma in children, is a risk factor for respiratory adverse events in the peri-operative period. The presence of activated eosinophils in the lungs and mast cell degranulation can contribute to bronchial hyperreactivity. Eosinophil cationic protein is released by activated eosinophils and tryptase reflects mast cell degranulation. This study focused on the relationship of respiratory mechanics, eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid in asthmatic and healthy children under general anaesthesia. We measured eosinophil cationic protein and tryptase levels in bronchoalveolar lavage fluid from 21 asthmatic and 21 healthy children following induction of general anaesthesia. Respiratory system resistance and dynamic compliance were measured during mechanical ventilation. Eosinophil cationic protein was more common in bronchoalveolar lavage fluid from asthmatics (12/21) than from controls (4/21, p = 0.01) and was present at higher levels (p = 0.002). Tryptase was also more common in the asthmatics (8/21 vs 1/21, p = 0.01). Respiratory resistance was significantly higher in asthmatic children with detectable eosinophil cationic protein levels than in those with undetectable eosinophil cationic protein levels (p = 0.019). Furthermore, 50% of the asthmatics with detectable eosinophil cationic protein exhibited bronchospasm after s ling their bronchoalveolar lavage fluid. These findings suggested that high levels of eosinophil cationic protein in the bronchoalveolar lavage fluid are associated with irritable airways, presumably secondary to airway inflammation, and this might be a useful marker for respiratory adverse events in the peri-operative period.

Assessing adherence and factors associated with adherence in young children with asthma

Publisher: Wiley

Date: 15-04-2008

DOI: 10.1111/J.1440-1843.2008.01292.X

Abstract: Adherence with preventive asthma medication by young children is an important factor when evaluating a suboptimal response to treatment. However, few data exist regarding the accuracy of subjective measures of adherence and factors associated with adherence in young children. Fifty-one asthmatic children aged 18 months to 7 years had their use of preventive asthma medication monitored using an electronic monitoring device (Smartinhaler) for 1 month. At a follow-up visit the child's parent was asked how often medication had been given and they also completed a confidential questionnaire that included questions about medication usage, barriers to optimal adherence and parenting. The treating physician made an estimate of the child's likely use of medication. The median use of medication as determined by the Smartinhaler was 70.5% (range 21.4-100%). The parents' verbal reports (85.1%) and questionnaire responses (84.2%) overestimated medication usage. The physician was not able to determine which parents correctly estimated their child's use of medication (P = 0.28). The child's age, level of parental education and annual family income did not influence adherence. Parents reported simply 'forgetting' or their child's 'reaction to being given medication' as the principal barriers to adherence. There was a significant association between how stressful the parent found parenting and adherence (P = 0.05). Adherence with preventive medication, even within the context of a research study, was generally low and highly variable. Subjective measures of adherence were found to overestimate adherence in young asthmatics.

Interleukin-10/Interleukin-5 responses at birth predict risk for respiratory infections in children with atopic family history

Publisher: American Thoracic Society

Date: 02-2009

DOI: 10.1164/RCCM.200803-438OC

The effects of respiratory infections, atopy, and breastfeeding on childhood asthma

Publisher: European Respiratory Society (ERS)

Date: 05-2002

DOI: 10.1183/09031936.02.00103602

Abstract: The objectives of the present study were to quantify the association of atopy and respiratory infections with asthma, and exclusive breastfeeding with respiratory illness, atopy and asthma in children. A cohort study of 2,602 children enrolled prior to birth and followed prospectively, provided data on respiratory illness, the method of feeding in the first year of life, as reported on a prospective diary card, and current asthma at the age of 6 yrs (defined as doctor-diagnosed asthma with wheeze in the last year or cough without a cold, and currently taking either preventer or reliever asthma medication), as reported by parental questionnaire. Atopy was defined by a positive skin-prick test assessed at the age of 6 yrs. Wheezing lower respiratory illness (LRI) in the first year of life, particularly multiple episodes of wheezing LRI, increased the risk for current asthma in both nonatopic (odds ratio (OR) 4.10, p< or =0.0005) and atopic children (OR 9.00, p< or =0.0005), but did not increase the risk for atopy. In contrast, up to three upper respiratory tract infections demonstrated a negative association and four or more a positive risk for current asthma in unadjusted (p=0.006) and adjusted (p=0.057) analysis. Following adjustment, exclusive breastfeeding for <4 months was associated with an increased risk for current asthma (OR 1.36, 95% confidence interval 1.00-1.85, p=0.047). Wheezing lower respiratory illness in the first year of life and atopy are independently associated with increased risk for current asthma at the age of 6 yrs, suggesting that their effects are mediated via different causal pathways and that these risk factors are multiplicative when they operate concomitantly within in idual children. Exclusive breastfeeding protects against asthma via effects on both these pathways, as well as through other as yet undefined mechanisms.

Sevoflurane for Patients with Asthma

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 07-2000

DOI: 10.1097/00000539-200007000-00051

Validation of a questionnaire for asthma case identification in pre‐schools in Latin America

Publisher: Wiley

Date: 24-06-2015

DOI: 10.1111/RESP.12575

Abstract: We recently developed and validated a screening questionnaire for determining which school-aged children may need further investigation to diagnose and manage asthma. In the present study we sought to extend this to pre-school aged children. Questions from the school-aged questionnaire and literature on pre-school asthma were used to inform a focus group of parents with pre-school-aged children with asthma to develop a screening questionnaire. Parents of children attending 6 randomly selected kindergartens in Trelew, Argentina (n = 639) were invited to respond to the questionnaire. A reliability test-retest was undertaken in 187 randomly selected parents who completed the same questionnaire twice within 2-5 weeks. Clinical assessment included a standardized history and physical examination, spirometry before and after a β-agonist inhaler, and chest X-ray. Asthma was diagnosed by the pulmonologist. Completed surveys were returned for 620 children, 607 of whom underwent clinical evaluation. The mean age was 4.21 years (range of 3.01-5.50) and included 82.5% white and 49.4% male children. Asthma was diagnosed in 103 (17.0%) children) 72 (69.9%) of these children did not have a previous diagnosis of asthma. The specificity, sensitivity, positive predictive value and negative predictive value of the questionnaire were 93.2%, 86.1%, 57.8% and 98.4%, respectively. We have demonstrated the utility of a screening questionnaire for identifying pre-school-aged children who may benefit from further assessment for asthma.

In vitro assessment of an ultrasonic flowmeter for use in ventilated infants

Publisher: European Respiratory Society (ERS)

Date: 03-2000

DOI: 10.1034/J.1399-3003.2000.15.23.X

Abstract: An ultrasonic flowmeter could be advantageous over a differential pressure pneumotachograph having a constant error in varying conditions. The in vitro accuracy of ultrasonic tidal volume (VT) estimates for ventilated infants were evaluated. Flow linearity and frequency response were tested, as was the influence of humidity and oxygen content on the accuracy of VT estimates. The linearity was within the 5% limits between -350 and 350 mL x sec(-1) and was not affected by the presence of an endotracheal tube (ET). The frequency response was flat and unaffected by an ET up to 4.5 Hz. The VT in the range 7-100 mL, in air showed a mean error of 0.1% (95% confidence interval (CI) -0.2-0.4%) with a maximum and minimum of 6.5 and -3.5% respectively. Humidity did not affect accuracy. After calibration in air, the maximal mean error for measurements in pure oxygen was 3.0% (95% CI 1.9-4.1%). Repeated measurements over 5.5 h had a mean error of 0.4% (95% CI -0.7-0.1%). The in vitro evaluation of an ultrasonic flowmeter showed stable accuracy in mechanical ventilation conditions. Changing connection geometry and oxygen content did not increase the error to a clinically relevant degree. The flowmeter could therefore be a better alternative than the pneumotachograph for ventilated infants.

Adherence with Preventive Medication in Childhood Asthma

Publisher: Hindawi Limited

Date: 2011

DOI: 10.1155/2011/973849

Abstract: Suboptimal adherence with preventive medication is common and often unrecognised as a cause of poor asthma control. A number of risk factors for nonadherence have emerged from well-conducted studies. Unfortunately, patient report a physician's estimation of adherence and knowledge of these risk factors may not assist in determining whether non-adherence is a significant factor. Electronic monitoring devices are likely to be more frequently used to remind patients to take medication, as a strategy to motivate patients to maintain adherence, and a tool to evaluate adherence in subjects with poor disease control. The aim of this paper is to review non-adherence with preventive medication in childhood asthma, its impact on asthma control, methods of evaluating non-adherence, risk factors for suboptimal adherence, and strategies to enhance adherence.

Alveolar macrophages and CC chemokines are increased in children with cystic fibrosis

Publisher: European Respiratory Society (ERS)

Date: 22-04-2009

DOI: 10.1183/09031936.00178508

Abstract: Airway inflammation is an important component of cystic fibrosis (CF) lung disease. We sought to determine whether alveolar macrophages were involved in early CF lung disease. Children with CF (median age 3.1 yrs) participated in a surveillance programme that included annual bronchoalveolar lavage (BAL). Control s les were obtained from non-CF children (median age 3.1 yrs n = 24) investigated for persistent respiratory symptoms. Pulmonary infection was detected in 31% (16 out of 51) and 38% (nine out of 24) of children from the CF and non-CF groups, respectively. Alveolar macrophages in BAL were increased in CF compared with non-CF in the absence of infection (223x10(3) versus 85x10(3) cells.mL(-1) p = 0.001) and were associated with elevations in the CC chemokines (macrophage inflammatory protein (MIP)-3alpha (chemokine (C-C motif) ligand (CCL)20 355.8 versus 46.0 pg.mL(-1) p<0.001), monocyte chemotactic protein-1 (CCL2 263.5 versus 25.3 pg.mL(-1) p<0.001), MIP-1alpha (CCL3 38.2 versus 4.9 pg.mL(-1) p<0.001) and MIP-1beta (CCL4 326.6 versus 27.5 pg.mL(-1) p<0.001)). Total cell counts and neutrophil numbers increased in the presence of infection however, there was no additional effect of CF. Alveolar macrophages and CC chemokines are elevated in the lungs in young children with CF even in the absence of pulmonary infection. Longitudinal studies are required to determine the clinical relevance of these findings.

The Impact of Birth Weight on Peak Lung Function in Young Adults

Publisher: Elsevier BV

Date: 12-2012

DOI: 10.1378/CHEST.11-2976

Abstract: Poor fetal growth rate, as indicated by lower birth weight, is associated with lower respiratory function in childhood however, findings in adult life remain inconsistent. A birth cohort provides the opportunity to study the association between birth weight and adult respiratory function. The present study data are from a longitudinal birth cohort, the Mater-University of Queensland Study of Pregnancy. Prospective data were available from 2,368 young adults who underwent standard spirometry when 21 years old. Pregnancy and birth-related variables collected were birth weight, placental weight, parental height, maternal educational status, maternal smoking history in pregnancy, and maternal history of alcohol, tea, and coffee consumption during pregnancy. The impact of birth weight on adult lung function was assessed using univariate and multivariate analyses. For every 100-g increase in birth weight, FVC (95% CI) at 21 years increased by 24 mL (15-32) in men and 20 mL (13-27) in women, and the increase in FEV1 (CI) was 22 mL (15-30) and 16 mL (11-22), respectively. These associations remain after adjusting for lifestyle factors during pregnancy, current smoking, and parental height. However, further adjustment for adult height reduces the strength of association and remains significant for FEV1: 8 mL (1-14) in men and 5 mL (1-10) in women, but not for FVC: 7 mL (-1-14) in men and 5 mL (-1-11) in women. Our longitudinal cohort study provides evidence of robust links between birth weight and adult lung function at the age of 21 years. Various estimates of the effect size in the literature may be related to the age at assessment.

Lung Function in Infants with Cystic Fibrosis Diagnosed by Newborn Screening

Publisher: American Thoracic Society

Date: 15-12-2008

DOI: 10.1164/RCCM.200804-551OC

Preserving Lung Function: The Holy Grail in Managing Cystic Fibrosis

Publisher: American Thoracic Society

Date: 06-2017

DOI: 10.1513/ANNALSATS.201703-254ED

International consensus on (ICON) pediatric asthma

Publisher: Wiley

Date: 15-06-2012

DOI: 10.1111/J.1398-9995.2012.02865.X

Sexual dimorphism in lung function responses to acute influenza A infection

Publisher: Wiley

Date: 21-03-2011

DOI: 10.1111/J.1750-2659.2011.00236.X

Evolution of pulmonary inflammation and nutritional status in infants and young children with cystic fibrosis

Publisher: BMJ

Date: 12-03-2011

DOI: 10.1136/THX.2010.139493

Abstract: Improved nutrition is the major proven benefit of newborn screening programmes for cystic fibrosis (CF) and is associated with better clinical outcomes. It was hypothesised that early pulmonary inflammation and infection in infants with CF is associated with worse nutrition. Weight, height and pulmonary inflammation and infection in bronchoalveolar lavage (BAL) were assessed shortly after diagnosis in infants with CF and again at 1, 2 and 3 years of age. Body mass index (BMI) was expressed as z-scores. Inflammatory cells and cytokines (interleukin 1β (IL-1β), IL-6, IL-8 and tumour necrosis factor α (TNFα)), free neutrophil elastase activity and myeloperoxidase were measured in BAL. Mixed effects modelling was used to assess longitudinal associations between pulmonary inflammation, pulmonary infection (Staphylococcus aureus and Pseudomonas aeruginosa) and BMI z-score after adjusting for potential confounding factors. Forty-two infants were studied (16 (38%) male 39 (93%) pancreatic insufficient) 36 were diagnosed by newborn screening (at median age 4 weeks) and six by early clinical diagnosis (meconium ileus). Thirty-one (74%) received antistaphylococcal antibiotics. More than two-thirds were asymptomatic at each assessment. Mean BMI z-scores were -1.5 at diagnosis and 0.5, -0.2 and -0.1 at 1, 2 and 3 years, respectively. Neutrophil elastase and infection with S aureus were associated with lower BMI, whereas age (p=0.01) and antistaphylococcal antibiotics (p=0.013) were associated with increased BMI. On average, each log(10) increase in free neutrophil elastase activity was associated with a 0.43 (95% CI 0.06 to 0.79) reduction in BMI z-score. Early nutritional status is associated with the underlying pulmonary pathophysiology in CF, and better understanding of these relationships is required. Studies are required to assess whether interventions can decrease pulmonary inflammation and improve nutrition. Early surveillance will enable such targeted interventions with the aim of improving these important clinical outcomes.

