Showing papers by "Peter G. Gibson published in 2009"

An official American Thoracic Society/European Respiratory Society statement: asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice.

Abstract: Background: The assessment of asthma control is pivotal to the evaluation of treatment response in individuals and in clinical trials. Previously, asthma control, severity, and exacerbations were defined and assessed in many different ways.Purpose: The Task Force was established to provide recommendations about standardization of outcomes relating to asthma control, severity, and exacerbations in clinical trials and clinical practice, for adults and children aged 6 years or older.Methods: A narrative literature review was conducted to evaluate the measurement properties and strengths/weaknesses of outcome measures relevant to asthma control and exacerbations. The review focused on diary variables, physiologic measurements, composite scores, biomarkers, quality of life questionnaires, and indirect measures.Results: The Task Force developed new definitions for asthma control, severity, and exacerbations, based on current treatment principles and clinical and research relevance. In view of current knowledge ...

The overlap syndrome of asthma and COPD: what are its features and how important is it?

Abstract: There is a need to re-evaluate the concept of asthma and chronic obstructive pulmonary disease (COPD) as separate conditions, and to consider situations when they may coexist, or when one condition may evolve into the other. Epidemiological studies show that in older people with obstructive airway disease, as many as half or more may have overlapping diagnoses of asthma and COPD (overlap syndrome). These people are typically excluded from current therapy trials, which limit the generalisability of these trials, and this presents a problem for evidence-based guidelines for obstructive airway diseases. Studying overlap syndrome may shed light on the mechanisms of COPD development. Overlap syndrome is recognised by the coexistence of increased variability of airflow in a patient with incompletely reversible airway obstruction. Patients typically have inflammatory features that resemble COPD, with increased airway neutrophilia, as well as features of airway wall remodelling. Overlap syndrome can develop when there is accelerated decline in lung function, or incomplete lung growth, or both. The risk factors for these events are shared, such that increasing age, bronchial hyper-responsiveness, tobacco smoke exposure, asthma and lower respiratory infections/exacerbations are significant risk factors for both incomplete lung growth and accelerated loss of lung function. Studying these events may offer new insights into the mechanisms and treatment of obstructive airway diseases.

Interventions for educating children who are at risk of asthma-related emergency department attendance

Abstract: Background Asthma is the most common chronic childhood illness and is a leading cause for paediatric admission to hospital. Asthma management for children results in substantial costs. There is evidence to suggest that hospital admissions could be reduced with effective education for parents and children about asthma and its management. Objectives To conduct a systematic review of the literature and update the previous review as to whether asthma education leads to improved health outcomes in children who have attended the emergency room for asthma. Search methods We searched the Cochrane Airways Group Trials Register, including the MEDLINE, EMBASE and CINAHL databases, and reference lists of trials and review articles (last search May 2008). Selection criteria We included randomised controlled trials of asthma education for children who had attended the emergency department for asthma, with or without hospitalisation, within the previous 12 months. Data collection and analysis Two authors independently assessed trial quality and extracted data. We contacted study authors for additional information. We pooled dichotomous data with a fixed-effect risk ratio. We used a random-effects risk ratio for sensitivity analysis of heterogenous data. Main results A total of 38 studies involving 7843 children were included. Following educational intervention delivered to children, their parents or both, there was a significantly reduced risk of subsequent emergency department visits (RR 0.73, 95% CI 0.65 to 0.81, N = 3008) and hospital admissions (RR 0.79, 95% CI 0.69 to 0.92, N = 4019) compared with control. There were also fewer unscheduled doctor visits (RR 0.68, 95% CI 0.57 to 0.81, N = 1009). Very few data were available for other outcomes (FEV1, PEF, rescue medication use, quality of life or symptoms) and there was no statistically significant difference between education and control. Authors' conclusions Asthma education aimed at children and their carers who present to the emergency department for acute exacerbations can result in lower risk of future emergency department presentation and hospital admission. There remains uncertainty as to the long-term effect of education on other markers of asthma morbidity such as quality of life, symptoms and lung function. It remains unclear as to what type, duration and intensity of educational packages are the most effective in reducing acute care utilisation.

