Impact of post-COVID-19 condition on health status and activities of daily living: the PRIME post-COVID study.

OBJECTIVE: To assess health and activities of daily living (ADL) in SARS-CoV-2-positive adults with and without post-COVID-19 condition (PCC) and compare this with negative tested individuals. Furthermore, different PCC case definitions were compared with SARS-CoV-2-negative individuals. METHODS: All adults tested PCR positive for SARS-CoV-2 at the Public Health Service South Limburg (Netherlands) between June 2020 and November 2021 (n=41 780) and matched PCR negative individuals (2:1, on age, sex, year-quarter test, municipality; n=19 875) were invited by email. Health (five-level EuroQol five-dimension (EQ5D) index and EuroQol visual analogue scale (EQVAS)) and ADL impairment were assessed. PCC classification was done using the WHO case definition and five other common definitions. RESULTS: In total, 8409 individuals (6381 SARS-CoV-2 positive; 53±15 years; 57% female; 9 (7-11) months since test) were included. 39.4% of positives had PCC by the WHO case definition (EQVAS: 71±20; EQ5D index: 0.800±0.191; ADL impairment: 30 (10-70)%) and perceived worse health and more ADL impairment than negatives, that is, difference of -8.50 points (95% CI -9.71 to -7.29; p<0.001) for EQVAS, which decreased by 1.49 points (95% CI 0.86 to 2.12; p<0.001) in individuals with PCC for each comorbidity present, and differences of -0.065 points (95% CI -0.074 to -0.056; p<0.001) for EQ5D index, and +16.72% (95% CI 15.01 to 18.43; p<0.001) for ADL impairment. Health and ADL impairment were similar in negatives and positives without PCC. Replacing the WHO case definition with other PCC definitions yielded comparable results. CONCLUSIONS: Individuals with PCC have substantially worse health and more ADL impairment than negative controls, irrespective of the case definition. Authorities should inform the public about the associated burden of PCC and enable adequate support.

Fatigue and symptom-based clusters in post COVID-19 patients: a multicentre, prospective, observational cohort study.

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.

Impact and timing of pulmonary rehabilitation in patients undergoing bronchoscopic lung volume reduction with endobronchial valves: A multicentre randomized controlled trial in patients with severe emphysema.

BACKGROUND AND OBJECTIVE: Both bronchoscopic lung volume reduction with endobronchial valves (BLVR-EBV) and pulmonary rehabilitation (PR) are effective treatments for improving exercise capacity and patient-reported outcomes in patients with severe Chronic Obstructive Pulmonary Disease (COPD). According to current recommendations, all BLVR-EBV patients should have undergone PR first. Our aim was to study the effects of PR both before and after BLVR-EBV compared to BLVR-EBV alone. METHODS: We included patients with severe COPD who were eligible for BLVR-EBV and PR. Participants were randomized into three groups: PR before BLVR-EBV, PR after BLVR-EBV or BLVR-EBV without PR. The primary outcome was change in constant work rate cycle test (CWRT) endurance time at 6-month follow-up of the PR groups compared to BLVR-EBV alone. Secondary endpoints included changes in 6-minute walking test, daily step count, dyspnoea and health-related quality of life. RESULTS: Ninety-seven participants were included. At 6-month follow-up, there was no difference in change in CWRT endurance time between the PR before BLVR-EBV and BLVR-EBV alone groups (median: 421 [IQR: 44; 1304] vs. 787 [123; 1024] seconds, p = 0.82) or in any of the secondary endpoints, but the PR after BLVR-EBV group exhibited a smaller improvement in CWRT endurance time (median: 107 [IQR: 2; 573], p = 0.04) and health-related quality of life compared to BLVR-EBV alone. CONCLUSION: The addition of PR to BLVR-EBV did not result in increased exercise capacity, daily step count or improved patient-reported outcomes compared to BLVR-EBV alone, neither when PR was administered before BLVR-EBV nor when PR was administered after BLVR-EBV.

Effects of ActiGraph's filter, epoch length and non-wearing time algorithm on step counts in people with COPD.

