ORCID Profile
0000-0002-4288-5973
Current Organisations
University of Toronto
,
University of Oxford
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Publisher: Elsevier BV
Date: 09-2010
Abstract: The upregulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be monitored easily in exhaled air. It is now possible to estimate the predominant site of increased fraction of exhaled NO (FeNO) and its potential pathologic and physiologic role in various pulmonary diseases. In asthma, increased FeNO reflects eosinophilic-mediated inflammatory pathways moderately well in central and/or peripheral airway sites and implies increased inhaled and systemic corticosteroid responsiveness. Recently, five randomized controlled algorithm asthma trials reported only equivocal benefits of adding measurements of FeNO to usual clinical guideline management including spirometry however, significant design issues may exist. Overall, FeNO measurement at a single expiratory flow rate of 50 mL/s may be an important adjunct for diagnosis and management in selected cases of asthma. This may supplement standard clinical asthma care guidelines, including spirometry, providing a noninvasive window into predominantly large-airway-presumed eosinophilic inflammation. In COPD, large/central airway maximal NO flux and peripheral/small airway/alveolar NO concentration may be normal and the role of FeNO monitoring is less clear and therefore less established than in asthma. Furthermore, concurrent smoking reduces FeNO. Monitoring FeNO in pulmonary hypertension and cystic fibrosis has opened up a window to the role NO may play in their pathogenesis and possible clinical benefits in the management of these diseases.
Publisher: Wiley
Date: 21-07-2022
DOI: 10.1111/RESP.14325
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent and complex diseases that require personalized management. Although a strategy based on treatable traits (TTs) has been proposed, the prevalence and relationship of TTs to the diagnostic label and disease severity established by the attending physician in a real‐world setting are unknown. We assessed how the presence/absence of specific TTs relate to the diagnosis and severity of ‘asthma’, ‘COPD’ or ‘asthma + COPD’. The authors selected 30 frequently occurring TTs from the NOVELTY study cohort (NOVEL observational longiTudinal studY NCT02760329), a large ( n = 11,226), global study that systematically collects data in a real‐world setting, both in primary care clinics and specialized centres, for patients with ‘asthma’ ( n = 5932, 52.8%), ‘COPD’ ( n = 3898, 34.7%) or both (‘asthma + COPD’ n = 1396, 12.4%). The results indicate that (1) the prevalence of the 30 TTs evaluated varied widely, with a mean ± SD of 4.6 ± 2.6, 5.4 ± 2.6 and 6.4 ± 2.8 TTs atient in those with ‘asthma’, ‘COPD’ and ‘asthma + COPD’, respectively ( p 0.0001) (2) there were no large global geographical variations, but the prevalence of TTs was different in primary versus specialized clinics (3) several TTs were specific to the diagnosis and severity of disease, but many were not and (4) both the presence and absence of TTs formed a pattern that is recognized by clinicians to establish a diagnosis and grade its severity. These results provide the largest and most granular characterization of TTs in patients with airway diseases in a real‐world setting to date.
Publisher: European Respiratory Society (ERS)
Date: 04-02-2016
DOI: 10.1183/13993003.01882-2015
Abstract: The aim of this review was to evaluate the clinical effectiveness of fractional exhaled nitric oxide ( F eNO ) measured in a clinical setting for the management of asthma in adults. 13 electronic databases were searched and studies were selected against predefined inclusion criteria. Quality assessment was conducted using QUADAS-2. Class effect meta-analyses were performed. Six studies were included. Despite high levels of heterogeneity in multiple study characteristics, exploratory class effect meta-analyses were conducted. Four studies reported a wider definition of exacerbation rates (major or severe exacerbation) with a pooled rate ratio of 0.80 (95% CI 0.63–1.02). Two studies reported rates of severe exacerbations (requiring oral corticosteroid use) with a pooled rate ratio of 0.89 (95% CI 0.43–1.72). Inhaled corticosteroid use was reported by four studies, with a pooled standardised mean difference of −0.24 (95% CI −0.56–0.07). No statistically significant differences for health-related quality of life or asthma control were found. F eNO guided management showed no statistically significant benefit in terms of severe exacerbations or inhaled corticosteroid use, but showed a statistically significant reduction in exacerbations of any severity. However, further research is warranted to clearly define which management protocols (including cut-off points) offer best efficacy and which patient groups would benefit the most.
