Effect of Bronchial Thermoplasty on Alarmin (S100A7/A8/A9) Expression in Severe Asthma.

Abstract

<b>Introduction:</b> Bronchial thermoplasty (BT) is an endoscopic approach to treat uncontrolled severe asthma. BT has been shown to reduce smooth muscle mass, mucin production and subepithelial basement membrane thickness. BT was associated with better asthma control and reduced exacerbations. However, biological mechanisms explaining asthma control improvement following BT are still not well understood. Transcriptomic analysis performed on bronchial epithelial cells (BEC) showed a significant decrease in S100 alarmins post-BT treatment. S100 protein family belongs to the damage-associated molecular patterns. <b>Objective:</b> Evaluation of alarmins expression in BEC obtained from severe asthmatics before and one year post-BT and validation of their expression in bronchial biopsies. <b>Method:</b> BEC and biopsies were collected from severe asthmatics before and more than one year after BT. BEC controls were isolated from participants without asthma or allergy. Alarmins expression was evaluated by immunohistochemistry in bronchial biopsies. Gene expression was assessed by qPCR and proteins by Western blot in BEC. <b>Results:</b> S100A7/A8/A9 genes and proteins are highly expressed in BEC of severe asthmatic patients compared to BEC from controls. BT treatment of severe asthmatics showed a significant decrease in alarmins expression in BEC and in biopsies. Change in S100A7/A8/A9 expression correlates with change in annual exacerbation rate and change in quality of life. <b>Conclusion:</b> BT induces a significant decrease in alarmins expression in severe asthmatic patients which could&nbsp;contribute to better asthma control. S100A7/A8/A9 expression might be useful biomarkers in assessing asthma severity and therapy approaches.