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Introduction and Objectives: The 6-min walk test (6MWT) is used to assess functional capacity in patients with COPD. A significant number of studies have shown that most patients walk further in a second 6MWT. Research on a further increase in the 6-min walk distance (6MWD) during a 3rd test performed in accordance with current guidelines has not been done. Therefore, this study aimed to investigate 1) the reproducibility of three 6MWTs in patients with COPD referred for pulmonary rehabilitation (PR) and 2) predictors of improvement on a third 6MWT., Materials and Methods: Before the start of PR, 1167 COPD patients (50 % male, age: 62 ± 9 years; FEV1: 42 ± 18%pred) performed three 6MWTs (6MWT1, 6MWT2, and 6MWT3). A predetermined threshold of ≥42m improvement in 6MWD in consecutive 6MWT's was used to identify improvers. Reproducibility between tests was assessed using a Bland-Altman plot and logistic regression analyses were performed to assess effects of sex, age, body mass index, GOLD-stage, 6MWD, use of supplemental oxygen and use of walking aids., Results: Generally, the 6MWD improved (6MWT1: 343 ± 115m; 6MWT2: 367 ± 115m; 6MWT3: 381 ± 116m). 210 patients (18 %) improved ≥42m from 6MWT2 to 6MWT3. The Bland-Altman plot showed that the 95 % limits of agreement of 6MWT3 vs 6MWT2 exceeded 42m, indicating that 6MWT2 is not reproducible. Predictors of improvement in 6MWT3 were GOLD stage I/II and a low 6MWD (<350m) in the previous two 6MWTs., Conclusions: These results indicate that three 6MWTs may be required to obtain the largest pre-PR functional capacity in COPD patients. Patients with a 6MWD <350m and GOLD-stage I/II are more likely to improve ≥42m in a third 6MWT., Competing Interests: Declaration of competing interest Jeannet M. Delbressine, Anouk W. Vaes, Wieteke A. M. Stoop, Dirk van Ranst and Alex J. van ’t Hul report no conflict of interest. Martijn A. Spruit reports grants from Lung Foundation Netherlands, Stichting Astma Bestrijding, Boehringer Ingelheim, AstraZeneca, TEVA, Chiesi and Sanofi, and fees from Boehringer Ingelheim, AstraZeneca, TEVA, GSK and Chiesi, all outside the submitted work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Evaluating variability and stability using measures for nonlinear dynamics may provide additional insight into the structure of the locomotor system, reflecting the neuromuscular system's organization of gait. This is in particular of interest when this system is affected by a respiratory disease and it's extrapulmonary manifestations. This study assessed stride-to-stride fluctuations and gait stability in patients with chronic obstructive pulmonary disease (COPD) during a self-paced, treadmill 6-minute walk test (6MWT) and its association with clinical outcomes. In this cross-sectional study, eighty patients with COPD (age 62±7y; forced expiratory volume in first second 56±19%predicted) and 39 healthy older adults (62±7y) were analyzed. Gait parameters including stride-to-stride fluctuations (coefficient of variation (CoV), predictability (sample entropy) and stability (Local Divergence Exponent (LDE)) were calculated over spatiotemporal parameters and center of mass velocity. Independent t-test, Mann-Whitney U test and ANCOVA analyses were conducted. Correlations were calculated between gait parameters, functional mobility using Timed Up and Go Test, and quadriceps muscle strength using dynamometry. Patients walked slower than healthy older adults. After correction for Speed, patients demonstrated increased CoV in stride length (F(1,116) = 5.658, p = 0.019), and increased stride length predictability (F(1,116) = 3.959, p = 0.049). Moderate correlations were found between mediolateral center of mass velocity LDE and normalized maximum peak torque (ρ = -0.549). This study showed that patients with COPD demonstrate alterations in stride length fluctuations even when adjusted for walking speed, highlighting the potential of nonlinear measures to detect alterations in gait function in patients with COPD. Association with clinical outcomes were moderate to weak, indicating that these clinical test are less discriminative for gait alterations., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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: 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.)

