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Am. J. Respir. Crit. Care Med., Volume 158, Number 6, December 1998, 1936-1944

Collagen Deposition in Large Airways May Not Differentiate Severe Asthma from Milder Forms of the Disease

HONG WEI CHU, JANET L. HALLIDAY, RICHARD J. MARTIN, DONALD Y. M. LEUNG, STANLEY J. SZEFLER, and SALLY E. WENZEL

Department of Medicine, National Jewish Medical and Research Center and the University of Colorado Health Sciences Center, Denver, Colorado

Chronic airway inflammation and remodeling, including fibrosis, have been proposed as important contributors to asthma pathophysiology. Previous studies of airway fibrosis have been performed mainly in mild and moderate asthmatics at the subepithelial "basement membrane" (SBM) level. The current study was designed to evaluate the large airway SBM thickness and submucosal collagen deposition, as measured by three different collagen staining methods, in endobronchial biopsies from 17 severe, nine moderate, and seven mild asthmatics, as well as eight normal control subjects. Tissue eosinophils and transforming growth factor-beta (TGF-beta ) immunoreactivity were also examined. There were no statistically significant differences in the SBM thickness, submucosal collagen deposition, eosinophil numbers, or TGF-beta positive cells among the three groups of asthmatics and the normal control subjects. It was only when examining all asthmatics (n = 33) together, that a modestly thickened SBM (p = 0.04), as evaluated by collagen type III immunostaining, was observed as compared with normal control subjects. Despite this difference, no significant differences were found in the amount of submucosal collagen deposition and the number of eosinophils or TGF-beta expressing cells when comparing total asthmatics and normal control subjects. Additionally, no significant correlations were found between collagen deposition and eosinophil count, TGF-beta expression level, FEV1, or duration of asthma. These results suggest that although increased collagen deposition in the SBM at the large airway level is a characteristic of asthma, it may not explain the differences in severity of asthma.




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