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Background and Objective. Obstructive sleep apnoea (OSA) affects an estimated 936 million people worldwide, yet only 15% receive a definitive diagnosis. Diagnosis of OSA poses challenges due to the dynamic nature of physiological signals such as oxygen saturation (SpO 2 ) and heart rate variability (HRV). Linear analysis methods may not fully capture the irregularities present in these signals. The application of entropy of routine physiological signals offers a promising method to better measure variabilities in dynamic biological data. This review aims to explore entropy changes in physiological signals among individuals with OSA. Approach. Keyword and title searches were performed on Medline, Embase, Scopus, and CINAHL databases. Studies had to analyse physiological signals in OSA using entropy. Quality assessment used the Newcastle-Ottawa Scale. Evidence was qualitatively synthesised, considering entropy signals, entropy type, and time-series length. Main results. Twenty-two studies were included. Multiple physiological signals related to OSA, including SpO 2 , HRV, and the oxygen desaturation index (ODI), have been investigated using entropy. Results revealed a significant decrease in HRV entropy in those with OSA compared to control groups. Conversely, SpO 2 and ODI entropy values were increased in OSA. Despite variations in entropy types, time scales, and data extraction devices, studies using receiver operating characteristic curves demonstrated a high discriminative accuracy (>80% AUC) in distinguishing OSA patients from control groups. Significance . This review highlights the potential of SpO 2 entropy analysis in developing new diagnostic indices for patients with OSA. Further investigation is needed before applying this technique clinically., (Creative Commons Attribution license.)

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: More than 90% of the morbidity and mortality from chronic respiratory disease occurs in low-income and middle-income countries (LMICs), with substantial economic impact. Preserved ratio impaired spirometry (PRISm) is a prevalent lung function abnormality associated with increased mortality in high-income countries. We aimed to conduct a post-hoc analysis of a cross-sectional study to assess the prevalence of, the risk factors for, and the impact of PRISm in three diverse LMIC settings., Methods: We recruited a random, age-stratified and sex-stratified sample of the population in semi-urban Bhaktapur, Nepal; urban Lima, Peru; and rural Nakaseke, Uganda. Quality-assured post-bronchodilator spirometry was performed to American Thoracic Society standards and PRISm was defined as a forced expiratory volume in one second (FEV 1 ) of less than 80% predicted with a FEV 1 /forced vital capacity ratio of 0·70 or more. We used t tests and χ 2 analyses to assess the relationships between demographic, biometric, and comorbidity variables with PRISm. Multivariable logistic models with random intercept by site were used to estimate odds ratios (ORs) with 95% CIs., Findings: 10 664 participants were included in the analysis, with a mean (SD) age of 56·3 (11·7) years and an equal distribution by sex. The prevalence of PRISm was 2·5% in Peru, 9·1% in Nepal, and 16·0% in Uganda. In multivariable analysis, younger age (OR for each decile of age 0·87, 95% CI 0·82-0·92) and being female (1·37, 1·18-1·58) were associated with increased odds of having PRISm. Biomass exposure was not consistently associated with PRISm across sites. Individuals with PRISm had impairment in respiratory-related quality of life as measured by the St George's Respiratory Questionnaire (OR by decile 1·18, 95% CI 1·10-1·25)., Interpretation: The prevalence of PRISm is heterogeneous across LMIC settings and associated with age, female sex, and biomass exposure, a common exposure in LMICs. A diagnosis of PRISm was associated with worse health status when compared with those with normal lung function. Health systems in LMICs should focus on all spirometric abnormalities as opposed to obstruction alone, given the disease burden, reduced quality of life, and size of the undiagnosed population at risk., Funding: Medical Research Council., Competing Interests: Declaration of interests TS reports grants or contracts from the Australian Lung Health Initiative; consulting fees from Verona Pharmaceuticals; and a leadership or fiduciary role in board, society, committee, or advocacy groups for 4D Medical. OF-F reports a Global Emerging Leader Award grant from the Fogarty International Centre. JJM reports grant support and payments made to their institution from the Alliance for Health Policy and Systems Research, Bloomberg Philanthropies, FONDECYT via CIENCIACTIVA and CONCYTEC, the British Council, British Embassy, the Newton-Paulet Fund, the UK Department for International Development, the UK Medical Research Council, the Wellcome Global Health Trials partnership, the Fogarty International Center, Grand Challenges Canada, the International Development Research Center Canada, Inter-American Institute for Global Change Research, the National Cancer Institute, National Heart, Lung, and Blood Institute, National Institute of Mental Health, the Swiss National Science Foundation, the UK Research and Innovation (UKRI) Biotechnology and Biological Sciences Research Council, the UKRI Engineering and Physical Sciences Research Council, the UKRI Medical Research Council, the Wellcome Trust, and the World Diabetes Foundation; a contract from Health Action International; consulting fees from the Pan American Health Organization and Bloomberg Philanthropies; participation on data safety monitoring or advisory boards for the Nigeria Sodium Study, the Intensive care bundle with blood pressure Reduction in Acute Cerebral haemorrhage Trial, the Latin American Brain Health institute, Universidad Adolfo Ibáñez (Chile), Programa de Gastronomía, Facultad de Estudios Interdisciplinarios, Pontificia Universidad Católica del Perú, and the InterAmerican Heart Foundation; being Co-chair of the Independent Group of Scientists, 2023 Global Sustainable Development Report, UN; being a member of the Scientific Expert Committee, Global Data Collaborative for CV Population Health, the World Health Federation, Microsoft, and Novartis Foundation; being a member of the Scientific and Technical Advisory Committee for the Alliance for Health Policy and Systems Research, WHO; being a member of WHO's Technical Advisory Group on non-communicable disease-related research and innovation, Non-communicable Diseases Department, WHO; and being a member of the Advisory Scientific Committee, Instituto de Investigación Nutricional, Peru. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Rationale: Chronic obstructive pulmonary disease (COPD) is associated with 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 versus dual therapy with glycopyrrolate/formoterol fumarate (GFF) or budesonide/formoterol fumarate (BFF). However, the effect of BGF on cardiovascular events versus GFF remains unevaluated. Further, the effect of BGF on time to first severe exacerbation has not been reported. Objective: Assess the effects of BGF 320/18/9.6 μg (BGF 320) and other ICS-containing arms on cardiovascular and severe cardiopulmonary endpoints versus GFF in patients with COPD from ETHOS. 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 pre-specified endpoint; post-hoc cardiovascular and severe cardiopulmonary endpoints included time to first major adverse cardiac event (MACE), time to first cardiovascular adverse event (AE) of special interest (CVAESI), 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 CVAESI (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.

