SABINA + Hong Kong: a territory wide study of prescribing trends and outcomes associated with the use of short-acting ß2 agonists in the Chinese population.

BACKGROUND: Excessive use of short-acting ß2 agonists (SABA) in patients with asthma continues to be a notable concern due to its link to higher mortality rates. Global relevance of SABA overuse in asthma management cannot be understated, it poses significant health risk to patients with asthma and imposes burden on healthcare systems. This study, as part of global SABINA progamme, aimed to describe the prescribing patterns and clinical outcomes associated with SABA use in the Chinese population. METHODS: Retrospective cohort study was conducted using anonymized electronic healthcare records of Clinical Data Analysis and Reporting System (CDARS) from Hong Kong Hospital Authority (HA). Patients newly diagnosed with asthma between 2011 and 2018 and aged ≥12 years were included, stratified by SABA use (≤2, 3-6, 7-10, or ≥11 canisters/year) during one-year baseline period since asthma diagnosis date. Patients were followed up from one-year post-index until earliest censoring of events: outcome occurrence and end of study period (31 December 2020). Cox proportional regression and negative binomial regression were used to estimate the mortality risk and frequency of hospital admissions associated with SABA use respectively, after adjusting for age, sex, Charlson Comorbidity Index (CCI), and inhaled corticosteroid (ICS) dose. Outcomes include all-cause, asthma-related, and respiratory-related mortality, frequency of hospital admissions for any cause, and frequency of hospital admissions due to asthma. RESULTS: 17,782 patients with asthma (mean age 46.7 years, 40.8% male) were included and 59.1% of patients were overusing SABA (≥ 3 canisters per year). Each patient was prescribed a median of 5.61 SABA canisters/year. SABA overuse during baseline period was associated with higher all-cause mortality risk compared to patients with ≤2 canisters/year. Association was dose-dependent, highest risk in those used ≥11 canisters/year (adjusted hazard ratio: 1.42, 95% CI: 1.13, 1.79) and 3-6 canisters/year (adjusted hazard ratio: 1.22, 95% CI: 1.00, 1.50). Higher SABA prescription volume associated with increased frequency of hospital admissions with greatest risk observed in 7-10 canisters/year subgroup (adjusted rate ratio: 4.81, 95% CI: 3.66, 6.37). CONCLUSIONS: SABA overuse is prevalent and is associated with increased all-cause mortality risk and frequency of hospital admissions among the patients with asthma in Hong Kong.

Subsegmental pulmonary embolism and anticoagulant therapy: the impact of clinical context.

BACKGROUND: Anticoagulation for subsegmental pulmonary embolism (SSPE) is controversial. AIM: To assess the impact of clinical context on anticoagulation and outcomes of SSPE. METHODS: We electronically searched computed tomography pulmonary angiogram reports to identify SSPE. We extracted demographic, risk factor, investigations and outcome data from the electronic medical record. We stratified patients according to anticoagulation and no anticoagulation. RESULTS: From 1 January 2017 to 31 December 2019, we identified 166 patients with SSPE in 5827 pulmonary angiogram reports. Of these, 123 (74%) received anticoagulation. Compared with non-anticoagulated patients, such patients had a different clinical context: higher rates of previous venous thromboembolism (11% vs 0%; P = 0.019), more recent surgery (26% vs 9%; P = 0.015), more elevated serum D-dimer (22% vs 5%; P = 0.004), more lung parenchymal abnormalities (76% vs 61%; P = 0.037) and were almost twice as likely to require inpatient care (76% vs 42%; P < 0.001). Such patients also had twice the all-cause mortality at 1 year (32% vs 16%). CONCLUSIONS: SSPE is diagnosed in almost 3% of pulmonary angiograms and is associated with high mortality, regardless of anticoagulation, due to coexistent disease processes rather than SSPE. Anticoagulation appears dominant but markedly affected by the clinical context of risk factors, alternative indications and illness severity. Thus, the controversy is partly artificial because anticoagulation after SSPE is clinically contextual with SSPE as only one of several factors.

Thunderstorm asthma in seasonal allergic rhinitis: The TAISAR study.

