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Rationale: Chronic obstructive pulmonary disease (COPD) is associated with an increased risk of cardiovascular and cardiopulmonary events. In the phase III, 52-week ETHOS trial (NCT02465567), triple therapy with budesonide/glycopyrrolate/formoterol fumarate (BGF) reduced rates of moderate/severe exacerbations and all-cause mortality compared with dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Furthermore, the effect of BGF on time to first severe exacerbation has not been reported. Objectives: To assess the effects of BGF 320/18/9.6 μg (BGF 320) and other inhaled corticosteroid-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from the ETHOS trial. Methods: Patients with moderate to very severe COPD and a history of exacerbations were randomized to twice-daily BGF 320, BGF 160/18/9.6 μg, BFF 320/9.6 μg, or GFF 18/9.6 μg (GFF). Time to first severe COPD exacerbation was a prespecified endpoint; post hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event, time to first cardiovascular adverse event (AE) of special interest, time to first cardiac AE, and time to the composite endpoint of first severe cardiopulmonary event. Measurements and Main Results: BGF 320 reduced the rate of first occurrence (hazard ratio [95% confidence interval]) of cardiovascular and severe cardiopulmonary events versus GFF, including for time to first cardiovascular adverse event of special interest (0.63 [0.48, 0.82]), cardiac AE (0.60 [0.48, 0.76]), and severe cardiopulmonary event (0.80 [0.67, 0.95]). Conclusions: BGF had a benefit on cardiovascular endpoints and severe cardiopulmonary events versus GFF in patients with moderate to very severe COPD.

Background: We evaluated the inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β 2 -agonist (ICS/LAMA/LABA) triple therapy with budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) versus dual LAMA/LABA and ICS/LABA therapies in patients with chronic obstructive pulmonary disease (COPD) and phenotypic features of asthma (bronchodilator reversibility and elevated blood eosinophils), but no asthma diagnosis, for whom treatment guidelines are limited., Patients and Methods: KRONOS (NCT02497001) and ETHOS (NCT02465567) enrolled patients with moderate-to-very-severe COPD, no current asthma diagnosis, and either ≥0 (KRONOS) or ≥1 (ETHOS) moderate/severe exacerbations in the prior year. This pooled post hoc analysis evaluated trough forced expiratory volume in 1 second (FEV 1 ) and FEV 1 area under the curve from hours 0 to 4 (AUC 0-4 ) change from baseline over 12-24 weeks, moderate/severe exacerbation rates, and St George's Respiratory Questionnaire (SGRQ) total score over 24 weeks with ICS/LAMA/LABA (BGF 320/14.4/10 µg), LAMA/LABA (glycopyrronium/formoterol fumarate dihydrate [GFF] 14.4/10 µg), and ICS/LABA (budesonide/formoterol fumarate dihydrate [BFF] 320/10 µg) in patients with phenotypic features of asthma defined as reversibility to salbutamol and blood eosinophils ≥300 cells/mm 3 . Analyses were not adjusted for multiplicity., Results: BGF improved trough FEV 1 and FEV 1 AUC 0-4 versus GFF (least squares mean [LSM] difference [95% confidence interval (CI)] 125 [39-211] and 153 [59-247] mL) and BFF (LSM difference [95% CI] 118 [30-207] and 146 [49-243] mL). Exacerbation rates were estimated to be lower with BGF versus GFF and BFF (respective rate ratios [95% CI] 0.28 [0.19-0.43] and 0.69 [0.45-1.05]) and SGRQ total score was estimated to be improved with BGF versus GFF and BFF (respective LSM differences [95% CI] -5.18 [-8.11 to -2.24] and -1.09 [-4.08 to 1.91])., Conclusion: BGF was estimated to have benefits on lung function, exacerbations, and health-related quality of life versus dual therapies in patients with COPD and phenotypic features of asthma., Trial Registration: ClinicalTrials.gov NCT02497001 and NCT02465567., Competing Interests: SM has received lecture fees from AstraZeneca, GlaxoSmithKline, KYORIN Pharmaceutical, Nippon Boehringer Ingelheim, and Novartis Pharma. MS is an employee of AstraZeneca K.K. and holds stock and/or stock options in the company. JRH reports grants from AstraZeneca, consulting fees from AstraZeneca; speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi, and Takeda; travel support from AstraZeneca; and receipt of equipment from Nonin. DP, JM, KB, PFD, AM, and MP are employees of AstraZeneca and hold stock and/or stock options in the company. EAD is a former employee of AstraZeneca and held stock and/or stock options in the company., (© 2024 Muro et al.)

Introduction: Chronic obstructive pulmonary disease (COPD) ranks among the top three global causes of death, with 90% of fatalities concentrated in low- and middle-income countries (LMICs). The projected rise in COPD burden, especially in LMICs, emphasizes the need to address the challenges for effective control and reversal of this trend. We aimed to provide an overview, and propose potential solutions to these challenges., Areas Covered: We highlight the challenges faced in managing COPD in LMICs and put forward the potential approaches to mitigate the same., Expert Opinion: In LMICs, the effective management of COPD encounters numerous barriers. These include limited access to critical diagnostic services, inadequately trained healthcare personnel, shortages of inhaler medications, oxygen therapy, insufficient access to vaccines, and pulmonary rehabilitation programs. Compounding the above challenges is the late presentation due to misdiagnosis by health workers, and limited access to vital diagnostics. Moreover, the pharmacological armamentarium for optimal COPD therapy, notably inhaled therapies, face constraints in both access and affordability. We propose multi-level and multifaceted interventions to address the urgent need for enhanced respiratory care, human resource capacity building, relevant diagnostic approaches, increased access to medications, government, regional and global efforts to achieve optimal COPD management in LMICs.

Background: Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular disease (CVD). The extent to which the excess CVD risk is captured by risk factors in QRISK, a widely used CVD risk scoring tool, is not well studied., Methods: We created an incidence cohort of diagnosed COPD patients from the United Kingdom (UK) Clinical Practice Research Datalink GOLD database (January 1998-July 2018). The outcome was a composite of fatal or non-fatal CVD events. Sex-specific age-standardised incidence ratios (SIR) were compared with values for the UK primary-care population. The observed 10-year CVD risk was derived using the Kaplan-Meier estimator and was compared with predicted 10-year risk from the QRISK3 tool., Results: 13 208 patients (mean age 64.9 years, 45% women) were included. CVD incidence was 3.53 events per 100 person-years. The SIR of CVD was 1.71 (95% CI 1.61 to 1.75) in women and 1.62 (95%CI 1.54-1.64) in men. SIR was particularly high among patients younger than 65 years (women=2.13 (95% CI 1.94 to 2.19); men=1.86 (95% CI 1.74 to 1.90)). On average, the observed 10-year risk was 52% higher than QRISK predicted score (33.5% vs 22.1%). The difference was higher in patients younger than 65 years (observed risk 82% higher than predicted)., Conclusion: People living with COPD are at a significantly heightened risk of CVD over and beyond their predicted risk. This is particularly the case for younger people whose 10-year CVD risk can be >80% higher than predicted. Risk scoring tools must be validated and revised to provide accurate CVD predictions in patients with COPD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Rationale: COPD and bronchiectasis are commonly reported together. Studies report varying impacts of co-diagnosis on outcomes, which may be related to different definitions of disease used across studies. Objectives: To investigate the prevalence of chronic obstructive pulmonary disease (COPD) associated with bronchiectasis and its relationship with clinical outcomes. We further investigated the impact of implementing the standardized ROSE criteria (radiological bronchiectasis [R], obstruction [FEV 1 /FVC ratio <0.7; O], symptoms [S], and exposure [⩾10 pack-years of smoking; E]), an objective definition of the association of bronchiectasis with COPD. Methods: Analysis of the EMBARC (European Bronchiectasis Registry), a prospective observational study of patients with computed tomography-confirmed bronchiectasis from 28 countries. The ROSE criteria were used to objectively define the association of bronchiectasis with COPD. Key outcomes during a maximum of 5 years of follow-up were exacerbations, hospitalization, and mortality. Measurements and Main Results: A total of 16,730 patients with bronchiectasis were included; 4,336 had a clinician-assigned codiagnosis of COPD, and these patients had more exacerbations, worse quality of life, and higher severity scores. We observed marked overdiagnosis of COPD: 22.2% of patients with a diagnosis of COPD did not have airflow obstruction and 31.9% did not have a history of ⩾10 pack-years of smoking. Therefore, 2,157 patients (55.4%) met the ROSE criteria for COPD. Compared with patients without COPD, patients who met the ROSE criteria had increased risks of exacerbations and exacerbations resulting in hospitalization during follow-up (incidence rate ratio, 1.25; 95% confidence interval, 1.15-1.35; vs. incidence rate ratio, 1.69; 95% confidence interval, 1.51-1.90, respectively). Conclusions: The label of COPD is often applied to patients with bronchiectasis who do not have objective evidence of airflow obstruction or a smoking history. Patients with a clinical label of COPD have worse clinical outcomes.

