Evidence of remodeling in peripheral airways of patients with mild to moderate asthma: Effect of hydrofluoroalkane-flunisolide

Background: We have shown previously that inflammation in asthma is not restricted to central airways but can also be demonstrated in peripheral airways. It is not clear whether inflammation of the peripheral airways is associated with structural changes and whether this remodeling process can be modulated by deposition of inhaled corticosteroids (ICSs). Objectives: To compare remodeling in peripheral and central airways and to investigate the effects of hydrofluoroalkane (HFA)-ICS on remodeling at these sites. Methods: Transbronchial and endobronchial biopsies were obtained from 12 patients with mild to moderate asthma before and after a 6-week course of HFA-ICS (flunisolide). Total collagen deposition, expression of collagen III, TGF-beta, and alpha-smooth muscle actin were examined by using Van Gieson staining and immunocytochemistry, respectively Results: Total collagen occupied 37.7% of the wall area of peripheral airways, compared with 54.5% of the wall area of central airways (P =.04). There was no significant difference in central versus peripheral airways for collagen III or alpha-smooth muscle actin immunoreactivity and in the number of TGF-beta(+) cells in the submucosa. The only significant effect of HFA-flunisolide was a decrease in alpha-smooth muscle actin area in peripheral airways (13.4% vs 4.6%; P =.01) that correlated with the percentage increase in forced expiratory How at 25% to 75% of vital capacity (r(s) = -1.00; P =.00). Conclusion: Our data show that there is a considerable degree of airway remodeling in peripheral airways in patients with asthma and confirm the inability of ICS to modulate collagen deposition and TGF-beta expression. Treatment with HFA-flunisolide is associated with a significant decrease in the expression of alpha-smooth muscle actin in peripheral airways, which correlated with improvement in peripheral airway function.