Metabolomics analysis identifies different metabotypes of asthma severity

[摘要] In this study; we sought to determine whether asthma has a metabolic profile and whether this profile is related to disease severity.We characterised the serum from 22 healthy individuals and 54 asthmatics (12 mild; 20 moderate; 22 severe) using liquid chromatographyxe2x80x93high-resolution mass spectrometry-based metabolomics. Selected metabolites were confirmed by targeted mass spectrometry assays of eicosanoids; sphingolipids and free fatty acids.We conclusively identified 66 metabolites; 15 were significantly altered with asthma (pxe2x89xa40.05). Levels of dehydroepiandrosterone sulfate; cortisone; cortisol; prolylhydroxyproline; pipecolate and N-palmitoyltaurine correlated significantly (p<0.05) with inhaled corticosteroid dose; and were further shifted in individuals treated with oral corticosteroids. Oleoylethanolamide increased with asthma severity independently of steroid treatment (p<0.001). Multivariate analysis revealed two patterns: 1) a mean difference between controls and patients with mild asthma (p=0.025); and 2) a mean difference between patients with severe asthma and all other groups (p=1.7xc3x9710xe2x88x924). Metabolic shifts in mild asthma; relative to controls; were associated with exogenous metabolites (e.g. dietary lipids); while those in moderate and severe asthma (e.g.xc2xa0oleoylethanolamide; sphingosine-1-phosphate; N-palmitoyltaurine) were postulated to be involved in activating the transient receptor potential vanilloid type 1 (TRPV1) receptor; driving TRPV1-dependent pathogenesis in asthma.Our findings suggest that asthma is characterised by a modest systemic metabolic shift in a disease severity-dependent manner; and that steroid treatment significantly affects metabolism.

[学科分类] 呼吸医学