Background: Falls risk is elevated in chronic obstructive pulmonary disease (COPD). However, there is a lack of evidence regarding the contributing factors. Here, we examined the feasibility of, and initial responses to, large walking perturbations in COPD, as well as the adaptation potential of people with COPD to repeated walking perturbations that might indicate potential for perturbation-based balance training in COPD., Methods: 12 participants with COPD undergoing inpatient pulmonary rehabilitation and 12 age-gender-matched healthy control participants walked on an instrumented treadmill and experienced repeated treadmill-belt acceleration perturbations (leading to a forward balance loss). Three-dimensional motion capture was used to quantify the stability of participants body position during perturbed walking. Feasibility, stability following the initial perturbations and adaptation to repeated perturbations were assessed., Findings: Using perturbations in this manner was feasible in this population (no harness assists and participants completed the minimum number of perturbations). No clear, specific deficit in reactive walking stability in COPD was found (no significant effects of participant group on stability or recovery step outcomes). There were mixed results for the adaptability outcomes which overall indicated some adaptability to repeated perturbations, but not to the same extent as the healthy control participants., Interpretation: Treadmill-based perturbations during walking are feasible in COPD. COPD does not appear to result in significant deficits in stability following sudden perturbations and patients do demonstrate some adaptability to repeated perturbations. Perturbation-based balance training may be considered for fall prevention in research and practice in people with COPD., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

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.

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.)

Introduction: Persons with chronic obstructive pulmonary disease (COPD) are often limited in performing their activities of daily living (ADLs). However, it remains unknown whether and to what extent problematic ADLs change over time and whether exacerbation-related hospitalisations affect problematic ADLs. Therefore, we investigated self-reported problematic ADLs of persons with COPD during 1 year of usual care (i.e. without a specific experimental intervention)., Methods: Stable persons with moderate to very severe COPD (n = 137) were included in this longitudinal study (registered in the Dutch Trial Register [NTR 3941]). Participants were visited at home at baseline and after 1 year. Participants with an exacerbation-related hospitalisation during follow-up were visited additionally within 2 weeks after hospital discharge. During all visits, participants' personalised problematic ADLs were assessed using the Canadian Occupational Performance Measure (COPM), and perceived performance and satisfaction of important problematic ADLs were rated on a 10-point scale., Results: In total, 90% of the participants reported at least one new important problematic ADL after 1 year. In the subgroup of participants with an exacerbation-related hospitalisation (n = 31), 92% of the participants reported new problematic ADLs 2 weeks after discharge and 90% reported new problematic ADLs again after 1 year. Only the satisfaction score of problematic ADLs as mentioned during baseline improved after 1-year follow-up in all participants (p = .002) and in participants without an exacerbation-related hospitalisation (n = 106; p = .014)., Conclusion: Problematic ADLs changed during 1 year of usual care, which underlines the need for regular assessment of problematic ADLs and referral to treatment options like monodisciplinary occupational therapy and/or a comprehensive pulmonary rehabilitation programme., (© 2020 Occupational Therapy Australia.)

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.

Purpose: Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease characterized by airflow limitation and is associated with decreased balance and increased fall risk. Since falls are related to increased mortality, interventions targeting balance and fall risk could reduce morbidity and mortality. The objective of this review was to systematically assess the effects of exercise-based interventions on fall risk and balance in patients with COPD., Methods: PubMed, Web of Science, EMBASE, and CINAHL were screened for randomized controlled trails and within-group studies evaluating effects of exercise-based interventions on fall risk or balance in patients with COPD. Data were presented in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement., Results: Fifteen studies were identified, 6 randomized controlled trails and 9 within-group studies. All interventions reported positive effects on balance outcomes. No studies reported fall risk. Taking current recommendations of balance outcome measures in patients with COPD into account, pulmonary rehabilitation combined with balance training had the highest effect size. Nine papers had concerns regarding bias, mostly due to the lack of blinding outcome assessors., Conclusions: Exercise-based interventions have a positive effect on balance in patients with COPD. Pulmonary rehabilitation with balance training seems to have the most beneficial effect on balance. The effects on fall risk, as well as the long-term intervention effects remain unclear. A standardized balance assessment and research on long-term effects and fall risk are recommended.

