Airways remodeling is a distinctive feature of asthma and is related to severity of disease

Purpose: Airways remodeling, evaluated as the subepithelial layer thickness, was compared in asthmatic patients with that of healthy subjects, and was related to clinical grading of disease, presence of atopy, and length of asthmatic history. Subjects and methods: Thirty-four patients with stable asthma (mean age +/- SD: 26.5 +/- 9.2 years; 10 female) treated with only inhaled beta(2)-agonists and eight healthy volunteers (mean age +/- SD: 24.6 +/- 2.5 years; four female) were recruited for the study. Twenty-seven of 34 asthmatics had atopy. Eleven patients had newly diagnosed conditions (duration of disease less than or equal to 1 year), nine patients had long asthmatic history (>1 year and less than or equal to 10 years), and 14 had prolonged asthmatic history (>10 years). Bronchial responsiveness to methacholine (M) was expressed as provocative concentration of M causing a 20% fall in FEV1 (PC20) (mg/mL). Degree of asthma severity was assessed using a 0- to 12-point score based on symptoms, bronchodilator use, and daily peak expiratory flow variability over a 3-week period. Bronchoscopy and bronchial biopsy were performed successfully for all subjects; the subepithelial layer thickness, in biopsy samples, was measured from the base of bronchial epithelium to the outer limit of reticular lamina. Results: In asthmatics, baseline FEV1 values (percent of predicted) ranged from 75.7 to 137.0%, and. PC20 M ranged from 0.15 to 14.4 mg/mL. According to the asthma severity score, 13 asthmatics were classified as having mild disease, 14 as having moderate disease, and six as having severe disease. 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). Subepithelial layer thickness of those with severe asthma differed significantly from 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, respectively). Moreover, in asthmatics, degree of thickening was positively correlated to asthma severity score (Spearman rank correlation coefficient [rs] = 0.581; p<0.001), and negatively correlated with baseline FEV1 (rs = -0.553; p<0.001) and PC20 M (rs = -0.510; p<0.01). No difference was found between degree of thickening observed in atopic asthmatics, compared with that of nonatopic asthmatics, or between degree of thickening in patients with different lengths of asthmatic history. Lastly, 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 distinctive and characteristic pathologic finding of asthma. We also demonstrated that it is related to the clinical and functional severity of asthma, but not to atopy or length of asthmatic history.