Disease burden, comorbidities and antecedents of chronic cough phenotypes in Australian adults.

BACKGROUND AND OBJECTIVES: While adult chronic cough has high burden, its phenotypes, particularly those without aetiologically related underlying conditions, are understudied. We investigated the prevalence, lung function and comorbidities of adult chronic cough phenotypes. METHODS: Data from 3608 participants aged 53 years from the Tasmanian Longitudinal Health Study (TAHS) were included. Chronic cough was defined as cough on most days for >3 months in a year. Chronic cough was classified into "explained cough" if there were any one of four major cough-associated conditions (asthma, COPD, gastroesophageal reflux disease or rhinosinusitis) or "unexplained cough" if none were present. Adjusted regression analyses investigated associations between these chronic cough phenotypes, lung function and non-respiratory comorbidities at 53 years. RESULTS: The prevalence of chronic cough was 10% (95%CI 9.1,11.0%) with 46.4% being "unexplained". Participants with unexplained chronic cough had lower FEV1/FVC (coefficient: -1.2% [95%CI:-2,3, -0.1]) and increased odds of comorbidities including obesity (OR=1.6 [95%CI: 1.2, 2.3]), depression (OR=1.4 [95%CI: 1.0, 2.1]), hypertension (OR=1.7 [95%CI: 1.2, 2.4]) and angina, heart attack or myocardial infarction to a lesser extent, compared to those without chronic cough. Participants with explained chronic cough also had lower lung function than both those with unexplained chronic cough and those without chronic cough. CONCLUSIONS: Chronic cough is prevalent in middle-age and a high proportion is unexplained. Unexplained cough contributes to poor lung function and increased comorbidities. Given unexplained chronic cough is not a symptom of major underlying respiratory conditions it should be targeted for better understanding in both clinical settings and research.

Mould-sensitized adults have lower Th2 cytokines and a higher prevalence of asthma than those sensitized to other aeroallergens.

BACKGROUND: Evidence suggests that specific allergen sensitizations are associated with different allergic diseases which may reflect different underlying immune profiles. We aimed to examine the cytokine profiles of individuals sensitized to eight common aeroallergens. METHODS: We used data from the Tasmanian Longitudinal Health Study a population-based cohort study of 45-year-olds. Serum cytokines (IL-4, IL-5, IL-6, IL-8, IL-10, TNF-α) were measured in 1157 subjects using the LINCOplex assays. Participants underwent skin prick testing for house dust mite, cat, grasses and moulds. Multivariable linear regression was used to compare serum cytokine levels between sensitized and nonatopic subjects. RESULTS: The prevalence of allergic sensitization to any aeroallergen was 51% (95% CI 47-54). Being sensitized to any aeroallergen was strongly associated with current asthma (OR = 3.7, 95% CI 2.6-5.3), and being sensitized to any moulds was associated with a very high risk of current asthma (OR = 6.40, 95% CI 4.06-10.1). The geometric mean (GM) levels of Th2 cytokines (IL-4, IL-5 and IL-6) for adults sensitized to Cladosporium were significantly lower than the levels for nonatopic individuals (IL-4 ratio of GMs = 0.25, 95% CI 0.10-0.62, P = 0.003; IL-5 GM = 0.55, 95% CI 0.30-0.99, P = 0.05; and IL-6 GM = 0.50, 95% CI 0.24-1.07, P = 0.07). Individuals sensitized to other aeroallergens all showed elevated Th2 cytokine levels. CONCLUSION: Our study is the first large population-based study to demonstrate reduced Th2 cytokines levels in people sensitized to mould. Underlying biological mechanisms driving allergic inflammatory responses in adults sensitized to moulds may differ from those sensitized to other aeroallergens. These findings suggest that it may be necessary to tailor treatments in individuals sensitized to moulds compared with other aeroallergens in order to optimize outcomes.

Prospective outcomes in patients with acute exacerbations of chronic obstructive pulmonary disease presenting to hospital: a generalisable clinical audit.

