Endobronchial Biopsy: A Guide for Asthma Therapy Selection in the Era of Bronchial Thermoplasty

Abstract

Objective. Bronchial thermoplasty (BT) reduces airway smooth muscle in patients with severe asthma. We developed a novel standardized histologic grading system assessing inflammation and structural remodeling on endobronchial biopsy (EBBx) in severe persistent asthma and evaluated airway structure before and after BT. In addition, we correlated invasive and non-invasive inflammatory markers in severe persistent asthma. Methods. Thirty-three patients with severe persistent asthma underwent bronchoscopy, including bronchoalveolar lavage (BAL) and diagnostic EBBx. The control group (N = 41) underwent EBBx for other clinical indications. Biopsies were graded for airway inflammation and epithelial and submucosal structural features. We also evaluated airway histology in three patients before and after BT. Results. Compared to the control group, patients with severe persistent asthma more often had intraepithelial eosinophils and lymphocytes (67% vs. 17% and 61% vs. 27%; p < .001 and p = .005, respectively) and prominent smooth muscle and goblet cell hyperplasia (88% vs. 29% and 47% vs. 22%, p < .001 and p = .004, respectively). Other features including epithelial denudation and basement membrane thickening were not significantly different. Following BT, airway smooth muscle was no longer prominent due to partial replacement by fibrosis. Increased submucosal eosinophilic inflammation and BAL eosinophilia correlated with exhaled nitric oxide (eNO, p = .05 for both). Conclusions. We developed a clinically applicable standardized histologic grading system which identified structural but not inflammatory changes before and after BT in severe persistent asthmatics. Additionally, we demonstrated that eNO is representative of submucosal eosinophilia in this population. This semi-quantitative assessment will be useful for practicing pathologists assessing EBBx from severe persistent asthma patients for diagnostic and clinical research purposes.