Using fractional exhaled nitric oxide to guide asthma therapy: design and methodological issues for ASthma TReatment ALgorithm studies.

Abstract: Summary Background Current asthma guidelines recommend treatment based on the assessment of asthma control using symptoms and lung function. Noninvasive markers are an attractive way to modify therapy since they offer improvedselection of active treatment(s) based on individual response, and improvedtitration of treatment using markers that are better related to treatment outcomes. Aims: To review the methodological and design features of noninvasive marker studies in asthma. Methods Systematic assessment of published randomized trials of asthma therapy guided by fraction of exhaled nitric oxide(FENO). Results FENO has appeal as a marker to adjust asthma therapy since it is readily measured, gives reproducible results, and is responsive to changes in inhaled corticosteroid doses. However, the five randomised trials of FENO guided therapy have had mixed results. This may be because there are specific design and methodological issues that need to be addressed in the conduct of ASthma TReatment ALgorithm(ASTRAL) studies. There needs to be a clear dose response relationship for the active drugs used and the outcomes measured. The algorithm decision points should be based on outcomes in the population of interest rather than the range of values in healthy people, and the algorithm used needs to provide a sufficiently different result to clinical decision making in order for there to be any discernible benefit. A new metric is required to assess the algorithm performance, and the discordance:concordance(DC) ratio can assist with this. Conclusion Incorporating these design features into future FENO studies should improve the study performance and aid in obtaining a better estimate of the value of FENO guided asthma therapy.

Inflammatory phenotypes in adult asthma: clinical applications.

Abstract: Background: The pattern of granulocyte infiltration can be used to identify different inflammatory phenotypes in asthma. Recognized granulocyte phenotypes using induced sputum are eosinophilic (EA), neutrophilic, mixed granulocytic and paucigranulocytic asthma. Methods: The recognition and importance of inflammatory phenotype analysis using induced sputum in adult asthma are reviewed using published literature. Results: Knowledge of inflammatory phenotype is useful because it relates to treatment response, mechanistic pathways involved in disease pathogenesis and future disease risk. The population attributable risk of asthma because of eosinophilic inflammation is about 50%, and conversely, this means that up to 50% of asthma cannot be attributed to eosinophilic inflammation, and represents asthma associated with non-eosinophilic processes. In these patients, bronchial biopsy shows significantly fewer eosinophils in the bronchial mucosa than subjects with EA. This confirms that non-eosinophilic asthma is a consistent pattern/phenotype in the airway lumen and the airway mucosa. A key aspect of asthma inflammatory phenotype analysis is that it can be applied to individual patients. The underlying principle relates to the association between a clinical response to corticosteroids and the presence of a selective sputum eosinophilia. Conclusions: Clinically useful applications of induced sputum analysis are the detection of non-adherence to corticosteroid therapy, assessment of adequacy of inhaled corticosteroid therapy, long-term therapy management in asthma, oral corticosteroid dose adjustment in refractory asthma and assessment of occupational asthma. Please cite this paper as: Gibson PG. Inflammatory phenotypes in adult asthma: clinical applications. The Clinical Respiratory Journal 2009; 3: 198–206.

Diversity in the bronchial epithelial cell response to infection with different rhinovirus strains.

