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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

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

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