Pathophysiology underlying muscle dysfunction and its most relevant associated clinical factors in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) induces skeletal muscle (SkM) dysfunction, particularly affecting the lower-limbs. This condition is characterized by fiber-type shifts, muscle wasting, and mitochondrial dysfunction, collectively reducing oxidative metabolism in SkM, which manifests clinically as decreased muscle performance and exercise intolerance. Clinical evaluation of SkM-dysfunction encompasses cardiopulmonary exercise testing, field-based functional assessment, balance testing, and muscle mass measurements. Each provides complementary information on the severity of SkM impairment. Reports describing functional improvements without changes in SkM physiology underscore other concomitant adaptations in muscle efficiency, neuromuscular activation, and mechanical properties. No single test fully reflects SkM-dysfunction complexity in COPD; however, the 1-min sit-to-stand test appears particularly sensitive to impairment of lower-limb force production, whereas the 6-min walk test provides complementary prognostic information by reflecting whole-body cardiorespiratory capacity. Thus, multimodal assessment strategies may facilitate early identification of SkM dysfunction and drive targeted interventions that combine nutritional strategies and exercise-based pulmonary rehabilitation to mitigate disability and improve quality of life.