BACKGROUND AND AIM: To determine predictors of short- and long-term outcomes in patients with acute exacerbation of chronic obstructive pulmonary disease (COPD) (AECOPD) presenting to hospital. METHODS: A prospective clinical audit of AECOPD attendances to the only public acute general hospital in Southern Tasmania, Australia. Out of 416 attendances with AECOPD to the emergency department (ED) between November 2006 and July 2008, 150 patients with 218 attendances were followed to March 2009. Predictors of hospital admission from ED, in-hospital death, length of hospital stay, post-discharge mortality and re-attendance rate for AECOPD were the main outcomes. RESULTS: There were no clear differences between patients admitted to hospital and those sent home from ED. Predictors of in-hospital death were initial physiologic parameters, that is, arterial pH, PaCO2 , oxygen saturation and blood pressure. Longer hospital stay was associated with older age, current smoking, hyperglycaemia, lower blood pressure and lower oxygen saturation. Risk of mortality after discharge was associated with a history of myocardial infarction, nursing home residence and severity of COPD. Re-attendance rate was associated with osteoporosis, younger age and severity of COPD. CONCLUSIONS: Further investigation into the process of decision making about which AECOPD patients are admitted from the ED is required. Short-term outcomes, in-hospital death and length of hospital stay are mainly predicted by severity of the acute exacerbation and patient demographics. Although severity of COPD was a predictor of long-term outcomes, the main predictors of these were presence of co-morbidities.

An observational study of PM10 and hospital admissions for acute exacerbations of chronic respiratory disease in Tasmania, Australia 1992-2002.

OBJECTIVE: Particulate matter with a diameter below 10 µ (PM10) has been a major concern in the Tamar Valley, Launceston, where wood heaters are extensively used. We examined the relationship between PM10 levels, meteorological variables, respiratory medications and hospital admissions for respiratory disease over the decade 1992-2002. METHODS: PM10 levels were provided by the Department of Primary Industry Water, Parks and Environment, and meteorological variables from the Bureau of Meteorology. We obtained hospital discharge codes for the Launceston General Hospital. Poisson regression was used for statistical analyses. RESULTS: Mean daily PM10 levels declined from 50.7 to 16.5 µg/m(3). Hospitalisations for asthma decreased from 29 to 21 per month, whereas chronic obstructive pulmonary disease (COPD) increased and bronchitis/bronchiolitis remained unchanged. We found a 10 µg/m(3) increase in PM10 to be associated with a 4% increase in admissions for acute bronchitis/bronchiolitis (p0.05), but no association with asthma or COPD was found. All respiratory diseases showed seasonal patterns of hospitalisation. CONCLUSIONS: This is the first long-term study in Australia to demonstrate an association between PM10 levels and respiratory diseases. Reducing exposure to PM10 may decrease hospital admissions for respiratory diseases. IMPLICATION: Better preventive measures, including sustained public health initiatives to combat air pollution, are required to reduce respiratory morbidity.

Cardiovascular effects of methacholine-induced airway obstruction in man.

Cardiovascular disease is the most frequent cause of death in people with chronic respiratory disease. The cause of this association has been attributed to airway obstruction leading to cardiovascular dysfunction (increased central blood pressure (BP) and aortic stiffness). However, this has never been experimentally tested. Methacholine is routinely used to stimulate airway function changes that mimic airway pathology. This study aimed to determine the cardiovascular effects of methacholine-induced airway obstruction. Fifteen healthy young adults (aged 22.9±2.5 years; 4 male; mean±S.D.) underwent a bronchial challenge test (randomized, blinded, cross-over design) in which they received nebulized methacholine inhalation in serially increasing concentrations (from 0.39 to 25 mg/ml) or saline (0.9%; control) on two separate days. Bronchoconstriction was assessed by forced expiratory volume at one second (FEV1) and cardiovascular effects by augmentation index, brachial BP, central BP, heart rate and aortic stiffness. Methacholine significantly decreased FEV1 from baseline to peak inhaled concentration compared with saline (-0.48±0.34 vs. -0.07±0.16 L; p<0.001), but there was no between-group change in augmentation index (1.6±7.0 vs. 3.7±10.2% p=0.49), brachial systolic BP (-3.3±7.6 vs. -4.7±5.7 mmHg; p=0.59), central systolic BP (-1.1±5.2 vs. -0.3±5.5 mmHg; p=0.73), heart rate (0.4±7.1 vs. -0.8±6.6 bpm; p=0.45) or aortic stiffness (0.2±1.3 vs. 0.8±1.8 m/s; p=0.20; n=12). Thus, methacholine induced airway obstruction does not acutely change brachial BP or central haemodynamics. This finding refutes the notion that airway obstruction per se leads to cardiovascular dysfunction, at least in healthy individuals in the acute setting.

