Association between very to moderate preterm births, lung function deficits, and COPD at age 53 years: analysis of a prospective cohort study.

BACKGROUND: Prematurity has been linked to reduced lung function up to age 33 years, but its long-term effects on lung function and chronic obstructive pulmonary disease (COPD) are unknown. To address this question, we investigated associations between prematurity, lung function, and COPD in the sixth decade of life using data from the Tasmanian Longitudinal Health Study (TAHS). METHODS: Data were analysed from 1445 participants in the TAHS. Lung function was measured at 53 years of age. Gestational ages were very preterm (28 weeks to <32 weeks), moderate preterm (32 weeks to <34 weeks), late preterm (34 weeks to <37 weeks) and term (≥37 weeks). Linear and logistic regression models were fitted to investigate associations of prematurity with lung function measures (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, forced expiratory flow at 25-75% of FVC [FEF25-75%], diffusing capacity for carbon monoxide [DLCO]) and COPD (post-bronchodilator FEV1/FVC less than the lower limit of normal), adjusting for sex, age, height, parental smoking during pregnancy, number of older siblings, maternal age at birth, and childhood socioeconomic status. Interactions with smoking and asthma were also investigated. RESULTS: Of 3565 individuals with available data on gestational age from the TAHS cohort, 1445 (41%) participants were included in this study, 740 (51%) of whom were female. Compared with term birth, very to moderate preterm birth was significantly associated with an increased risk of COPD at age 53 years (odds ratio 2·9 [95% CI 1·1-7·7]). Very-to-moderate preterm birth was also associated with lower post-bronchodilator FEV1/FVC ratio (beta-coefficient -2·9% [95% CI -4·9 to -0·81]), FEV1 (-190 mL [-339 to -40]), DLCO (-0·55 mmol/min/kPa [-0·97 to -0·13]), and FEF25-75% (-339 mL/s [-664 to -14]). The association between very-to-moderate preterm birth and FEV1/FVC ratio was only significant among smokers (pinteraction=0·0082). Similar findings were observed for moderate preterm birth when analysed as a separate group. Compared with term birth, late preterm birth was not associated with lower FEV1/FVC ratio or COPD. INTERPRETATION: This is the first study to investigate the effect of prematurity on lung function into middle-age. Data show that very-to-moderate prematurity is associated with obstructive lung function deficits including COPD well into the sixth decade of life and that this effect is compounded by personal smoking. FUNDING: National Health and Medical Research Council (NHMRC) of Australia, European Union's Horizon 2020, The University of Melbourne, Clifford Craig Medical Research Trust of Tasmania, The Victorian, Queensland & Tasmanian Asthma Foundations, The Royal Hobart Hospital, Helen MacPherson Smith Trust, and GlaxoSmithKline.

Ten-year prediction model for post-bronchodilator airflow obstruction and early detection of COPD: development and validation in two middle-aged population-based cohorts.

BACKGROUND: Classifying individuals at high chronic obstructive pulmonary disease (COPD)-risk creates opportunities for early COPD detection and active intervention. OBJECTIVE: To develop and validate a statistical model to predict 10-year probabilities of COPD defined by post-bronchodilator airflow obstruction (post-BD-AO; forced expiratory volume in 1 s/forced vital capacity<5th percentile). SETTING: General Caucasian populations from Australia and Europe, 10 and 27 centres, respectively. PARTICIPANTS: For the development cohort, questionnaire data on respiratory symptoms, smoking, asthma, occupation and participant sex were from the Tasmanian Longitudinal Health Study (TAHS) participants at age 41-45 years (n=5729) who did not have self-reported COPD/emphysema at baseline but had post-BD spirometry and smoking status at age 51-55 years (n=2407). The validation cohort comprised participants from the European Community Respiratory Health Survey (ECRHS) II and III (n=5970), restricted to those of age 40-49 and 50-59 with complete questionnaire and spirometry/smoking data, respectively (n=1407). STATISTICAL METHOD: Risk-prediction models were developed using randomForest then externally validated. RESULTS: Area under the receiver operating characteristic curve (AUCROC) of the final model was 80.8% (95% CI 80.0% to 81.6%), sensitivity 80.3% (77.7% to 82.9%), specificity 69.1% (68.7% to 69.5%), positive predictive value (PPV) 11.1% (10.3% to 11.9%) and negative predictive value (NPV) 98.7% (98.5% to 98.9%). The external validation was fair (AUCROC 75.6%), with the PPV increasing to 17.9% and NPV still 97.5% for adults aged 40-49 years with ≥1 respiratory symptom. To illustrate the model output using hypothetical case scenarios, a 43-year-old female unskilled worker who smoked 20 cigarettes/day for 30 years had a 27% predicted probability for post-BD-AO at age 53 if she continued to smoke. The predicted risk was 42% if she had coexistent active asthma, but only 4.5% if she had quit after age 43. CONCLUSION: This novel and validated risk-prediction model could identify adults aged in their 40s at high 10-year COPD-risk in the general population with potential to facilitate active monitoring/intervention in predicted 'COPD cases' at a much earlier age.