The influence of the ActiGraph® processing criteria on estimating step counts in chronic obstructive pulmonary disease (COPD) remains uncertain. This study aimed to assess the influence of filters, epoch lengths and non-wearing time (NWT) algorithms on steps/day in people with COPD. ActiGraph GT3X+ was worn on the waist for seven days. Steps were detected using different filters (normal and low-frequency extension [LFE]), epoch lengths (15s and 60s), and NWT algorithms (Choi and Troiano). Linear mixed-effects model was applied to assess the effects of filter, epoch length, NWT algorithm on steps/day. Lin's concordance correlation and Bland-Altman were used to measure agreement. A total of 136 people with COPD (107 male; 69 ± 8 years; FEV1 51 ± 17% predicted) were included. Significant differences were found between filters (p < 0.001), but not between epoch lengths or NWT algorithms. The LFE increased, on average, approximately 7500 steps/day compared to the normal filter (p < 0.001). Agreement was poor (<0.3) and proportional bias was significant when comparing steps/day computed with different filters, regardless of the epoch length and NWT algorithm. Filter choice but not epoch lengths or NWT algorithms seem to impact measurement of steps/day. Future studies are needed to recommend the most accurate technique for measuring steps/day in people with COPD.

Effects of Asthma on the Performance of Activities of Daily Living: A Retrospective Study.

The study aim was to identify the most problematic self--reported activities of daily living (ADLs). In a retrospective study, 1935 problematic ADLs were reported by 538 clients with 95% experiencing two or more problematic ADLs. Problematic ADLs were assessed by occupational therapists using the Canadian Occupational Performance Measure with walking (67%), household activities (41%), and climbing the stairs (41%) identified as the most prevalent problematic ADLs. Significant but weak associations were found between clinical determinants (e.g. physical, psychosocial) and problematic ADLs. The wide variety of problematic ADLs and the absence of a strong association with clinical determinants emphasizes the need for using individualized interview-based performance measures in clients with asthma.

Core outcome set for pulmonary rehabilitation of patients with COPD: results of a modified Delphi survey.

INTRODUCTION: There is high heterogeneity of outcomes and measures reported in pulmonary rehabilitation (PR) trials of people with chronic obstructive pulmonary disease (COPD). This hinders study comparability and benchmarking of PR. We have developed a core outcome set (COS) to overcome these challenges. METHODS: This study was informed by a systematic review and two qualitative studies and had patient involvement since its inception. A two-round Delphi survey was available in seven languages. Outcomes (n=63) scored 7-9 (crucial) by ≥70% of the participants and 1-3 (not that important) by ≤15% of participants from both groups in the Likert scale were automatically included in the COS, while outcomes that were considered crucial by only one of the groups were further discussed by the authors in a meeting. RESULTS: A total of 299 people (n=229 healthcare professionals/researchers/policy-makers; n=70 people with COPD and informal caregivers) participated in the survey (83% retention), which covered 29 countries/five continents. After the second round, six outcomes were included and three were added in the meeting. The final COS contains dyspnoea, fatigue, functional exercise capacity, health-related quality of life, health behaviours/lifestyle, knowledge about the disease, lower limb muscle function, personal goals and problematic activities of daily living. CONCLUSION: A COS for PR of people with COPD is now available and can be used by different stakeholders to improve consistency and comparability of studies, benchmark PR and improve the quality of care provided. Future research should establish the core measures and investigate the uptake of this COS.

Symptom-based clusters in people with ME/CFS: an illustration of clinical variety in a cross-sectional cohort.

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.

Post-Pulmonary Embolism Syndrome and Functional Outcomes after Acute Pulmonary Embolism.

