Muscle dysfunction, systemic inflammation and exercise in COPD - a narrative review

Abstract

This narrative review summarizes the mechanisms linking chronic obstructive pulmonary disease (COPD), skeletal and respiratory muscle dysfunction, systemic inflammation, and the effects of exercise-based rehabilitation. Muscle dysfunction in COPD is a clinically relevant systemic manifestation that contributes to dyspnea, reduced exercise tolerance, poor quality of life, and mortality. The peripheral muscles, particularly the quadriceps, typically show reduced oxidative capacity, fiber-type redistribution, impaired capillarization, mitochondrial dysfunction, oxidative stress, and activation of catabolic pathways. By contrast, the diaphragm is influenced by both intrinsic remodeling and mechanical disadvantage related to hyperinflation, with adaptive features that differ from those observed in limb muscles. Systemic inflammation, whose source in COPD is debated, together with ageing, multimorbidity, malnutrition, hypoxemia, exposure to corticosteroids, and physical inactivity, may amplify muscle protein breakdown and impair anabolic signaling. However, the causal contribution of systemic inflammation to muscle loss and dysfunction in COPD patients remains incompletely proven. Exercise training is firmly supported as a cornerstone of non-pharmacological COPD management because it improves muscle function, exercise capacity, symptoms, and functional autonomy. Nevertheless, current evidence does not consistently demonstrate a parallel reduction in circulating inflammatory biomarkers after training. The main unresolved question is to determine the optimal training modality, intensity and duration, and the most effective phenotype-specific rehabilitation strategy for improving muscle outcomes, and to establish whether these benefits are mediated by chronic adaptations to regular training in the cardiac, respiratory and muscular systems, or also by systemic anti-inflammatory effects. Not applicable.