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Support statement: This work was supported by Fundação de Apoio à Pesquisa do Estado de São Paulo (FAPESP) (numbers process: 2015/12763-4; 2015/26501-1 (Project grant); 2021/03493-4 (NTL scholarship)). The funding source had no involvement in this analysis or in the writing of this manuscript. Funding information for this article has been deposited with the Crossref Funder Registry. Projeto financiado: Bolsa de doutoramento da FAPESP (Brasil). 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. info:eu-repo/semantics/publishedVersion

Malik A Althobiani,1,2 Bilal Khan,1 Amar J Shah,1,3 Yatharth Ranjan,4 Renata G Mendes,1,5 Amos Folarin,4 Swapna Mandal,1,3 Joanna C Porter,1,6 John R Hurst1,3 1UCL Respiratory, University College London, London, UK; 2Department of Respiratory Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah, Saudi Arabia; 3Department of Respiratory Medicine, Royal Free London NHS Foundation Trust, London, UK; 4Department of Health Informatics and Biostatistics, Institute of Psychiatry, Psychology and Neuroscience, Kings College London, London, UK; 5Department of Physical Therapy, Cardiopulmonary Physiotherapy Laboratory, Federal University of São Carlos, São Paulo, Brazil; 6Department of Respiratory Medicine, University College London Hospital (UCLH), London, UKCorrespondence: Malik A Althobiani, UCL Respiratory, University College London, London, UK, Email malik.althobiani.20@ucl.ac.ukObjective: 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.Keywords: wearable technology, COPD exacerbations, clinicians’ perspectives

BACKGROUND: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation.METHODS: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness.RESULTS: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21).CONCLUSIONS: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.

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 in LMIC populations with COPD identified through screening. OBJECTIVE: To describe unmet therapeutic need in screening-detected COPD in LMIC settings. METHODS: We compared interventions recommended by the international 'GOLD' COPD strategy document, with that received, in 1000 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 non-pharmacological interventions was for education and vaccinations (applicable to all), pulmonary rehabilitation (49%), smoking cessation (30%) and advice on biomass smoke exposure (26%). 95% of cases were previously undiagnosed and few were receiving therapy (4.5% had short-acting beta-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 more than a low-skilled workers' daily average wage. CONCLUSION: We found significant missed opportunity to reduce the burden of COPD in LMIC settings, with most cases undiagnosed. Whilst there is unmet need in developing novel therapies, in LMICs where the burden is greatest, better diagnosis together with access to affordable interventions could translate to immediate benefit.

Persistent breathlessness >28 days after acute COVID-19 infection has been identified as a highly debilitating post-COVID symptom. However, the prevalence, risk factors, mechanisms and treatments for post-COVID breathlessness remain poorly understood. We systematically searched PubMed and Embase for relevant studies published from 1 January 2020 to 1 November 2021 (PROSPERO registration number: CRD42021285733) and included 119 eligible papers. Random-effects meta-analysis of 42 872 patients with COVID-19 reported in 102 papers found an overall prevalence of post-COVID breathlessness of 26% (95% CI 23-29) when measuring the presence/absence of the symptom, and 41% (95% CI 34-48) when using Medical Research Council (MRC)/modified MRC dyspnoea scale. The pooled prevalence decreased significantly from 1-6 months to 7-12 months post-infection. Post-COVID breathlessness was more common in those with severe/critical acute infection, those who were hospitalised and females, and was less likely to be reported by patients in Asia than those in Europe or North America. Multiple pathophysiological mechanisms have been proposed (including deconditioning, restrictive/obstructive airflow limitation, systemic inflammation, impaired mental health), but the body of evidence remains inconclusive. Seven cohort studies and one randomised controlled trial suggested rehabilitation exercises may reduce post-COVID breathlessness. There is an urgent need for mechanistic research and development of interventions for the prevention and treatment of post-COVID breathlessness.

Trishul Siddharthan,1,2 Adaeze C Wosu,2,3 Suzanne L Pollard,1,2 Shakir Hossen,1,2 Patricia Alupo,4,5 Timothy Shade,1,2 Robert Kalyesubula,4 Shumonta Quaderi,6 Robert A Wise,1 John R Hurst,6 Bruce Kirenga,4,5 William Checkley1,2 On behalf of LiNK Cohort Study Investigators1Division of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, Baltimore, MD, USA; 2Center for Global Non-Communicable Disease Research and Training, Johns Hopkins University, Baltimore, MD, USA; 3Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA; 4School of Medicine, College of Health Sciences, Makerere University, Kampala, Uganda; 5Makerere Lung Institute, Makerere University, Kampala, Uganda; 6UCL Respiratory, University College London, London, UKCorrespondence: William CheckleyDivision of Pulmonary and Critical Care, School of Medicine, Johns Hopkins University, 1800 Orleans Ave Suite 9121, Baltimore, MD 21287, USATel +1 443-287-4587Email wcheckl1@jhmi.eduBackground: Low- and middle-income countries (LMICs) account for > 90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings. Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings.Methods: We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV1/FVC z-score below the 5th percentile as the gold standard. We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD. We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%. We evaluated for calibration and discrimination using standard approaches. The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow.Results: We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry. The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61– 0.75) with higher scores conferring greater odds of COPD. The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78– 0.88) with a positive predictive value of 50% and a negative predictive value of 96%. The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow.Conclusion: COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings.Keywords: low- and middle-income countries, COPD, COLA, respiratory symptom

Konstantinos Kostikas,1 Chin Kook Rhee,2 John R Hurst,3 Piergiuseppe Agostoni,4,5 Hui Cao,6 Robert Fogel,6 Rupert Jones,7 Janwillem WH Kocks,8– 10 Karen Mezzi,1 Simon Wan Yau Ming,8 Ronan Ryan,8 David B Price8,11 1Novartis Pharma AG, Basel, Switzerland; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea; 3UCL Respiratory, University College London, London, UK; 4Centro Cardiologico Monzino, IRCCS, Milan, Italy; 5Department of Clinical Science and Community Health, University of Milan, Milan, Italy; 6Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA; 7Plymouth University, Faculty of Medicine and Dentistry, Plymouth, UK; 8Observational and Pragmatic Research Institute, Singapore, Singapore; 9General Practitioners Research Institute, Groningen, the Netherlands; 10Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, Groningen, the Netherlands; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UKTel +65 6802 9724Email dprice@opri.sgPurpose: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) often occur concomitantly, presenting diagnostic and therapeutic challenges for clinicians. We examined the characteristics of patients prescribed adequate versus inadequate therapy within 3 months after newly diagnosed comorbid COPD or HF.Patients and Methods: Eligible patients in longitudinal UK electronic medical record databases had pre-existing HF and newly diagnosed COPD (2017 GOLD groups B/C/D) or pre-existing COPD and newly diagnosed HF. Adequate COPD therapy was defined as long-acting bronchodilator(s) with/without inhaled corticosteroid; adequate HF therapy was defined as beta-blocker plus angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker.Results: Of 2439 patients with HF and newly diagnosed COPD (mean 75 years, 61% men), adequate COPD therapy was prescribed for 726 (30%) and inadequate for 1031 (42%); 682 (28%) remained untreated for COPD. Adequate (vs inadequate) COPD therapy was less likely for women (35%) than men (45%), smokers (36%) than ex-/non-smokers (45%), and non-obese (41%) than obese (47%); spirometry was recorded for 57% prescribed adequate versus 35% inadequate COPD therapy. Of 12,587 patients with COPD and newly diagnosed HF (mean 75 years, 60% men), adequate HF therapy was prescribed for 2251 (18%) and inadequate for 5332 (42%); 5004 (40%) remained untreated for HF. Adequate (vs inadequate) HF therapy was less likely for smokers (27%) than ex-/non-smokers (32%) and non-obese (30%) than obese (35%); spirometry was recorded for 65% prescribed adequate versus 39% inadequate HF therapy.Conclusion: Many patients with comorbid COPD/HF receive inadequate therapy after new diagnosis. Improved equity of access to integrated care is needed for all patient subgroups.Keywords: beta-blocker, long-acting bronchodilator, integrated care, multimorbidity