Adult serum cytokine concentrations and the persistence of asthma.

BACKGROUND: Cytokines play a pivotal role in regulating the development and persistence of the inflammatory process in asthma. Our aim was to investigate whether asthma persistence or remission is associated with a specific cytokine profile. METHODS: The Tasmanian Longitudinal Health Study followed participants from 7 to 44 years of age. Serum concentrations of interleukin (IL)-4, IL-5, IL-6, IL-8, IL-10 and tumor necrosis factor-alpha (TNF-α) were measured at age 44 years. Participants were categorized into five phenotypes (early-onset noncurrent asthma, early-onset current asthma, late-onset noncurrent asthma and late-onset current asthma). Those who had never had asthma formed the reference group. Multivariable linear regression was used to compare serum cytokine concentrations between each phenotype and the reference group. RESULTS: IL-10 concentrations were significantly lower in serum from the early-onset current asthma group than in the reference group (ratio of geometric means 0.58; 95% confidence interval 0.33-0.99; p = 0.048). IL-6 concentrations for the late-onset remitted group were also significantly lower than in the reference group (p = 0.009). The TNF-α concentrations were significantly lower for both early-and late-onset remitted asthma phenotypes when compared with the reference group. No associations were detected between serum concentrations of IL-4, IL-5 or IL-8 and these specific longitudinal asthma phenotypes. CONCLUSION: Our findings suggest a possible role for deficient IL-10 responses in the persistence of early-onset asthma. Lower IL-6 and TNF-α concentrations in serum from those with remitted asthma suggest that these proinflammatory cytokines may be actively suppressed during asthma remission.

Uptake and effectiveness of a community pharmacy intervention programme to improve asthma management.

WHAT IS KNOWN AND OBJECTIVE: Pharmacists frequently see patients with asthma in the community who have suboptimal management. This study aimed to compare the uptake and effectiveness of pharmacist-initiated mailed and face-to-face interventions for patients whose asthma may not be well managed. METHODS: Seventy-one community pharmacies in South Australia, Tasmania and Victoria (Australia) installed a software application that data-mined dispensing records, generating a list of patients who had received six or more asthma reliever inhalers in the preceding 12 months. The pharmacists were randomized, by pharmacy, to perform either a mailed or face-to-face intervention, whereby these patients received educational material and a referral to their general practitioner (GP) for an asthma management review. Matching patients from each pharmacy were also randomly assigned to a control group for 'usual care'. RESULTS AND DISCUSSION: A total of 1483 patients were identified and grouped as follows: 510 (34·4%) mailed intervention, 480 (32·4%) face-to-face intervention and 493 (33·2%) controls. Significantly fewer face-to-face interventions were offered than mailed interventions (66·6% vs. 89·4%, respectively; χ(2) = 64·2, P < 0·0001). There were significant improvements in the preventer-to-reliever ratio after the intervention period (P < 0·0001) in each group. In a per-protocol analysis, the magnitude of improvement in the face-to-face intervention group was greater than in the mailed intervention group. The reverse was true in an intention-to-treat analysis. The improvement in the P : R ratios was mainly due to significant decreases in reliever usage. WHAT IS NEW AND CONCLUSION: Community pharmacy dispensing records can effectively identify patients with suboptimal asthma management, who can then be referred to their GP for review. Time constraints in busy pharmacies may limit the uptake and effectiveness of face-to-face interventions in the 'real world' setting, making mailed interventions an attractive option.

The sustainability of a community pharmacy intervention to improve the quality use of asthma medication.