Publisher: Springer Science and Business Media LLC
Date: 2007
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.
Publisher: Elsevier BV
Date: 09-2008
Publisher: BMJ
Date: 05-2008
Publisher: Wiley
Date: 13-09-2015
DOI: 10.1111/ALL.12686
Abstract: Several unmet needs have been identified in allergic rhinitis: identification of the time of onset of the pollen season, optimal control of rhinitis and comorbidities, patient stratification, multidisciplinary team for integrated care pathways, innovation in clinical trials and, above all, patient empowerment. MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) is a simple system centred around the patient which was devised to fill many of these gaps using Information and Communications Technology (ICT) tools and a clinical decision support system (CDSS) based on the most widely used guideline in allergic rhinitis and its asthma comorbidity (ARIA 2015 revision). It is one of the implementation systems of Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA). Three tools are used for the electronic monitoring of allergic diseases: a cell phone-based daily visual analogue scale (VAS) assessment of disease control, CARAT (Control of Allergic Rhinitis and Asthma Test) and e-Allergy screening (premedical system of early diagnosis of allergy and asthma based on online tools). These tools are combined with a clinical decision support system (CDSS) and are available in many languages. An e-CRF and an e-learning tool complete MASK. MASK is flexible and other tools can be added. It appears to be an advanced, global and integrated ICT answer for many unmet needs in allergic diseases which will improve policies and standards.
Publisher: International Union Against Tuberculosis and Lung Disease
Date: 11-2014
Abstract: Chronic inflammatory airway diseases, including asthma and chronic obstructive pulmonary disease, are responsible for a large global disease burden. The recognition of airway disease phenotypes is important for the application of new therapies targeted at specific underlying biological mechanisms. Biomarkers are indicators of biological or pathogenic processes that are objectively measured. In airway disease, biomarkers will ideally provide predictive information regarding diagnosis, disease mechanisms, phenotypes, treatment responses and prognosis or future risk. Non-invasive biomarkers that aid phenotyping are crucial to the development of targeted and more efficacious treatment, leading to personalised approaches to airway disease management. Sputum and peripheral blood eosinophils and fractional exhaled nitric oxide (FeNO) are current ex les of potential biomarkers. However, recent advances in technology have demonstrated the role for airway transcriptomics in biomarker discovery. This perspective piece discusses the need for biomarkers in airway disease, the use of eosinophil counts and FeNO as biomarkers, the use of transcriptomics for biomarker discovery, and the application of biomarkers in clinical and research settings. A combined approach incorporating clinical information with biological markers such as eosinophils, FeNO and inflammatory gene markers is likely to have the most success in predicting patient outcomes.
Publisher: European Respiratory Society (ERS)
Date: 31-01-2016
DOI: 10.1183/13993003.01359-2015
Abstract: Asthma and chronic obstructive pulmonary disease (COPD) are two prevalent chronic airway diseases that have a high personal and social impact. They likely represent a continuum of different diseases that may share biological mechanisms ( i.e. endotypes), and present similar clinical, functional, imaging and/or biological features that can be observed ( i.e. phenotypes) which require in idualised treatment. Precision medicine is defined as “treatments targeted to the needs of in idual patients on the basis of genetic, biomarker, phenotypic, or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations”. In this Perspective, we propose a precision medicine strategy for chronic airway diseases in general, and asthma and COPD in particular.