Lung function trajectory and biomarkers in the Tasmanian Longitudinal Health Study.

BACKGROUND AND OBJECTIVE: Different lung function trajectories through life can lead to COPD in adulthood. This study investigated whether circulating levels of biomarkers can differentiate those with accelerated (AD) from normal decline (ND) trajectories. METHODS: The Tasmanian Longitudinal Health Study (TAHS) is a general population study that measured spirometry and followed up participants from ages 7 to 53 years. Based on their forced expiratory volume in 1 s (FEV1) trajectories from age 7 to 53 years, this analysis included those with COPD at age 53 years (60 with AD and 94 with ND) and controls (n=720) defined as never-smokers with an average FEV1 trajectory. Circulating levels of selected biomarkers determined at 53 and 45 years of age were compared between trajectories. RESULTS: Results showed that CC16 levels (an anti-inflammatory protein) were lower and C-reactive protein (CRP) (a pro-inflammatory marker) higher in the AD than in the ND trajectory. Higher CC16 levels were associated with a decreased risk of belonging to the AD trajectory (OR=0.79 (0.63-0.98) per unit increase) relative to ND trajectory. Higher CRP levels were associated with an increased risk of belonging to the AD trajectory (OR=1.07, 95% CI: 1.00-1.13, per unit increase). Levels of CC16 (area under the curve (AUC)=0.69, 95% CI: 0.56-0.81, p=0.002), CRP (AUC=0.63, 95% CI: 0.53-0.72, p=0.01) and the combination of both (AUC=0.72, 95% CI: 0.60-0.83, p<0.001) were able to discriminate between the AD and ND trajectories. Other quantified biomarkers (interleukin (IL)-4, IL-5, IL-6, IL-10 and tumour necrosis factor-α (TNF-α)) were not significantly different between AD, ND and controls. CONCLUSIONS: Circulating levels of CRP and CC16 measured in late adulthood identify different lung function trajectories (AD versus ND) leading to COPD at age 53 years.

Exposure to household air pollution over 10†years is related to asthma and lung function decline.

INTRODUCTION: We investigated if long-term household air pollution (HAP) is associated with asthma and lung function decline in middle-aged adults, and whether these associations were modified by glutathione S-transferase (GST) gene variants, ventilation and atopy. MATERIALS AND METHODS: Prospective data on HAP (heating, cooking, mould and smoking) and asthma were collected in the Tasmanian Longitudinal Health Study (TAHS) at mean ages 43 and 53 years (n=3314). Subsamples had data on lung function (n=897) and GST gene polymorphisms (n=928). Latent class analysis was used to characterise longitudinal patterns of exposure. Regression models assessed associations and interactions. RESULTS: We identified seven longitudinal HAP profiles. Of these, three were associated with persistent asthma, greater lung function decline and % reversibility by age 53 years compared with the "Least exposed" reference profile for those who used reverse-cycle air conditioning, electric cooking and no smoking. The "All gas" (OR 2.64, 95% CI 1.22-5.70), "Wood heating/smoking" (OR 2.71, 95% CI 1.21-6.05) and "Wood heating/gas cooking" (OR 2.60, 95% CI 1.11-6.11) profiles were associated with persistent asthma, as well as greater lung function decline and % reversibility. Participants with the GSTP1 Ile/Ile genotype were at a higher risk of asthma or greater lung function decline when exposed compared with other genotypes. Exhaust fan use and opening windows frequently may reduce the adverse effects of HAP produced by combustion heating and cooking on current asthma, presumably through increasing ventilation. CONCLUSIONS: Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation.

Comparative Responses in Lung Function Measurements with Tiotropium in Adolescents and Adults, and Across Asthma Severities: A Post Hoc Analysis.