Introduction: The burden of multimorbidity is recognised increasingly in low- and middle-income countries (LMICs), creating a strong emphasis on the need for effective evidence-based interventions. Core outcome sets (COS) appropriate for the study of multimorbidity in LMICs do not presently exist. These are required to standardise reporting and contribute to a consistent and cohesive evidence-base to inform policy and practice. We describe the development of two COS for intervention trials aimed at preventing and treating multimorbidity in adults in LMICs., Methods: To generate a comprehensive list of relevant prevention and treatment outcomes, we conducted a systematic review and qualitative interviews with people with multimorbidity and their caregivers living in LMICs. We then used a modified two-round Delphi process to identify outcomes most important to four stakeholder groups (people with multimorbidity/caregivers, multimorbidity researchers, healthcare professionals and policymakers) with representation from 33 countries. Consensus meetings were used to reach agreement on the two final COS., Registration: https://www.comet-initiative.org/Studies/Details/1580., Results: The systematic review and qualitative interviews identified 24 outcomes for prevention and 49 for treatment of multimorbidity. An additional 12 prevention and 6 treatment outcomes were added from Delphi round 1. Delphi round 2 surveys were completed by 95 of 132 round 1 participants (72.0%) for prevention and 95 of 133 (71.4%) participants for treatment outcomes. Consensus meetings agreed four outcomes for the prevention COS: (1) adverse events, (2) development of new comorbidity, (3) health risk behaviour and (4) quality of life; and four for the treatment COS: (1) adherence to treatment, (2) adverse events, (3) out-of-pocket expenditure and (4) quality of life., Conclusion: Following established guidelines, we developed two COS for trials of interventions for multimorbidity prevention and treatment, specific to adults in LMIC contexts. We recommend their inclusion in future trials to meaningfully advance the field of multimorbidity research in LMICs., Prospero Registration Number: CRD42020197293., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Rationale: Long-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA., Methods: Randomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months., Results: A total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment. Clinical trial registration: ClinicalTrials.gov, NCT05563675., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sivapalan, Rømer, Wirenfeldt Klausen, Dyrby Johansen, Pareek, Modin, Mathioudakis, Vestbo, Eklöf, Jordan, Hurst, Biering-Sørensen and Jensen.)

Few studies have investigated the acceptability of wearable technology in patients with long-term respiratory disease. We conducted a 24-item cross-sectional survey (September 2022-February 2023), developed using four common themes universal to previously described models of technology acceptance and social behavioural therapy, to explore the acceptability of wearable technology spanning the breadth of chronic respiratory disease. A total of 74 valid survey responses were analysed with 50 % aged 51-70years; 72 % female; 63 % white British ethnicity; 79 % having an income less than £50,000, and 93 % having at least obstructive airways disease. A third of participants current used wearables with 85 % using smart watches. Most of these participants used wearables to monitor their symptoms (69 %) and as a general health measurement device (85 %). Likert scale questions (ranked 1-7) showed that participants valued accuracy and approval of wearables by regulatory bodies (median (IQR) rank score 7 (Huberty et al., 2015; Preusse et al., 2016) 6-76-7 and felt that wearables would increase their confidence in managing their long-term health condition (median (IQR) rank score 6 (Huberty et al., 2015; Preusse et al., 2016) 6-76-7. Favourable product characteristics for wearables were accuracy (73 %), easy to learn (63 %) and easy to use (50 %). They were less concerned about aesthetics (23 %) and battery life (27 %). This survey will guide future developers to produce a wearable for a population with chronic respiratory disease which will improve acceptability, usability and longevity., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Multimorbidity is an emerging challenge for health systems globally. It is commonly defined as the co-occurrence of two or more chronic conditions in one person, but its meaning remains a lively area of academic debate, and the utility of the concept beyond high-income settings is uncertain. This article presents the findings from an interdisciplinary research initiative that drew together 60 academic and applied partners working in 10 African countries to answer the questions: how useful is the concept of multimorbidity within Africa? Can the concept be adapted to context to optimise its transformative potentials? During a three-day concept-building workshop, we investigated how the definition of multimorbidity was understood across diverse disciplinary and regional perspectives, evaluated the utility and limitations of existing concepts and definitions, and considered how to build a more context-sensitive, cross-cutting description of multimorbidity. This iterative process was guided by the principles of grounded theory and involved focus- and whole-group discussions during the workshop, thematic coding of workshop discussions, and further post-workshop development and refinement. Three thematic domains emerged from workshop discussions: the current focus of multimorbidity on constituent diseases; the potential for revised concepts to centre the priorities, needs, and social context of people living with multimorbidity (PLWMM); and the need for revised concepts to respond to varied conceptual priorities amongst stakeholders. These themes fed into the development of an expanded conceptual model that centres the catastrophic impacts multimorbidity can have for PLWMM, families and support structures, service providers, and health systems., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Dixon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: This study explores clinicians' diagnostic practices and perceptions in the context of granulomatous-lymphocytic interstitial lung disease (GLILD), a pulmonary manifestation of common variable immunodeficiency disorder. The aim was to gain valuable insights into key aspects, such as the utilization of radiological features for diagnostic purposes, indications for lung biopsy, preferred biopsy techniques, and the relative importance of different histopathological findings in confirming GLILD., Method: A survey targeting expert clinicians was conducted, focusing on their experiences, practices, and attitudes towards lung biopsy in suspected GLILD cases., Results: The survey revealed that the majority of respondents accepted high-resolution computed tomography as a sufficient alternative to biopsy for making a probable GLILD diagnosis in most patients. There was a consensus among most respondents that the presence of extrapulmonary granulomatous disease is adequate for making a diagnosis of GLILD where the chest imaging and clinical picture are consistent. When a biopsy was recommended, there was notable variation in the preferred initial biopsy technique, with 35% favouring transbronchial biopsy., Conclusion: Our findings underscore the complexity of diagnosing GLILD, indicating varied clinician opinions on the necessity and efficacy of lung biopsies. They highlight the need for further research and the development of consistent diagnostic criteria and management protocols, ultimately aiming to enhance the accuracy and safety of GLILD diagnosis and treatment strategies., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