Publisher: European Respiratory Society (ERS)
Date: 07-2020
DOI: 10.1183/23120541.00359-2019
Abstract: Although most patients with asthma have mild disease, data on how mild asthma is defined, and how frequently exacerbations occur in this patient population are scarce, so we aimed to redress this. We searched Medline and Medline In-Process (PubMed), and Embase in OVID for English-language publications containing “mild asthma” plus at least one relevant therapy and outcome/keyword, limited to randomised controlled trials (RCTs) and observational studies published between January 1990 and February 2019. Publications were filtered to ensure appropriate data extraction. The main outcomes were the definitions of mild asthma and exacerbations, baseline exacerbation rates and exacerbation data for placebo recipients in prospective studies. Meta-analysis of exacerbation rates was planned. Of 4064 articles identified, 64 were included in our review (49 743 subjects) 54 RCTs and 10 observational/other studies. Six main types of definitions of mild asthma were identified. While care was taken to ensure inclusion only of patients with mild asthma, marked heterogeneity was revealed in the definitions of mild asthma and hence the study populations. Reporting of exacerbations also varied widely between studies, precluding meta-analysis. Between 0–22% of patients were hospitalised for asthma or had a severe exacerbation in the previous year, according to baseline data from prospective studies. In RCTs, severe exacerbation rates in placebo recipients taking only short-acting β 2 -agonist therapy ranged from 0.20–2.88 per year. These data provide new evidence of the burden of exacerbations in mild asthma and highlight the need for standardised definitions of mild asthma and of exacerbations to progress further research.
Publisher: European Respiratory Society (ERS)
Date: 04-2016
Publisher: BMJ
Date: 06-08-2021
DOI: 10.1136/THORAXJNL-2021-217325
Abstract: Reduction of the risk of asthma attacks is a major goal of current asthma management. We propose to derive a risk scale predicting asthma attacks based on the blood eosinophil count and exhaled nitric oxide (FeNO). Biomarker-stratified trial-level attack rates were extracted and pooled from the control arms of the Novel START, CAPTAIN, QUEST, Benralizumab Phase 2b, PATHWAY, STRATOS 1–2 and DREAM trials (n=3051). These were used to derive rate ratios and the predicted asthma attack rate for different patient groups. The resultant prototype risk scale shows potential to predict asthma attacks, which may be prevented by anti-inflammatory treatment.
Publisher: National Institute for Health and Care Research
Date: 10-2015
DOI: 10.3310/HTA19820
Abstract: High fractions of exhaled nitric oxide (FeNO) in the breath of patients with symptoms of asthma are correlated with high levels of eosinophils and indicate that a patient is likely to respond to inhaled corticosteroids. This may have a role in the diagnosis and management of asthma. To assess the diagnostic accuracy, clinical effectiveness and cost-effectiveness of the hand-held electrochemical devices NIOX MINO ® (Aerocrine, Solna, Sweden), NIOX VERO ® (Aerocrine) and NObreath ® (Bedfont Scientific, Maidstone, UK) for the diagnosis and management of asthma. Systematic searches were carried out between March 2013 and April 2013 from database inception. Databases searched included MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, Science Citation Index Expanded and Conference Proceedings Citation Index – Science. Trial registers such as ClinicalTrials.gov and the meta Register of Controlled Trials were also searched in March 2013. All searches were updated in September 2013. A rapid review was conducted to assess the equivalence of hand-held and chemiluminescent FeNO monitors. Systematic reviews of diagnostic accuracy and management efficacy were conducted. A systematic review of economic analyses was also conducted and two de novo health economic models were developed. All three reviews were undertaken according to robust high-quality methodology. The rapid review (27 studies) found varying levels of agreement between monitors (Bland–Altman 95% limits of agreement up to ±10 parts per billion), with better agreement at lower FeNO values. Correlation was good (generally r 0.9). The diagnostic accuracy review identified 22 studies in adults (all ages) and four in children. No studies used NObreath or NIOX VERO and seven used NIOX MINO. Estimates of diagnostic accuracy varied widely. FeNO used in combination with another test altered diagnostic accuracy only slightly. High levels of heterogeneity precluded meta-analysis. Limited observations included that FeNO may be more reliable and useful as a rule-in than as a rule-out test lower cut-off values in children and in smokers may be appropriate and FeNO may be less reliable in the elderly. The management review identified five randomised controlled trials in adults, one in pregnant asthmatics and seven in children. Despite clinical heterogeneity, exacerbation rates were lower in all studies but not generally statistically significantly so. Effects on inhaled corticosteroid (ICS) use were inconsistent, possibly because of differences in management protocols, differential effectiveness in adults and children and differences in population severity. One UK diagnostic model and one