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Rein Posthuma,1– 3 Lowie EGW Vanfleteren,4,5 Swetlana Gaffron,6 Anouk W Vaes,1 Frits ME Franssen,1– 3 Martijn A Spruit1– 3 1Department of Research and Development, CIRO+, Center of Expertise for Chronic Organ Failure, Horn, the Netherlands; 2NUTRIM, School of Nutrition and Translational Research in Metabolism, Faculty of Health, Medicine and Life Sciences, Maastricht, the Netherlands; 3Department of Respiratory Medicine, Maastricht University Medical Center (MUMC+), Maastricht, the Netherlands; 4COPD Center, Department of Respiratory Medicine and Allergology, Sahlgrenska University Hospital, Gothenburg, Sweden; 5Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 6Viscovery Software GmbH, Vienna, AustriaCorrespondence: Rein Posthuma, CIRO+, Center of expertise for chronic organ failure, Hornerheide 1, Horn, 6085 NM, the Netherlands, Email reinposthuma@ciro-horn.nlPurpose: Long-acting bronchodilators (LABD), in general, reduce respiratory symptoms, improve exercise endurance time and pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, there might be heterogeneity in improvement for several outcomes on an individual level. Therefore, we aimed to profile the multidimensional response in patients receiving tiotropium/olodaterol (T/O) using self-organizing maps (SOM).Materials and Methods: This is a secondary analysis of the TORRACTO study: a multicenter, multinational, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the effects of T/O (2.5/5 and 5/5 μg) compared with placebo after 6 and 12 weeks of treatment in patients with COPD. In the current study, we used endurance time, forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), inspiratory capacity (IC) at rest and IC at isotime (ICiso) to identify clusters by means of SOM in patients treated with T/O.Results: Six clusters with distinct response profiles were generated at week 12 in COPD patients receiving T/O (n = 268). Patients in cluster 1 improved significantly on all outcomes, whilst cluster 5 showed strong improvement in endurance time (357s); contrarily, FEV1, FVC, ICrest and ICiso decreased when compared to baseline.Conclusion: Individual responses on endurance time and pulmonary function after 12 weeks of T/O are heterogeneous. This study identified clusters in COPD patients with markedly different multidimensional response on LABD.Keywords: COPD, long-acting bronchodilators, outcomes

Reem Kayyali,1 Bassel Odeh,1 Inéz Frerichs,2 Nikki Davies,3 Eleni Perantoni,4 Shona D’arcy,5 Anouk W Vaes,6 John Chang,3 Martijn A Spruit,6 Brenda Deering,7 Nada Philip,1 Roshan Siva,3 Evangelos Kaimakamis,8 Ioanna Chouvarda,8 Barbara Pierscionek,1 Norbert Weiler,2 Emiel FM Wouters,6 Andreas Raptopoulos,9 Shereen Nabhani-Gebara1 1Faculty of Science, Engineering and Computing, Kingston University, Kingston-Upon-Thames, UK; 2Department of Anaesthesiology and Intensive Care Medicine, University Medical Centre Schleswig-Holstein, Kiel, Germany; 3Chest Clinic and Research and Development, Croydon University Hospital, Croydon, UK; 4Pulmonary Clinic, AHEPA University Hospital, Thessaloniki, Greece; 5Department of Medicine, Royal College of Surgeons in Ireland, Dublin, Ireland; 6Research and Education, CIRO – Centre of Expertise for Chronic Organ Failure, Horn, the Netherlands; 7COPD Outreach, Beaumont Hospital, Dublin, Ireland; 8Medical School, Aristotle University, Thessaloniki, 9Research and Development, Exodus Information Technology SA, Athens, Greece Background: COPD is among the leading causes of chronic morbidity and mortality in the European Union with an estimated annual economic burden of €25.1 billion. Various care pathways for COPD exist across Europe leading to different responses to similar problems. Determining these differences and the similarities may improve health and the functioning of health services.Objective: The aim of this study was to compare COPD patients’ care pathway in five European Union countries including England, Ireland, the Netherlands, Greece, and Germany and to explore health care professionals’ (HCPs) perceptions about the current pathways.Methods: HCPs were interviewed in two stages using a qualitative, semistructured email interview and a face-to-face semistructured interview.Results: Lack of communication among different health care providers managing COPD and comorbidities was a common feature of the studied care pathways. General practitioners/family doctors are responsible for liaising between different teams/services, except in Greece where this is done through pulmonologists. Ireland and the UK are the only countries with services for patients at home to shorten unnecessary hospital stay. HCPs emphasized lack of communication, limited resources, and poor patient engagement as issues in the current pathways. Furthermore, no specified role exists for pharmacists and informal carers.Conclusion: Service and professional integration between care settings using a unified system targeting COPD and comorbidities is a priority. Better communication between health care providers, establishing a clear role for informal carers, and enhancing patients’ engagement could optimize current care pathways resulting in a better integrated system. Keywords: COPD, comorbidities, care delivery pathway, comparative analysis

Exercise limitation and physical inactivity are separate, but related constructs. Both are commonly present in individuals with COPD, contribute to disease burden over and above the respiratory impairments, and are independently predictive of adverse outcomes. Because of this, clinicians should consider assessing these variables in their patients with COPD. Field tests of exercise performance such as the 6-min walk test and the incremental and endurance shuttle walk tests require limited additional resources, and results correlate with negative outcomes. Laboratory measures of exercise performance using a treadmill or cycle ergometer assess exercise capacity, provide prognostic information and have the advantage of explaining physiological mechanisms (and their interactions) underpinning exercise limitation. Limitations in exercise capacity ( i.e. "cannot do") and physical inactivity ( i.e. "do not do") are both associated with mortality; exercise limitation appears to be the more important driver of this outcome., Competing Interests: Conflict of interest: All authors have no perceived conflict of interest., (Copyright ©ERS 2024.)

Background: In the Netherlands, the prevalence of post COVID-19 condition is estimated at 12.7% at 90-150 days after SARS-CoV-2 infection. This study aimed to determine the occurrence of fatigue and other symptoms, to assess how many patients meet the Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) criteria, to identify symptom-based clusters within the P4O2 COVID-19 cohort and to compare these clusters with clusters in a ME/CFS cohort., Methods: In this multicentre, prospective, observational cohort in the Netherlands, 95 post COVID-19 patients aged 40-65 years were included. Data collection at 3-6 months after infection included demographics, medical history, questionnaires, and a medical examination. Follow-up assessments occurred 9-12 months later, where the same data were collected. Fatigue was determined with the Fatigue Severity Scale (FSS), a score of ≥ 4 means moderate to high fatigue. The frequency and severity of other symptoms and the percentage of patients that meet the ME/CFS criteria were assessed using the DePaul Symptom Questionnaire-2 (DSQ-2). A self-organizing map was used to visualize the clustering of patients based on severity and frequency of 79 symptoms. In a previous study, 337 Dutch ME/CFS patients were clustered based on their symptom scores. The symptom scores of post COVID-19 patients were applied to these clusters to examine whether the same or different clusters were found., Results: According to the FSS, fatigue was reported by 75.9% of the patients at 3-6 months after infection and by 57.1% of the patients 9-12 months later. Post-exertional malaise, sleep disturbances, pain, and neurocognitive symptoms were also frequently reported, according to the DSQ-2. Over half of the patients (52.7%) met the Fukuda criteria for ME/CFS, while fewer patients met other ME/CFS definitions. Clustering revealed specific symptom patterns and showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort, where 2 clusters had > 10 patients., Conclusions: This study shows persistent fatigue and diverse symptomatology in post COVID-19 patients, up to 12-18 months after SARS-CoV-2 infection. Clustering showed that post COVID-19 patients occurred in 11 of the clusters that have been observed in the ME/CFS cohort., (© 2024. The Author(s).)