Philip W Stone,1 Cosetta Minelli,1 Johanna Feary,1 C Michael Roberts,2 Jennifer K Quint,1,2,* John R Hurst2,3,* 1National Heart and Lung Institute, Imperial College London, London, UK; 2National Asthma and COPD Audit Programme, Royal College of Physicians of London, London, UK; 3UCL Respiratory, University College London, London, UK*These authors contributed equally to this workCorrespondence: John R Hurst, UCL Respiratory, University College London, London, UK, Email j.hurst@ucl.ac.ukIntroduction: 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.Keywords: COPD, exacerbation, hospital, NEWS2, severity

Luis Alves,1 Rachel Pullen,2 John R Hurst,3 Marc Miravitlles,4 Victoria Carter,5 Rongchang Chen,6 Amy Couper,2 Mark Dransfield,7 Alexander Evans,5 Antony Hardjojo,2 David Jones,5 Rupert Jones,8 Margee Kerr,5 Konstantinos Kostikas,9 Jonathan Marshall,10 Fernando Martinez,11 Marije van Melle,5 Ruth Murray,5 Shigeo Muro,12 Clementine Nordon,10 Michael Pollack,13 Chris Price,5 Anita Sharma,14 Dave Singh,15 Tonya Winders,16 David B Price2 1EPIUnit - Epidemiology Research Unit, ITR - Laboratory for Integrative and Translational Research in Population Health, Instituto de Saúde Pública da Universidade do Porto, Porto, Portugal; 2Observational and Pragmatic Research Institute, Singapore, Singapore; 3UCL Respiratory, University College London, London, UK; 4Pneumology Dept, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 5Optimum Patient Care, Cambridge, UK; 6Key Laboratory of Respiratory Disease of Shenzhen, Shenzhen Institute of Respiratory Disease, Shenzhen People’s Hospital (Second Affiliated Hospital of Jinan University, First Affiliated Hospital of South University of Science and Technology of China), Shenzhen, Guangdong, People’s Republic of China; 7Division of Pulmonary, Allergy, and Critical Care Medicine, Lung Health Center, University of Alabama at Birmingham, Birmingham, AL, USA; 8Research and Knowledge Exchange, Plymouth Marjon University, Plymouth, UK; 9Respiratory Medicine Department, University of Ioannina School of Medicine, Ioannina, Greece; 10BioPharmaceuticals Medical, AstraZeneca, Cambridge, UK; 11New York-Presbyterian Weill Cornell Medical Center, New York, NY, USA; 12Department of Respiratory Medicine, Nara Medical University, Nara, Japan; 13BioPharmaceuticals Medical, AstraZeneca, Wilmington, DE, USA; 14Platinum Medical Centre, Chermside, QLD, Australia; 15Division of Infection, Immunity & Respiratory Medicine, University of Manchester, Manchester, UK; 16USA & Global Allergy & Airways Patient Platform, Vienna, AustriaCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgAbstract: The COllaboration on QUality improvement initiative for achieving Excellence in STandards of COPD care (CONQUEST) aims to improve the quality of COPD care in primary care. The CONQUEST target population includes patients diagnosed with COPD, and those undiagnosed but with COPD-like exacerbations, who are at high but modifiable risk of COPD exacerbations, increased morbidity, and mortality. Timely diagnosis and optimized management to reduce these risks is vital. There is a need for a quality improvement program (QIP) that enables long-term improvement of patient clinical outcomes via integration of the program into routine clinical care. Core to the CONQUEST program is the adoption of four specifically designed, globally applicable, and expert-agreed quality standards (QS) for modifiable high-risk COPD patients. Translation of the QS into clinical practice, and implementation of the QIP, is guided by the CONQUEST global operational protocol provided to sites meeting the minimum healthcare system requirements. Initial analyses of current practices are conducted to generate baseline assessments of need within healthcare systems and sites looking to implement the QIP. Implementation is supported by the provision of CONQUEST resources and tools, such as clinical decision support, that promote prompt identification and treatment of patients. Utilization of electronic medical record (EMR) and patient-reported data are integral components of the QIP. Regular, automated collection and analysis of data, combined with a cyclical review of the implementation process, will be conducted for long-term, continuous improvement and health impact evaluation. The CONQUEST QIP will be an important resource in the identification and management of patients with modifiable high-risk COPD. Embedding the CONQUEST QS into routine clinical practice with regular evaluation and feedback will result in long-term quality of care improvement.Keywords: patient-reported outcome, patient-reported information, clinical decision support, primary care, quality standards, integrated care

Several chronic lung diseases, like idiopathic pulmonary fibrosis (IPF) are characterised by abnormal dilatation of the airways. Quantification of airway features on computed tomography (CT) can help characterise disease progression. Physics based airway measurement algorithms have been developed, but have met with limited success in part due to the sheer diversity of airway morphology seen in clinical practice. Supervised learning methods are also not feasible due to the high cost of obtaining precise airway annotations. We propose synthesising airways by style transfer using perceptual losses to train our model, Airway Transfer Network (ATN). We compare our ATN model with a state-of-the-art GAN-based network (simGAN) using a) qualitative assessment; b) assessment of the ability of ATN and simGAN based CT airway metrics to predict mortality in a population of 113 patients with IPF. ATN was shown to be quicker and easier to train than simGAN. ATN-based airway measurements were also found to be consistently stronger predictors of mortality than simGAN-derived airway metrics on IPF CTs. Airway synthesis by a transformation network that refines synthetic data using perceptual losses is a realistic alternative to GAN-based methods for clinical CT analyses of idiopathic pulmonary fibrosis. Our source code can be found at https://github.com/ashkanpakzad/ATN that is compatible with the existing open-source airway analysis framework, AirQuant., Comment: 11 Pages, 4 figures. Source code available: https://github.com/ashkanpakzad/ATN. Initial submission version, to be published in MICCAI Workshop on Deep Generative Models 2022

Additional file1: Table S1. Search strategies. Table S2. List of included studies with linked publications. Table S3. Study characteristics across the 76 included studies. Table S4. Clinical characteristics of the patients assessed across the included studies.

Additional file 2: Fig. S1. Sex (male vs female) as a risk factor for moderate-to-severe exacerbations. Fig. S2. Sex (male vs female) as a risk factor for severe exacerbations.