Chronic obstructive pulmonary disease (COPD) constitutes a major global health burden and is the third leading cause of death worldwide. A high proportion of patients with COPD have cardiovascular disease, but there is also evidence that COPD is a risk factor for adverse outcomes in cardiovascular disease. Patients with COPD frequently die of respiratory and cardiovascular causes, yet the identification and management of cardiopulmonary risk remain suboptimal owing to limited awareness and clinical intervention. Acute exacerbations punctuate the progression of COPD in many patients, reducing lung function and increasing the risk of subsequent exacerbations and cardiovascular events that may lead to early death. This narrative review defines and summarises the principles of COPD-associated cardiopulmonary risk, and examines respiratory interventions currently available to modify this risk, as well as providing expert opinion on future approaches to addressing cardiopulmonary risk., (© 2024. The Author(s).)

Introduction: Chronic Obstructive Pulmonary Disease (COPD) and cardiovascular diseases (CVD) commonly co-exist. Outcomes of people living with both conditions are poor in terms of symptom burden, receiving evidence-based treatment and mortality. Increased understanding of the underlying mechanisms may help to identify treatments to relieve this disease burden. This narrative review covers the overlap of COPD and CVD with a focus on clinical presentation, mechanisms, and interventions. Literature up to December 2023 are cited., Areas Covered: 1. What is COPD 2. The co-existence of COPD and cardiovascular disease 3. Mechanisms of cardiovascular disease in COPD. 4. Populations with COPD are at risk of CVD 5. Complexity in the co-diagnosis of COPD in those with cardiovascular disease. 6. Therapy for COPD and implications for cardiovascular events and risk. 7. Cardiovascular risk and exacerbations of COPD. 8. Pro-active identification and management of CV risk in COPD., Expert Opinion: The prospective identification of co-morbid COPD in CVD patients and of CVD and CV risk in people with COPD is crucial for optimizing clinical outcomes. This includes the identification of novel treatment targets and the design of clinical trials specifically designed to reduce the cardiovascular burden and mortality associated with COPD. Databases searched: Pubmed, 2006-2023.

Introduction: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition with varied clinical and pathophysiological characteristics. Although there is increasing evidence that COPD in low-income and middle-income countries may have different clinical characteristics from that in high-income countries, little is known about COPD phenotypes in these settings. We describe the clinical characteristics and risk factor profile of a COPD population in Uganda., Methods: We cross sectionally analysed the baseline clinical characteristics of 323 patients with COPD aged 30 years and above who were attending 2 national referral outpatient facilities in Kampala, Uganda between July 2019 and March 2021. Logistic regression was used to determine factors associated with spirometric disease severity., Results: The median age was 62 years; 51.1% females; 93.5% scored COPD Assessment Test >10; 63.8% modified medical research council (mMRC) >2; 71.8% had wheezing; 16.7% HIV positive; 20.4% had a history of pulmonary tuberculosis (TB); 50% with blood eosinophilic count >3%, 51.7% had 3 or more exacerbations in the past year. Greater severity by Global initiative for Chronic Obstructive Lung Disease (GOLD) stage was inversely related to age (aOR=0.95, 95% CI 0.92 to 0.97), and obesity compared with underweight (aOR=0.25, 95% CI 0.07 to 0.82). Regarding clinical factors, more severe airflow obstruction was associated with SPO 2 <93% (aOR=3.79, 95% CI 2.05 to 7.00), mMRC ≥2 (aOR=2.21, 95% CI 1.08 to 4.53), and a history of severe exacerbations (aOR=2.64, 95% CI 1.32 to 5.26)., Conclusion: Patients with COPD in this population had specific characteristics and risk factor profiles including HIV and TB meriting tailored preventative approaches. Further studies are needed to better understand the pathophysiological mechanisms at play and the therapeutic implications of these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Chronic obstructive pulmonary disease (COPD) disproportionately affects low- and middle-income countries. Health systems are ill prepared to manage the increase in COPD cases. Methods: We performed a pilot effectiveness-implementation randomized field trial of a community health worker (CHW)-supported, 1-year self-management intervention in individuals with COPD grades B-D. The study took place in low-resource settings of Nepal, Peru, and Uganda. The primary outcome was the St. George's Respiratory Questionnaire (SGRQ) score at 1 year. We evaluated differences in moderate to severe exacerbations, all-cause hospitalizations, and the EuroQol score (EQ-5D-3 L) at 12 months. Measurements and Main Results: We randomly assigned 239 participants (119 control arm, 120 intervention arm) with grades B-D COPD to a multicomponent, CHW-supported intervention or standard of care and COPD education. Twenty-five participants (21%) died or were lost to follow-up in the control arm compared with 11 (9%) in the intervention arm. At 12 months, there was no difference in mean total SGRQ score between the intervention and control arms (34.7 vs. 34.0 points; adjusted mean difference, 1.0; 95% confidence interval, -4.2, 6.1; P  = 0.71). The intervention arm had a higher proportion of hospitalizations than the control arm (10% vs. 5.2%; adjusted odds ratio, 2.2; 95% confidence interval, 0.8, 7.5; P  = 0.15) at 12 months. Conclusions: A CHW-based intervention to support self-management of acute exacerbations of COPD in three resource-poor settings did not result in differences in SGRQ scores at 1 year. Fidelity was high, and intervention engagement was moderate. Although these results cannot differentiate between a failed intervention or implementation, they nonetheless suggest that we need to revisit our strategy. Clinical trial registered with www.clinicaltrials.gov (NCT03359915).

Objective: To translate and cross-culturally adapt the COPD in Low- and middle-income countries (LMICs) Assessment (COLA) questionnaire into Brazilian Portuguese, a case-finding instrument for chronic obstructive pulmonary disease (COPD)., Methods: Translation and cross-cultural adaptation were completed in six steps: the original version was translated into Brazilian Portuguese by two native speakers of the target language; the translated versions were synthesized; back-translation was performed by two native speakers of the original language; the back-translation and the Brazilian Portuguese version of the COLA were reviewed and harmonized by an expert committee of specialists; and, then, the pre-final version was tested by 30 health professionals who were asked if the items were clear to understand. The acceptability, clarity, and understandability of the translated version were evaluated. A final review of the questionnaire was produced by the authors and approved by the author of the original questionnaire., Results: Some idiomatic, semantic, and experiential inconsistencies were identified and properly adjusted. Item 3 was considered the most unclear item (23,3%). Items 7, 8, and 9 presented clarity above 80% (93%, 90%, and 90%, respectively). Suggestions were discussed and incorporated into the tool and COLA was found to be clear and easy to understand., Conclusions: The Brazilian version of the COLA was easily understood by healthcare professionals and adapted to Brazilian culture. Translation and cultural adaptation of the COLA instrument into Brazilian Portuguese can be an important case-finding instrument for chronic obstructive pulmonary disease in Brazil.

Discharge bundles, comprising evidence-based practices to be implemented prior to discharge, aim to optimise patient outcomes. They have been recommended to address high readmission rates in patients who have been hospitalised for an exacerbation of chronic obstructive pulmonary disease (COPD). Hospital readmission is associated with increased morbidity and healthcare resource utilisation, contributing substantially to the economic burden of COPD. Previous studies suggest that COPD discharge bundles may result in fewer hospital readmissions, lower risk of mortality and improvement of patient quality of life. However, evidence for their effectiveness is inconsistent, likely owing to variable content and implementation of these bundles. To ensure consistent provision of high-quality care for patients hospitalised with an exacerbation of COPD and reduce readmission rates following discharge, we propose a comprehensive discharge protocol, and provide evidence highlighting the importance of each element of the protocol. We then review care bundles used in COPD and other disease areas to understand how they affect patient outcomes, the barriers to implementing these bundles and what strategies have been used in other disease areas to overcome these barriers. We identified four evidence-based care bundle items for review prior to a patient's discharge from hospital, including (1) smoking cessation and assessment of environmental exposures, (2) treatment optimisation, (3) pulmonary rehabilitation, and (4) continuity of care. Resource constraints, lack of staff engagement and knowledge, and complexity of the COPD population were some of the key barriers inhibiting effective bundle implementation. These barriers can be addressed by applying learnings on successful bundle implementation from other disease areas, such as healthcare practitioner education and audit and feedback. By utilising the relevant implementation strategies, discharge bundles can be more (cost-)effectively delivered to improve patient outcomes, reduce readmission rates and ensure continuity of care for patients who have been discharged from hospital following a COPD exacerbation., (© 2023. The Author(s).)

Rationale: Chronic obstructive pulmonary disease (COPD) is a prevalent and burdensome condition in low- and middle-income countries (LMICs). Challenges to better care include more effective diagnosis and access to affordable interventions. There are no previous reports describing therapeutic needs of populations with COPD in LMICs who were identified through screening. Objectives: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. Methods: We compared interventions recommended by the international Global Initiative for Chronic Obstructive Lung Disease COPD strategy document, with that received in 1,000 people with COPD identified by population screening at three LMIC sites in Nepal, Peru, and Uganda. We calculated costs using data on the availability and affordability of medicines. Measurement and Main Results: The greatest unmet need for nonpharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%), and advice on biomass smoke exposure (26%). Ninety-five percent of the cases were previously undiagnosed, and few were receiving therapy (4.5% had short-acting β-agonists). Only three of 47 people (6%) with a previous COPD diagnosis had access to drugs consistent with recommendations. None of those with more severe COPD were accessing appropriate maintenance inhalers. Even when available, maintenance treatments were unaffordable, with 30 days of treatment costing more than a low-skilled worker's daily average wage. Conclusions: We found a significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Although there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis combined with access to affordable interventions could translate to immediate benefit.