BACKGROUND: Asthma epidemics associated with thunderstorms have had catastrophic effects on individuals and emergency services. Seasonal allergic rhinitis (SAR) is present in the vast majority of people who develop thunderstorm asthma (TA), but there is little evidence regarding risk factors for TA among the SAR population. OBJECTIVE: We sought to identify risk factors for a history of TA and hospital presentation in a cohort of individuals with SAR. METHODS: This multicenter study recruited adults from Melbourne, Australia, with a past diagnosis of TA and/or self-reported SAR. Clinical information, spirometry results, white blood cell count, ryegrass pollen-specific (RGP-sp) IgE concentration, and fractional exhaled nitric oxide were measured to identify risk factors for a history of TA in individuals with SAR. RESULTS: From a total of 228 individuals with SAR, 35% (80 of 228) reported SAR only (the I-SAR group), 37% (84 of 228) reported TA symptoms but had not attended hospital for treatment (the O-TA group), and 28% (64 of 228) had presented to the hospital for TA (the H-TA group). All patients in the H-TA group reported a previous asthma diagnosis. Logistic regression analysis of factors associated with O-TA and H-TA indicated that lower FEV1 value and an Asthma Control Questionnaire score higher than 1.5 were associated with H-TA. Higher blood RGP-sp IgE concentration, eosinophil counts, and fractional exhaled nitric oxide level were significantly associated with both O-TA and H-TA. Receiver operating curve analysis showed an RGP-sp IgE concentration higher than 10.1 kU/L and a prebronchodilator FEV1 value of 90% or lower to be biomarkers of increased H-TA risk. CONCLUSION: Clinical tests can identify risk of a history of TA in individuals with SAR and thereby inform patient-specific treatment recommendations.

Telerehabilitation for chronic respiratory disease: a randomised controlled equivalence trial.

RATIONALE: Pulmonary rehabilitation is an effective treatment for people with chronic respiratory disease but is delivered to <5% of eligible individuals. This study investigated whether home-based telerehabilitation was equivalent to centre-based pulmonary rehabilitation in people with chronic respiratory disease. METHODS: A multicentre randomised controlled trial with assessor blinding, powered for equivalence was undertaken. Individuals with a chronic respiratory disease referred to pulmonary rehabilitation at four participating sites (one rural) were eligible and randomised using concealed allocation to pulmonary rehabilitation or telerehabilitation. Both programmes were two times per week for 8 weeks. The primary outcome was change in Chronic Respiratory Disease Questionnaire Dyspnoea (CRQ-D) domain at end-rehabilitation, with a prespecified equivalence margin of 2.5 points. Follow-up was at 12 months. Secondary outcomes included exercise capacity, health-related quality of life, symptoms, self-efficacy and psychological well-being. RESULTS: 142 participants were randomised to pulmonary rehabilitation or telerehabilitation with 96% and 97% included in the intention-to-treat analysis, respectively. There were no significant differences between groups for any outcome at either time point. Both groups achieved meaningful improvement in dyspnoea and exercise capacity at end-rehabilitation. However, we were unable to confirm equivalence of telerehabilitation for the primary outcome ΔCRQ-D at end-rehabilitation (mean difference (MD) (95% CI) -1 point (-3 to 1)), and inferiority of telerehabilitation could not be excluded at either time point (12-month follow-up: MD -1 point (95% CI -4 to 1)). At end-rehabilitation, telerehabilitation demonstrated equivalence for 6-minute walk distance (MD -6 m, 95% CI -26 to 15) with possibly superiority of telerehabilitation at 12 months (MD 14 m, 95% CI -10 to 38). CONCLUSION: telerehabilitation may not be equivalent to centre-based pulmonary rehabilitation for all outcomes, but is safe and achieves clinically meaningful benefits. When centre-based pulmonary rehabilitation is not available, telerehabilitation may provide an alternative programme model. TRIAL REGISTRATION NUMBER: ACtelerehabilitationN12616000360415.