Lung function and exhaled nitric oxide in healthy unsedated African infants

Publisher: Wiley

Date: 07-2015

DOI: 10.1111/RESP.12579

Airway hyperresponsiveness is associated with activated CD4+ T cells in the airways

Publisher: American Physiological Society

Date: 08-2009

DOI: 10.1152/AJPLUNG.00053.2009

Abstract: It is widely accepted that atopic asthma depends on an allergic response in the airway, yet the immune mechanisms that underlie the development of airway hyperresponsiveness (AHR) are poorly understood. Mouse models of asthma have been developed to study the pathobiology of this disease, but there is considerable strain variation in the induction of allergic disease and AHR. The aim of this study was to compare the development of AHR in BALB/c, 129/Sv, and C57BL/6 mice after sensitization and challenge with ovalbumin (OVA). AHR to methacholine was measured using a modification of the forced oscillation technique in anesthetized, tracheostomized mice to distinguish between airway and parenchymal responses. Whereas all strains showed signs of allergic sensitization, BALB/c was the only strain to develop AHR, which was associated with the highest number of activated (CD69 + ) CD4 + T cells in the airway wall and the highest levels of circulating OVA-specific IgG 1 . AHR did not correlate with total or antigen-specific IgE. We assessed the relative contribution of CD4 + T cells and specific IgG 1 to the development of AHR in BALB/c mice using adoptive transfer of OVA-specific CD4 + T cells from DO11.10 mice. AHR developed in these mice in a progressive fashion following multiple OVA challenges. There was no evidence that antigen-specific antibody had a synergistic effect in this model, and we concluded that the number of antigen-specific T cells activated and recruited to the airway wall was crucial for development of AHR.

Evaluation of Combined Live, Attenuated Respiratory Syncytial Virus and Parainfluenza 3 Virus Vaccines in Infants and Young Children

Publisher: Oxford University Press (OUP)

Date: 15-12-2004

DOI: 10.1086/425981

Abstract: We evaluated a combination respiratory syncytial virus (RSV) and parainfluenza 3 virus (PIV3) live, attenuated intranasal vaccine for safety, viral replication, and immunogenicity in doubly seronegative children 6-18 months old. RSV cpts-248/404 and PIV3-cp45 vaccines were combined in a dose of 10(5) plaque-forming units of each per 0.5-mL dose and compared with monovalent vaccines or placebo. The virus shedding pattern of RSV was not different between monovalent RSV cpts-248/404 vaccine and combination vaccine. Modest reductions in the shedding of PIV3-cp45 vaccine virus were found after the administration of RSV cpts-248/404 and PIV3-cp45 vaccine, relative to monovalent PIV3 vaccine 16 (76%) of 21 children given combination vaccine shed PIV3-cp45 versus 11 (92%) of 12 of those given monovalent PIV3 vaccine. Both vaccines were immunogenic, and antibody responses were similar between the monovalent groups and the combination group. Combined RSV/PV3 vaccine is feasible for simultaneous administration, and further studies are warranted.

CO2 degassing and melting of metasomatized mantle lithosphere during rifting – Numerical study

Publisher: Elsevier BV

Date: 07-2019

DOI: 10.1016/J.GSF.2018.11.003

A multi-disciplinary approach for defining nickel and gold mineral systems; Halls Creek Orogen, Western Australia

Publisher: Informa UK Limited

Date: 11-11-2019

DOI: 10.1080/22020586.2019.12072939

Lack of long-term effects of respiratory syncytial virus infection on airway function in mice

Publisher: Elsevier BV

Date: 06-2007

DOI: 10.1016/J.RESP.2006.11.009

Abstract: Epidemiological data suggests lower respiratory infections (LRI) with respiratory syncytial virus (RSV) are capable of causing long-term abnormalities in airway function. To directly test the effects of RSV LRI, we infected adult and weanling BALB/c mice with RSV (A2) or vehicle. Respiratory system impedance was used to assess baseline airway function and responses to iv methacholine (MCh) at 4, 8, 24 and 34 weeks post infection. In vitro airway responses were measured 24 weeks post infection using electrical field stimulation and MCh. Mice infected as adults showed no alterations in airway function. Mice infected as weanlings had increased MCh responses 24 weeks post infection. However, the increased response was not present 34 weeks post infection nor accompanied by alterations in in vitro responses or airway morphometry. This study did not detect long-lasting changes in airway function following RSV infection in mice. These data do not provide support for alterations in airway structure or function being responsible for the observed relationship between RSV infection in infants and asthma in later life.

Suppression of the asthmatic phenotype by ultraviolet B-induced, antigen-specific regulatory cells

Publisher: Wiley

Date: 26-07-2007

DOI: 10.1111/J.1365-2222.2007.02750.X

Abstract: Over recent decades, there has been a significant global increase in the prevalence of asthma, an inflammatory disease of the respiratory system. While ultraviolet radiation (UV) has been used successfully in the treatment of inflammatory conditions such as psoriasis, studies of UV-induced regulation of allergic respiratory responses have been rare, and have not analysed in vivo measurements of airway hyperresponsiveness (AHR) or the antigen specificity of the UV-induced effects. To investigate the regulatory properties of erythemal ultraviolet B (UVB) irradiation of the skin and the induction of allergen-induced airway immunity in a murine asthma model, and to examine the mechanisms involved. BALB/c mice were exposed to a single erythemal dose of UV 3 days before intraperitonial sensitization (day 0) and boost (day 14) with the antigen, ovalbumin (OVA). Airway-associated, asthma-like responses to aerosolized OVA at day 21 were analysed including (a) AHR measured in vivo, (b) OVA-specific proliferative responses and cytokine production by cells from the lung-draining lymph nodes (LDLN), and (c) inflammatory cells and cytokines in the bronchoalveolar lavage fluid. To determine UVB-induced mechanisms of regulation, LDLN cells from UVB irradiated, OVA-sensitized mice were adoptively transferred into naïve BALB/c mice that were subsequently sensitized and challenged with OVA, or a non-specific antigen. UVB irradiation of skin significantly suppressed AHR to methacholine and OVA-specific responses in the LDLN and in the lung compartment. Reduced OVA-specific responses by LDLN cells from both UVB irradiated mice and mice that received 5 x 10(6) LDLN cells from UVB irradiated, but not from non-irradiated, OVA-sensitized mice suggested that UVB-induced regulatory cells are responsible for many of the asthma-reducing effects of dorsal UVB exposure. UVB irradiation of skin suppresses AHR and cellular responses of the airways to respiratory allergens. Further, this study implicates UVB or its downstream mediators as a potential approach to reducing the severity of asthma.

Macrolide antibiotics in diffuse panbronchiolitis and in cystic fibrosis

Publisher: European Respiratory Society (ERS)

Date: 12-1997

DOI: 10.1183/09031936.97.10122926

Interactions between Innate Antiviral and Atopic Immunoinflammatory Pathways Precipitate and Sustain Asthma Exacerbations in Children

Publisher: The American Association of Immunologists

Date: 15-08-2009

DOI: 10.4049/JIMMUNOL.0900695

Abstract: Severe asthma exacerbations in children requiring hospitalization are typically associated with viral infection and occur almost exclusively among atopics, but the significance of these comorbidities is unknown. We hypothesized that underlying interactions between immunoinflammatory pathways related to responses to aeroallergen and virus are involved, and that evidence of these interactions is detectable in circulating cells during exacerbations. To address this hypothesis we used a genomics-based approach involving profiling of PBMC subpopulations collected during exacerbation vs convalescence by microarray and flow cytometry. We demonstrate that circulating T cells manifest the postactivated “exhausted” phenotype during exacerbations, whereas monocyte/dendritic cell populations display up-regulated CCR2 expression accompanied by phenotypic changes that have strong potential for enhancing local inflammation after their recruitment to the atopic lung. Notably, up-regulation of FcεR1, which is known to markedly lify capacity for allergen uptake resentation to Th2 effector cells via IgE-mediated allergen capture, and secondarily programming of IL-4/IL-13-dependent IL-13R+ alternatively activated macrophages that have been demonstrated in experimental settings to be a potent source of autocrine IL-13 production. We additionally show that this disease-associated activation profile can be reproduced in vitro by cytokine exposure of atopic monocytes, and furthermore that IFN-α can exert both positive and negative roles in the process. Our findings suggest that respiratory viral infection in atopic children may initiate an atopy-dependent cascade that lifies and sustains airway inflammation initiated by innate antiviral immunity via harnessing underlying atopy-associated mechanisms. These interactions may account for the unique susceptibility of atopics to severe viral-induced asthma exacerbations.

Prophylactic use of sublingual allergen immunotherapy in high-risk children: A pilot study

Publisher: Elsevier BV

Date: 02-2097

DOI: 10.1016/J.JACI.2013.04.049

Inflammatory profile in nasal secretions of infants hospitalized with acute lower airway tract infections

Publisher: Wiley

Date: 06-2005

DOI: 10.1111/J.1440-1843.2005.00721.X

Abstract: The aim of this study was to determine whether the regulatory immune response (interleukin (IL)-10 response) differed between children hospitalized with acute respiratory infections and wheezing. Infants with signs and symptoms of acute viral respiratory infection, admitted during winter 2000 to Princess Margaret Hospital for Children, Perth, WA, Australia, were enrolled in this study. Nasopharyngeal aspirates were collected in the first 48 h of admission. Total cell count and differential cell counts were assessed. S les were tested for the presence of respiratory viruses. The concentrations of the anti-inflammatory cytokine IL-10, and pro-inflammatory cytokines IL-8, interferon-gamma, and IL-11 were determined by ELISA. Children with acute bronchiolitis (AB n = 36), recurrent wheeze (RW n = 17) and upper respiratory infection (URI n = 18) were enrolled. Respitory syncytial virus was the most commonly detected virus in all groups. IL-10 concentrations were significantly increased in AB (median, 0.019 ng/mL) when compared to URI (median, 0.006 ng/mL) or to RW (median, 0.007 ng/mL P < 0.05). Neutrophils were the predominant cells in the cytological analysis in all subjects. These data argue that host-response factors are important in determining the clinical phenotype, independent of the causative virus.

Peripheral airway dysfunction in prematurity‐associated obstructive lung disease identified by oscillometry

Publisher: Wiley

Date: 13-09-2023

DOI: 10.1002/PPUL.26658

Cord‐blood respiratory syncytial virus antibodies and respiratory health in first 5 years of life

Publisher: Wiley

Date: 29-09-2021

DOI: 10.1002/PPUL.25688

Abstract: To determine the potential longer‐term effects of maternal antenatal respiratory syncytial virus (RSV) vaccination, we examined the association between cord‐blood RSV‐neutralizing antibodies (RSV‐NA) and RSV infections in the first 2 years of life, RSV‐NA at 3 years, and respiratory health to age 5 years. Two community‐based Australian birth cohorts were combined. For children with at least one atopic parent, paired serum RSV‐NA levels were compared in cord blood and at age 3 years. Weekly nasal swabs were collected in one cohort and during acute respiratory infections (ARI) in the other. Wheeze history up to age 5 years and physician‐diagnosed asthma at 5 years was collected by parent report. In 264 children, each log 10 increase of cord‐blood RSV‐NA level was associated with 37% decreased risk (adjusted incidence‐rate‐ratio [aIRR] 0.63 95% confidence interval [CI]: 0.40–1.01) of RSV‐ARI and 49% decreased risk (aIRR 0.51 95% CI: 0.25–1.02) of RSV acute lower respiratory infections (ALRI) at 12–24 months of age. However, higher cord‐blood RSV‐NA was associated with increased risk of all‐cause ALRI (aIRR 1.29 95% CI: 0.99–1.69), wheeze‐associated ALRI (aIRR 1.75 95% CI: 1.08–2.82), and severe ALRI (aIRR 2.76 95% CI: 1.63–4.70) at age 6– months. Cord‐blood RSV‐NA was not associated with RSV‐ARI in the first 6‐months, RSV‐NA levels at 3 years, or wheeze or asthma at 5 years. Higher levels of cord‐blood RSV‐NA did not protect against RSV infections during the first 6‐months‐of‐life, time‐to‐first RSV‐ARI, or wheeze or asthma in the first 5 years of life. Additional strategies to control RSV‐related illness in childhood are needed.

Persistent organic pollutants in matched breast milk and infant faeces samples

Publisher: Elsevier BV

Date: 2015

DOI: 10.1016/J.CHEMOSPHERE.2014.09.076

Abstract: Assessing blood concentration of persistent organic pollutants (POPs) in infants is difficult due to the ethical and practical difficulties in obtaining sufficient quantities of blood. To determine whether measuring POPs in faeces might reflect blood concentration during infancy, we measured the concentrations of a range of POPs (i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs)) in a pilot study using matched breast milk and infant faecal s les obtained from ten mother–child pairs. All infants were breast fed, with 8 of them also receiving solid food at the time of faecal s ling. In this small dataset faecal concentrations (range 0.01–41 ng g(−1) lipid) are strongly associated with milk concentrations (range 0.02–230 ng g(−1) lipid). Associations with other factors generally could not be detected in this dataset, with the exception of a small effect of age or growth. Different sources (external or internal) of exposure appeared to directly influence faecal concentrations of different chemicals based on different inter-in idual variability in the faeces-to-milk concentration ratio Rfm. Overall, the matrix of faeces as an external measure of internal exposure in infants looks promising for some chemicals and is worth assessing further in larger datasets.

Volume dependence of airway and tissue impedances in mice

Publisher: American Physiological Society

Date: 04-2003

DOI: 10.1152/JAPPLPHYSIOL.00596.2002

Abstract: We measured respiratory input impedance (1–25 Hz) in mice and obtained parameters for airway and tissue mechanics by model fitting. Lung volume was varied by inflating to airway opening pressure (Pao) between 0 and 20 cmH 2 O. The expected pattern of changes in respiratory mechanics with increasing lung volume was seen: a progressive fall in airway resistance and increases in the coefficients of tissue d ing and elastance. A surprising pattern was seen in hysteresivity (η), with a plateau at low lung volumes (Pao 10 cmH 2 O), a sharp fall occurring between 10 and 15 cmH 2 O, and η approaching a second (lower) plateau at higher lung volumes. Studies designed to elucidate the mechanism(s) behind this behavior revealed that this was not due to chest wall properties, differences in volume history at low lung volume, time dependence of volume recruitment, or surface-acting forces. Our data are consistent with the notion that at low lung volumes the mechanics of the tissue matrix determine η, whereas at high lung volumes the properties of in idual fibers (collagen) become more important.

Respiratory effects of air pollution on children

Publisher: Wiley

Date: 24-07-2015

DOI: 10.1002/PPUL.23262

Abstract: A substantial proportion of the global burden of disease is directly or indirectly attributable to exposure to air pollution. Exposures occurring during the periods of organogenesis and rapid lung growth during fetal development and early post-natal life are especially damaging. In this State of the Art review, we discuss air toxicants impacting on children's respiratory health, routes of exposure with an emphasis on unique pathways relevant to young children, methods of exposure assessment and their limitations and the adverse health consequences of exposures. Finally, we point out gaps in knowledge and research needs in this area. A greater understanding of the adverse health consequences of exposure to air pollution in early life is required to encourage policy makers to reduce such exposures and improve human health.