Introduction: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period., Methods: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period., Ethics and Dissemination: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language)., Trial Registration Number: ISRCTN15988757., Competing Interests: Competing interests: ADS has received speakers fees or advisory board fees from AstraZeneca, Bayer, GSK, Insmed, Novartis, Gilead and Zambon and has received grants from AstraZeneca, GSK, Novartis and the US COPD Foundation., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Hospitalised patients with exacerbations of COPD (ECOPD) may have physical and functional impairments that impact morbidity and readmission. Therefore, it is crucial to properly identify reduced functionality in these patients to support a personalised rehabilitation. The objective of this study is to summarise and compare the measurement properties of functionality performance-based outcome measures for hospitalised patients with ECOPD., Methods: A systematic review based on the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) was performed. The PubMed, Embase, PEDro and Cochrane databases were searched using terms related to functionality, hospitalised patients with ECOPD and measurement properties. Studies were selected and extracted by two researchers. The COSMIN Risk of Bias checklist was applied to assess the methodological quality of the studies and measurement property results were compared with the criteria for good measurement properties. Quality of evidence was graded using a modified Grades of Recommendation, Assessment, Development and Evaluation approach., Results: 13 studies were included with nine outcome measures, namely the 6-min pegboard ring test, the de Morton mobility index, the incremental shuttle walk test (ISWT), the 6-min walk test (6MWT), maximum inspiratory pressure (MIP), the Berg balance scale, 4-m gait speed, handgrip strength and the 6-min stepper test. Construct validity was rated as sufficient, except for the ISWT. Responsiveness, assessed only for MIP, was considered insufficient and measurement errors for the ISWT and 6MWT were insufficient, with a very low quality of evidence for all measurement properties., Conclusion: Measurement properties of performance-based outcome measures to assess functionality in patients hospitalised with ECOPD are still scarce, with very low evidence supporting validity and a lack of evidence of responsiveness and reliability. Further studies are needed to address this topic and guide assertive and personalised management., Competing Interests: Conflict of interest: N.T. Leonardi reports support for the present manuscript from FAPESP (São Paulo Research Foundation) in the form of English review and article processing charges, as well as support in attending meetings and travels to present products/results of the project. J.R. Hurst reports consulting fees from AstraZeneca, GSK; lecture honoraria from Boehringer Ingelheim, Chiesi, Sanofi, Takeda; travel support and advisory board participation from AstraZeneca; donation of oximeters from Nonin; outside the submitted work. J. Cruz reports travel support to attend the European Respiratory Society Congress 2022 as the representative of the Early Career Members of Assembly 9; and is a member of the Editorial Board of ERJ Open Research (unpaid); outside the submitted work. R.G. Mendes reports support for the present manuscript from FAPESP (São Paulo Research Foundation), in the form of project funding providing support for buying laboratory consumables materials and equipment and also article processing charges and maintenance costs, as well as attending meetings and travels to present products/results of the project. All other authors have nothing to disclose., (Copyright ©The authors 2023.)

Objective: To investigate clinicians' perspectives on the current use of wearable technology for detecting COPD exacerbations, and to identify potential facilitators and barriers to its adoption in clinical settings., Methods: A mixed-method survey was conducted through an online survey platform involving clinicians working with COPD patients. The questionnaires were developed by an expert panel specialising in respiratory medicine at UCL. The questionnaire evaluated clinicians' perspectives on several aspects: the current extent of wearable technology utilisation, the perceived feasibility, and utility of these devices, as well as the potential facilitators and barriers that hinder its wider implementation., Results: Data from 118 clinicians were included in the analysis. Approximately 80% of clinicians did not currently use information from wearable devices in routine clinical care. A majority of clinicians did not have confidence in the effectiveness of wearables and their consequent impact on health outcomes. However, clinicians highlighted the potential value of wearables in helping deliver personalised care and more rapid assistance. Ease of use, technical support and accessibility of data were considered facilitating factors for wearable utilisation. Costs and lack of technical knowledge were the most frequently reported barriers to wearable utilisation., Conclusion: Clinicians' perspectives of the use of wearable technology to detect and monitor COPD exacerbations are variable. While accessibility and technical support facilitate wearable implementation, cost, technical issues, and knowledge act as barriers. Our findings highlight the facilitators and barriers to using wearables in patients with COPD and emphasise the need to assess patients' perspectives on wearable acceptability., Competing Interests: Dr Swapna Mandal reports grants from Imperial College, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2023 Althobiani et al.)

Background: This review aims to synthesise available evidence on the prevalence of chronic obstructive pulmonary disease (COPD), associated risk factors, hospitalisations and COPD readmissions in Africa., Method: Using the Met-Analyses and Systematic Reviews of Observational Studies guideline, electronic databases were searched from inception to 1 October 2021. The quality of studies was assessed using the Newcastle-Ottawa Scale. Evidence from retrieved articles was synthesised, and a random-effect model meta-analysis was conducted. The protocol was registered on PROSPERO., Results: Thirty-nine studies met the inclusion criteria, with 13 included in the meta-analysis. The prevalence of COPD varied between the Global Initiative for Chronic Obstructive Lung Disease (2%-24%), American Thoracic Society/European Respiratory Society (1%-17%) and Medical Research Council chronic bronchitis (2%-11%) criteria, respectively. Increasing age, wheezing and asthma were consistent risk factors for COPD from studies included in the narrative synthesis. Our meta-analysis indicated that prior tuberculosis ((OR 5.98, 95% CI 4.18 to 8.56), smoking (OR 2.80, 95% CI: 2.19 to 3.59) and use of biomass fuel (OR 1.52, 95% CI: 1.39 to 1.67)) were significant risk factors for COPD. Long-term oxygen therapy (HR 4.97, 95% CI (1.04 to 23.74)) and frequent hospitalisation (≥3 per year) (HR 11.48, 95% CI (1.31 to 100.79)) were risk factors associated with 30-day COPD readmission., Conclusion: This study not only highlights specific risk factors for COPD risk in Africa but also demonstrates the paucity and absence of research in several countries in a continent with substantial COPD-related mortality. Our findings contribute towards the development of evidence-based clinical guidelines for COPD in Africa.PROSPERO registration numberCRD42020210581., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

In 2022, over 3 million people died of chronic obstructive pulmonary disease (COPD) and the global burden of the disease is expected to increase over the coming decades. Recommendations for the treatment and management of patients with COPD are published by the Global Initiative for Chronic Obstructive Lung Disease, and updated annually with scientific evidence-based recommendations. The 2023 updates, published in November 2022, contain key changes to recommendations for diagnosis and treatment of COPD that are anticipated to have a significant impact on clinical practice for patients with COPD. Updates to how COPD is defined and diagnosed, including the expansion of contributing factors beyond tobacco use, have the potential to lead to the diagnosis of more patients and to allow for the implementation of early interventions for patients during early stages of the disease. Simplification of the treatment algorithms, and placement of triple therapy within these algorithms, will support clinicians in providing appropriate, timely treatment for patients with COPD with a focus on reducing the risk of future exacerbations. Finally, recognition of mortality reduction as a treatment goal in COPD supports an increase in the use of triple therapy, the only pharmacological intervention that has been demonstrated to improve survival for patients with COPD. Although further guidance and clarification are needed in some areas, such as use of blood eosinophil counts in guiding treatment decisions and implementation of treatment protocols following hospitalizations, recent updates to the GOLD recommendations will support clinicians in addressing current gaps in patient care. Clinicians should utilize these recommendations to drive the early diagnosis of patients with COPD, the identification of exacerbations, and the selection of appropriate, timely treatments for patients., Competing Interests: Diana R Tamondong-Lachica has received consultancy fees from AstraZeneca. Neil Skolnik has received speaker/consultancy fees from Abbott, AstraZeneca, Bayer, Boehringer Ingelheim, Lilly, Genentech, GlaxoSmithKline, Idorsia, Merck, Novartis, Sanofi, Sanofi Pasteur, and Teva; and research funding from AstraZeneca, Bayer, GlaxoSmithKline, Novo Nordisk, and Sanofi. John R Hurst has received speaker/consultancy fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, and Takeda. Nathaniel Marchetti has received speaker/consultancy fees from AstraZeneca; grants from CSL Behring and NIH; and research funding from AstraZeneca, Chiesi, GlaxoSmithKline, and Sanofi. Adrian Paul J Rabe is an employee of AstraZeneca. Maria Montes de Oca has received speaker fees from AstraZeneca and GlaxoSmithKline. Bartolome R Celli has received speaker/consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Gala Therapeutics, GlaxoSmithKline, Menarini, Novartis, Pulmonx, and Sanofi-Aventis; neither he, nor any member of his family, has shares or interest in any company; and he has not received or had any relationship with money from the tobacco industry. The authors report no other conflicts of interest in this work., (© 2023 Tamondong-Lachica et al.)

