Specificity of basement membrane thickening in severe asthma

Background: Reticular basement membrane (RBM) thickness is considered a hallmark for airway remodeling in airway diseases such as asthma. It is still unclear whether this measurement could be associated with disease severity or apply to chronic obstructive pulmonary disease (COPD). A wide range of results, at baseline or after therapeutic intervention, have been reported using different measurement methods. Objective: To determine whether increased RBM thickness could be associated specifically with severe asthma and in COPD in large samples. Methods: We blindly measured RBM thickness in endobronchial biopsies from 50 patients with severe asthma (mean age, 53 years; FEV1 66% predicted, inhaled steroids >= 1500 mu g and 20 mg daily dose of oral corticosteroids, lifelong nonsmokers), 50 untreated patients with mild asthma mean age, 33 years; FEV, 93%pred, lifelong nonsmokers), 50 patients with COPD (mean age, 57 years; FEV1 53%pred, all current smokers), and 18 control subjects using 2 different validated quantitative and computer-assisted methods (repeated multiple point-to-point vs area by length ratio). Results: Reticular basement membrane thickness was higher in severe asthma compared with mild asthma and COPD (P =.0053). On the basis of receiver operating characteristic curves, RBM thickness was effective in differentiating severe asthma from other groups (sensitivity and specificity, 98% and 95%, respectively, above a threshold of 5 mu m vs control, 70% and 75% at 7 mu m vs mild, 83% and 68% at 6 mu m vs COPD). Conclusion: Increased RBM thickness was specifically associated with severe asthma, whereas surprisingly, COPD and mild asthma had similar remodeling features. Clinical implications: Reticular basement membrane thickness can be considered a hallmark of severe asthma.