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.)

Background: The long-term outcomes of COVID-19 hospitalisation in individuals with pre-existing airway diseases are unknown., Methods: Adult participants hospitalised for confirmed or clinically suspected COVID-19 and discharged between 5 March 2020 and 31 March 2021 were recruited to the Post-hospitalisation COVID-19 (PHOSP-COVID) study. Participants attended research visits at 5 months and 1 year post discharge. Clinical characteristics, perceived recovery, burden of symptoms and health-related quality of life (HRQoL) of individuals with pre-existing airway disease ( i.e. , asthma, COPD or bronchiectasis) were compared to the non-airways group., Results: A total of 615 out of 2697 (22.8%) participants had a history of pre-existing airway diseases (72.0% diagnosed with asthma, 22.9% COPD and 5.1% bronchiectasis). At 1 year, the airways group participants were less likely to feel fully recovered (20.4% versus 33.2%, p<0.001), had higher burden of anxiety (29.1% versus 22.0%, p=0.002), depression (31.2% versus 24.7%, p=0.006), higher percentage of impaired mobility using short physical performance battery ≤10 (57.4% versus 45.2%, p<0.001) and 27% had a new disability (assessed by the Washington Group Short Set on Functioning) versus 16.6%, p=0.014. HRQoL assessed using EQ-5D-5L Utility Index was lower in the airways group (mean±SD 0.64±0.27 versus 0.73±0.25, p<0.001). Burden of breathlessness, fatigue and cough measured using a study-specific tool was higher in the airways group., Conclusion: Individuals with pre-existing airway diseases hospitalised due to COVID-19 were less likely to feel fully recovered, had lower physiological performance measurements, more burden of symptoms and reduced HRQoL up to 1 year post-hospital discharge., Competing Interests: Conflict of interest: J.R. Hurst has received support to attend meetings, research grants, and personal payment and payment to his employer from pharmaceutical companies that make medicines to treat airways diseases. J.K. Quint reports grants from Industrial Strategy Challenge Fund, the Medical Research Council, Health Data Research, GlaxoSmithKline (GSK), Boehringer Ingelheim (BI), Asthma+Lung UK and AstraZeneca (AZ), and consulting fees from GSK, Evidera, Chiesi, AZ and Insmed outside the submitted work. P.E. Pfeffer reports grants from NIHR and GSK, Honoraria payments for lectures from AZ, GSK, Sanofi and Chiesi and travel fees from AZ, GSK, Sanofi outside the submitted work. N.J. Greening reports grants from GSK and BioAge, and personal fees and travel grants from Genentech, Roche, Chiesi, AZ, GSK, Pulmonx and Chiesi outside the submitted work. J.D. Chalmers is an associate editor of this journal. A. Horsley reports grants from UKRI, NIHR and NIHR Manchester BRC during the conduct of this study and unenumerated role as the chair of NIHR Translational Research Collaboration. A. Sheikh has served on AZ's thrombotic thrombocytopenic taskforce, and on a number of UK and Scottish Government COVID-19 advisory bodies; all these roles were unremunerated. B. Raman reports grant from BHF Oxford CRE and speaker fees from Axcella Therapeutics. R.A. Evans reports grants from UKRI/MRC, DHSC/NIHR, Wolfson Foundation and Genentec/Roche during the conduct of this study, travel and speaker fees from AZ/Evidera, Boehringer Ingelheim (BI), Moderna and Chiesi, and unremunerated leadership roles in ERS/ATS outside the submitted work. C.E. Brightling declares that their institute was awarded a grant from UKRI/NIHR to complete this work; the author reports grants from GSK, AZ, Sanofi, Regeneron, BI, Chiesi, Novartis, Roche, Genentech, Mologic and 4DPharma; and consultancy fees paid to their institution from GSK, AZ, Sanofi, BI, Chiesi, Novartis, Roche, Genentech, Mologic, 4DPharma and Areteia. A. De Soyza declares receiving personal consulting fees and travel grants from AZ, Bayer, GSK, Chiesi, Novartis, Pfizer, Insmed, Gilead and 30T outside the submitted work. All other authors declare no competing interests., (Copyright ©The authors 2024.)

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).)