Patients with chronic obstructive pulmonary disease (COPD) may suffer from acute episodes of worsening dyspnea, often associated with increased cough, sputum, and/or sputum purulence. These exacerbations of COPD (ECOPDs) impact health status, accelerate lung function decline, and increase the risk of hospitalization. Importantly, close to 20% of patients are readmitted within 30 days after hospital discharge, with great cost to the person and society. Approximately 25% and 65% of patients hospitalized for an ECOPD die within 1 and 5 years, respectively. Patients with COPD are usually older and frequently have concomitant chronic diseases, including heart failure, coronary artery disease, arrhythmias, interstitial lung diseases, bronchiectasis, asthma, anxiety, and depression, and are also at increased risk of developing pneumonia, pulmonary embolism, and pneumothorax. All of these morbidities not only increase the risk of subsequent ECOPDs but can also mimic or aggravate them. Importantly, close to 70% of readmissions after an ECOPD hospitalization result from decompensation of other morbidities. These observations suggest that in patients with COPD with worsening dyspnea but without the other classic characteristics of ECOPD, a careful search for these morbidities can help detect them and allow appropriate treatment. For most morbidities, a thorough clinical evaluation supplemented by appropriate clinical investigations can guide the healthcare provider to make a precise diagnosis. This perspective integrates the currently dispersed information available and provides a practical approach to patients with COPD complaining of worsening respiratory symptoms, particularly dyspnea. A systematic approach should help improve outcomes and the personal and societal cost of ECOPDs.

The management of many chronic lung diseases involves multiple antibiotic prescriptions either to treat acute exacerbations or as prophylactic therapy to reduce the frequency of exacerbations and improve patients' quality of life., Aim: To investigate the effects of antibiotics on the homeostasis of bacterial communities in the airways, and how this may contribute to antimicrobial resistance (AMR) among respiratory pathogens and microbiota., Methods: Within an observational cohort study, sputum was collected from 84 patients with chronic obstructive pulmonary disease and/or bronchiectasis at stable state: 47 were receiving antibiotic prophylaxis therapy. V3-V4 16S-rRNA sequencing on Illumina MiSeq, quantitative PCR for typical respiratory pathogens, bacteriology cultures and antimicrobial susceptibility testing of sputum isolates, resistome analysis on a subset of 17 sputum samples using MinION metagenomics sequencing were performed., Finding: The phylogenetic α-diversity and the total bacterial density in sputum were significantly lower in patients receiving prophylactic antibiotics (p=0.014 and 0.029, respectively). Antibiotic prophylaxis was associated with significantly lower relative abundance of respiratory pathogens such as Pseudomonas aeruginosa , Moraxella catarrhalis and members of family Enterobacteriaceae in the airway microbiome, but not Haemophilus influenzae and Streptococcus pneumoniae . No major definite directional shifts in the microbiota composition were identified with prophylactic antibiotic use at the cohort level. Surveillance of AMR and resistome analysis revealed a high frequency of resistance to macrolide and tetracycline in the cohort. AMR expressed by pathogenic bacterial isolates was associated with antibiotics prescribed as 'rescue packs' for prompt initiation of self-treatment of exacerbations (Spearman's rho=0.408, p=0.02)., Conclusions: Antibiotic prophylactic therapy suppresses recognised pathogenic bacteria in the sputum of patients with chronic lung disease. The use of antibiotic rescue packs may be driving AMR in this cohort rather than prophylactic antibiotics., Competing Interests: Competing interests: Newton Mosharafa funds by British Council Egypt and Egyptian Ministry of Higher Education sponsored the PhD of SR., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Inhaled corticosteroids (ICS) are associated with an increased risk of clinical pneumonia among patients with chronic obstructive pulmonary disease (COPD). It is unknown whether the risk of microbiologically verified pneumonia such as pneumococcal pneumonia is increased in ICS users., Methods: The study population consists of all COPD patients followed in outpatient clinics in eastern Denmark during 2010-2017. ICS use was categorized into four categories based on accumulated use. A Cox proportional hazard regression model was used adjusting for age, body mass index, sex, airflow limitation, use of oral corticosteroids, smoking, and year of cohort entry. A propensity score matched analysis was performed for sensitivity analyses., Findings: A total of 21,438 patients were included. Five hundred and eighty-two (2.6%) patients acquired a positive lower airway tract sample with  S. pneumoniae  during follow-up. In the multivariable analysis ICS-use was associated with a dose-dependent risk of  S. pneumoniae as follows: low ICS dose: HR 1.11, 95% CI 0.84 to 1.45, p = 0.5; moderate ICS dose: HR 1.47, 95% CI 1.13 to 1.90, p = 0.004; high ICS dose: HR 1.77, 95% CI 1.38 to 2.29, p < 0.0001, compared to no ICS use. Sensitivity analyses confirmed these results., Interpretation: Use of ICS in patients with severe COPD was associated with an increased and dose-dependent risk of acquiring  S. pneumoniae , but only for moderate and high dose. Caution should be taken when administering high dose of ICS to patients with COPD. Low dose of ICS seemed not to carry this risk., Competing Interests: The authors declare that there are no conflicts of interest regarding this article. However, to ensure full transparency, we disclose the following potential conflicts of interest: PS received payment for lectures by Boehringer Ingelheim AstraZeneca, and GSK. TBS received grants from Sanofi Pasteur, Novo Nordisk Foundation, and Lundbeck foundation, received Consulting fees from Sanofi Pasteur, and Amgen, and received payment for lectures by Sanofi Pasteur, and GSK. TBS participates on Data Safety Monitoring Board or Advisory Board for Sanofi Pasteur and Amgen. ZBH received support for meetings and/or travel by Phizer. AKB received support for meetings and/or travel by PulmonX and reports non-financial support from GSK, during the conduct of the study. AGM received grants from Boehringer Ingelheim and is associated with the startup “Healthy network” producing automated e-stethoscopes. JRH received consulting fees from AstraZeneca, received payment for lectures by Boehringer Ingelheim, and Takeda, and received support to meetings and/or travel by AstraZeneca, and participates in AstraZeneca’s Advisory board and British Thoracic Society. MP received grants from Roche, received consulting fees from Takeda, Therakos, Zambon, and received payment for lectures by Mallinckrodt, PulmonX, and Glaxo-smith Kline, received support for meetings and/or travel by Boehringer-Ingelheim and is Chair of Danish transplant Society, and associated with The ERS group for transplantation. All other authors declare no competing interests in this work., (© 2023 Heerfordt et al.)

Background: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) have decreased exercise tolerance, which may persist for months. In this context, little is known about the associations between muscle strength and recovery of exercise capacity., Objective: To assess whether respiratory and peripheral muscle strength influence recovery of exercise capacity in patients hospitalized due to AECOPD., Methods: Twenty-seven AECOPD patients (aged 69 ± 7 years, 56% male) were included. The following assessments were performed within 24 to 72 h of hospital admission: (i) respiratory muscle strength, measured by maximal inspiratory and expiratory pressures (MIP and MEP); (ii) peripheral muscle strength, assessed by handgrip and quadriceps muscle strength; and (iii) exercise capacity, measured by 6-min walking distance (6MWD). The 6MWD was reassessed 30 days later to determine the recovery of exercise capacity., Results: After 30 days, while 63% of the patients showed clinically important improvement in the 6MWD (recovery ≥ 30 m), 37% showed no change (recovery < 30 m). During hospital stay, the non-recovered group had lower quadriceps muscle strength compared to the recovered group (15 ± 5 vs. 22 ± 6 kgf; P = 0.006), with no significant difference for MIP, MEP and handgrip strength. Only quadriceps muscle strength was associated with recovery of exercise capacity (r = 0.56; P = 0.003)., Conclusion: AECOPD patients with quadriceps muscle weakness during hospitalization have poor recovery of exercise capacity after 30 days. This finding suggests the importance of early rehabilitation to improve quadriceps strength and accelerate functional recovery after AECOPD., Competing Interests: Declarations of Competing Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: COPD is a major comorbidity in lung cancer screening (LCS) cohorts, with a high prevalence of undiagnosed COPD. Combining symptom assessment with spirometry in this setting may enable earlier diagnosis of clinically significant COPD and facilitate increased understanding of lung cancer risk in COPD. In this study, we wished to understand the prevalence, severity, clinical phenotype and lung cancer risk of individuals with symptomatic undiagnosed COPD in a LCS cohort., Methods: 16 010 current or former smokers aged 55-77 years attended a lung health check as part of the SUMMIT Study. A respiratory consultation and spirometry were performed alongside LCS eligibility assessment. Those with symptoms, no previous COPD diagnosis and airflow obstruction were labelled as undiagnosed COPD. Baseline low-dose computed tomography (LDCT) was performed in those at high risk of lung cancer (PLCO m2012 score ≥1.3% and/or meeting USPSTF 2013 criteria)., Results: Nearly one in five (19.7%) met criteria for undiagnosed COPD. Compared with those previously diagnosed, those undiagnosed were more likely to be male (59.1% versus 53.2%; p<0.001), currently smoking (54.9% versus 47.6%; p<0.001) and from an ethnic minority group (p<0.001). Undiagnosed COPD was associated with less forced expiratory volume in 1 s impairment (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1 and 2: 85.3% versus 68.4%; p<0.001) and lower symptom/exacerbation burden (GOLD A and B groups: 95.6% versus 77.9%; p<0.001) than those with known COPD. Multivariate analysis demonstrated that airflow obstruction was an independent risk factor for lung cancer risk on baseline LDCT (adjusted OR 2.74, 95% CI 1.73-4.34; p<0.001), with a high risk seen in those with undiagnosed COPD (adjusted OR 2.79, 95% CI 1.67-4.64; p<0.001)., Conclusions: Targeted case-finding within LCS detects high rates of undiagnosed symptomatic COPD in those most at risk. Individuals with undiagnosed COPD are at high risk for lung cancer., Competing Interests: Conflict of interest: S. Tisi, J.L. Dickson, C. Horst, H. Hall and P. Verghese are all funded or part-funded through GRAIL Inc., as part of the SUMMIT Study. S.M. Janes was a Wellcome Trust Senior Fellow in Clinical Science (WT107963AIA); is supported by Cancer Research UK (CRUK) programme grant EDDCPGM\100002, the Rosetrees Trust, the Roy Castle Lung Cancer foundation, the Garfield Weston Trust and UCLH Charitable Foundation; and reports fees for advisory board work from AstraZeneca, Bard1 Bioscience, Achilles Therapeutics and Jansen, assistance for travel to meetings from AstraZeneca and Takeda, grant income from GRAIL Inc. and Owlstone, and share options from Optellum and Bard1 Lifescience Ltd. S.L. Quaife is supported by a Cancer Research UK (CRUK) Population Research Fellowship (C50664/A24460) and Barts Charity (MRC&U0036). A. Nair is part-funded through the UCLH Biomedical Research Centre. A. Devaraj reports personal fees from Boehringer Ingelheim, Roche, Galacto Biotech, Galapagos and Vicore. A. Hackshaw reports consulting fees from Evidera Inc. and assistance for travel to meetings from GRAIL Inc. J.R. Hurst reports assistance for travel from AstraZeneca and Boehringer Ingelheim, and payment for lectures and presentations from AstraZeneca, Boehringer Ingelheim, Nutricia and Takeda. There are no disclosures from K. Gyertson, V. Bowyer, C. Levermore, A-M. Mullin, J. Teague and L. Farrelly., (Copyright ©The authors 2022.)

