Factors contributing to muscle wasting and dysfunction in COPD patients.

Many patients with chronic obstructive pulmonary disease (COPD) suffer from exercise intolerance. In about 40% of the patients exercise capacity is limited by alterations in skeletal muscle rather than pulmonary problems. Indeed, COPD is often associated with muscle wasting and a slow-to-fast shift in fiber type composition resulting in weakness and an earlier onset of muscle fatigue, respectively. Clearly, limiting muscle wasting during COPD benefits the patient by improving the quality of life and also the chance of survival. To successfully combat muscle wasting and remodeling during COPD a clear understanding of the causes and mechanisms is needed. Disuse, hypoxemia, malnutrition, oxidative stress and systemic inflammation may all cause muscle atrophy. Particularly when systemic inflammation is elevated muscle wasting becomes a serious complication. The muscle wasting may at least partly be due to an increased activity of the ubiquitin proteasome pathway and apoptosis. However, it might well be that an impaired regenerative potential of the muscle rather than the increased protein degradation is the crucial factor in the loss of muscle mass during COPD with a high degree of systemic inflammation. Finally, we briefly discuss the various treatments and rehabilitation strategies available to control muscle wasting and fatigue in patients with COPD.