Introduction: Minimally important differences (MIDs) for common outcomes of pulmonary rehabilitation are well documented for people with chronic obstructive pulmonary disease (COPD). It is not known whether MIDs differ based on COPD disease characteristics. This study aimed to estimate MIDs for clinical outcomes of pulmonary rehabilitation dependent upon baseline characteristics., Methods: A database containing 2791 people with COPD was split into derivation (n=2245; age 66±9 years; 50% males; FEV 1 47±20% predicted) and comparator (n=546; age 66±9 years; 47% males; FEV 1 46±21% predicted) cohorts. MIDs were estimated using 0.5 x SD (symmetrically distributed) or 0.5 x IQR (non-symmetrically distributed) for: 6-minute walk test (6MWT), constant work rate test (CWRT), COPD assessment test (CAT), St. George's respiratory questionnaire (SGRQ), hospital anxiety and depression scale (HADS), and fat-free mass index (FFMI). MIDs were estimated based on baseline outcome scores, lung function, modified medical research council (mMRC) grade and FFMI., Results: MID estimates were comparable to previously reported values. MIDs for SGRQ domains (Symptom=8.7 points, Activity=7.1 points, Impact=8.1 points) and FFMI were produced (0.36kg/m 2 ). There was greater variation of change in 6MWT, SGRQ-activity, SGRQ-impact, HADS and FFMI on which the MIDs were determined when categorising for baseline values (all, p<0.05). Greater variation of change in 6MWT on which the MIDs were determined was evident with COPD disease severity grouping (p<0.05). The magnitude of change in 6MWT, CAT, CWRT, SGRQ-activity, and FFMI with baseline mMRC score categorisation resulted in greater variation on which the MIDs were determined (all, p<0.05). Baseline stratification for FFMI resulted in greater variation of change in CWRT (p<0.001) and HADS-depression (p = 0.043) on which MIDs were determined., Discussion: Findings suggest that baseline presentation should be considered for people with COPD when assessing the efficacy of pulmonary rehabilitation. However, clinical significance of the variation underpinning MIDs is yet to be determined., Competing Interests: Conflicts of interest The authors declare no conflicts of interest in relation to the production of this manuscript., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Current knowledge regarding the measurement properties of the 6-minute walk test (6MWT) in patients with asthma is limited. Therefore, the aim of this study was to assess the test-retest reliability, measurement error and construct validity of the 6MWT and identify determinants of 6-minute walk distance (6MWD) in patients with asthma., Patients and Methods: 201 asthma patients referred for pre-pulmonary rehabilitation assessment, were retrospectively analyzed (age 61±12 years, 42% male, FEV 1 78±27% predicted). Patients performed two 6MWTs on subsequent days using a 30 m straight walking course. Other measurements included resting dyspnea, maximal exercise capacity, body composition, pulmonary function, pulmonary and quadriceps muscle strength and symptoms of anxiety and depression. Measurement error (absolute reliability) was tested using standard error of measurement (SEM), minimal detectable change at 95% confidence interval (MDC95%) and Bland and Altman 95% limits of agreement, whereas test-retest reliability (relative reliability) and construct validity were assessed using the intra-class correlation coefficient (ICC 2,1 ) and correlations, respectively., Results: The 6MWD showed excellent test-retest reliability (ICC 2,1 : 0.91). The mean change in 6MWD after the second 6MWT was 18m (95%CI 11-24m), with 73% of the patients walking further in the second test. The SEM and MDC95% for the 6MWT were 35 m and 98 m, respectively. The best 6MWD correlated strongly with peak oxygen uptake during CPET and resting dyspnea (r = 0.61-0.64) and had no-to-moderate correlations with body composition, pulmonary function, respiratory and quadriceps muscle strength and symptoms of anxiety and depression (r = 0.02-0.45). Multiple linear regression was able to identify maximal workload, BMI, rollator use, maximal expiratory pressure, FEV 1 and DL CO as independent determinants of the best 6MWD (R 2  = 0.58)., Conclusions: The 6MWT was considered to be reliable and valid in patients with asthma, which strengthens its clinical utility. However, the majority of patients demonstrated a considerable learning effect in the second 6MWT, providing a strong rationale for performing two 6MWTs., Competing Interests: Conflicts of interest FMEF reports grants and personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, grants and personal fees from Novartis, personal fees from TEVA, outside the submitted work. BvdB reports personal fees from AstraZeneca and Boehringer Ingelheim, outside the submitted work. MAS reports grants from Netherlands Lung Foundation, grants from AstraZeneca, grants from Boehringer Ingelheim, and a grant from Stichting Astma Bestrijding, all outside the submitted work. RM, SMJJ, AWV, AAFS, HWHvH, PHK, CB, AJvH have nothing to declare., (Copyright © 2022 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Rationale: The six-minute walk test (6MWT) is a practical and simple field-based test to assess physical capacity. Several reference equations for six-minute walking distance (6MWD, m) exist, but have a number of limitations that decrease their clinical utility. In addition, no reference equations exist for the 6MWT-derived outcome six-minute walk work (6MWORK, kg.m)., Objectives: To establish new reference equations for 6MWD and 6MWORK on a 20 m course using data from the population-based Canadian Cohort Obstructive Lung Disease study., Methods and Measurements: A total of 335 participants without obstructive or restrictive pulmonary function, with normal self-reported health status, normal exercise capacity, and <30 pack years cigarette smoking history were selected to create a representative sample of Canadian adults aged ≥40 years. All participants performed two 6MWTs. Reference equations were derived using multiple regression analyses., Main Results: On average, 6MWD and 6MWORK were 541±98 m and 41.3 ± 11.2 kg.m, respectively. All outcomes were significantly greater in males than females. Sex-specific reference equations were derived from the results of 6MWD and 6MWORK with an explained variance of 24 to 35%., Conclusions: This study established reference equations for 6MWD and 6MWORK on a 20 m course in Caucasian males and females aged ≥40 years with normal pulmonary function, self-reported health status and exercise capacity. These newly derived reference equations add value to the assessment of functional capacity in clinical practice., Competing Interests: Conflicts of interest The CanCOLD study is and/or was funded by the Canadian Respiratory Research Network, the Canadian Institutes of Health Research, AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline Canada Ltd, Novartis, the Respiratory Health Network of the Fonds de la recherche en santé du Québec, the Foundation of the McGill University Health Centre, Almirall, Merck, Nycomed, Pfizer Canada Ltd and Theratechnologies and the UBC centre for Heart Lung innovation Vancouver Jean Bourbeau reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from AstraZeneca Canada Ltd, Boehringer Ingelheim Canada Ltd, GlaxoSmithKline, Pfizer Canada Ltd and Trudell Canada Ltd, outside the submitted work. Dennis Jensen reports a grant and consulting fees from Boehringer Ingelheim, outside the submitted work. Martijn A. Spruit reports grants or contracts from Netherlands Lung Foundation, Stichting Astmabestrijding, Astra Zeneca, TEVA, Boehringer Ingelheim and Chiesi, outside the present work. Alex van ‘t Hul, Anouk Vaes, Jeannet Delbressine, Bita Haijan, Pei Li and Wan Tan report no conflicts of interest., (Copyright © 2023 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) is a complex, heterogenous disease. It has been suggested that subgroups of people with ME/CFS exist, displaying a specific cluster of symptoms. Investigating symptom-based clusters may provide a better understanding of ME/CFS. Therefore, this study aimed to identify clusters in people with ME/CFS based on the frequency and severity of symptoms., Methods: Members of the Dutch ME/CFS Foundation completed an online version of the DePaul Symptom Questionnaire version 2. Self-organizing maps (SOM) were used to generate symptom-based clusters using severity and frequency scores of the 79 measured symptoms. An extra dataset (n = 252) was used to assess the reproducibility of the symptom-based clusters., Results: Data of 337 participants were analyzed (82% female; median (IQR) age: 55 (44-63) years). 45 clusters were identified, of which 13 clusters included ≥ 10 patients. Fatigue and PEM were reported across all of the symptom-based clusters, but the clusters were defined by a distinct pattern of symptom severity and frequency, as well as differences in clinical characteristics. 11% of the patients could not be classified into one of the 13 largest clusters. Applying the trained SOM to validation sample, resulted in a similar symptom pattern compared the Dutch dataset., Conclusion: This study demonstrated that in ME/CFS there are subgroups of patients displaying a similar pattern of symptoms. These symptom-based clusters were confirmed in an independent ME/CFS sample. Classification of ME/CFS patients according to severity and symptom patterns might be useful to develop tailored treatment options., (© 2023. The Author(s).)

Background: Persistent symptoms, described as long COVID or post-COVID-19 condition, pose a potential public health problem. Here, the design and recruitment of the PRIME post-COVID study is described. PRIME post-COVID is a large-scale population-based observational study that aims to improve understanding of the occurrence, risk factors, social, physical, mental, emotional, and socioeconomic impact of post-COVID-19 condition., Methods: An observational open cohort study was set up, with retrospective and prospective assessments on various health-conditions and health-factors (medical, demographic, social, and behavioral) based on a public health COVID-19 test and by self-report (using online questionnaires in Dutch language). Invited for participation were, as recorded in a public health registry, adults (18 years and older) who were tested for COVID-19 and had a valid Polymerase Chain Reaction (PCR) positive or negative test result, and email address. In November 2021, 61,655 individuals were invited by email to participate, these included all eligible adults who tested PCR positive between 1 June 2020 and 1 November 2021, and a sample of adults who tested negative (2:1), comparable in distribution of age, sex, municipality of residence and year-quarter of testing. New recruitment periods are planned as well. Participants are followed over time by regular follow-up measurements. Data are analyzed using the appropriate data-analyses methods., Discussion: The PRIME post-COVID study will provide insights into various health-related aspects of post-COVID-19 condition in the context of various stages of the COVID-19 pandemic. Results will inform practical guidance for society, clinical and public health practice for the prevention and care for long-term impact of COVID-19., Trial Registration Clinicaltrialsgov Identifier: NCT05128695., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Pagen, van Bilsen, Brinkhues, Moonen, Van Herck, Konings, den Heijer, Mujakovic, ter Waarbeek, Bouwmeester-Vincken, Vaes, Spruit, Hoebe and Dukers-Muijrers.)

