Muscle dysfunction in patients with lung diseases: a growing epidemic.

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The lung is tasked with the provision of oxygen to fuel oxidative phosphorylation and with the removal of its byproduct carbon dioxide and is therefore a key player in organismal metabolism. When viewed from this perspective, it is unsurprising that lung dysfunction is associated with suboptimal function of other metabolic organs, most notably of skeletal muscle. A prevalent example is observed in patients with chronic obstructive pulmonary disease (COPD), which is a leading cause of death worldwide and one of the few major diseases for which mortality continues to climb (1). Skeletal muscle dysfunction, defined as the loss of either muscle strength or endurance, is a prominent comorbidity in patients with COPD that impairs their exercise capacity, quality of life, and disease prognosis (2–8). For example, quadriceps muscle dysfunction, which is primarily characterized by reduced muscle force generation, is observed in one-third of all patients with COPD even at very early stages of their disease, where it is associated with decreased exercise tolerance, a reduced quality of life, and increased mortality (2–8). In patients with COPD, other comorbidities, including muscle wasting, malnutrition, chronic heart failure, exacerbations, and reduced physical activity, can further impair muscle function (4, 7). Sarcopenia, the age-associated loss of skeletal muscle mass and function, is present in as many as 10% of older hospitalized adults (9, 10). Although limb muscle dysfunction is often the most clinically evident problem in patients with COPD, respiratory muscle dysfunction is also present and may contribute to the development and persistence of hypoventilatory respiratory failure in these patients (11, 12). Combined, the presence of respiratory and peripheral muscle dysfunction and underlying sarcopenia results in prolonged hospitalizations and reduced rates of physical activity, creating a vicious circle of progressive muscle dysfunction and morbidity.