Survivors of acute pulmonary embolism (PE) are at risk of developing persistent, sometimes disabling symptoms of dyspnea and/or functional limitations despite adequate anticoagulant treatment, fulfilling the criteria of the post-PE syndrome (PPES). PPES includes chronic thromboembolic pulmonary hypertension (CTEPH), chronic thromboembolic pulmonary disease, post-PE cardiac impairment (characterized as persistent right ventricle impairment after PE), and post-PE functional impairment. To improve the overall health outcomes of patients with acute PE, adequate measures to diagnose PPES and strategies to prevent and treat PPES are essential. Patient-reported outcome measures are very helpful to identify patients with persistent symptoms and functional impairment. The primary concern is to identify and adequately treat patients with CTEPH as early as possible. After CTEPH is ruled out, additional diagnostic tests including cardiopulmonary exercise tests, echocardiography, and imaging of the pulmonary vasculature may be helpful to rule out non-PE-related comorbidities and confirm the ultimate diagnosis. Most PPES patients will show signs of physical deconditioning as main explanation for their clinical presentation. Therefore, cardiopulmonary rehabilitation provides a good potential treatment option for this patient category, which warrants testing in adequately designed and executed randomized trials. In this review, we describe the definition and characteristics of PPES and its diagnosis and management.

Effectiveness of Non-pharmacologic Interventions on Device-measured Physical Activity in Adults With Cancer, and Methodology Used for Assessment: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the effectiveness of different types of interventions aimed at enhancing device-measured physical activity (PA) and summarize the devices and methodologies used to measure PA in adults with cancer. DATA SOURCES: A systematic review was prospectively registered on PROSPERO (CRD42020199466). The search was conducted in PubMed, The Cochrane Library, EMBASE (via Ovid), and PEDro from 2005 onward. STUDY SELECTION: Prospective interventional studies (randomized controlled trials [RCTs], non-randomized controlled trials, and single-group trials), that included adults within 12 months from cancer diagnosis, and device-measured PA before and after commencement of an intervention were included. Studies were excluded if PA was measured at a single time point. Two independent reviewers screened 3033 records and 30 articles met the inclusion criteria. DATA EXTRACTION: Two reviewers independently extracted the data. PEDro scale and GRADE approach were used to assess methodological quality of RCTs and overall quality of evidence, respectively. A meta-analysis of relevant RCTs was conducted. DATA SYNTHESIS: Thirty studies were identified, mainly including adults with multiple cancer types. Interventions were behavior change interventions (n=15), exercise training (n=13), neuromuscular electrostimulation (n=1), or a nutritional program (n=1). The meta-analysis showed improvements on moderate-to-vigorous intensity PA (MVPA) in the experimental group (8 studies; standardized mean difference (SMD)=0.23; 95% CI 0.06-0.39); with subgroup analysis showing that findings were mainly driven by behavior change interventions (5 studies; SMD=0.23, 95% CI 0.05-0.41). An uncertain effect on sedentary behavior, daily steps, and light intensity PA was found. PA was measured with medical devices and commercial wearables, quality of the methodology was variable. CONCLUSIONS: Behavior change interventions increased device-derived MVPA in adult cancer patients who underwent the intervention within 12 months of the cancer diagnosis. Various devices and methodologies were used to assess PA, which limits comparisons across the studies.

Analysis of retinal blood vessel diameters in patients with COPD undergoing a pulmonary rehabilitation program.

BACKGROUND: Regular exercise positively affects cardiovascular physiology, translating into the adequate capacity of microvascular blood vessels to dilate in response to acute bouts of exercise. However, this remains unstudied in patients with chronic obstructive pulmonary disease (COPD), who often suffer from cardiovascular comorbidity. Therefore, we studied acute changes in retinal blood vessel diameters in response to high-intensity exercise in patients with COPD. The effect of an exercise-based 8-week pulmonary rehabilitation (PR) program was evaluated. We consider changes in these retinal metrics as an indicator of microvascular reactivity. METHODS: Demographics and clinical characteristics of 41 patients were collected at the start and end of the PR program. Patients performed a high-intensity exercise test on a cycle ergometer at the start and end of the PR program, during which we collected retinal images. Fundus images were taken immediately before and 0, 5, 10, 15, and 30 min after the ergometer test. Widths of retinal blood vessels, represented as Central Retinal Arteriolar and Venular Equivalents (CRAE and CRVE), were calculated. RESULTS: Thirty patients with COPD completed the study protocol (57% males; mean age: 64 ± 7 years; mean FEV1: 45 ± 17%pred). We did not observe a change in retinal vessel widths following the ergometer test at the start of the PR program. This null result remained at the end of the 8-week PR program. Our observations did not alter when considering responders and non-responders to PR. CONCLUSION: Retinal blood vessel diameters of patients with COPD did not change following an exercise test on an ergometer. The exercise-based PR program of eight weeks did not counteract the blunted retinal microvascular response.