Background: Fatigue is frequently reported in people with a non-communicable chronic disease. More insight in the nature of this symptom may enhance targeted treatment of fatigue. In this study, we aimed to gain more insight in the prevalence of different types of fatigue and in current prescribed treatment strategies to reduce fatigue in non-communicable chronic diseases., Methods: People with non-communicable chronic diseases were contacted via public, non-profit, disease-specific health funds and patient associations and invited to complete a web-based survey. The survey included a general question about the experience ("Do you now or have you ever had complaints of fatigue?") and nature of fatigue (physically/mentally/combination), the Checklist Individual Strength-subscale subjective fatigue (CIS-Fatigue; 8-56 points), self-constructed questions for the distinction between physical and mental fatigue (both 3-21 points) and questions on prescribed treatments for fatigue., Results: In total, 4199 participants (77% females) completed the online survey. 3945 participants (94.0%) reported experiencing fatigue, of which 64.4% reported a combination of both physical and mental fatigue. Median CIS-Fatigue score was 41 (32-48) points, with 68% of the participants reporting severe fatigue (≥36 points). Median scores for physical and mental fatigue were 15 (11-18) and 12 (8-16) points, respectively. In 55% of the participants, fatigue was only occasionally or never discussed with the healthcare professional, and only 23% of the participants were prescribed a treatment for fatigue. Participants often reported no effect or even an increase in fatigue after treatment., Conclusions: Findings indicate that both physical and mental fatigue are often experienced simultaneously in people with non-communicable chronic diseases, but can also occur separately. Fatigue is often only occasionally or never discussed, let alone treated, highlighting the need to raise awareness among healthcare professionals. Future studies are needed to gain more insight in underlying factors of fatigue in non-communicable chronic diseases, its impact on daily life and development and evaluation of targeted treatment strategies.Key messages:Both physical and mental fatigue are frequently present in people with non-communicable chronic diseases.Fatigue is often only occasionally or never discussed during consultation with the physician, highlighting the need to raise awareness among healthcare professionals for adequate screening and evaluating of fatigue in people with non-communicable chronic diseases.Only less than a quarter of the people with non-communicable chronic diseases who reported to experience fatigue were prescribed a treatment for fatigue, which was often experienced as ineffective.

Background: Isokinetic testing of peripheral muscle function is valid and reliable in patients with chronic obstructive pulmonary disease (COPD)., Objective: To evaluate whether and to what extent isokinetic testing of quadriceps function meets pre-defined test criteria in patients with COPD; to determine the response to pulmonary rehabilitation (PR), and to calculate minimal important differences (MIDs) of isokinetic quadriceps function., Methods: Retrospective analysis of 2033 patients with COPD (age: 65±9 years, body mass index: 26±6 kg/m 2 , FEV 1 : 49±22% predicted) who followed a comprehensive PR program. Pre and post PR isokinetic quadriceps function was assessed with 30 maximal extension-flexion contractions at an angular speed of 90°/s on a computerized dynamometer. The chosen anchors were 6-min walk test and COPD assessment test., Results: Pre PR, 27% of the patients performed the isokinetic test incorrectly. In male and female patients with a correct pre and post PR isokinetic test, peak torque (Δ=10±13 Nm or 9% and Δ=7±9 Nm or 10%, respectively) and total work (Δ=263±270 J or 14% and Δ=198±190 J or 15%, respectively) improved significantly. There was no change in work fatigue index following PR. Using distribution-based calculations, MID estimates for peak torque and total work ranged between 6-7 Nm and 97-135 J in males and between 4-5 Nm and 62-99 J in females., Conclusions: Based on the current test criteria, three in four patients with COPD performed the isokinetic quadriceps test correctly during baseline PR assessment. Furthermore, peak torque and total work, but not work fatigue index, were responsive to PR and sex-specific MIDs were established., Competing Interests: Conflict of interest The BASES consortium is financially supported by Lung Foundation, the Netherlands [#5.1.18.232]. Drs. Jana De Brandt is funded by the Flemish government. The Research of FWO Aspirant Jana De Brandt is sponsored by FWO-grant [#11B4718N]. Dr. F.M.E. Franssen is supported by grants and personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, grants and personal fees from Novartis, personal fees from TEVA, outside the submitted work. Dr. B. van den Borst is supported by personal lecture fees from AstraZeneca and Boehringer Ingelheim bv. Drs. A.A.F. Stoffels, R. Meys, Dr. H.W.H. van Hees, A.J. van ‘t Hul, P.H. Klijn, A.W. Vaes, J. De Brandt and Prof. Dr. C. Burtin and M.A. Spruit declare that they do not have a conflict of interest, (Copyright © 2022 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: There is high heterogeneity of outcomes and measures reported in the literature for pulmonary rehabilitation (PR), which might limit benchmarking and an effective evidence synthesis. A core outcome set (COS) can minimise this problem. It is however unclear which outcomes and measures are most important and suitable for different stakeholders., Methods: A multicentre qualitative study with one-to-one semi-structured interviews with people with chronic obstructive pulmonary disease (COPD), healthcare professionals (HCPs), researchers and policy makers was conducted. Manifest content analysis was conducted to explore the frequency of outcomes viewed as crucial or not. Thematic analysis was performed to better understand stakeholders' views., Results: 37 participants (17 people with COPD and 20 HCPs/researchers/policy makers) from 14 countries and 4 continents were included. Participants expressed that i) core outcomes need to be meaningful to people with COPD and show PR benefits; ii) there should be comprehensive assessment and similar outcomes across settings; iii) a balance between optimal and practical measures is needed; iv) the COS is needed to benchmark PR and advance knowledge; and v) reluctance to change outcomes/measures used by HCPs and using the COS as a maximum set of outcomes might be the pitfalls. 28 outcomes were identified as crucial, and 12 as not crucial., Conclusions: This study provided important insights into outcome measurement in PR from the perspectives of different key international stakeholders and a list of outcomes that will inform a future consensus study., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Evidence suggests sex-related differences in chronic obstructive pulmonary disease (COPD). Whether these differences are reflected in the prevalence of treatable traits remains unknown. Methods: Two samples of patients referred to secondary (n = 530) or tertiary care (n = 2012) were analyzed. Men and women were matched for age, forced expiratory volume in 1 s and body mass index. Sex-related differences were tested using t-tests, Mann-Whitney U, or chi-square tests. Results: Frequent exacerbations (30.5 vs. 19.7%), high cardiovascular risk (88.1 vs. 66.2%) and activity-related severe dyspnea (50.9 vs. 34.8%) were more prevalent in women in secondary care (p < 0.05). Severe hyperinflation (43.0 vs. 25.4%), limited diffusing capacity (79.6 vs. 70.1%), impaired mobility (44.0 vs. 28.7%), frequent exacerbations (66.8 vs. 57.4%), frequent hospitalizations (47.5 vs. 41.6%), severe activity-related dyspnea (89.1 vs. 85.0%), symptoms of anxiety (56.3 vs. 42.0%) and depression (50.3 vs. 44.8%), and poor health status (79.9 vs. 71.0%) were more prevalent in women in tertiary care (p < 0.05). Severe inspiratory muscle weakness (14.6 vs. 8.2%) and impaired exercise capacity (69.1 vs. 59.6%) were more prevalent among men (p < 0.05) in tertiary care. Conclusions: Sex-related differences were found, with most traits more prevalent and severe among women. Care providers should be aware of these differences to adjust treatment.