Breast feeding and respiratory morbidity in infancy: a birth cohort study

Publisher: BMJ

Date: 03-2003

DOI: 10.1136/ADC.88.3.224

Abstract: To examine the relation between the duration of breast feeding and morbidity as a result of respiratory illness and infection in the first year of life. Prospective birth cohort study of 2602 live born children ascertained through antenatal clinics at the major tertiary obstetric hospital in Perth, Western Australia. Main outcome measures were hospital, doctor, or clinic visits, and hospital admissions for respiratory illness and infection in the first year of life. Main exposure measures were the duration of predominant breast feeding (defined as the age other milk was introduced) and partial (any) breast feeding (defined as the age breast feeding was stopped). Main confounders were gender, gestational age less than 37 weeks, smoking in pregnancy, older siblings, maternal education, and maternal age. Hospital, doctor, or clinic visits for four or more upper respiratory tract infections were significantly greater if predominant breast feeding was stopped before 2 months or partial breast feeding was stopped before 6 months. Predominant breast feeding for less than six months was associated with an increased risk for two or more hospital, doctor, or clinic visits and hospital admission for wheezing lower respiratory illness. Breast feeding for less than eight months was associated with a significantly increased risk for two or more hospital, doctor, or clinic visits or hospital admissions because of wheezing lower respiratory illnesses. Predominant breast feeding for at least six months and partial breast feeding for up to one year may reduce the prevalence and subsequent morbidity of respiratory illness and infection in infancy.

Maternal oxidative stress during pregnancy associated with emotional and behavioural problems in early childhood: implications for foetal programming

Publisher: Springer Science and Business Media LLC

Date: 16-10-2023

DOI: 10.1038/S41380-023-02284-9

An Apparatus to Deliver Mannitol Powder for Bronchial Provocation in Children Under Six Years Old

Publisher: Mary Ann Liebert Inc

Date: 12-2015

DOI: 10.1089/JAMP.2015.1208

Abstract: Currently bronchial provocation testing (BPT) using mannitol powder cannot be performed in children under 6 years. A primary reason is it is challenging for children at this age to generate a consistent inspiratory effort to inhale mannitol efficiently from a dry powder inhaler. A prototype system, which does not require any inhalation training from the pediatric subject, is reported here. It uses an external source of compressed air to disperse mannitol powder into a commercial holding chamber. Then the subject uses tidal breathing to inhale the aerosol. The setup consists of a commercially available powder disperser and Volumatic™ holding chamber. Taguchi experimental design was used to identify the effect of dispersion parameters (flow rate of compressed air, time compressed air is applied, mass of powder, and the time between dispersion and inhalation) on the fine particle dose (FPD). The prototype was tested in vitro using a USP throat connected to a next generation impactor. The aerosols from the holding chamber were drawn at 10 L/min. A scaling factor for estimating the provoking dose to induce a 15% reduction in forced expiratory volume in 1 second (FEV1) (PD15) was calculated using anatomical dimensions of the human respiratory tract at various ages combined with known dosing values from the adult BPT. Consistent and doubling FPDs were successfully generated based on the Taguchi experimental design. The FPD was reliable over a range of 0.8 (±0.09) mg to 14 (±0.94) mg. The calculated PD15 for children aged 1-6 years ranged from 7.1-30 mg. The FPDs generated from the proposed set up are lower than the calculated PD15 and therefore are not expected to cause sudden bronchoconstriction. A prototype aerosol delivery system has been developed that is consistently able to deliver doubling doses suitable for bronchial provocation testing in young children.

Seismic evidence of two cryptic sutures in Northwestern Australia

Publisher: Elsevier BV

Date: 02-2022

DOI: 10.1016/J.EPSL.2021.117342

Assessment of bronchodilator responsiveness in preschool children using forced oscillations

Publisher: BMJ

Date: 09-2007

DOI: 10.1136/THX.2006.071290

E-Waste: A Global Hazard

Publisher: Ubiquity Press, Ltd.

Date: 25-11-2014

DOI: 10.1016/J.AOGH.2014.10.001

Abstract: Waste from end-of-life electrical and electronic equipment, known as e-waste, is a rapidly growing global problem. E-waste contains valuable materials that have an economic value when recycled. Unfortunately, the majority of e-waste is recycled in the unregulated informal sector and results in significant risk for toxic exposures to the recyclers, who are frequently women and children. The aim of this study was to document the extent of the problems associated with inappropriate e-waste recycling practices. This was a narrative review that highlighted where e-waste is generated, where it is recycled, the range of adverse environmental exposures, the range of adverse health consequences, and the policy frameworks that are intended to protect vulnerable populations from inappropriate e-waste recycling practices. The amount of e-waste being generated is increasing rapidly and is compounded by both illegal exportation and inappropriate donation of electronic equipment, especially computers, from developed to developing countries. As little as 25% of e-waste is recycled in formal recycling centers with adequate worker protection. The health consequences of both direct exposures during recycling and indirect exposures through environmental contamination are potentially severe but poorly studied. Policy frameworks aimed at protecting vulnerable populations exist but are not effectively applied. E-waste recycling is necessary but it should be conducted in a safe and standardized manor. The acceptable risk thresholds for hazardous, secondary e-waste substances should not be different for developing and developed countries. However, the acceptable thresholds should be different for children and adults given the physical differences and pronounced vulnerabilities of children. Improving occupational conditions for all e-waste workers and striving for the eradication of child labor is non-negotiable.

Sex differences in response to steroids in preterm sheep lungs are not explained by glucocorticoid receptor number or binding affinity

Publisher: Wiley

Date: 07-2001

DOI: 10.1002/PPUL.1082

Abstract: We recently reported that prenatal glucocorticoid therapy is less effective at promoting an improvement in lung function in male than in female sheep. This observation, and the higher incidence of respiratory distress syndrome in human males, suggests that the male fetal lung may be less responsive to glucocorticoids than is the female fetal lung. Since glucocorticoids are known to exert their effects via specific cytoplasmic glucocorticoid receptors (GR), we hypothesized that there may be sexual dimorphism in either the number or binding affinity of lung GR. To test the hypothesis, binding of dexamethasone (a synthetic glucocorticoid, 0.5-40 nM) by cytosolic fractions of male (n = 16) and female (n = 16) fetal sheep lung was measured at 125 days gestation (term = 148 days). Scatchard analysis of dexamethasone binding showed that the total number of GR (Bmax) did not significantly differ between male (346 +/- 42 fmol/mg protein) and female (277 +/- 23 fmol/mg protein) fetuses. The measured binding affinity (Kd) in male fetal lungs (6.85 +/- 0.43 nM) was not significantly different from that in females (8.46 +/- 1.02 nM). In conclusion, this study suggests that sex differences in fetal sheep lung responses to glucocorticoid therapy are not due to differences in the number or binding affinity of lung GR.

Occurrence and management of acute respiratory illnesses in early childhood

Publisher: Wiley

Date: 16-02-2007

DOI: 10.1111/J.1440-1754.2007.01033.X

Abstract: Acute respiratory illnesses (ARI) impose massive economic burden on health services. The growing costs, limited benefits of pharmacotherapeutic agents, and alarming rise in antibiotic resistance poses a major health challenge. Analysis of the nature and burden of ARI through well-designed epidemiologic studies will help in the development of a uniform public health approach to identify methods to reduce disease transmission and maximise prevention strategies. The aim of this study was to analyse the nature and magnitude of the burden of ARI encountered by a cohort of children in the first 5 years of life. This community-based prospective study of ARI followed a cohort of children from birth until 5 years of age. Information on all episodes of ARI encountered, and their management, was collected through daily symptom diary and fortnightly telephone calls. Four episodes of ARI/year were reported in the first 2 years and 2-3 episodes/year between 2 and 5 years. The majority were upper respiratory infections. 53% had at least one lower respiratory infection in the first year. For the majority, symptoms lasted 1-2 weeks. 53% were treated with antitussives or cough mixtures, 44% with paracetamol and 23% with antibiotics. A total of 46% of the episodes presented to a family physician, with younger children and those with lower respiratory infection more likely to seek attention. ARI are common in childhood and although symptoms may last for 4 weeks, the majority resolve spontaneously. Use of medication does not appear to significantly alter the course or duration of symptoms of ARI.

The association between Staphylococcus aureus and subsequent bronchiectasis in children with cystic fibrosis

Publisher: Elsevier BV

Date: 07-2018

DOI: 10.1016/J.JCF.2017.12.002

Abstract: Staphylococcus aureus (S. aureus) may be related to more rapid progression of cystic fibrosis (CF) lung disease. In the AREST CF cohort study, children diagnosed with CF undergo annual bronchoscopies with bronchoalveolar lavage and ultra-low-dose, chest computed tomography (CT) up to 6-years-old. Spirometry was assessed 3-monthly from the age of 4years. Associations between de novo S. aureus acquisition before school age and CT and lung function at ages 5-7years were investigated. Models were adjusted for multiple markers of disease severity at baseline. De novo S. aureus acquisition at 3-years-old (n/N=12/122) was associated with increased bronchiectasis score at age 5-6years. This association decreased but remained significant after adjustment for confounders. S. aureus at 3 was associated with significantly reduced FEF De novo S. aureus acquisition at age 3 is associated with later bronchiectasis and FEF

Association of rhinovirus and potentially pathogenic bacterial detections in the first 3 months of life with subsequent wheezing in childhood

Publisher: Wiley

Date: 06-09-2023

DOI: 10.1002/PPUL.26667

High IFN-γ production by CD8+ T cells and early sensitization among infants at high risk of atopy

Publisher: Elsevier BV

Date: 04-2004

DOI: 10.1016/J.JACI.2003.12.585

Severity and persistence of asthma and mental health: a birth cohort study

Publisher: Cambridge University Press (CUP)

Date: 29-08-2012

DOI: 10.1017/S0033291712001754

Abstract: The goal of the current study was to investigate asthma and mental health among youth in the community, and to consider the role of asthma severity and persistence in this link. Data were drawn from the Raine Study, a population-based birth cohort study in Western Australia. Logistic regression models and generalized estimating equations were used to examine the relationship between asthma at age 5 years and the range of internalizing and externalizing mental health problems at ages 5–17 years. Analyses were stratified by asthma severity and persistence, and adjusted for a range of potential confounders. More severe and persistent asthma at age 5 was associated with significantly increased odds of affective, anxiety, somatic, oppositional defiant and conduct problems at ages 5–17. Mild asthma and remitted asthma were not associated with heightened vulnerability to mental disorders. Our results suggest that youth with symptomatic asthma are more likely to suffer from a wide range of mental health problems, and that the likelihood of mental health problems appears to increase as a function of asthma severity. Youth with poorly controlled and/or more severe and persistent asthma may be considered a vulnerable group who might benefit from mental health screening in clinical, school and community settings.

Early respiratory infection is associated with reduced spirometry in children with cystic fibrosis

Publisher: American Thoracic Society

Date: 15-11-2014

DOI: 10.1164/RCCM.201407-1277OC

Ethical Issues in Measuring Biomarkers in Children’s Environmental Health

Publisher: Environmental Health Perspectives

Date: 08-2009

DOI: 10.1289/EHP.0800480

Impact of Childhood Anthropometry Trends on Adult Lung Function

Publisher: Elsevier BV

Date: 04-2201

DOI: 10.1378/CHEST.14-0698

Abstract: Poor fetal growth rate is associated with lower respiratory function however, there is limited understanding of the impact of growth trends and BMI during childhood on adult respiratory function. The current study data are from the Mater-University of Queensland Study of Pregnancy birth cohort. Prospective data were available from 1,740 young adults who performed standard spirometry at 21 years of age and whose birth weight and weight, height, and BMI at 5, 14, and 21 years of age were available. Catch-up growth was defined as an increase of 0.67 Z score in weight between measurements. The impact of catch-up growth on adult lung function and the relationship between childhood BMI trends and adult lung function were assessed using regression analyses. Lung function was higher at 21 years in those demonstrating catch-up growth from birth to 5 years (FVC, men: 5.33 L vs 5.54 L women: 3.78 L vs 4.03 L and FEV1, men: 4.52 L/s vs 4.64 L/s women: 3.31 L/s vs 3.45 L/s). Subjects in the lowest quintile of birth (intrauterine growth retardation) also showed improved lung function if they had catch-up growth in the first 5 years of life. There was a positive correlation between increasing BMI and lung function at 5 years of age. However, in the later measurements when BMI increased into the obese category, a drop in lung function was observed. These data show evidence for a positive contribution of catch-up growth in early life to adult lung function. However, if weight gain or onset of obesity occurs after 5 years of age, an adverse impact on adult lung function is noted.

RAGE deficiency predisposes mice to virus-induced paucigranulocytic asthma

Publisher: eLife Sciences Publications, Ltd

Date: 18-01-2017

DOI: 10.7554/ELIFE.21199

Abstract: Asthma is a chronic inflammatory disease. Although many patients with asthma develop type-2 dominated eosinophilic inflammation, a number of in iduals develop paucigranulocytic asthma, which occurs in the absence of eosinophilia or neutrophilia. The aetiology of paucigranulocytic asthma is unknown. However, both respiratory syncytial virus (RSV) infection and mutations in the receptor for advanced glycation endproducts (RAGE) are risk factors for asthma development. Here, we show that RAGE deficiency impairs anti-viral immunity during an early-life infection with pneumonia virus of mice (PVM a murine analogue of RSV). The elevated viral load was associated with the release of high mobility group box-1 (HMGB1) which triggered airway smooth muscle remodelling in early-life. Re-infection with PVM in later-life induced many of the cardinal features of asthma in the absence of eosinophilic or neutrophilic inflammation. Anti-HMGB1 mitigated both early-life viral disease and asthma-like features, highlighting HMGB1 as a possible novel therapeutic target.