WHAT IS KNOWN AND OBJECTIVE: A previously published asthma intervention used a software application to data mine pharmacy dispensing records and generate a list of patients with potentially suboptimal management of their asthma; in particular, a high rate of provision of reliever medication. These patients were sent educational material from their community pharmacists and advised to seek a review of their asthma management from their general practitioner. The intervention resulted in a 3-fold improvement in the ratio of dispensed preventer medication (inhaled corticosteroids) to reliever medication (short-acting beta-2 agonists). This follow-up study aimed to determine the long-term effects of the intervention programme on the preventer-to-reliever (P:R) ratio. METHODS: The same data mining software was modified so that it could re-identify patients who were originally targeted for the intervention. Community pharmacists who participated in the previous intervention installed the modified version of the software. The dispensing data were then de-identified, encrypted and transferred via the Internet to a secure server. The follow-up dispensing data for all patients were compared with their pre- and post-intervention data collected originally. RESULTS AND DISCUSSION: Of the 1551 patients who were included in the original study, 718 (46·3%) were eligible to be included in the follow-up study. The improved P:R ratio was sustained for at least 12 months following the intervention (P < 0·01). The sustained increase in the P:R ratio was attributed to significant decreases in the average daily usage of reliever medication (P < 0·0001). WHAT IS NEW AND CONCLUSION: The follow-up study demonstrated a sustained improvement in the ratio of dispensed preventer medication to reliever medication for asthma. The intervention has the potential to show long-lasting and widespread improvements in asthma management, improved health outcomes for patients, and ultimately, a reduced burden on the health system.

Ambient wood smoke exposure and respiratory symptoms in Tasmania, Australia.

Wood smoke exposure has been associated with adverse respiratory health outcomes, with much of the current research focused on wood smoke from domestic heating and cooking. This study examined the association between respiratory symptoms and outdoor wood smoke in Launceston, Tasmania, where ~30% of homes use wood burners for domestic heating. This ecological study examined data from participants of the 2004 Tasmanian Longitudinal Health Study postal survey and compared the prevalence of respiratory symptoms in Launceston (n=601) with that in Hobart (n=1071), a larger Tasmanian city with much less wood smoke. Multivariate logistic regression models were used to investigate the associations of interest while adjusting for gender, atopy, history of allergic disease and current smoking status. There were no significant differences in symptom prevalence between Launceston and Hobart. Two subgroup analyses, which examined participants with pre-existing chronic respiratory disease, and those who reported actively using a wood burner in their home, also did not find significant differences. Any impact of wood smoke on non-specific respiratory symptoms might have been overshadowed by other important determinants of respiratory health, such as vehicle exhaust and tobacco smoking, or were too small to have been detected. However, the lack of detectable differences in symptom prevalence might also reflect the success of regulatory action by local governments to reduce wood smoke emissions in Launceston. The results of other epidemiological studies support an association between ambient wood smoke exposure and adverse respiratory health. Further investigations of wood smoke exposure in Australian settings are needed to investigate the lack of significant associations found in this study, especially studies of indoor air quality and health impacts in children and elderly populations.

Poor lung function and tonsillectomy in childhood are associated with mortality from age 18 to 44.

BACKGROUND: The aim of this analysis was to examine associations between lung health in childhood and mortality between ages 18 and 44 years in the Tasmanian Longitudinal Health Study (TAHS). METHODS: The 1961 Tasmanian birth cohort who attended school in 1968 (n=8583) were linked to the Australian National Death Index (NDI) to identify deaths. Additional deaths were notified by families through a 37 year follow-up postal questionnaire. Information on lung health at age 7 years and on potential confounders was obtained from the original 1968 TAHS survey and school medical records. Cox proportional hazards modelling was used to assess determinants of mortality. RESULTS: A total of 264 (3%) deaths were identified. The principal causes of death were external injury (56.1%, n=97) and cancer (17.9%, n=31). Males were more likely than females to have died (p=<0.1). Only two (1.1%) participants had died from respiratory conditions. Having an FEV(1)<80% predicted at 7 years of age was associated with a 2-fold increased incidence of death. Tonsillectomy before age 7 years was associated with a 1.5-fold increase in mortality (p=0.05); being male with a 3.6-fold increase in mortality (p=0.0001); and repeated chest illnesses at age 7 years causing >30 days confinement in the last year, was associated with a 2.2-fold increase in mortality (p=0.03). CONCLUSIONS: Childhood lung health appears to be associated with increased mortality in adulthood, perhaps by affecting the ability to survive trauma, major illnesses and other physical stresses.

