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).

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.

Exercise training in pulmonary rehabilitation.

Exercise training remains a cornerstone of pulmonary rehabilitation (PR) in patients with chronic respiratory disease. The choice of type of exercise training depends on the physiologic requirements and goals of the individual patient as well as the available equipment at the PR center. Current evidence suggests that, at ground walking exercise training, Nordic walking exercise training, resistance training, water-based exercise training, tai chi, and nonlinear periodized exercise are all feasible and effective in (subgroups) of patients with chronic obstructive pulmonary disease. In turn, these exercise training modalities can be considered as part of a comprehensive, interdisciplinary PR program.

Nonlinear exercise training in advanced chronic obstructive pulmonary disease is superior to traditional exercise training. A randomized trial.

RATIONALE: The optimal exercise training intensity and strategy for individualized exercise training in chronic obstructive pulmonary disease (COPD) is not clear. OBJECTIVES: This study compares the effects of nonlinear periodized exercise (NLPE) training used in athletes to traditional endurance and progressive resistance (EPR) training in patients with severe COPD. METHODS: A total of 110 patients with severe COPD (FEV1 32% predicted) were randomized to EPR or NLPE. Exercise training was performed three times per week for 10 weeks. The primary outcomes were cycling endurance time and health-related quality of life using the Chronic Respiratory Questionnaire. The difference in change between EPR and NLPE was assessed using linear mixed-effects modeling. MEASUREMENTS AND MAIN RESULTS: NLPE resulted in significantly greater improvements in cycling endurance time compared with EPR. The difference in change was +300.6 seconds (95% confidence interval [CI] = 197.2-404.2 s; P < 0.001). NLPE also resulted in significantly greater improvements in all domains of the Chronic Respiratory Questionnaire compared with EPR, ranging from +0.48 (95% CI = 0.19-0.78) for the domain, emotions, to +0.96 (95% CI = 0.57-1.35) for dyspnea. CONCLUSIONS: NLPE results in greater improvements in cycle endurance and health-related quality of life in patients with severe COPD than traditional training methods. Clinical trial registered with www.trialregister.nl (The Netherlands Trial Register; NTR 1045).

Dietary supplementation with multiple micronutrients: no beneficial effects in pediatric cystic fibrosis patients.

BACKGROUND: Cystic fibrosis (CF) patients are subjected to increased oxidative stress due to chronic pulmonary inflammation and recurrent infections. Additionally, these patients have diminished skeletal muscle performance and exercise capacity. We hypothesize that a mixture of multiple micronutrients could have beneficial effects on pulmonary function and muscle performance. METHODS: A double-blind, randomized, placebo controlled, cross-over trial with a mixture of multiple micronutrients (ML1) was performed in 22 CF patients (12.9+/-2.5 yrs) with predominantly mild lung disease. Anthropometric measures, pulmonary function, exercise performance by bicycle ergometry, muscular strength and vitamins A and E were determined. RESULTS: Analysis was performed using the paired Student t-test comparing the change in each parameter during ML1 and placebo. Plasma vitamin E and A levels increased during ML1 when compared to placebo. However, no significant difference between the effect of the ML1 or placebo was observed neither for FEV1, FVC, anthropometry, nor for the parameters for muscle performance. CONCLUSIONS: The micronutrient mixture was not superior to placebo with respect to changes in pulmonary function or muscle performance in pediatric CF patients, despite a significant increase in plasma vitamin E concentrations.