COPD-X Australian guidelines for the diagnosis and management of chronic obstructive pulmonary disease: 2022 update.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a treatable and preventable disease characterised by persistent respiratory symptoms and chronic airflow limitation on spirometry. COPD is highly prevalent and is associated with exacerbations and comorbid conditions. "COPD-X" provides quarterly updates in COPD care and is published by the Lung Foundation Australia and the Thoracic Society of Australia and New Zealand. MAIN RECOMMENDATIONS: The COPD-X guidelines (version 2.65) encompass 26 recommendations addressing: case finding and confirming diagnosis; optimising function; preventing deterioration; developing a plan of care; and managing an exacerbation. CHANGES IN MANAGEMENT AS A RESULT OF THESE GUIDELINES: Both non-pharmacological and pharmacological strategies are included within these recommendations, reflecting the importance of a holistic approach to clinical care for people living with COPD to delay disease progression, optimise quality of life and ensure best practice care in the community and hospital settings when managing exacerbations. Several of the new recommendations, if put into practice in the appropriate circumstances, and notwithstanding known variations in the social determinants of health, could improve quality of life and reduce exacerbations, hospitalisations and mortality for people living with COPD.

Thoracic Society of Australia and New Zealand Position Statement on Acute Oxygen Use in Adults: 'Swimming between the flags'.

Oxygen is a life-saving therapy but, when given inappropriately, may also be hazardous. Therefore, in the acute medical setting, oxygen should only be given as treatment for hypoxaemia and requires appropriate prescription, monitoring and review. This update to the Thoracic Society of Australia and New Zealand (TSANZ) guidance on acute oxygen therapy is a brief and practical resource for all healthcare workers involved with administering oxygen therapy to adults in the acute medical setting. It does not apply to intubated or paediatric patients. Recommendations are made in the following six clinical areas: assessment of hypoxaemia (including use of arterial blood gases); prescription of oxygen; peripheral oxygen saturation targets; delivery, including non-invasive ventilation and humidified high-flow nasal cannulae; the significance of high oxygen requirements; and acute hypercapnic respiratory failure. There are three sections which provide (1) a brief summary, (2) recommendations in detail with practice points and (3) a detailed explanation of the reasoning and evidence behind the recommendations. It is anticipated that these recommendations will be disseminated widely in structured programmes across Australia and New Zealand.

ACP provided 2 conditional recommendations on use of high-flow nasal oxygen in acute respiratory failure.

SOURCE CITATION: Qaseem A, Etxeandia-Ikobaltzeta I, Fitterman N, et al. Appropriate use of high-flow nasal oxygen in hospitalized patients for initial or postextubation management of acute respiratory failure: a clinical guideline from the American College of Physicians. Ann Intern Med. 2021;174:977-84. 33900796.

Home oxygen therapy.

Long-term home oxygen therapy improves survival in patients with chronic obstructive pulmonary disease and persistent, severe hypoxaemia. It is uncertain that this benefit extends to patients with other chronic lung diseases. Oxygen is a treatment for hypoxaemia, not breathlessness. To confirm hypoxaemia, blood gas analysis is recommended before prescribing oxygen. There is limited and conflicting evidence that portable oxygen for exertional use is of benefit to patients with chronic obstructive pulmonary disease who do not have severe hypoxaemia. Laboratory studies show improvements in exercise capacity and dyspnoea, but these do not translate into significant benefits in the home setting. Patients should be educated regarding the expected benefits, risks and burdens of home oxygen therapy. It is particularly important that the patient does not smoke.

Referral criteria to palliative care for patients with respiratory disease: a systematic review.

AIMS: Advanced nonmalignant respiratory diseases are associated with significant patient morbidity, yet access to palliative care occurs late, if at all. Our aim was to examine referral criteria for palliative care among patients with advanced nonmalignant respiratory disease, with a view to developing a standardised set of referral criteria. METHODS: We performed a systematic review of all studies reporting on referral criteria to palliative care in advanced nonmalignant respiratory disease, with a focus on chronic obstructive pulmonary disease and interstitial lung disease. The systematic review was conducted and reported according to the PRISMA guidelines, and was undertaken using electronic databases (Ovid, MEDLINE, Ovid Embase and PubMed). RESULTS: Searches yielded 2052 unique titles, which were screened for eligibility and resulted in 62 studies addressing referral criteria to palliative care in advanced nonmalignant respiratory disease. Of 18 categories put forward for referral to palliative care, the most commonly discussed factors were hospital use (69% of papers), indicators of poor respiratory status (47%), physical and emotional symptoms (37%), functional decline (29%), need for advanced respiratory therapies (27%), and disease progression (26%). CONCLUSION: Clinicians consider referral to specialist palliative care for a wide range of disease- and needs-based criteria. Our findings highlight the need to standardise palliative care access by developing consensus referral criteria for patients with advanced nonmalignant respiratory illnesses.

