INHALED CORTICOSTEROID REDUCED LAMINA RETICULARIS OF THE BASEMENT-MEMBRANE BY MODULATION OF INSULIN-LIKE-GROWTH-FACTOR (IGF)-I EXPRESSION IN BRONCHIAL-ASTHMA

Background Pathological studies of bronchial biopsy specimens have con firmed the apparent thickening of lamina reticularis of the epithelial basement membrane. Corticosteroids have proven to be most effective i n modifying airway inflammation. However, there is not much data on th e effects of corticosteroid-treatment on the basement membrane. Object ive To investigate the effects of inhaled beclomethasone dipropionate (BDP) on the thickness of basement membrane and cellular infiltration into the branchial mucosa, and the expression of,growth factors in pat ients with asthma.Methods We studied bronchial biopsies from 24 asthma tic patients before and after treatment with inhaled BDP, 400 mu g twi ce a day or placebo, for 6 months in a double-blind manner. Each subje ct recorded daily asthma symptoms and peak expiratory flow (PEF). Lung function and bronchial responsiveness to methacholine were measured b efore and after treatment. The thickness of the basement membrane was determined by electron microscopy. Inflammatory cells and the expressi on of growth factors were examined by immunohistochemistry in endobron chial biopsy specimens. Results After 6 months of treatment, we observ ed a significant improvement of asthma symptoms (P<0.01), PEF (P<0.01) , diurnal variation of PEF (P<0.05), and airway responsiveness (P<0.05 ) in the BDP group compared with the placebo group. This was accompani ed by a significant decrease in the thickness of the lamina reticulari s (P < 0.001), and in the number of activated eosinophils (P<0.01), T- lymphocytes (P<0.01), and fibroblasts (P < 0.05) in BDP-treated patien ts. There was also a reduction in the expression of insulin-like growt h factor (IGF)-I (P < 0.01). Significant correlation was found between the IGF-I expression and collagen thickening (r(s) = 0.34, P<0.01), a nd the number of fibroblasts (r(s) = 0.45, P<0.01). Conclusion These r esults suggest that corticosteroid treatment in asthma can reduce the lamina reticular thickness by modulation of IGF-I expression with cons equent inhibition of the airway infiltration by inflammatory cells, an d therefore may help to prevent remodelling of the airways.