Lower limb muscle dysfunction in COPD : The effects of resistance training and nutritional supplementation

Introduction: Weakness and wasting of the lower limb muscles is a frequent extra-pulmonary manifestation of Chronic Obstructive Pulmonary Disease (COPD). Although the underlying lung pathology is largely irreversible, the impact of the disease on the lower limbs is potentially treatable. Resistance training (RT) is an effective intervention for improving lower limb function in COPD, while nutritional supplementation as an adjunct to RT can provide additional benefits in older adults. The functional impact of this therapeutic combination and the accompanying muscle cellular and molecular changes has not been previously explored in COPD. Methods: This thesis explored the functional, molecular, and cellular responses of the lower limb muscles in COPD patients in response to high-intensity quadriceps isokinetic RT. The primary hypothesis was that RT-induced increases in lower limb muscle mass and strength in COPD patients would be mediated through the expression of genes and proteins associated with muscle mass regulation in humans (chapter 6). Secondary aims were to determine whether protein-carbohydrate supplementation at the time of training would augment the gains in functional performance in COPD (chapter 5), to study the muscle inflammatory and satellite cell profile in response to RT (chapter 7), and to measure the training-induced changes in lower limb muscle mass using portable ultrasound (chapter 8). Results: All participants demonstrated significant improvements in lower limb muscle mass and strength following RT, but protein-carbohydrate supplementation did not provide additional benefits. Absolute work done during RT was lower throughout in COPD when compared to healthy controls (HCs). Except for myogenic signalling, the increased expression of anabolic, catabolic, and transcription factor proteins was blunted in COPD patients, and nutritional supplementation did not alter this response. Inflammatory cells in the lower limb muscles increased in response to acute RT in COPD, but returned to baseline with chronic training. Portable ultrasound was shown to be a reproducible and sensitive technique for measuring changes in lower limb muscle mass following RT in COPD. Conclusions: This thesis demonstrates that the potential for lower limb muscle rehabilitation in response to RT is preserved in COPD, while post-exercise protein-carbohydrate supplementation did not augment the functional or molecular responses. Except for myogenic proteins, the molecular responses to training were uncoupled from the functional gains, and more closely related to the absolute workloads performed during training.