Objectives: To develop a computer-based decision support tool (DST) for key decision makers to safely explore the impact on chronic obstructive pulmonary disease (COPD) care of service changes driven by restrictions to prevent the spread of COVID-19., Design: The DST is powered by discrete event simulation which captures the entire patient pathway. To estimate the number of COPD admissions under different scenario settings, a regression model was developed and embedded into the tool. The tool can generate a wide range of patient-related and service-related outputs. Thus, the likely impact of possible changes (eg, COVID-19 restrictions and pandemic scenarios) on patients with COPD and care can be estimated., Setting: COPD services (including outpatient and inpatient departments) at a major provider in central London., Results: Four different scenarios (reflecting the UK government's Plan A, Plan B and Plan C in addition to a benchmark scenario) were run for 1 year. 856, 616 and 484 face-to-face appointments (among 1226 clinic visits) are expected in Plans A, B and C, respectively. Clinic visit quality in Plan A is found to be marginally better than in Plans B and C. Under coronavirus restrictions, lung function tests decreased more than 80% in Plan C as compared with Plan A. Fewer COPD exacerbation-related admissions were seen (284.1 Plan C vs 395.1 in the benchmark) associated with stricter restrictions. Although the results indicate that fewer quality-adjusted life years (in terms of COPD management) would be lost during more severe restrictions, the wider impact on physical and mental health must also be established., Conclusions: This DST will enable COPD services to examine how the latest developments in care delivery and management might impact their service during and beyond the COVID-19 pandemic, and in the event of future pandemics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. COPD exacerbations are associated with a worsening of lung function, increased disease burden, and mortality, and, therefore, preventing their occurrence is an important goal of COPD management. This review was conducted to identify the evidence base regarding risk factors and predictors of moderate-to-severe exacerbations in patients with COPD., Methods: A literature review was performed in Embase, MEDLINE, MEDLINE In-Process, and the Cochrane Central Register of Controlled Trials (CENTRAL). Searches were conducted from January 2015 to July 2019. Eligible publications were peer-reviewed journal articles, published in English, that reported risk factors or predictors for the occurrence of moderate-to-severe exacerbations in adults age ≥ 40 years with a diagnosis of COPD., Results: The literature review identified 5112 references, of which 113 publications (reporting results for 76 studies) met the eligibility criteria and were included in the review. Among the 76 studies included, 61 were observational and 15 were randomized controlled clinical trials. Exacerbation history was the strongest predictor of future exacerbations, with 34 studies reporting a significant association between history of exacerbations and risk of future moderate or severe exacerbations. Other significant risk factors identified in multiple studies included disease severity or bronchodilator reversibility (39 studies), comorbidities (34 studies), higher symptom burden (17 studies), and higher blood eosinophil count (16 studies)., Conclusions: This systematic literature review identified several demographic and clinical characteristics that predict the future risk of COPD exacerbations. Prior exacerbation history was confirmed as the most important predictor of future exacerbations. These prognostic factors may help clinicians identify patients at high risk of exacerbations, which are a major driver of the global burden of COPD, including morbidity and mortality., (© 2022. The Author(s).)

Exacerbations of chronic obstructive pulmonary disease are important events to people living with this condition and a common cause of emergency hospital admission. In the absence of a confirmatory biomarker, an exacerbation remains a clinical diagnosis of exclusion and clinicians must be alert to alternative diagnoses. Most exacerbations are caused by airway infection, particularly with respiratory viruses. The mainstay of exacerbation treatment is an increase in the dose and/or frequency of short-acting beta-agonists, with short-course oral corticosteroids and/or antibiotics. Although there have been no new interventions to treat exacerbations in many years, there is still much variation in care and opportunity to improve outcomes. There has been a new focus on both the management of comorbidities and the optimisation of future care to reduce the risk of further events. This review summarises advances in managing exacerbations of chronic obstructive pulmonary disease, focusing on hospitalised patients.

Chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) are prevalent respiratory conditions that are independently associated with increased cardiovascular disease (CVD). It is not clear from current evidence whether COPD-OSA overlap syndrome confers an additive risk. This systematic review and meta-analysis investigated whether CVD was more prevalent in patients with overlap syndrome compared to either condition alone. We searched four electronic databases, screened 1826 records against the inclusion criteria. After screening, 18 retrospective, observational studies involving 4613 overlap patients, 16,046 OSA patients and 1679 COPD patients met the inclusion criteria. A random-effects meta-analysis of five studies (I 2  = 61%) showed that overlap was associated with a significantly higher risk of hypertension compared to patients with COPD alone (OR = 1.68, 95%CI 1.21-2.35). Overlap was also associated with an increased risk of peripheral vascular disease compared to OSA alone (OR = 3.30 95%CI 2.66-4.10), with a subset of studies also suggesting an increased risk of ischaemic heart disease, heart failure, and cerebrovascular disease. However, it is worth noting that the findings are limited by the considerable heterogeneity of the studies, all of which were observational and retrospective in nature. This review highlights that patients with overlap syndrome have a high prevalence of CVD with some suggestion of an increased risk compared to patients with either condition alone., Competing Interests: Conflicts of interest The authors do not have any conflicts of interest to disclose., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Despite being a leading cause of death worldwide, chronic obstructive pulmonary disease (COPD) is underdiagnosed and underprioritized within healthcare systems. Existing healthcare policies should be revisited to include COPD prevention and management as a global priority. Here, we propose and describe health system quality standard position statements that should be implemented as a consistent standard of care for patients with COPD., Methods: A multidisciplinary group of clinicians with expertise in COPD management together with patient advocates from eight countries participated in a quality standards review meeting convened in April 2021. The principal objective was to achieve consensus on global health system priorities to ensure consistent standards of care for COPD. These quality standard position statements were either evidence-based or reflected the combined views of the panel., Results: On the basis of discussions, the experts adopted five quality standard position statements, including the rationale for their inclusion, supporting clinical evidence, and essential criteria for quality metrics. These quality standard position statements emphasize the core elements of COPD care, including (1) diagnosis, (2) adequate patient and caregiver education, (3) access to medical and nonmedical treatments aligned with the latest evidence-based recommendations and appropriate management by a respiratory specialist when required, (4) appropriate management of acute COPD exacerbations, and (5) regular patient and caregiver follow-up for care plan reviews., Conclusions: These practical quality standards may be applicable to and implemented at both local and national levels. While universally applicable to the core elements of appropriate COPD care, they can be adapted to consider differences in healthcare resources and priorities, organizational structure, and care delivery capabilities of individual healthcare systems. We encourage the adoption of these global quality standards by policymakers and healthcare practitioners alike to inform national and regional health system policy revisions to improve the quality and consistency of COPD care worldwide., (© 2022. The Author(s).)

Reports suggest an increased risk of tuberculosis (TB) in people with chronic airway diseases (CADs) such as chronic obstructive pulmonary disease (COPD), but evidence has not been systematically reviewed. We performed a systematic review by searching MEDLINE and Embase for studies published from 1 January 1993 to 15 January 2021 reporting the association between the incident risk of TB in people with CADs (asthma, COPD and bronchiectasis). Two reviewers independently assessed the quality of individual studies. We included nine studies, with two from low-income high TB burden countries. Three cohort studies reported a statistically significant independent association between COPD and the risk of TB in high-income countries (n=711 389). Hazard ratios for incident TB ranged from 1.44 to 3.14 adjusted for multiple confounders including age, sex and comorbidity. There was large between-study heterogeneity (I2=97.0%) across studies. The direction of effect on the TB risk from asthma was inconsistent. Chronic bronchitis or bronchiectasis studies were limited. The small number of available studies demonstrated an increased risk of TB in people with COPD; however, the magnitude of the increase varies by setting and population. Data in high TB burden countries and for other CADs are limited., (© The Author(s) 2021. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene.)