Telerehabilitation for chronic respiratory disease.

BACKGROUND: Pulmonary rehabilitation is a proven, effective intervention for people with chronic respiratory diseases including chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and bronchiectasis. However, relatively few people attend or complete a program, due to factors including a lack of programs, issues associated with travel and transport, and other health issues. Traditionally, pulmonary rehabilitation is delivered in-person on an outpatient basis at a hospital or other healthcare facility (referred to as centre-based pulmonary rehabilitation). Newer, alternative modes of pulmonary rehabilitation delivery include home-based models and the use of telehealth. Telerehabilitation is the delivery of rehabilitation services at a distance, using information and communication technology. To date, there has not been a comprehensive assessment of the clinical efficacy or safety of telerehabilitation, or its ability to improve uptake and access to rehabilitation services, for people with chronic respiratory disease. OBJECTIVES: To determine the effectiveness and safety of telerehabilitation for people with chronic respiratory disease. SEARCH METHODS: We searched the Cochrane Airways Trials Register, and the Cochrane Central Register of Controlled Trials; six databases including MEDLINE and Embase; and three trials registries, up to 30 November 2020. We checked reference lists of all included studies for additional references, and handsearched relevant respiratory journals and meeting abstracts. SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials of telerehabilitation for the delivery of pulmonary rehabilitation were eligible for inclusion. The telerehabilitation intervention was required to include exercise training, with at least 50% of the rehabilitation intervention being delivered by telerehabilitation. DATA COLLECTION AND ANALYSIS: We used standard methods recommended by Cochrane. We assessed the risk of bias for all studies, and used the ROBINS-I tool to assess bias in non-randomised controlled clinical trials. We assessed the certainty of evidence with GRADE. Comparisons were telerehabilitation compared to traditional in-person (centre-based) pulmonary rehabilitation, and telerehabilitation compared to no rehabilitation. We analysed studies of telerehabilitation for maintenance rehabilitation separately from trials of telerehabilitation for initial primary pulmonary rehabilitation. MAIN RESULTS: We included a total of 15 studies (32 reports) with 1904 participants, using five different models of telerehabilitation. Almost all (99%) participants had chronic obstructive pulmonary disease (COPD). Three studies were controlled clinical trials. For primary pulmonary rehabilitation, there was probably little or no difference between telerehabilitation and in-person pulmonary rehabilitation for exercise capacity measured as 6-Minute Walking Distance (6MWD) (mean difference (MD) 0.06 metres (m), 95% confidence interval (CI) -10.82 m to 10.94 m; 556 participants; four studies; moderate-certainty evidence). There may also be little or no difference for quality of life measured with the St George's Respiratory Questionnaire (SGRQ) total score (MD -1.26, 95% CI -3.97 to 1.45; 274 participants; two studies; low-certainty evidence), or for breathlessness on the Chronic Respiratory Questionnaire (CRQ) dyspnoea domain score (MD 0.13, 95% CI -0.13 to 0.40; 426 participants; three studies; low-certainty evidence). Participants were more likely to complete a program of telerehabilitation, with a 93% completion rate (95% CI 90% to 96%), compared to a 70% completion rate for in-person rehabilitation. When compared to no rehabilitation control, trials of primary telerehabilitation may increase exercise capacity on 6MWD (MD 22.17 m, 95% CI -38.89 m to 83.23 m; 94 participants; two studies; low-certainty evidence) and may also increase 6MWD when delivered as maintenance rehabilitation (MD 78.1 m, 95% CI 49.6 m to 106.6 m; 209 participants; two studies; low-certainty evidence). No adverse effects of telerehabilitation were noted over and above any reported for in-person rehabilitation or no rehabilitation. AUTHORS' CONCLUSIONS: This review suggests that primary pulmonary rehabilitation, or maintenance rehabilitation, delivered via telerehabilitation for people with chronic respiratory disease achieves outcomes similar to those of traditional centre-based pulmonary rehabilitation, with no safety issues identified. However, the certainty of the evidence provided by this review is limited by the small number of studies, of varying telerehabilitation models, with relatively few participants. Future research should consider the clinical effect of telerehabilitation for individuals with chronic respiratory diseases other than COPD, the duration of benefit of telerehabilitation beyond the period of the intervention, and the economic cost of telerehabilitation.