management model were identified. Aerocrine also submitted diagnostic and management models. All had significant limitations including short time horizons and the selective use of efficacy evidence. The de novo diagnostic model suggested that the expected difference in quality-adjusted life-year (QALY) gains between diagnostic options is likely to be very small. Airway hyper-responsiveness by methacholine challenge test is expected to produce the greatest QALY gain but with an expected incremental cost-effectiveness ratio (ICER) compared with FeNO (NObreath) in combination with bronchodilator reversibility of £1.125M per QALY gained. All remaining options are expected to be dominated. The de novo management model indicates that the ICER of guidelines plus FeNO monitoring using NObreath compared with guidelines alone in children is expected to be approximately £45,200 per QALY gained. Within the adult subgroup, FeNO monitoring using NObreath compared with guidelines alone is expected to have an ICER of approximately £2100 per QALY gained. The results are particularly sensitive to assumptions regarding changes in ICS use over time, the number of nurse visits for FeNO monitoring and duration of effect. Limitations of the evidence base impose considerable uncertainty on all analyses. Equivalence of devices was assumed but not assured. Evidence for diagnosis is difficult to interpret in the context of inserting FeNO monitoring into a diagnostic pathway. Evidence for management is also inconclusive, but largely consistent with FeNO monitoring resulting in fewer exacerbations, with a small or zero reduction in ICS use in adults and a possible increased ICS use in children or patients with more severe asthma. It is unclear which specific management protocol is likely to be most effective. The economic analysis indicates that FeNO monitoring could have value in diagnostic and management settings. The diagnostic model indicates that FeNO monitoring plus bronchodilator reversibility dominates many other diagnostic tests. FeNO-guided management has the potential to be cost-effective, although this is largely dependent on the duration of effect. The conclusions drawn from both models require strong technical value judgements with respect to several aspects of the decision problem in which little or no empirical evidence exists. There are many potential directions for further work, including investigations into which management protocol is best and long-term follow-up in both diagnosis and management studies. This study is registered as PROSPERO CRD42013004149. The National Institute for Health Research Health Technology Assessment programme.
Publisher: European Respiratory Society (ERS)
Date: 09-2008
DOI: 10.1183/09031936.00155307
Abstract: Concepts of asthma severity and control are important in the evaluation of patients and their response to treatment but the terminology is not standardised and the terms are often used interchangeably. This review, arising from the work of an American Thoracic Society/European Respiratory Society Task Force, identifies the need for separate concepts of control and severity, describes their evolution in asthma guidelines and provides a framework for understanding the relationship between current concepts of asthma phenotype, severity and control. "Asthma control" refers to the extent to which the manifestations of asthma have been reduced or removed by treatment. Its assessment should incorporate the dual components of current clinical control (e.g. symptoms, reliever use and lung function) and future risk (e.g. exacerbations and lung function decline). The most clinically useful concept of asthma severity is based on the intensity of treatment required to achieve good asthma control, i.e. severity is assessed during treatment. Severe asthma is defined as the requirement for (not necessarily just prescription or use of) high-intensity treatment. Asthma severity may be influenced by the underlying disease activity and by the patient's phenotype, both of which may be further described using pathological and physiological markers. These markers can also act as surrogate measures for future risk.
Publisher: JMIR Publications Inc.
Date: 23-06-2023
DOI: 10.2196/46741
Abstract: Asthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. The primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. BOOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. The last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. We will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. DERR1-10.2196/46741
Publisher: Wiley
Date: 13-02-2017
DOI: 10.1111/CEA.12867
Abstract: To identify and synthesize evidence on the diagnostic accuracy of Systematic searches (nine key biomedical databases and trial registers) were carried out on November 2014. Records were included if they recruited patients with the symptoms of asthma used a single set of inclusion criteria measured A total of 4861 records were identified originally and 1312 in an update. Twenty-seven studies were included. Heterogeneity precluded meta-analysis. Results varied even within subgroups of studies. Cut-off values for the best sum of sensitivity and specificity varied from 12 to 55 p.p.b., but did not produce high accuracy. 100% sensitivity or 100% specificity was reported by some studies indicating potential use as a rule-in or rule-out strategy.