Increased vascular permeability precedes cellular inflammation as asthma control deteriorates.

BACKGROUND: Airway microcirculation is abnormal in asthma but the role of vascular changes in asthma deteriorations remains poorly defined. We prospectively assessed the vascular changes accompanying worsening of asthma control by using an inhaled corticosteroid (ICS) dose-reduction model. OBJECTIVES: To evaluate airway vascularity, vascular permeability and expression of vascular endothelial growth factor (VEGF) in early asthma deterioration induced by ICS back-titration. METHODS: Twenty mild-to-moderate persistent symptomatic asthmatics on low-to-moderate ICS were recruited and treated with 4 weeks of high-dose fluticasone propionate (1000 microg/day) to achieve symptom control. This was followed by dose reduction to half of the pre-study doses for 4-8 weeks until the symptoms began to return. Endobronchial biopsy and bronchoalveolar lavage (BAL) samples were obtained after both treatment periods. RESULTS: Vascularity as measured by the number and size of blood vessels, as well as VEGF expression did not change following ICS reduction. Even on high-dose ICS, perivascular albumin staining and BAL microalbumin levels in asthmatic subjects, as markers of permeability, were elevated when compared with normal subjects and both further increased significantly after ICS reduction. There was a significant association between changes in vascular leakiness and clinical deterioration. Increases in airway albumin correlated with previously reported increases in airway wall infiltration with T lymphocytes. CONCLUSIONS: Our results suggest that airway vascular leakage is a major pathophysiologic feature of early asthma deterioration, occurring before recrudescence of cellular inflammation.

Adherence to asthma management guidelines by middle-aged adults with current asthma.

BACKGROUND: With the increasing burden of asthma worldwide, much effort has been given to developing and updating management guidelines. Using data from the Tasmanian Longitudinal Health Study (TAHS), the adequacy of asthma management for middle-aged adults with asthma was investigated. METHODS: Information about spirometry, medication history and current asthma status was collected by the most recent TAHS when participants were in their mid 40s. Only those who reported ever having asthma were eligible for analysis. RESULTS: Of the 702 participants who reported ever having asthma, 50% had current asthma (n = 351) of whom 71% were categorised as having persistent asthma (n = 98 mild, n = 92 moderate, n = 58 severe). The majority (85.2%) of participants with current asthma had used some form of asthma medication in the past 12 months, but the proportion of the use of minimally adequate preventer medication was low (26%). Post-bronchodilator airflow obstruction increased progressively from mild to severe persistent asthma for those inadequately managed, but not for those on adequate therapy. CONCLUSION: Appropriate use of asthma medication by this middle-aged group of adults with current asthma was inadequate, especially for those with adult-onset moderate or severe persistent disease and without a family history of asthma. These results suggest that proper use of preventer medication could protect against the progressive decline in lung function associated with increasing severity. This has implications not just for poor quality of life, but also for the development of fixed airflow obstruction.

Relevance of the hygiene hypothesis to early vs. late onset allergic rhinitis.

