Metabolic differences between bronchial epithelium from healthy individuals and asthma patients and the effect of bronchial thermoplasty

Abstract Background Asthma is a heterogeneous disease with differences in onset, severity and inflammation. Bronchial epithelial cells (BEC) contribute to asthma pathophysiology. Objective We determined whether transcriptomes of BEC reflect heterogeneity in inflammation and severity in asthma, and whether this was affected in BEC in severe asthma after their regeneration by bronchial thermoplasty. Methods RNA-sequencing was performed on BEC obtained by bronchoscopy from healthy controls (n=16), mild (n=17), moderate (n=5) and severe (n=17) asthma patients and, from the latter, also 6 months after bronchial thermoplasty from treated and untreated airways (n=23). Lipidome and metabolome analyses were performed on cultured BEC from healthy controls (n=7), severe asthmatics (n=9) and, for comparison, COPD patients (n=7). Results Transcriptome analysis of BEC from patients showed a reduced expression of oxidative phosphorylation (OXPHOS) genes, most profoundly in severe asthma, but less and more heterogeneous in mild asthma. Genes related to fatty acid metabolism were significantly upregulated in asthma. Lipidomics revealed enhanced levels of lipid species (phosphatidylcholines, lysophosphatidylcholines and bis(monoacylglycerol)phosphate), whereas OXPHOS metabolites were reduced in BEC from severe asthma patients. BEC from mild asthma patients characterised by hyperresponsive production of mediators implicated in neutrophilic inflammation had decreased OXPHOS genes compared to that from mild patients with normoresponsive production. BEC obtained after thermoplasty had significantly increased expression of OXPHOS genes and decreased expression of fatty acid metabolism genes compared to BEC obtained from untreated airways. Conclusion In asthma, BECs are metabolically different from those of healthy individuals. These differences link with inflammation, asthma severity and can be reversed by bronchial thermoplasty.