Clinical drivers of skeletal muscle dysfunction in COPD and other chronic respiratory diseases

Skeletal muscle dysfunction, manifested as reduced strength and/or endurance of respiratory and limb muscles, is a major modifiable determinant of symptoms, functional capacity, and prognosis in chronic respiratory diseases (CRDs). In chronic obstructive pulmonary disease (COPD), two main clinical drivers predominate: physical inactivity leading to limb muscle deconditioning and hyperinflation, imposing mechanical disadvantage on inspiratory muscles. Additional systemic contributors include inflammation-oxidative stress, hypoxemia, nutritional abnormalities, drug effects (notably corticosteroids), exacerbations, endocrine alterations, and impaired regenerative capacity. These systemic drivers also operate in other CRDs, such as asthma, interstitial lung diseases (ILDs), cystic fibrosis (CF), non-CF bronchiectasis, chest wall deformities, and neuromuscular disorders, although disease-specific mechanical constraints differ. Clinically, muscle dysfunction increases dyspnea, reduces exercise tolerance, complicates rehabilitation, and predicts hospitalizations and mortality. Assessment combines bedside measures with laboratory techniques and body composition or physical activity profiling. Effective interventions include pulmonary rehabilitation, targeted exercise and inspiratory muscle training, correction of hyperinflation and hypoxemia, and nutritional optimization.