Background: The co-occurrence of chronic diseases and acute infectious events exacerbates disability and diminishes quality of life, yet research in Low- and Middle-Income countries is scarce. We aimed to investigate the relationship between infectious events and multimorbidity in resource-constrained settings., Methods: We conducted a sequential mixed-method study in Lima and Tumbes, Peru, with participants having multimorbidity from the CRONICAS Cohort Study. They completed a questionnaire on the occurrence, treatment, and health-seeking behaviour related to acute infectious events. Qualitative interviews explored the perceptions and links between multimorbidity and acute infectious events for a subgroup of participants., Findings: Among individuals with multimorbidity, low awareness of chronic conditions and poor medication adherence. The cumulative incidence for respiratory and gastrointestinal infections, the most reported acute conditions, was 2.0 [95%CI: 1.8-2.2] and 1.6 [1.2-1.9] events per person per year, respectively. Individuals with cancer (6.4 [1.6-11.2] events per person per year) or gastrointestinal reflux (7.2 [4.4-10.1] events per person per year) reported higher cumulative incidence of infectious events than others, such as those with cardiovascular and metabolic conditions (5.2 [4.6-5.8] events per person per year). Those with three or more chronic conditions had a slightly higher cumulative incidence compared with individuals with two conditions (5.7 [4.4-7.0] vs 5.0 [4.4-5.6] events per person per year). Around 40% of individuals with multimorbidity sought healthcare assistance, while others chose drugstores or didn't seek help. Our qualitative analysis showed diverse perceptions among participants regarding the connections between chronic and acute conditions. Those who recognized a connection emphasized the challenges in managing these interactions., Interpretation: Our study advances understanding of multimorbidity challenges in resource-limited settings, highlighting the impact of acute infections on patients' existing multimorbidity burden., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Interstitial lung diseases (ILDs) refer to a heterogeneous and complex group of conditions characterized by inflammation, fibrosis, or both, in the interstitium of the lungs. This results in impaired gas exchange, leading to a worsening of respiratory symptoms and a decline in lung function. While the etiology of some ILDs is unclear, most cases can be traced back to factors such as genetic predispositions, environmental exposures (including allergens, toxins, and air pollution), underlying autoimmune diseases, or the use of certain medications. There has been an increase in research and evidence aimed at identifying etiology, understanding epidemiology, improving clinical diagnosis, and developing both pharmacological and non-pharmacological treatments. This review provides a comprehensive overview of the current state of knowledge in the field of interstitial lung diseases., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Althobiani, Russell, Jacob, Ranjan, Folarin, Hurst and Porter.)

Introduction: Sarcopenia and sarcopenic obesity (SO) have emerged as significant contributors to negative health outcomes in the past decade. We aimed to estimate the prevalence of probable sarcopenia, sarcopenia, and SO in a community-dwelling population of 1151 adults aged ≥55 years in Lima, Peru., Methods: This cross-sectional study was conducted between 2018 and 2020. Sarcopenia was defined as the presence of low muscle strength (LMS) and low muscle mass (LMM) according to European (EWGSOP2), US (FNIH) and Asian (AWGS2) guidelines. We measured muscle strength by maximum handgrip strength and muscle mass using bioelectrical impedance analyzer. SO was defined as a body mass index ≥ 30 kg/m2 and sarcopenia., Results: The study participants had a mean age of 66.2 years (SD 7.1), age range between 60 to 92 years old, of which 621 (53.9%) were men. Among the sample, 41.7% were classified as obese (BMI ≥30.0 kg/m²). The prevalence of probable sarcopenia was estimated to be 22.7% (95%CI: 20.3-25.1) using the EWGSOP2 criteria and 27.8% (95%CI: 25.2-30.4) using the AWGS2 criteria. Sarcopenia prevalence, assessed using skeletal muscle index (SMI), was 5.7% (95%CI: 4.4-7.1) according to EWGSOP2 and 8.3% (95%CI: 6.7-9.9) using AWGS2 criteria. The prevalence of sarcopenia based on the FNIH criteria was 18.1% (95%CI: 15.8-20.3). The prevalence of SO, considering different sarcopenia definitions, ranged from 0.8% (95%CI: 0.3-1.3) to 5.0% (95%CI: 3.8-6.3)., Conclusion: Our findings reveal substantial variation in the prevalence of sarcopenia and SO, underscoring the necessity for context-specific cut-off values. Although the prevalence of SO was relatively low, this result may be underestimated. Furthermore, the consistently high proportion of probable sarcopenia and sarcopenia point to a substantial public health burden., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Flores-Flores et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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.

Background: The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive biomarker that potentially predicts acute exacerbations of chronic obstructive pulmonary disease (AECOPDs). We evaluated the association of baseline NLR and respiratory hospitalization risk within one year among chronic obstructive pulmonary disease (COPD) patients in Uganda, a low- and middle-income country., Methods: A total of 312 COPD patients were followed for one year. Clinical characteristics and exacerbation rates were collected. Poisson regression with robust variance estimators was used to measure the association between NLR and hospital admissions due to COPD exacerbations. Receiver-operator characteristic (ROC) curves and the area under the curve were used to assess the ability of NLR to predict AECOPDs., Results: The median (Q 1, Q 3) age was 64 years (53, 71). Females comprised 50.96% (n=159) of the cohort, and 71.2% (n=222) of participants had moderate or severe COPD. A total of 9.9% (n=31) of participants experienced a COPD exacerbation during the period of follow-up. At baseline, the median (Q 1, Q 3) NLR ratio among participants who experienced an exacerbation was 1.46 (0.92, 2.33) compared to 1.03 (0.72,1.42) among those who did not experience one during the follow-up period ( p =0.002). Using Youden and Liu's methods, the optimal NLR cutoff for predicting COPD exacerbation was 1.17. This cutoff resulted in a ROC curve area of 0.64 (95% confidence interval: 0.56, 0.73)., Conclusion: The NLR could be used as a risk predictor, in low- and middle-income countries, for hospital admissions due to COPD exacerbations. A cutoff of 1.17 was an independent predictor of hospitalization due to acute exacerbations of COPD within one year., (JCOPDF © 2024.)

