• COPD exacerbations
• long-term oxygen therapy (LTOT)
• lung physiology
• non-invasive ventilation
• pulmonary rehabilitation

Over the past 2 decades, there has been increasing interest in the extrapulmonary manifestations of chronic obstructive pulmonary disease (COPD). This is supported by the clinical observation that patients show significant improvements in functional performance and health-related quality of life with pulmonary rehabilitation in the absence of lung function changes.1 Furthermore, the forced expiratory volume in 1 s is an imperfect predictor of mortality in severe patients with COPD,2 and when forced expiratory volume in 1 s is corrected after double lung transplantation, peak exercise remains only approximately 50% of predicted up to 1–2 years after surgery.3 This limitation in exercise and functional capacity has led to a particular focus upon the skeletal muscle compartment. Certainly, a surprisingly high proportion of patients with COPD terminate exercise complaining of muscle effort.4 Cross-sectional studies have typically demonstrated muscle weakness5 and reduced endurance,6 particularly of the lower limbs, in COPD compared with age-matched controls. This is corroborated by biopsy findings of muscle fibre atrophy and muscle fibre shift from type I to type II fibres.7 Skeletal muscle dysfunction seems to be clinically relevant in COPD, as loss of skeletal muscle mass and strength are associated with poor health status,8 increased healthcare use9 and even mortality,2 10 independent of lung function parameters.

Debate continues as to the relative importance of systemic and local factors in the aetiology of skeletal …