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Chronic obstructive pulmonary disease (COPD) was traditionally thought to be caused by tobacco smoking. However, recognition of the importance of non-smoking-related risk factors for COPD has increased over the past decade, with evidence on the burden, risk factors, and clinical presentations of COPD in never-smokers. About half of all COPD cases worldwide are due to non-tobacco-related risk factors, which vary by geographical region. These factors include air pollution, occupational exposures, poorly controlled asthma, environmental tobacco smoke, infectious diseases, and low socioeconomic status. Impaired lung growth during childhood, caused by a range of early-life exposures, is associated with an increased risk of COPD. Potential mechanisms for the pathogenesis of COPD in never-smokers include inflammation, oxidative stress, airway remodelling, and accelerated lung ageing. Compared with smokers who develop COPD, never-smokers with COPD have relatively mild chronic respiratory symptoms, little or no emphysema, milder airflow limitation, and fewer comorbidities; however, exacerbations can still be frequent. Further research-including epidemiological, translational, clinical, and implementation studies-is needed to address gaps in understanding and to advance potential solutions to reduce the burden of COPD in never-smokers.

Objective To determine whether disrupting the renin angiotensin system with angiotensin receptor blockers will improve clinical outcomes in people with covid-19. Design CLARITY was a pragmatic, adaptive, multicentre, phase 3, randomised controlled trial. Setting 17 hospital sites in India and Australia. Participants Participants were at least 18 years old, previously untreated with angiotensin receptor blockers, with a laboratory confirmed diagnosis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection who had been admitted to hospital for management of covid-19. Intervention Oral angiotensin receptor blockers (telmisartan in India) or placebo (1:1) for 28 days. Main outcome measures The primary endpoint was covid-19 disease severity using a modified World Health Organization Clinical Progression Scale (WHO scale) at day 14. Secondary outcomes were WHO scale scores at day 28, mortality, intensive care unit admission, and respiratory failure. Analyses were evaluated on an ordinal scale in the intention-to-treat population. Results Between 3 May 2020 and 13 November 2021, 2930 people were screened for eligibility, with 393 randomly assigned to angiotensin receptor blockers (of which 388 (98.7%) to telmisartan 40 mg/day) and 394 to the control group. 787 participants were randomised: 778 (98.9%) from India and nine (1.1%) from Australia. The median WHO scale score at day 14 was 1 (interquartile range 1-1) in 384 participants assigned angiotensin receptor blockers and 1 (1-1) in 382 participants assigned placebo (adjusted odds ratio 1.51 (95% credible interval 1.02 to 2.23), probability of an odds ratio of >1 (Pr(OR>1)=0.98). WHO scale scores at day 28 showed little evidence of difference between groups (1.02 (0.55 to 1.87), Pr(OR>1)=0.53). The trial was stopped when a prespecified futility rule was met. Conclusions In patients admitted to hospital for covid-19, mostly with mild disease, not requiring oxygen, no evidence of benefit, based on disease severity score, was found for treatment with angiotensin receptor blockers, using predominantly 40 mg/day of telmisartan. Trial registration ClinicalTrials.gov NCT04394117 .

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

Thomas Bradbury,1 Gian Luca Di Tanna,1 Anish Scaria,1 Allison Martin,1 Fu-Qiang Wen,2 Nan-Shan Zhong,3 Jin-Ping Zheng,3 Peter J Barnes,4 Bartolome Celli,5 Norbert Berend,1 Christine R Jenkins1 On behalf of the TASCS Investigators1Respiratory Group, The George Institute for Global Health, Sydney, NSW 2042, Australia; 2West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 3State Key Laboratory of Respiratory Disease, National Clinical Research Centre for Respiratory Disease, First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 4National Heart & Lung Institute, Imperial College, London, UK; 5Pulmonary and Critical Care Division, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USACorrespondence: Thomas BradburyRespiratory Group, The George Institute for Global Health, Level 5, 1 King St, Newtown, Sydney, NSW 2042, Australia, Tel +61 2 8052 4413, Email tbradbury@georgeinstitute.org.auBackground and Objectives: The burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention.Methods: This was a post-hoc analysis of the TASCS dataset – a double-blinded, placebo-controlled trial conducted in patients with moderate–severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥ 300 eosinophils/μL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate.Results: Of 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (± 8) years and a predicted forced expiratory volume in 1s (FEV1) of 43% (± 16). The annualized moderate–severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06– 1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George’s Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups.Conclusion: Combination low-dose theophylline and prednisone was associated with a significant increase in the annual moderate-severe exacerbation rate in participants with a blood eosinophil count ≥ 300 cells/μL compared to placebo.Keywords: eosinophil, COPD, clinical trial, China, theophylline, prednisone

