AIRWAYS REMODELING IS A DISTINCTIVE FEATURE OF ASTHMA AND IS RELATED TO SEVERITY OF DISEASE

Purpose: Airways remodeling, evaluated as the subepithelial layer thic kness, was compared in asthmatic patients with that of healthy subject s, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. Subjects and methods: Thirty-four pat ients with stable asthma (mean age +/- SD: 26.5 +/- 9.2 years; 10 fema le) treated with only inhaled beta(2)-agonists and eight healthy volun teers (mean age +/- SD: 24.6 +/- 2.5 years; four female) were recruite d for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patie nts had newly diagnosed conditions (duration of disease less than or e qual to 1 year), nine patients had long asthmatic history (>1 year and less than or equal to 10 years), and 14 had prolonged asthmatic histo ry (>10 years). Bronchial responsiveness to methacholine (M) was expre ssed as provocative concentration of M causing a 20% fall in FEV1 (PC2 0) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-po int score based on symptoms, bronchodilator use, and daily peak expira tory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelia l layer thickness, in biopsy samples, was measured from the base of br onchial epithelium to the outer limit of reticular lamina. Results: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 7 5.7 to 137.0%, and. PC20 M ranged from 0.15 to 14.4 mg/mL. According t o the asthma severity score, 13 asthmatics were classified as having m ild disease, 14 as having moderate disease, and six as having severe d isease. The mean values of subepithelial layer thickness were 12.4 +/- 3.3 mu m (range, 6.8 to 22.1 mu m) in asthmatics, and 4.4 +/- 0.5 mu m (range, 3.8 to 5.2 mu m) in healthy subjects (p<0.001). Subepithelia l layer thickness of those with severe asthma differed significantly f rom that of patients with moderate and mild asthma (16.7 +/- 3.1 mu m vs 12.1 +/- 2.7 mu m and 10.8 +/- 2.4 mu m, p<0.01 and p<0.003, respec tively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coeffic ient [rs] = 0.581; p<0.001), and negatively correlated with baseline F EV1 (rs = -0.553; p<0.001) and PC20 M (rs = -0.510; p<0.01). No differ ence was found between degree of thickening observed in atopic asthmat ics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. La stly, multiple regression analysis revealed that asthma severity score was the significant predictive factor for thickness of subepithelial layer. Conclusions: We confirmed that airways remodeling is a very dis tinctive and characteristic pathologic finding of asthma. We also demo nstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.