Introduction: There is currently no accepted way to risk-stratify hospitalised exacerbations of chronic obstructive pulmonary disease (COPD). We hypothesised that the revised UK National Early Warning Score (NEWS2) calculated at admission would predict inpatient mortality, need for non-invasive ventilation (NIV) and length-of-stay., Methods: We included data from 52,284 admissions for exacerbation of COPD. Data were divided into development and validation cohorts. Logistic regression was used to examine relationships between admission NEWS2 and outcome measures. Predictive ability of NEWS2 was assessed using area under receiver operating characteristic curves (AUC). We assessed the benefit of including other baseline data in the prediction models and assessed whether these variables themselves predicted admission NEWS2., Results: 53% of admissions had low risk, 24% medium risk and 23% a high risk NEWS2 in the development cohort. The proportions dying as an inpatient were 2.2%, 3.6% and 6.5% by NEWS2 risk category, respectively. The proportions needing NIV were 4.4%, 9.2% and 18.0%, respectively. NEWS2 was poorly predictive of length-of-stay (AUC: 0.59[0.57-0.61]). In the external validation cohort, the AUC (95% CI) for NEWS2 to predict inpatient death and need for NIV were 0.72 (0.68-0.77) and 0.70 (0.67-0.73). Inclusion of patient demographic factors, co-morbidity and COPD severity improved model performance. However, only 1.34% of the variation in admission NEWS2 was explained by these baseline variables., Conclusion: The generic NEWS2 risk assessment tool, readily calculated from simple physiological data, predicts inpatient mortality and need for NIV (but not length-of-stay) at exacerbations of COPD. NEWS2 therefore provides a classification of hospitalised COPD exacerbation severity., Competing Interests: Professor John R Hurst reports personal fees, and non-financial support from pharmaceutical companies that make medicines to treat respiratory disease, outside the submitted work. Mr Philip W Stone and Professor Jennifer K Quint report grants from Royal College of Physicians, during the conduct of the study. Professor C Michael Roberts reports grants from Healthcare Quality Improvement Partnership, during the conduct of the study. The authors report no other conflicts of interest in this work., (© 2022 Stone et al.)

Systemic inflammation is a well-established feature of Chronic Obstructive Pulmonary Disease, COPD, but less is known about inflammation in the upper airways in the disease. In the current study, we investigated the inflammatory profile in the upper airway and in serum in a cohort of patients with COPD. Patients were examined with inflammatory profiles measured on material from the upper airway and in serum using a 14-plex Bioplex multiplex immunoassay containing the following cytokines: IL-1-beta, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17, IL-18, Interferon-gamma, Tumour Necrosis Factor-alpha, Tumour Necrosis Factor beta, and GM-CSF. We evaluated COPD disease burden using the CAT questionnaire and symptoms from the upper airways with the nasal domain of the 22 items Sino Nasal Outcome Test (SNOT22 nasal ). We included 180 patients (female 55%, age 67 (±8) years, FEV1% 52.4 (±16.6). Using a SNOT22 nasal threshold of ≥6, we divided patients into high upper airways symptoms (high UAS), n = 74 (41%) and low upper airway symptoms (low UAS), n = 106 (59%). High UAS was significantly associated with higher levels of IL-1 beta and IL-3 in nasal samples (p = 0.016 and 0.02, respectively) and higher serum levels of IL-1 beta (p = 0.003). Upper airway scores correlated positively with nasal levels of IL-3 (rho = 0.195, p = 0.01) and serum levels of IL-1 beta (rho = 0.226, p = 0.005). Patients with COPD and high upper airway symptoms displayed signs of eosinophilic and neutrophilic inflammation with elevated levels of IL-1 beta and IL-3 in the nose and elevated IL-1 beta in serum., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD., Methods: Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission., Results: 28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81))., Conclusion: Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions., Competing Interests: Competing interests: PWS reports grants from Royal College of Physicians, during the conduct of the study. AA reports grants from Royal College of Physicians, during the conduct of the study. JRH reports grants, personal fees and non-financial support from pharmaceutical companies that make medicines to treat COPD, outside the submitted work. CMR reports personal fees from Astra Zeneca, personal fees from Pfizer, outside the submitted work. JKQ reports grants from Royal College of Physicians, during the conduct of the study; grants and personal fees from AZ, grants and personal fees from Bayer, grants and personal fees from BI, grants and personal fees from Chiesi, grants and personal fees from GSK, grants from MRC, grants from The Health Foundation, outside the submitted work., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Most of the global morbidity and mortality in chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries (LMICs), with significant economic effects., Objective: To assess the discriminative accuracy of 3 instruments using questionnaires and peak expiratory flow (PEF) to screen for COPD in 3 LMIC settings., Design, Setting, and Participants: A cross-sectional analysis of discriminative accuracy, conducted between January 2018 and March 2020 in semiurban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda, using a random age- and sex-stratified sample of the population 40 years or older., Exposures: Three screening tools, the COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk (CAPTURE; range, 0-6; high risk indicated by a score of 5 or more or score 2-5 with low PEF [<250 L/min for females and <350 L/min for males]), the COPD in LMICs Assessment questionnaire (COLA-6; range, 0-5; high risk indicated by a score of 4 or more), and the Lung Function Questionnaire (LFQ; range, 0-25; high risk indicated by a score of 18 or less) were assessed against a reference standard diagnosis of COPD using quality-assured postbronchodilator spirometry. CAPTURE and COLA-6 include a measure of PEF., Main Outcomes and Measures: The primary outcome was discriminative accuracy of the tools in identifying COPD as measured by area under receiver operating characteristic curves (AUCs) with 95% CIs. Secondary outcomes included sensitivity, specificity, positive predictive value, and negative predictive value., Results: Among 10 709 adults who consented to participate in the study (mean age, 56.3 years (SD, 11.7); 50% female), 35% had ever smoked, and 30% were currently exposed to biomass smoke. The unweighted prevalence of COPD at the 3 sites was 18.2% (642/3534 participants) in Nepal, 2.7% (97/3550) in Peru, and 7.4% (264/3580) in Uganda. Among 1000 COPD cases, 49.3% had clinically important disease (Global Initiative for Chronic Obstructive Lung Disease classification B-D), 16.4% had severe or very severe airflow obstruction (forced expiratory volume in 1 second <50% predicted), and 95.3% of cases were previously undiagnosed. The AUC for the screening instruments ranged from 0.717 (95% CI, 0.677-0.774) for LFQ in Peru to 0.791 (95% CI, 0.770-0.809) for COLA-6 in Nepal. The sensitivity ranged from 34.8% (95% CI, 25.3%-45.2%) for COLA-6 in Nepal to 64.2% (95% CI, 60.3%-67.9%) for CAPTURE in Nepal. The mean time to administer the instruments was 7.6 minutes (SD 1.11), and data completeness was 99.5%., Conclusions and Relevance: This study demonstrated that screening instruments for COPD were feasible to administer in 3 low- and middle-income settings. Further research is needed to assess instrument performance in other low- and middle-income settings and to determine whether implementation is associated with improved clinical outcomes.