INTRODUCTION: The hygiene hypothesis proposes that reduced exposure to infections in early life increases the risk of developing allergic conditions including allergic rhinitis. We examined the association between markers of the hygiene hypothesis and allergic rhinitis that developed before 7 years of age and allergic rhinitis that developed after 7 years of age. METHODS: The Tasmanian Longitudinal Health Study (TAHS) is a population-based cohort (n=8583) study of respiratory disease. Participants have been followed from 7 to 44 years of age. Information on potential risk factors, allergies and respiratory symptoms was collected longitudinally. Using multi-nomial logistic regression, exposure to siblings, infections, tonsillectomy and farm residence during childhood were examined as risk factors for allergic rhinitis that developed before or after 7 years of age. All analyses were adjusted for gender, maternal and paternal atopy, mother's age at participant's birth, paternal socio-economic status in 1968 and personal socio-economic status in 2004. RESULTS: Greater cumulative exposure to siblings before the age of 2 years was strongly inversely associated with early onset allergic rhinitis (<1 year sib exposure: OR=0.6, 95% CI 0.3-1.0; 1-3 years sib exposure: OR=0.6, 95% CI 0.4-0.9; >3 years sib exposure: OR=0.4, 95% CI 0.3-0.8) less so with later onset allergic rhinitis. The risk of early onset allergic rhinitis decreased with increasing viral infections (OR=0.7, 95% CI 0.5-0.9) during childhood. Having a tonsillectomy before 7 years of age increased the risk of early onset allergic rhinitis (OR=1.7, 95% CI 1.2-2.5). None of these factors was associated with later onset allergic rhinitis. CONCLUSIONS: Exposures relevant to the hygiene hypothesis were important predictors for the development of early onset but less so for later onset allergic rhinitis. The exact mechanisms by which siblings and infections protect against allergic rhinitis are unclear. The stronger findings for earlier onset allergic rhinitis suggest that family structure and infections have most impact on disease risk in early life. Further research should focus on early onset allergic rhinitis when exploring causal explanations for any sibling effect.

Prediction equations for single breath diffusing capacity (Tlco) in a middle aged caucasian population.

BACKGROUND: There are many reference equations for the measurement of single breath carbon monoxide diffusing capacity of the lung (Tlco). However, the testing methodologies vary and there are no well documented studies that have developed reference equations for Tlco and alveolar volume (Va) in middle aged and older populations. AIMS: (1) Develop reference equations for Tlco in a middle aged population using the current American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines; (2) compare the equations with those commonly used in laboratories around the world. METHODS: Healthy subjects (498 male and 474 female) aged 45-71 years were recruited as part of a larger epidemiological study. All participants completed a respiratory questionnaire and had spirometry and single breath Tlco (corrected for haemoglobin) measurements following ATS/ERS guidelines. RESULTS: Mean age was 58 years for males and 57 years for females. For males, factors that predicted Tlco were: height, age, agexheight interaction and being an ex-smoker. For females, factors that predicted Tlco were: height, age, weight and an agexheight interaction. CONCLUSION: We have described new prediction equations for Tlco in a middle aged population that require validation in other populations.

A mixed methods study to compare models of spirometry delivery in primary care for patients at risk of COPD.

BACKGROUND: To increase recognition of airflow obstruction in primary care, we compared two models of spirometry delivery in a target group at risk of chronic obstructive pulmonary disease (COPD). METHODS: A 6 month qualitative/quantitative cluster randomised study in eight practices compared opportunistic spirometry by "visiting trained nurses" (TN) with optimised "usual care" (UC) from general practitioners (GPs) for smokers and ex-smokers, aged over 35 years. Outcomes were: spirometry uptake and quality, new diagnoses of COPD and GPs' experiences of spirometry. RESULTS: In the eligible target population, 531/904 (59%) patients underwent spirometry in the TN model and 87/1130 (8%) patients in the UC model (p < 0.0001). ATS spirometry standards for acceptability and reproducibility were met by 76% and 44% of tests in the TN and UC models, respectively (p < 0.0001). 125 (24%) patients tested with the TN model and 38 (44%) with the UC model reported a pre-existing respiratory diagnosis (p < 0.0001). Three months after spirometry, when the ratio of forced expiratory volume in 1 s/forced vital capacity (FEV(1)/FVC) was < 0.7 and no prior COPD diagnosis was reported, nine (8%) participants had a new doctor recorded COPD diagnosis in practices with the TN model and two (8%) participants in practices with the UC model. Mislabelling of participants with a diagnosis of COPD when FEV(1)/FVC was > or = 0.7 was present in both models prior to and after spirometry. GPs valued high quality spirometry and increased testing of patients at risk of COPD in the TN model. They identified limitations, including the need for better systematic follow-up of abnormal spirometry and support with interpretation, which may explain persisting underdiagnosis of COPD in practice records. CONCLUSIONS: Although opportunistic testing by visiting trained nurses substantially increased and improved spirometry performance compared with usual care, translating increased detection of airflow obstruction into diagnosis of COPD requires further development of the model. TRIAL REGISTRATION NUMBER: Australian Clinical Trials Registry: registration No 12605000019606.

