BRONCHIAL RESPONSIVENESS TO DISTILLED WATER AND METHACHOLINE AND ITS RELATIONSHIP TO INFLAMMATION AND REMODELING OF THE AIRWAYS IN ASTHMA

Although bronchial hyperresponsiveness in asthma is associated with in flammation within the airways, it is not known whether the degree and type of inflammation influence the response to different stimuli and w hether pathologic changes of airway structure influence the bronchocon strictive responses. Therefore, number of inflammatory cells in the ep ithelium and the lamina propria and the basement membrane thickness we re estimated from bronchial biopsies taken in 27 asthmatic subjects (r ange percent predicted FEV(1): 75.6 to 132.1, range of daily PEF varia bility: 1.9% to 20%) and related to the degree of bronchial responsive ness to ultrasonically nebulized distilled water (UNDW) and methacholi ne (M). PD20UNDW (provocative dose) was measurable in 15 of 27 patient s and ranged between 1.01 and 20.4 mi. PC(20)M (provocative concentrat ion) ranged between 0.15 and 31.7 mg/ml. In the 15 responders to UNDW, total inflammatory cells (p < 0.04) and eosinophils (p < 0.015) withi n the epithelium were higher than in 12 nonresponders to UNDW (PD20 > 34.8 mi). There was no correlation between PD20UNDW and any cell count s whereas negative correlations were found between PC(20)M and both to tal inflammatory cells (r(s) = -0.57; p < 0.005) and eosinophils (rs = -0.63; p < 0.0015) within the epithelium. The degree of thickening of subepithelial layer ranged between 7 and 16 mu m (n = 26). Thickness correlates both with total inflammatory cells (r(s) = 0.49; p < 0.025) and eosinophils (r(s) = 0.61; p < 0.003) within the epithelium. Moreo ver, it was correlated with baseline FEV(1) (r(s) = -0.57; p < 0.003) and daily peak expiratory flow (PEF) variability (r(s) = 0.51; p < 0.0 1). A weak but significant correlation was also found between subepith elial layer thickness and PC(20)M (r(s) = -0.42; p < 0.04). The result s of this study demonstrate that eosinophilic inflammation of bronchia l epithelium plays a role in determining UN DW and M responsiveness in asthma. Moreover, they suggest that remodeling of the airways such as thickening of subepithelial layer correlates with indices of asthma s everity and could contribute to the degree of M but not to UNDW respon siveness.