Skeletal muscle weakness is a common and serious finding in patients with advanced chronic obstructive pulmonary disease (COPD) and contributes to their morbidity and mortality, increasing the risk of exacerbations, hospitalisations and death by 3–4-fold.1 2 The treatment for muscle dysfunction of COPD is extremely limited, and the multitude of interventions to address poor muscle performance has not been fully explored in these patients. Over the past decade, there has been an explosion of interest and research on this topic. Despite that, the pathophysiological mechanisms linking the lung disease of COPD with skeletal muscle dysfunction remains largely unknown. Identifying a link between lung disease and muscle performance might indeed be a daunting task because of the influence of other comorbid conditions (and medications), previous musculoskeletal injury and the history of physical activity that might influence the current status of skeletal muscle in this condition. There are, however, several observations that are widely known and accepted. Firstly, skeletal muscle weakness increases with progression of disease. Secondly, histologically, biopsies of large limb muscles consistently demonstrate a reduction in muscle mass, especially of the anaerobic type-IIx fibres, a shift of fibre type from type 1 fibres to a predominance of type 2 fibres and the depletion of mitochondrial oxidative enzymes leading to uncoupling of oxidative phosphorylation and reduced aerobic capacity.3 Interestingly, these muscles also demonstrate increased oxidative stress and accelerated …