Pulmonary embolus in patients with COVID-19: an Australian perspective.

Pulmonary embolus (PE) is a known complication of coronavirus disease 2019 (COVID-19). The diagnosis of PE in our hospitalised patients with COVID-19 correlated with more severe disease and occurred despite the use of routine thromboprophylaxis. Higher D-dimers were seen on admission in patients who developed PE and rose at PE diagnosis, suggesting a role for D-dimer in risk stratification.

Excess mortality at Christmas due to cardiovascular disease in the HUNT study prospective population-based cohort in Norway.

BACKGROUND: Although it is known that winter inclusive of the Christmas holiday period is associated with an increased risk of dying compared to other times of the year, very few studies have specifically examined this phenomenon within a population cohort subject to baseline profiling and prospective follow-up. In such a cohort, we sought to determine the specific characteristics of mortality occuring during the Christmas holidays. METHODS: Baseline profiling and outcome data were derived from a prospective population-based cohort with longitudinal follow-up in Central Norway - the Trøndelag Health (HUNT) Study. From 1984 to 1986, 88% of the target population comprising 39,273 men and 40,353 women aged 48 ± 18 and 50 ± 18 years, respectively, were profiled. We examined the long-term pattern of mortality to determine the number of excess (all-cause and cause-specific) deaths that occurred during winter overall and, more specifically, the Christmas holidays. RESULTS: During 33.5 (IQR 17.1-34.4) years follow-up, 19,879 (50.7%) men and 19,316 (49.3%) women died at age-adjusted rate of 5.3 and 4.6 deaths per 1000/annum, respectively. Overall, 1540 (95% CI 43-45 deaths/season) more all-cause deaths occurred in winter (December to February) versus summer (June to August), with 735 (95% CI 20-22 deaths per season) of these cardiovascular-related. December 25th-27th was the deadliest 3-day period of the year; being associated with 138 (95% CI 96-147) and 102 (95% CI 72-132) excess all-cause and cardiovascular-related deaths, respectively. Accordingly, compared to 1st-21st December (equivalent winter conditions), the incidence rate ratio of all-cause mortality increased to 1.22 (95% CI 1.16-1.27) and 1.17 (95% 1.11-1.22) in men and women, respectively, during the next 21 days (Christmas/New Year holidays). All observed differences were highly significant (P < 0.001). A less pronounced pattern of mortality due to respiratory illnesses (but not cancer) was also observed. CONCLUSION: Beyond a broader pattern of seasonally-linked mortality characterised by excess winter deaths, the deadliest time of year in Central Norway coincides with the Christmas holidays. During this time, the pattern and frequency of cardiovascular-related mortality changes markedly; contrasting with a more stable pattern of cancer-related mortality. Pending confirmation in other populations and climates, further research to determine if these excess deaths are preventable is warranted.

High intensity interval training versus moderate intensity continuous training for people with interstitial lung disease: protocol for a randomised controlled trial.