International audience; An individual's sex (nominally 'male' or 'female', based on biological attributes) and gender (a complex term, referring to socially constructed roles, behaviors, and expressions of identity) influences the clinical course of asthma in several ways. The physiological development of the lungs and effects of sex hormones may explain why more boys have asthma than girls, and post-puberty, more women have asthma than men. Female sex hormones have an impact throughout the lifespan and are associated with poor asthma control. Gender may influence exposure to asthma triggers, and sex and gender can influence the prevalence of comorbidities and interactions with healthcare professionals (HCPs). Despite widely reported sex and gender-based differences in asthma and asthma management, these issues are frequently not considered by HCPs. There is also inconsistency around use of 'sex' and 'gender' in scientific discourse, and research is needed to better define sex and gender-based differences and how they might interact to influence asthma outcomes. This review outlines the impact an individual's sex and gender can have on the pathogenesis, clinical course, diagnosis, treatment, and management of asthma.

Background Around 10% of adults suffer from clinically significant breathlessness. High quality and actionable patient education materials (PEMs) and patient decision aids (PDAs) have an important role for shared decision making and patient self-management. Objective To systematically assess the effectiveness of patient education materials (PEMs) and patient decision aids (PDAs) on clinical outcomes. Secondly, to assess the quality of PEMs and PDAs for breathlessness that are accessible online. Methods A systematic review of PEM or PDA intervention for breathlessness published between 1 January 2010 and November 2020 was conducted. An environmental scan and quality assessment of publicly available PEMs and PDAs was also conducted. Results Out of 2985 records, five studies were eligible for inclusion in this systematic review. Results of two randomised controlled trials suggest potential effectiveness of PEMs to improve patient reported outcomes and reduce healthcare utilization. In the environmental scan, 88 materials were included. Minimum reading age for most was high (Grade 10) and PEMs scored an average of 87% for understandability and 67% for actionability. Based on the DISCERN tool only 10 were classified as high quality. Conclusion There is a paucity of evidence on the effectiveness of PEMs and PDAs for improvement in breathlessness. There is a need to develop higher quality PEMs for breathlessness.

Wildfires are increasing and cause health effects. The immediate and ongoing health impacts of prolonged wildfire smoke exposure in severe asthma are unknown. This longitudinal study examined the experiences and health impacts of prolonged wildfire (bushfire) smoke exposure in adults with severe asthma during the 2019/2020 Australian bushfire period. Participants from Eastern/Southern Australia who had previously enrolled in an asthma registry completed a questionnaire survey regarding symptoms, asthma attacks, quality of life and smoke exposure mitigation during the bushfires and in the months following exposure. Daily individualized exposure to bushfire particulate matter (PM2.5) was estimated by geolocation and validated modelling. Respondents (n = 240) had a median age of 63 years, 60% were female and 92% had severe asthma. They experienced prolonged intense PM2.5 exposure (mean PM2.5 32.5 μg/m3 on 55 bushfire days). Most (83%) of the participants experienced symptoms during the bushfire period, including: breathlessness (57%); wheeze/whistling chest (53%); and cough (50%). A total of 44% required oral corticosteroid treatment for an asthma attack and 65% reported reduced capacity to participate in usual activities. About half of the participants received information/advice regarding asthma management (45%) and smoke exposure minimization strategies (52%). Most of the participants stayed indoors (88%) and kept the windows/doors shut when inside (93%), but this did not clearly mitigate the symptoms. Following the bushfire period, 65% of the participants reported persistent asthma symptoms. Monoclonal antibody use for asthma was associated with a reduced risk of persistent symptoms. Intense and prolonged PM2.5 exposure during the 2019/2020 bushfires was associated with acute and persistent symptoms among people with severe asthma. There are opportunities to improve the exposure mitigation strategies and communicate these to people with severe asthma.

Non-invasive ventilation (NIV) improves outcomes in patients with acute exacerbations of COPD (AECOPD); however, the efficacy in relieving dyspnoea is uncertain. The objective of this systematic review was to identify, synthesize and interpret the data regarding the relief of dyspnoea afforded by NIV in patients admitted with acute respiratory failure occurring during AECOPD.Randomized controlled trials (RCTs) comparing usual medical care (UMC) to UMC plus NIV and reporting dyspnoea as a patient-reported outcome were identified by searching relevant databases and manual searching. The full text of potentially relevant articles was retrieved. Data describing the impact of NIV on dyspnoea was extracted.Four RCTs met the review criteria. One found NIV did not relieve dyspnoea. The other three RCTs reported NIV relieving dyspnoea. The degree of dyspnoea relief was clinically significant in two of these three studies. However, in all but one RCT, methodological or reporting limitations constrain the confidence that can be had in this conclusion.Limited data exist to determine if NIV relieves subjective dyspnoea in AECOPD. Due to limitations in these studies, it is not possible to definitively conclude if NIV relieves dyspnoea. Standardized reporting and analysis of patient reported outcomes will facilitate objective comparisons of interventions with respect to symptom relief. Future studies involving NIV should routinely incorporate patient reported outcomes in order to answer the important clinical question: 'Does NIV relieve dyspnoea?'