Abstract: Background and objective: Infection with rhinovirus (RV) is the most common trigger for acute asthma and COPD. The aim of this study was to characterize the variability in the response of primary bronchial epithelial cells to infection with several strains of RV. Methods: RV strains, RV-43, RV-48 (major group RV), RV-47 (minor) and EV-68 (enterovirus), were cultured from subjects with acute asthma and compared with the laboratory RV strains, RV-16, RV-14 (major) and RV-1B (minor). Primary bronchial epithelial cells were obtained from healthy control and asthmatic subjects by endobronchial brushing. Response to infection was assessed by the release of IL-6, interferon (IFN)-γ induced protein (IP)-10 and IFN-β, as measured by ELISA. Viral replication was assessed by serial titration assays and cell viability by flow cytometry. Results: Major group RV strains and EV-68 all efficiently infected and replicated in epithelial cells causing little cell death. The clinical major group RV strains caused greater release of IL-6 and IP-10 compared with laboratory major group RV strains. Infection with minor group RV resulted in greater release of IP-10, IL-6 and IFN-β that was associated with induction of apoptosis and less efficient viral replication. Asthmatic bronchial epithelial cells were less able to respond by releasing IFN-β following infection with RV-1B. Conclusions: Considerable diversity exists in the response to RV strains, especially between minor and major group RV. The impaired IFN-β response in asthmatic bronchial epithelial cells may make them particularly susceptible to minor group RV.

Systemic corticosteroids for acute exacerbations of chronic obstructive pulmonary disease (Review)

Abstract: Background COPD is a common condition, mainly related to smoking. Acute exacerbations of COPD, usually related to superimposed infection, occur commonly and systemic corticosteroids are widely used in their management in combination with other treatments including antibiotics, oxygen supplementation and bronchodilators. Objectives To determine the efficacy of corticosteroids, administered either parenterally or orally, on the outcomes of acute exacerbations of COPD. Search strategy Searches were carried out using the Cochrane Airways Group COPD RCT register with additional studies sought in the bibliographies of randomised controlled trials and review articles. Authors of identified randomised controlled trials were contacted for other published and unpublished studies. The last search was carried out in August 2008. Selection criteria Randomised controlled trials comparing corticosteroids, administered either parenterally or orally, with appropriate placebo control. Other interventions e.g. bronchodilators and antibiotics were standardised. Clinical studies of acute asthma were excluded. Data collection and analysis Data were extracted independently by two reviewers. Data measured but not reported were sought from authors of included studies. Trials were combined using Review Manager for analyses. Main results Eleven studies (n=1081) fulfilled the inclusion criteria and 10 studies contributed data for analyses (n=1051). There were significantly fewer treatment failures within thirty days in patients given corticosteroid treatment, Odds Ratio (OR) 0.50; 95% confidence interval (CI) 0.36 to 0.69 and Hazard Ratio 0.78; 95% CI 0.63 to 0.97. It would have been necessary to treat 10 patients (95%CI 7 to 16) with corticosteroids to avoid one treatment failure in this time period. Duration of hospitalisation was significantly shorter with corticosteroid treatment, mean difference -1.22 days; 95% CI -2.26 to -0.18. For FEV1 there were significant treatment benefits with mean differences at the early time point (to 72 hours), 140 ml; 95% CI 90 to 190 ml and at end of treatment (up to 15 days) 80 ml; 95% confidence interval 10 to 160. There was a significant improvement in breathlessness and blood gases at both time points. There was no significant effect on mortality but an increased likelihood of an adverse event associated with corticosteroid treatment, OR 2.33; 95% CI 1.60 to 3.40. Overall one extra adverse effect occurred for every 5 people treated (95% CI 4 to 9). The risk of hyperglycaemia was significantly increased, OR 4.95; 95% CI 2.47 to 9.91.

Maternal and neonatal outcomes of pregnancies complicated by asthma in an Australian population.

