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).

Profiling of Patients with COPD for Adequate Referral to Exercise-Based Care: The Dutch Model.

A loss of physical functioning (i.e., a low physical capacity and/or a low physical activity) is a common feature in patients with chronic obstructive pulmonary disease (COPD). To date, the primary care physiotherapy and specialized pulmonary rehabilitation are clearly underused, and limited to patients with a moderate to very severe degree of airflow limitation (GOLD stage 2 or higher). However, improved referral rates are a necessity to lower the burden for patients with COPD and for society. Therefore, a multidisciplinary group of healthcare professionals and scientists proposes a new model for referral of patients with COPD to the right type of exercise-based care, irrespective of the degree of airflow limitation. Indeed, disease instability (recent hospitalization, yes/no), the burden of disease (no/low, mild/moderate or high), physical capacity (low or preserved) and physical activity (low or preserved) need to be used to allocate patients to one of the six distinct patient profiles. Patients with profile 1 or 2 will not be referred for physiotherapy; patients with profiles 3-5 will be referred for primary care physiotherapy; and patients with profile 6 will be referred for screening for specialized pulmonary rehabilitation. The proposed Dutch model has the intention to get the right patient with COPD allocated to the right type of exercise-based care and at the right moment.