BACKGROUND: Interstitial lung disease is a debilitating condition associated with significant dyspnoea, fatigue, and poor exercise tolerance. Pulmonary rehabilitation is an effective and key intervention in people with interstitial lung disease. However, despite the best efforts of patients and clinicians, many of those who participate are not achieving clinically meaningful benefits. This assessor-blinded, multi-centre, randomised controlled trial aims to compare the clinical benefits of high intensity interval exercise training versus the standard pulmonary rehabilitation method of continuous training at moderate intensity in people with fibrotic interstitial lung disease. METHODS: Eligible participants will be randomised to either a standard pulmonary rehabilitation group using moderate intensity continuous exercise training or high intensity interval exercise training. Participants in both groups will undertake an 8-week pulmonary rehabilitation program of twice-weekly supervised exercise training including aerobic (cycling) and strengthening exercises. In addition, participants in both groups will be prescribed a home exercise program. Outcomes will be assessed at baseline, upon completion of the intervention and at six months following the intervention by a blinded assessor. The primary outcome is endurance time on a constant work rate test. Secondary outcomes are functional capacity (6-min walk distance), health-related quality of life (Chronic Respiratory Disease Questionnaire (CRQ), St George's Respiratory Questionnaire idiopathic pulmonary fibrosis specific version (SGRQ-I), breathlessness (Dyspnoea 12, Modified Medical Research Council Dyspnoea Scale), fatigue (fatigue severity scale), anxiety (Hospital Anxiety and Depression Scale), physical activity level (GeneActiv), skeletal muscle changes (ultrasonography) and completion and adherence to pulmonary rehabilitation. DISCUSSION: The standard exercise training strategies used in pulmonary rehabilitation may not provide an optimal exercise training stimulus for people with interstitial lung disease. This study will determine whether high intensity interval training can produce equivalent or even superior changes in exercise performance and symptoms. If high intensity interval training proves effective, it will provide an exercise training strategy that can readily be implemented into clinical practice for people with interstitial lung disease. Trial registration ClinicalTrials.gov Registry (NCT03800914). Registered 11 January 2019, https://clinicaltrials.gov/ct2/show/NCT03800914 Australian New Zealand Clinical Trials Registry ACTRN12619000019101. Registered 9 January 2019, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=376050&isReview=true.

Asthma self-management with regular support reduces health care use and improves QoL at 8 mo.

SOURCE CITATION: Hodkinson A, Bower P, Grigoroglou C, et al. Self-management interventions to reduce healthcare use and improve quality of life among patients with asthma: systematic review and network meta-analysis. BMJ. 2020;370:m2521. 32816816.

"Willingness to Pay": The Value Attributed to Program Location by Pulmonary Rehabilitation Participants.

The "contingent valuation" method is used to quantify the value of services not available in traditional markets, by assessing the monetary value an individual ascribes to the benefit provided by an intervention. The aim of this study was to determine preferences for home or center-based pulmonary rehabilitation for participants with chronic obstructive pulmonary disease (COPD) using the "willingness to pay" (WTP) approach, the most widely used technique to elicit strengths of individual preferences. This is a secondary analysis of a randomized controlled equivalence trial comparing center-based and home-based pulmonary rehabilitation. At their final session, participants were asked to nominate the maximum that they would be willing to pay to undertake home-based pulmonary rehabilitation in preference to a center-based program. Regression analyses were used to investigate relationships between participant features and WTP values. Data were available for 141/163 eligible study participants (mean age 69 [SD 10] years, n = 82 female). In order to undertake home-based pulmonary rehabilitation in preference to a conventional center-based program, participants were willing to pay was mean $AUD176 (SD 255) (median $83 [IQR 0 to 244]). No significant difference for WTP values was observed between groups (p = 0.98). A WTP value above zero was related to home ownership (odds ratio [OR] 2.95, p = 0.02) and worse baseline SF-36 physical component score (OR 0.94, p = 0.02). This preliminary evidence for WTP in the context of pulmonary rehabilitation indicated the need for further exploration of preferences for treatment location in people with COPD to inform new models of service delivery.

Community Participation by People with Chronic Obstructive Pulmonary Disease.