Background: Alpha 1 Antitrypsin Deficiency (AATD) is a rare, inherited lung disease which shares features with Chronic Obstructive Pulmonary Disease (COPD) but has a greater burden of proteinase related tissue damage. These proteinases are associated with cardiovascular disease (CVD) in the general population. It is unclear whether patients with AATD have a greater risk of CVD compared to usual COPD, how best to screen for this, and whether neutrophil proteinases are implicated in AATD-associated CVD. This study had three aims. To compare CVD risk in never-augmented AATD patients to non-AATD COPD and healthy controls (HC). To assess relationships between CVD risk and lung physiology. To determine if neutrophil proteinase activity was associated with CVD risk in AATD. Cardiovascular risk was assessed by QRISK2® score and aortic stiffness measurements using carotid-femoral (aortic) pulse wave velocity (aPWV). Medical history, computed tomography scans and post-bronchodilator lung function parameters were reviewed. Systemic proteinase 3 activity was measured. Patients were followed for 4 years, to assess CVD development., Results: 228 patients with AATD, 50 with non-AATD COPD and 51 healthy controls were recruited. In all COPD and HC participants, QRISK2® and aPWV gave concordant results (with both measures either high or in the normal range). This was not the case in AATD. Once aPWV was adjusted for age and smoking history, aPWV was highest and QRISK2® lowest in AATD patients compared to the COPD or HC participants. Higher aPWV was associated with impairments in lung physiology, the presence of emphysema on CT scan and proteinase 3 activity following adjustment for age, smoking status and traditional CVD risk factors (using QRISK2® scores) in AATD. There were no such relationships with QRISK2® in AATD. AATD patients with confirmed CVD at four-year follow up had a higher aPWV but not QRISK2® at baseline assessment., Conclusion: aPWV measured CVD risk is elevated in AATD. This risk is not captured by QRISK2®. There is a relationship between aPWV, lung disease and proteinase-3 activity. Proteinase-driven breakdown of elastin fibres in large arteries and lungs is a putative mechanism and forms a potential therapeutic target for CVD in AATD., (© 2024. The Author(s).)

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.)

Streptococcus pyogenes is a human-specific pathogen that commonly colonizes the upper respiratory tract and skin, causing a wide variety of diseases ranging from pharyngitis to necrotizing fasciitis and toxic shock syndrome. S. pyogenes has a repertoire of secreted virulence factors that promote infection and evasion of the host immune system including the cytolysins streptolysin O (SLO) and streptolysin S (SLS). S. pyogenes does not naturally infect the upper respiratory tract of mice although mice transgenic for MHC class II human leukocyte antigens (HLA) become highly susceptible. Here we used HLA-transgenic mice to assess the role of both SLO and SLS during both nasopharyngeal and skin infection. Using S. pyogenes MGAS8232 as a model strain, we found that an SLS-deficient strain exhibited a 100-fold reduction in bacterial recovery from the nasopharynx and a 10-fold reduction in bacterial burden in the skin, whereas an SLO-deficient strain did not exhibit any infection defects in these models. Furthermore, depletion of neutrophils significantly restored the bacterial burden of the SLS-deficient bacteria in skin, but not in the nasopharynx. In mice nasally infected with the wildtype S. pyogenes, there was a marked change in localization of the tight junction protein ZO-1 at the site of infection, demonstrating damage to the nasal epithelia that was absent in mice infected with the SLS-deficient strain. Overall, we conclude that SLS is required for the establishment of nasopharyngeal infection and skin infection in HLA-transgenic mice by S. pyogenes MGAS8232 and provide evidence that SLS contributes to nasopharyngeal infection through the localized destruction of nasal epithelia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Shannon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Rates of mortality and re-admission after a hospitalised exacerbation of COPD are high and resistant to change. COPD guidelines do not give practical advice about the optimal selection of inhaled drugs and device in this situation. We hypothesised that a failure to optimise inhaled drug and drug delivery prior to discharge from hospital after an exacerbation would be associated with a modifiable increased risk of re-admission and death. We designed a study to 1) develop a practical inhaler selection tool to use at the point of hospital discharge and 2) implement this tool to understand the potential impact on modifying inhaler prescriptions, clinical outcomes, acceptability to clinicians and patients, and the feasibility of delivering a definitive trial to demonstrate potential benefit., Methods: We iteratively developed an inhaler selection tool for use prior to discharge following a hospitalised exacerbation of COPD using surveys with multiprofessional clinicians and a focus group of people living with COPD. We surveyed clinicians to understand their views on the minimum clinically important difference (MCID) for death and re-admission following a hospitalised exacerbation of COPD. We conducted a mixed-methods implementation feasibility study using the tool at discharge, and collated 30- and 90-day follow-up data including death and re-admissions. Additionally, we observed the tool being used and interviewed clinicians and patients about use of the tool in this setting., Results: We completed the design of an inhaler selection tool through two rounds of consultations with 94 multiprofessional clinicians, and a focus group of four expert patients. Regarding MCIDs, there was majority consensus for the following reductions from baseline being the MCID: 30-day readmissions 5-10%, 90-day readmissions 10-20%, 30-day mortality 5-10% and 90-day mortality 5-10%. 118 patients were assessed for eligibility and 26 had the tool applied. A change in inhaled medication was recommended in nine (35%) out of 26. Re-admission or death at 30 days was seen in 33% of the switch group and 35% of the no-switch group. Re-admission or death at 90 days was seen in 56% of the switch group and 41% of the no-switch group. Satisfaction with inhalers was generally high, and switching was associated with a small increase in the Feeling of Satisfaction with Inhaler questionnaire of 3 out of 50 points. Delivery of a definitive study would be challenging., Conclusion: We completed a mixed-methods study to design and implement a tool to aid optimisation of inhaled pharmacotherapy prior to discharge following a hospitalised exacerbation of COPD. This was not associated with fewer re-admissions, but was well received and one-third of people were eligible for a change in inhalers., Competing Interests: Conflict of interest: A. De Soyza declares research grants in support of investigator and investigator-initiated trials from Sanofi-Aventis, Lilly, Boehringer Ingelheim and AstraZeneca; consulting fees from AstraZeneca, Insmed, Sanofi, Bayer, GSK, Boehringer Ingelheim and Zambon; speakers’ fees from AstraZeneca, Insmed, Sanofi, Bayer, GSK, Boehringer Ingelheim and Zambon; and advisory board membership for AstraZeneca, Insmed, Sanofi, Bayer, GSK, Boehringer Ingelheim and Zambon, all in the 36 months prior to manuscript submission. Conflict of interest: M. Dobson declares NIHR Research for Patient Benefit co-applicant funding to their institution in relation to the present work. Conflict of interest: C. Echevarria declares research grants from GlaxoSmithKline and NIHR, in the 36 months prior to manuscript submission. Conflict of interest: G. Martin declares NIHR Research for Patient Benefit co-applicant funding to their institution in relation to the present work. Conflict of interest: R.G. Mendes declares payment for participation in scientific events from Fundação de Apoio à Pesquisa do Estado de São Paulo. Conflict of interest: E. Sapey declares NIHR Research for Patient Benefit co-applicant funding to their institution in relation to the present work. Conflict of interest: J.R. Hurst declares funding for a PhD studentship from AstraZeneca; consulting fees to them and their institution from AstraZeneca and GlaxoSmithKline; payment or honoraria to themselves for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from AstraZeneca, Boehringer Ingelheim, Chiesi, Sanofi and Takeda; support in kind for attending meetings from AstraZeneca; payment to them and their institution for participation on an Advisory Board for AstraZeneca; and donation of oximeters from Nonin, all in the 36 months prior to manuscript submission. Conflict of interest: All other authors declare no competing interests., (Copyright ©The authors 2024.)

