EXPRESSION OF GROWTH-FACTORS AND REMODELING OF THE AIRWAY WALL IN BRONCHIAL-ASTHMA

Background - Bronchial asthma is characterised by airway structural ch anges, including mucosal inflammatory infiltration and subepithelial c ollagen deposition, that may represent the morphological basis for the chronicity of the disease. The relationship between airway wall thick ness and growth factors in asthma has not been elucidated. Methods - B ronchial biopsy specimens were obtained from 21 asthmatic patients and eight healthy subjects and the basement membrane thickness was measur ed by light microscopy and electron microscopy. At the same time the n umbers of eosinophils and fibroblasts were assessed and the expression of transforming growth factor beta(1) (TGF-beta(1)), platelet derived growth factor (PDGF), and insulin like growth factor (IGF) I in the b ronchial mucosa was examined by immunostaining. The relationship betwe en the degree of thickening of the subepithelial layer and both the cl inical data and pulmonary function were also investigated. Results - T he basement membrane of the asthmatic patients was thicker than that o f the healthy controls (median 8.09 versus 4.02 mu m). Electron micros copic examination of the basement membrane revealed thickening of the subepithelial lamina reticularis; this thickening significantly correl ated with the number of fibroblasts in the submucosa in the asthmatic subjects (r(s) = 0.88) but not in the controls (r(s) = 0.70). There wa s a significantly higher number of eosinophils in the airways of the a sthmatic subjects than in the healthy subjects (EG1 + cells: 52.0 vers us 2.0/mm(2), EG2 + cells: 56.0 versus 1.5/mm(2)). The expression of e ach growth factor in the bronchial mucosa was similar in asthmatic and healthy subjects (TGF-beta(1): 18.0% versus 16.0%, PDGF: 37.0% versus 32.5%, IGF-I: 15.0% versus 8.0%). A weak but statistically significan t correlation was found between the number of fibroblasts and the expr ession of TGF-beta(1) in asthmatic subjects (r(s) = 0.50). There was a significant correlation between the thickness of the subepithelial la yer in asthmatic subjects and the attack score (r(s) = 0.58) and a sig nificant inverse correlation between the subepithelial collagen thickn ess in asthmatic subjects and airway hypersensitivity (r(s) = -0.65). Conclusions - These findings indicate that the thickening of the subep ithelial layer in bronchial asthma is due to an increase in fibroblast s, and that the thickness of the subepithelial collagen appears to be linked to an increase in bronchial responsiveness and exacerbation of clinical manifestations.