Abstract: Objective: To determine if there are sex differences in risk and incidence of stillbirth, preterm delivery and small-for-gestational age (SGA) in pregnancies complicated by maternal asthma relative to a non-asthmatic population. Study design: Univariant and multiple regression analysis of the incidence of preterm delivery, SGA and stillbirth in singleton pregnancies complicated by asthma in Newcastle, NSW, Australia, from 1995 to 1999. Results: Asthma complicated 12% of all singleton pregnancies. The incidence of preterm delivery was not significantly different between asthmatic (13%) and non-asthmatic (11%) pregnancies. Male fetuses (53%) were more likely to deliver preterm than female fetuses (47%) in both asthmatic and non-asthmatic populations. There were significantly more male neonates of pregnancies complicated by asthma that were SGA at term relative to those of the non-asthmatic population. There were significantly more preterm female neonates that were SGA in pregnancies complicated by asthma relative to those of the non-asthmatic population. Male fetuses were more likely to be associated with a stillbirth in pregnancies complicated by asthma than female fetuses. Conclusion: The presence of maternal asthma during pregnancy increases the risk of stillbirth for the male fetus and is associated with changes in fetal growth, but does not increase the incidence of a preterm delivery.

Chronic cough and laryngeal dysfunction improve with specific treatment of cough and paradoxical vocal fold movement

Abstract: Chronic persistent cough can be associated with laryngeal dysfunction that leads to symptoms such as dysphonia, sensory hyperresponsiveness to capsaicin, and motor dysfunction with paradoxical vocal fold movement and variable extrathoracic airflow obstruction (reduced inspiratory airflow). Successful therapy of chronic persistent cough improves symptoms and sensory hyperresponsiveness. The effects of treatment for chronic cough on laryngeal dysfunction are not known. The aim of this study was to investigate effects of therapy for chronic cough and paradoxical vocal fold movement. Adults with chronic cough (n = 24) were assessed before and after treatment for chronic persistent cough by measuring quality of life, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity and fibreoptic laryngoscopy to observe paradoxical vocal fold movement. Subjects with chronic cough were classified into those with (n = 14) or without (n = 10) paradoxical vocal fold movement based on direct observation at laryngoscopy. Following treatment there was a significant improvement in cough related quality of life and cough reflex sensitivity in both groups. Subjects with chronic cough and paradoxical vocal fold movement also had additional improvements in extrathoracic airway hyperresponsiveness and paradoxical vocal fold movement. The degree of improvement in cough reflex sensitivity correlated with the improvement in extrathoracic airway hyperresponsiveness. Laryngeal dysfunction is common in chronic persistent cough, where it is manifest as paradoxical vocal fold movement and extrathoracic airway hyperresponsiveness. Successful treatment for chronic persistent cough leads to improvements in these features of laryngeal dysfunction.

Randomized trial of a decision aid for patients with cystic fibrosis considering lung transplantation.

Abstract: Rationale: We developed an evidence-based decision aid for patients with advanced cystic fibrosis considering referral for lung transplantation.Objectives: To prospectively evaluate whether use of the decision aid increased knowledge about the options, improved realistic expectations, and decreased decisional conflict in adult patients.Methods: We performed a single-blind randomized controlled trial involving 149 adult patients with cystic fibrosis with an FEV1 ≤ 40% predicted from 14 Canadian and Australian centers. All participants received an education and counseling session from their cystic fibrosis team and were then randomized to receive the decision aid or usual care. The decision aid is available online at http://decisionaid.ohri.ca/decaids.html.Measurements and Main Results: The primary end points measured were participants' knowledge, realistic expectations, and decisional conflict evaluated 3 weeks after randomization. Patients randomized to the decision aid had greater knowledge about their o...

Oncostatin M (OSM) is increased in asthma with incompletely reversible airflow obstruction.

Abstract: Oncostatin M, a unique member of the interleukin (IL)-6 cytokine family, is thought to be involved in airway remodeling. The expression of oncostatin M in the lower airways is unknown. The aim of this study was to measure the sputum expression of oncostatin M in patients with asthma with and without irreversible airflow obstruction. Induced sputum was collected from nonsmoking adults with stable asthma (n = 53), 31 with incomplete reversibility of airflow obstruction. Peripheral blood cells were isolated and stimulated with lipopolysaccharide in 10 participants with asthma and irreversible airflow obstruction. Oncostatin M protein levels were determined in supernatant, whereas RNA was extracted to determine Oncostatin M mRNA expression using real-time polymerase chain reaction (PCR). Oncostatin M mRNA expression and protein levels were significantly higher in the sputum of asthmatics with irreversible airflow obstruction. Sputum oncostatin M levels were highest in people with severe airflow obstruction and were localized to airway neutrophils and macrophages. Peripheral blood neutrophils released more oncostatin M when stimulated with lipopolysaccharide compared with unstimulated neutrophils. Sputum oncostatin M is increased in asthma with irreversible airflow obstruction and is present in airway neutrophils and macrophages. Oncostatin M may link airway inflammation to remodeling in asthma.

