Quality of aerobic training description and its relation to intervention efficacy in chronic obstructive pulmonary disease trials: study protocol for a systematic review, meta-analysis and meta-regression.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is a major global health concern, characterised by ventilatory constraints, decreased cardiovascular fitness and reduced limb muscle function, profoundly affecting patients' quality of life. Aerobic training plays a crucial role in the treatment of COPD, but the variability in methodologies and incomplete reporting of key components in aerobic training trials limits the assessment of their effectiveness. This systematic review aims to critically evaluate the application of training principles and reporting of key components in aerobic training trials in randomised controlled trials (RCTs) in the COPD literature. METHODS AND ANALYSIS: The protocol adheres to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol guidelines. The review will include RCTs utilising aerobic training in individuals with COPD. A comprehensive search, following a predefined search strategy will identify studies published from 2007 to 2024 in English from MEDLINE, Embase, CINAHL, CENTRAL and PEDro. Studies including people with COPD and any aerobic training intervention will be included. Two reviewers will independently screen abstracts and titles for inclusion. Two reviewers will independently conduct the screening of full-text documents and data extraction. Study quality will be assessed using the Tool for the assESsment of sTudy quality and bias in Exercise, specifically developed for exercise training studies. The certainty of the evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation approach. A systematic synthesis will be provided, with meta-analyses and meta-regression when appropriate. ETHICS AND DISSEMINATION: As this review will involve the analysis of published data, ethical approval is not required. The findings of this review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42021247343.

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.

Relationship between Volitional and Non-Volitional Quadriceps Muscle Endurance in Patients with Chronic Obstructive Pulmonary Disease.

Volitional assessment of quadriceps muscle endurance is clinically relevant in patients with chronic obstructive pulmonary disease (COPD). However, studies that determine the construct validity of volitional tests by comparing them to non-volitional measures are lacking. Therefore, the aim of the current study is to evaluate the correlation between volitional and non-volitional quadriceps muscle endurance in patients with COPD. Quadriceps muscle endurance was evaluated in twenty-six patients with COPD. A volitional isometric and a volitional isokinetic protocol were performed on a computerised dynamometer to determine the isometric time and isokinetic work fatigue index, respectively. Non-volitional assessment of quadriceps muscle endurance was evaluated using repetitive electrical stimulations to establish the isometric muscle force decline. Sixteen patients (61 ± 8 years, 63% male, FEV1 47 (32-53)%) performed all three quadriceps endurance tests conforming to pre-defined test criteria. Both volitional isometric time and isokinetic work fatigue index did not significantly correlate with non-volitional muscle force decline (both p > 0.05). There was a strong correlation between volitional isometric time and isokinetic work fatigue index (rho = -0.716, p = 0.002). To conclude, this study suggests that volitional measures evaluate partly different aspects of quadriceps muscle endurance compared to non-volitional measures. Accordingly, these outcome measures cannot be used interchangeably.

Frequency and Functional Consequences of Low Appendicular Lean Mass and Sarcopenic Obesity in Patients with Asthma Referred for Pulmonary Rehabilitation.

INTRODUCTION: One of the most prominent extrapulmonary manifestations in patients with chronic respiratory disease is changes in body weight and composition. However, the frequency and functional consequences of low appendicular lean mass (ALM) or sarcopenic obesity (SO) in patients with asthma are largely unknown. Therefore, the aim of the current study was to assess the frequency and functional consequences of low appendicular lean mass index (ALMI) and SO in patients with asthma. METHODS: A retrospectively analyzed cross-sectional study was conducted in 687 patients with asthma (60% female, 58 ± 13 years, FEV1 76 ± 25% pred) referred for comprehensive pulmonary rehabilitation (PR). Body composition, pulmonary function, exercise capacity, quadriceps muscle function, and quality of life were assessed. Patients were classified as presenting low ALMI according to the 10th percentiles of age-sex-body mass index (BMI)-specific reference values and as having SO according to the diagnostic procedure proposed by the 2022 ESPEN/EASO consensus. In addition, clinical outcomes between patients with normal and low ALMI or with and without SO were compared. RESULTS: The frequency of patients classified as low ALMI was 19%, whereas 45% of the patients were obese. Among the obese patients, 29% had SO. In patients with normal weight, those with low ALMI were younger and had worse pulmonary function, exercise capacity and quadriceps muscle function than those with normal ALMI (all p < 0.05). Overweight patients with low ALMI presented poorer pulmonary function and quadriceps muscle function (both strength and total work capacity). In obese class I patients, those with low ALMI showed lower quadriceps strength and maximal oxygen uptake acquired during cardiopulmonary exercise testing. Both male and female patients with SO showed lower quadriceps muscle function and reduced maximal exercise capacity compared to non-SO asthma patients. CONCLUSION: Approximately one in five asthma patients presented low ALM when age-sex-BMI-specific ALMI cutoffs were applied. Obesity is common among patients with asthma referred for PR. Among the obese patients, a significant proportion presented SO. Low ALM and SO were associated with worse functional outcomes.