Differential effects of nitric oxide synthase inhibitors in an in vivo allergic rat model

Publisher: European Respiratory Society (ERS)

Date: 05-2000

DOI: 10.1034/J.1399-3003.2000.15E10.X

Abstract: The in vivo role of nitric oxide in inflammatory cell migration, vascular permeability and the development of hyperresponsiveness to methacholine (MCh) was studied in rats 24 h following ovalbumin (OVA) challenge. The NO synthase (NOS) inhibitors N(G)-mono-methyl-L-arginine (L-NMMA nonselective), aminoguanidine (two-fold inducible NOS-selective), N(omega)-nitro-L-arginine methyl ester (L-NAME 2000-fold endothelial cell NOS-selective) or S-methyl-L-thiocitrulline (100-fold neuronal NOS-selective) were administered (100 mg x kg(-1) s.c.) to OVA-sensitized Piebald-Virol-Glaxo rats on 3 consecutive days during which they were challenged with allergen (1% OVA). Responses to inhaled MCh were measured in anaesthetized animals 24 h after OVA challenge. Cellular inflammation and vascular permeability were assessed using bronchoalveolar lavage (BAL) fluid collected 30 min after administration of Evans blue (50 mg x kg(-1) i.v.). OVA challenge in sensitized animals induced hyperresponsiveness to MCh, inflammatory cell influx and increased leakage of Evans blue into the BAL fluid (n=9, p<0.001). Aminoguanidine was effective in inhibiting the allergen-induced cellular influx and microvascular leakage (n=9, p<0.001) without altering responses to MCh. This effect was reserved by L-arginine. L-NAME (n=5, p<0.01) and S-methyl-L-thiocitrulline (n=6, p<0.001) further potentiated the allergen-induced hyperresponsiveness without altering cellular inflammation. L-NMMA attenuated both the OVA-induced cellular influx and Evans blue leakage (n=8, p<0.001) as well as further potentiating the hyperresponsiveness to MCh (p<0.05). From these studies, it is suggested that, in allergic Piebald-Virol-Glaxo rats, nitric oxide production by inducible nitric oxide synthase plays a role in the migration of inflammatory cells and increase in vascular permeability following allergen challenge, whereas nitric oxide produced by the constitutively expressed neuronal nitric oxide synthase limits hyperresponsiveness to methacholine.

Reduced Expression of Anti-Viral Molecules by Blood Mononuclear Cells is Associated With Asthma. but not with Atopy per se.

Publisher: Elsevier BV

Date: 02-2009

DOI: 10.1016/J.JACI.2008.12.849

Antibacterial antibody responses associated with the development of asthma in house dust mite-sensitised and non-sensitised children

Publisher: BMJ

Date: 21-11-2012

DOI: 10.1136/THORAXJNL-2011-200650

Abstract: Infants who develop house dust mite (HDM) allergy and HDM-sensitised children with severe persistent asthma have low antibody responses to the P6 antigen of Haemophilus influenzae. To measure the development of antibody to two ubiquitous bacteria of the respiratory mucosa in a prospective birth cohort at high risk of allergic disease and to assess which responses are associated with asthma and atopy. IgG1 and IgG4 antibody to H influenzae (P4 and P6) and Streptoccocus pneumoniae (PspA and PspC) surface antigens was measured in yearly blood s les of children aged 1-5 years. IgE to the P6 antigen was examined for the 5-year group. The children were stratified based on HDM sensitisation and asthma at 5 years of age. HDM-sensitised children had lower IgG1 antibody titres to the bacterial antigens, and early responses (<3 years and before the development of HDM sensitisation and asthma) corrected for multiple antigens were significantly reduced for P4, P6 and PspC (p=0.008, p=0.004 and p=0.028, respectively). Similar associations with asthma were also found (p=0.008, p=0.004 and p=0.032 for P4, P6 and PspC, respectively). The IgG4 antibody titre and prevalence were similar in both HDM-sensitised and non-sensitised groups, but sensitised children had a slower downregulation of the IgG4 response. Children with asthma (27/145 at 5 years) had lower anti-P6 IgE responses (p<0.05). HDM-sensitised children have early defective antibody responses to bacteria that are associated with asthma. Surprisingly, antibacterial IgE was associated with a reduced risk for asthma.

The influence of breathhold on peak expiratory flow in normal and asthmatic children

Publisher: European Respiratory Society (ERS)

Date: 06-1996

DOI: 10.1183/09031936.96.09071363

Abstract: We have previously demonstrated a 10% reduction in peak expiratory flow (PEF) in healthy adults following a breathhold at total lung capacity (TLC). This fall was attributed to dissipation of airway wall viscoelasticity, increasing airway wall compliance (Caw). To investigate this phenomenon in children and to determine whether the effect of breathhold would be greater in asthmatics than in normal children, 15 asthmatics and 14 normal children (aged 10-15 yrs) performed maximal post expirations (MFE) with and without a 5 s breathhold at TLC. The entire study was repeated following the inhalation of salbutamol (800 micrograms) to relax the airway smooth muscle (and to increase Caw). Breathhold at TLC resulted in a significant decrease in PEF both in the asthmatics (group mean fall 5.8% p < 0.01) and normal children (group mean fall 10.3% p < 0.05). Salbutamol diminished this fall, becoming nonsignificant in the normal children. Similar patterns were also seen in forced expiratory volume in one second (FEV1) and in maximal expiratory flow at 50% vital capacity (V'50). These data are consistent with the proposal that breathhold at total lung capacity dissipated viscoelastic energy (increasing airway compliance) and decreased maximal expiratory flows both in normal and asthmatic children. They also demonstrate the need to standardize the forced vital capacity manoeuvre to decrease the variability in the flows recorded during the subsequent forced expiration.

Children's environmental health—from knowledge to action

Publisher: Elsevier BV

Date: 04-2011

DOI: 10.1016/S0140-6736(10)60929-4

Effect of omega-3 fatty acids supplementation during pregnancy on lung function in preschoolers: a clinical trial

Publisher: Informa UK Limited

Date: 04-04-2018

DOI: 10.1080/02770903.2018.1452934

Abstract: Prenatal omega-3 fatty acids improve alveolarization, diminish inflammation, and improve pulmonary growth, but it is unclear whether these outcomes translate into improved postnatal lung function. We assessed the effect of prenatal supplementation with docosahexaenoic acid (DHA) on offspring lung function through 60 months of age. We included a cohort of 772 Mexican preschoolers whose mothers participated in a clinical trial (NCT00646360) of supplementation with DHA or a placebo from week 18-22 of gestation through delivery. The children were followed after birth and anthropometric measurements and forced oscillation tests were performed at 36, 48, and 60 months of age. The effect of DHA was tested using a longitudinal mixed effect models. Overall, mean (Standard Deviation) of the measurements of respiratory system resistance and respiratory system reactance at 6, 8, and 10 Hz during follow up period were 11.3 (2.4), 11.1 (2.4), 10.3 (2.2) and -5.2 (1.6), -4.8 (1.7), -4.6 (1.6), respectively. There were no significant differences in pulmonary function by treatment group. DHA did not affect the average lung function or the trajectories through 60 months. Prenatal DHA supplementation did not influence pulmonary function in this cohort of Mexican preschoolers.

Indoor determinants of dustborne allergens in Mexican homes

Publisher: Oceanside Publications Inc.

Date: 03-2015

DOI: 10.2500/AAP.2015.36.3801

Preface

Publisher: Elsevier

Date: 2008

DOI: 10.1016/B978-032304048-8.50004-9

Anti-infective proteins in breast milk and asthma-associated phenotypes during early childhood

Publisher: Wiley

Date: 10-2014

DOI: 10.1111/PAI.12265

Abstract: The impact of breast milk feeding on susceptibility to asthma in childhood is highly controversial, due in part to failure of the majority of studies in the area to adequately account for key confounders exemplified by respiratory infection history, plus the effects of recall bias. As part of a prospective cohort study on the role of respiratory infections in asthma development in high-risk children, we measured the concentration of a panel of anti-infective proteins in maternal milk s les and analyzed associations between these and subsequent atopy-, infection-, and asthma-related outcomes prospectively to age 10 years. We observed significant but transient inverse associations between the concentration of milk proteins and susceptibility to upper respiratory infections in year 1 only, and parallel but positive transient associations with early lower respiratory infections and atopy. No associations were seen with asthma-related outcomes. Breast milk feeding may influence the expression of inflammatory symptoms associated with respiratory infections and atopy in early life, but these effects appear to be inconsistent and transient. The heterogeneous nature of breast-feeding effects suggests it may influence systemic immunoinflammatory function at several different levels.

Environmental Factors in Children’s Asthma and Respiratory Effects

Publisher: Elsevier

Date: 2015

DOI: 10.1016/B978-0-12-409548-9.09490-2

Indigenous health and environmental risk factors: an Australian problem with global analogues?

Publisher: Informa UK Limited

Date: 29-04-2014

DOI: 10.3402/GHA.V7.23766

Commentary

Publisher: Wiley

Date: 1991

DOI: 10.1002/PPUL.1950100206

Life-Long Implications of Developmental Exposure to Environmental Stressors: New Perspectives

Publisher: The Endocrine Society

Date: 21-07-2015

DOI: 10.1210/EN.2015-1350

Abstract: The Developmental Origins of Health and Disease (DOHaD) paradigm is one of the most rapidly expanding areas of biomedical research. Environmental stressors that can impact on DOHaD encompass a variety of environmental and occupational hazards as well as deficiency and oversupply of nutrients and energy. They can disrupt early developmental processes and lead to increased susceptibility to disease/dysfunctions later in life. Presentations at the fourth Conference on Prenatal Programming and Toxicity in Boston, in October 2014, provided important insights and led to new recommendations for research and public health action. The conference highlighted vulnerable exposure windows that can occur as early as the preconception period and epigenetics as a major mechanism than can lead to disadvantageous “reprogramming” of the genome, thereby potentially resulting in transgenerational effects. Stem cells can also be targets of environmental stressors, thus paving another way for effects that may last a lifetime. Current testing paradigms do not allow proper characterization of risk factors and their interactions. Thus, relevant exposure levels and combinations for testing must be identified from human exposure situations and outcome assessments. Testing of potential underpinning mechanisms and biomarker development require laboratory animal models and in vitro approaches. Only few large-scale birth cohorts exist, and collaboration between birth cohorts on a global scale should be facilitated. DOHaD-based research has a crucial role in establishing factors leading to detrimental outcomes and developing early preventative/remediation strategies to combat these risks. (Endocrinology 156: 3408-3415, 2015)

Disease surveillance using bronchoalveolar lavage

Publisher: Elsevier BV

Date: 09-2008

DOI: 10.1016/J.PRRV.2008.01.002

Abstract: The role of pulmonary infection and inflammation in the pathogenesis of destructive lung disease in cystic fibrosis (CF) is undisputed. The use of bronchoscopy and bronchoalveolar lavage (BAL) has demonstrated that these processes may begin early in life and be present in the absence of overt clinical symptoms. Some children diagnosed following newborn screening can be infected with Pseudomonas aeruginosa in infancy. Studies using BAL have demonstrated a relationship between lower airway inflammation and bacterial load in the lungs however, inflammation may occur in the absence of obvious current infection. BAL has the potential to provide a greater understanding of the pathogenesis of CF lung disease and microbiological surveillance provides the opportunity for early detection and eradication of P. aeruginosa. Lack of standardization inhibits the ability to compare data from different centres and to optimize treatment strategies. This review discusses the recommendations from a workshop held in early 2007 aimed at achieving a standardized approach to BAL in infants and young children with CF.

Factors influencing the assessment of lung function in mice with influenza-induced lung disease

Publisher: Wiley

Date: 08-11-2013

DOI: 10.1111/IRV.12034

Sensitivity Analysis of Respiratory Parameter Estimates in the Constant-Phase Model

Publisher: Springer Science and Business Media LLC

Date: 06-2004

DOI: 10.1023/B:ABME.0000030257.88945.81

Abstract: The constant-phase model is increasingly used to fit low-frequency respiratory input impedance (Zrs), highlighting the need for a better understanding of the use of the model. Of particular interest is the extent to which Zrs would be affected by changes in parameters of the model, and conversely, how reliable are parameters estimated from model fits to the measured Zrs. We performed sensitivity analysis on respiratory data from 6 adult mice, at functional residual capacity (FRC), total lung capacity (TLC), and during bronchoconstriction, obtained using a 1-25 Hz oscillatory signal. The partial derivatives of Zrs with respect to each parameter were first examined. The limits of the 95% confidence intervals, 2-dimensional pairwise and p-dimensional joint confidence regions were then calculated. It was found that airway resistance was better estimated at FRC, as determined by the confidence region limits, whereas tissue d ing and elastance were better estimated at TLC. Airway inertance was poorly estimated at this frequency range, as expected. During methacholine-evoked pulmonary constriction, there was an increase in the uncertainty of airway resistance and tissue d ing, but this can be compensated for by using the relative (weighted residuals) in preference over the absolute (unweighted residuals) fitting criterion. These results are consistent with experimental observation and physiological understanding.

Postnatal alveolar development of the rabbit

Publisher: American Physiological Society

Date: 08-2002

DOI: 10.1152/JAPPLPHYSIOL.01044.2001

Abstract: Previous studies of alveolarization have used rats or lambs however, neither closely reflects human alveolar development. We characterized alveolar development in rabbits ( n = 3–7 /group) at 28 days gestation (dg) to 9 mo to determine whether they followed the human pattern more closely. The right lung was made up of 30% alveolar and 50% duct space at 28 dg to 3 days and of 50 and 30%, respectively, at 14 days to 9 mo. Tissue fraction and alveolar wall thickness decreased by 40% 28 dg to birth. At birth, ∼4.5% of the number of alveoli seen at 9 mo were present, with alveolar number increasing progressively well into adulthood. The rate of alveolar formation was high around birth, decreasing progressively with age. Alveolar volume increased more than twofold (28 dg to birth) and continued to increase postnatally to 16 wk. Surface fraction decreased by 17% (28 dg to 3 days), after which it remained uniform. Our findings suggest that the timing of onset of alveolarization in humans and rabbits is similar and that rabbits may be used to model postnatal influences on alveolar development.

Is home monitoring of lung function worthwhile for children with asthma?

Publisher: BMJ

Date: 03-2001

DOI: 10.1136/THORAX.56.3.164

Oxidized glutathione and uric acid as biomarkers of early cystic fibrosis lung disease

Publisher: Elsevier BV

Date: 03-2017

DOI: 10.1016/J.JCF.2016.10.012

Abstract: In cystic fibrosis (CF) there is an urgent need for earlier diagnosis of pulmonary infections and inflammation using blood- and urine-based biomarkers. Using mass spectrometry, oxidation products of glutathione and uric acid were measured in matched s les of bronchoalveolar lavage (BAL), serum and urine from 36 infants and children with CF, and related to markers of neutrophilic inflammation and infection in BAL. Oxidation products of glutathione (glutathione sulfonamide, GSA) and uric acid (allantoin), were elevated in BAL of children with pulmonary infections with Pseudomonas aeruginosa (PsA) compared to those without (p<0.05) and correlated with other markers of neutrophilic inflammation. Serum GSA was significantly elevated in children with PsA infections (p<0.01). Urinary GSA correlated with pulmonary GSA (r=0.42, p<0.05) and markers of neutrophilic inflammation. This proof-of-concept study demonstrates that urinary GSA but not allantoin shows promise as a non-invasive marker of neutrophilic inflammation in early CF lung disease.