Lycopene enrichment of cultured airway epithelial cells decreases the inflammation induced by rhinovirus infection and lipopolysaccharide.

Abstract: Rhinovirus infection results in increased release of inflammatory mediators from airway epithelial cells in asthma. As an antioxidant, lycopene offers protection from adverse effects of inflammation. The aim of this study was to find an appropriate method of lycopene enrichment of airway epithelial cells and to determine the effects of lycopene enrichment on the inflammatory response of cells infected by rhinovirus or exposed to lipopolysaccharide. Lycopene enrichment of airway epithelial cells using solubilisation in tetrahydrofuran versus incorporation in liposomes was compared. After determining that solubilisation of lycopene in tetrahydrofuran was the most suitable method of lycopene supplementation, airway epithelial cells (Calu-3) were incubated with lycopene (dissolved in tetrahydrofuran) for 24 h, followed by rhinovirus infection or lipopolysaccharide exposure for 48 h. The release of interleukin-6, interleukin-8 and interferon-gamma induced protein-10 (IP-10) and their messenger RNA levels were measured using enzyme linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. Viral replication was measured by tissue culture infective dose of 50% assay. Lycopene concentration of cells and media were analysed using high-performance liquid chromatography. Preincubation of airway epithelial cells with lycopene (dissolved in tetrahydrofuran) delivered lycopene into the cells and resulted in a 24% reduction in interleukin-6 after rhinovirus-1B infection, 31% reduction in IP-10 after rhinovirus-43 infection and 85% reduction in rhinovirus-1B replication. Lycopene also decreased the release of IL-6 and IP-10 following exposure to lipopolysaccharide. We conclude that lycopene has a potential role in suppressing rhinovirus induced airway inflammation.

Lycopene enrichment of cultured airway epithelial cells decreases the inflammation induced by rhinovirus infection and lipopolysaccharide | NOVA. The University of Newcastle's Digital Repository

Abstract: Rhinovirus infection results in increased release of inflammatory mediators from airway epithelial cells in asthma. As an antioxidant, lycopene offers protection from adverse effects of inflammation. The aim of this study was to find an appropriate method of lycopene enrichment of airway epithelial cells and to determine the effects of lycopene enrichment on the inflammatory response of cells infected by rhinovirus or exposed to lipopolysaccharide. Lycopene enrichment of airway epithelial cells using solubilisation in tetrahydrofuran versus incorporation in liposomes was compared. After determining that solubilisation of lycopene in tetrahydrofuran was the most suitable method of lycopene supplementation, airway epithelial cells (Calu-3) were incubated with lycopene (dissolved in tetrahydrofuran) for 24 h, followed by rhinovirus infection or lipopolysaccharide exposure for 48 h. The release of interleukin-6, interleukin-8 and interferon-gamma induced protein-10 (IP-10) and their messenger RNA levels were measured using enzyme linked immunosorbent assay and reverse transcription polymerase chain reaction, respectively. Viral replication was measured by tissue culture infective dose of 50% assay. Lycopene concentration of cells and media were analysed using high-performance liquid chromatography. Preincubation of airway epithelial cells with lycopene (dissolved in tetrahydrofuran) delivered lycopene into the cells and resulted in a 24% reduction in interleukin-6 after rhinovirus-1B infection, 31% reduction in IP-10 after rhinovirus-43 infection and 85% reduction in rhinovirus-1B replication. Lycopene also decreased the release of IL-6 and IP-10 following exposure to lipopolysaccharide. We conclude that lycopene has a potential role in suppressing rhinovirus induced airway inflammation.