INTRODUCTION: Airway obstruction is usually assessed by measuring forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow (PEF). This post hoc study investigated comparative responses of lung function measurements in adults and adolescents (full analysis set, N = 3873) following treatment with tiotropium Respimat®. METHODS: Lung function outcomes were analysed from five phase III trials in adults (≥ 18 years) with symptomatic severe, moderate and mild asthma (PrimoTinA-asthma®, MezzoTinA-asthma® and GraziaTinA-asthma®, respectively), and one phase III trial in adolescents (12-17 years) with symptomatic moderate asthma (RubaTinA-asthma®). Changes from baseline versus placebo in FEV1, FVC, PEF and FEV1/FVC ratio with tiotropium 5 µg or 2.5 µg added to at least stable inhaled corticosteroids at week 24 (week 12 in GraziaTinA-asthma) were analysed. RESULTS: All lung function measures improved in all studies with tiotropium 5 µg (mean change from baseline versus placebo), including peak FEV1 (110-185 mL), peak FVC (57-95 mL) and morning PEF (15.8-25.6 L/min). Changes in adolescents were smaller than those in adults, and were statistically significant primarily for FEV1 and PEF, but not for FVC. CONCLUSION: Consistent improvements were seen across all lung function measures with the addition of tiotropium to other asthma treatments in adults across all severities, whereas the improvements with tiotropium in adolescents primarily impacted measures of flow rather than lung volume. This may reflect less pronounced airway remodelling and air trapping in adolescents with asthma versus adults.

Asthma is characterised by problems with the way that the lungs work, particularly narrowing of the airways. Doctors can measure the effect of asthma on someone's breathing in different ways. We looked to see whether these different methods work for different people with asthma, and whether treatment affects all measurements in a similar way. Lung function was measured after treatment with a drug that opens the airways (tiotropium), and comparisons were made between adults and adolescents with asthma. We also looked at people with severe asthma and those whose asthma was less severe. Tiotropium improved all the measures of lung function in both age groups and across severities. One measure improved more in adults than in adolescents. This may be because adolescents had better lung function at the start and thus less room for improvement, or because the adolescents had not had asthma for as long, and so may have had less long-term damage to their airways than adults.Trial Registration Numbers: NCT00772538, NCT00776984, NCT01172808, NCT01172821, NCT01316380, NCT01257230.

Parental and life-course influences on symptomatic airflow obstruction.

Few studies have examined the contribution of life-course factors in explaining familial aggregation of chronic lung conditions. Using data from the 1958 British Birth Cohort, a life-course approach was used to examine whether, and how, exposure to risk factors through one's life explained the association between parental respiratory disease history and symptomatic airflow obstruction (AO). Cohort participants (n=6212) were characterised in terms of parental respiratory disease history and symptomatic AO at 45 years. Life-course factors (e.g. smoking, asthma and early-life factors) were operationalised as life period-specific and cumulative measures. Logistic regression and path analytic models predicting symptomatic AO adjusted for parental respiratory disease history were used to test different life-course models (critical period, accumulation- and chain-of-risks models). While some life-course factors (e.g. childhood passive smoking and occupational exposure) were individually associated with parental respiratory disease history and symptomatic AO, asthma (OR 6.44, 95% CI 5.01-8.27) and persistent smoking in adulthood (OR 5.42, 95% CI 4.19-7.01) had greater impact on the association between parental respiratory disease history and symptomatic AO. A critical period model provided a better model fit compared with an accumulation-of-risk model and explained 57% of the effect of parental respiratory disease history on symptomatic AO. Adulthood asthma and smoking status explained around half of the effect of parental respiratory disease history on chronic obstructive pulmonary disease. Beyond smoking history, the combination of parental respiratory disease history and adulthood asthma may provide an opportunity for early diagnosis and intervention.

Factors influencing management of chronic respiratory diseases in general and chronic obstructive pulmonary disease in particular in Saudi Arabia: An overview.

The prevalence of chronic obstructive pulmonary disease in Saudi Arabia is 4.2% among the general population and 14.2% among smokers. Studies showed that management of respiratory diseases is inadequate. In this article, we have elaborated on how factors as health economic factors, lack of health-care providers, culture, attitude, lifestyle (such as smoking and physical inactivity), and lack of adherence to the evidence-based practice guidelines may influence chronic respiratory disease management in Saudi Arabia. We have to conclude that these factors should be taken into account while seeking to improve and optimize the quality of care for patients with respiratory diseases in Saudi Arabia.

Childhood Respiratory Risk Factor Profiles and Middle-Age Lung Function: A Prospective Cohort Study from the First to Sixth Decade.