Cough and a reduction in vital capacity have recently been reported following breath-hold dives to depths of 25-75 m. We sought to investigate whether repetitive dives to depths of less than 30 m would elicit similar effects.Participants in a single-day spearfishing competition were recruited. Subjects performed spirometry before and after the 5-h event. Demographics, medical and diving history, respiratory symptoms and competition diving statistics were collected.Twenty-five subjects (two females), age 33 years (11) (mean (SD)), were studied. During the competition each subject completed 76 (33) dives, to 10 (3) m depth, with each dive lasting 0.9 (0.3) min. Maximum depth was 17 (4) m. No respiratory symptoms were reported. There was no difference in spirometry before and after competition except for FEF(25-75%), which increased by 0.16(0.34) L (P0.05).Pulmonary oedema or lung injury is not common after repetitive breath-hold diving to depths to 25 m, or is too mild to be reflected in symptoms or spirometry.

Glossopharyngeal insufflation (GI) is a technique practised by competitive breath-hold divers to enhance their performance. Using the oropharyngeal musculature, air is pumped into the lungs to increase the lung volume above physiological TLC. Experienced breath-hold divers can increase their lung volumes by up to 3 L. Although the potential for lung injury is evident, there is limited information available. The aim of this study was to examine whether there is any evidence of lung injury following GI, independent of diving.Six male, competitive breath-hold divers were studied. CT of the thorax was performed during breath-holding at supramaximal lung volumes following GI (CT(GI)), and subsequently at baseline TLC (CT(TLC)). CT scans were performed a minimum of 3 days apart. Images were analysed for evidence of pneumomediastinum or pneumothorax by investigators who were blinded to the procedure.None of the subjects showed symptoms or signs of pneumomediastinum. However, in five of six subjects a pneumomediastinum was detected during the CT(GI). In three subjects a pneumomediastinum was detected on the CT(GI), but had resolved by the time of the CT(TLC). In two subjects a pneumomediastinum was seen on both the CT(GI) and the CT(TLC), and these were larger on the day that a maximal GI manoeuvre had been performed. The single subject, in whom a pneumomediastinum was not detected, was demonstrated separately to not be proficient at GI.Barotrauma was observed in breath-hold divers who increased their lung volumes by GI. The long-term effects of this barotrauma are uncertain and longitudinal studies are required to assess cumulative lung damage.

Osteoporosis is common in patients with COPD, but its prevalence and progression are not well characterized. Concerns have been raised over the possible deleterious effect of long-term therapy with inhaled corticosteroids (ICSs) on bone density in this population. Here, we investigated the long-term effects of therapy with fluticasone propionate (FP) alone, salmeterol (SAL) alone, and a SAL/FP combination (SFC) on bone mineral density (BMD) and bone fractures in patients with moderate-to-severe COPD in the TOwards a Revolution in COPD Health (TORCH) study.A randomized, double-blind, parallel-group, placebo-controlled study conducted at 88 US centers involving 658 patients (a subset of 6,184 international subjects in TORCH). Therapy with placebo, SAL (50 microg), FP (500 microg), or SFC (SAL 50 microg/FP 500 microg) twice daily was administered for 3 years. Baseline and yearly measurements of BMD at the hip and lumbar spine were performed. The incidence of traumatic and nontraumatic bone fractures was recorded.At baseline, 18% of men and 30% of women had osteoporosis, and 42% of men and 41% of women had osteopenia based on BMD assessments. Forty-three percent of subjects completed all testing. The changes in BMD at the hip and lumbar spine over 3 years were small. No significant differences were observed between treatment arms (adjusted mean percent change from baseline at hip was -3.1% for placebo, -1.7% for SAL, -2.9% for FP, and -3.2% for SFC therapy, respectively; while, the corresponding changes for the lumbar spine were 0, 1.5%, -0.3%, and -0.3% for placebo, respectively, SAL, FP, and SFC therapy). The incidence of fractures was low and was similar for all treatments (5.1% to 6.3%).Osteoporosis is highly prevalent in patients with COPD, irrespective of gender. In the TORCH study, no significant effect on BMD was detected for ICS therapy compared with placebo.ClinicalTrials.gov Identifier: NTC00268216.

Asthma is prevalent among elderly Australians but is often misdiagnosed and undertreated. Asthma presents with the same clinical features in the elderly as in the younger population.This article identifies current knowledge about the needs of elderly people with asthma, as well as the knowledge gaps currently existing in this area of health care.A significant proportion of elderly people with asthma go undiagnosed. Elderly patients under-report symptoms and attribute breathlessness to age and other comorbidities. Other difficulties include impaired perception of asthma severity, poor medication adherence, physical disability, cognitive dysfunction, and a passive self management approach. These all contribute to poorer asthma outcomes among the elderly. The management of asthma among the elderly is likely to improve if specific needs are addressed with tailored educational interventions and appropriate care.