Isokinetic testing of quadriceps function in COPD: feasibility, responsiveness, and minimal important differences in patients undergoing pulmonary rehabilitation.

BACKGROUND: Isokinetic testing of peripheral muscle function is valid and reliable in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: To evaluate whether and to what extent isokinetic testing of quadriceps function meets pre-defined test criteria in patients with COPD; to determine the response to pulmonary rehabilitation (PR), and to calculate minimal important differences (MIDs) of isokinetic quadriceps function. METHODS: Retrospective analysis of 2033 patients with COPD (age: 65±9 years, body mass index: 26±6 kg/m2, FEV1: 49±22% predicted) who followed a comprehensive PR program. Pre and post PR isokinetic quadriceps function was assessed with 30 maximal extension-flexion contractions at an angular speed of 90°/s on a computerized dynamometer. The chosen anchors were 6-min walk test and COPD assessment test. RESULTS: Pre PR, 27% of the patients performed the isokinetic test incorrectly. In male and female patients with a correct pre and post PR isokinetic test, peak torque (Δ=10±13 Nm or 9% and Δ=7±9 Nm or 10%, respectively) and total work (Δ=263±270 J or 14% and Δ=198±190 J or 15%, respectively) improved significantly. There was no change in work fatigue index following PR. Using distribution-based calculations, MID estimates for peak torque and total work ranged between 6-7 Nm and 97-135 J in males and between 4-5 Nm and 62-99 J in females. CONCLUSIONS: Based on the current test criteria, three in four patients with COPD performed the isokinetic quadriceps test correctly during baseline PR assessment. Furthermore, peak torque and total work, but not work fatigue index, were responsive to PR and sex-specific MIDs were established.

Longitudinal Analysis of Quadriceps Muscle Strength in Patients with Previous COVID-19 Hospitalization and in Patients with Post-Acute Sequelae following Mild COVID-19.

Muscle weakness is a prominent symptom in post-acute sequelae of COVID-19 (PASC). However, few studies have objectively and longitudinally assessed muscle strength after varying COVID-19 severity grades. This observational study aimed to explore the prevalence, determinants, and 1.5 years change of quadriceps muscle weakness in 98 patients discharged from COVID-19 hospitalization and in 50 patients with PASC following mild COVID-19. Isometric quadriceps maximal voluntary contraction (MVC) was assessed on a computerized dynamometer at three visits. Also, in a subgroup of 14 post-COVID-19 patients with quadriceps muscle weakness, muscle thickness and echo intensity were determined by muscle ultrasound of nine upper and lower extremity muscles. Muscle weakness was found in 59% of post-hospitalized patients and in 65% of those with PASC following mild COVID-19 at ~14 weeks after acute COVID-19. Whereas during ~1.5 years follow-up MVC modestly improved, muscle weakness prevalence remained unchanged. Hospital length of stay and diabetes mellitus were identified as possible predictors of muscle weakness following COVID-19 hospitalization. No predictors could be identified in those with PASC following mild COVID-19. Ultrasound outcomes revealed no large structural abnormalities. In conclusion, clinically relevant muscle weakness is common after COVID-19 and its long-term improvement is poor. Future studies with relevant control groups are warranted to confirm our data.

Moderate Intensity Exercise Training Improves Skeletal Muscle Performance in Symptomatic and Asymptomatic Statin Users.