Microbial exposure, interferon gamma gene demethylation in naïve T-cells, and the risk of allergic disease

Publisher: Wiley

Date: 23-02-2009

DOI: 10.1111/J.1398-9995.2009.01970.X

Abstract: The period of immune programming during early life presents a critical window of opportunity for the prevention of allergic diseases. There is mounting evidence that inappropriate immune programming may involve disruption of specific epigenetic modifications (switches) at immune-related genes. This novel area of research has great potential, as epigenetic changes are known to be sensitive to environmental factors and may therefore provide a mechanistic link for the observed association between specific environmental cues, faulty immune development, and the risk of allergic disease. In addition, the dynamic and potentially reversible nature of epigenetic modifications offers potentially novel targets for therapeutic and/or preventative interventions. We review the evidence that (1) failure to up-regulate the interferon gamma (IFNgamma) response during infancy is an important determinant of the risk of allergic disease, (2) expression of the IFNgamma gene in naïve T-cells is regulated by epigenetic mechanisms, and (3) failure to up-regulate IFNgamma gene expression of naïve T-cells associated with low early life microbial exposure. Taken together, these lines of evidence suggest that low microbial exposure during early life increases the risk of allergic disease by reducing demethylation (activation) of the IFNgamma gene of naive T-cells.

Medical Research Results in the General Media: worthwhile and rewarding if presented well, potentially harmful if prepared poorly

Publisher: Elsevier BV

Date: 12-2011

DOI: 10.1016/J.PRRV.2011.01.013

Abstract: There are a number of advantages to communicating research results via the general media, including: fulfilling the obligation imposed by publicly-funded research to return research results to the public enhancing the reputation of the in idual researcher and of their institution in their community and acting as an advocate for the research areas of interest. The choice of media outlet depends on the nature and importance of the results to be communicated. In idual researchers, especially early in their career, need adequate support from appropriately trained staff in dealing with the media. However, if done correctly, dealing with the media can be a worthwhile and rewarding experience. Before contacting the press, it is important that researchers decide on their key message to be conveyed, define any area of their research they do not wish to discuss in public, and prepare answers to the most likely questions the journalist may ask.

Viral co-detection in infants hospitalized with respiratory disease: is it important to detect?

Publisher: Jornal de Pediatria

Date: 23-08-2011

DOI: 10.2223/JPED.2117

Management of childhood asthma in Western Australia

Publisher: Wiley

Date: 03-2009

DOI: 10.1111/J.1440-1754.2008.01441.X

Abstract: The study aimed to determine how childhood asthma is managed in Western Australia by general practitioners (GPs) and specialist paediatricians. A questionnaire survey was sent to 992 GPs and specialist paediatricians, asking about practice and preferences regarding maintenance management of childhood asthma and treatment of acute asthma. Questions about asthma in infants, pre-school and school-aged children were asked separately. The overall response rate was 24.7%, with 188/878 (21.4%) of GPs and 44/62 (71.0%) of paediatricians returning the questionnaire. The decision to start maintenance therapy was generally based on symptom frequency and severity. The first choice for maintenance treatment in all age groups was inhaled corticosteroids (ICS). The second most common treatment varied according to age group, with short-acting beta(2)-agonist (SBA) preferred for infants, montelukast or short-acting beta(2)-agonist for pre-schoolers and combination therapy (ICS + long action beta(2)-agonist) for school-aged children. Objective monitoring of lung function with peak flow or spirometry, was used by 40% of GPs and 59% of paediatricians. Acute asthma was primarily managed with inhaled salbutamol and oral corticosteroids. There were few differences in treatment choice between GPs and paediatricians. Many GPs indicated that they did not treat asthma in infants without specialist consultation. These data show good compliance by the minority of GPs responding to the survey and by paediatricians practising in Western Australia with current Australian asthma management guidelines. Major differences in treatment preferences between the groups were not detected.

Antenatal Intraamniotic Endotoxin Stimulates Lung Maturation in Preterm Sheep

Publisher: Springer Science and Business Media LLC

Date: 04-1999

DOI: 10.1203/00006450-199904020-01203

Assessment of Early Bronchiectasis in Young Children With Cystic Fibrosis Is Dependent on Lung Volume

Publisher: Elsevier BV

Date: 10-2013

DOI: 10.1378/CHEST.12-2589

Abstract: The aim of this study was to determine whether assessment of early CT scan-detected bronchiectasis in young children with cystic fibrosis (CF) depends on lung volume. This study, approved by the hospital ethics committee, included 40 young children with CF from a newborn screened population contributing paired volume-controlled inspiratory and expiratory volumetric chest CT scans acquired under general anesthesia while clinically stable. Bronchiectasis was assessed with a semiquantitative CT scan score in inspiration and expiration, and the sensitivity of the expiratory CT scan to detect bronchiectasis was compared with the inspiratory CT scan by sensitivity and intraclass correlation coefficient analysis and Bland-Altman plots. Matched inspiratory and expiratory airway-vessel measurements were obtained in a subset of 10 children, and the relationship between lung volume and airway:vessel ratio after adjusting for age and vessel size was examined with the use of a linear regression model with generalized estimating equations. The number of visible airways in inspiration and expiration was compared in all 40 children by Wilcoxon signed rank test. Expiratory scans had poor sensitivity (0.46) to detect bronchiectasis, underestimating disease extent (P .001). Airway:vessel ratios were consistently higher in inspiration, independent of age and vessel size (P .001), with significantly more airways visible in inspiration than in expiration, independent of age (median, 71 vs 28, respectively P .001). In young children with CF, radiologic assessment of early bronchiectasis with chest CT scan depends on lung volume thus, expiratory scans may not be appropriate for evaluating bronchiectasis in this population. Lung volume during CT image acquisition should be standardized to evaluate airway dimensions in young children.

Respiratory Function Testing in Infants and Preschool-Aged Children

Publisher: Elsevier

Date: 2008

DOI: 10.1016/B978-032304048-8.50016-5

E-cigarettes: risk mitigation for smokers or a public health disaster?

Publisher: Walter de Gruyter GmbH

Date: 26-09-2017

DOI: 10.1515/REVEH-2017-0022

Dendritic cell immaturity during infancy restricts the capacity to express vaccine-specific T-cell memory

Publisher: American Society for Microbiology

Date: 02-2006

DOI: 10.1128/IAI.74.2.1106-1112.2006

Abstract: The capacity of the immune system in infants to develop stable T-cell memory in response to vaccination is attenuated, and the mechanism(s) underlying this developmental deficiency in humans is poorly understood. The present study focuses on the capacity for expression of in vitro recall responses to tetanus and diphtheria antigens in lymphocytes from 12-month-old infants vaccinated during the first 6 months of life. We demonstrate that supplementation of infant lymphocytes with “matured” dendritic cells (DC) cultured from autologous CD14 + precursors unmasks previously covert cellular immunity in the form of Th2-skewed cytokine production. Supplementation of adult lymphocytes with comparable prematured autologous DC also boosted vaccine-specific T-cell memory expression, but in contrast to the case for the infants, these cytokine responses were heavily Th1 skewed. Compared to adults, infants had significantly fewer circulating myeloid DC ( P 0.0001) and plasmacytoid DC ( P 0.0001) as a proportion of peripheral blood mononuclear cells. These findings suggest that deficiencies in the numbers of antigen-presenting cells and their functional competence at 12 months of age limit the capacity to express effector memory responses and are potentially a key factor in reduced vaccine responsiveness in infants.

Age-Related trends in urinary excretion of bisphenol a in australian children and adults: Evidence from a pooled sample study using samples of convenience

Publisher: Informa UK Limited

Date: 17-09-2013

DOI: 10.1080/15287394.2013.834856

Abstract: Bisphenol A (BPA or 4,4'-(propane-2,2-diyl)diphenol) is a chemical intermediate in the production of polycarbonate and epoxy resins, and is used in a wide range of applications. BPA has attracted significant attention in the past decade due to its frequency of detection in human populations worldwide, and has demonstrated animal toxicity and potential impact on human health, particularly during critical periods of development. The aim of this study was to perform a preliminary assessment of age-related trends in urinary concentration and to estimate daily excretion of BPA in Australian children (aged >0 to <5 yr) and adults (≥15 to <75 yr). This was achieved using 79 s les pooled by age and gender, created from 868 in idual s les of convenience collected as part of routine, community-based pathology testing. Total BPA was analyzed using online solid phase extraction (SPE)-liquid chromatography tandem mass spectrometry (LC-MS/MS) and detected in all s les with a range of 0.65-265 ng/ml. No significant differences were observed between males and females. A urine flow model was constructed from published values and was used to provide an estimate of daily excretion per unit body weight for each pooled s le. The daily excretion estimates ranged from 26.2 to 18,200 ng/kg-d for children, and from 20.1 to 165 ng/kg-d for adults. Urinary concentrations and estimated excretion rates were inversely associated with age, and estimated daily excretion in infants and young children was significantly higher than in adults (geometric mean: 107 and 47.0 ng/kg-d, respectively). Higher excretion of BPA in children may be explained by their higher food consumption relative to body weight compared to adults and adolescents, and may also reflect alternative exposure pathways and sources.

Measurement of lung function in preschool children using the interrupter technique

Publisher: BMJ

Date: 09-2003

DOI: 10.1136/THORAX.58.9.742

Erratum: A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: evidence for a major susceptibility locus on chromosome 2p

Publisher: Springer Science and Business Media LLC

Date: 24-05-2007

DOI: 10.1038/SJ.EJHG.5201840

Systematic Error in Respiratory Impedance Using Commercial Equipment Calibrated according to the Manufacturer’s Instructions

Publisher: American Thoracic Society

Date: 15-02-2018

DOI: 10.1164/RCCM.201704-0713LE

Changing Prevalence of Lower Airway Infections in Young Children with Cystic Fibrosis

Publisher: American Thoracic Society

Date: 09-2019

DOI: 10.1164/RCCM.201810-1919OC

Lung volume recruitment maneuvers and respiratory system mechanics in mechanically ventilated mice

Publisher: Elsevier BV

Date: 12-2009

DOI: 10.1016/J.RESP.2009.09.012

Abstract: The study aim was to establish how recruitment maneuvers (RMs) influence lung mechanics and to determine whether RMs produce lung injury. Healthy BALB/c mice were allocated to receive positive end-expiratory pressure (PEEP) at 2 or 6 cmH(2)O and volume- (20 or 40 mL/kg) or pressure-controlled (25 cmH(2)O) RMs every 5 or 75 min for 150 min. The low-frequency forced oscillation technique was used to measure respiratory input impedance. Large RMs resulting in peak airway opening pressures (P(ao))>30 cmH(2)O did not increase inflammatory response or affect transcutaneous oxygen saturation but significantly lowered airway resistance, tissue d ing and tissue elastance the latter changes are likely associated with the bimodal pressure-volume behavior observed in mice. PEEP increase alone and application of RMs producing peak P(ao) below 25 cmH(2)O did not prevent or reverse changes in lung mechanics whereas frequent application of substantial RMs on top of elevated PEEP levels produced stable lung mechanics without signs of lung injury.

The Spectrum of Lower Respiratory Tract Illness in Children after Pneumococcal Conjugate Vaccination

Publisher: American Thoracic Society

Date: 2017

DOI: 10.1164/RCCM.201607-1461ED

Atypical mycobacterial pulmonary disease and bronchial obstruction in HIV-negative children

Publisher: Wiley

Date: 12-1998

DOI: 10.1002/(SICI)1099-0496(199812)26:6<380::AID-PPUL2>3.0.CO;2-I

Abstract: Atypical mycobacterial infection in HIV-negative children usually presents with cervical lymphadenopathy. We report on 10 children who are HIV-negative and who presented with pulmonary disease, in whom either culture-proven atypical mycobacterium infection (four), positive avian Mantoux test (five), or lack of response to human tuberculosis treatment (one) had been observed. One case was subsequently diagnosed as chronic granulomatous disease and illustrates that children with atypical mycobacterial pulmonary infection should have their immune status fully investigated. Bronchial obstruction was observed in eight cases, and of these, endobronchial disease was found in six children. The diagnosis of atypical mycobacterial disease is difficult, and a negative avian Mantoux test does not exclude the diagnosis. The availability of clarithromycin and rifabutin has offered new therapeutic options in treating atypical mycobacterial pulmonary infection, but management of these cases can be prolonged and difficult.

Use of Peak Expiratory Flow Rates in Treating Patients-Reply

Publisher: American Medical Association (AMA)

Date: 08-1986

DOI: 10.1001/ARCHPEDI.1986.02140220020008

Trajectories of psychosocial environmental factors and their associations with asthma symptom trajectories among children in Australia

Publisher: Wiley

Date: 26-10-2023

DOI: 10.1002/PPUL.26733

Assessment of respiratory mechanics with forced oscillations in healthy newborns

Publisher: Wiley

Date: 25-08-2014

DOI: 10.1002/PPUL.23103

Abstract: Lung function data in healthy newborn infants are scarce largely due to lack of suitable techniques, although data for developmental and prenatal exposure studies are much needed. We have modified the forced oscillation technique (FOT) for the measurement of respiratory mechanical impedance (Zrs) in unsedated sleeping infants in the first 3 days of life. Zrs was measured during 30-s epochs of quiet sleep in term neonates born via spontaneous vaginal delivery with a non-invasive FOT between 8 and 48 Hz. Total respiratory resistance (R), compliance (C) and inertance (I) were obtained by fitting Zrs spectra. Cluster analysis was used to determine a set of minimal Zrs spectra representing optimal respiratory mechanics for each infant. Successful measurements were obtained in each of the first 3 days in 30/38 (78.9%) neonates. Group mean (± SD) values of R, C, I, and resonant frequency pooled for the 3 days were 45.9 ± 16.6 hPa s L(-1), 0.97 ± 0.21 ml hPa(-1), 0.082 ± 0.031 hPa s(2) L(-1) and 19.2 ± 3.2 Hz, respectively. Within-session variability represented by coefficient of variation was 5.34 ± 3.18% for R and 13.80 ± 8.57% for C. Greater between-session variability was observed for the in idual infants however, the only statistically significant change over time was a 13% increase in R from day 1 to day 2. Parameter interdependence was significant (r(2) = 0.63) between R and I reflecting the large contribution of the upper airways to the total Zrs. Noninvasive measurement of Zrs can be made in neonates during natural sleep with a high success rate, even in the first hours of life.

Maternal carriage of Prevotella during pregnancy associates with protection against food allergy in the offspring

Publisher: Springer Science and Business Media LLC

Date: 24-03-2020

DOI: 10.1038/S41467-020-14552-1

Abstract: In mice, the maternal microbiome influences fetal immune development and postnatal allergic outcomes. Westernized populations have high rates of allergic disease and low rates of gastrointestinal carriage of Prevotella , a commensal bacterial genus that produces short chain fatty acids and endotoxins, each of which may promote the development of fetal immune tolerance. In this study, we use a prebirth cohort ( n = 1064 mothers) to conduct a nested case-cohort study comparing 58 mothers of babies with clinically proven food IgE mediated food allergy with 258 randomly selected mothers. Analysis of the V4 region of the 16S rRNA gene in fecal s les shows maternal carriage of Prevotella copri during pregnancy strongly predicts the absence of food allergy in the offspring. This association was confirmed using targeted qPCR and was independent of infant carriage of P. copri . Larger household size, which is a well-established protective factor for allergic disease, strongly predicts maternal carriage of P. copri .