Characterization of laryngeal dysfunction in chronic persistent cough.

Abstract: Objectives/Hypothesis: Laryngeal symptoms are increasingly recognized to occur in chronic persistent cough and may result from the sensory hyperresponsiveness that characterizes this condition Apart from cough, the motor consequences of sensory activation have not been well described in chronic persistent cough The efficacy of speech pathology treatment for chronic cough suggests that laryngeal dysfunction may be relevant in chronic persistent cough This study investigated the relationship between cough reflex sensitivity and laryngeal dysfunction, which was assessed as paradoxical vocal cord movement (PVCM) and extrathoracic airway hyperresponsiveness, in patients with chronic cough Study Design: Cross-sectional case-control comparison of subjects with chronic cough and healthy controls Methods: Adults with chronic persistent cough (n = 25) and healthy controls (n = 11) were assessed by cough-specific quality of life questionnaire, extrathoracic airway hyperresponsiveness to hypertonic saline provocation, capsaicin cough reflex hypersensitivity, and fibreoptic laryngoscopy to assess PVCM Results: Laryngeal dysfunction was present in many patients with chronic persistent cough PVCM was present in 56% of subjects with chronic cough and accompanied by cough reflex hypersensitivity and impaired quality of life Inspiratory airflows were reduced in cough with PVCM, and there was significant extrathoracic airway hyperresponsiveness Conclusions: Laryngeal dysfunction is common in chronic cough, where it is manifest as paradoxical vocal cord movement and extrathoracic airway hyperresponsiveness Laryngeal dysfunction in chronic cough is associated with reduced quality of life Laryngeal hypersensitivity may be a common mechanism that can be effectively treated by speech language therapy Laryngoscope, 2009

Immune responses of airway neutrophils are impaired in asthma.

Abstract: Neutrophilic inflammation is a key effector arm of the innate immune response Neutrophils may contribute significantly to airway inflammation in certain asthma subtypes The objective of this study is to investigate the innate immune responses of isolated airway and circulating neutrophils in asthma Participants with asthma (n = 17) and healthy volunteers (n = 11) underwent induced sputum and blood collection Neutrophils were isolated from dispersed selected sputum and blood granulocytes using magnetic cell separation Neutrophils were cultured with or without lipopolysaccharide (100 ng/mL) for 24 hours Innate immune mediators were measured by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR) Airway neutrophils from participants with asthma spontaneously released lower levels of interleukin (IL)-8, IL-1β and tumor necrosis factor-α proteins, and had lower levels of cytokine gene expression compared to healthy controls Toll-like receptor 4 (TLR4) gene expression

The nutrigenomics of asthma: molecular mechanisms of airway neutrophilia following dietary antioxidant withdrawal

Abstract: Depletion of antioxidants through consumption of a low antioxidant diet has been reported to increase neutrophilic airway inflammation and worsen symptoms of asthma. Using a nutrigenomics approach, this study explores the mechanisms of airway neutrophilic inflammation due to depletion of dietary antioxidants. Induced sputum samples were collected at baseline and after participants consumed a low antioxidant diet for 14 days. Genome-wide gene expression profiles were generated from sputum RNA samples from participants with a >10% change in sputum neutrophils using Illumina Humanref-8 expression microarrays. There were 104 genes differentially expressed following the dietary change. Upregulated genes were involved in the innate immune response and included the innate immune receptors TLR2, IL1R2, CD93, the signaling molecules IRAK2, IRAK3, and neutrophil proteases MMP25 and CPD. Downregulated genes included those involved in endogenous antioxidant defenses (GSTA1, GSTA2) and protease inhibition (SLPI, SERPINB3). Altered expression of five genes (TLR2, IRAK2, IL1R2, C20orf114, and SERPINB3) was confirmed using real-time polymerase chain reaction (PCR). These observations suggest that depletion of dietary antioxidants in asthma may result in upregulation of genes involved in the innate immune response. A diet low in antioxidants may be contributing to the development of neutrophilic asthma through activation of the innate immune response.