Little is known regarding community participation in individuals with chronic obstructive pulmonary disease (COPD). The aim of this study was to explore community participation in individuals with COPD and to determine whether there is an association between community participation and activity-related outcome variables commonly collected during pulmonary rehabilitation assessment. We also sought to investigate which of these variables might influence community participation in people with COPD. Ninety-nine individuals with COPD were enrolled (67 ± 9 years, FEV1: 55 ± 22% predicted). We assessed community participation (Community Participation Indicator (CPI) and European Social Survey (ESS) for formal and informal community participation), daily physical activity levels (activity monitor), exercise capacity (6-minute walk test), breathlessness (Modified Medical Research Council, MMRC scale), self-efficacy (Pulmonary Rehabilitation Adapted Index of Self-Efficacy) and anxiety and depression (Hospital Anxiety and Depression Scale). Higher levels of community participation on the CPI were associated with older age and greater levels of physical activity (total, light and moderate-to-vigorous) (all rs = 0.30, p < 0.05). Older age and more moderate-to-vigorous physical activity independently predicted greater community participation measured by CPI. Higher levels of depression symptoms were associated with less formal and informal community participation on ESS (rs = -0.25). More formal community participation on ESS was weakly (rs = 0.2-0.3) associated with older age, better lung function, exercise capacity and self-efficacy, and less breathlessness. Self-efficacy, exercise capacity, and age independently predicted formal community participation in individuals with COPD. Strategies to optimize self-efficacy and improve exercise capacity may be useful to enhance community participation in people with COPD.

Regular, sustained-release morphine for chronic breathlessness: a multicentre, double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Morphine may decrease the intensity of chronic breathlessness but data from a large randomised controlled trial (RCT) are lacking. This first, large, parallel-group trial aimed to test the efficacy and safety of regular, low-dose, sustained-release (SR) morphine compared with placebo for chronic breathlessness. METHODS: Multisite (14 inpatient and outpatient cardiorespiratory and palliative care services in Australia), parallel-arm, double-blind RCT. Adults with chronic breathlessness (modified Medical Research Council≥2) were randomised to 20 mg daily oral SR morphine and laxative (intervention) or placebo and placebo laxative (control) for 7 days. Both groups could take ≤6 doses of 2.5 mg, 'as needed', immediate-release morphine (≤15 mg/24 hours) as required by the ethics review board. The primary endpoint was change from baseline in intensity of breathlessness now (0-100 mm visual analogue scale; two times per day diary) between groups. Secondary endpoints included: worst, best and average breathlessness; unpleasantness of breathlessness now, fatigue; quality of life; function; and harms. RESULTS: Analysed by intention-to-treat, 284 participants were randomised to morphine (n=145) or placebo (n=139). There was no difference between arms for the primary endpoint (mean difference -0.15 mm (95% CI -4.59 to 4.29; p=0.95)), nor secondary endpoints. The placebo group used more doses of oral morphine solution during the treatment period (mean 8.7 vs 5.8 doses; p=0.001). The morphine group had more constipation and nausea/vomiting. There were no cases of respiratory depression nor obtundation. CONCLUSION: No differences were observed between arms for breathlessness, but the intervention arm used less rescue immediate-release morphine. TRIAL REGISTRATION NUMBER: ACTRN12609000806268.

Childhood pneumonia, pleurisy and lung function: a cohort study from the first to sixth decade of life.

INTRODUCTION: Adult spirometry following community-acquired childhood pneumonia has variably been reported as showing obstructive or non-obstructive deficits. We analysed associations between doctor-diagnosed childhood pneumonia/pleurisy and more comprehensive lung function in a middle-aged general population cohort born in 1961. METHODS: Data were from the prospective population-based Tasmanian Longitudinal Health Study cohort. Analysed lung function was from ages 7 years (prebronchodilator spirometry only, n=7097), 45 years (postbronchodilator spirometry, carbon monoxide transfer factor and static lung volumes, n=1220) and 53 years (postbronchodilator spirometry and transfer factor, n=2485). Parent-recalled histories of doctor-diagnosed childhood pneumonia and/or pleurisy were recorded at age 7. Multivariable linear and logistic regression were used. RESULTS: At age 7, compared with no episodes, childhood pneumonia/pleurisy-ever was associated with reduced FEV1:FVC for only those with current asthma (beta-coefficient or change in z-score=-0.20 SD, 95% CI -0.38 to -0.02, p=0.028, p interaction=0.036). At age 45, for all participants, childhood pneumonia/pleurisy-ever was associated with a restrictive pattern: OR 3.02 (1.5 to 6.0), p=0.002 for spirometric restriction (FVC less than the lower limit of normal plus FEV1:FVC greater than the lower limit of normal); total lung capacity z-score -0.26 SD (95% CI -0.38 to -0.13), p<0.001; functional residual capacity -0.16 SD (-0.34 to -0.08), p=0.001; and residual volume -0.18 SD (-0.31 to -0.05), p=0.008. Reduced lung volumes were accompanied by increased carbon monoxide transfer coefficient at both time points (z-score +0.29 SD (0.11 to 0.49), p=0.001 and +0.17 SD (0.04 to 0.29), p=0.008, respectively). DISCUSSION: For this community-based population, doctor-diagnosed childhood pneumonia and/or pleurisy were associated with obstructed lung function at age 7 for children who had current asthma symptoms, but with evidence of 'smaller lungs' when in middle age.

