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* From the Department of Pulmonary Diseases, University Hospital Maastricht, Maastricht, the Netherlands.
Correspondence to: E. F. M. Wouters, MD, PhD, FCCP, Department of Pulmonary Diseases, University Hospital Maastricht, PO Box 5800, 6202 Az Maastricht, the Netherlands;
The pathogenesis and clinical manifestations of COPD are not restricted to pulmonary inflammation and structural remodeling. Rather, this disorder is associated with clinically significant systemic alterations in biochemistry and organ function. The systemic aspects of COPD include oxidative stress and altered circulating levels of inflammatory mediators and acute-phase proteins. Indeed, an impaired endogenous oxidant-antioxidant balance has been reported in patients experiencing exacerbations of COPD, and others have observed altered circulating levels of several cytokines and adhesion molecules in patients with stable disease. As in other chronic inflammatory conditions, weight loss, muscle wasting, and tissue depletion are commonly seen in COPD patients. Selective wasting of fat-free mass coupled with impaired respiratory and peripheral muscle function and a reduced capacity for exercise occur in COPD patients. Indeed, weight loss may directly impact poor prognosis in COPD patients. The mechanisms underlying weight loss and muscle wasting are incompletely understood but likely involve an imbalance in ongoing processes of protein degradation and replacement. This may include alterations in the relative levels or activities of endocrine hormones such as insulin, growth hormone, testosterone, and glucocorticoids. Furthermore, chronic systemic inflammation involving cytokines such as interleukin-1 and tumor necrosis factor-
may be associated with these hormonal changes and muscle wasting in COPD patients. This review includes a discussion of the mechanisms of skeletal muscle fiber protein metabolism/catabolism, the potential roles of endogenous cytokines in protein loss, and the possibility that novel drugs that inhibit cytokine signaling may provide benefits by reducing muscle wasting and cachexia, thereby improving the prognosis and quality of life among COPD patients.
Key Words: body weight • COPD • fat-free mass • muscle protein catabolism • prognosis • systemic effects • systemic inflammation • tumor necrosis factor-
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