Tackling asthma phenotypes in community studies

Abstract: Episodic wheezing with variable airflow obstruction (asthma) defines a syndrome that is well recognised and much studied. It is now clear that this syndrome is heterogeneous in its clinical features, treatment response, prognosis and pathophysiological mechanisms. Causation remains elusive, yet the differences in asthma prevalence across the world,1 the effect of migration on changing asthma prevalence2 and the rise in asthma prevalence in the past decades highlight very potent gene and environmental effects that modify the clinical expression of asthma.3 Studying asthma heterogeneity is a useful way to disentangle these complex issues.4 The intense focus on allergic mechanisms has given us very precise understanding of the Th2–eosinophil mechanistic pathway, effective and specific treatment—for example, anti-immunoglobulin E (IgE) monoclonal antibody treatment—and shown that a primary prevention strategy based on this approach is not likely to be beneficial. Current attention is focusing on patterns of granulocyte infiltration, specifically the presence or absence of eosinophils and neutrophils.5 There is clear heterogeneity in these responses among adults with asthma, where a non-eosinophilic pattern of response is associated with more severe persistent asthma, non-response to corticosteroid therapy and certain specific trigger factors such as tobacco smoking and occupational exposures. Furthermore, it is also possible to link the granulocyte response patterns to key immunological mechanisms, such as eosinophils with Th2 lymphocyte responses and neutrophils with dysfunctional innate immune responses.6 This approach integrates basic mechanisms with clinical asthma heterogeneity to yield endogenous asthma phenotypes, or “endotypes”.7 While the application of the …

Pneumococcal vaccines for allergic airways diseases.

Abstract: Background: Asthma is a common global health problem. Environmental exposures such as bacteria may protect against asthma development. Objective: This review aims to examine the possible protective...

Asthma in older adults: a holistic, person-centred and problem-oriented approach.

Abstract: Regardless of how obstructive lung disease is labelled, targeting treatment to components of the problem is the best solution.

Early life chlamydial infection enhances allergic airways disease through age-dependent differences in immunopathology

Abstract: BACKGROUND Asthma typically originates in early-life, and the impact of infection during immunologic maturation is a critical factor in disease pathogenesis. The progression of aberrant T(H)2 cell responses and disease development has been attributed to a lack of infections. However, exposure to specific pathogens such as Chlamydia may alter immunologic programming and predispose to asthma. OBJECTIVE To investigate the effects of chlamydial infection at different ages on allergic airways disease in later life. METHODS Neonatal, infant, or adult BALB/c mice were infected and 6 weeks later were sensitized and subsequently challenged with ovalbumin. Hallmark features of allergic airways disease were compared with uninfected allergic and nonallergic controls. RESULTS Early-life (neonatal and infant) but not adult chlamydial infection enhanced the development of hallmark features of asthma in ovalbumin-induced allergic airways disease. Notably early-life infection increased mucus-secreting cell numbers, IL-13 expression, and airway hyperresponsiveness. Neonatal infection attenuated eosinophil influx and ovalbumin-specific T(H)2 cytokine release and numbers of activated myeloid dendritic cells (DCs) in lymph nodes. By contrast, infant infection augmented features of allergic inflammation with increased airway eosinophils, T(H)2 cytokine, and DC responses. Both neonatal and infant infection increased systemic DC-induced IL-13 release from CD4(+) T cells. The timing of infection had significant effects on lung structure because neonatal but not infant or adult infection induced increases in alveolar diameter. CONCLUSION Early-life respiratory chlamydial infections modulate immune responses, alter lung function and structure, and enhance the severity of allergic airways disease in later life.