Prevalence of hyperventilation in patients with asthma.

OBJECTIVE: Asthma is frequently accompanied by dysfunctional breathing of which hyperventilation has been recognized as a subtype. The prevalence of hyperventilation in stable asthma has been scantily studied using blood gas analysis. Hence, a reliable estimate of its prevalence is lacking. It is unknown whether the Nijmegen Questionnaire (NQ) is a useful screening tool for hyperventilation in asthma. Therefore, the primary aim of this study was to determine the prevalence of hyperventilation in a large sample of patients with asthma in a stable state of disease. Secondary aims were to compare the clinical characteristics between patients with and without hyperventilation, and, to examine the concurrent validity of the NQ to detect hypocapnia in patients with asthma. METHODS: A real-world, observational, multicenter study was conducted. Capillary blood gas analysis was performed in adults with a confirmed diagnosis of stable asthma. A subset of patients completed the NQ. RESULTS: A blood gas analysis was obtained in 1006 patients. In 17% of the patients an acute hyperventilation was found, and in another 23% a chronic hyperventilation was uncovered. Patients with a chronic hyperventilation blood gas were more often female, were younger and had a better spirometric outcomes. The NQ appeared not to correlate with PCO2. CONCLUSION: Hyperventilation is common in patients with stable asthma. Chronic hyperventilation is more often found in females of younger age and with the best spirometric outcomes compared to patients without hyperventilation. The NQ is not a suitable screening tool for the presence of hyperventilation in stable asthmatics.

Patient Activation for Self-Management in Patients with Idiopathic Pulmonary Fibrosis or Sarcoidosis.

BACKGROUND: Self-management is considered important in the management of patients with idiopathic pulmonary fibrosis (IPF) or sarcoidosis. However, data about the degree of activation for self-management is lacking. OBJECTIVES: The aim of the study was to determine the degree of activation for self-management in patients with IPF or sarcoidosis using the Patient Activation Measure (PAM) and to evaluate the association between PAM scores, clinical characteristics, and health-related outcomes. STUDY DESIGN AND METHODS: This cross-sectional prospective study assessed besides the PAM also demographics, lung function, dyspnea (modified Medical Research Council [mMRC]), fatigue (Checklist Individual Strength-Fatigue [CIS-Fatigue]), anxiety/depression (Hospital Anxiety and Depression Scale [HADS-A/HADS-D]), and generic health status (EuroQol five-dimensional-five-level [EQ-5D-5L]). RESULTS: Mean PAM was 55.0 (9.1) points in patients with IPF (n = 59) and low levels of patient activation for self-management (PAM ≤55.1 points) were present in 56% of the patients. PAM Scores correlated significantly (p < 0.05) with mMRC (ρ = -0.476), HADS-A (ρ = -0.326), HADS-D (ρ = -0.459), and EQ-5D-5L (ρ = 0.393). In patients with sarcoidosis (n = 59), the mean PAM score was 55.7 (11.0) points, and 46% of the patients reported low PAM levels. Significant correlations were found with mMRC (ρ = -0.356), HADS-A (ρ = -0.394), HADS-D (ρ = -0.478), and EQ-5D-5L (ρ = 0.313). CONCLUSION: About half of the outpatients with IPF or sarcoidosis have a low degree of activation for self-management, and these patients generally report more dyspnea, anxiety, depression, and a lower health status. Whether patients with a low degree of activation can be successful in self-managing their disease remains to be determined.

Effects of Pulmonary Rehabilitation Including Inspiratory Muscle Training in Patients with Chronic Obstructive Pulmonary Disease after Stratification by the Degree of Static Hyperinflation.