Background: Longitudinal data on the detectability of monkeypox virus (MPXV) genetic material in different specimen types are scarce., Methods: We describe MPXV-specific polymerase chain reaction (PCR) results from adults with confirmed mpox infection from Toronto, Canada, including a cohort undergoing weekly collection of specimens from multiple anatomic sites until 1 week after skin lesions had fully healed. We quantified the time from symptom onset to resolution of detectable viral DNA (computed tomography [Ct] ≥ 35) by modeling exponential decay in Ct value as a function of illness day for each site, censoring at the time of tecovirimat initiation., Results: Among 64 men who have sex with men, the median (interquartile range [IQR]) age was 39 (32.75-45.25) years, and 49% had HIV. Twenty received tecovirimat. Viral DNA was detectable (Ct < 35) at baseline in 74% of genital/buttock/perianal skin swabs, 56% of other skin swabs, 44% of rectal swabs, 37% of throat swabs, 27% of urine, 26% of nasopharyngeal swabs, and 8% of semen samples. The median time to resolution of detectable DNA (IQR) was longest for genital/buttock/perianal skin and other skin swabs at 30.0 (23.0-47.9) and 22.4 (16.6-29.4) days, respectively, and shortest for nasopharyngeal swabs and semen at 0 (0-12.1) and 0 (0-0) days, respectively. We did not observe an effect of tecovirimat on the rate of decay in viral DNA detectability in any specimen type (all P > .05)., Conclusions: MPXV DNA detectability varies by specimen type and persists for over 3-4 weeks in skin specimens. The rate of decay did not differ by tecovirimat use in this nonrandomized study., Competing Interests: Potential conflicts of interest. D.H.S.T.'s institution has received research support for investigator-initiated research studies from AbbVie and Gilead and support for participation in industry-sponsored clinical trials from Glaxo Smith Kline. All other authors declare no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Many survivors of preterm birth will have abnormal lung development, reduced peak lung function and, potentially, an increased rate of physiological lung function decline, each of which places them at increased risk of chronic obstructive pulmonary disease across the lifespan. Current rates of preterm birth indicate that by the year 2040, around 50 years since the introduction of surfactant therapy, more than 700 million individuals will have been born prematurely-a number that will continue to increase by about 15 million annually. In this Personal View, we describe current understanding of the impact of preterm birth on lung function through the life course, with the aim of putting this emerging health crisis on the radar for the respiratory community. We detail the potential underlying mechanisms of prematurity-associated lung disease and review current approaches to prevention and management. Furthermore, we propose a novel way of considering lung disease after preterm birth, using a multidimensional model to determine individual phenotypes of lung disease-a first step towards optimising management approaches for prematurity-associated lung disease., Competing Interests: Declaration of interests SJS and JH have received funding from the European Respiratory Society and the Government of Western Australia for the Prematurity's Effects on the Lungs in Children and Adults Network (PELICAN) clinical research collaboration. All authors, except KG, are members of PELICAN. CDB, DJE, JTDG, MV, TH, KG, EL, SS, JRH, PU-B, LWD, and SK declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The introduction of community infection control measures during the COVID-19 pandemic was associated with a reduction in acute exacerbations of lung disease. We aimed to understand the acceptability of continued use of infection control measures among people with chronic lung disease and to understand the barriers and facilitators of use., Methods: Australian adults with chronic lung disease were invited to an online survey (last quarter of 2021) to specify infection control measures they would continue themselves post-pandemic and those they perceived should be adopted by the community. A subset of survey participants were interviewed (first quarter of 2022) with coded transcripts deductively mapped to the COM-B model and Theoretical Domains Framework., Results: 193 people (COPD 84, bronchiectasis 41, interstitial lung disease 35, asthma 33) completed the survey. Physical distancing indoors (83%), handwashing (77%), and avoidance of busy places (71%) or unwell family and friends (77%) were measures most likely to be continued. Policies for the wider community that received most support were those during the influenza season including hand sanitiser being widely available (84%), wearing of face coverings by healthcare professionals (67%) and wearing of face coverings by the general population on public transport (66%). Barriers to use of infection control measures were related to physical skills, knowledge, environmental context and resources, social influences, emotion, beliefs about capabilities and beliefs about consequences., Conclusions: Adults with chronic lung diseases in Australia are supportive of physical distancing indoors, hand hygiene, and avoidance of busy places or unwell family and friends as long-term infection control measures., Competing Interests: Conflict of interest: Authors disclose the following: leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid (A.E. Holland: Thoracic Society of Australia and NZ; N.S. Hopkinson: ASH, Asthma+Lung UK); consulting fees (J.R. Hurst: AstraZeneca, GSK); payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events (J.R. Hurst: Boehringer Ingelheim, Chiesi, Sanofi and Takeda); support for attending meetings and/or travel (J.R. Hurst: AstraZeneca); participation on a data safety monitoring or advisory board (J.R. Hurst: AstraZeneca); receipt of equipment, materials, drugs, medical writing, and gifts or other services (J.R. Hurst: Nonin). Conflict of interest: The other co-authors have nothing to declare., (Copyright ©The authors 2024.)