Pulmonary rehabilitation (PR) improves lower-limb muscle function in patients with chronic obstructive pulmonary disease (COPD). However, it remains unclear whether patients improve gait characteristics, in particular stride-to-stride fluctuations that are associated with fall risks. This study aims to identify whether, and to what extent, PR affects positively gait characteristics in COPD. In this prospective observational study, 44 COPD patients (aged: 62 ± 7 years; Forced expiratory volume in 1 s 56 ± 20% predicted) performed self-paced, treadmill 6-min-walk tests (Gait Real-time Analysis Interactive Lab) before and after PR, while spatiotemporal parameters and center of mass position were recorded (100 Hz, Vicon Nexus). Standard deviation, coefficient of variation, predictability (sample entropy), and consistency in organization (local divergence exponent) were calculated. Sub-analysis was performed to identify gait differences between good and poor responders (<30 m change in a 6-min-walk distance). Patients demonstrated shorter stride times ( p = 0.001) and improved lower-limb muscle function ( p < 0.001) following PR. The good responders had a greater increase in stride length ( p < 0.001) and a greater decrease in stride time ( p < 0.001) compared to the poor responders. Current PR improved stride time in patients, while movement patterns within stride-to-stride fluctuations did not change. Training programs specifically targeting balance issues and gait function may be beneficial in improving gait characteristics in COPD.

Background and Aim: Overground gait assessment is limited by the analysis of multiple strides or both spatiotemporal gait characteristics, while fixed speed treadmill walking restricts natural gait speed variations. The Gait Real-time Analysis Interactive Lab (GRAIL)-based 6-minute walk test (6MWT) enables 3D motion analysis and self-paced treadmill walking, and could provide insight in gait alterations in patients with chronic obstructive pulmonary disease (COPD). The aim of this study is to compare spatiotemporal gait characteristics between patients with COPD and healthy elderly during the GRAIL-based 6MWT., Materials and Methods: Eighty COPD patients (60% male; 62±7 years; FEV1:56±19% predicted) and 38 healthy elderly (63% male; 62±6 years; FEV1:119±17% predicted) performed two GRAIL-based 6MWTs. Mean differences and coefficient of variation of spatiotemporal gait characteristics were calculated using the trial with the largest walk distance. Sub-analyses were conducted to account for walking speed differences between groups, and muscle strength and COPD severity within the patient group., Results: COPD patients showed increased temporal gait characteristics, decreased stride and step lengths, and increased gait variability compared to healthy elderly (p<0.01). Stride length variability remained increased in COPD after correction for walking speed (MD:0.98%, CI:0.36-1.61, p = 0.003). Reduced quadriceps strength did not translate into altered gait characteristics, while COPD severity is associated with stride time (left MD:-0.02s, CI:-0.04-0.01, p = 0.003; right MD:-0.02s, CI:-0.04-0.01, p = 0.003)., Discussion: COPD patients performed the GRAIL-based 6MWT differently compared to healthy elderly. Further research should use other variability measures to investigate gait characteristics in COPD, to assess subtle alterations in gait and to enable development of rehabilitation strategies to improve gait, and possibly balance and fall risk in COPD. Other lower limb muscle groups should be considered when investigating gait alterations in COPD., Conclusion: COPD patients have different gait characteristics compared to healthy elderly. Independent of walking speed, COPD patients demonstrate increased stride length variability during the GRAIL-based 6MWT compared to healthy elderly.