The early origins of asthma: who is really at risk?

Publisher: Ovid Technologies (Wolters Kluwer Health)

Date: 02-2011

DOI: 10.1097/ACI.0B013E328342309D

Diagnosis of cystic fibrosis after newborn screening: The Australasian experience - Twenty years and five million babies later: A consensus statement from the Australasian Paediatric Respiratory Group

Publisher: Wiley

Date: 05-2005

DOI: 10.1002/PPUL.20191

Abstract: Newborn screening for cystic fibrosis has been used in Australia and New Zealand for over 20 years. In that time, considerable experience has been developed regarding the early diagnosis of cystic fibrosis after newborn screening. To date, there has not been a consensus on the process of screening and clinical evaluation leading to the diagnosis of cystic fibrosis in infants, many of whom are not symptomatic at time of notification of the screening result. The aim of this paper is to provide some consensus on the important issues of a cystic fibrosis diagnosis arising from newborn screening, based on the experience gained in Australia and New Zealand over the last 20 years.

Identification of a novel asthma susceptibility gene on chromosome 1qter and its functional evaluation

Publisher: Oxford University Press (OUP)

Date: 12-03-2008

DOI: 10.1093/HMG/DDN087

Abstract: Asthma is a multifactorial disease, in which the intricate interplay between genetic and environmental factors underlies the overall phenotype of the disease. Using a genome-wide scan for linkage in a population comprising of Danish families, we identified a novel linked locus on chromosome 1qter (LOD 3.6, asthma) and supporting evidence for this locus was identified for both asthma and atopic-asthma phenotypes in the GAIN (Genetics of Asthma International Network) families. The putative susceptibility gene was progressively localized to a 4.5 Mb region on chromosome 1q adjacent to the telomere, through a series of genotyping screens. Further screening using the pedigree-based association test (PBAT) identified polymorphisms in the OPN3 and CHML genes as being associated with asthma and atopic asthma after correcting for multiple comparisons. We observed that polymorphisms flanking the OPN3 and CHML genes wholly accounted for the original linkage in the Danish population and the genetic association was also confirmed in two separate studies involving the GAIN families. OPN3 and CHML are unique genes with no known function that are related to the pathophysiology of asthma. Significantly, analysis of gene expression at both RNA and protein levels, clearly demonstrated OPN3 expression in lung bronchial epithelia as well as immune cells, while CHML expression appeared minimal. Moreover, OPN3 down-regulation by siRNA knock-down in Jurkat cells suggested a possible role for OPN3 in modulation of T-cell responses. Collectively, these data suggest that OPN3 is an asthma susceptibility gene on 1qter, which unexpectedly may play a role in immune modulation.

Risk assessment for respiratory complications in paediatric anaesthesia: a prospective cohort study

Publisher: Elsevier BV

Date: 09-2010

DOI: 10.1016/S0140-6736(10)61193-2

Viscosity and density of common anaesthetic gases: implications for flow measurements

Publisher: Elsevier BV

Date: 10-2001

DOI: 10.1093/BJA/87.4.602

Abstract: Although viscosity (mu) is a crucial factor in measurements of flow with a pneumotachograph, and density (rho) also plays a role in the presence of turbulent flow, these material constants are not available for the volatile anaesthetic agents commonly administered in clinical practice. Thus, we determined experimentally mu and rho of pure volatile anaesthetic agents. Input impedance of a rigid-wall polyethylene tube (Zt) was measured when the tube was filled with various mixtures of carrier gases (air, 100% oxygen, 50% oxygen+50% nitrogen) to which different concentrations of volatile anaesthetic inhalation agents (halothane, isoflurane, sevoflurane, and desflurane) had been added. Mu and rho were calculated from real and imaginary portions of Zt, respectively, using the appropriate physical equations. Multiple linear regression was applied to estimate mu and rho of pure volatile agents. Viscosity values of pure volatile agents were markedly lower than those for oxygen or nitrogen. Clinically applied concentrations, however, did not markedly affect the viscosity of the gas mixture (maximum of 3.5% decrease in mu for 2 MAC desflurane). In contrast, all of the volatile agents significantly affected rho even at routinely used concentrations. Our results suggest that the composition of the carrier gas has a greater impact on viscosity than the amount and nature of the volatile anaesthetic agent whereas density is more influenced by volatile agent concentrations. Thus, the need for a correction factor in flow measurements with a pneumotachograph depends far more on the carrier gas than the concentration of volatile agent administered, although the latter may play a role in particular experimental or clinical settings.

Negative impact of the noseclip on high-frequency respiratory impedance measurements

Publisher: Elsevier BV

Date: 2009

DOI: 10.1016/J.RESP.2008.10.014

Abstract: The noseclip is conventionally used in lung function testing to prevent leakage via the nasal compartments. However, some subjects exhibit a velum-opening reflex which may affect results. We performed forced oscillation measurements at frequencies (8-256 Hz) that include the first antiresonance, comparing the noseclip with a cotton wool nose plug to eliminate upper airway contribution. Three sets of measurements were made in 18 adults: with and without noseclip, and with cotton wool. Velum opening during noseclip measurements was monitored using a nasal pressure transducer. A significantly greater proportion of subjects produced a characteristic distortion to the first antiresonance with the noseclip than with either no noseclip or with cotton wool. Distortion of the spectrum coincided with the transmission of oscillations into the nasal cavity. Thus, the noseclip cannot be used in high-frequency forced oscillation measurements because of the velum reflex. The cotton wool plug offers a simple alternative. This effect has unknown impact in other lung function tests.

Contemporaneous maturation of immunologic and respiratory functions during early childhood: Implications for development of asthma prevention strategies

Publisher: Elsevier BV

Date: 07-2005

DOI: 10.1016/J.JACI.2005.04.017

Abstract: The term asthma refers to a spectrum of wheezing syndromes resulting from airways inflammation triggered by a range of environmental stimuli, the most important of which are aeroallergens and viruses. We describe below a model for the cause of atopic asthma in which discrete sets of developmental factors governing the postnatal maturation of the immune and respiratory systems play central and complementary roles in disease causality. Within the immune system, the relevant developmental processes involve maturation of TH1 and associated innate immune functions that combat infection and concomitantly antagonize the early programming of TH2-polarized immunologic memory against inhalant allergens. Within the respiratory system, the relevant developmental processes involve intensive lung growth and airway remodeling during infancy. We hypothesize that delayed maturation of TH1-associated functions during early postnatal life increases the risk for sensitization to aeroallergens and for severe respiratory infection, resulting in airway inflammation at a crucial stage in lung development and precipitating changes in lung growth that are the harbingers of susceptibility to persistent asthma. We further hypothesize that protection of the growing lung against the effects of inflammation during infancy and early childhood has unique potential as a generic strategy for asthma prophylaxis.

Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis

Publisher: BMJ

Date: 17-04-2014

DOI: 10.1136/THORAXJNL-2014-205213

Maternal Asthma, Pregnancy Complications, and Offspring Wheeze. Untangling the Web

Publisher: American Thoracic Society

Date: 2019

DOI: 10.1164/RCCM.201808-1584ED

Early-life risk factors for chronic nonrespiratory diseases

Publisher: European Respiratory Society (ERS)

Date: 13-11-2014

DOI: 10.1183/09031936.00070214

Abstract: We have witnessed a change in disease patterns contributing to the global burden of disease, with a shift from early childhood deaths due to the classic infectious communicable diseases to years lived with disability from chronic noncommunicable diseases. In both developing and developed countries, the years lived with disability attributable to chronic disease have increased: cardiovascular diseases by 17.7% chronic respiratory disease by 8.5% neurological conditions by 12.2% diabetes by 30.0% and mental and behavioural disorders by 5.0% over the past 20 years. Recognition of the contribution made by adverse environmental exposures in early life to noncommunicable diseases in later life is increasing. These early-life exposures appear to contribute to both chronic respiratory and chronic nonrespiratory diseases. In this State of the Art article, we aim to examine early-life environmental exposures that have an epidemiological association with chronic nonrespiratory diseases, such as obesity and type II diabetes, cardiovascular disease, and neurocognitive and behavioural problems. We will highlight the potential overlap in environmental risks with respiratory diseases, and point out knowledge gaps and research opportunities.

Tidal forced expirations

Publisher: European Respiratory Society (ERS)

Date: 10-2000

DOI: 10.1034/J.1399-3003.2000.16D29.X

Abstract: The progress of infant lung function testing has been retarded by both the lack of user-friendly, widely available and affordable equipment and the lack of standardized methodology. The European Respiratory Society/American Thoracic Society Task Force on Standards for Infant Respiratory Function Testing was formed in an attempt to address these deficiencies. This document represents the consensus of investigators with vast experience in the measurement of lung function in infants. The present recommendations deal with equipment requirements, study procedures and reporting of data for measurements of forced expiration at end-tidal inspiration. They represent the "state of the art" in 1999. They are not meant to inhibit further developments in this technique. The authors anticipate that these guidelines will be updated regularly as knowledge progresses.

Early‐onset atopy is associated with enhanced lymphocyte cytokine responses in 11‐year‐old children

Publisher: Wiley

Date: 03-2007

DOI: 10.1111/J.1365-2222.2007.02668.X

Abstract: Early age at onset of atopy is associated with more severe asthma and increased airway responsiveness (AR) the underlying mechanism is unclear but may involve T cell responses. To test the hypothesis that enhanced T cell responses may be associated with early-onset atopy. In a longitudinal study, atopy was determined in infancy and at 6 and 11 years of age. In iduals were categorized as persistent infant-onset atopy (PIOA), early childhood-onset atopy (ECOA) and later childhood-onset atopy (LCOA). At 11 years of age, peripheral blood T cell cytokine responses, AR, exhaled nitric oxide (FE(NO)) and forced expiratory volume in 1 s were determined. The age at onset of atopy was determined for 60 children, of whom 15 had PIOA, 24 had ECOA and 21 had LCOA. An additional 76 children who were never atopic were also included. T cell responses to house dust mite, including interleukin-5, -9, -10 and tumour necrosis factor alpha, were higher among children with PIA and ECOA, and lower in children with LCOA, P<0.05. In contrast, those children with LCOA or who were not atopic had the highest IL-10 response to PHA (P=0.014). Children with PIOA and ECOA, but not LCOA, had higher AR and FE(NO) compared with non-atopic children (P<0.05). The group with PIOA were more likely among the atopic children to be admitted to hospital for asthma (P<0.05) and also had lower %FEV(1) compared with non-atopic children (P=0.023). Early age at sensitization is associated with enhanced T cell cytokine responses and indices of adverse asthma outcome. T cell cytokine responses might be programmed at the time of initial atopic sensitization.

Gender-specific effects of cytokine gene polymorphisms on childhood vaccine responses

Publisher: Elsevier BV

Date: 07-2008

DOI: 10.1016/J.VACCINE.2008.05.011

Abstract: Cytokine gene polymorphisms affect vaccine responses and gender-specific effects are known for many phenotypes. Therefore, this study investigated gender-specific effects of cytokine gene polymorphisms on vaccine responses. In 263 2-year-old subjects selected for parental history of atopy, boys with IL-4 C-589T and IL-4Ralpha I50V genotypes associated with atopy had increased Diptheria Toxoid (DiphTox) and Tetanus Toxoid (TetTox) responses compared with the remaining alleles (IL-4 C-589T: DipTox p=0.01, TetTox p=0.04 IL-4Ralpha.I50V: DipTox p=0.04, TetTox p=0.08). Contrastingly, girls with IL-10 -592C genotypes associated with atopy had lower levels of DiphTox (p=0.03) and TetTox (p=0.02) responses compared with the remaining allele. Additionally, interaction effects were found for IL-4 C-589T (p=0.01) and IL-4Ralpha I50V (p=0.04) polymorphisms. In conclusion, these findings support the interaction of primary genetic and modifying factors on vaccine responses and the importance of atopic genetics to these responses.

The Pacific Basin Consortium for Environment and Health

Publisher: Walter de Gruyter GmbH

Date: 2014

DOI: 10.1515/REVEH-2014-0003

Pirenzepine Blunts the Pulmonary Parenchymal Response to Inhaled Methacholine

Publisher: Elsevier BV

Date: 04-1995

DOI: 10.1006/PULP.1995.1015

Abstract: To determine the role of M1 muscarinic receptors in the response of the pulmonary parenchyma to inhaled methacholine (MCh), 20 mongrel, out-bred puppies, 8-10 weeks of age were challenged following pretreatment with either saline (control), UH-AH37 (a combined M1 & M3 receptor blocker), or pirenzepine (a relatively selective M1 receptor blocker). In addition, eight fox hound-beagle puppies, born and raised in a clean animal house, were studied. Relatively selective doses of pirenzepine produced a dose-dependent shift to the right of the parenchymal dose-response curves (P = 0.031), with no effect on the airway dose-response curve (P = 0.102). The fox hound-beagle puppies showed less parenchymal response (P <0.0005), but equivalent airway response (P = 0.468), to MCh compared with the mongrel puppies. High doses of pirenzepine (10 000 mu g/kg) and UH-AH37 (3 mg/kg) markedly inhibited both the parenchymal and airway responses to MCh. Data from the present study demonstrate that: (1) while both the airway and pulmonary parenchyma respond to inhaled MCh, the mechanisms by which they respond differ (2) stimulation of M1 subtype muscarinic receptors are responsible, at least partly, for the parenchymal response and (3) experimental conditions, such as the breed and housing conditions of animals, may have major influences on the parenchymal response to inhalational challenge tests.

Environmental threats to children's health in Southeast Asia and the Western Pacific.

Publisher: Environmental Health Perspectives

Date: 03-2003

DOI: 10.1289/EHP.6059

Abstract: The Southeast Asia and Western Pacific regions contain half of the world's children and are among the most rapidly industrializing regions of the globe. Environmental threats to children's health are widespread and are multiplying as nations in the area undergo industrial development and pass through the epidemiologic transition. These environmental hazards range from traditional threats such as bacterial contamination of drinking water and wood smoke in poorly ventilated dwellings to more recently introduced chemical threats such as asbestos construction materials arsenic in groundwater methyl isocyanate in Bhopal, India untreated manufacturing wastes released to landfills chlorinated hydrocarbon and organophosphorous pesticides and atmospheric lead emissions from the combustion of leaded gasoline. To address these problems, pediatricians, environmental health scientists, and public health workers throughout Southeast Asia and the Western Pacific have begun to build local and national research and prevention programs in children's environmental health. Successes have been achieved as a result of these efforts: A cost-effective system for producing safe drinking water at the village level has been devised in India many nations have launched aggressive antismoking c aigns and Thailand, the Philippines, India, and Pakistan have all begun to reduce their use of lead in gasoline, with resultant declines in children's blood lead levels. The International Conference on Environmental Threats to the Health of Children, held in Bangkok, Thailand, in March 2002, brought together more than 300 representatives from 35 countries and organizations to increase awareness on environmental health hazards affecting children in these regions and throughout the world. The conference, a direct result of the Environmental Threats to the Health of Children meeting held in Manila in April 2000, provided participants with the latest scientific data on children's vulnerability to environmental hazards and models for future policy and public health discussions on ways to improve children's health. The Bangkok Statement, a pledge resulting from the conference proceedings, is an important first step in creating a global alliance committed to developing active and innovative national and international networks to promote and protect children's environmental health.

