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Background: Phenotypes and endotypes predicting optimal response to bronchial thermoplasty (BT) in patients with severe asthma remain elusive., Objective: Our aim was to compare the clinical characteristics and hallmarks of airway inflammation and remodeling before and after BT in responder and partial responder patients with severe asthma refractory to oral steroids and to omalizumab., Methods: In all, 23 patients with severe refractory asthma were divided into BT responders (n = 15) and BT partial responders (n = 8), according to the decrease in asthma exacerbations at 12 months after BT. Clinical parameters were compared at baseline and 12 months after BT, and hallmarks of airway inflammation and remodeling were analyzed by immunohistochemistry in bronchial biopsy specimens before and 3 months after BT., Results: At baseline, the BT responders were around 8 years younger than the BT partial responders (P = .02) and they had a greater incidence of atopy, higher numbers of blood eosinophils (both P = .03) and IgE levels, higher epithelial IFN-α expression, and higher numbers of mucosal eosinophils and IL-33-positive cells (P ≤ .05). A reduction in blood eosinophil count, serum IgE level, type 2 airway inflammation, and numbers of mucosal IL-33-positive cells and mast cells associated with augmented epithelial MUC5AC and IFN-α/β immunostaining was noted after BT in responders, whereas the numbers of mucosal IL-33-positive cells were augmented in BT partial responders. Most of these changes were correlated with clinical parameters. Subepithelial membrane thickening and airway smooth muscle area were similar in the 2 patient groups at baseline and after BT., Conclusion: By reducing allergic type 2 inflammation and increasing epithelial MUC5AC and anti-viral IFN-α/β expression, BT may enhance host immune responses and thus attenuate exacerbations and symptoms in BT responders. Instead, targeting IL-33 may provide a clinical benefit in BT partial responders., (Copyright © 2021 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)