RATIONALE: Childhood risk factors for long-term lung health often coexist and their specific patterns may affect subsequent lung function differently. OBJECTIVES: To identify childhood risk factor profiles and their influence on lung function and chronic obstructive pulmonary disease (COPD) in middle age, and potential pathways. METHODS: Profiles of 11 childhood respiratory risk factors, documented at age 7, were identified in 8,352 participants from the Tasmanian Longitudinal Health Study using latent class analysis. We investigated associations between risk profiles and post-bronchodilator lung function and COPD at age 53, mediation by childhood lung function and adult asthma, and interaction with personal smoking. RESULTS: Six risk profiles were identified: 1) unexposed or least exposed (49%); 2) parental smoking (21.5%); 3) allergy (10%); 4) frequent asthma, bronchitis (8.7%); 5) infrequent asthma, bronchitis (8.3%); and 6) frequent asthma, bronchitis, allergy (2.6%). Profile 6 was most strongly associated with lower forced expiratory volume in 1 second (FEV1) (-261; 95% confidence interval, -373 to -148 ml); lower FEV1/forced vital capacity (FVC) (-3.4; -4.8 to -1.9%) and increased COPD risk (odds ratio, 4.9; 2.1 to 11.0) at age 53. The effect of profile 6 on COPD was largely mediated by adult active asthma (62.5%) and reduced childhood lung function (26.5%). Profiles 2 and 4 had smaller adverse effects than profile 6. Notably, the effects of profiles 2 and 6 were synergistically stronger for smokers. CONCLUSIONS: Profiles of childhood respiratory risk factors predict middle-age lung function levels and COPD risk. Specifically, children with frequent asthma attacks and allergies, especially if they also become adult smokers, are the most vulnerable group. Targeting active asthma in adulthood (i.e., a dominant mediator) and smoking (i.e., an effect modifier) may block causal pathways and lessen the effect of such established early-life exposures.

Childhood predictors of lung function trajectories and future COPD risk: a prospective cohort study from the first to the sixth decade of life.

BACKGROUND: Lifetime lung function is related to quality of life and longevity. Over the lifespan, individuals follow different lung function trajectories. Identification of these trajectories, their determinants, and outcomes is important, but no study has done this beyond the fourth decade. METHODS: We used six waves of the Tasmanian Longitudinal Health Study (TAHS) to model lung function trajectories measured at 7, 13, 18, 45, 50, and 53 years. We analysed pre-bronchodilator FEV1 z-scores at the six timepoints using group-based trajectory modelling to identify distinct subgroups of individuals whose measurements followed a similar pattern over time. We related the trajectories identified to childhood factors and risk of chronic obstructive pulmonary disease (COPD) using logistic regression, and estimated population-attributable fractions of COPD. FINDINGS: Of the 8583 participants in the original cohort, 2438 had at least two waves of lung function data at age 7 years and 53 years and comprised the study population. We identified six trajectories: early below average, accelerated decline (97 [4%] participants); persistently low (136 [6%] participants); early low, accelerated growth, normal decline (196 [8%] participants); persistently high (293 [12%] participants); below average (772 [32%] participants); and average (944 [39%] participants). The three trajectories early below average, accelerated decline; persistently low; and below average had increased risk of COPD at age 53 years compared with the average group (early below average, accelerated decline: odds ratio 35·0, 95% CI 19·5-64·0; persistently low: 9·5, 4·5-20·6; and below average: 3·7, 1·9-6·9). Early-life predictors of the three trajectories included childhood asthma, bronchitis, pneumonia, allergic rhinitis, eczema, parental asthma, and maternal smoking. Personal smoking and active adult asthma increased the impact of maternal smoking and childhood asthma, respectively, on the early below average, accelerated decline trajectory. INTERPRETATION: We identified six potential FEV1 trajectories, two of which were novel. Three trajectories contributed 75% of COPD burden and were associated with modifiable early-life exposures whose impact was aggravated by adult factors. We postulate that reducing maternal smoking, encouraging immunisation, and avoiding personal smoking, especially in those with smoking parents or low childhood lung function, might minimise COPD risk. Clinicians and patients with asthma should be made aware of the potential long-term implications of non-optimal asthma control for lung function trajectory throughout life, and the role and benefit of optimal asthma control on improving lung function should be investigated in future intervention trials. FUNDING: National Health and Medical Research Council of Australia; European Union's Horizon 2020; The University of Melbourne; Clifford Craig Medical Research Trust of Tasmania; The Victorian, Queensland & Tasmanian Asthma Foundations; The Royal Hobart Hospital; Helen MacPherson Smith Trust; and GlaxoSmithKline.