Supplemental material, sj-docx-1-tar-10.1177_17534666221107314 for Predictive modeling of COPD exacerbation rates using baseline risk factors by Dave Singh, John R. Hurst, Fernando J. Martinez, Klaus F. Rabe, Mona Bafadhel, Martin Jenkins, Domingo Salazar, Paul Dorinsky and Patrick Darken in Therapeutic Advances in Respiratory Disease

Supplemental material, sj-docx-1-tar-10.1177_17534666221107314 for Predictive modeling of COPD exacerbation rates using baseline risk factors by Dave Singh, John R. Hurst, Fernando J. Martinez, Klaus F. Rabe, Mona Bafadhel, Martin Jenkins, Domingo Salazar, Paul Dorinsky and Patrick Darken in Therapeutic Advances in Respiratory Disease

BACKGROUND: The impact of COVID-19 on physical and mental health and employment after hospitalisation with acute disease is not well understood. The aim of this study was to determine the effects of COVID-19-related hospitalisation on health and employment, to identify factors associated with recovery, and to describe recovery phenotypes. METHODS: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a multicentre, long-term follow-up study of adults (aged ≥18 years) discharged from hospital in the UK with a clinical diagnosis of COVID-19, involving an assessment between 2 and 7 months after discharge, including detailed recording of symptoms, and physiological and biochemical testing. Multivariable logistic regression was done for the primary outcome of patient-perceived recovery, with age, sex, ethnicity, body-mass index, comorbidities, and severity of acute illness as covariates. A post-hoc cluster analysis of outcomes for breathlessness, fatigue, mental health, cognitive impairment, and physical performance was done using the clustering large applications k-medoids approach. The study is registered on the ISRCTN Registry (ISRCTN10980107). FINDINGS: We report findings for 1077 patients discharged from hospital between March 5 and Nov 30, 2020, who underwent assessment at a median of 5·9 months (IQR 4·9-6·5) after discharge. Participants had a mean age of 58 years (SD 13); 384 (36%) were female, 710 (69%) were of white ethnicity, 288 (27%) had received mechanical ventilation, and 540 (50%) had at least two comorbidities. At follow-up, only 239 (29%) of 830 participants felt fully recovered, 158 (20%) of 806 had a new disability (assessed by the Washington Group Short Set on Functioning), and 124 (19%) of 641 experienced a health-related change in occupation. Factors associated with not recovering were female sex, middle age (40-59 years), two or more comorbidities, and more severe acute illness. The magnitude of the persistent health burden was substantial but only weakly associated with the severity of acute illness. Four clusters were identified with different severities of mental and physical health impairment (n=767): very severe (131 patients, 17%), severe (159, 21%), moderate along with cognitive impairment (127, 17%), and mild (350, 46%). Of the outcomes used in the cluster analysis, all were closely related except for cognitive impairment. Three (3%) of 113 patients in the very severe cluster, nine (7%) of 129 in the severe cluster, 36 (36%) of 99 in the moderate cluster, and 114 (43%) of 267 in the mild cluster reported feeling fully recovered. Persistently elevated serum C-reactive protein was positively associated with cluster severity. INTERPRETATION: We identified factors related to not recovering after hospital admission with COVID-19 at 6 months after discharge (eg, female sex, middle age, two or more comorbidities, and more acute severe illness), and four different recovery phenotypes. The severity of physical and mental health impairments were closely related, whereas cognitive health impairments were independent. In clinical care, a proactive approach is needed across the acute severity spectrum, with interdisciplinary working, wide access to COVID-19 holistic clinical services, and the potential to stratify care. FUNDING: UK Research and Innovation and National Institute for Health Research.

Granulomatous–lymphocytic interstitial lung disease (GLILD) has been defined as “a distinct clinico-radio-pathological ILD [interstitial lung disease] occurring in patients with CVID [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded… usually seen in the context of multisystem granulomatous/inflammatory involvement” [1]. The immune and inflammatory complications of CVID such as GLILD are important and associated with reduced survival [2]. However, as a rare manifestation of a rare disease, the scientific understanding and evidence basis to inform effective diagnosis and management of GLILD [3] are limited. There are challenges with the definition of GLILD presented above and the terminology more widely of ILD in people with CVID, which requires further consensus. In this manuscript, we use the term GLILD to describe the heterogeneous ILD seen as part of multisystem immune dysregulation in a substantial minority of people with CVID. A recent international survey of clinicians found little uniformity in diagnostic and therapeutic interventions, identifying an urgent need for new evidence to support consensus guidance [4]. In 2019, the European Respiratory Society (ERS) established a Clinical Research Collaboration to address GLILD (eGLILDnet) [5]. eGLILDnet aims to promote the exchange of research ideas among clinicians and scientists in order to plan, conduct, evaluate and publish clinical and translational studies. Better evidence to diagnose and manage GLILD requires new multicentre research and to this end, we have conducted and here report the results of an international research prioritisation exercise in GLILD. This was a partnership between multiprofessional clinicians and people living with GLILD., The first ever research prioritisation exercise in GLILD: this survey identified areas of interest in the diagnosis, treatment and management of GLILD, which can be used as a roadmap for future research https://bit.ly/3nVuzti

John R Hurst,1 Mohd Kashif Siddiqui,2 Barinder Singh,3 Precil Varghese,4 Ulf Holmgren,5 Enrico de Nigris6 1UCL Respiratory, University College London, London, UK; 2HEOR and RWE Analytics, Regulatory Access, Parexel International Ltd, Mohali, India; 3HEOR Evidence Evaluation, Parexel International Ltd, Mohali, India; 4Biopharmaceuticals Medical, Respiratory and Immunology, AstraZeneca, Gothenburg, MD, USA; 5Real World Science and Digital, Biopharmaceutical Medical, AstraZeneca, Gothenburg, Sweden; 6Global Product and Portfolio Strategy, AstraZeneca, Cambridge, UKCorrespondence: John R HurstUCL Respiratory, Royal Free Campus, London, NW3 2QG, UKTel +44 203 108 7761Email j.hurst@ucl.ac.ukBackground: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide, causing substantial economic and social burden.Objective: This review assessed the patient-reported humanistic burden associated with moderate to very severe COPD, specifically the impact on health-related quality of life (HRQoL), symptoms, limitations in daily life, and emotional implications, through the use of HRQoL instruments.Methods: A systematic review was conducted to retrieve relevant clinical data from published literature using a representative sample of countries where healthcare systems provide wide availability of COPD medications and/or universal coverage includes respiratory medicines (Australia, Canada, China, France, Germany, Italy, Spain, the UK, and the USA). The primary inclusion criteria were patients with moderate to very severe COPD. HRQoL was quantified with non-disease-specific and disease-specific questionnaires.Results: In total, 82 studies from 95 publications presented HRQoL data from patients with moderate to very severe COPD. Patient-reported HRQoL declined with worsening airflow limitation, advancing GOLD group, and increasing exacerbation frequency. Both increasing frequency of hospitalization for COPD exacerbations and recurrent hospitalization adversely impacted HRQoL. Comorbidity incidence was higher in patients with increased airflow limitation. It was associated with a further decline in HRQoL and increased depression and anxiety, particularly as disease-associated pain worsened. Physical activity improved HRQoL over time.Conclusion: This review highlighted the impact of exacerbations and associated hospitalizations on the humanistic burden of COPD. These findings underline the importance of managing COPD actively, including prompt and appropriate use of pharmacological and non-pharmacological therapies that can improve symptoms and reduce the risk of exacerbations, thereby lessening the humanistic burden. Future reviews could consider a broader range of countries and publications to further assess the humanistic impact of COPD in low- and middle-income economies.Keywords: chronic obstructive pulmonary disease, quality of life, humanistic burden, patient-reported outcomes