Background: Small Airways Disease (SAD) is a recognised part of the pathology in Chronic Obstructive Pulmonary Disease (COPD) and contributes to the symptom burden in the disease. Upper airway symptoms in COPD is an emerging field of study, and in this study, we sought to examine the co-existence of SAD and upper airways symptoms in a cohort of COPD patients METHODS: We investigated a cohort of patients with COPD for the presence of SAD with three different modalities. We performed High-Resolution CT (HRCT) with Parametric Response Mapping (PRM) analysis and recorded distribution of emphysema (PRM Emph ) and functional Small Airways Disease (PRM fSAD ). We measured central and peripheral lung resistance using Impulse Oscillometry (IOS) and recorded R5Hz, R20Hz, R5-R20Hz, X5, Fres and Ax. Static lung function parameters were obtained using Body Plethysmography. Data on upper and lower airway symptoms were evaluated using the Upper Airway subdomain of the 22 items Sino Nasal Outcome Test (SNOT22 nasal ) and the COPD Assessment Test (CAT), respectively., Findings: We recruited a total of 112 patients. (female sex: 58%, Age 68 (±8) years, FEV1%predicted: 53% (±16%), GOLD stage: A: 23%, B: 55%, C:1% D: 21%). Forty-five (40%) were classified as having high upper airway symptoms (UAS), defined as SNOT22 nasal ≥6. Eighty-seven per cent showed signs of SAD using IOS (R5-R20Hz > 0.07 kPa/L/s). No significant differences were found between UAS groups in IOS, PRM or Body Plethysmography parameters., Conclusion: In patients with COPD, the prevalence of small airways disease was very high, but no association between upper airway symptoms and small airways disease was demonstrated., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Demographic and disease characteristics have been associated with the risk of chronic obstructive pulmonary disease (COPD) exacerbations. Using previously collected multinational clinical trial data, we developed models that use baseline risk factors to predict an individual's rate of moderate/severe exacerbations in the next year on various pharmacological treatments for COPD., Methods: Exacerbation data from 20,054 patients in the ETHOS, KRONOS, TELOS, SOPHOS, and PINNACLE-1, PINNACLE-2, and PINNACLE-4 studies were pooled. Machine learning was used to identify predictors of moderate/severe exacerbation rates. Important factors were selected for generalized linear modeling, further informed by backward variable selection. An independent test set was held back for validation., Results: Prior exacerbations, eosinophil count, forced expiratory volume in 1 s percent predicted, prior maintenance treatments, reliever medication use, sex, COPD Assessment Test score, smoking status, and region were significant predictors of exacerbation risk, with response to inhaled corticosteroids (ICSs) increasing with higher eosinophil counts, more prior exacerbations, or additional prior treatments. Model fit was similar in the training and test set. Prediction metrics were ~10% better in the full model than in a simplified model based only on eosinophil count, prior exacerbations, and ICS use., Conclusion: These models predicting rates of moderate/severe exacerbations can be applied to a broad range of patients with COPD in terms of airway obstruction, eosinophil counts, exacerbation history, symptoms, and treatment history. Understanding the relative and absolute risks related to these factors may be useful for clinicians in evaluating the benefit: risk ratio of various treatment decisions for individual patients.Clinical trials registered with www.clinicaltrials.gov (NCT02465567, NCT02497001, NCT02766608, NCT02727660, NCT01854645, NCT01854658, NCT02343458, NCT03262012, NCT02536508, and NCT01970878).

Objective: To assess the impact of interventions for improving the management of chronic obstructive pulmonary disease (COPD), specifically increased use of pulmonary rehabilitation (PR) on patient outcomes and cost-benefit analysis., Data Sources: We used the national Hospital Episode Statistics (HES) datasets in England, local data and experts from the hospital setting, National Prices and National Tariffs, reports and the literature around the effectiveness of PR programs., Study Design: The COPD pathway was modeled using discrete event simulation (DES) to capture the patient pathway to an adequate level of detail as well as randomness in the real world. DES was further enhanced by the integration of a health economic model to calculate the net benefit and cost of treating COPD patients based on key sets of interventions., Data Collection/extraction Methods: A total of 150 input parameters and 75 distributions were established to power the model using the HES dataset, outpatient activity data from the hospital and community services, and the literature., Principal Findings: The simulation model showed that increasing referral to PR (by 10%, 20%, or 30%) would be cost-effective (with a benefit-cost ratio of 5.81, 5.95, and 5.91, respectively) by having a positive impact on patient outcomes and operational metrics. Number of deaths, admissions, and bed days decreased (ie, by 3.56 patients, 4.90 admissions, and 137.31 bed days for a 30% increase in PR referrals) as well as quality of life increased (ie, by 5.53 QALY among 1540 patients for the 30% increase)., Conclusions: No operational model, either statistical or simulation, has previously been developed to capture the COPD patient pathway within a hospital setting. To date, no model has investigated the impact of PR on COPD services, such as operations, key performance, patient outcomes, and cost-benefit analysis. The study will support policies around extending availability of PR as a major intervention., (© Health Research and Educational Trust.)

Background: Individuals with chronic obstructive pulmonary disease (COPD) commonly experience exacerbations, which may require hospital admission. Early detection of exacerbations, and therefore early treatment, could be crucial in preventing admission and improving outcomes. Our previous research has demonstrated that the pattern analysis of peripheral oxygen saturation (S p O 2 ) fluctuations provides novel insights into the engagement of the respiratory control system in response to physiological stress (hypoxia). Therefore, this pilot study tested the hypothesis that the pattern of S p O 2 variations in overnight recordings of individuals with COPD would distinguish between stable and exacerbation phases of the disease., Methods: Overnight pulse oximetry data from 11 individuals with COPD, who exhibited exacerbation after a period of stable disease, were examined. Stable phase recordings were conducted overnight and one night prior to exacerbation recordings were also analyzed. Pattern analysis of S p O 2 variations was carried examined using sample entropy (for assessment of irregularity), the multiscale entropy (complexity), and detrended fluctuation analysis (self-similarity)., Results: S p O 2 variations displayed a complex pattern in both stable and exacerbation phases of COPD. During an exacerbation, S p O 2 entropy increased (p = 0.029) and long-term fractal-like exponent (α2) decreased (p = 0.002) while the mean and standard deviation of S p O 2 time series remained unchanged. Through ROC analyses, S p O 2 entropy and α2 were both able to classify the COPD phases into either stable or exacerbation phase. With the best positive predictor value (PPV) for sample entropy (PPV = 70%) and a cut-off value of 0.454. While the best negative predictor value (NPV) was α2 (NPV = 78%) with a cut-off value of 1.00., Conclusion: Alterations in S p O 2 entropy and the fractal-like exponent have the potential to detect exacerbations in COPD. Further research is warranted to examine if S p O 2 variability analysis could be used as a novel objective method of detecting exacerbations., (© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Introduction: Low- and middle-income countries (LMICs) bear a high proportion of the global morbidity and mortality caused by COPD. Increased exposure to risk factors throughout life (e.g. malnutrition, indoor and outdoor air pollution, and smoking) is associated with higher COPD prevalence in LMICs and the lack of treatment availability increases avoidable harm., Areas Covered: This review covers the epidemiology and burden of COPD in LMICs, and challenges and recommendations related to health-care systems, prevention, diagnosis, and treatment. Main challenges are related to under-resourced health-care systems (such as limited availability of spirometry, rehabilitation, and medicines). Lack of policy and practical local guidelines on COPD diagnosis and management further contribute to the low diagnostic and treatment rates. In the absence of, or limited number of respiratory specialists, primary care practitioners (general practitioners, nurses, pharmacists, physiotherapists, and community health workers) play an even more pivotal role in COPD management in LMICs., Expert Opinion: Raising awareness on COPD, educating health-care workers, patients, and communities on cost-effective preventive measures as well as improving availability, affordability and proper use of diagnostic and pharmacological and non-pharmacologic treatment in primary care are the key interventions needed to improve COPD prevention, diagnosis, and care in LMICs.

Background: Therapeutic inertia, defined as failure to escalate or initiate adequate therapy when treatment goals are not met, contributes to poor management of COPD exacerbations., Methods: A multidisciplinary panel of five expert clinicians actively managing COPD and representative of UK practice developed action points to reduce exacerbation risk, based on evidence, clinical expertise, and experience. The action points are applicable despite changing circumstances (eg, virtual clinics). The panel agreed areas where further evidence is needed., Results: The four action points were (1) an experienced HCP, such as a GP or member of the multi-professional COPD team should review patients within one month of every exacerbation that requires oral steroids, antibiotics, or hospitalization to address modifiable risk factors, optimize non-pharmacological measures, and evaluate pharmacological therapy. (2) Presenting to hospital with an exacerbation defines an important window of opportunity to reduce the risk of further exacerbations. Follow-up by a GP, or member of the multi-professional specialist COPD team within one month of discharge with a full management review and appropriate escalation of pharmacological treatment is essential. (3) Healthcare professionals (HCPs) in all healthcare settings should be able to recognize COPD exacerbations, refer as appropriate and document the episode accurately in medical records across service boundaries. HCPs should support patients to recognize and report exacerbations. (4) HCPs should intervene proactively based on risk assessments, disease activity and any treatable traits at or as soon as possible after diagnosis and annually thereafter. Delivering these action points needs coordinated action with policymakers, funders, and service providers., Conclusion: These action points should be a fundamental part of clinical practice to determine if a change in management is necessary to reduce the risk of exacerbations. Policymakers should use these action points to develop systems and initiatives that reduce the risk of further exacerbations., Competing Interests: Claire Adams: Honoraria and speaker fees from AstraZeneca; Boehringer Ingelheim; Chiesi; Napp; GlaxoSmithKline; Mona Bafadhel: Research Grants from AstraZeneca. Educational Talks with AstraZeneca, Cipla and GlaxoSmithKline. Scientific Advisor to ProAxsis and Albus Health and is supported by the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). Steve Holmes: Honoraria and speaker fees in the last 2 years from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Napp, Roche, Teva, Trudell, Viatris. John R Hurst: Support to attend meetings, and personal payment and payment to his employer (UCL) for educational and advisory work from pharmaceutical companies that make medicines to treat COPD including AstraZeneca, Chiesi and Boehringer Ingelheim. Dave Singh: Grants and personal fees from Aerogen, AstraZeneca, CSL Behring, Boehringer Ingelheim, Chiesi, Cipla, Epiendo, Genentech, GlaxoSmithKline, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, Pulmatrix, Sanofi, Synairgen, Teva, Theravance and Verona, and is supported by the National Institute for Health Research (NIHR) Manchester Biomedical Research Centre (BRC). The authors report no other conflicts of interest relevant to this work., (© 2021 Singh et al.)

