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 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.

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.

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.

Implementation of Bronchoscopic Lung Volume Reduction Using One-Way Endobronchial Valves: A Retrospective Single-Centre Cohort Study.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR) using 1-way endobronchial valves (EBV) has become a guideline treatment in patients with advanced emphysema. Evidence from this minimally invasive treatment derives mainly from well-designed controlled trials conducted in high-volume specialized intervention centres. Little is known about real-life outcome data in hospitals setting up this novel treatment and which favourable conditions are required for a continuous successful program. OBJECTIVES: In this study, we aim to evaluate the eligibility rate for BLVR and whether the implementation of BLVR in our academic hospital is feasible and yields clinically significant outcomes. METHOD: A retrospective evaluation of patients treated with EBV between January 2016 and August 2019 was conducted. COPD assessment test (CAT), forced expiratory volume in 1 s (FEV1), residual volume (RV), and 6-min walking test (6MWT) were measured at baseline and 3 months after intervention. Paired sample t tests were performed to compare means before and after intervention. RESULTS: Of 350 subjects screened, 283 (81%) were not suitable for intervention mostly due to lack of a target lobe. The remaining 67 subjects (19%) underwent bronchoscopic assessment, and if suitable, valves were placed in the same session. In total, 55 subjects (16%) were treated with EBV of which 10 did not have complete follow-up: 6 subjects had their valves removed because of severe pneumothorax (n = 2) or lack of benefit (n = 4) and the remaining 4 had missing follow-up data. Finally, 45 patients had complete follow-up at 3 months and showed an average change ± SD in CAT -4 ± 6 points, FEV1 +190 ± 140 mL, RV -770 ± 790 mL, and +37 ± 65 m on the 6MWT (all p < 0.001). After 1-year follow-up, 34 (76%) subjects had their EBV in situ. CONCLUSION: Implementing BLVR with EBV is feasible and effective. Only 16% of screened patients were eligible, indicating that this intervention is only applicable in a small subset of highly selected subjects with advanced emphysema, and therefore a high volume of COPD patients is essential for a sustainable BLVR program.

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.

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.

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.

Severe Fatigue in Long COVID: Web-Based Quantitative Follow-up Study in Members of Online Long COVID Support Groups.

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.

Skin auto-fluorescence as a measure of advanced glycation end-products is associated with microvascular health in patients with COPD.

BACKGROUND AND OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and oxidative stress. These physiological processes can lead to increased formation and accumulation of advanced glycation end-products (AGEs), that can play a role in vascular complications. In this cross-sectional study, we determined the association between skin AGEs and microvascular health in patients with COPD. METHODS: Clinical characteristics and cardiovascular parameters, including pulmonary function, metabolic and inflammatory parameters, and blood pressure, were obtained in this observational study with patients with COPD. Skin concentrations of AGEs were assessed non-invasively by measuring skin autofluorescence (AF). Retinal vessel analysis was used as a marker of microvascular health. RESULTS: 62 patients with COPD (52% males; mean age: 64.4 ± 8.4 years; mean FEV1: 45.0 ± 20.7%pred.) were analysed. Mean skin AF was 2.75 ± 0.64 arbitrary units. Skin AF in patients with COPD was negatively associated with retinal arteriolar diameter (ß -0.021, 95% CI -0.040 to -0.002; p = 0.031) and arteriole-to-venular ratio (ß -7.233, 95% CI -9.732 to -4.734; p < 0.001) and positively associated with retinal venular diameter (ß 0.029, 95% CI 0.019 to 0.038; p < 0.001) after adjustment for sex, age, lung function, pack-years of smoking and conventional cardiovascular risk factors. CONCLUSION: We document for the first time that skin AF in patients with COPD is independently associated with retinal arteriolar and venular vessel diameters, biological indicators for microvascular health. This adds to the evidence that AGEs are an accessible marker of microvascular health.

Phenotypic Characteristics of Patients With Chronic Obstructive Pulmonary Disease After Stratification for the Short Physical Performance Battery Summary Score.