Fish oil supplementation in chronic obstructive pulmonary disease: feasibility of conducting a randomised controlled trial.

BACKGROUND: Long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFAs) may act as an effective adjunct therapy for chronic obstructive pulmonary disease (COPD), a condition characterised by persistent airflow limitation and inflammation. However, the nature of this illness presents challenges for evaluating potential benefits. The aim of this study was to determine the feasibility of undertaking a randomised controlled trial of LCn-3PUFA supplementation in adults with COPD. METHODS: A 16-week parallel, double-blind, randomised, placebo-controlled dietary supplementation trial was conducted. Participants diagnosed with COPD were randomly allocated to take six 1-g capsules of fish oil (3.6 g LCn-3PUFA) or corn oil (placebo) daily for 16 weeks. Key outcomes used to determine the feasibility of the trial included recruitment rate, participant retention rate and supplement adherence (blood biomarker and returned capsule count). An estimate of the effect size for clinical outcomes such as pulmonary function and functional exercise capacity was calculated. RESULTS: None of the key feasibility criteria were met. The enrolment target was 40 participants in 52 weeks; however, only 13 were finally enrolled, with just seven in the first 52 weeks. Eight participants completed the study (retention rate 62%). Targets for compliance were not achieved; red blood cell LCn-3PUFA content (expressed as percentage of total fatty acids) did not increase by more than 2% in the fish oil group; capsule counts were unreliable. As the target sample size was not achieved and only a small number of participants completed the study, it was not possible to use the variance in clinical outcomes to estimate a sample size for a future study. CONCLUSIONS: This study highlights major difficulties, especially with recruitment, in conducting this LCn-3PUFA supplementation trial in people with COPD, rendering the protocol unfeasible by predetermined criteria. A modified approach is needed to investigate potential health benefits of fish oil in people with COPD. A multicentre study with changes to inclusion and exclusion criteria is recommended. TRIAL REGISTRATION: Australia and New Zealand Clinical Trials Register (ANZCTR), ACTRN12612000158864.