BACKGROUND: The combination of statin therapy and physical activity reduces cardiovascular disease risk in patients with hyperlipidemia more than either treatment alone. However, mitochondrial dysfunction associated with statin treatment could attenuate training adaptations. OBJECTIVES: This study determined whether moderate intensity exercise training improved muscle and exercise performance, muscle mitochondrial function, and fiber capillarization in symptomatic and asymptomatic statin users. METHODS: Symptomatic (n = 16; age 64 ± 4 years) and asymptomatic statin users (n = 16; age 64 ± 4 years) and nonstatin using control subjects (n = 20; age 63 ± 5 years) completed a 12-week endurance and resistance exercise training program. Maximal exercise performance (peak oxygen consumption), muscle performance and muscle symptoms were determined before and after training. Muscle biopsies were collected to assess citrate synthase activity, adenosine triphosphate (ATP) production capacity, muscle fiber type distribution, fiber size, and capillarization. RESULTS: Type I muscle fibers were less prevalent in symptomatic statin users than control subjects at baseline (P = 0.06). Exercise training improved muscle strength (P < 0.001), resistance to fatigue (P = 0.01), and muscle fiber capillarization (P < 0.01), with no differences between groups. Exercise training improved citrate synthase activity in the total group (P < 0.01), with asymptomatic statin users showing less improvement than control subjects (P = 0.02). Peak oxygen consumption, ATP production capacity, fiber size, and muscle symptoms remained unchanged in all groups following training. Quality-of-life scores improved only in symptomatic statin users following exercise training (P < 0.01). CONCLUSIONS: A moderate intensity endurance and resistance exercise training program improves muscle performance, capillarization, and mitochondrial content in both asymptomatic and symptomatic statin users without exacerbating muscle complaints. Exercise training may even increase quality of life in symptomatic statin users. (The Effects of Cholesterol-Lowering Medication on Exercise Performance [STATEX]; NL5972/NTR6346).

Correlates of variability in endurance shuttle walk test time in patients with chronic obstructive pulmonary disease.

BACKGROUND: The endurance shuttle walk test (ESWT) is used to evaluate exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). The recommended pre-intervention tolerated duration (Tlim) is between 3-8 minutes for optimal interpretation of treatment effects. However, this window may be exceeded and factors determining ESWT Tlim are not completely understood. Therefore, we aimed to determine whether pulmonary function, physical and incremental shuttle walk test (ISWT) performance measures are associated with ESWT Tlim in COPD patients. METHODS: Assessment data from patients eligible for pulmonary rehabilitation was retrospectively analyzed. Inclusion criteria were: diagnosis of COPD and complete data availability regarding ESWT and ISWT. Patients performed an ESWT at 85% of ISWT speed and were divided into three groups (ESWT Tlim: <3 minutes, 3-8 minutes, >8 minutes). Subject characteristics, severity of complaints, pulmonary function, physical capacity and activity, exercise tolerance and quadriceps muscle strength were evaluated. RESULTS: 245 COPD patients (FEV1 38 (29-52)% predicted) were included. Median ESWT Tlim was 6.0 (3.7-10.3) minutes, 41 (17%) patients walked <3 minutes and 80 (33%) patients walked >8 minutes. Body mass index, maximal oxygen consumption, Tlim on constant work rate cycle test, physical activity level, maximal ISWT speed, dyspnoea Borg score at rest and increase of leg fatigue Borg score during ISWT independently predicted Tlim in multivariate regression analysis (R2 = 0.297, p<0.001). CONCLUSION: This study reported a large variability in ESWT Tlim in COPD patients. Secondly, these results demonstrated that next to maximal ISWT speed, other ISWT performance measures as well as clinical measures of pulmonary function, physical capacity and physical activity were independent determinants of ESWT Tlim. Nevertheless, as these determinants only explained ~30% of the variability, future studies are needed to establish whether additional factors can be used to better adjust individual ESWT pace in order to reduce ESWT Tlim variability.

Beta-alanine supplementation in patients with COPD receiving non-linear periodised exercise training or neuromuscular electrical stimulation: protocol of two randomised, double-blind, placebo-controlled trials.

INTRODUCTION: Exercise intolerance is common in patients with chronic obstructive pulmonary disease (COPD) and, although multifactorial, it is largely caused by lower-limb muscle dysfunction. Research has shown that patients with severe to very severe COPD have significantly lower levels of muscle carnosine, which acts as a pH buffer and antioxidant. Beta-alanine (BA) supplementation has been shown to consistently elevate muscle carnosine in a variety of populations and may therefore improve exercise tolerance and lower-limb muscle function. The primary objective of the current studies is to assess the beneficial effects of BA supplementation in enhancing exercise tolerance on top of two types of exercise training (non-linear periodised exercise (NLPE) training or neuromuscular electrical stimulation (NMES)) in patients with COPD. METHODS AND ANALYSIS: Two randomised, double-blind, placebo-controlled trials have been designed. Patients will routinely receive either NLPE (BASE-TRAIN trial) or NMES (BASE-ELECTRIC trial) as part of standard exercise-based care during their 8-to-10 week pulmonary rehabilitation (PR) programme. A total of 222 patients with COPD (2×77 = 154 patients in the BASE-TRAIN trial and 2×34 = 68 patients in the BASE-ELECTRIC trial) will be recruited from two specialised PR centres in The Netherlands. For study purposes, patients will receive 3.2 g of oral BA supplementation or placebo per day. Exercise tolerance is the primary outcome, which will be assessed using the endurance shuttle walk test (BASE-TRAIN) or the constant work rate cycle test (BASE-ELECTRIC). Furthermore, quadriceps muscle strength and endurance, cognitive function, carnosine levels (in muscle), BA levels (in blood and muscle), markers of oxidative stress and inflammation (in blood, muscles and lungs), physical activity and quality of life will be measured. ETHICS AND DISSEMINATION: Both trials were approved by CMO Regio Arnhem-Nijmegen, The Netherlands (NL70781.091.19. and NL68757.091.19). TRIAL REGISTRATION NUMBER: NTR8427 (BASE-TRAIN) and NTR8419 (BASE-ELECTRIC).