Abnormal airway dilatation, termed traction bronchiectasis, is a typical feature of idiopathic pulmonary fibrosis (IPF). Volumetric computed tomography (CT) imaging captures the loss of normal airway tapering in IPF. We postulated that automated quantification of airway abnormalities could provide estimates of IPF disease extent and severity. We propose AirQuant, an automated computational pipeline that systematically parcellates the airway tree into its lobes and generational branches from a deep learning based airway segmentation, deriving airway structural measures from chest CT. Importantly, AirQuant prevents the occurrence of spurious airway branches by thick wave propagation and removes loops in the airway-tree by graph search, overcoming limitations of existing airway skeletonisation algorithms. Tapering between airway segments (intertapering) and airway tortuosity computed by AirQuant were compared between 14 healthy participants and 14 IPF patients. Airway intertapering was significantly reduced in IPF patients, and airway tortuosity was significantly increased when compared to healthy controls. Differences were most marked in the lower lobes, conforming to the typical distribution of IPF-related damage. AirQuant is an open-source pipeline that avoids limitations of existing airway quantification algorithms and has clinical interpretability. Automated airway measurements may have potential as novel imaging biomarkers of IPF severity and disease extent., Comment: 14 pages, 8 Figures, for associated source code, see https://github.com/ashkanpakzad/AirQuant

BACKGROUND: Guidelines are critical for facilitating cost-effective COPD care. Development and implementation in low-and middle-income countries (LMICs) is challenging. To guide future strategy, an overview of current global COPD guidelines is required. RESEARCH QUESTION: We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation. STUDY DESIGN AND METHODS: Scoping review of national COPD management guidelines. We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards. LMICs guidelines were compared with those from high-income countries (HICs). RESULTS: Of the 61 national COPD guidelines identified, 30 were from LMICs. Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines. Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities. More than 90% of all guidelines included smoking cessation advice. Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%). LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05). LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05). INTERPRETATION: Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation. Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated. Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources.

Bojidar A Rangelov,1 Alexandra L Young,1– 3 Joseph Jacob,1,4 Anthony P Cahn,5 Sarah Lee,6 Frederick J Wilson,5 David J Hawkes,1 John R Hurst4 1Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK; 2Department of Computer Science, University College London, London, UK; 3Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, UK; 4UCL Respiratory, University College London, London, UK; 5GlaxoSmithKline Research and Development, Stevenage, UK; 6Amallis Consulting LTD, London, UKCorrespondence: John R Hurst Email j.hurst@ucl.ac.ukAbstract: Exacerbations of chronic obstructive pulmonary disease (COPD) are currently diagnosed based on changes in respiratory symptoms. Characterizing the imaging manifestation of exacerbations could be useful for objective diagnosis of exacerbations in the clinic and clinical trials, as well as provide a mechanism for monitoring exacerbation treatment and recovery. In this systematic review, we employed a comprehensive search across three databases (Medline, EMBASE, Web of Science) to identify studies that performed imaging of the thorax at COPD exacerbation. We included 51 from a total of 5,047 articles which met all our inclusion criteria. We used an adapted version of the Modified Newcastle-Ottawa Quality Assessment Scale for cohort studies to assess the quality of the included studies. Conclusions were weighted towards higher-quality articles. We identified a total of 36 thoracic imaging features studied at exacerbation of COPD. Studies were generally heterogeneous in their measurements and focus. Nevertheless, considering studies which performed consecutive imaging at stable state and exacerbation, which scored highest for quality, we identified salient imaging biomarkers of exacerbations. An exacerbation is characterized by airway wall and airway calibre changes, hyperinflation, pulmonary vasoconstriction and imaging features suggestive of pulmonary arterial hypertension. Most information was gained from CT studies. We present the first ever composite imaging signature of COPD exacerbations. While imaging during an exacerbation is comparatively new and not comprehensively studied, it may uncover important insights into the acute pathophysiologic changes in the cardiorespiratory system during exacerbations of COPD, providing objective confirmation of events and a biomarker of recovery and treatment response.Keywords: COPD, radiology and other imaging, emphysema

Rationale: The decades-long progression of chronic obstructive pulmonary disease (COPD) renders identifying different trajectories of disease progression challenging.Objectives: To identify subtypes of patients with COPD with distinct longitudinal progression patterns using a novel machine-learning tool called "Subtype and Stage Inference" (SuStaIn) and to evaluate the utility of SuStaIn for patient stratification in COPD.Methods: We applied SuStaIn to cross-sectional computed tomography imaging markers in 3,698 Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1-4 patients and 3,479 controls from the COPDGene (COPD Genetic Epidemiology) study to identify subtypes of patients with COPD. We confirmed the identified subtypes and progression patterns using ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints) data. We assessed the utility of SuStaIn for patient stratification by comparing SuStaIn subtypes and stages at baseline with longitudinal follow-up data.Measurements and Main Results: We identified two trajectories of disease progression in COPD: a "Tissue→Airway" subtype (n = 2,354, 70.4%), in which small airway dysfunction and emphysema precede large airway wall abnormalities, and an "Airway→Tissue" subtype (n = 988, 29.6%), in which large airway wall abnormalities precede emphysema and small airway dysfunction. Subtypes were reproducible in ECLIPSE. Baseline stage in both subtypes correlated with future FEV1/FVC decline (r = -0.16 [P

Background: Low- and middle-income countries (LMICs) account for >90% of deaths and illness episodes related to COPD; however, this condition is commonly underdiagnosed in these settings. Case-finding instruments for COPD may improve diagnosis and identify individuals that need treatment, but few have been validated in resource-limited settings. Methods: We conducted a population-based cross-sectional study in Uganda to assess the diagnostic accuracy of a respiratory symptom, exposure and functional questionnaire in combination with peak expiratory flow for COPD diagnosis using post-bronchodilator FEV1/FVC z-score below the 5th percentile as the gold standard. We included locally relevant exposure questions and statistical learning techniques to identify the most important risk factors for COPD. We used 80% of the data to develop the case-finding instrument and validated it in the remaining 20%. We evaluated for calibration and discrimination using standard approaches. The final score, COLA (COPD in LMICs Assessment), included seven questions, age and pre-bronchodilator peak expiratory flow. Results: We analyzed data from 1,173 participants (average age 47 years, 46.9% male, 4.5% with COPD) with acceptable and reproducible spirometry. The seven questions yielded a cross-validated area-under-the-curve [AUC] of 0.68 (95% CI 0.61-0.75) with higher scores conferring greater odds of COPD. The inclusion of peak expiratory flow and age improved prediction in a validation sample (AUC=0.83, 95% CI 0.78-0.88) with a positive predictive value of 50% and a negative predictive value of 96%. The final instrument (COLA) included seven questions, age and pre-bronchodilator peak expiratory flow. Conclusion: COLA predicted COPD in urban and rural settings in Uganda has high calibration and discrimination, and could serve as a simple, low-cost screening tool in resource-limited settings.

supplemenary for Nutritional supplementation during pulmonary rehabilitation in COPD: A systematic review by Abdulelah M Aldhahir, Ahmed M Al Rajeh, Yousef S Aldabayan, Salifu Drammeh, Vanitha Subbu, Jaber S Alqahtani, John R Hurst and Swapna Mandal in Chronic Respiratory Disease

