Wijsman PC, Goorsenberg AWM, Keijzer N, d’Hooghe JNS, Ten Hacken NHT, Shah PL, Weersink EJM, de Brito JM, de Souza Xavier Costa N, Mauad T, Nawijn MC, Vonk JM, Annema JT, Burgess JK, Bonta PI. J Allergy Clin Immunol. 2024 Feb;153(2):435-446.e4. doi: 10.1016/j.jaci.2023.09.035.
Background
Airway remodeling is a prominent feature of asthma, which involves increased airway smooth muscle mass and altered extracellular matrix composition. Bronchial thermoplasty (BT), a bronchoscopic treatment for severe asthma, targets airway remodeling.
Objective
We sought to investigate the effect of BT on extracellular matrix composition and its association with clinical outcomes.
Methods
This is a substudy of the TASMA trial. Thirty patients with severe asthma were BT-treated, of whom 13 patients were treated for 6 months with standard therapy (control group) before BT. Demographic data, clinical data including pulmonary function, and bronchial biopsies were collected. Biopsies at BT-treated and nontreated locations were analyzed by histological and immunohistochemical staining. Associations between histology and clinical outcomes were explored.
Results
Six months after treatment, it was found that the reticular basement membrane thickness was reduced from 7.28 μm to 5.74 μm (21% relative reduction) and the percentage area of tissue positive for collagen increased from 26.3% to 29.8% (13% relative increase). Collagen structure analysis revealed a reduction in the curvature frequency of fibers. The percentage area positive for fibulin-1 and fibronectin increased by 2.5% and 5.9%, respectively (relative increase of 124% and 15%). No changes were found for elastin. The changes in collagen and fibulin-1 negatively associated with changes in FEV1 reversibility.
Conclusions
Besides reduction of airway smooth muscle mass, BT has an impact on reticular basement membrane thickness and the extracellular matrix arrangement characterized by an increase in tissue area occupied by collagen with a less dense fiber organization. Both collagen and fibulin-1 are negatively associated with the change in FEV1 reversibility.