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.

Patient activation is a treatable trait in patients with chronic airway diseases: An observational study.

Background: Self-management is key for reducing the burden of disease in chronical illness. However, applying self-management presupposes behavioral change. Sufficient knowledge, skills, confidence and motivation to make the needed behavior changes are important prerequisites. During the past years the Integral Diagnostic Trajectory was developed for patients with asthma or COPD which aims to identify treatable traits and activating patients for self-management. Objective: In the present study the effects of the Integral Diagnostic Trajectory on the Patient Activation Measure (PAM®) were examined. In addition, predictive variables for PAM baseline scores and change scores were sought. Materials and methods: A total of 241 patients with asthma or COPD referred to the pulmonologist at the Radboud university medical center, location Dekkerswald, Nijmegen were included. Patient activation was measured before the first visit and after the intervention with the 13-item PAM®. Additional, patient characteristics and health status were measured with the Nijmegen Clinical Screening Instrument (NCSI), modified Medical Research Council (mMRC), Asthma Control Questionnaire (ACQ), and COPD Clinical Questionnaire (CCQ). Results: Fifty percent of the patients with asthma and seventy percent of the patients with COPD had low levels of activation at baseline (PAM level 1-2). Baseline PAM scores could be explained in patients with asthma for 7% by number of severe problems in health status. And for 18% in patients with COPD by number of severe problems, age and employment status. After the intervention both groups significantly improved on the PAM (T0: 56.0 ± 13.1 vs. T1:63.3 ± 14.0 in asthma, and T0: 50.0 ± 8.8 vs. 58.4 ± 11.1 in COPD). Multivariate stepwise regression analysis showed that only 24% of the change in score could be explained by baseline PAM score and being employed in patients with asthma, and 18% of the variance in change score could be predicted by baseline PAM score in COPD. Conclusion: The present study showed that low level of activation is a common feature in patients with asthma and COPD. With a relatively short and seemingly simple intervention patients can reach higher levels of patient activation, which is a prerequisite for adopting self-management techniques in daily life.

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.

"Can Do, Do Do" Quadrants and 6-Year All-Cause Mortality in Patients With COPD.

BACKGROUND: Physical capacity (PC; "can do") and physical activity (PA; "do do") are prognostic indicators in COPD and can be used to subdivide patients with COPD into four exclusive subgroups (the so-called "can do, do do" quadrants). This concept may be useful to understand better the impact of PC and PA on all-cause mortality in patients with COPD. RESEARCH QUESTION: What is the 6-year all-cause mortality risk of the "can do, do do" quadrants of patients with COPD? STUDY DESIGN AND METHODS: This retrospective study used data from patients with COPD who underwent a comprehensive assessment at their first-ever outpatient consultation. PC was assessed using the 6-min walk distance and physical activity was assessed using an accelerometer (steps per day). All-cause mortality data were obtained from the Municipal Personal Records Database. Receiver operating characteristic curves were used to determine threshold values for PC and PA to predict 6-year all-cause mortality. Using the derived threshold values, male and female patients were divided into the four "can do, do do" quadrants. RESULTS: Data from 829 patients were used for analyses. Best discriminatory values for 6-year mortality were 404 m and 4,125 steps/day for men and 394 m and 4,005 steps/day for women. During a median follow-up of 55 months (interquartile range, 37-71 months), 129 patients (15.6%) died. After controlling for established prognostic factors, patients in the "can do, don't do" quadrant and "can do, do do" quadrant showed significantly lower mortality risk compared with patients in the "can't do, don't do" quadrant: hazard ratios of 0.36 (95% CI, 0.14-0.93) and 0.24 (95% CI, 0.09-0.61) for men and 0.37 (95% CI, 0.38-0.99) and 0.29 (95% CI, 0.10-0.87) for women, respectively. No significant differences were found between the "can't do, do do" and "can't do, don't do" quadrants. INTERPRETATION: Patients with COPD with a preserved PC seem to have a significantly lower 6-year mortality risk compared with patients with a decreased PC, regardless of physical activity level.

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.

Specific Contribution of Quadriceps Muscle Strength, Endurance, and Power to Functional Exercise Capacity in People With Chronic Obstructive Pulmonary Disease: A Multicenter Study.