Simon Wan Yau Ming,1 John Haughney,2 Dermot Ryan,3 Iain Small,4 Federico Lavorini,5 Alberto Papi,6 Dave Singh,7 David MG Halpin,8 John R Hurst,9 Shishir Patel,10 Matthias Ochel,10 Janwillem Kocks,1,11,12 Victoria Carter,1 Antony Hardjojo,1 David B Price1,2 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 3Optimum Patient Care, Cambridge, UK; 4Peterhead Health Centre, Aberdeen, UK; 5Department of Experimental and Clinical Medicine, Careggi University Hospital, Florence, Italy; 6University of Ferrara, Ferrara, Italy; 7University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 8Royal Devon and Exeter Hospital, Exeter, UK; 9UCL Respiratory, University College London, London, UK; 10Chiesi Limited, Manchester, UK; 11General Practitioners Research Institute, Groningen, the Netherlands; 12University of Groningen, University Medical Center Groningen, GRIAC Research Institute, Groningen, the NetherlandsCorrespondence: David B PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD, UKTel +65 6802 9724Email dprice@opri.sgIntroduction: The Fostair® 100/6 (BDP/FF) pressurized metered-dose inhaler, delivering an extrafine formulation, is licensed for asthma and COPD in the UK. However, its real-life effectiveness for COPD has not been evaluated. This study compared the clinical effectiveness of BDP/FF against other licensed ICS/LABA combination inhalers: the Seretide® Accuhaler® (FP/SAL) and the Symbicort® Turbohaler® (BUD/FF).Methods: A matched historical cohort study was conducted using records of patients with diagnostic codes for COPD from the Optimum Patient Care Research Database (OPCRD). Patients who had received BDP/FF as their first ICS/LABA were matched 1:1 with patients who had received FP/SAL or BUD/FF, resulting in two matched comparisons. Additional analysis was conducted on patients who had never had diagnostic codes for asthma. Noninferiority in terms of the proportion of patients with moderate/severe COPD exacerbations on the different inhalers in the following year was assessed. Noninferiority was achieved if the upper CI limit were ≤ 1.2.Results: This study included 537 and 540 patient pairs in the BDP/FF vs FP/SALcohort and the BDP/FF vs BUD/FF cohort, respectively. The proportion of patients with COPD exacerbations in the BDP/FF group was not significantly different from either the FP/SAL (68.7% vs 70.2%, AOR 0.89, 95% CI 0.67– 1.19) or BUD/FF group (68.5% vs 69.4%, AOR 0.79, 95% CI 0.58– 1.08). Noninferiority of BDP/FF in preventing COPD exacerbations was fulfilled in both comparisons. In patients without asthma, BDP/FF was also noninferior to BUD/FF (proportion with COPD exacerbations, 67.8% vs 64.7%, AOR 0.79, 95% CI 0.51– 1.1997). Additionally, a significantly lower proportion of patients prescribed BDP/FF had COPD exacerbations than FP/SAL (64.8% vs 73.7%, AOR 0.64 95% CI 0.43– 0.96).Conclusion: Initiating ICS/LABA treatment of COPD with extrafine-formulation BDP/FF was noninferior in preventing moderate/severe exacerbations compared to FP/SAL and BUD/FF.Keywords: metered-dose inhaler, dry-powder inhaler, chronic obstructive pulmonary disease, treatment efficacy, cost-effectiveness

05.02 - Monitoring Airway Disease 11549 Investigation of shortened lung clearance index (LCI) in the Bronch-UK Clinimetrics study.Bronchiectasis, Lung function testingK. O'Neill1, G. R. Lakshmipathy1, C. Neely1, D. Cosgrove2, K. Ferguson2, J. D. Chalmers3, A. Desoyza4, T. Gatheral5, A. T. Hill6, J. R. Hurst7, M. R. Loebinger8, J. S. Elborn9, J. M. Bradley101Wellcome-Wolfson Institute for Experimental Medicine, Queen's University - Belfast (United Kingdom), 2Belfast Health and Social Care Trust - Belfast (United Kingdom), 3University of Dundee, College of Medicine - Dundee (United Kingdom), 4Institute of Cellular Medicine, Newcastle University, National Institute of Health Research Biomedical Research Centre - Newcastle (United Kingdom), 5Department of Respiratory Medicine, University Hospitals of Morecambe Bay NHS Foundation Trust - Kendal (United Kingdom), 6Royal Infirmary and University of Edinburgh - Edinburgh (United Kingdom), 7University College London Respiratory, University College London - London (United Kingdom), 8Host Defence Unit, Royal Brompton Hospital, Imperial College London - London (United Kingdom), 9Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast; Host Defence Unit, Royal Brompton Hospital, Imperial College London - London (United Kingdom), 10Clinical Research Facility, Queen’s University - Belfast (United Kingdom)Background: LCI has good intravisit repeatability with better sensitivity in detecting lung disease on CT scan compared to FEV1 in adults with bronchiectasis (BE) (Rowan et al. 2014). However, the test can be prolonged. Shortened LCI may provide sufficient information on ventilation distribution and reduce test time.Aim:To compare the intravisit repeatability (CV%) of LCI2.5 (standard LCI) and LCI5 (shortened LCI) relationship between FEV1% predicted and LCI2.5 and LCI5.time duration of the triplicate washout for LCI2.5 and LCI5.Methods: Multiple Breath Nitrogen Washout data (Exhalyzer D) from the first 98 patients across 5 UK centres (November 2015- June 2017) were over-read centrally for quality control. LCI2.5 (LCI at 2.5% N2) and LCI5 (LCI at 5% N2) data were summarised. CV% and duration of tests (minutes) were compared using paired sample t–tests. Pearson correlation were used to assess relationships.Results: Subjects (n=98), M:F 37:61, had a mean age (SD) 64.8 (11.6) years, FEV1% predicted=74.7 (20.9), LCI2.5 =12.6 (3.2) turnovers, LCI5=7.8 (1.6) turnovers. Mean (SD) CV% of LCI2.5 and LCI5 was 3.8 (2.1) and 2.9 (1.8) respectively (p=0.03). Mean (SD) duration (minutes) of LCI .5 and LCI5 washout time was 15.2 (7.8) and 7.8 (3.6) respectively (pConclusions: In this study, LCI5 had reduced variability (CV%), a comparable strength of correlation with FEV1% predicted and a significant time saving compared with LCI2.5. Investigation of LCI5 in BE clinical trials as a surrogate outcome is warranted.

Purpose: This paper proposes a pipeline to acquire a scalar tapering measurement from the carina to the most distal point of an individual airway visible on CT. We show the applicability of using tapering measurements on clinically acquired data by quantifying the reproducibility of the tapering measure. Methods: We generate a spline from the centreline of an airway to measure the area and arclength at contiguous intervals. The tapering measurement is the gradient of the linear regression between area in log space and arclength. The reproducibility of the measure was assessed by analysing different radiation doses, voxel sizes and reconstruction kernel on single timepoint and longitudinal CT scans and by evaluating the effct of airway bifurcations. Results: Using 74 airways from 10 CT scans, we show a statistical difference, p = 3.4 $\times$ 10$^{-4}$ in tapering between healthy airways (n = 35) and those affected by bronchiectasis (n = 39). The difference between the mean of the two populations was 0.011mm$^{-1}$ and the difference between the medians of the two populations was 0.006mm$^{-1}$. The tapering measurement retained a 95\% confidence interval of $\pm$0.005mm$^{-1}$ in a simulated 25 mAs scan and retained a 95% confidence of $\pm$0.005mm$^{-1}$ on simulated CTs up to 1.5 times the original voxel size. Conclusion: We have established an estimate of the precision of the tapering measurement and estimated the effect on precision of simulated voxel size and CT scan dose. We recommend that the scanner calibration be undertaken with the phantoms as described, on the specific CT scanner, radiation dose and reconstruction algorithm that is to be used in any quantitative studies. Our code is available at https://github.com/quan14/AirwayTaperingInCT, 55 pages, 18 figures, The manuscript was originally published in Journal of Medical Imaging