Self-management interventions including action plans for exacerbations versus usual care in patients with chronic obstructive pulmonary disease.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) self-management interventions should be structured but personalised and often multi-component, with goals of motivating, engaging and supporting the patients to positively adapt their behaviour(s) and develop skills to better manage disease. Exacerbation action plans are considered to be a key component of COPD self-management interventions. Studies assessing these interventions show contradictory results. In this Cochrane Review, we compared the effectiveness of COPD self-management interventions that include action plans for acute exacerbations of COPD (AECOPD) with usual care. OBJECTIVES: To evaluate the efficacy of COPD-specific self-management interventions that include an action plan for exacerbations of COPD compared with usual care in terms of health-related quality of life, respiratory-related hospital admissions and other health outcomes. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register of trials, trials registries, and the reference lists of included studies to May 2016. SELECTION CRITERIA: We included randomised controlled trials evaluating a self-management intervention for people with COPD published since 1995. To be eligible for inclusion, the self-management intervention included a written action plan for AECOPD and an iterative process between participant and healthcare provider(s) in which feedback was provided. We excluded disease management programmes classified as pulmonary rehabilitation or exercise classes offered in a hospital, at a rehabilitation centre, or in a community-based setting to avoid overlap with pulmonary rehabilitation as much as possible. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted data. We resolved disagreements by reaching consensus or by involving a third review author. Study authors were contacted to obtain additional information and missing outcome data where possible. When appropriate, study results were pooled using a random-effects modelling meta-analysis. The primary outcomes of the review were health-related quality of life (HRQoL) and number of respiratory-related hospital admissions. MAIN RESULTS: We included 22 studies that involved 3,854 participants with COPD. The studies compared the effectiveness of COPD self-management interventions that included an action plan for AECOPD with usual care. The follow-up time ranged from two to 24 months and the content of the interventions was diverse.Over 12 months, there was a statistically significant beneficial effect of self-management interventions with action plans on HRQoL, as measured by the St. George's Respiratory Questionnaire (SGRQ) total score, where a lower score represents better HRQoL. We found a mean difference from usual care of -2.69 points (95% CI -4.49 to -0.90; 1,582 participants; 10 studies; high-quality evidence). Intervention participants were at a statistically significant lower risk for at least one respiratory-related hospital admission compared with participants who received usual care (OR 0.69, 95% CI 0.51 to 0.94; 3,157 participants; 14 studies; moderate-quality evidence). The number needed to treat to prevent one respiratory-related hospital admission over one year was 12 (95% CI 7 to 69) for participants with high baseline risk and 17 (95% CI 11 to 93) for participants with low baseline risk (based on the seven studies with the highest and lowest baseline risk respectively).There was no statistically significant difference in the probability of at least one all-cause hospital admission in the self-management intervention group compared to the usual care group (OR 0.74, 95% CI 0.54 to 1.03; 2467 participants; 14 studies; moderate-quality evidence). Furthermore, we observed no statistically significant difference in the number of all-cause hospitalisation days, emergency department visits, General Practitioner visits, and dyspnoea scores as measured by the (modified) Medical Research Council questionnaire for self-management intervention participants compared to usual care participants. There was no statistically significant effect observed from self-management on the number of COPD exacerbations and no difference in all-cause mortality observed (RD 0.0019, 95% CI -0.0225 to 0.0263; 3296 participants; 16 studies; moderate-quality evidence). Exploratory analysis showed a very small, but significantly higher respiratory-related mortality rate in the self-management intervention group compared to the usual care group (RD 0.028, 95% CI 0.0049 to 0.0511; 1219 participants; 7 studies; very low-quality evidence).Subgroup analyses showed significant improvements in HRQoL in self-management interventions with a smoking cessation programme (MD -4.98, 95% CI -7.17 to -2.78) compared to studies without a smoking cessation programme (MD -1.33, 95% CI -2.94 to 0.27, test for subgroup differences: Chi² = 6.89, df = 1, P = 0.009, I² = 85.5%). The number of behavioural change techniques clusters integrated in the self-management intervention, the duration of the intervention and adaptation of maintenance medication as part of the action plan did not affect HRQoL. Subgroup analyses did not detect any potential variables to explain differences in respiratory-related hospital admissions among studies. AUTHORS' CONCLUSIONS: Self-management interventions that include a COPD exacerbation action plan are associated with improvements in HRQoL, as measured with the SGRQ, and lower probability of respiratory-related hospital admissions. No excess all-cause mortality risk was observed, but exploratory analysis showed a small, but significantly higher respiratory-related mortality rate for self-management compared to usual care.For future studies, we would like to urge only using action plans together with self-management interventions that meet the requirements of the most recent COPD self-management intervention definition. To increase transparency, future study authors should provide more detailed information regarding interventions provided. This would help inform further subgroup analyses and increase the ability to provide stronger recommendations regarding effective self-management interventions that include action plans for AECOPD. For safety reasons, COPD self-management action plans should take into account comorbidities when used in the wider population of people with COPD who have comorbidities. Although we were unable to evaluate this strategy in this review, it can be expected to further increase the safety of self-management interventions. We also advise to involve Data and Safety Monitoring Boards for future COPD self-management studies.

Fatigue in COPD: association with functional status and hospitalisations.

This study aimed to examine the importance of fatigue as a clinical indicator in chronic obstructive pulmonary disease (COPD), by analysing its relationship with COPD severity and ability to predict risk of hospitalisation, and by comparing the intensity of fatigue in stable COPD patients with levels of fatigue reported by patients with other chronic conditions. We studied 100 consecutive patients attending assessment clinics before pulmonary rehabilitation. Both questionnaire and physiological data were collected. Partial correlations, multiple linear regressions and Cox proportional hazard models/negative binomial regressions were used to address the research questions. A significant relationship existed between fatigue and COPD severity. Fatigue reports predicted future hospitalisation risk. Compared to the lowest third of patients, the third of patients reporting the most intense fatigue showed a 10-fold increase in risk of hospitalisation (fatigue experiences hazard ratio (HR) 10.2, 95% CI 2.66-38.86; fatigue impacts HR 10.7, 95% CI 2.76-41.65). Our COPD sample reported fatigue scores of similar intensity to colorectal cancer patients and HIV-positive patients. While fatigue is significantly related to COPD functional severity, fatigue data also capture independent information. Fatigue reports can contribute to predictions of hospitalisation risk.

Which chronic obstructive pulmonary disease care recommendations have low implementation and why? A pilot study.