Publisher: BMJ
Date: 17-02-2012
Publisher: BMJ
Date: 23-07-2015
Publisher: Wiley
Date: 02-2016
DOI: 10.1002/PPUL.23371
Abstract: Fractional exhaled nitric oxide (FeNO) is a non-invasive biomarker of eosinophilic inflammation which may be used to guide the management of asthma in childhood. To synthesise the available evidence on the efficacy of FeNO-guided management of childhood asthma. Databases including MEDLINE and the Cochrane Library were searched, and randomised controlled trials (RCTs) comparing FeNO-guided management with any other monitoring strategy were included. Study quality was assessed using the Cochrane risk of bias tool for RCTs, and a number of outcomes were examined, including: exacerbations, medication use, quality of life, adverse events, and other markers of asthma control. Meta-analyses were planned if multiple studies with suitable heterogeneity were available. However, due to wide variations in study characteristics, meta-analysis was not possible. Seven RCTs were identified. There was some evidence that FeNO-guided monitoring results in improved asthma control during the first year of management, although few results attained statistical significance. The impact on severe exacerbations was unclear. Similarly, the impact on use of anti-asthmatic drugs was unclear, and appears to depend on the step up/down protocols, and the clinical characteristics of patients. The potential benefit of FeNO monitoring is equivocal. Trends toward reduced exacerbation and increased medication use were seen, but typically failed to reach statistical significance. There are a number of issues that complicate data interpretation, including differences in the likely severity of included cohorts and variations in treatment algorithms. Further work is needed to systematically explore the impact of these parameters.
Publisher: European Respiratory Society (ERS)
Date: 03-09-2014
DOI: 10.1183/09031936.00217813
Abstract: Reports from in idual centres suggest a preponderance of females with chronic cough. Females also have heightened cough reflex sensitivity. Here we have reviewed the age and sex of unselected referrals to 11 cough clinics. To investigate the cause of any observed sex dimorphism, functional magnetic resonance imaging of putative cough centres was analysed in normal volunteers. The demographic profile of consecutive patients presenting with chronic cough was evaluated. Cough challenge with capsaicin was undertaken in normal volunteers to construct a concentration-response curve. Subsequent functional magnetic resonance imaging during repeated inhalation of sub-tussive concentrations of capsaicin observed areas of activation within the brain and differences in the sexes identified. Of the 10 032 patients presenting with chronic cough, two-thirds (6591) were female (mean age 55 years). The patient profile was largely uniform across centres. The most common age for presentation was 60–69 years. The maximum tolerable dose of inhaled capsaicin was lower in females however, a significantly greater activation of the somatosensory cortex was observed. Patients presenting with chronic cough from erse racial and geographic backgrounds have a strikingly homogeneous demographic profile, suggesting a distinct clinical entity. The preponderance of females may be explained by sex-related differences in the central processing of cough sensation.
Publisher: European Respiratory Society (ERS)
Date: 04-02-2016
Publisher: Springer Science and Business Media LLC
Date: 26-06-2023
DOI: 10.1038/S41467-023-39487-1
Abstract: The interleukin-1 family members, IL-1β and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1β processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori . Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori -induced pathology.
Publisher: Wiley
Date: 29-07-2016
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.JACI.2016.03.025
Abstract: The selection of pharmacotherapy for patients with allergic rhinitis (AR) depends on several factors, including age, prominent symptoms, symptom severity, control of AR, patient preferences, and cost. Allergen exposure and the resulting symptoms vary, and treatment adjustment is required. Clinical decision support systems (CDSSs) might be beneficial for the assessment of disease control. CDSSs should be based on the best evidence and algorithms to aid patients and health care professionals to jointly determine treatment and its step-up or step-down strategy depending on AR control. Contre les MAladies Chroniques pour un VIeillissement Actif en Languedoc-Roussillon (MACVIA-LR [fighting chronic diseases for active and healthy ageing]), one of the reference sites of the European Innovation Partnership on Active and Healthy Ageing, has initiated an allergy sentinel network (the MACVIA-ARIA Sentinel Network). A CDSS is currently being developed to optimize AR control. An algorithm developed by consensus is presented in this article. This algorithm should be confirmed by appropriate trials.