Background: The psychological impact of COVID-19 can be substantial. However, knowledge about long-term psychological outcomes in patients with COVID-19 is scarce., Objective: In this longitudinal, observational study, we aimed to reveal symptoms of posttraumatic stress disorder (PTSD) and symptoms of anxiety and depression up to 6 months after the onset of COVID-19-related symptoms in patients with confirmed COVID-19 and persistent complaints. To demonstrate the impact in nonhospitalized patients, we further aimed to compare these outcomes between nonhospitalized and hospitalized patients., Methods: Demographics, symptoms of PTSD (Trauma Screening Questionnaire [TSQ] ≥6 points) and symptoms of anxiety and depression (Hospital Anxiety and Depression Scale [HADS] ≥8 points) were assessed at 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID-19 peer support groups., Results: Data from 239 patients with confirmed COVID-19 (198/239, 82.8% female; median age: 50 [IQR 39-56] years) were analyzed. At the 3-month follow-up, 37.2% (89/239) of the patients had symptoms of PTSD, 35.6% (85/239) had symptoms of anxiety, and 46.9% (112/239) had symptoms of depression, which remained high at the 6-month follow-up (64/239, 26.8%, P=.001; 83/239, 34.7%, P=.90; 97/239, 40.6%, P=.08, respectively; versus the 3-month follow-up). TSQ scores and HADS anxiety and depression scores were strongly correlated at the 3- and 6-month follow-ups (r=0.63-0.71, P<.001). Symptoms of PTSD, anxiety, and depression were comparable between hospitalized (n=62) and nonhospitalized (n=177) patients., Conclusions: A substantial percentage of patients with confirmed COVID-19 and persistent complaints reported symptoms of PTSD, anxiety, or depression 3 and 6 months after the onset of COVID-19-related symptoms. The prevalence rates of symptoms of PTSD, anxiety, and depression were comparable between hospitalized and nonhospitalized patients and merely improved over time. Health care professionals need to be aware of these psychological complications and intervene on time in post-COVID-19 patients with persistent complaints., Trial Registration: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705., (©Sarah Houben-Wilke, Yvonne MJ Goërtz, Jeannet M Delbressine, Anouk W Vaes, Roy Meys, Felipe VC Machado, Maarten van Herck, Chris Burtin, Rein Posthuma, Frits ME Franssen, Herman Vijlbrief, Yvonne Spies, Alex J van 't Hul, Martijn A Spruit, Daisy JA Janssen. Originally published in JMIR Mental Health (https://mental.jmir.org), 24.02.2022.)

Physical activity (PA) is of key importance for health among healthy persons and individuals with chronic obstructive pulmonary disease (COPD). PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper, therefore, describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure on how to monitor PA using objective assessments, and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should further clarify the relationship between PA and clinical outcomes, test the impact of treatment interventions on PA in individuals with COPD, and successfully propose a PA endpoint for regulatory qualification in the future., (JCOPDF © 2021.)

(1) To evaluate the prevalence of severe and chronic fatigue in subjects with and without chronic disease; (2) to assess to which extent multi-morbidity contributes to severe and chronic fatigue; and (3) to identify predisposing and associated factors for severe and chronic fatigue and whether these are disease-specific, trans-diagnostic, or generic. The Dutch Lifelines cohort was used, including 78,363 subjects with (n = 31,039, 53 ± 12 years, 33% male) and without (n = 47,324, 48 ± 12 years, 46% male) ≥ 1 of 23 chronic diseases. Fatigue was assessed with the Checklist Individual Strength-Fatigue. Compared to participants without a chronic disease, a higher proportion of participants with ≥ 1 chronic disease were severely (23% versus 15%, p < 0.001) and chronically (17% versus 10%, p < 0.001) fatigued. The odds of having severe fatigue (OR [95% CI]) increased from 1.6 [1.5-1.7] with one chronic disease to 5.5 [4.5-6.7] with four chronic diseases; for chronic fatigue from 1.5 [1.5-1.6] to 4.9 [3.9-6.1]. Multiple trans-diagnostic predisposing and associated factors of fatigue were found, explaining 26% of variance in fatigue in chronic disease. Severe and chronic fatigue are highly prevalent in chronic diseases. Multi-morbidity increases the odds of having severe and chronic fatigue. Several trans-diagnostic factors were associated with fatigue, providing a rationale for a trans-diagnostic approach., (© 2021. The Author(s).)

Background: Fatigue is the most commonly reported symptom in patients with persistent complaints following COVID-19 (ie, long COVID). Longitudinal studies examining the intensity of fatigue and differentiating between physical and mental fatigue are lacking., Objective: The objectives of this study were to (1) assess the severity of fatigue over time in members of online long COVID peer support groups, and (2) assess whether members of these groups experienced mental fatigue, physical fatigue, or both., Methods: A 2-wave web-based follow-up study was conducted in members of online long COVID peer support groups with a confirmed diagnosis approximately 3 and 6 months after the onset of infectious symptoms. Demographics, COVID-19 diagnosis, received health care (from medical professionals or allied health care professionals), fatigue (Checklist Individual Strength-subscale subjective fatigue [CIS-Fatigue]; 8-56 points), and physical and mental fatigue (self-constructed questions; 3-21 points) were assessed. Higher scores indicated more severe fatigue. A CIS-Fatigue score ≥36 points was used to qualify patients as having severe fatigue., Results: A total of 239 patients with polymerase chain reaction/computed tomography-confirmed COVID-19 completed the survey 10 weeks (SD 2) and 23 weeks (SD 2) after onset of infectious symptoms, respectively (T1 and T2). Of these 239 patients, 198 (82.8%) were women; 142 (59.4%) had no self-reported pre-existing comorbidities; 208 (87%) self-reported being in good health before contracting COVID-19; and 62 (25.9%) were hospitalized during acute infection. The median age was 50 years (IQR 39-56). The vast majority of patients had severe fatigue at T1 and T2 (n=204, 85.4%, and n=188, 78.7%, respectively). No significant differences were found in the prevalence of normal, mild, and severe fatigue between T1 and T2 (P=.12). The median CIS-Fatigue score was 48 points (IQR 42-53) at T1, and it decreased from T1 to T2 (median change: -2 points, IQR -7 to 3; P<.001). At T1, a median physical fatigue score of 19 points (IQR 16-20) and a median mental fatigue score of 15 points (IQR 10-17) were reported; these scores were lower at T2 for physical but not for mental fatigue (median change for physical fatigue -1 point, IQR -3 to 0, P<.001; median change for mental fatigue 0 points, IQR -3 to 3, P=.52). At the time of completing the follow-up survey, 194/239 (81.2%) and 164/239 (68.6%) of all patients had received care from at least one medical professional and one allied health care professional, respectively., Conclusions: Fatigue in members of online long COVID support groups with a confirmed COVID-19 diagnosis decreases from 10 to 23 weeks after onset of symptoms. Despite this, severe fatigue remains highly prevalent. Both physical and mental fatigue are present. It remains unclear whether and to what extent fatigue will resolve spontaneously in the longer term., Trial Registration: Netherlands Trial Register NTR8705; https://www.trialregister.nl/trial/8705., (©Maarten Van Herck, Yvonne M J Goërtz, Sarah Houben-Wilke, Felipe V C Machado, Roy Meys, Jeannet M Delbressine, Anouk W Vaes, Chris Burtin, Rein Posthuma, Frits M E Franssen, Bita Hajian, Herman Vijlbrief, Yvonne Spies, Alex J van 't Hul, Daisy J A Janssen, Martijn A Spruit. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 21.09.2021.)

To determine the association between quadriceps muscle strength (QMS) and endurance (QME) and exercise capacity in patients with COPD after stratification for sex and resting lung function (LF). Data were collected from 3,246 patients with COPD (60% men, 64 ± 9 yr), including measures of exercise capacity [peak aerobic capacity (peakV̇o 2 ), 6-min walk distance (6MWD)] and isokinetic QMS and QME. Patients were stratified for sex, forced expiratory volume in 1 s (>50/≤50% predicted), single breath carbon monoxide diffusing capacity (>50/≤50% predicted), and residual volume (>140/≤140% predicted). After stratification for resting LF, QMS and QME were significantly associated with peakV̇o 2 ( r range: 0.47-0.61 and 0.49-0.65 for men and 0.53-0.66 and 0.48-0.67 for women, respectively) and 6MWD ( r range: 0.29-0.42 and 0.44-0.55 for men and 0.25-0.54 and 0.34-0.55 for women, respectively) ( P < 0.001). Regression models demonstrated that QMS and QME were significant determinants of peakV̇o 2 (explained variance R 2 range: 35.6%-48.8% for men and 36.8%-49.0% for women) and 6MWD ( R 2 range: 24.3%-43.3% for men and 28.4%-40.3% for women), independent of age and fat-free mass. Quadriceps muscle function was significantly associated with peakV̇o 2 and 6MWD in male and female patients with COPD after stratification for resting LF, in which QME appear to be a more important determinant than QMS. This underlines the importance of systematically evaluating both quadriceps muscle strength and endurance in in all patients with COPD. NEW & NOTEWORTHY Our findings identified quadriceps muscle function as an important determinant of exercise capacity across a wide spectrum of lung function. Quadriceps muscle endurance appears to be a more important determinant than quadriceps muscle strength, underlining the importance of including both the measurement of quadriceps muscle strength and endurance in routine assessment for all patient with COPD.