Background: Resident loved ones of patients with COPD can play an important role in helping these patients engage in physical activity. We aimed to compare activity levels and exercise motivation between patients with COPD and their resident loved ones; to compare the same outcome measures in patients after stratification for the physical activity level of the loved ones; and to predict the likelihood of being physically active in patients with a physically active resident loved one., Methods: One hundred twenty-five patient/loved one dyads were cross-sectionally and simultaneously assessed. Sedentary behavior, light activities, and moderate to vigorous physical activity (MVPA) were measured with a triaxial accelerometer during free-living conditions for at least 5 days. Five exercise-motivation constructs were investigated: amotivation, external regulation, introjected regulation, identified regulation, and intrinsic regulation., Results: Patients spent more time in sedentary behavior and less time in physical activity than their loved ones (P < .0001). More intrinsic regulation was observed in loved ones compared with patients (P = .003), with no differences in other constructs. Despite similar exercise motivation, patients with an active loved one spent more time in MVPA (mean 31 min/d; 95% CI, 24-38 min/d vs mean, 18 min/d; 95% CI, 14-22 min/d; P = .002) and had a higher likelihood of being active (OR, 4.36; 95% CI, 1.41-13.30; P = .01) than did patients with an inactive loved one after controlling for age, BMI, and degree of airflow limitation., Conclusions: Patients with COPD are more physically inactive and sedentary than their loved ones, despite relatively similar exercise motivation. Nevertheless, patients with an active loved one are more active themselves and have a higher likelihood of being active., Trial Registry: Dutch Trial Register (NTR3941)., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background and Objective: Loved ones (proxies) of patients with COPD are confronted with the patients' limitations in activities of daily living (ADLs). However, it remains unknown whether proxies are able to correctly estimate the problematic ADLs of the patient. Therefore, we aimed to investigate the level of agreement between patient-reported and proxy-reported problematic ADLs of the patient., Methods: Stable outpatients with moderate to very severe COPD (n = 194) and their resident proxies (n = 194) were included in this cross-sectional study. Patients' problematic ADLs were assessed in the domains 'self-care', 'mobility', 'productivity' and 'leisure' using the Canadian Occupational Performance Measure (COPM) in both patients and resident proxies. Furthermore, the perceived performance and satisfaction for important problematic ADLs were rated on a 10-point scale., Results: In total, 830 problematic ADLs were reported by patients, and 735 by proxies. Agreement in reporting problematic ADLs within a domain was poor (productivity and leisure; κ; = 0.20 and 0.16, respectively) to fair (self-care and mobility; κ = 0.32 and 0.22, respectively). Similar performance and satisfaction scores, for equally reported problematic ADLs, were given by 24.0% and 17.6% of the pairs, respectively., Conclusion: Proxies were often not able to identify the patients' most important problematic ADLs. Moreover, when patient and proxy agreed about the presence of a specific problematic ADL, the perception of the performance and the satisfaction with that performance differed within most pairs. This emphasizes the importance of involving proxies, besides patients alone, in identifying patients' problematic ADLs., (© 2016 Asian Pacific Society of Respirology.)

Background: The 6-minute walk test (6MWT) in a regular hallway is commonly used to assess functional exercise capacity in patients with chronic obstructive pulmonary disease (COPD). However, treadmill walking might provide additional advantages over overground walking, especially if virtual reality and self-paced treadmill walking are combined. Therefore, this study aimed to assess the reproducibility and validity of the 6MWT using the Gait Real-time Analysis Interactive Lab (GRAIL) in patients with COPD and healthy elderly., Methodology/results: Sixty-one patients with COPD and 48 healthy elderly performed two 6MWTs on the GRAIL. Patients performed two overground 6MWTs and healthy elderly performed one overground test. Differences between consecutive 6MWTs and the test conditions (GRAIL vs. overground) were analysed. Patients walked further in the second overground test (24.8 m, 95% CI 15.2-34.4 m, p<0.001) and in the second GRAIL test (26.8 m, 95% CI 13.9-39.6 m). Healthy elderly improved their second GRAIL test (49.6 m, 95% CI 37.0-62.3 m). The GRAIL 6MWT was reproducible (intra-class coefficients = 0.65-0.80). The best GRAIL 6-minute walk distance (6MWD) in patients was shorter than the best overground 6MWD (-27.3 ± 49.1 m, p<0.001). Healthy elderly walked further on the GRAIL than in the overground condition (23.6 ± 41.4 m, p<0.001). Validity of the GRAIL 6MWT was assessed and intra-class coefficient values ranging from 0.74-0.77 were found., Conclusion: The GRAIL is a promising system to assess the 6MWD in patients with COPD and healthy elderly. The GRAIL 6MWD seems to be more comparable to the 6MWDs assessed overground than previous studies on treadmills have reported. Furthermore, good construct validity and reproducibility were established in assessing the 6MWD using the GRAIL in patients with COPD and healthy elderly., Competing Interests: The authors have declared that no competing interests exist.