Publisher: Wiley
Date: 27-12-2016
DOI: 10.1002/PPUL.23370
Abstract: Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status. The study design was a randomized double-blind placebo-controlled study design with an iso-nitrogenous placebo. The primary analysis was intention to treat, and the primary outcome was change in induced sputum neutrophils. Thirty-nine in iduals were recruited and thirty-six completed the study. Glutamine supplementation had no impact on any of the outcome measures in the intention-to-treat analysis. In the per protocol analysis, glutamine supplementation was associated with an increase in induced sputum neutrophils (P = 0.046), total cells (P = 0.03), and in Pseudomonas isolation agar colony forming units (P = 0.04) compared to placebo. There was no effect of glutamine supplementation on markers of pulmonary inflammation in the intention-to-treat analysis.
Publisher: European Respiratory Society (ERS)
Date: 12-06-2014
DOI: 10.1183/09031936.00014614
Abstract: The objective of Integrated Care Pathways for Airway Diseases (AIRWAYS-ICPs) is to launch a collaboration to develop multi-sectoral care pathways for chronic respiratory diseases in European countries and regions. AIRWAYS-ICPs has strategic relevance to the European Union Health Strategy and will add value to existing public health knowledge by: 1) proposing a common framework of care pathways for chronic respiratory diseases, which will facilitate comparability and trans-national initiatives 2) informing cost-effective policy development, strengthening in particular those on smoking and environmental exposure 3) aiding risk stratification in chronic disease patients, using a common strategy 4) having a significant impact on the health of citizens in the short term (reduction of morbidity, improvement of education in children and of work in adults) and in the long-term (healthy ageing) 5) proposing a common simulation tool to assist physicians and 6) ultimately reducing the healthcare burden (emergency visits, avoidable hospitalisations, disability and costs) while improving quality of life. In the longer term, the incidence of disease may be reduced by innovative prevention strategies. AIRWAYSICPs was initiated by Area 5 of the Action Plan B3 of the European Innovation Partnership on Active and Healthy Ageing. All stakeholders are involved (health and social care, patients, and policy makers).
Publisher: European Respiratory Society (ERS)
Date: 31-03-2022
DOI: 10.1183/13993003.02583-2021
Abstract: Asthma treatment goals currently focus on symptom and exacerbation control rather than remission. Remission is not identical to cure, but is a step closer. This review considers the current definitions of remission in asthma, the prevalence and predictors, the pathophysiology of remission, the possibility of achieving it using the available treatment options, and the future research directions. Asthma remission is characterised by a high level of disease control, including the absence of symptoms and exacerbations, and normalisation or optimisation of lung function with or without ongoing treatment. Even in those who develop a symptomatic remission of asthma, persistent pathological abnormalities are common, leading to a risk of subsequent relapse at any time. Complete remission requires normalisation or stabilisation of any underlying pathology in addition to symptomatic remission. Remission is possible as part of the natural history of asthma, and the prevalence of remission in the adult asthma population varies between 2% and 52%. The factors associated with remission include mild asthma, better lung function, better asthma control, younger age, early-onset asthma, shorter duration of asthma, milder bronchial hyperresponsiveness, fewer comorbidities and smoking cessation or never smoking. Although previous studies have not targeted treatment-induced remission, there is some evidence to show that the current long-term add-on therapies such as biologics and azithromycin can achieve some criteria for asthma remission on treatment, at least in a subgroup of patients. However, more research is required. Long-term remission could be included as a therapeutic goal in studies of asthma treatments.
