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Published ahead of print on July 11, 2003, doi:10.1164/rccm.200209-1070OC

Am. J. Respir. Crit. Care Med., Volume 168, Number 6, September 2003, 706-713

A more recent version of this article appeared on September 15, 2003
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Submitted on September 24, 2002
Accepted on July 3, 2003

HUMAN DIAPHRAGM REMODELING ASSOCIATED WITH COPD: CLINICAL IMPLICATIONS

Sanford Levine1*, Taitan Nguyen1, Larry R Kaiser2, Neal A Rubinstein2, Greg Maislin2, Christopher Gregory3, Lawrence C Rome4, Gary A Dudley5, Gary C Sieck3, and Joseph B Shrager1

1 Surgical and Research Services, VA Medical Center, Philadelphia, PA, USA; Surgery, Medicine, Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 2 Surgery, Medicine, Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA, 3 Physiology and Biophysics, and Anesthesiology, Mayo Medical School, Clinic, and Foundation, Rochester, MN, USA, 4 Biology, University of Pennsylvania School of Arts and Sciences, Philadelphia, PA, USA, 5 Exercise Science, University of Georgia, Athens, GA, USA

* To whom correspondence should be addressed. E-mail: sdlevine{at}mail.med.upenn.edu.

Diaphragm remodeling associated with 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 FEV1.0, we obtained costal diaphragm biopsies on 40 subjects whose FEV1.0 ranged from 118-to-16% predicted normal. First, we noted that our exponential regression model indicated that changes in FEV1.0 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 maximum 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 FEV1.0 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: COPD, fiber type transformations, within fiber type adaptations, single fiber physiology, specific force




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