BACKGROUND: Inspiratory muscle training (IMT) improves inspiratory muscle strength, exercise capacity and health status in patients with chronic obstructive pulmonary disease (COPD). However, there is no additional effect on top of comprehensive pulmonary rehabilitation (PR). It is unclear whether patients with different baseline degrees of static hyperinflation respond differentially to IMT as part of a PR program. Therefore, the aim was to study the effects of IMT as an add-on on PR after stratification for baseline degrees of static hyperinflation. METHODS: In this single center retrospective study data were extracted between June 2013 and October 2020 of COPD patients who participated in a comprehensive PR program including IMT. IMT was performed twice daily, one session consisted of 3 series of 10 breaths and training intensity was set initially at a load of approximately 50% of patients' maximal static inspiratory mouth pressure (MIP). The primary outcome measure was MIP. Secondary outcomes were the distance achieved on the 6-min walk test (6MWD), endurance cycling exercise capacity at 75% of the peak work rate (CWRT) and disease-specific health status using the COPD assessment test. RESULTS: 754 patients with COPD were screened for eligibility and 328 were excluded because of repeated PR programs, missing data or baseline residual volume (RV) > 350%. In total, 426 COPD patients were categorized into RV categories 50-130% (n = 84), 131-165% (n = 86), 166-197% (n = 86), 198-234% (n = 85) and 235-349% (n = 85). In the whole sample, MIP, endurance exercise capacity and health status improved significantly. The change in 6MWD was higher in the lowest baseline degree of static hyperinflation [+ 39 (9-92) m] compared with the baseline highest degree of static hyperinflation [+ 11 (- 18-54) m] (p < 0.05). CONCLUSIONS: IMT as part of a PR program in patients with COPD with different baseline degrees improved MIP irrespective of the degree of static lung hyperinflation. Improvement in functional exercise capacity was significantly higher in the group with the lowest degree of static hyperinflation compared with the patients with the highest degree of static hyperinflation.

Standardized exercise training is feasible, safe, and effective in pulmonary arterial and chronic thromboembolic pulmonary hypertension: results from a large European multicentre randomized controlled trial.

AIMS: This prospective, randomized, controlled, multicentre study aimed to evaluate efficacy and safety of exercise training in patients with pulmonary arterial (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). METHODS AND RESULTS: For the first time a specialized PAH/CTEPH rehabilitation programme was implemented in 11 centres across 10 European countries. Out of 129 enrolled patients, 116 patients (58 vs. 58 randomized into a training or usual care control group) on disease-targeted medication completed the study [85 female; mean age 53.6 ± 12.5 years; mean pulmonary arterial pressure 46.6 ± 15.1 mmHg; World Health Organization (WHO) functional class II 53%, III 46%; PAH n = 98; CTEPH n = 18]. Patients of the training group performed a standardized in-hospital rehabilitation with mean duration of 25 days [95% confidence interval (CI) 17-33 days], which was continued at home. The primary endpoint, change of 6-min walking distance, significantly improved by 34.1 ± 8.3 m in the training compared with the control group (95% CI, 18-51 m; P < 0.0001). Exercise training was feasible, safe, and well-tolerated. Secondary endpoints showed improvements in quality of life (short-form health survey 36 mental health 7.3 ± 2.5, P = 0.004), WHO-functional class (training vs. control: improvement 9:1, worsening 4:3; χ2P = 0.027) and peak oxygen consumption (0.9 ± 0.5 mL/min/kg, P = 0.048) compared with the control group. CONCLUSION: This is the first multicentre and so far the largest randomized, controlled study on feasibility, safety, and efficacy of exercise training as add-on to medical therapy in PAH and CTEPH. Within this study, a standardized specialized training programme with in-hospital start was successfully established in 10 European countries.

Characteristics and treatable traits of patients with chronic obstructive pulmonary disease (COPD) with and without paid employment.