Introduction: Patients diagnosed with Interstitial Lung Diseases (ILD) use devices to self-monitor their health and well-being. Little is known about the range of devices, selection, frequency and terms of use and overall utility. We sought to quantify patients' usage and experiences with home digital devices, and further evaluate their perceived utility and barriers to adaptation., Methods: A team of expert clinicians and patient partners interested in self-management approaches designed a 48-question cross-sectional electronic survey; specifically targeted at individuals diagnosed with ILD. The survey was critically appraised by the interdisciplinary self-management group at Royal Devon University Hospitals NHS Foundation Trust during a 6-month validation process. The survey was open for participation between September 2021 and December 2022, and responses were collected anonymously. Data were analysed descriptively for quantitative aspects and through thematic analysis for qualitative input., Results: 104 patients accessed the survey and 89/104 (86%) reported a diagnosis of lung fibrosis, including 46/89 (52%) idiopathic pulmonary fibrosis (IPF) with 57/89 (64%) of participants diagnosed >3 years and 59/89 (66%) female. 52/65(80%) were in the UK; 33/65 (51%) reported severe breathlessness medical research council MRC grade 3-4 and 32/65 (49%) disclosed co-morbid arthritis or joint problems. Of these, 18/83 (22%) used a hand- held spirometer, with only 6/17 (35%) advised on how to interpret the readings. Pulse oximetry devices were the most frequently used device by 35/71 (49%) and 20/64 (31%) measured their saturations more than once daily. 29/63 (46%) of respondents reported home-monitoring brought reassurance; of these, for 25/63 (40%) a feeling of control. 10/57 (18%) felt it had a negative effect, citing fluctuating readings as causing stress and 'paranoia'. The most likely help-seeking triggers were worsening breathlessness 53/65 (82%) and low oxygen saturation 43/65 (66%). Nurse specialists were the most frequent source of help 24/63 (38%). Conclusion: Patients can learn appropriate technical skills, yet perceptions of home-monitoring are variable; targeted assessment and tailored support is likely to be beneficial., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: AMR reports grants, personal fees and other from Boerhinger Ingelheim, personal fees from Hoffman La Roche, outside the submitted work. AMR is a NIHR Senior Research Leader. The views expressed in this publication are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care. MAG and SL report travel grants and honoraria from Boerhinger Ingelheim for speaking / participation at meetings outside the submitted work. JL has received research grants from GSK and Astra Zeneca outside the submitted work., (Copyright: © 2024 Althobiani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The morphology and distribution of airway tree abnormalities enable diagnosis and disease characterisation across a variety of chronic respiratory conditions. In this regard, airway segmentation plays a critical role in the production of the outline of the entire airway tree to enable estimation of disease extent and severity. Furthermore, the segmentation of a complete airway tree is challenging as the intensity, scale/size and shape of airway segments and their walls change across generations. The existing classical techniques either provide an undersegmented or oversegmented airway tree, and manual intervention is required for optimal airway tree segmentation. The recent development of deep learning methods provides a fully automatic way of segmenting airway trees; however, these methods usually require high GPU memory usage and are difficult to implement in low computational resource environments. Therefore, in this study, we propose a data-centric deep learning technique with big interpolated data, Interpolation-Split, to boost the segmentation performance of the airway tree. The proposed technique utilises interpolation and image split to improve data usefulness and quality. Then, an ensemble learning strategy is implemented to aggregate the segmented airway segments at different scales. In terms of average segmentation performance (dice similarity coefficient, DSC), our method (A) achieves 90.55%, 89.52%, and 85.80%; (B) outperforms the baseline models by 2.89%, 3.86%, and 3.87% on average; and (C) produces maximum segmentation performance gain by 14.11%, 9.28%, and 12.70% for individual cases when (1) nnU-Net with instant normalisation and leaky ReLU; (2) nnU-Net with batch normalisation and ReLU; and (3) modified dilated U-Net are used respectively. Our proposed method outperformed the state-of-the-art airway segmentation approaches. Furthermore, our proposed technique has low RAM and GPU memory usage, and it is GPU memory-efficient and highly flexible, enabling it to be deployed on any 2D deep learning model., Competing Interests: Competing interestsJJ declares fees from Boehringer Ingelheim, F. Hoffmann-La Roche, GlaxoSmithKline, NHSX, Takeda, Wellcome Trust, Gilead Sciences, Microsoft Research unrelated to the submitted work and UK patent Application numbers 2113765.8 and GB2211487.0., (© The Author(s) 2024.)

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death and is associated with multiple medical and psychological comorbidities. Therefore, future strategies to improve COPD management and outcomes are needed for the betterment of patient care. Wearable technology interventions offer considerable promise in improving outcomes, but prior reviews fall short of assessing their role in the COPD population. In this systematic review and meta-analysis we searched ovid-MEDLINE, ovid-EMBASE, CINAHL, CENTRAL, and IEEE databases from inception to April 2023 to identify studies investigating wearable technology interventions in an adult COPD population with prespecified outcomes of interest including physical activity promotion, increasing exercise capacity, exacerbation detection, and quality-of-life. We identified 7396 studies, of which 37 were included in our review. Meta-analysis showed wearable technology interventions significantly increased: the mean daily step count (mean difference (MD) 850 (494-1205) steps/day) and the six-minute walk distance (MD 5.81 m (1.02-10.61 m). However, the impact was short-lived. Furthermore, wearable technology coupled with another facet (such as health coaching or pulmonary rehabilitation) had a greater impact that wearable technology alone. Wearable technology had little impact on quality-of-life measures and had mixed results for exacerbation avoidance and prediction. It is clear that wearable technology interventions may have the potential to form a core part of future COPD management plans, but further work is required to translate this into meaningful clinical benefit., (© 2023. The Author(s).)

