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Published ahead of print on July 11, 2003, doi:10.1164/rccm.200209-1070OC
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American Journal of Respiratory and Critical Care Medicine Vol 168. pp. 706-713, (2003)
© 2003 American Thoracic Society

Original Article

Human Diaphragm Remodeling Associated with Chronic Obstructive Pulmonary Disease

Clinical Implications

Sanford Levine, Taitan Nguyen, Larry R. Kaiser, Neal A. Rubinstein, Greg Maislin, Christopher Gregory, Lawrence C. Rome, Gary A. Dudley, Gary C. Sieck and Joseph B. Shrager

Surgical, and Research Services, Philadelphia Veterans Affairs Medical Center, and Departments of Surgery, Medicine, and Cell and Developmental Biology, University of Pennsylvania School of Medicine; Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania; Departments of Physiology and Biophysics, and Anesthesiology, Mayo Medical School, Clinic, and Foundation, Rochester, Minnesota; and Department of Exercise Science, University of Georgia, Athens, Georgia

Correspondence and requests for reprints should be addressed to Sanford Levine, M.D., 1345 Bobarn Drive, Narberth, PA 19072. E-mail: sdlevine{at}mail.med.upenn.edu

Diaphragm remodeling associated with chronic obstructive pulmonary disease (COPD) consists of a fast-to-slow fiber type transformation as well as adaptations within each fiber type. To try to explain disparate findings in the literature regarding the relationship between fiber type proportions and FEV1, we obtained costal diaphragm biopsies on 40 subjects whose FEV1 ranged from 118 to 16% of the predicted normal value. First, we noted that our exponential regression model indicated that changes in FEV1 can account for 72% of the variation in the proportion of Type I fibers. Second, to assess the impact of COPD on diaphragm force generation, we measured maximal specific force generated by single permeabilized fibers prepared from the diaphragms of two patients with normal pulmonary function tests and two patients with severe COPD. We noted that fibers prepared from the diaphragms of severe COPD patients generated a lower specific force than control fibers (p < 0.001) and Type I fibers generated a lower specific force than Type II fibers (p < 0.001). Our finding of an exponential relationship between the proportion of Type I fibers and FEV1 accounts for discrepancies in the literature. Moreover, our single-fiber results suggest that COPD-associated diaphragm remodeling decreases diaphragmatic force generation by adaptations within each fiber type as well as by fiber type transformations.

Key Words: chronic obstructive pulmonary disease • fiber type transformations • single fiber physiology • specific force • within-fiber type adaptations




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