Publisher: BMJ
Date: 2022
DOI: 10.1136/BMJOPEN-2020-048537
Abstract: As-needed low-dose combination budesonide-formoterol is recommended by asthma guidelines in many countries as an alternative to maintenance inhaled corticosteroids (ICS) for treatment of mild asthma, but there are few data on patient attitudes toward these regimens. This study explored the comparative implementation experiences and future treatment preferences of mild asthma patients who had experienced these two treatment regimens. A subgroup of adults randomised to maintenance ICS or as-needed ICS-formoterol in a multinational, 52-week open-label randomised controlled trial (NovelSTART) in mild asthma patients were interviewed to explore their motivations for treatment use during the study and their preferences for future treatment. Semistructured interviews were conducted with 74 participants (Maintenance group: n=39, As-needed group n=35, mean age 38 (range 19–69)) and thematically analysed from transcribed audiorecordings. Emergent themes from analysis comprised: ‘How much my asthma affects me’ (how their asthma’s impact affected their self-management motivation) ‘What I know about asthma’ (limited knowledge impeded appropriate self-management decision making) ‘How much effort this treatment regimen involves for me’ (treatment complexity and/or difficulty establishing a medication routine impeded implementation, particularly in the Maintenance group) and ‘My beliefs about the benefits and risks of this treatment’ (patients who considered their treatment as ineffective, eg, limited difference in symptoms relative to salbutamol (both groups) or slower onset of relief (As-needed group) had poor motivation to use the treatment). Due to the simplicity of the as-needed combination strategy, this was the preferred future regimen, even by patients who had not yet tried it. Key patient perspectives on the implementation of preventer treatments for mild asthma included factors relating to perceived asthma burden, disease knowledge, treatment complexity and treatment usefulness or safety. The as-needed budesonide-formoterol regimen was preferred to maintenance ICS treatment in mild asthma though patient education is urgently needed to address implementation motivation. ACTRN12615000999538.
Publisher: American Thoracic Society
Date: 07-2009
Publisher: JMIR Publications Inc.
Date: 28-03-2023
Abstract: sthma attacks are a common and important problem. Someone experiences an asthma attack in the United Kingdom every 10 seconds. Asthma attacks cause coughing, wheezing, breathlessness, and chest tightness and are highly stressful for patients. They result in reduced quality of life, with days lost from work or school. Asthma attacks are treated with oral corticosteroids (OCSs), but these have many short- and long-term side effects. Asthma monoclonal antibodies (mAbs) have revolutionized the treatment of severe asthma by reducing asthma attacks and OCS burden by over 50%, but some people still experience attacks while on mAbs. The MEX study showed that residual asthma attacks are broadly eosinophilic (high fractional exhaled nitric oxide [FeNO]) or noneosinophilic (low FeNO), but it did not measure response to OCS treatment. There is an evidence gap in understanding the clinical and inflammatory responses that occur when using OCSs to treat residual asthma attacks in patients taking asthma mAbs. he primary objective is to compare the clinical recovery between high-FeNO and low-FeNO attacks after acute treatment with oral prednisolone among people established on long-term asthma mAb treatment. The exploratory objective is to compare the inflammatory response to acute treatment with oral prednisolone between high-FeNO and low-FeNO attacks. OOST (Breakthrough Asthma Attacks Treated With Oral Steroids) is a single-center, prospective observational study of 60 adults established on long-term asthma mAb treatment who receive acute treatment with oral prednisolone (usual care) for an asthma attack. The primary outcome will be the proportion of treatment failure (the need to start oral prednisolone or antibiotics or an unscheduled health care visit for asthma, following an attack) at day 28. The secondary outcomes will be the change in forced expiratory volume in 1 second and the change in visual analogue scale symptom score between the stable state, attack, day 7, and day 28 visits. The exploratory outcomes include the changes in sputum, nasal, and blood inflammometry between the stable state, attack, day 7, and day 28 visits. he last asthma attack visit is anticipated to occur in December 2023. Data analysis and publication will take place in 2024. e will test the hypothesis that there is a difference in the rate of recovery of clinical and inflammatory measures between high-FeNO and low-FeNO asthma attacks that occur in patients on mAb therapy. The study data will help power a future randomized placebo-controlled trial of prednisolone treatment for nonsevere attacks in patients treated with asthma mAbs and will provide important information on whether corticosteroid treatment should be FeNO-directed. ERR1-10.2196/46741
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Ian Pavord.