Background and Objective: Walking aids, such as rollator or draisine, improve mobility and functional exercise performance in individuals with chronic obstructive pulmonary disease (COPD) during an indoor 6-min walk test. However, this test does not reflect everyday walking, which is the most frequently reported problematic activity of daily life in individuals with COPD. To date, efficacy of walking aids during self-paced outdoor walking remains unknown. Therefore, we aimed to determine the efficacy of a rollator and draisine on self-paced outdoor walking in individuals with COPD., Methods: Fifteen individuals with COPD (68% men; age: 63 ± 8 years; forced expiratory volume in 1 s: 40 ± 14% predicted) performed three self-paced outdoor walking tests on two consecutive days: test 1 unaided, and tests 2 and 3 with rollator or draisine in random order. Participants had to walk as long as possible at their own pace. The test ended when participants needed to stop, with a maximum duration of 30 min., Results: The use of rollator resulted in the highest walk distance and time (P < 0.05 vs unaided and draisine). Furthermore, individuals with COPD walked significantly further and longer during an unaided test compared with a draisine aided test (P < 0.05). Moreover, use of draisine resulted in a significantly higher walking speed, fewer strides, greater stride length, and higher step and stride variability (P < 0.05 vs unaided and rollator)., Conclusion: To conclude, a rollator improves the self-paced outdoor walk distance and time in individuals with moderate and advanced COPD and a poor functional exercise capacity, whereas the use of a draisine had a detrimental effect compared with unaided walking., (© 2015 Asian Pacific Society of Respirology.)

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.

Rationale: Strength training and neuromuscular electrical stimulation (NMES) improve lower-limb muscle function in dyspnoeic individuals with chronic obstructive pulmonary disease (COPD). However, high-frequency NMES (HF-NMES) and strength training have never been compared head-to-head; and effects of low-frequency NMES (LF-NMES) have never been studied in COPD. Therefore, the optimal training modality to improve lower-limb muscle function, exercise performance and other patient-related outcomes in individuals with severe COPD remains unknown., Objectives: To study prospectively the efficacy of HF-NMES (75 Hz), LF-NMES (15 Hz) or strength training in severely dyspnoeic individuals with COPD with quadriceps muscle weakness at baseline., Methods: 120 individuals with COPD (FEV1: 33±1% predicted, men: 52%, age: 64.8±0.8 years) were randomised to HF-NMES, LF-NMES or strength training as part of a comprehensive inpatient pulmonary rehabilitation programme. No treadmill walking or stationary cycling was provided., Measurements and Main Results: Groups were comparable at baseline. Quadriceps muscle strength increased after HF-NMES (+10.8 Newton-metre (Nm)) or strength training (+6.1 Nm; both p<0.01), but not after LF-NMES (+1.4 Nm; p=0.43). Quadriceps muscle endurance, exercise performance, lower-limb fat-free mass, exercise-induced symptoms of dyspnoea and fatigue improved significantly compared with baseline after HF-NMES, LF-NMES or strength training. The increase in quadriceps muscle strength and muscle endurance was greater after HF-NMES than after LF-NMES., Conclusions: HF-NMES is equally effective as strength training in severely dyspnoeic individuals with COPD and muscle weakness in strengthening the quadriceps muscles and thus may be a good alternative in this particular group of patients. HF-NMES, LF-NMES and strength training were effective in improving exercise performance in severely dyspnoeic individuals with COPD and quadriceps weakness., Trial Registration: NTR2322., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous respiratory disease with important extra-pulmonary features and comorbidities. The aim of this study was to assess clinical heterogeneity in a well-defined subgroup of individuals with COPD GOLD D, including possible gender differences., Methods: Pulmonary function, arterial blood gases, exercise performance, quadriceps muscle function, problematic activities of daily life, dyspnea, health status and comorbidities have been assessed in 117 individuals with a MRC dyspnea grade 4/5 and COPD GOLD D entering pulmonary rehabilitation., Results: A broad range of values were found for diffusion capacity, exercise capacity, quadriceps muscle function and health status. Indeed, the high coefficients of variation were found for these outcomes. Problematic activities of daily life as well as objectified comorbidities also varied to a great extent. Moreover, significant gender differences were found for exercise performance, lower-limb muscle function and various comorbidities., Conclusion: The current findings emphasize that COPD is a heterogeneous disease whose clinical presentation varies significantly, even in individuals with very severe COPD with the same degree of dyspnea and all classified as GOLD D., Trial Registration: NTR2322., (Copyright © 2013 Elsevier Ltd. All rights reserved.)