Ahmed M Alrajeh,1,2 Yousef S Aldabayan,1,2 Abdulelah M Aldhair,1,3 Elisha Pickett,1 Shumonta A Quaderi,1 Jaber S Alqahtani,1,4 Marc Lipman,1 John R Hurst11UCL Respiratory, University College London, London, UK; 2Department of Respiratory Care, King Faisal University, Al Ahsa, Saudi Arabia; 3Department of Respiratory Care, Jazan University, Jazan, Saudi Arabia; 4Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dhahran, Saudi ArabiaIntroduction: Advances in technology offer various solutions that might help optimize the care provided to patients living with chronic non-communicable diseases such as chronic obstructive pulmonary disease (COPD). However, the efficacy of tele-health in COPD is still controversial. Despite this, there appears to be widespread adoption of this technology.Aim: To explore the international use of tele-heath for COPD, to assess the perceptions of clinicians employing tele-health in COPD, and to summarize the techniques that have been used by health care providers to personalize alarm limits for patients with COPD enrolled on tele-health programs.Methods: A cross-sectional survey consisting of 15 questions was distributed and advertised to health care professionals worldwide. Questions were designed to cover five different aspects of tele-health in COPD: purpose of use, equipment type, clinician perceptions, variables monitored, and personalization of alarm limits.Results: A total of 138 participants completed the survey from 29 different countries. As high as 59% of the participants had ever used tele-health for COPD, and 33% still provided tele-health services to patients with COPD. Tele-health was most commonly used for baseline monitoring, with 90% believing it to be effective. The three most commonly monitored variables were oxygen saturation, heart rate, and the use of rescue medication.Conclusion: Twenty-nine different countries use tele-health for managing COPD and therefore there is widespread international use of tele-health in COPD. The majority of providers thought tele-health was effective despite evidence to the contrary.Keywords: chronic obstructive pulmonary disease, COPD, tele-health, home monitoring, alarm limits, perception

supplementarymaterial for Outcome measures in a combined exercise rehabilitation programme for adults with COPD and chronic heart failure: A preliminary stakeholder consensus event by Amy V Jones, Rachael A Evans, William D-C Man, Charlotte E Bolton, Samantha Breen, Patrick J Doherty, Nikki Gardiner, Linzy Houchen-Wolloff, John R Hurst, Kate Jolly, Matthew Maddocks, Jennifer K Quint, Olivia Revitt, Lauren B Sherar, Rod S Taylor, Amye Watt, Jennifer Wingham, Janelle Yorke and Sally J Singh in Chronic Respiratory Disease

Combined exercise rehabilitation for chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF) is potentially attractive. Uncertainty remains as to the baseline profiling assessments and outcome measures that should be collected within a programme. Current evidence surrounding outcome measures in cardiac and pulmonary rehabilitation were presented by experts at a stakeholder consensus event and all stakeholders (n = 18) were asked to (1) rank in order of importance a list of categories, (2) prioritise outcome measures and (3) prioritise baseline patient evaluation measures that should be assessed in a combined COPD and CHF rehabilitation programme. The tasks were completed anonymously and related to clinical rehabilitation programmes and associated research. Health-related quality of life, exercise capacity and symptom evaluation were voted as the most important categories to assess for clinical purposes (median rank: 1, 2 and 3 accordingly) and research purposes (median rank; 1, 3 and 4.5 accordingly) within combined exercise rehabilitation. All stakeholders agreed that profiling symptoms at baseline were 'moderately', 'very' or 'extremely' important to assess for clinical and research purposes in combined rehabilitation. Profiling of frailty was ranked of the same importance for clinical purposes in combined rehabilitation. Stakeholders identified a suite of multidisciplinary measures that may be important to assess in a combined COPD and CHF exercise rehabilitation programme.

Comment -No Abstract available.

Background Chronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings. Methods/design We aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40 years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPD in to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B–D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education and standard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George’s Respiratory Questionnaire (SGRQ) every 3 months over a period of 1 year. The primary endpoint is SGRQ at 12 months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD. Discussion This study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings. Trial registration NCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2). Electronic supplementary material The online version of this article (10.1186/s13063-018-2909-8) contains supplementary material, which is available to authorized users.

BackgroundChronic obstructive pulmonary disease (COPD) is the end result of a susceptible individual being exposed to sufficiently deleterious environmental stimuli. More than 90% of COPD-related deaths occur in low- and middle-income countries (LMICs). LMICs face unique challenges in managing COPD; for example, deficient primary care systems present challenges for proper diagnosis and management. Formal diagnosis of COPD requires quality-assured spirometry, which is often limited to urban health centres. Similarly, standard treatment options for COPD remain limited where few providers are trained to manage COPD. The Global Excellence in COPD Outcomes (GECo) studies aim to assess the performance of a COPD case-finding questionnaire with and without peak expiratory flow (PEF) to diagnose COPD, and inform the effectiveness and implementation of COPD self-management Action Plans in LMIC settings. The ultimate goal is to develop simple, low-cost models of care that can be implemented in LMICs. This study will be carried out in Nepal, Peru and Uganda, three distinct LMIC settings.Methods/designWe aim to assess the diagnostic accuracy of a simple questionnaire with and without PEF to case-find COPD (GECo1), and examine the effectiveness, cost-effectiveness and implementation of a community-health-worker-supported self-management Action Plan strategy for managing exacerbations of COPD (GECo2). To achieve the first aim, we will enrol a randomly selected sample of up to 10,500 adults aged ≥ 40years across our three sites, with the goal to enrol 240 participants with moderate-to-severe COPDin to GECo2. We will apply two case-finding questionnaires (Lung Function Questionnaire and CAPTURE) with and without PEF and compare performance against spirometry. We will report ROC areas, sensitivity and specificity. Individuals who are identified as having COPD grades B-D will be invited to enrol in an effectiveness-implementation hybrid randomised trial of a multi-faceted COPD self-management Action Plan intervention delivered by CHWs. The intervention group will receive (1) COPD education, (2) facilitated-self management Action Plans for COPD exacerbations and (3) monthly visits by community health workers. The control group will receive COPD education andstandard of care treatment provided by local health providers. Beginning at baseline, we will measure quality of life with the EuroQol-5D (EQ-5D) and St. George's Respiratory Questionnaire (SGRQ) every 3months over a period of 1 year. The primary endpoint is SGRQ at 12months. Quality-adjusted life years (QALYs) using the Short-Form 36 version 2 will also be calculated. We will additionally assess the acceptability and feasibility of implementing COPD Action Plans in each setting among providers and individuals with COPD.DiscussionThis study should provide evidence to inform the use of pragmatic models of COPD diagnosis and management in LMIC settings.Trial registrationNCT03359915 (GECo1). Registered on 2 December 2017 and NCT03365713 (GECo2). Registered on 7 December 2017. Trial acronym: Global Excellence in COPD Outcomes (GECo1; GECo2).

Introduction Chronic obstructive pulmonary disease (COPD) will soon be the third leading global cause of death and is increasing rapidly in low/middle-income countries. There is a need for local validation of the Saint George’s Respiratory Questionnaire (SGRQ), which can be used to identify those experiencing lifestyle impairment due to their breathing. Methods The SGRQ was professionally translated into Luganda and reviewed by our field staff and a local pulmonologist. Participants included a COPD-confirmed clinic sample and COPD-positive and negative members of the community who were enrolled in the Lung Function in Nakaseke and Kampala (LiNK) Study. SGRQs were assembled from all participants, while demographic and spirometry data were additionally collected from LiNK participants. Results In total, 103 questionnaires were included in analysis: 49 with COPD from clinic, 34 community COPD-negative and 20 community COPD-positive. SGRQ score varied by group: 53.5 for clinic, 34.4 for community COPD-positive and 4.1 for community COPD-negative (p