BACKGROUND: Clinical care components for people with COPD are recommended in guidelines if high-level evidence exists. However, there are gaps in their implementation, and factors which act as barriers or facilitators to their uptake are not well described. The aim of this pilot study was to explore implementation of key high-evidence COPD guideline recommendations in patients admitted to hospital with a disease exacerbation, to inform the development of a larger observational study. METHODS: This study recruited consecutive COPD patients admitted to a tertiary hospital. Patient demographic, disease and admission characteristics were recorded. Information about implementation of target guideline recommendations (smoking cessation, pulmonary rehabilitation referral, influenza vaccination, medication use and long-term oxygen use if hypoxaemic) was gained from medical records and patient interviews. Interviews with hospital-based doctors examined their perspectives on recommendation implementation. RESULTS: Fifteen patients (aged 76(9) years, FEV1%pred 58(15), mean(SD)) and nine doctors participated. Referral to pulmonary rehabilitation (5/15 patients) was underutilised by comparison with other high-evidence recommendations. Low awareness of pulmonary rehabilitation was a key barrier for patients and doctors. Other barriers for patients were access difficulties, low perceived health benefits, and co-morbidities. Doctors reported they tended to refer patients with severe disease and frequent hospital attendance, a finding supported by the quantitative data. CONCLUSIONS: This study provides justification for a larger observational study to test the hypothesis that pulmonary rehabilitation referral is low in suitable COPD patients, and closer investigation of the reasons for this evidence-practice gap.

Treatments for anxiety and depression in patients with chronic obstructive pulmonary disease: a literature review.

Chronic obstructive pulmonary disease (COPD) is a serious contemporary health issue. Psychological co-morbidities such as anxiety and depression are common in COPD. Current evidence for treatment options to reduce anxiety and depression in patients with COPD was examined. There is evidence available for the efficacy of pharmacological treatments, cognitive behavioural therapy, pulmonary rehabilitation, relaxation therapy and palliative care in COPD. Therapeutic modalities that have not been proven effective in decreasing anxiety and depression in COPD, but which have theoretical potential among patients, include interpersonal psychotherapy, self-management programmes, more extensive disease management programmes, supportive therapy and self-help groups. Besides pulmonary rehabilitation that is only available for a small percentage of patients, management guidelines make scant reference to other options for the treatment of mental health problems. The quantity and quality of research on mental health treatments in COPD have historically been insufficient to support their inclusion in COPD treatment guidelines. In this review, recommendations regarding assessment, treatment and future research in this important field were made.

Simplified COPD screening: validation of the PiKo-6® in primary care.

AIMS: To determine the accuracy of the forced expiratory volume ratio at one and six seconds (FEV1/FEV6) using a hand-held, expiratory flow meter (PiKo-6®, nSpire Health, Inc.) to screen for chronic obstructive pulmonary disease (COPD) in primary care settings. METHODS: Current and former smokers (≥ 50 years old) with no previous respiratory diagnosis (case finding [CF] = 204 subjects) or with an asthma diagnosis (differential diagnosis [DD] = 93 subjects) were evaluated using validated questionnaires, pre-bronchodilator (BD) FEV1/FEV6 and post-BD FEV1/forced vital capacity (FVC) spirometry. RESULTS: The PiKo-6® FEV1/FEV6 showed good sensitivity and specificity (areas under the Receiver Operating Characteristic curves [95% confidence intervals]: CF = 0.85 [0.79, 0.90]; DD = 0.88 [0.80, 0.96]) and exceeded the accuracy of the questionnaires. An FEV1/FEV6 cutoff < 0.75 provided optimal sensitivity (CF = 81%; DD = 86%) and specificity (CF = 71%; DD = 67%) for COPD screening. CONCLUSIONS: The PiKo-6® allows simple and reliable screening for COPD which could optimise early referral for spirometry and early, targeted interventions for COPD.

Why are some evidence-based care recommendations in chronic obstructive pulmonary disease better implemented than others? Perspectives of medical practitioners.

BACKGROUND: Clinical guidelines for management of patients with chronic obstructive pulmonary disease (COPD) include recommendations based on high levels of evidence, but gaps exist in their implementation. The aim of this study was to examine the perspectives of medical practitioners regarding implementation of six high-evidence recommendations for the management of people with COPD. METHODS: Semi-structured interviews were conducted with medical practitioners involved with care of COPD patients in hospital and general practice. Interviews sought medical practitioners' experience regarding implementation of smoking cessation, influenza vaccination, pulmonary rehabilitation, guideline-based medications, long-term oxygen therapy for hypoxemia and plan and advice for future exacerbations. Interviews were audiotaped, transcribed verbatim and analyzed using content analysis. RESULTS: Nine hospital-based medical practitioners and seven general practitioners participated. Four major categories were identified which impacted on implementation of the target recommendations in the care of patients with COPD: (1) role clarity of the medical practitioner; (2) persuasive communication with the patient; (3) complexity of behavioral change required; (4) awareness and support available at multiple levels. For some recommendations, strength in all four categories provided significant enablers supporting implementation. However, with regard to pulmonary rehabilitation and plans and advice for future exacerbations, all identified categories that presented barriers to implementation. CONCLUSION: This study of medical practitioner perspectives has indicated areas where significant barriers to the implementation of key evidence-based recommendations in COPD management persist. Developing strategies to target the identified categories provides an opportunity to achieve greater implementation of those high-evidence recommendations in the care of people with COPD.

Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial.

BACKGROUND: Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients. METHODS: Adults from outpatient clinics at nine sites in Australia, the USA, and the UK were eligible for enrolment in this double-blind, randomised controlled trial if they had life-limiting illness, refractory dyspnoea, and partial pressure of oxygen in arterial blood (PaO(2)) more than 7.3 kPa. Participants were randomly assigned in a 1:1 ratio by a central computer-generated system to receive oxygen or room air via a concentrator through a nasal cannula at 2 L per min for 7 days. Participants were instructed to use the concentrator for at least 15 h per day. The randomisation sequence was stratified by baseline PaO(2) with balanced blocks of four patients. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice a day (morning and evening). All randomised patients who completed an assessment were included in the primary analysis for that data point (no data were imputed). This study is registered, numbers NCT00327873 and ISRCTN67448752. FINDINGS: 239 participants were randomly assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients assigned to receive oxygen and 99 (83%) assigned to receive room air completed all 7 days of assessments. From baseline to day 6, mean morning breathlessness changed by -0.9 points (95% CI -1.3 to -0.5) in patients assigned to receive oxygen and by -0.7 points (-1.2 to -0.2) in patients assigned to receive room air (p=0.504). Mean evening breathlessness changed by -0.3 points (-0.7 to 0.1) in the oxygen group and by -0.5 (-0.9 to -0.1) in the room air group (p=0.554). The frequency of side-effects did not differ between groups. Extreme drowsiness was reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14 (13%) of 108 patients assigned to receive room air. Two (2%) patients in the oxygen group reported extreme symptoms of nasal irritation compared with seven (6%) in the room air group. One patient reported an extremely troublesome nose bleed (oxygen group). INTERPRETATION: Since oxygen delivered by a nasal cannula provides no additional symptomatic benefit for relief of refractory dyspnoea in patients with life-limiting illness compared with room air, less burdensome strategies should be considered after brief assessment of the effect of oxygen therapy on the individual patient. FUNDING: US National Institutes of Health, Australian National Health and Medical Research Council, Duke Institute for Care at the End of Life, and Doris Duke Charitable Foundation.

Chronic obstructive pulmonary disease (COPD) is a major personal and public health burden in Australia.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a serious disease that is increasing in prevalence, yet is under-diagnosed and under-recognised in Australia. The goal is to bring this to the attention of public health and offer recommendations in order to reduce the present and future burden from COPD. APPROACH: The increase in prevalence, particularly in women, and the impact upon personal and public health demonstrate that COPD is a major public health issue. A proactive approach for public health is suggested, including strategies to increase smoking cessation among at-risk groups, reduce delayed diagnosis, extend disease management strategies, and establish an Australian research base. CONCLUSION: The reduction of the burden from COPD is contingent upon a proactive approach by public health that includes approaching it as a research priority and the provision of adequately resourced prevention and management strategies.

Trends in hospital admissions and mortality from asthma and chronic obstructive pulmonary disease in Australia, 1993-2003.

OBJECTIVE: To examine evolving changes in asthma and chronic obstructive pulmonary disease (COPD) in South Australia and Australia as a whole from the perspective of hospital admissions, ventilatory support and mortality data. DESIGN: Retrospective analyses, for the period 1993-2003, of hospital separations data from the Australian Institute of Health and Welfare and the Integrated South Australian Activity Collection, and mortality data from the Australian Bureau of Statistics and South Australian hospital morbidity collection. MAIN OUTCOME MEASURES: Hospital separations, ventilatory support episodes, mortality rates, burden-of-disease rankings. RESULTS: Between 1993 and 2003, in SA and nationally, hospital separations for asthma declined but separations for COPD increased significantly. Falling mortality rates from asthma in both men and women, and from COPD in men, contrast with increasing rates of COPD-related hospitalisation and mortality in women. CONCLUSIONS: Hospital admissions and mortality associated with asthma have fallen. Admission rates for COPD are declining for men, but there is no indication that admission rates for women have reached a peak. There is a need for higher prioritisation of COPD, including policies to reduce smoking in women, and medical practice initiatives to support primary and secondary prevention, pulmonary rehabilitation and appropriate drug therapies.