Eosinophils in chronic obstructive pulmonary disease: are they just another biomarker?

PURPOSE OF REVIEW: Interest in blood eosinophils as a biomarker of responsiveness to therapy in chronic obstructive pulmonary disease (COPD) continues to grow, with recommendations regarding their adjunctive use incorporated into the GOLD 2019 treatment algorithm. The present review summarizes some key recent papers referencing differential treatment effects based on blood eosinophil counts. RECENT FINDINGS: Post-hoc analyses of trials of inhaled corticosteroids in COPD have shown greater treatment responses in patients with higher blood eosinophil levels, with some exceptions. Eosinophil-directed treatment with oral corticosteroids showed equivalent benefits to noneosinophil-directed therapy, with reduced corticosteroid exposure. Prespecified analyses of recent prospective trials of therapies incorporating inhaled corticosteroids were generally supportive of previous findings, so evidence for the use of blood eosinophils as biomarkers is gathering. Nonetheless, the anti-interleukin (IL)-5 receptor antagonist benralizumab, which depletes blood eosinophils, showed no treatment benefit in patients with COPD selected for eosinophilic phenotype and treatment of COPD with the IL-5 antagonist, mepolizumab showed inconsistent results. SUMMARY: The 2019 GOLD COPD Strategy document embraced the use of the blood eosinophil to guide ICS therapy in management of patients with stable COPD and frequent exacerbations. Although post-hoc and several prospective studies with prespecified subgroup analyses have supported this approach, questions still remain about how to incorporate this new assessment tool into real-life management of COPD and more research is required to validate its adoption into clinical practice. There is an absence of data to support the use of biologic therapy in patients with an eosinophilic COPD phenotype at this stage.

Home-based pulmonary rehabilitation for COPD using minimal resources: An economic analysis.

BACKGROUND AND OBJECTIVE: This study aimed to compare the cost-effectiveness and cost-utility of home and centre-based pulmonary rehabilitation for adults with stable chronic obstructive pulmonary disease (COPD). METHODS: Prospective economic analyses were undertaken from a health system perspective alongside a randomized controlled equivalence trial in which participants referred to pulmonary rehabilitation undertook a standard 8-week outpatient centre-based or a new home-based programme. Participants underwent clinical assessment prior to programme commencement, immediately following completion and 12 months following programme completion. They provided data for utility (quality-adjusted life years (QALY) determined using SF6D (utility scores for health states) calculated from 36-Item Short Form Health Survey version 2) and effectiveness (change in distance walked on 6-min walk test (Δ6MWD) following pulmonary rehabilitation ). Individual-level cost data for the 12 months following programme completion was sourced from healthcare administration and government databases. RESULTS: Between-group mean difference point estimates for cost (-$4497 (95% CI: -$12 250 to $3257), utility (0.025 (-0.038 to 0.086) QALY) and effectiveness (14 m (-11 to 39) Δ6MWD) favoured the home-based group. Cost-utility analyses demonstrated 63% of estimates falling in the dominant southeast quadrant and the probability that the new home-based model was cost-effective at a $0 threshold for willingness to pay was 78%. Results were robust to a range of sensitivity analyses. Programme completion was associated with significantly lower healthcare costs in the following 12 months. CONCLUSION: Home-based pulmonary rehabilitation provides a cost-effective alternative model for people with COPD who cannot access traditional centre-based programmes.