Metabolic Differences In Bronchial Epithelium From Asthma Patients And Impact Of Bronchial Thermoplasty

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.