OBJECTIVE: Various functional muscle properties affect different aspects of functional exercise capacity in people with chronic obstructive pulmonary disease (COPD). The purpose of this study was to investigate the contribution of quadriceps muscle strength, endurance, and power to 6-Minute Walking Distance (6MWD) and 1-minute sit-to-stand test (1STS) performance in people with COPD. METHODS: The study was a prospective, multicenter, cross-sectional study. Anthropometrics, Medical Research Council dyspnea scale, lung function, 6MWD, and 1STS number of repetitions were assessed. Isometric quadriceps strength and endurance, isotonic quadriceps endurance, isokinetic quadriceps strength, and power were assessed on a computerized dynamometer while functional quadriceps power was determined during 5 sit-to-stand repetitions. Univariate and multivariate analyses were performed to determine the contribution of functional muscle properties to the 6MWD and the 1STS number of repetitions. RESULTS: The study included 70 people with COPD (mean % predicted forced expiratory volume in 1 second = 58.9 [SD = 18.2]). The 6MWD correlated with each functional muscle property except the isometric quadriceps endurance. The number of repetitions during the 1STS correlated with each functional muscle property except isometric measurements. Multivariate models explained 60% and 39% of the variance in the 6MWD and 1STS number of repetitions, respectively, with quadriceps power determined during 5 sit-to-stand repetitions being the muscle functional property with the strongest contribution to the models. CONCLUSION: Except for isometric endurance, quadriceps strength, endurance, and power were associated with functional exercise capacity in people with moderate COPD. Among these functional muscle properties, muscle power contributed the most to the 6MWD and 1STS number of repetitions, suggesting that muscle power is more relevant to functional exercise capacity than muscle strength or endurance in people with COPD. IMPACT: Understanding the individual contribution of muscle properties to functional status is important to designing interventions. This study provides the guidance that muscle power may be more important to functional exercise capacity than muscle strength or endurance in people with COPD.

Comprehensive Health Assessment 3 Months After Recovery From Acute Coronavirus Disease 2019 (COVID-19).

BACKGROUND: Long-term health sequelae of coronavirus disease 2019 (COVID-19) may be multiple but have thus far not been systematically studied. METHODS: All patients discharged after COVID-19 from the Radboud University Medical Center, Nijmegen, the Netherlands, were consecutively invited to a multidisciplinary outpatient facility. Also, nonadmitted patients with mild disease but with symptoms persisting >6 weeks could be referred by general practitioners. Patients underwent a standardized assessment including measurements of lung function, chest computed tomography (CT)/X-ray, 6-minute walking test, body composition, and questionnaires on mental, cognitive, health status, and quality of life (QoL). RESULTS: 124 patients (59 ±â€…14 years, 60% male) were included: 27 with mild, 51 with moderate, 26 with severe, and 20 with critical disease. Lung diffusion capacity was below the lower limit of normal in 42% of discharged patients. 99% of discharged patients had reduced ground-glass opacification on repeat CT imaging, and normal chest X-rays were found in 93% of patients with mild disease. Residual pulmonary parenchymal abnormalities were present in 91% of discharged patients and correlated with reduced lung diffusion capacity. Twenty-two percent had low exercise capacity, 19% low fat-free mass index, and problems in mental and/or cognitive function were found in 36% of patients. Health status was generally poor, particularly in the domains functional impairment (64%), fatigue (69%), and QoL (72%). CONCLUSIONS: This comprehensive health assessment revealed severe problems in several health domains in a substantial number of ex-COVID-19 patients. Longer follow-up studies are warranted to elucidate natural trajectories and to find predictors of complicated long-term trajectories of recovery.

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.

Effect and feasibility of non-linear periodized resistance training in people with COPD: study protocol for a randomized controlled trial.

BACKGROUND: In people with chronic obstructive pulmonary disease (COPD), limb-muscle dysfunction is one of the most troublesome systemic manifestations of the disease, which at the functional level is evidenced by reduced strength and endurance of limb muscles. Improving limb-muscle function is an important therapeutic goal of COPD management, for which resistance training is recommended. However, current guidelines for resistance training in COPD mainly focus on improving muscle strength which only reflects one aspect of limb-muscle function and does not address the issue of reduced muscle endurance. The latter is of importance considering that the reduction in limb-muscle endurance often is greater than that of muscle weakness, and also, limb-muscle endurance seems to be closer related to walking capacity as well as arm function than to limb-muscle strength within this group of people. Thus, strategies targeting multiple aspects of the decreased muscle function are warranted to increase the possibility for an optimal effect for the individual patient. Periodized resistance training, which represents a planned variation of resistance training variables (i.e., volume, intensity, frequency, etc.), is one strategy that could be used to target limb-muscle strength as well as limb-muscle endurance within the same exercise regimen. METHODS: This is an international, multicenter, randomized controlled trial comparing the effect and feasibility of non-linear periodized resistance training to traditional non-periodized resistance training in people with COPD. Primary outcomes are dynamic limb-muscle strength and endurance. Secondary outcomes include static limb-muscle strength and endurance, functional performance, quality of life, dyspnea, intramuscular adaptations as well as the proportion of responders. Feasibility of the training programs will be assessed and compared on attendance rate, duration, satisfaction, drop-outs as well as occurrence and severity of any adverse events. DISCUSSION: The proposed trial will provide new knowledge to this research area by investigating and comparing the feasibility and effects of non-linear periodized resistance training compared to traditional non-periodized resistance training. If the former strategy produces larger physiological adaptations than non-periodized resistance training, this project may influence the prescription of resistance training in people with COPD. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03518723 . Registered on 13 April 2018.

Respiratory Muscle Effort during Expiration in Successful and Failed Weaning from Mechanical Ventilation.

WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Respiratory muscle weakness in critically ill patients is associated with difficulty in weaning from mechanical ventilation. Previous studies have mainly focused on inspiratory muscle activity during weaning; expiratory muscle activity is less well understood. The current study describes expiratory muscle activity during weaning, including tonic diaphragm activity. The authors hypothesized that expiratory muscle effort is greater in patients who fail to wean compared to those who wean successfully. METHODS: Twenty adult patients receiving mechanical ventilation (more than 72 h) performed a spontaneous breathing trial. Tidal volume, transdiaphragmatic pressure, diaphragm electrical activity, and diaphragm neuromechanical efficiency were calculated on a breath-by-breath basis. Inspiratory (and expiratory) muscle efforts were calculated as the inspiratory esophageal (and expiratory gastric) pressure-time products, respectively. RESULTS: Nine patients failed weaning. The contribution of the expiratory muscles to total respiratory muscle effort increased in the "failure" group from 13 ± 9% at onset to 24 ± 10% at the end of the breathing trial (P = 0.047); there was no increase in the "success" group. Diaphragm electrical activity (expressed as the percentage of inspiratory peak) was low at end expiration (failure, 3 ± 2%; success, 4 ± 6%) and equal between groups during the entire expiratory phase (P = 0.407). Diaphragm neuromechanical efficiency was lower in the failure versus success groups (0.38 ± 0.16 vs. 0.71 ± 0.36 cm H2O/µV; P = 0.054). CONCLUSIONS: Weaning failure (vs. success) is associated with increased effort of the expiratory muscles and impaired neuromechanical efficiency of the diaphragm but no difference in tonic activity of the diaphragm.

Diaphragm Atrophy and Weakness in the Absence of Mitochondrial Dysfunction in the Critically Ill.

RATIONALE: The clinical significance of diaphragm weakness in critically ill patients is evident: it prolongs ventilator dependency and increases morbidity, duration of hospital stay, and health care costs. The mechanisms underlying diaphragm weakness are unknown, but might include mitochondrial dysfunction and oxidative stress. OBJECTIVES: We hypothesized that weakness of diaphragm muscle fibers in critically ill patients is accompanied by impaired mitochondrial function and structure, and by increased markers of oxidative stress. METHODS: To test these hypotheses, we studied contractile force, mitochondrial function, and mitochondrial structure in diaphragm muscle fibers. Fibers were isolated from diaphragm biopsies of 36 mechanically ventilated critically ill patients and compared with those isolated from biopsies of 27 patients with suspected early-stage lung malignancy (control subjects). MEASUREMENTS AND MAIN RESULTS: Diaphragm muscle fibers from critically ill patients displayed significant atrophy and contractile weakness, but lacked impaired mitochondrial respiration and increased levels of oxidative stress markers. Mitochondrial energy status and morphology were not altered, despite a lower content of fusion proteins. CONCLUSIONS: Critically ill patients have manifest diaphragm muscle fiber atrophy and weakness in the absence of mitochondrial dysfunction and oxidative stress. Thus, mitochondrial dysfunction and oxidative stress do not play a causative role in the development of atrophy and contractile weakness of the diaphragm in critically ill patients.

The role of calpains in ventilator-induced diaphragm atrophy.

BACKGROUND: Controlled mechanical ventilation (CMV) is associated with diaphragm dysfunction. Dysfunction results from muscle atrophy and injury of diaphragm muscle fibers. Enhanced proteolysis and reduced protein synthesis play an important role in the development of atrophy. The current study is to evaluate the effects of the calpains inhibitor calpeptin on the development of diaphragm atrophy and activation of key enzymes of the ubiquitin-proteasome pathway in rats under CMV. METHODS: Three groups of rats were studied: control animals (CON, n = 8), rats subjected to 24 h of MV (CMV, n = 8), and rats subjected to 24 h of MV after administration of the calpain inhibitor calpeptin (CMVC, n = 8). The diaphragm was analyzed for calpain activity, myosin heavy chain (MHC) content, and cross-sectional area (CSA) of diaphragmatic muscle fibers as a marker for muscle atrophy. In addition, key enzymes of the ubiquitin-proteasome pathway (MAFbx and MuRF1) were also studied. RESULTS: CMV resulted in loss of both MHCfast and MHCslow. Furthermore, the CSA of diaphragmatic muscle fibers was significantly decreased after 24 h of CMV. However, calpain inhibitor calpeptin prevented loss of MHC and CSA after CMV. In addition, calpeptin prevented the increase in protein expression of calpain1 and calpain2 and reduced calpain activity as indicated by reduced generation of the calpain cleavage product αII-spectrin in the diaphragm. CMV-induced upregulation of both MAFbx and MuRF1 protein levels was attenuated by treatment with calpeptin. CONCLUSIONS: The calpain inhibitor calpeptin prevents MV-induced muscle atrophy. In addition, calpeptin attenuated the expression of key proteolytic enzymes known to be involved in ventilator-induced diaphragm atrophy, including MAFbx and MuRF1.