Self-management education for patients with chronic obstructive pulmonary disease.

BACKGROUND: There is great interest in chronic obstructive pulmonary disease (COPD) and the associated large burden of disease. COPD is characterised by frequent day by day fluctuations, and repetitive clinical exacerbations are typical. Self-management is a term applied to educational programmes aimed at teaching skills needed to carry out medical regimens specific to the disease, guide health behaviour change, and provide emotional support for patients to control their disease and live functional lives. In COPD, the value of self-management education is not yet clear. The first Cochrane review about self-management was published in 2003. It was intended to shed light on the effectiveness of self-management programmes in COPD and the relative efficacy of their constitutive elements. No conclusions about the effectiveness of self-management could be drawn because of the large variation in outcome measures used in the limited number of included studies. This article describes the first update of this review. OBJECTIVES: The objective of this review was to assess the settings, methods and efficacy of COPD self-management education programmes on health outcomes and use of health care services. SEARCH STRATEGY: We searched the Cochrane Airways Group trial register, MEDLINE (January 1985 to January 2006), reference lists, and abstracts of medical conferences. SELECTION CRITERIA: Controlled trials (randomised and non-randomised) of self-management education in patients with COPD. Studies focusing mainly on pulmonary rehabilitation and studies without usual care as a control group were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed study quality and extracted data. Investigators were contacted for additional information. MAIN RESULTS: The reviewers included 15 group comparisons drawn from 14 trials. They assessed a broad-spectrum of interventions and health outcomes with different follow-up times. Meta-analyses could often not appropriately be performed because of heterogeneity among studies. The studies showed a significant reduction in the probability of at least one hospital admission among patients receiving self-management education compared to those receiving usual care (OR 0.64; 95% CI (0.47 to 0.89)). This translates into a one year NNT ranging from 10 (6 to 35) for patients with a 51% risk of exacerbation, to an NNT of 24 (16 to 80) for patients with a 13% risk of exacerbation. On the disease specific SGRQ, differences reached statistical significance at the 5% level on the total score (WMD -2.58; 95% CI (-5.14 to -0.02)) and impact domain (WMD -2.83; 95% CI (-5.65 to -0.02)), but these difference did not reach the clinically relevant improvement of 4 points. A small but significant reduction was detected in dyspnoea measured with the BORG-scale (WMD -0.53; 95% CI (-0.96 to -0.10)). No significant effects were found either in number of exacerbations, emergency department visits, lung function, exercise capacity, and days lost from work. Inconclusive results were observed in doctor and nurse visits, on symptoms other than dyspnoea, the use of courses of oral corticosteroids and antibiotics, and the use of rescue medication. AUTHORS' CONCLUSIONS: It is likely that self-management education is associated with a reduction in hospital admissions with no indications for detrimental effects in other outcome parameters. This would in itself already be enough reason for recommending self-management education in COPD. However, because of heterogeneity in interventions, study populations, follow-up time, and outcome measures, data are still insufficient to formulate clear recommendations regarding the form and contents of self-management education programmes in COPD. There is an evident need for more large RCTs with a long-term follow-up, before more conclusions can be drawn.

Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling.

In the present review of airway remodelling and its response to therapies, clinical observations about airway physiological abnormalities, assumed to be caused by remodelling processes, are related to what is known about the components of structural changes from airway sampling and histopathological analysis. The review focuses on three important diseases: asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome (BOS), which occurs commonly after lung transplantation as a manifestation of chronic rejection. The present authors chose to use BOS as an issue, because with routine bronchoscopic surveillance after lung transplantation there has been more opportunity to directly study airway pathology longitudinally than in more everyday conditions. In addition, the present authors have reviewed animal models of induced airway remodelling, where most information is available on the potential of therapeutic intervention. Finally, the limited information that can be gained from the literature on the effects of commonly used airway medications on remodelling components is reviewed. In conclusion, the present authors have detailed some of the gaps in knowledge surrounding the potential to improve or modulate remodelling processes in human disease. The areas where it is believed urgent research needs to be focused have also been highlighted.