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) will soon be the third leading global cause of death and is increasing rapidly in low/middle-income countries. There is a need for local validation of the Saint George's Respiratory Questionnaire (SGRQ), which can be used to identify those experiencing lifestyle impairment due to their breathing. METHODS: The SGRQ was professionally translated into Luganda and reviewed by our field staff and a local pulmonologist. Participants included a COPD-confirmed clinic sample and COPD-positive and negative members of the community who were enrolled in the Lung Function in Nakaseke and Kampala (LiNK) Study. SGRQs were assembled from all participants, while demographic and spirometry data were additionally collected from LiNK participants. RESULTS: In total, 103 questionnaires were included in analysis: 49 with COPD from clinic, 34 community COPD-negative and 20 community COPD-positive. SGRQ score varied by group: 53.5 for clinic, 34.4 for community COPD-positive and 4.1 for community COPD-negative (p

Bronchiectasis is the permanent dilation of airways. Patients with the disease can suffer recurrent exacerbations, reducing their quality of life. The gold standard to diagnose and monitor bronchiectasis is accomplished by inspection of chest computed tomography (CT) scans. A clinician examines the broncho-arterial ratio to determine if an airway is brochiectatic. The visual analysis assumes the blood vessel diameter remains constant, although this assumption is disputed in the literature. We propose a simple measurement of tapering along the airways to diagnose and monitor bronchiectasis. To this end, we constructed a pipeline to measure the cross-sectional area along the airways at contiguous intervals, starting from the carina to the most distal point observable. Using a phantom with calibrated 3D printed structures, the precision and accuracy of our algorithm extends to the sub voxel level. The tapering measurement is robust to bifurcations along the airway and was applied to chest CT images acquired in clinical practice. The result is a statistical difference in tapering rate between airways with bronchiectasis and controls. Our code is available at https://github.com/quan14/AirwayTaperingInCT., Comment: 12 pages, 7 figures. Previously submitted for SPIE Medical Imaging, 2018, Houston, Texas, United States

A fully automated, unsupervised lobe segmentation algorithm is presented based on a probabilistic segmentation of the fissures and the simultaneous construction of a populationmodel of the fissures. A two-class probabilistic segmentation segments the lung into candidate fissure voxels and the surrounding parenchyma. This was combined with anatomical information and a groupwise fissure prior to drive non-parametric surface fitting to obtain the final segmentation. The performance of our fissure segmentation was validated on 30 patients from the chronic obstructive pulmonary disease COPDGene cohort, achieving a high median F

This document provides clinical recommendations for treatment of chronic obstructive pulmonary disease (COPD) exacerbations. Comprehensive evidence syntheses, including meta-analyses, were performed to summarise all available evidence relevant to the Task Force's questions. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of COPD experts. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made: 1) a strong recommendation for noninvasive mechanical ventilation of patients with acute or acute-on-chronic respiratory failure; 2) conditional recommendations for oral corticosteroids in outpatients, oral rather than intravenous corticosteroids in hospitalised patients, antibiotic therapy, home-based management, and the initiation of pulmonary rehabilitation within 3 weeks after hospital discharge; and 3) a conditional recommendation against the initiation of pulmonary rehabilitation during hospitalisation. The Task Force provided recommendations related to corticosteroid therapy, antibiotic therapy, noninvasive mechanical ventilation, home-based management, and early pulmonary rehabilitation in patients having a COPD exacerbation. These recommendations should be reconsidered as new evidence becomes available.

Kieran J Rothnie,1,2 Hana Müllerová,3 Sara L Thomas,2 Joht S Chandan,4 Liam Smeeth,2 John R Hurst,5 Kourtney Davis,3 Jennifer K Quint1,2 1Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, UK; 2Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK; 3Respiratory Epidemiology, GlaxoSmithKline R&D, Uxbridge, London; 4Medical School, 5UCL Respiratory, University College London, London, UK Background: Accurate identification of hospitalizations for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) within electronic health care records is important for research, public health, and to inform health care utilization and service provision. We aimed to develop a strategy to identify hospitalizations for AECOPD in secondary care data and to investigate the validity of strategies to identify hospitalizations for AECOPD in primary care data. Methods: We identified patients with chronic obstructive pulmonary disease (COPD) in the Clinical Practice Research Datalink (CPRD) with linked Hospital Episodes Statistics (HES) data. We used discharge summaries for recent hospitalizations for AECOPD to develop a strategy to identify the recording of hospitalizations for AECOPD in HES. We then used the HES strategy as a reference standard to investigate the positive predictive value (PPV) and sensitivity of strategies for identifying AECOPD using general practice CPRD data. We tested two strategies: 1) codes for hospitalization for AECOPD and 2) a code for AECOPD other than hospitalization on the same day as a code for hospitalization due to unspecified reason. Results: In total, 27,182 patients with COPD were included. Our strategy to identify hospitalizations for AECOPD in HES had a sensitivity of 87.5%. When compared with HES, using a code suggesting hospitalization for AECOPD in CPRD resulted in a PPV of 50.2% (95% confidence interval [CI] 48.5%–51.8%) and a sensitivity of 4.1% (95% CI 3.9%–4.3%). Using a code for AECOPD and a code for hospitalization due to unspecified reason resulted in a PPV of 43.3% (95% CI 42.3%–44.2%) and a sensitivity of 5.4% (95% CI 5.1%–5.7%). Conclusion: Hospitalization for AECOPD can be identified with high sensitivity in the HES database. The PPV and sensitivity of strategies to identify hospitalizations for AECOPD in primary care data alone are very poor. Primary care data alone should not be used to identify hospitalizations for AECOPD. Instead, researchers should use data that are linked to data from secondary care. Keywords: validation, linked data, COPD, hospitalization, cause-specific hospitalization

Background: There are limited data on the burden of cardiovascular comorbidities in people with bronchiectasis. Our cross-sectional study estimates the burden of pre-existing diagnoses of coronary heart disease (CHD) and stroke in people with bronchiectasis compared with the general population. The historical cohort study investigates if individuals with bronchiectasis are at increased risk of incident CHD and stroke events. Methods: We used primary care electronic records from the Clinical Practice Research Datalink. The cross-sectional study used logistic regression to quantify the association between bronchiectasis and recorded diagnoses of CHD or stroke. Cox regression was used to investigate if people with bronchiectasis experienced increased incident CHD and strokes compared with the general population, adjusting for age, sex, smoking habit and other risk factors for cardiovascular disease. Results Pre-existing diagnoses of CHD (OR 1.33, 95% CI 1.25 to 1.41) and stroke (OR 1.92, 95% CI 1.85 to 2.01) were higher in people with bronchiectasis compared with those without bronchiectasis, after adjusting for age, sex, smoking and risk factors for cardiovascular disease. The rate of first CHD and stroke were also higher in people with bronchiectasis (HR for CHD 1.44 (95% CI 1.27 to 1.63) and HR for stroke 1.71 (95% CI 1.54 to 1.90)). Conclusion: The risk of CHD and stroke are higher among people with bronchiectasis compared with the general population. An increased awareness of these cardiovascular comorbidities in this population is needed to provide a more integrated approach to the care of these patients.