Background: Patients with chronic respiratory diseases and those in the postdischarge period following hospitalization because of COVID-19 are particularly vulnerable, and little is known about the changes in their symptoms and physiological parameters. Continuous remote monitoring of physiological parameters and symptom changes offers the potential for timely intervention, improved patient outcomes, and reduced health care costs., Objective: This study investigated whether a real-time multimodal program using commercially available wearable technology, home-based Bluetooth-enabled spirometers, finger pulse oximeters, and smartphone apps is feasible and acceptable for patients with chronic respiratory diseases, as well as the value of low-burden, long-term passive data collection., Methods: In a 3-arm prospective observational cohort feasibility study, we recruited 60 patients from the Royal Free Hospital and University College Hospital. These patients had been diagnosed with interstitial lung disease, chronic obstructive pulmonary disease, or post-COVID-19 condition (n=20 per group) and were followed for 180 days. This study used a comprehensive remote monitoring system designed to provide real-time and relevant data for both patients and clinicians. Data were collected using REDCap (Research Electronic Data Capture; Vanderbilt University) periodic surveys, Remote Assessment of Disease and Relapses-base active app questionnaires, wearables, finger pulse oximeters, smartphone apps, and Bluetooth home-based spirometry. The feasibility of remote monitoring was measured through adherence to the protocol, engagement during the follow-up period, retention rate, acceptability, and data integrity., Results: Lowest-burden passive data collection methods, via wearables, demonstrated superior adherence, engagement, and retention compared with active data collection methods, with an average wearable use of 18.66 (SD 4.69) hours daily (77.8% of the day), 123.91 (SD 33.73) hours weekly (72.6% of the week), and 463.82 (SD 156.70) hours monthly (64.4% of the month). Highest-burden spirometry tasks and high-burden active app tasks had the lowest adherence, engagement, and retention, followed by low-burden questionnaires. Spirometry and active questionnaires had the lowest retention at 0.5 survival probability, indicating that they were the most burdensome. Adherence to and quality of home spirometry were analyzed; of the 7200 sessions requested, 4248 (59%) were performed. Of these, 90.3% (3836/4248) were of acceptable quality according to American Thoracic Society grading. Inclusion of protocol holidays improved retention measures. The technologies used were generally well received., Conclusions: Our findings provide evidence supporting the feasibility and acceptability of remote monitoring for capturing both subjective and objective data from various sources for respiratory diseases. The high engagement level observed with passively collected data suggests the potential of wearables for long-term, user-friendly remote monitoring in respiratory disease management. The unique piloting of certain features such as protocol holidays, alert notifications for missing data, and flexible support from the study team provides a reference for future studies in this field., International Registered Report Identifier (irrid): RR2-10.2196/28873., (©Malik A Althobiani, Yatharth Ranjan, Joseph Jacob, Michele Orini, Richard James Butler Dobson, Joanna C Porter, John R Hurst, Amos A Folarin. Originally published in JMIR Formative Research (https://formative.jmir.org), 24.11.2023.)

Traditional bibliometric assessments of research impact do not correlate with online attention scores in asthma, COPD and COVID-19. https://bit.ly/3FbwC3O., Competing Interests: Conflict of interest: The authors have nothing to disclose., (Copyright ©The authors 2023.)

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).

Objectives: The study examined whether quantified airway metrics associate with mortality in idiopathic pulmonary fibrosis (IPF)., Methods: In an observational cohort study (n = 90) of IPF patients from Ege University Hospital, an airway analysis tool AirQuant calculated median airway intersegmental tapering and segmental tortuosity across the 2nd to 6th airway generations. Intersegmental tapering measures the difference in median diameter between adjacent airway segments. Tortuosity evaluates the ratio of measured segmental length against direct end-to-end segmental length. Univariable linear regression analyses examined relationships between AirQuant variables, clinical variables, and lung function tests. Univariable and multivariable Cox proportional hazards models estimated mortality risk with the latter adjusted for patient age, gender, smoking status, antifibrotic use, CT usual interstitial pneumonia (UIP) pattern, and either forced vital capacity (FVC) or diffusion capacity of carbon monoxide (DLco) if obtained within 3 months of the CT., Results: No significant collinearity existed between AirQuant variables and clinical or functional variables. On univariable Cox analyses, male gender, smoking history, no antifibrotic use, reduced DLco, reduced intersegmental tapering, and increased segmental tortuosity associated with increased risk of death. On multivariable Cox analyses (adjusted using FVC), intersegmental tapering (hazard ratio (HR) = 0.75, 95% CI = 0.66-0.85, p < 0.001) and segmental tortuosity (HR = 1.74, 95% CI = 1.22-2.47, p = 0.002) independently associated with mortality. Results were maintained with adjustment using DLco., Conclusions: AirQuant generated measures of intersegmental tapering and segmental tortuosity independently associate with mortality in IPF patients. Abnormalities in proximal airway generations, which are not typically considered to be abnormal in IPF, have prognostic value., Clinical Relevance Statement: Quantitative measurements of intersegmental tapering and segmental tortuosity, in proximal (second to sixth) generation airway segments, independently associate with mortality in IPF. Automated airway analysis can estimate disease severity, which in IPF is not restricted to the distal airway tree., Key Points: • AirQuant generates measures of intersegmental tapering and segmental tortuosity. • Automated airway quantification associates with mortality in IPF independent of established measures of disease severity. • Automated airway analysis could be used to refine patient selection for therapeutic trials in IPF., (© 2023. The Author(s).)

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.