Development of Interleukin-12-Producing Capacity throughout Childhood

Publisher: American Society for Microbiology

Date: 12-2002

DOI: 10.1128/IAI.70.12.6583-6588.2002

Abstract: Increasing evidence indicates that the capacity to induce protective Th1 immune responses is impaired in early childhood, an observation that can be partially attributed to deficiencies in antigen-presenting-cell function. Synthesis of interleukin 12 (IL-12), a key Th1-trophic cytokine, is markedly reduced in the neonatal period, though there is a paucity of knowledge concerning the ontogeny of IL-12-synthetic capacity throughout the childhood years. Hence, we examined the production of bioactive IL-12 p70 by circulating mononuclear cells in a population of healthy in iduals. As expected, the capacity to synthesize IL-12 p70 in response to either lipopolysaccharide or heat-killed Staphylococcus aureus was markedly impaired at birth, even after priming of cells with gamma interferon. Surprisingly however, IL-12 p70 synthesis by peripheral blood mononuclear cells from both 5- and 12-year-old children was still substantially below that seen in adults, and this did not appear to be related to excessive production of IL-10. In contrast, dendritic cells from adults and neonates, derived from monocytes with granulocyte-macrophage colony-stimulating factor and IL-4, synthesized equivalent amounts of IL-12 p70 in response to microbial stimulation. This indicates that the impaired capacity for IL-12 synthesis in childhood is not an intrinsic property of circulating mononuclear cells but rather can be readily overcome in response to appropriate maturational stimuli. Because IL-12 arose predominantly from circulating HLA-DR + cells that lacked B-cell- and monocyte-specific markers, we propose that the slow maturation of IL-12-synthetic capacity in the childhood years can be attributed to deficiencies in the number and/or function of dendritic cells.

Editorial

Publisher: Walter de Gruyter GmbH

Date: 2013

DOI: 10.1515/REVEH-2013-0999

An exposome perspective: Early-life events and immune development in a changing world

Publisher: Elsevier BV

Date: 07-2017

DOI: 10.1016/J.JACI.2017.05.015

Abstract: Advances in metagenomics, proteomics, metabolomics, and systems biology are providing a new emphasis in research interdisciplinary work suggests that personalized medicine is on the horizon. These advances are illuminating sophisticated interactions between human-associated microbes and the immune system. The result is a transformed view of future prevention and treatment of chronic noncommunicable diseases, including allergy. Paradigm-shifting gains in scientific knowledge are occurring at a time of rapid global environmental change, urbanization, and bio ersity losses. Multifactorial and multigenerational implications of total environmental exposures, the exposome, require coordinated interdisciplinary efforts. It is clear that the genome alone cannot provide answers to urgent questions. Here we review the historical origins of exposome research and define a new concept, the metaexposome, which considers the bidirectional effect of the environment on human subjects and the human influence on all living systems and their genomes. The latter is essential for human health. We place the metaexposome in the context of early-life immune functioning and describe how various aspects of a changing environment, especially through microbiota exposures, can influence health and disease over the life course.

Pre-flight testing of preterm infants with neonatal lung disease: a retrospective review

Publisher: BMJ

Date: 04-2006

DOI: 10.1136/THX.2005.048769

Respiratory impedance and bronchodilator response in healthy Italian preschool children

Publisher: Wiley

Date: 26-10-2010

DOI: 10.1002/PPUL.21292

Abstract: To define normal values for respiratory resistance (R(rs)) and reactance (X(rs)) and bronchodilator response (BDR) in a population of healthy Italian preschool children using a commercially available forced oscillation device. R(rs) and X(rs) were measured in kindergartens in Viterbo, Italy. Regression analysis was performed taking into account height, weight, age, gender, and reference equations calculated. The coefficient of repeatability (CR) between two tests performed 15 min apart was calculated in a subset of children. BDR was assessed by repeating the measurements 15 min after the administration of 200 µg of inhaled salbutamol and calculated as an absolute change in R(rs) and X(rs) at 8 Hz, as a percent change in baseline, and as a change in Z-score calculated from the reference equations. Lung function was attempted in 175 healthy children and successful in 163 (81 male, median age 4.8, range 2.9-6.1 years). R(rs) and X(rs) at 6, 8, and 10 Hz were related to height but not other variables. The CR was 1.53 hPa s L(-1) for R(rs8) and 0.91 hPa s L(-1) for X(rs8). The 5th percentile for absolute R(rs8) BDR was -3.16 hPa s L(-1), whereas the 95th percentile for absolute X(rs8) BDR was 2.25 hPa s L(-1). These cut-off values corresponded to a change in the Z-score of -1.88 and 2.48, respectively. We have established reference equations for R(rs) and X(rs) in healthy Italian preschool children using forced oscillations. We recommend a change in Z-score of -1.88 for R(rs8) and 2.48 for X(rs8) as cut-off values for a positive BDR.

Disturbance in Respiratory Mechanics with Extreme Truncal Flexion during Anaesthesia in Children

Publisher: SAGE Publications

Date: 05-1991

DOI: 10.1177/0310057X9101900212

Abstract: Respiratory mechanics were studied in five anaesthetised children, aged 3 to 33 months undergoing urological surgery, in both the supine position and with extreme truncal flexion. Extreme truncal flexion was associated with a reduced respiratory system compliance. Dynamic compliance decreased significantly, by 30% (range 12–55%) and static compliance decreased significantly, by 40% (range 18–65%). There were no changes in respiratory system resistance. Tidal volume was also significantly reduced (mean 20%) despite a significant increase (mean 22%) in peak ventilator pressure. These changes in mechanics must be recognised to avoid alveolar hypoventilation, with a consequent decrease in gas exchange during surgery.

Atopy, eczema and breast milk fatty acids in a high‐risk cohort of children followed from birth to 5 yr

Publisher: Wiley

Date: 20-12-2005

DOI: 10.1111/J.1399-3038.2005.00340.X

Abstract: The incidence of atopic diseases such as eczema is increasing in westernized societies. The suggestion that there is a "protective" association between the unique fatty acid composition of breast milk, particularly the omega-3 (n-3) and omega-6 (n-6) essential polyunsaturated fatty acid content, and the development of atopic disease in children was investigated in a cohort study of 263 infants born into families with a history of allergy (one or both parents had asthma, hayfever, eczema). The objectives of this study were to determine the lipid profile [specifically in relation to long-chain polyunsaturated fatty acid (LC-PUFA) composition] in maternal breast milk s les collected at 6 wk and at 6 months following birth, and to investigate the potential role of these fatty acids in modulating the phenotype of children at high genetic risk of developing atopic disease. Breast milk s les were available from 91 atopic mothers at their child's ages of 6 wk and 6 months. These s les were analysed for the fatty acid spectrum. Analysis of variance was used to detect differences between groups of outcomes (no atopy or eczema, non-atopic eczema, atopy, atopic eczema) at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to isolate the parameters producing the different results (F-test, LSD test). For the exposure variables, n-3 and n-6 fatty acids are expressed as weight percentage and as a ratio (at both time-points). The fatty acid profiles of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of n-6: n-3 fatty acids in both 6 wk and 6 month milk s les was associated with non-atopic eczema (p < 0.005) but not atopy alone or atopic eczema. We found milk fatty acids were a significant modulator of non-atopic eczema but not atopy or atopic eczema in infants at 6 months. In mothers with a history of asthma, hayfever or eczema, their 6-month-old infants were more likely to develop non-atopic eczema if their milk had a higher ratio of n-6: n-3 LC-PUFA.

Allergen-enhanced thrombomodulin (blood dendritic cell antigen 3, CD141) expression on dendritic cells is associated with a TH2-skewed immune response

Publisher: Elsevier BV

Date: 2009

DOI: 10.1016/J.JACI.2008.09.009

Abstract: Dendritic cells (DCs) are important in allergic diseases such as asthma, although little is known regarding the mechanisms by which DCs induce T(H)2-polarized responses in atopic in iduals. It has been suggested that intrinsic properties of allergens can directly stimulate T(H)2 polarizing functions of DCs, but little is known of the underlying mechanisms. To identify novel genes expressed by house dust mite (HDM) allergen-exposed DCs. We screened for allergen-induced gene expression by microarray, and validated differentially expressed genes at the mRNA and protein levels. Thrombomodulin (CD141, blood dendritic cell antigen 3) expression by microarray was higher on HDM-stimulated DCs from atopic (relative to nonatopic) in iduals. These findings were confirmed at both the mRNA and protein levels in an independent group. Purified thrombomodulin(+) DCs induced a strongly T(H)2-polarized cytokine response by allergen-specific T cells compared with DCs lacking thrombomodulin. In vivo, thrombomodulin(+) circulating DCs were significantly more frequent in subjects with HDM allergy and asthma, compared with control subjects. Furthermore, thrombomodulin expression in blood leukocytes was higher in children with acute asthma than at convalescence 6 weeks later. Thrombomodulin expression on DCs may be involved in the pathogenesis of atopy and asthma.

Partitioning of alterations in pulmonary mechanics due to vascular engorgement in piglets

Publisher: Wiley

Date: 1998

DOI: 10.1002/(SICI)1099-0496(199801)25:1<45::AID-PPUL5>3.0.CO;2-N

Abstract: The aim of our study was to determine the effects of pulmonary vascular engorgement on airways and pulmonary tissues in juvenile animals before and after methacholine (Mch)-induced changes in lung function. Five anesthetized, paralyzed, and thoracotomized piglets were studied before and during pulmonary vascular engorgement, induced by inflating a left atrial balloon catheter and by calculating respiratory mechanics from measurements of airway opening (Pao) and alveolar pressures (PA), respiratory flow (V'), and volume (V) recorded during mechanical ventilation, using the multilinear regression technique. A maximal increase of 15 mmHg in pulmonary artery pressure (Ppa) resulted in a mean increase in total lung elastance (EL) of 28.6% and in total lung resistance (RL) of 14.9%. Mch increased EL by 21.7% and RL by 29.0%. Inflation of the left atrial balloon with an associated increase in Ppa by 15 mmHg in the presence of Mch resulted in an increase in EL by a further 12.4% (to 135.4% of baseline) and in RL by a further 9.0% (to 139.5% of baseline). The change in RL was associated with a qualitatively similar change in both tissue resistance (Vti) and airway resistance (Raw) before and after Mch-induced changes in lung function. We conclude that increasing pulmonary vascular pressures, by increasing left partial pressure, alters lung function in juvenile animals by altering the mechanical properties of both airways and lung tissues. The methods used in the present study allow a direct assessment of the site of action of vascular engorgement in the lungs and provide a useful model for studying this phenomenon further.

Improved safety with equivalent asthma control in adults with chronic severe asthma on high-dose fluticasone propionate

Publisher: Wiley

Date: 08-09-2001

DOI: 10.1046/J.1440-1843.2001.00329.X

Abstract: High-dose inhaled corticosteroids (ICS) have been associated with the same side-effects as oral corticosteroids. Beclomethasone dipropionate (BDP) and budesonide (BUD) in doses greater than 2000 microg/day are used regularly in severe asthma, despite the fact that safety and efficacy data at such high doses are limited. Fluticasone propionate (FP) has been promoted as being twice as potent clinically as BDP or BUD at doses of 2000 microg/day or less with a similar safety profile. The aim of this study was to compare the efficacy and safety of FP with BDP and BUD in 133 symptomatic adult asthmatics requiring at least 1750 microg/day of BDP or BUD. Patients fulfilling the entry criteria were randomized to receive either their regular ICS medication or FP at approximately half the microgram dose for 6 months in an open, parallel group study. The primary efficacy measure was based on morning peak expiratory flow measurements recorded by patients on daily record cards, while determination of safety was based on a number of endpoints including changes in bone turnover indices, the incidence of topical side-effects and assessments of quality of life. It was shown that patients who were switched to FP, but not those continuing with BDP or BUD, had significant increases in levels of morning serum cortisol and the urine cortisol:creatinine ratio while maintaining asthma control. Serum osteocalcin and the pyridinoline:creatinine ratio, as well as the deoxypyridinoline:creatinine ratio, were also shown to increase only in the FP group. Subjective assessments such as quality of life score, the incidence and ease of bruising, and reports of hoarseness also favoured the FP group. It is concluded that, at the doses studied and with the delivery devices used clinically, FP is at least as effective as BDP/BUD in the management of severe asthma and may offer clinical advantages with respect to steroid-related adverse effects.

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice

Publisher: Environmental Health Perspectives

Date: 10-2013

DOI: 10.1289/EHP.1306748

In vitro evaluation of an asthma dosing device: The smart-inhaler

Publisher: Elsevier BV

Date: 05-2006

DOI: 10.1016/J.RMED.2005.09.004

Abstract: Monitoring devices attached to pressurised metered dose inhalers provide an important objective measurement of patient adherence with asthma medications in clinical and research settings. The Smart-inhaler is a relatively new device that has not been previously validated. This study examines the accuracy of the Smart-inhaler in a bench-top experiment and compares it with a previously validated device, the Doser. Ten Smart-inhalers and five Dosers were actuated twice on two occasions per day for 30 days (120 doses). Six Smart-inhalers were also actuated 30 times in rapid succession to examine the ability of the Smart-inhaler to detect "dumping". Five Smart-inhalers failed to detect the first one or two doses. However, when the aerosol canister was placed more firmly in the device, actuating the device in the process, the following two doses were recorded accurately in all ten devices. Otherwise all ten Smart-inhalers and five Dosers recorded all actuations faithfully and there were no spurious recordings. The six Smart-inhalers recorded all 30 doses delivered in rapid succession. The Smart-inhaler and Doser are both highly accurate at measuring actuated doses and no spurious doses were recorded in an in vitro setting.

Lack of vagal influence on pulmonary visco-elasticity in puppies

Publisher: Elsevier BV

Date: 05-1991

DOI: 10.1016/0034-5687(91)90112-V

Abstract: We recently demonstrated that most of the change in lung function following inhaled histamine in 8-10 week old puppies was due to changes in the tissue visco-elastic properties and argued that vagally-mediated reflexes may be responsible for this phenomenon (Sly and Lanteri, J. Appl. Physiol. 1990 68: 1562-1567). To test this hypothesis we compared 5 puppies treated with inhaled lignocaine or bilateral cervical vagotomy did not alter baseline pulmonary mechanics and there were no differences in the response to histamine challenge between the three groups. These results show that vagal reflexes, mediated via the central nervous system, are not involved in the response of the pulmonary tissues to inhaled histamine, but do not exclude the possible involvement of local axonal reflexes.