INTRODUCTION: Patients with COPD are vulnerable to workforce detachment. Better knowledge of features associated with paid work loss might be of help to design and select appropriate interventions. METHOD: This cross-sectional study aimed to explore the presence of treatable traits in COPD patients without paid work. Patients with COPD below 65 years at first referral to a hospital-based patient clinic were included. Using binary logistic regression analysis, the relationship between paid work and the following characteristics was explored: low daily physical activity, exercise, active smoking, Medical Research Council dyspnea scale (MRC), poor nutritional status, exacerbations, and fatigue (checklist individual strength (CIS)). Variables were adjusted for age, sex, forced expiratory volume in 1 s (FEV 1), and education level. RESULTS: In total, 191 patients (47.3%) were without paid work. The following treatable traits were related to not being in paid work: < 5000 steps/day (OR 2.36, 95% CI (1.52-3.68)), MRC ≥ 3 (OR 1.78, 95%CI (1.14-2.77)), CIS ≥ 36 points (OR 1.78, 95% CI (1.10-2.87)), six-minute walk distance (6MWD) < 70% of predicted (OR 2.62, 95% CI (1.69-4.06)), and ≥ 2 exacerbations per year (OR 1.80, 95% CI (1.12-2.92)). Significant differences were also seen in age (OR 1.06, 95% CI (1.02-1.10) per year), FEV 1% predicted (OR 0.98, 95% CI (0.97-1.00) per % predicted increase), and medium/high education level (OR 0.62, 95% CI (0.41-0.93)). When adjusting for all variables the only treatable trait that remained significant was 6MWD. CONCLUSION: Patients without paid work are more likely to have treatable traits with 6MWD revealing the most significant association.

Frequency and functional translation of low muscle mass in overweight and obese patients with COPD.

BACKGROUND: Cut offs for fat-free mass index (FFMI) and appendicular skeletal muscle mass index (ASMI) are available for diagnosing low muscle mass in patients with COPD. This study aimed to investigate: (1) the frequency of low muscle mass (FFMI and ASMI) applying different cut-offs and (2) the functional translation (clinical impact) of low muscle mass, in patients with COPD stratified into BMI categories. METHODS: Patients with COPD were assessed regarding body composition, exercise capacity, quadriceps muscle strength, symptoms of anxiety and depression, dyspnea and quality of life upon referral to pulmonary rehabilitation. The proportion of patients with low muscle mass was compared among BMI categories. Clinical outcomes between patients with normal and low muscle mass within each BMI category were compared. RESULTS: 469 patients with COPD were included for analyses. The frequency of patients classified as low FFMI varied significantly according to the choice of cut-off (32 to 54%; P < 0.05), whereas the frequency of patients with low ASMI was 62%. When applying age-gender-BMI-specific cut-offs, 254 patients (54%) were classified as low FFMI. The choice of the cut-off affected the frequency of patients with low muscle mass in all BMI categories. Overweight and obese patients with low muscle mass were more frequently males and presented worse pulmonary function, exercise capacity and muscle strength compared with overweight and obese patients with normal muscle mass. CONCLUSIONS: Approximately half of the overweight and obese patients with COPD have low muscle mass when applying age-gender-BMI-specific cut-offs. Low muscle mass is associated with worse functional outcomes in overweight and obese COPD patients.

Construct validity of the Post-COVID-19 Functional Status Scale in adult subjects with COVID-19.

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.

Longitudinal changes in total and regional body composition in patients with chronic obstructive pulmonary disease.

BACKGROUND AND OBJECTIVE: Low fat-free mass (FFM) is common in patients with chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality. Few studies have evaluated longitudinal changes in body composition in patients with COPD compared with non-COPD controls. This study aimed to compare longitudinal changes in total and regional body composition between patients with COPD and non-COPD controls and investigate predictors of changes in body composition in COPD. METHODS: Patients with COPD and non-COPD controls participating in the Individualized COPD Evaluation in relation to Ageing (ICE-Age) study, a single-centre, longitudinal, observational study, were included. Subjects were assessed at baseline and after 2 years of follow-up. Among other procedures, body composition was measured by dual-energy X-ray absorptiometry scan. The number of exacerbations/hospitalizations 1 year before inclusion and during follow-up were assessed in patients with COPD. RESULTS: A total of 405 subjects were included (205 COPD, 87 smoking and 113 non-smoking controls). Patients with COPD and smoking controls presented a significant decline in total FFM (mean [95% CI]: -1173 [-1527/-820] g and -486 [-816/-156] g, respectively) while body composition remained stable in non-smoking controls. In patients with COPD, the decline in FFM was more pronounced in legs (-174 [-361/14] g) and trunk (-675 [-944/406] g) rather than in arms (54 [-19/126] g). The predictors of changes in total and regional FFM in patients with COPD were gender, number of previous hospitalizations, baseline values of FFM and BMI. CONCLUSION: Patients with COPD present a significant decline in FFM after 2 years of follow-up, this decline is more pronounced in their legs and trunk.

