TY - JOUR
T1 - Airway wall extracellular matrix changes induced by bronchial thermoplasty in severe asthma
AU - Wijsman, Pieta C.
AU - Goorsenberg, Annika W. M.
AU - Keijzer, Noa
AU - d'Hooghe, Julia N. S.
AU - ten Hacken, Nick H. T.
AU - Shah, Pallav L.
AU - Weersink, Els J. M.
AU - de Brito, J. se Mara
AU - de Souza Xavier Costa, Natalia
AU - Mauad, Thais
AU - Nawijn, Martijn C.
AU - Vonk, Judith M.
AU - Annema, Jouke T.
AU - Burgess, Janette K.
AU - Bonta, Peter I.
N1 - Funding Information: This study was supported by the Netherlands Lung Foundation (grant no. 5.2.13.064JO ), Stichting Astma Bestrijding (grant no. 1018/041 ), The Netherlands Organization for Health Research and Development (grant no. 90713477 ), and Boston Scientific Corporation. It was also supported by Nederlandse Organisatie voor Wetenschappelijk Onderzoek Aspasia-premie subsidienummer (grant no. 015.013.010 to J.K.B.). Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Airway remodeling
KW - FEV reversibility
KW - bronchial thermoplasty
KW - collagen
KW - extracellular matrix
KW - fibronectin
KW - severe asthma
UR - http://www.scopus.com/inward/record.url?scp=85175620000&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.jaci.2023.09.035
DO - https://doi.org/10.1016/j.jaci.2023.09.035
M3 - Article
C2 - 37805024
SN - 0091-6749
JO - Journal of allergy and clinical immunology
JF - Journal of allergy and clinical immunology
ER -