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Am. J. Respir. Crit. Care Med., Volume 163, Number 7, June 2001, 1654-1659

Diaphragm Injury in Individuals with Airflow Obstruction

NORI A. MACGOWAN, KENNETH G. EVANS, JEREMY D. ROAD, and W. DARLENE REID

School of Rehabilitation Sciences, Department of Medicine, and McDonald Research Laboratory, University of British Columbia, Vancouver, British Columbia, Canada

The purpose of this study was to describe the nature of diaphragm injury, to quantify the injury and number of macrophages at the light microscopic level, and to determine their association with airflow obstruction in humans. Partial-thickness diaphragm biopsies were obtained from 21 subjects going for thoracotomy surgery (FEV1: 74 ± 34% predicted; range: 16 to 122% predicted). Cross sections cut from frozen diaphragm were processed with H&E or processed for immunohistochemistry using the monoclonal antibody Ber-MAC3 (DAKO Corp., Carpinteria, CA) to label macrophages. Area fractions (AA) or the proportions of the cross- sectional area were determined by point counting all viable fields of H&E-stained diaphragm cross sections. AA were 66.2 ± 9.0% for normal muscle, 17.6 ± 7.2% for abnormal muscle, and 16.3 ± 4.2% for connective tissue. Percent predicted FEV1 was inversely related to the AA of abnormal muscle (r = -0.53, p < 0.01) and directly related to the AA of normal muscle (r = 0.37, p < 0.05). The number of macrophages was not related to % predicted FEV1 (mean ± SD: 0.41 ± 0.18/fiber; 52 ± 19/mm2). We conclude that increasing severity of airflow obstruction is associated with an increased AA of abnormal diaphragm and a decreased AA of normal diaphragm.




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