Association between patient-reported outcomes and exercise test outcomes in patients with COPD before and after pulmonary rehabilitation.

BACKGROUND: Over the years, the scope of outcomes assessment in chronic obstructive pulmonary disease (COPD) has broadened, allowing for the evaluation of various patient-reported outcomes (PROs). As it still remains unclear whether and to what extent PROs mirror the exercise performance of patients with COPD, the current study aimed to assess the association between different exercise test outcomes and PROs, before and after pulmonary rehabilitation (PR). METHODS: Correlations between PROs used to describe health-related quality of life (HRQoL), mood status, level of care dependency and dyspnea in patients with COPD and commonly used laboratory- and field-based exercise test outcomes were evaluated in 518 individuals with COPD attending PR. RESULTS: Overall, correlations between PROs and exercise test outcomes at baseline were statistically significant. The correlation between modified Medical Research Council (mMRC) dyspnea score and 6-min walking distance (6MWD) was strongest (ρ:-0.65; p<0.001). HRQoL related PROs showed weak correlations with exercise outcomes at baseline. Moderate correlations were found between St George's Respiratory Questionnaire total score and 6MWD (r:-0.53; p<0.001) and maximal workload achieved during cardiopulmonary exercise testing (ρ:-0.48; p<0.001); and between Clinical COPD Questionnaire (CCQ) total score and 6MWD (r:-0.48; p<0.001) and maximal workload (ρ:-0.43; p<0.001). When significant, correlations between changes in exercise test outcomes and changes in PROs after PR were generally very weak or weak. The highest correlation was found between changes in CCQ total score and changes in 6MWD (ρ: - 0.36; p<0.001). CONCLUSIONS: PROs and exercise test outcomes, although significantly correlated with each other, assess different disease features in patients with COPD. Individual PROs need to be supported by additional functional measurements whenever possible, in order to get a more detailed insight in the effectiveness of a PR program. TRIAL REGISTRATION: Netherlands Trial Register ( NL3263 /NTR3416). Registered 2 May 2012.

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.

Impact of mild-to-moderate exacerbations on outcomes of neuromuscular electrical stimulation (NMES) in patients with COPD.

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common among patients attending pulmonary rehabilitation (PR) and may compromise its outcomes. Neuromuscular electrical stimulation (NMES) seems one of the few exercise modalities that can actually be continued during AECOPD, due to its low burden on the impaired respiratory and cardiovascular system. However, the quality of evidence is low. The purpose of this study was to assess the impact of mild-to-moderate AECOPD on adherence/outcomes of a high-frequency (HF) or low-frequency (LF) NMES training program, as part of inpatient PR, in severely dyspneic, weakened individuals with COPD. 62 patients who received NMES as the sole supervised muscle training modality during an 8-week PR program (HF-NMES: n = 33; LF-NMES: n = 29) were analyzed retrospectively. 48.4% experienced ≥1 AECOPD during PR and were classified as exacerbators. Exacerbators completed 75 NMES sessions (interquartile range: 73-78) and were able to increase training intensity with 24 mA (15-39), while non-exacerbators completed 76 sessions (73-79) and increased training intensity with 35 mA (22-50), with no between-group differences (p = 0.474 and p = 0.065, respectively). The median change in 6-min walking distance, cycle endurance time, and isokinetic quadriceps strength and endurance did not differ between the exacerbation and non-exacerbation group. To conclude, the occurrence of mild-to-moderate AECOPD during a PR program primarily focused on NMES, does not affect adherence, intensity, and clinical outcomes in patients with severe COPD. Continuing NMES seems a feasible way to potentially counteract exacerbation-related lower-limb muscle dysfunction and improve outcomes of PR, with HF-NMES being the preferential muscle training modality.