OBJECTIVE: To assess the phenotypic characteristics of patients with chronic obstructive pulmonary disease (COPD) after stratification for Short Physical Performance Battery (SPPB) summary scores and to determine phenotypic characteristics of the SPPB summary score at the start of pulmonary rehabilitation (PR). DESIGN: Retrospective, cross-sectional. SETTING: Baseline assessment for PR program. PARTICIPANTS: Patients with COPD (n=900; age 65±8y, 52% male, forced expiratory volume in the first second of expiration, 43% [interquartile range, 31%-62%] predicted). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients were stratified according to their SPPB summary scores into low-performance (LP), moderate-performance (MP), or high-performance (HP) groups. Furthermore, lung function, arterial blood gases, body composition, physical capacity, lower limb muscle strength and endurance, and symptoms of anxiety and depression were assessed. RESULTS: Generally, physical capacity and muscle function were lower and scores for symptoms of anxiety and depression were higher in LP patients than MP and HP patients (all values, P<.01). However, 25% of HP patients with COPD scored high on symptoms of anxiety and/or depression (≥10 points), and HP patients still had on average an impaired physical capacity (median, 6-minute walk test [6MWT] distance of 69% predicted). Furthermore, age and 6MWT distance (m) were the only independent predictors in a multivariate regression model, explaining 29% of the variance in SPPB summary score. CONCLUSIONS: In COPD, LP patients have the worst physical and emotional functioning. However, HP patients can still exhibit physical and emotional impairments. Because the explained variance in SPPB summary score is low, SPPB should not be considered as a test to discriminate between patients with COPD with a low or preserved physical capacity and emotional status.

Physical activity patterns and clusters in 1001 patients with COPD.

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 [FEV1], 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 FEV1, 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.

Efficacy of walking aids on self-paced outdoor walking in individuals with COPD: A randomized cross-over trial.

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.

Efficacy of lower-limb muscle training modalities in severely dyspnoeic individuals with COPD and quadriceps muscle weakness: results from the DICES trial.

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.

Changes in physical activity and all-cause mortality in COPD.

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.

An official European Respiratory Society statement on physical activity in COPD.

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).

Metabolic load during strength training or NMES in individuals with COPD: results from the DICES trial.

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.

Treatable traits in advanced emphysema patients eligible for bronchoscopic lung volume reduction with endobronchial valves.

INTRODUCTION: Patients with advanced emphysema eligible for bronchoscopic lung volume reduction (BLVR) using endobronchial valves (EBV) are characterized by severe static lung hyperinflation, which can be considered a treatable trait. Other treatable traits (TTs), which are assumed to be present in this highly selected patient group, have not been studied in detail nor how they may affect health-related quality of life (HRQL). AIMS: We aimed to evaluate a spectrum of TTs in COPD patients eligible for EBV treatment and their association with HRQL. METHODS: The SoLVE study (NCT03474471) was a prospective multicenter randomized controlled trial to examine the impact of pulmonary rehabilitation in COPD patients receiving EBV. The presence/absence of 16 TTs was based on pre-defined thresholds. HRQL was assessed with the St. George's Respiratory Questionnaire (SGRQ). Subjects were stratified into two groups, using the median split method, into higher or lower SGRQ total score. Logistic regression assessed the odds ratio (OR) of having a higher SGRQ total score per TT. RESULTS: Ninety-seven subjects were included, the mean number of TTs per patient was 8.1 ± 2.5. Low physical activity (95%), poor exercise capacity (94%) and severe fatigue (75%) were the most prevalent TTs. The sum of TTs present in a subject was associated with the SGRQ total score (r = 0.53; p < 0.001). Severe fatigue, depression, and anxiety were predictors of having a higher SGRQ total score. CONCLUSIONS: A high prevalence and co-occurrence of multiple TTs were identified in emphysema patients eligible for EBV. Patients with a higher number of TTs were more likely to have worse HRQL.