Background: A subgroup of patients recovering from COVID-19 experience persistent symptoms, decreased quality of life, increased dependency on others for personal care and impaired performance of activities of daily living. However, the long-term effects of COVID-19 on physical activity (PA) in this subgroup of patients with persistent symptoms remain unclear. Methods: Demographics, self-reported average time spent walking per week, as well as participation in activities pre-COVID-19 and after three and six months of follow-up were assessed in members of online long-COVID-19 peer support groups. Results: Two hundred thirty-nine patients with a confirmed COVID-19 diagnosis were included (83% women, median (IQR) age: 50 (39-56) years). Patients reported a significantly decreased weekly walking time after three months of follow-up (three months: 60 (15-120) min. vs. pre-COVID-19: 120 (60-240) min./week; p < 0.05). Six months after the onset of symptoms walking time was still significantly lower compared to pre-COVID-19 but significantly increased compared to three months of follow-up (three months: 60 (15-120) min. vs. six months: 90 (30-150) min.; p < 0.05). Conclusions: Patients who experience persistent symptoms after COVID-19 may still demonstrate a significantly decreased walking time six months after the onset of symptoms. More research is needed to investigate long-term consequences and possible treatment options to guide patients during the recovery fromCOVID-19.

Purpose: Not all patients with chronic obstructive pulmonary disease (COPD) experience similar benefits after pulmonary rehabilitation (PR). This pre-post PR study used a large sample of patients with COPD to determine whether PR-induced changes of oxygen uptake (V˙O2) kinetics and exercise responses of V˙O2, carbon dioxide output (V˙CO2), minute ventilation (V˙E), V˙E/V˙CO2, breathing frequency, and tidal volume differed between responders and nonresponders to PR., Methods: Responders to PR were defined as patients with a minimal clinically important increase in endurance time of 105 s. Isotime (=180 s) values of V˙O2, V˙CO2, V˙E, V˙E/V˙CO2, breathing frequency, and tidal volume; gains of V˙O2, V˙CO2, and V˙E; and V˙O2 mean response time of 183 patients with COPD (forced expiratory volume in 1 s: 56% ± 19% predicted) were compared between pre- and post-PR constant work rate tests., Results: After PR, only the group of responders significantly decreased V˙O2 mean response time (P < 0.05), V˙CO2 gain, V˙E gain, and isotime values of V˙CO2, V˙E, and V˙E/V˙CO2 (all, P < 0.001), while also improving their breathing pattern (e.g., decreased breathing frequency isotime value; P < 0.0001). These changes were not observed in the group of nonresponders. Changes in physiological exercise responses were correlated with changes in physical performance (e.g., correlation between changes in V˙O2 mean response time and endurance time: P = 0.0002, r = -0.32)., Conclusions: PR-induced changes in physiological exercise responses differed between responders and nonresponders. Physiological changes are relevant to explain the variable improvements of physical performance after PR in patients with COPD., (Copyright © 2020 by the American College of Sports Medicine.)

Background: It remains unknown whether and to what extent members of online "long COVID" peer support groups remain symptomatic and limited over time. Therefore, we aimed to evaluate symptoms in members of online long COVID peer support groups up to 6 months after the onset of coronavirus disease 2019 (COVID-19)-related symptoms., Methods: Demographics, symptoms, health status, work productivity, functional status and health-related quality of life were assessed about 3 and 6 months after the onset of COVID-19-related symptoms in members of online long COVID peer support groups., Results: Data from 239 patients with a confirmed COVID-19 diagnosis (83% women; median (interquartile range) age 50 (39-56) years) were analysed. During the infection, a median (interquartile range) of 15 (11-18) symptoms was reported, which was significantly lower 3 and 6 months later: 6 (4-9) and 6 (3-8), respectively (p<0.05). From 3 to 6 months follow-up, the proportion of patients without symptoms increased from 1.3% to only 5.4% (p<0.001). Patients also reported a significantly improved work productivity (work absenteeism and presenteeism: 73% versus 52% and 66% versus 60%, respectively), self-reported good health (9.2% versus 16.7%), functional status (mean±sd Post-COVID-19 Functional Status scale: 2.4±0.9 versus 2.2±1.0) and health-related quality of life (all p<0.05)., Conclusion: Although patients with confirmed COVID-19, who were all members of online long COVID peer support groups, reported significant improvements in work productivity, functional status and quality of life between 3 and 6 months follow-up, these data clearly highlight the long-term impact of COVID-19, as approximately 6 months after the onset of COVID-19-related symptoms a large proportion still experienced persistent symptoms, a moderate-to-poor health, moderate-to-severe functional limitations, considerable loss in work productivity, and/or an impaired quality of life. Action is needed to improve the management and healthcare of these patients., Competing Interests: Conflict of interest: A.W. Vaes has nothing to disclose. Conflict of interest: Y.M.J. Goërtz has nothing to disclose. Conflict of interest: M. Van Herck has nothing to disclose. Conflict of interest: F.V.C. Machado has nothing to disclose. Conflict of interest: R. Meys has nothing to disclose. Conflict of interest: J.M. Delbressine has nothing to disclose. Conflict of interest: S. Houben-Wilke has nothing to disclose. Conflict of interest: S. Gaffron has nothing to disclose. Conflict of interest: D. Maier reports Biomax provides data management and analysis services to CIRO. Conflict of interest: C. Burtin has nothing to disclose. Conflict of interest: R. Posthuma has nothing to disclose. Conflict of interest: N.P.H. van Loon has nothing to disclose. Conflict of interest: F.M.E. Franssen reports grants and personal fees from AstraZeneca, and personal fees from Boehringer Ingelheim, Chiesi, GSK and TEVA, outside the submitted work. Conflict of interest: B. Hajian has nothing to disclose. Conflict of interest: S.O. Simons reports personal fees from AstraZeneca and grants from GSK, outside the submitted work. Conflict of interest: J.F.M. Van Boven has nothing to disclose. Conflict of interest: F.A. Klok reports grants from Bayer, Bristol Meyer Squibb, Boehringer Ingelheim, MSD, Daiichi-Sankyo, Actelion, the Dutch Thrombosis Association, the Dutch Heart Foundation, and the Netherlands Organisation for Health Research and Development, outside the submitted work. Conflict of interest: B. Spaetgens has nothing to disclose. Conflict of interest: C.M.H. Pinxt has nothing to disclose. Conflict of interest: L.Y.L. Liu has nothing to disclose. Conflict of interest: G. Wesseling has nothing to disclose. Conflict of interest: Y. Spies has nothing to disclose. Conflict of interest: H. Vijlbrief has nothing to disclose. Conflict of interest: A.J. Van ’t Hul has nothing to disclose. Conflict of interest: D.J.A. Janssen reports personal fees from AstraZeneca, Boehringer Ingelheim and Novartis, outside the submitted work. Conflict of interest: M.A. Spruit reports grants from Lung Foundation Netherlands and Stichting Astma Bestrijding, and grants and personal fees from AstraZeneca and Boehringer Ingelheim, outside the submitted work., (Copyright ©The authors 2021.)

To become a proactive and informed partner in postacute coronavirus disease 2019 (COVID-19) management, patients need to have the knowledge, skills, and confidence to self-manage COVID-19-related health challenges. Due to several restrictions and consequently social isolation, online platforms and forums where people can share information and experiences became more popular and influential. Therefore, this study aimed to identify perceived information needs and care needs of members of 2 Facebook groups for patients with COVID-19 and persistent complaints in the Netherlands and Belgium and patients with COVID-19 who registered at a website of the Lung Foundation Netherlands. Besides demographics and clinical characteristics, the degree of satisfaction with care during and after the infection as well as satisfaction with available information were assessed. Open text fields revealed specific information needs which were summarized. Patients with confirmed or suspected COVID-19 perceive various unmet needs varying from specific information needs (eg, information about permanent lung damage) to general needs (eg, being heard and understood). These data lead to several recommendations to improve care for patients with COVID-19 and justify further development of online platforms specifically addressing these unmet needs., Competing Interests: Declaration of Conflicting Interests: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: FMEF reports grants and personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Chiesi, personal fees from GlaxoSmithKline, grants and personal fees from Novartis, personal fees from TEVA, outside the submitted work; DJAJ reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, outside the submitted work; MAS reports grants from Lung Foundation Netherlands, grants from Stichting Astma Bestrijding, grants and personal fees from Boeheringer Ingelheim, and grants and personal fees from AstraZeneca, outside the submitted work. SH-W, JMD, AWV, YMJG, RM, FVCM, MvH, CB, RP, NHPvL, HV, YS, and AvH have nothing to declare., (© The Author(s) 2021.)