Funder: UK Health Data Research BREATHE Hub, BACKGROUND: Persistence of respiratory symptoms, particularly breathlessness, after acute coronavirus disease 2019 (COVID-19) infection has emerged as a significant clinical problem. We aimed to characterise and identify risk factors for patients with persistent breathlessness following COVID-19 hospitalisation. METHODS: PHOSP-COVID is a multicentre prospective cohort study of UK adults hospitalised for COVID-19. Clinical data were collected during hospitalisation and at a follow-up visit. Breathlessness was measured by a numeric rating scale of 0-10. We defined post-COVID-19 breathlessness as an increase in score of ≥1 compared to the pre-COVID-19 level. Multivariable logistic regression was used to identify risk factors and to develop a prediction model for post-COVID-19 breathlessness. RESULTS: We included 1226 participants (37% female, median age 59 years, 22% mechanically ventilated). At a median 5 months after discharge, 50% reported post-COVID-19 breathlessness. Risk factors for post-COVID-19 breathlessness were socioeconomic deprivation (adjusted OR 1.67, 95% CI 1.14-2.44), pre-existing depression/anxiety (adjusted OR 1.58, 95% CI 1.06-2.35), female sex (adjusted OR 1.56, 95% CI 1.21-2.00) and admission duration (adjusted OR 1.01, 95% CI 1.00-1.02). Black ethnicity (adjusted OR 0.56, 95% CI 0.35-0.89) and older age groups (adjusted OR 0.31, 95% CI 0.14-0.66) were less likely to report post-COVID-19 breathlessness. Post-COVID-19 breathlessness was associated with worse performance on the shuttle walk test and forced vital capacity, but not with obstructive airflow limitation. The prediction model had fair discrimination (concordance statistic 0.66, 95% CI 0.63-0.69) and good calibration (calibration slope 1.00, 95% CI 0.80-1.21). CONCLUSIONS: Post-COVID-19 breathlessness was commonly reported in this national cohort of patients hospitalised for COVID-19 and is likely to be a multifactorial problem with physical and emotional components.

ObjectiveAlpha-1 antitrypsin deficiency (AATD) is a common, potentially lethal inborn disorder caused by mutations in alpha-1 antitrypsin (AAT). Homozygosity for the ‘Pi*Z’ variant of AAT (Pi*ZZ genotype) causes lung and liver disease, whereas heterozygous ‘Pi*Z’ carriage (Pi*MZ genotype) predisposes to gallstones and liver fibrosis. The clinical significance of the more common ‘Pi*S’ variant remains largely undefined and no robust data exist on the prevalence of liver tumours in AATD.DesignBaseline phenotypes of AATD individuals and non-carriers were analysed in 482 380 participants in the UK Biobank. 1104 participants of a multinational cohort (586 Pi*ZZ, 239 Pi*SZ, 279 non-carriers) underwent a comprehensive clinical assessment. Associations were adjusted for age, sex, body mass index, diabetes and alcohol consumption.ResultsAmong UK Biobank participants, Pi*ZZ individuals displayed the highest liver enzyme values, the highest occurrence of liver fibrosis/cirrhosis (adjusted OR (aOR)=21.7 (8.8–53.7)) and primary liver cancer (aOR=44.5 (10.8–183.6)). Subjects with Pi*MZ genotype had slightly elevated liver enzymes and moderately increased odds for liver fibrosis/cirrhosis (aOR=1.7 (1.2–2.2)) and cholelithiasis (aOR=1.3 (1.2–1.4)). Individuals with homozygous Pi*S mutation (Pi*SS genotype) harboured minimally elevated alanine aminotransferase values, but no other hepatobiliary abnormalities. Pi*SZ participants displayed higher liver enzymes, more frequent liver fibrosis/cirrhosis (aOR=3.1 (1.1–8.2)) and primary liver cancer (aOR=6.6 (1.6–26.9)). The higher fibrosis burden was confirmed in a multinational cohort. Male sex, age ≥50 years, obesity and the presence of diabetes were associated with significant liver fibrosis.ConclusionOur study defines the hepatobiliary phenotype of individuals with the most relevant AATD genotypes including their predisposition to liver tumours, thereby allowing evidence-based advice and individualised hepatological surveillance.

Rationale: Growth and development during adolescence may modify the respiratory and vascular differences seen among extremely preterm (EP) individuals in childhood and early adolescence.Objectives: To assess the trajectory of respiratory and cardiovascular outcomes during transition to adulthood in a national longitudinal cohort study of births before 26 weeks of gestation in the United Kingdom and Ireland.Methods: A total of 129 EP participants and 65 control subjects attended for a center-based evaluation at 19 years of age. Standardized measures of spirometry, hemodynamics, functional capacity, and markers of inflammation were obtained from EP subjects with and without neonatal bronchopulmonary dysplasia and term-born control subjects at 19 years of age and compared with previous assessments.Measurements and Main Results: Compared with the control group, the EP group was significantly impaired on all spirometric parameters (mean FEV1z-score, -1.08 SD [95% confidence interval, -1.40 to -0.77]) and had lower fractional exhaled nitric oxide concentrations (13.9 vs. 24.4 ppb; P < 0.001) despite a higher proportion with bronchodilator reversibility (27% vs. 6%). The EP group had significantly impaired exercise capacity. All respiratory parameters were worse after neonatal bronchopulmonary dysplasia, and respiratory function differences were similar at 11 and 19 years. The augmentation index was 6% higher in the EP group and associated with increased total peripheral resistance (difference in means, 96.4 [95% confidence interval, 26.6-166.2] dyne/s/cm-5) and elevation in central, but not peripheral, blood pressure. Central systolic and diastolic blood pressures increased more quickly during adolescence in the EP group than in the control group.Conclusions: Clinicians should address both cardiovascular and respiratory risks in adult survivors of extremely preterm birth.

Funder: Foundation for the National Institutes of Health; FundRef: http://dx.doi.org/10.13039/100000009, OBJECTIVES: To establish a database network for the study of alpha-1 antitrypsin deficiency (AATD) and compare the results to CT lung density as the most direct measure of emphysema. DESIGN: A central electronic database was established to permit the upload of anonymised patient data from remote sites. Prospectively collected CT data were recorded onto disc, anonymised, analysed at the coordinating centre and compared with the clinical features of the disease. SETTING: Tertiary referral centres with expertise in the management of AATD focused on academic Biomedical Research Units and Wellcome Clinical Research Facilities. PARTICIPANTS: Data were collected from 187 patients over 1 year from eight UK academic sites. This included patient demographics, postbronchodilator physiology, health status and CT. Analysis was undertaken at the coordinating centre in Birmingham. RESULTS: Patient recruitment in the 12 months reached 94% of target (set at 200) covering the whole spectrum of the disease from those with normal lung function to very severe chronic obstructive lung disease. CT scan suitable for analysis was available from 147 (79%) of the patients. CT density, analysed as the threshold for the lowest 15% of lung voxels, showed statistically significant relationships with the objective physiological parameters of lung function as determined by spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity staging (p

Studies of chest computed tomography (CT) in patients with primary antibody deficiency syndromes (ADS) suggest a broad range of bronchial pathology. However, there are as yet no multicentre studies to assess the variety of bronchial pathology in this patient group. One of the underlying reasons is the lack of a consensus methodology, a prerequisite to jointly document chest CT findings. We aimed to establish an international platform for the evaluation of bronchial pathology as assessed by chest CT and to describe the range of bronchial pathologies in patients with antibody deficiency. Ffteen immunodeficiency centres from 9 countries evaluated chest CT scans of patients with ADS using a predefined list of potential findings including an extent score for bronchiectasis. Data of 282 patients with ADS were collected. Patients with common variable immunodeficiency disorders (CVID) comprised the largest subgroup (232 patients, 82.3%). Eighty percent of CVID patients had radiological evidence of bronchial pathology including bronchiectasis in 61%, bronchial wall thickening in 44% and mucus plugging in 29%. Bronchiectasis was detected in 44% of CVID patients aged less than 20 years. Cough was a better predictor for bronchiectasis than spirometry values. Delay of diagnosis as well as duration of disease correlated positively with presence of bronchiectasis. The use of consensus diagnostic criteria and a pre-defined list of bronchial pathologies allows for comparison of chest CT data in multicentre studies. Our data suggest a high prevalence of bronchial pathology in CVID due to late diagnosis or duration of disease.