Background: Readmission following COPD exacerbation is a common and challenging clinical problem. New approaches to predicting readmissions are required to help mitigate risk and develop novel interventions., Methods: We conducted a prospective cohort study in 82 COPD patients admitted due to an exacerbation of COPD. Lung function measures [spirometry, forced oscillation technique (FOT) indices and peak inspiratory flow rate (PIFR)], inflammatory biomarkers and patient-reported outcomes including previous exacerbation history, breathlessness, quality of life and frailty were measured at admission and discharge. We prospectively followed patients for 30 and 90 days to identify predictors for readmission., Results: The readmission rate within 30 days was 38%, and 56% within 90 days. Previous exacerbations, higher COPD Assessment Test score at discharge, frailty, reduced PIFR and increased length of stay were significantly associated with 30-day readmission. PIFR at discharge and frailty had the highest predictive ability for 30-day readmission using area under receiver operating characteristic curves (AUC 0.86, 95% CI 0.78-0.95, p < 0.001 and AUC 0.81, 95% CI 0.71-0.90, p < 0.001, respectively). Ninety-day readmissions were significantly associated with previous exacerbations and hospitalisations, higher CAT score at discharge, frailty, depression, lower PIFR and greater expiratory flow limitation (EFL) in the supine position. The best predictive variable in multivariable analysis for both 30- and 90-day readmission was PIFR at discharge., Conclusion: PIFR, CAT score, frailty, and EFL were found to be associated with 30- and 90-day readmission following COPD exacerbation. These findings help identify those at highest risk and to optimise care prior to discharge., Competing Interests: Professor John R Hurst report grants, personal fees from Pharmaceutical companies that make medicines to treat COPD, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2021 Alqahtani et al.)

Background: Chronic obstructive pulmonary disease (COPD) are managed predominantly in primary care. However, key opportunities to optimize treatment are often not realized due to unrecognized disease and delayed implementation of appropriate interventions for both diagnosed and undiagnosed individuals. The COllaboratioN on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) is the first-of-its-kind, collaborative, interventional COPD registry. It comprises an integrated quality improvement program focusing on patients (diagnosed and undiagnosed) at a modifiable and higher risk of COPD exacerbations. The first step in CONQUEST was the development of quality standards (QS). The QS will be imbedded in routine primary and secondary care, and are designed to drive patient-centered, targeted, risk-based assessment and management optimization. Our aim is to provide an overview of the CONQUEST QS, including how they were developed, as well as the rationale for, and evidence to support, their inclusion in healthcare systems., Methods: The QS were developed (between November 2019 and December 2020) by the CONQUEST Global Steering Committee, including 11 internationally recognized experts with a specialty and research focus in COPD. The process included an extensive literature review, generation of QS draft wording, three iterative rounds of review, and consensus., Results: Four QS were developed: 1) identification of COPD target population, 2) assessment of disease and quantification of future risk, 3) non-pharmacological and pharmacological intervention, and 4) appropriate follow-up. Each QS is followed by a rationale statement and a summary of current guidelines and research evidence relating to the standard and its components., Conclusion: The CONQUEST QS represent an important step in our aim to improve care for patients with COPD in primary and secondary care. They will help to transform the patient journey, by encouraging early intervention to identify, assess, optimally manage and followup COPD patients with modifiable high risk of future exacerbations., Competing Interests: Rachel Pullen and Amy Couper are employees of the Observational and Pragmatic Research Institute, which is a research collaborator of the CONQUEST initiative with Optimum Patient Care and AstraZeneca. Marc Miravitlles reports speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols and research grants from GlaxoSmithKline and Grifols. Anita Sharma is a practising Primary Care Physician and Senior Lecturer, School of Clinical Medicine-Primary Care Clinical Unit, University of Queensland. She supervises clinical training of primary care doctors and serves on advisory boards for Diabetes, Heart Failure and Osteoporosis for Novartis, Merck Sharp & Dohme and Boehringer Ingelheim, Eli Lilley and Amgen. Dave Singh has received personal fees from Aerogen, AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Epiendo, Glenmark, Gossamerbio, Kinaset, Menarini, Novartis, PulmatrixSanofi, Theravance and Verona. Fernando Martinez has received personal fees and non-financial support from the American College of Chest Physicians, AstraZeneca, Boehringer Ingelheim, ConCert, Genentech, GSK, Inova Fairfax Health System, Miller Communications, National Society for Continuing Education, Novartis, Pearl Pharmaceuticals, PeerView Communications, Prime Communications, Puerto Rico Respiratory Society, Chiesi, Sunovion, Theravance, Potomac, University of Alabama Birmingham, Physicians Education Resource, Canadian Respiratory Network, Teva and Dartmouth; non-financial support from ProterrixBio, Gilead, Nitto and Zambon; and personal fees from Columbia University, Integritas, MD magazine, Methodist Hospital Brooklyn, New York University, UpToDate, WebMD/MedScape, Western Connecticut Health Network, Patara/Respivant, PlatformIQ, American Thoracic Society, Rockpointe, Rare Disease Healthcare Communications and France Foundation; grant support from NIH; and is a member of steering committees for Afferent/Merck, Biogen, Veracyte, Prometic, Bayer, Bridge Biotherapeutics and ProMedior. John Hurst has received personal payment and payment to his institution (UCL), including research grants, reimbursement for advisory work and educational activities, and support to attend meetings from pharmaceutical companies that make medicines to treat COPD, which includes AstraZeneca, Boehringer Ingelheim, Chiesi and Novartis. ; Luís Alves has served as an advisor or consultant for AstraZeneca, GlaxoSmithKline; served as a speaker or a member of a speakers bureau for Astra-Zeneca, BIAL, GlaxoSmithKline, and Novartis Pharmaceuticals Corporation. Luis Alves also reports personal fees from Optimum Patient Care Global Limited, during the conduct of the study. He is also a member of the Education Subcommittee of the International Primary Care Respiratory Group and a member of the of GRESP, the Portuguese Primary Care Study Group for Respiratory Diseases. Mark Dransfield has received grant support from the Department of Defense and NIH; personal fees from AstraZeneca, Boehringer Ingelheim, PneumRx/BTG, Genentech, BostonScientific, Quark Pharmaceuticals, Teva, and GSK; and contracted clinical trial support from Boehringer Ingelheim, Novartis, AstraZeneca, Yungjin, PneumRx/BTG, Pulmonx, Boston Scientific and GSK. Rongchang Chen has received grant support from AstraZeneca, Boehringer Ingelheim, and GSK; and reimbursement for advisory work and educational activities from AstraZeneca, Boehringer Ingelheim, GSK, Novartis. Shigeo Muro reported lecture and advisory fees from Novartis Pharma and AstraZeneca; lecture fees and grants from Boehringer Ingelheim and Fukuda Life Tech; advisory fees from GlaxoSmithKline; grants from Eisai Pharmaceutical, Otsuka Pharmaceutical and Fuji Film Medical; and lecture fees from Astellas Pharmaceutical, Kyorin Pharmaceutical and Meiji Seika Pharma. Tonya Winders has received personal fees from AstraZeneca, GSK, Novartis, Genentech, and Sanofi/Regeneron alliance. Allergy & Asthma Network & Global Allergy & Airways Patient Platform has received funds for unbranded disease awareness and education from AZ, BI, GSK, Novartis, Genentech, Viatris and Sanofi/Regeneron. Christopher Blango was an employee of AstraZeneca and hold stock and/or stock options in the company. Currently employed at the Janssen Pharmaceutical Companies of J&J. Hana Müllerová, Tamsin Morris, Frank Trudo and Paul Dorinsky are employees of AstraZeneca and hold stock and/or stock options in the company. AstraZeneca is a co-funder of the CONQUEST initiative. Marianna Alacqua was an employee of AstraZeneca at the time of manuscript development. Currently employed at CSL Behring SpA. Victoria Carter is an employee of Optimum Patient Care, a co-funder of the CONQUEST initiative. Rupert Jones declares grants from Astra Zeneca, Glaxo Smith Kline, Novartis and Teva and personal fees for consultancy, speakers fees or travel support from Astra Zeneca, Boehringer Ingelheim, Glaxo Smith Kline, Novartis and OPRI. Konstantinos Kostikas was an employee and shareholder of Novartis Pharma AG until 31.10.2018. He has received honoraria for presentations and consultancy fees from AstraZeneca, Boehringer Ingelheim, Chiesi, ELPEN, GSK, Menarini, Novartis and Sanofi. His department has received funding and grants from AstraZeneca, Boehringer Ingelheim, Chiesi, Innovis, ELPEN, GSK, Menarini, Novartis and NuvoAir. He is a member of the GOLD Assembly. Ruth Murray reports personal fees from OPC, during the conduct of the study. David B Price has board membership with AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Thermofisher; consultancy agreements with Airway Vista Secretariat, AstraZeneca, Boehringer Ingelheim, Chiesi, EPG Communication Holdings Ltd, FIECON Ltd, Fieldwork International, GlaxoSmithKline, Mylan, Mundipharma, Novartis, OM Pharma SA, PeerVoice, Phadia AB, Spirosure Inc, Strategic North Limited, Synapse Research Management Partners S.L., Talos Health Solutions, Theravance and WebMD Global LLC; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Mylan, Novartis, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Theravance and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals and Sanofi Genzyme; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 92.61% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the UK Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline. The authors report no other conflicts of interest in this work., (© 2021 Pullen et al.)