Background: An increasing number of subjects are recovering from COVID-19, raising the need for tools to adequately assess the course of the disease and its impact on functional status. We aimed to assess the construct validity of the Post-COVID-19 Functional Status (PCFS) Scale among adult subjects with confirmed and presumed COVID-19., Methods: Adult subjects with confirmed and presumed COVID-19, who were members of an online panel and two Facebook groups for subjects with COVID-19 with persistent symptoms, completed an online survey after the onset of infection-related symptoms. The number and intensity of symptoms were evaluated with the Utrecht Symptom Diary, health-related quality of life (HrQoL) with the 5-level EQ-5D questionnaire, impairment in work and activities with the Work Productivity and Activity Impairment questionnaire and functional status with the PCFS Scale., Results: 1939 subjects were included in the analyses (85% women, 95% non-hospitalized during infection) about 3 months after the onset of infection-related symptoms. Subjects classified as experiencing 'slight', 'moderate' and 'severe' functional limitations presented a gradual increase in the number/intensity of symptoms, reduction of HrQoL and impairment in work and usual activities. No differences were found regarding the number and intensity of symptoms, HrQoL and impairment in work and usual activities between subjects classified as experiencing 'negligible' and 'no' functional limitations. We found weak-to-strong statistical associations between functional status and all domains of HrQoL (r: 0.233-0.661). Notably, the strongest association found was with the 'usual activities' domain of the 5-level EQ-5D questionnaire., Conclusion: We demonstrated the construct validity of the PCFS Scale in highly-symptomatic adult subjects with confirmed and presumed COVID-19, 3 months after the onset of symptoms.

The impact of coronavirus disease 2019 (COVID-19) on quality of life appears to be highly underestimated, especially in patients who have not been admitted to the hospital. Therefore, our aim was to assess respiratory-specific quality of life in addition to generic quality of life in former patients with confirmed/suspected COVID-19 who have never been admitted to the hospital. Members of an online Belgian social support group for patients with confirmed/suspected COVID-19 with persistent complaints, completed an online survey. The five-level EQ-5D (EQ-5D-5L) and the Clinical COPD Questionnaire (CCQ) were used to assess generic and respiratory-specific quality of life, respectively. Data of 210 non-hospitalized patients (88% women, 45 ± 11 years, 79 ± 17 days after symptom onset) were included in the analyses. Mean EQ-5D index and visual analogue scale (EQ-VAS) score was 0.62 ± 0.19 and 50.71 ± 18.87, respectively, with 40% of the patients demonstrating an EQ-5D index that was below the fifth percentile of normative values, indicating poor generic quality of life. The mean CCQ score was 2.01 ± 0.98 points, while 123 respondents (59%) had a total score ≥1.9 points, indicating poor respiratory-specific quality of life. The correlation between EQ-5D index score/EQ-VAS score and CCQ total score was moderate (r = -0.524 and r = -0.374; both p < 0.001). In conclusion, both generic and respiratory-specific quality of life are affected in non-hospitalized patients with COVID-19, approximately three months after the onset of symptoms. The combined use of the EQ-5D and the CCQ could identify the broad impact of COVID-19 on quality of life.

Background: Many patients with COVID-19 did not require hospitalisation, nor underwent COVID-19 testing. There is anecdotal evidence that patients with "mild" COVID-19 may complain about persistent symptoms, even weeks after the infection. This suggests that symptoms during the infection may not resolve spontaneously. The objective of this study was to assess whether multiple relevant symptoms recover following the onset of symptoms in hospitalised and nonhospitalised patients with COVID-19., Methods: A total of 2113 members of two Facebook groups for coronavirus patients with persistent complaints in the Netherlands and Belgium, and from a panel of people who registered on a website of the Lung Foundation Netherlands, were assessed for demographics, pre-existing comorbidities, health status, date of symptoms onset, COVID-19 diagnosis, healthcare utilisation, and the presence of 29 symptoms at the time of the onset of symptoms (retrospectively) and at follow-up (mean±sd 79±17 days after symptoms onset)., Results: Overall, 112 hospitalised patients and 2001 nonhospitalised patients (confirmed COVID-19, n=345; symptom-based COVID-19, n=882; and suspected COVID-19, n=774) were analysed. The median number of symptoms during the infection reduced significantly over time (median (interquartile range) 14 (11-17) versus 6 (4-9); p<0.001). Fatigue and dyspnoea were the most prevalent symptoms during the infection and at follow-up (fatigue: 95% versus 87%; dyspnoea: 90% versus 71%)., Conclusion: In previously hospitalised and nonhospitalised patients with confirmed or suspected COVID-19, multiple symptoms are present about 3 months after symptoms onset. This suggests the presence of a "post-COVID-19 syndrome" and highlights the unmet healthcare needs in a subgroup of patients with "mild" or "severe" COVID-19., Competing Interests: Conflict of interest: Y.M.J. Goërtz has nothing to disclose. Conflict of interest: M. Van Herck has nothing to disclose. Conflict of interest: J.M. Delbressine has nothing to disclose. Conflict of interest: A.W. Vaes has nothing to disclose. Conflict of interest: R. Meys has nothing to disclose. Conflict of interest: F.V.C. Machado has nothing to disclose. Conflict of interest: S. Houben-Wilke has nothing to disclose. Conflict of interest: C. Burtin has nothing to disclose. Conflict of interest: R. Posthuma has nothing to disclose. Conflict of interest: F.M.E. Franssen reports personal fees from GlaxoSmithKline, Chiesi and Boehringer Inghelheim, grants and personal fees from AstraZeneca and Novartis, and personal fees from TEVA, outside the submitted work. Conflict of interest: N. van Loon has nothing to disclose. Conflict of interest: B. Hajian has nothing to disclose. Conflict of interest: Y. Spies has nothing to disclose. Conflict of interest: H. Vijlbrief has nothing to disclose. Conflict of interest: A.J. van ’t Hul has nothing to disclose. Conflict of interest: D.J.A. Janssen reports speaker fees from Novartis, Boehringer Ingelheim and AstraZeneca, outside the submitted work. Conflict of interest: M.A. Spruit reports grants from Lung Foundation Netherlands and Stichting Astma Bestrijding, and grants and personal fees from Boehringer Ingelheim and AstraZeneca, outside the submitted work., (Copyright ©ERS 2020.)

Background: A large sample of "mild" COVID-19 patients still experience multiple symptoms months after being infected. These persistent symptoms are associated with many clinically relevant outcomes, including poor health status and impaired functional status. To date, no information is available about care dependency. Therefore, we aimed to explore the level of care dependency and the need for assistance with personal care in non-hospitalized COVID-19 patients., Methods: Members of two Facebook groups for COVID-19 patients with persistent complaints in The Netherlands and Belgium, and from a panel of people who registered at a website of the Lung Foundation Netherlands, were assessed for demographics, pre-existing comorbidities, health status, and symptoms. In addition, patients were asked about their dependence on others for personal care before and after the infection. The level of care dependency was assessed with the Care Dependency Scale (CDS) in members of the Belgian Facebook group ( n = 210)., Results: The data of 1837 non-hospitalized patients (86% women; median (IQR) age: 47 (38-54)) were analyzed. Only a small proportion of patients needed help with personal care before COVID-19, but the care need increased significantly after the infection (on average 79 ± 17 days after the onset of symptoms; 7.7% versus 52.4%, respectively; p < 0.05). The patients had a median (IQR) CDS score of 72 (67-75) points, and 31% of the patients were considered as care-dependent (CDS score ≤ 68 points)., Conclusions: COVID-19 has an important impact on care dependency in non-hospitalized patients. About three months after the onset of symptoms, a considerable proportion of non-hospitalized patients were to some degree dependent on others for personal care. This indicates that the impact of COVID-19 on patients' daily lives is tremendous, and more attention is needed to identify optimal treatment strategies to restore patients' independency.

