TY - JOUR T1 - Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic JF - ERJ Open Research JO - erjor DO - 10.1183/23120541.LSC-2022.27 VL - 8 IS - suppl 8 SP - 27 AU - Celeste Michala Porsbjerg AU - Juan Jose Nieto-Fontarigo AU - Samuel Cerps AU - Sangheeta Ramu AU - Mandy Menzel AU - Morten Hvidtfeldt AU - Alexander Silberbrandt AU - Laurits Frøssing AU - Ditte Klein AU - Asger Sverrild AU - Lena Uller Y1 - 2022/03/10 UR - http://openres.ersjournals.com/content/8/suppl_8/27.abstract N2 - Background: Asthma is characterized by an aggravated immune response to respiratory viral infections: This phenomenon is a clinically well-recognized driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to virus is unclear.Objectives: To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation.Methods: In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 15 (25%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (TLR3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and anti-viral responses of BECs were analyzed using RT-qPCR and multiplex ELISA and compared across asthma phenotypes and severity of disease.Results: Patients with atopic asthma had increased production of IL-4, IFN-β, IL-6, TNF-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas patients with eosinophilic asthma and non-eosinophilic asthma did not differ in the response to poly (I:C). Patients with severe asthma displayed a decreased antiviral IFN-b, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Interestingly, release of IL-33 and TSLP in response to poly (I:C) was increased in severe eosinophilic asthma, but not in severe atopic asthma.Conclusions: The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severeties. FootnotesCite this article as ERJ Open Research 2022; 8: Suppl. 8, 27.This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only). ER -