Short Physical Performance Battery: Response to Pulmonary Rehabilitation and Minimal Important Difference Estimates in Patients With Chronic Obstructive Pulmonary Disease.

OBJECTIVE: To determine the response to a pulmonary rehabilitation (PR) program and minimal important differences (MIDs) for the Short Physical Performance Battery (SPPB) subtests and SPPB summary score in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective analysis using distribution- and anchor-based methods. SETTING: PR center in the Netherlands including a comprehensive 40-session 8-week inpatient or 14-week outpatient program. PARTICIPANTS: A total of 632 patients with COPD (age, 65±8y; 50% male; forced expiratory volume in the first second=43% [interquartile range, 30%-60%] predicted). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Baseline and post-PR results of the SPPB, consisting of 3 balance standing tests, 4-meter gait speed (4MGS), and 5-repetition sit-to-stand (5STS). The chosen anchors were the 6-Minute Walk Test and COPD Assessment Test. Patients were stratified according to their SPPB summary scores into low-performance, moderate-performance, and high-performance groups. RESULTS: 5STS (∆=-1.14 [-4.20 to -0.93]s) and SPPB summary score (∆=1 [0-2] points) improved after PR in patients with COPD. In patients with a low performance at baseline, balance tandem and 4MGS significantly increased as well. Based on distribution-based calculations, the MID estimates ranged between 2.19 and 6.33 seconds for 5STS and 0.83 to 0.96 points for SPPB summary score. CONCLUSIONS: The 5STS and SPPB summary score are both responsive to PR in patients with COPD. The balance tandem test and 4MGS are only responsive to PR in patients with COPD with a low performance at baseline. Based on distribution-based calculations, an MID estimate of 1 point for the SPPB summary score is recommended in patients with COPD. Future research is needed to confirm MID estimates for SPPB in different centers.

Clustering of patients with end-stage chronic diseases by symptoms: a new approach to identify health needs.

BACKGROUND: End-stage chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF) and chronic renal failure (CRF) are characterized by a high burden of daily symptoms that, irrespective of the primary organ failure, are widely shared. AIMS: To evaluate whether and to which extent symptom-based clusters of patients with end-stage COPD, CHF and CRF associate with patients' health status, mobility, care dependency and life-sustaining treatment preferences. METHODS: 255 outpatients with a diagnosis of advanced COPD (n = 95), advanced CHF (n = 80) or CRF requiring dialysis (n = 80) were visited in their home environment and underwent a multidimensional assessment: clinical characteristics, symptom burden using Visual Analog Scale (VAS), health status questionnaires, timed "Up and Go" test, Care Dependency Scale and willingness to undergo mechanical ventilation or cardiopulmonary resuscitation. Three clusters were obtained applying K-means cluster analysis on symptoms' severity assessed via VAS. Cluster characteristics were compared using non-parametric tests. RESULTS: Cluster 1 patients, with the least symptom burden, had a better quality of life, lower care dependency and were more willing to accept life-sustaining treatments than others. Cluster 2, with a high presence and severity of dyspnea, fatigue, cough, muscle weakness and mood problems, and Cluster 3, with the highest occurrence and severity of symptoms, reported similar care dependency and life-sustaining treatment preferences, while Cluster 3 reported the worst physical health status. DISCUSSION: Symptom-based clusters identify patients with different health needs and might help to develop palliative care programs. CONCLUSION: Clustering by symptoms identifies patients with different health status, care dependency and life-sustaining treatment preferences.