Cardiovascular diseases are frequently present in chronic obstructive pulmonary disease (COPD). Population-based studies found associations between retinal vessel diameters and cardiovascular health, but it is unknown whether this also applies to COPD patients. Therefore, we measured retinal vessel diameters in COPD patients and aimed to determine the association with cardiovascular risk factors, lung function, and functional outcomes. In addition, we investigated whether an exercise-based pulmonary rehabilitation (PR) program would change retinal vessel diameters, as a proxy for improved microvascular health. Demographics and clinical characteristics, including pulmonary function, exercise capacity, blood pressure, blood measurements and level of systemic inflammation were obtained from 246 patients during routine assessment before and after PR. Retinal vessel diameters were measured from digital retinal images. Older age and higher systolic blood pressure were associated with narrower retinal arterioles (β: -0.224; p = 0.042 and β: -0.136; p < 0.001, respectively). Older age, higher systolic blood pressure and lower level of systemic inflammation were associated with narrower retinal venules (β: -0.654; -0.229; and -13.767, respectively; p < 0.05). No associations were found between retinal vessel diameters and lung function parameters or functional outcomes. After PR, no significant changes in retinal venular or arteriolar diameter were found. To conclude, retinal vessel diameters of COPD patients were significantly associated with systolic blood pressure and systemic inflammation, whilst there was no evidence for an association with lung function parameters, functional outcomes or other cardiovascular risk factors. Furthermore, an exercise-based PR program did not affect retinal vessel diameter.

Background: Chronic obstructive pulmonary disease (COPD) patients can suffer from low blood oxygen concentrations. Peripheral blood oxygen saturation (SpO 2 ), as assessed by pulse oximetry, is commonly measured during the day using a spot check, or continuously during one or two nights to estimate nocturnal desaturation. Sampling at this frequency may overlook natural fluctuations in SpO 2 ., Objective: This study used wearable finger pulse oximeters to continuously measure SpO 2 during daily home routines of COPD patients and assess natural SpO 2 fluctuations., Methods: A total of 20 COPD patients wore a WristOx 2 pulse oximeter for 1 week to collect continuous SpO 2 measurements. A SenseWear Armband simultaneously collected actigraphy measurements to provide contextual information. SpO 2 time series were preprocessed and data quality was assessed afterward. Mean SpO 2 , SpO 2 SD, and cumulative time spent with SpO 2 below 90% (CT90) were calculated for every (1) day, (2) day in rest, and (3) night to assess SpO 2 fluctuations., Results: A high percentage of valid SpO 2 data (daytime: 93.27%; nocturnal: 99.31%) could be obtained during a 7-day monitoring period, except during moderate-to-vigorous physical activity (MVPA) (67.86%). Mean nocturnal SpO 2 (89.9%, SD 3.4) was lower than mean daytime SpO 2 in rest (92.1%, SD 2.9; P<.001). On average, SpO 2 in rest ranged over 10.8% (SD 4.4) within one day. Highly varying CT90 values between different nights led to 50% (10/20) of the included patients changing categories between desaturator and nondesaturator over the course of 1 week., Conclusions: Continuous SpO 2 measurements with wearable finger pulse oximeters identified significant SpO 2 fluctuations between and within multiple days and nights of patients with COPD. Continuous SpO 2 measurements during daily home routines of patients with COPD generally had high amounts of valid data, except for motion artifacts during MVPA. The identified fluctuations can have implications for telemonitoring applications that are based on daily SpO 2 spot checks. CT90 values can vary greatly from night to night in patients with a nocturnal mean SpO 2 around 90%, indicating that these patients cannot be consistently categorized as desaturators or nondesaturators. We recommend using wearable sensors for continuous SpO 2 measurements over longer time periods to determine the clinical relevance of the identified SpO 2 fluctuations., (©Joren Buekers, Jan Theunis, Patrick De Boever, Anouk W Vaes, Maud Koopman, Eefje VM Janssen, Emiel FM Wouters, Martijn A Spruit, Jean-Marie Aerts. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 06.06.2019.)

A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). We aimed to determine the effects of a comprehensive 8-wk pulmonary rehabilitation program on the physiologic response to and performance of ADLs in patients with COPD. Before and after pulmonary rehabilitation, 31 patients with COPD [71% men; mean age: 64.2 (SD 8.4) years; mean forced expiratory volume in the first second: 54.6 (SD 19.9) % predicted] performed physical function tests, the Canadian Occupational Performance Measure (COPM), and an ADL test consisting of the following: putting on socks, shoes, and vest; stair climbing; washing up four dishes, cups, and saucers; doing groceries and putting away groceries in a cupboard; folding eight towels; and vacuum cleaning for 4 min. Metabolic load, ventilation, and dynamic hyperinflation were assessed using an Oxycon mobile device. In addition, symptoms of dyspnea and fatigue and time to complete ADLs were recorded. After rehabilitation, patients with COPD used a significantly lower proportion of their peak aerobic capacity and ventilation to perform ADLs, accompanied by lower Borg scores for dyspnea and fatigue. Furthermore, patients needed significantly less time to complete ADLs. Dynamic hyperinflation occurred during the performance of ADLs, which did not change following pulmonary rehabilitation. Changes in physical function, including six-min walk distance, constant work rate test, quadriceps muscle strength, and COPM were significantly correlated with change in average total oxygen uptake during the performance of the ADL test. A comprehensive pulmonary rehabilitation program can improve the physiologic response to and actual performance of ADLs in patients with COPD. NEW & NOTEWORTHY A high proportion of patients with chronic obstructive pulmonary disease (COPD) experience problems during the performance of activities of daily living (ADLs). This study clearly demonstrated that a comprehensive pulmonary rehabilitation program can improve the performance of ADLs in patients with COPD, indicated by a significantly shorter time to perform ADLs and a lower metabolic load and dyspnea sensation.

Chronic obstructive pulmonary disease (COPD) is a complex disease with many patients suffering from cardiovascular comorbidity. However, cardiovascular diseases remain often undiagnosed in COPD. Assessment of the retinal microvasculature can provide value in cardiovascular profiling of these patients. Retinal microvascular assessment carried out via a noninvasive eye exam represents an easy to use tool when examining patients with COPD. The purpose of this review was to provide an overview of studies assessing structural and functional changes in the retinal microvasculature of patients with COPD. Findings demonstrated that structural and functional microvascular changes were more common and severe in COPD patients as compared to non-COPD controls, although few retinal investigations have been performed in patients with COPD. As cardiovascular comorbidities are highly prevalent in COPD, we advocate more research to investigate the value of an eye exam for microvascular phenotyping of COPD patients., (© 2018 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Background: Patients with COPD are frequently diagnosed with cardiovascular disease. Peripheral endothelial dysfunction is an underlying mechanism and can be used as an early marker of cardiovascular impairment. To date, little is known on the association between peripheral endothelial dysfunction, cardiovascular risk factors and measurements of exercise capacity in patients with COPD. Therefore, we aimed to determine the relation between endothelial function and patient characteristics, cardiovascular risk factors and (micro)vascular and functional performance in patient with CODP., Methods: Clinical and demographic data of patients with COPD were measured during routine pre-rehabilitation assessment. Cardiovascular risk factors, including blood pressure, ankle brachial index, arterial stiffness and retinal vessel widths were obtained. Peripheral endothelial function was measured using the EndoPAT-2000. Functional performance was assessed using cardiopulmonary exercise test, constant work rate test and six-minute walk test., Results: 40 patients with COPD completed the study protocol (65% males; mean age: 62.8 ± 7.3 years; mean FEV 1 : 45.8 ± 17.5 %pred). Peripheral endothelial dysfunction was observed in 55% of the patients. Patients with peripheral endothelial dysfunction had significantly worse aerobic exercise capacity and higher prevalence of cardiovascular risk factors. Stepwise multivariate regression models identified sex, systolic blood pressure and maximal aerobic capacity as independent correlates of peripheral endothelial function. After correction for sex, age and systolic blood pressure, there was a significant partial correlation between peripheral endothelial function and maximal aerobic capacity (R = 0.51, p = 0.004)., Conclusion: Peripheral endothelial function was positively associated with maximal aerobic capacity, when correcting for sex, age and systolic blood pressure. Establishing peripheral endothelial dysfunction as a determinant of impaired aerobic capacity in COPD can be valuable for developing interventions aiming to improve aerobic capacity, and in turn cardiovascular health., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

We described physical activity measures and hourly patterns in patients with chronic obstructive pulmonary disease (COPD) after stratification for generic and COPD-specific characteristics and, based on multiple physical activity measures, we identified clusters of patients. In total, 1001 patients with COPD (65% men; age, 67 years; forced expiratory volume in the first second [FEV 1 ], 49% predicted) were studied cross-sectionally. Demographics, anthropometrics, lung function and clinical data were assessed. Daily physical activity measures and hourly patterns were analysed based on data from a multisensor armband. Principal component analysis (PCA) and cluster analysis were applied to physical activity measures to identify clusters. Age, body mass index (BMI), dyspnoea grade and ADO index (including age, dyspnoea and airflow obstruction) were associated with physical activity measures and hourly patterns. Five clusters were identified based on three PCA components, which accounted for 60% of variance of the data. Importantly, couch potatoes (i.e. the most inactive cluster) were characterised by higher BMI, lower FEV 1 , worse dyspnoea and higher ADO index compared to other clusters ( p < 0.05 for all). Daily physical activity measures and hourly patterns are heterogeneous in COPD. Clusters of patients were identified solely based on physical activity data. These findings may be useful to develop interventions aiming to promote physical activity in COPD.

