Exercise and Rehabilitation Sciences Laboratory, School of Physical Therapy, Faculty of Rehabilitation Sciences, Universidad Andres Bello, 700 Fernández Concha, Las Condes, 7591538, Santiago, Chile.
Long Active Life Laboratory, Instituto de Ciencias de la Salud, Universidad de O'Higgins, Rancagua, Chile.
BMC Pulm Med. 2022 Jul 19;22(1):278. doi: 10.1186/s12890-022-02061-4.
Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide. COPD is characterised by dyspnoea, limited exercise tolerance, and muscle dysfunction. Muscle dysfunction has been linked to dysregulation between muscle protein synthesis, myogenesis and degradation mechanisms. Conventional concentric cycling has been shown to improve several clinical outcomes and reduce muscle wasting in COPD patients. Eccentric cycling is a less explored exercise modality that allows higher training workloads imposing lower cardio-metabolic demand during exercise, which has shown to induce greater muscle mass and strength gains after training. Interestingly, the combination of eccentric and concentric cycling training has scarcely been explored. The molecular adaptations of skeletal muscle after exercise interventions in COPD have shown equivocal results. The mechanisms of muscle wasting in COPD and whether it can be reversed by exercise training are unclear. Therefore, this study aims two-fold: (1) to compare the effects of 12 weeks of eccentric (ECC), concentric (CONC), and combined eccentric/concentric (ECC/CONC) cycling training on muscle mass and function, cardiometabolic health, physical activity levels and quality of life in severe COPD patients; and (2) to examine the molecular adaptations regulating muscle growth after training, and whether they occur similarly in specific muscle fibres (i.e., I, IIa and IIx).
Study 1 will compare the effects of 12 weeks of CONC, ECC, versus ECC/CONC training on muscle mass and function, cardiometabolic health, levels of physical activity and quality of life of severe COPD patients using a multicentre randomised trial. Study 2 will investigate the effects of these training modalities on the molecular adaptations regulating muscle protein synthesis, myogenesis and muscle degradation in a subgroup of patients from Study 1. Changes in muscle fibres morphology, protein content, genes, and microRNA expression involved in skeletal muscle growth will be analysed in specific fibre-type pools.
We aim to demonstrate that a combination of eccentric and concentric exercise could maximise the improvements in clinical outcomes and may be ideal for COPD patients. We also expect to unravel the molecular mechanisms underpinning muscle mass regulation after training in severe COPD patients.
Deutshches Register Klinischer Studien; Trial registration: DRKS00027331; Date of registration: 12 January 2022. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027331 .
慢性阻塞性肺疾病（COPD）是全球第三大致死原因。COPD 的特征是呼吸困难、运动耐量有限和肌肉功能障碍。肌肉功能障碍与肌肉蛋白合成、成肌和降解机制之间的失调有关。传统的向心循环已被证明能改善多种临床结局，并减少 COPD 患者的肌肉消耗。离心循环是一种探索较少的运动方式，它允许更高的训练工作量，在运动过程中对心肺代谢的需求较低，在训练后已被证明能引起更大的肌肉质量和力量增加。有趣的是，离心和向心循环训练的结合几乎没有被探索过。COPD 患者运动干预后的骨骼肌分子适应结果喜忧参半。COPD 中肌肉消耗的机制以及运动训练是否可以逆转这些机制尚不清楚。因此，本研究有两个目的：（1）比较 12 周的离心（ECC）、向心（CONC）和离心/向心（ECC/CONC）循环训练对严重 COPD 患者的肌肉质量和功能、心肺代谢健康、身体活动水平和生活质量的影响；（2）研究调节训练后肌肉生长的分子适应，以及它们是否在特定的肌纤维（即 I、IIa 和 IIx）中同样发生。
研究 1 将比较 12 周 CONC、ECC 与 ECC/CONC 训练对严重 COPD 患者肌肉质量和功能、心肺代谢健康、身体活动水平和生活质量的影响，采用多中心随机试验。研究 2 将在研究 1 的患者亚组中研究这些训练方式对调节肌肉蛋白合成、成肌和肌肉降解的分子适应的影响。将分析特定纤维类型池中的骨骼肌生长所涉及的肌纤维形态、蛋白含量、基因和 microRNA 表达的变化。
我们的目的是证明离心和向心运动的结合可以最大限度地提高临床结局的改善，并且可能是 COPD 患者的理想选择。我们还期望揭示严重 COPD 患者训练后肌肉质量调节的分子机制。
德国临床试验注册处；试验注册：DRKS00027331；注册日期：2022 年 1 月 12 日。https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027331 。
