TY - JOUR T1 - Metabolic differences in bronchial epithelium from asthma patients and impact of bronchial thermoplasty JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.congress-2020.3706 VL - 56 IS - suppl 64 SP - 3706 AU - Abilash Ravi AU - Annika Goorsenberg AU - Annemiek Dijkhuis AU - Barbara Dierdorp AU - Tamara Dekker AU - Yanaika Sabogal Piñeros AU - Peter J. Sterk AU - Frédéric Vaz AU - Jouke Annema AU - Peter Bonta AU - Rene Lutter Y1 - 2020/09/07 UR - http://erj.ersjournals.com/content/56/suppl_64/3706.abstract N2 - Introduction: Bronchial epithelial cells (BECs) contribute to asthma pathophysiology. Does the transcriptome of BECs reflect heterogeneity in inflammation, treatment response and severity in asthma?Methods: RNA-sequencing was performed on bronchoscopic brush-derived BECs from mild (n=17), moderate (n=5), severe (n=17) asthma patients and healthy controls (n=16), and on BECs obtained after bronchial thermoplasty in severe asthma (n=23). Cultured BECs from severe asthma (n=9) with healthy controls (n=7) were analysed for lipidome and metabolome.Results: Compared to BECs from healthy controls, transcriptome analysis in BECs from all patients showed a reduction in oxidative phosphorylation (OXPHOS) genes, most profoundly in severe asthma but less and more heterogeneous in mild asthma. Genes related to glycolysis were significantly upregulated in BECs from all patients. Functional validation with lipidomics also revealed enhanced levels of lipid species (phosphatidyl choline, lyso phosphatidylcholine and bis (monoacylglycero) phosphate), whereas metabolites were reduced trend-wise only in BECs from severe asthma patients compared to healthy controls. Mild asthma patients characterised by hyperresponsive production of neutrophilic mediators by BECs (Ravi, A. et al. ERJ 2019; 15:2) had decreased OXPHOS genes as compared to patient’s BECs with normoresponsive production. Bronchial thermoplasty normalized OXPHOS and glycolysis gene expression in PBECs from severe asthma patients.Conclusions: BECs in asthma are metabolically different from those of healthy individuals. These differences link with asthma severity and can be reversed by bronchial thermoplasty.FootnotesCite this article as: European Respiratory Journal 2020; 56: Suppl. 64, 3706.This abstract was presented at the 2020 ERS International Congress, in session “Respiratory viruses in the "pre COVID-19" era”.This is an ERS International Congress 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 -