Background: Chronic obstructive pulmonary disease (COPD) is a serious long-term lung disease in which the airflow from the lungs is progressively reduced. By 2030, COPD will become the third cause of mortality and seventh cause of morbidity worldwide. With advances in technology and mobile communications, significant progress in the mobile health (mHealth) sector has been recently observed. Mobile phones with app capabilities (smartphones) are now considered as potential media for the self-management of certain types of diseases such as asthma, cancer, COPD, or cardiovascular diseases. While many mobile apps for patients with COPD are currently found on the market, there is little published material on the effectiveness of most of them, their features, and their adoption in health care settings., Objectives: The aim of this study was to search the literature for current systems related to COPD and identify any missing links and studies that were carried out to evaluate the effectiveness of COPD mobile apps. In addition, we reviewed existing mHealth apps from different stores in order to identify features that can be considered in the initial design of a COPD support tool to improve health care services and patient outcomes., Methods: In total, 206 articles related to COPD management systems were identified from different databases. Irrelevant materials and duplicates were excluded. Of those, 38 articles were reviewed to extract important features. We identified 214 apps from online stores. Following exclusion of irrelevant apps, 48 were selected and 20 of them were downloaded to review some of their common features., Results: Our review found that out of the 20 apps downloaded, 13 (65%, 13/20) had an education section, 5 (25%, 5/20) consisted of medication and guidelines, 6 (30%, 6/20) included a calendar or diary and other features such as reminders or symptom tracking. There was little published material on the effectiveness of the identified COPD apps. Features such as (1) a social networking tool; (2) personalized education; (3) feedback; (4) e-coaching; and (5) psychological motivation to enhance behavioral change were found to be missing in many of the downloaded apps., Conclusions: This paper summarizes the features of a COPD patient-support mobile app that can be taken into consideration for the initial design of an integrated care system to encourage the self-management of their condition at home., (©Drishty D Sobnath, Nada Philip, Reem Kayyali, Shereen Nabhani-Gebara, Barbara Pierscionek, Anouk W Vaes, Martijn A Spruit, Evangelos Kaimakamis. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.02.2017.)

Objectives: To ascertain the stakeholders' views and devise recommendations for further stages of the Wearable Sensing and Smart Cloud Computing for Integrated Care to Chronic Obstructive Pulmonary Disease (COPD) Patients with Co-morbidities (WELCOME) system development. This system aims to create a wearable vest to monitor physiological signals for patients concerned incorporating an inhaler adherence monitoring, weight, temperature, blood pressure and glucose metres, and a mobile health application for communication with healthcare professionals (HCPs)., Design: A study of qualitative data derived from focus groups and semistructured interviews., Setting: 4 participating clinical sites in Greece, the UK, Ireland and the Netherlands., Participants: Purposive sampling was used to recruit 32 patients with COPD with heart failure, diabetes, anxiety or depression, 27 informal carers and 23 HCPs from 4 European Union (EU) countries for focus groups and interviews., Results: Most patients and HCPs described the WELCOME system as 'brilliant and creative' and felt it gave a sense of safety. Both users and HCPs agreed that the duration and frequency of vest wear should be individualised as should the mobile application functions. The parameters and frequency of monitoring should be personalised using a multidisciplinary approach. A 'traffic light' alert system was proposed by HCPs for abnormal results. Patients were happy to take actions in response., Conclusions: WELCOME stakeholders provided valuable views on the development of the system, which should take into account patient's individual comorbidities, circumstances and concerns. This will enable the development of the individualised system in each member state concerned., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 "Rehabilitation and Chronic Care" determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5-8 years)., (©ERS 2014.)

Little is known about changes in physical activity in subjects with chronic obstructive pulmonary disease (COPD) and its impact on mortality. Therefore, we aimed to study changes in physical activity in subjects with and without COPD and the impact of physical activity on mortality risk. Subjects from the Copenhagen City Heart Study with at least two consecutive examinations were selected. Each examination included a self-administered questionnaire and clinical examination. 1270 COPD subjects and 8734 subjects without COPD (forced expiratory volume in 1 s 67±18 and 91±15% predicted, respectively) were included. COPD subjects with moderate or high baseline physical activity who reported low physical activity level at follow-up had the highest hazard ratios of mortality (1.73 and 2.35, respectively; both p<0.001). In COPD subjects with low baseline physical activity, no differences were found in survival between unchanged or increased physical activity at follow-up. In addition, subjects without COPD with low physical activity at follow-up had the highest hazard ratio of mortality, irrespective of baseline physical activity level (p≤0.05). A decline to low physical activity at follow-up was associated with an increased mortality risk in subjects with and without COPD. These observational data suggest that it is important to assess and encourage physical activity in the earliest stages of COPD in order to maintain a physical activity level that is as high as possible, as this is associated with better prognosis., (©ERS 2014.)

Background: Strength training and neuromuscular electrical stimulation (NMES) are effective training modalities for improving muscle function, exercise performance and health status in individuals with COPD. The aim of the present study was to analyze the metabolic load of these training modalities at baseline, half-way, and at the end of an eight-week interdisciplinary pulmonary rehabilitation program in a subgroup of individuals with COPD of the DICES trial., Methods: Of 24 individuals with COPD (FEV1: 34 ± 2% predicted, men: 58%, age: 66 (61-68) years), peak oxygen uptake (VO2), peak minute ventilation (VE), heart rate, oxygen saturation and symptom scores were assessed during HF-NMES (75 Hz), LF-NMES (15 Hz) and strength training at three moments during their pulmonary rehabilitation program., Results: Intervention-related peak VO2 did not change over time during HF-NMES, LF-NMES or strength training. Intervention-related peak VE did not change over time during strength training or LF-NMES and increased slightly, but significantly over time during HF-NMES. Peak VO2 and VE were significantly higher during strength training compared to HF-NMES or LF-NMES. Oxygen saturation significantly decreased after the first measurements during HF-NMES and strength training group to baseline, while no significant changes in oxygen saturation were observed during the other measurements. Heart rate significantly increased compared to baseline in all groups at all moments and was significantly higher after strength training compared to HF-NMES or LF-NMES. Median end scores (points) for dyspnea, fatigue and muscle pain ranged from 1 to 3, from 0.5 to 2 and from 0 to 6 after HF-NMES, from 2 to 3, from 2 to 5 and from 0 to 9 after LF-NMES and from 2 to 5, from 1.5 to 4 and from 0 to 28 after strength training respectively., Conclusions: To conclude, the metabolic load and symptom scores remain acceptable low over time with increasing training loads during HF-NMES, LF-NMES or strength training., Trial Registration: NTR2322.

Background: Patients with COPD use a higher proportion of their peak aerobic capacity during the performance of domestic activities of daily life (ADLs) compared to healthy peers, accompanied by a higher degree of task-related symptoms. To date, the influence of body mass index (BMI) on the task-related metabolic demands remains unknown in patients with COPD. Therefore, the aim of our study was to determine the effects of BMI on metabolic load during the performance of 5 consecutive domestic ADLs in patients with COPD., Methodology: Ninety-four COPD patients and 20 healhty peers performed 5 consecutive, self-paced domestic ADLs putting on socks, shoes and vest; folding 8 towels; putting away groceries; washing up 4 dishes, cups and saucers; and sweeping the floor for 4 min. Task-related oxygen uptake and ventilation were assessed using a mobile oxycon, while Borg scores were used to assess task-related dyspnea and fatigue., Principal Findings: 1. Relative task-related oxygen uptake after the performance of domestic ADLs was increased in patients with COPD compared to healthy elderly, whereas absolute oxygen uptake is similar between groups; 2. Relative oxygen uptake and oxygen uptake per kilogram fat-free mass were comparable between BMI groups; and 3. Borg symptom scores for dyspnea en fatigue were comparable between BMI groups., Conclusion: Patients with COPD in different BMI groups perform self-paced domestic ADLs at the same relative metabolic load, accompanied by comparable Borg symptom scores for dyspnea and fatigue.