Comparison of Centers for Disease Control and Prevention and World Health Organization references/standards for height in contemporary Australian children: Analyses of the Raine Study and Australian National Children's Nutrition and Physical Activity cohorts

Publisher: Wiley

Date: 22-06-2014

DOI: 10.1111/JPC.12672

Abstract: (i) To compare the Centers for Disease Control and Prevention (CDC) reference and World Health Organization (WHO) standard/reference for height, particularly with respect to short stature and eligibility for growth hormone (GH) treatment by applying them to contemporary Australian children (ii) To examine the implications for identifying short stature and eligibility for GH treatment. Children from the longitudinal Raine Study were serially measured for height from 1991 to 2005 (2-15-year-old girls (660) and boys (702) from Western Australia). In the cross-sectional Australian National Children's Nutrition and Physical Activity survey (2-16-year-old boys (2415) and girls (2379) from all states), height was measured in 2007. Heights were converted to standard deviation scores (SDSs) based on CDC and WHO. Means and standard deviations of height-SDS varied between CDC and WHO definitions and with age and gender within each definition. However, both identified similar frequencies of short stature (<1st centile for GH eligibility), although these were very significantly less than the anticipated 1% (0.1-0.7%) of the Australian cohorts. Mean heights in the Australian cohorts were greater than both the WHO and CDC means. Neither CDC nor WHO height standardisations accurately reflect the contemporary Australian child population. Australian children are taller than the CDC or WHO height means, and significantly less than 1% of Australian children are defined as being short using either CDC or WHO. This study suggests there may be a case for an Australian-specific standard/reference for height.

Distribution of Early Structural Lung Changes due to Cystic Fibrosis Detected with Chest Computed Tomography

Publisher: Elsevier BV

Date: 07-2013

DOI: 10.1016/J.JPEDS.2012.12.042

Abstract: To examine the distribution of early structural lung changes in clinically stable infants and young children with cystic fibrosis using chest computed tomography (CT). This cross-sectional study included 62 children aged 1-6 years with volume-controlled volumetric chest CT scans performed under general anesthesia as part of an early surveillance program. Each lobe was scored for presence and extent of bronchiectasis, mucus plugging, and air trapping using a semiquantitative score. The topographic distribution of structural abnormalities was evaluated by comparing the presence and extent of abnormalities in different lung regions and examining relationships between components. Although bronchiectasis was most common in the right upper lobe, overall changes in lung structure were not more common or more extensive in the upper lobes. Rather, bronchiectasis was more common in the right lung (right lung 0.95, left lung 0.68, P = .003), and mucus plugging (upper 0.41, middle 0.41, lower 0.72, P = .028) and air trapping (upper 0.79, middle 0.48, lower 0.96, P < .001) were more common in the lower lobes. The extents of bronchiectasis (P < .001) and air trapping (P = .011) were greater in the right lung. Scans with bronchiectasis were also more likely to have coexisting mucus plugging (P = .008) and air trapping (P < .001). Early structural lung disease is heterogeneously distributed in the lung. Quantitative scoring tools for studies using chest CT as an end point, and mechanistic studies that seek to better understand the pathogenesis of early cystic fibrosis lung disease, should take account of this differential topographic expression of disease early in life.

Using the health beliefs model to explore children's attitudes and beliefs on air pollution

Publisher: Elsevier BV

Date: 07-2021

DOI: 10.1016/J.PUHE.2021.04.026

A Brief Targeted Review of Susceptibility Factors, Environmental Exposures, Asthma Incidence, and Recommendations for Future Asthma Incidence Research

Publisher: Environmental Health Perspectives

Date: 04-2006

DOI: 10.1289/EHP.8381

Abstract: Relative to research on effects of environmental exposures on exacerbation of existing asthma, little research on incident asthma and environmental exposures has been conducted. However, this research is needed to better devise strategies for the prevention of asthma. The U.S. Environmental Protection Agency (EPA) and National Institute of Environmental Health Sciences held a conference in October 2004 to collaboratively discuss a future research agenda in this area. The first three articles in this mini-monograph summarize the discussion on potential putative environmental exposure they include an overview of asthma and conclusions of the workshop participants with respect to public health actions that could currently be applied to the problem and research needs to better understand and control the induction and incidence of asthma, the potential role of indoor/outdoor air pollutants in the induction of asthma), and biologics in the induction of asthma. Susceptibility is a key concept in the U.S. EPA "Asthma Research Strategy" document and is associated with the U.S. EPA framework of protecting vulnerable populations from potentially harmful environmental exposures. Genetics, age, and lifestyle (obesity, diet) are major susceptibility factors in the induction of asthma and can interact with environmental exposures either synergistically or antagonistically. Therefore, in this fourth and last article we consider a number of "susceptibility factors" that potentially influence the asthmatic response to environmental exposures and propose a framework for developing research hypotheses regarding the effects of environmental exposures on asthma incidence and induction.

Inhalation of hypertonic saline as a bronchial challenge in children with mild asthma and normal children

Publisher: Elsevier BV

Date: 07-1989

DOI: 10.1016/0091-6749(89)90183-8

Abstract: The response to bronchial challenge with ultrasonically nebulized 4.5% saline was compared to the response to histamine and isocapneic hyperventilation in a group of children with mild asthma and control subjects. Challenge with 4.5% saline was found to have an accuracy of approximately 80%, compared to 90% for histamine and 80% for hyperventilation. The challenge test was well tolerated by all children. Increasing the dose of 4.5% saline delivered to the children by use of a nebulizer with a higher output improved the accuracy of challenge with 4.5% saline to approximately 90%. This finding suggests that the nebulizer output is an important determinant of the accuracy of bronchial challenge with 4.5% saline. Bronchial challenge with 4.5% saline appears to be a promising addition to the tests of bronchial responsiveness in children, but further studies, particularly documenting the reproducibility and the relationship to clinical asthma, are needed before it can replace the current standard tests.

Repeat measurement of respiratory mechanics using the forced oscillation technique in non-paralysed rats

Publisher: Elsevier BV

Date: 06-1999

DOI: 10.1006/PUPT.1999.0198

Developmental Origins of Health and Disease: Integrating Environmental Influences

Publisher: The Endocrine Society

Date: 21-07-2015

DOI: 10.1210/EN.2015-1394

Abstract: There are now robust data supporting the Developmental Origins of Health and Disease (DOHaD) paradigm. This includes human and animal data focusing on nutrition or environmental chemicals during development. However, the term DOHaD has not been generally accepted as the official term to be used when one is concerned with understanding the pathophysiological basis for how environmental influences acting during early development influence the risk of later noncommunicable diseases. Similarly, there is no global research or public health program built around the DOHaD paradigm that encompasses all aspects of environment. To better inform the global health efforts aimed at addressing the growing epidemic of chronic noncommunicable diseases of environmental origin, we propose a two-pronged approach: first, to make it clear that the current concept of DOHaD comprehensively includes a range of environmental factors and their relevance to disease occurrence not just throughout the life span but potentially across several generations and second, to initiate the discussion of how adoption of DOHaD can promote a more realistic, accurate, and integrative approach to understanding environmental disruption of developmental programming and better inform clinical and policy interventions. (Endocrinology 156: 3416–3421, 2015)

Acute Influenza A infection induces bronchial hyper-responsiveness in mice

Publisher: Elsevier BV

Date: 08-2008

DOI: 10.1016/J.RESP.2008.06.011

Abstract: This study aimed to determine whether the route of administration of methacholine (MCh) influenced the pattern of airway hyper-responsiveness (AHR) in mice. BALB/c mice were inoculated with a 50-microL volume containing 10(4.5)-pfu Influenza virus A/Mem/1/71(H3N1) or media. MCh responsiveness in vivo [inhaled (0.01-30 mg/mL), i.v. MCh (6-48 microg/min/kg)] and in vitro were measured at day 4 post-infection (D4) during acute lower respiratory infection (LRI) and following resolution of infection at day 20 (D20) using a low-frequency, forced oscillation technique. Inflammation was assessed in bronchoalveolar lavage fluid. Infected mice had pulmonary inflammation and heightened responsiveness to both inhaled (p<0.03) and intravenous (p<0.02) MCh on D4, but not on D20. In vitro responsiveness was not altered at either time point. Influenza A LRI results in AHR during acute infection associated with a marked inflammatory response and increased permeability of the alveolar-capillary barrier. These data suggest that intrinsic muscle properties are not altered but MCh has greater access to airway smooth muscle during acute infection.

Randomised controlled trials in cystic fibrosis: What, when and how?

Publisher: European Respiratory Society (ERS)

Date: 30-04-2011

DOI: 10.1183/09031936.00166810

Early life origins of allergy and asthma

Publisher: Elsevier

Date: 2006

DOI: 10.1016/B978-0-323-03227-8.50018-4

Respiratory syncytial virus seasonality in tropical Australia

Publisher: Elsevier BV

Date: 02-2015

DOI: 10.1111/1753-6405.12347

Abstract: Respiratory syncytial virus (RSV) is most common during the rainy season in a number of low- to middle-income tropical settings, a pattern driven by seasonal changes in climate and nutrition. We investigated the seasonality of RSV in the high-income tropical setting of North Queensland, Australia. We used RSV hospital admissions data from Cairns and Townsville to assess the seasonality of RSV. We examined the seasonal scale associations between selected meteorological exposures and RSV admissions using cross-correlation of weekly data. In both Cairns and Townsville, RSV admissions were highest in the latter half of the rainy season. In Cairns, RSV admissions were most strongly correlated with rainfall four weeks previously. In Townsville, RSV admissions were most strongly correlated with rainfall six weeks previously. The seasonality of RSV in the tropical setting of North Queensland appears to be driven by seasonal variations in rainfall. Further research is needed to assess the impact of climate on RSV incidence in the tropics.

Bisphenol A exposure is not associated with area-level socioeconomic index in Australian children using pooled urine samples

Publisher: Springer Science and Business Media LLC

Date: 16-04-2014

DOI: 10.1007/S11356-014-2882-Z

Abstract: Bisphenol A (BPA) is used extensively in food-contact materials and has been detected routinely in populations worldwide this exposure has been linked to a range of negative health outcomes in humans. There is some evidence of an association between BPA and different socioeconomic variables which may be the result of different dietary patterns. The aim of this study was to conduct a preliminary investigation of the association between BPA and socioeconomic status in Australian children using pooled urine specimens and an area-level socioeconomic index. Surplus pathology urine specimens collected from children aged 0-15 years in Queensland, Australia, as s les of convenience (n=469), were pooled by age, sex and area-level socioeconomic index (n=67 pools) and analysed for total BPA using online solid-phase extraction LC-MS/MS. Concentration ranged from 1.08 to 27.4 ng/ml with geometric mean 2.57 ng/ml, and geometric mean exposure was estimated as 70.3 ng/kg d(-1). Neither BPA concentration nor excretion was associated with age or sex, and the authors found no evidence of an association with socioeconomic status. These results suggest that BPA exposure is not associated with socioeconomic status in the Australian population due to relatively homogenous exposures in Australia, or that the socioeconomic gradient is relatively slight in Australia compared with other OECD countries.

Induction of Asthma and the Environment: What We Know and Need to Know

Publisher: Environmental Health Perspectives

Date: 04-2006

DOI: 10.1289/EHP.8376

Abstract: The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop "Environmental Influences on the Induction and Incidence of Asthma" to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment.

Environmental Microbial Exposure and Protection against Asthma

Publisher: Massachusetts Medical Society

Date: 24-12-2015

DOI: 10.1056/NEJMCIBR1511291

Pooled biological specimens for human biomonitoring of environmental chemicals: Opportunities and limitations

Publisher: Springer Science and Business Media LLC

Date: 06-11-2014

DOI: 10.1038/JES.2013.76

Abstract: Biomonitoring has become the "gold standard" in assessing chemical exposures, and has an important role in risk assessment. The pooling of biological specimens-combining multiple in idual specimens into a single s le-can be used in biomonitoring studies to monitor levels of exposure and identify exposure trends or to identify susceptible populations in a cost-effective manner. Pooled s les provide an estimate of central tendency and may also reveal information about variation within the population. The development of a pooling strategy requires careful consideration of the type and number of s les collected, the number of pools required and the number of specimens to combine per pool in order to maximise the type and robustness of the data. Creative pooling strategies can be used to explore exposure-outcome associations, and extrapolation from other larger studies can be useful in identifying elevated exposures in specific in iduals. The use of pooled specimens is advantageous as it saves significantly on analytical costs, may reduce the time and resources required for recruitment and, in certain circumstances, allows quantification of s les approaching the limit of detection. In addition, the use of pooled s les can provide population estimates while avoiding ethical difficulties that may be associated with reporting in idual results.

Paediatric origins of adult lung diseases bullet 2: Prevention of adult asthma by early intervention during childhood: potential value of new generation immunomodulatory drugs

Publisher: BMJ

Date: 08-2000

DOI: 10.1136/THORAX.55.8.700

Beoordeling en behandeling van astma bij kinderen

Publisher: Springer Science and Business Media LLC

Date: 03-1994

DOI: 10.1007/BF03075847

The route of antigen delivery determines the airway and lung tissue mechanical responses in allergic rats

Publisher: Wiley

Date: 1999

DOI: 10.1046/J.1365-2222.1999.00471.X

Abstract: Previous results have shown tissue constriction in allergic animals following inhalation of an antigen. Further studies have demonstrated a differing response pattern in airway and parenchymal mechanics following inhaled (i.h.) or intravenous (i.v.) delivery of methacholine (MCh). The purpose of this study was to compare the acute allergic response in airway and parenchymal mechanics following i.h. and i.v. antigen challenge. Brown Norway rats were sensitized to ovalbumin (OVA). Rats were anaesthetized, paralysed, and thoracotomized, and lung input impedance (ZL) between 0.5 and 21 Hz was measured using small- litude pseudo-random oscillations at control, after saline, and for up to 1 h after either i.h. (n = 7) or i.v. (n = 5) administration of OVA. ZL was evaluated in terms of airway resistance (Raw) and inertance (Iaw), and a constant phase tissue parenchymal d ing (G) and elastance (H). Following i.h. OVA challenge elevations were found in Raw [192 +/- 32 (SE) %], G (223 +/- 21%), and H (141 +/- 5%). Raw showed higher elevation after i.v. challenge (418 +/- 57%), whereas the elevation in G (278 +/- 30%) and H (130 +/- 4%) was approximately equal to those seen following inhalation of an antigen. Delivery (i.v.) of an antigen produces a significantly higher response in airway resistance, whereas inhaled antigen results in a mixed airway and parenchymal response.

Physiological basis of respiratory signs and symptoms

Publisher: Elsevier BV

Date: 06-2006