PT - JOURNAL ARTICLE AU - Stacey N. Reinke AU - Héctor Gallart-Ayala AU - Cristina Gómez AU - Antonio Checa AU - Alexander Fauland AU - Shama Naz AU - Muhammad Anas Kamleh AU - Ratko Djukanović AU - Timothy S.C. Hinks AU - Craig E. Wheelock TI - Metabolomics analysis identifies different metabotypes of asthma severity AID - 10.1183/13993003.01740-2016 DP - 2017 Mar 01 TA - European Respiratory Journal PG - 1601740 VI - 49 IP - 3 4099 - http://erj.ersjournals.com/content/49/3/1601740.short 4100 - http://erj.ersjournals.com/content/49/3/1601740.full SO - Eur Respir J2017 Mar 01; 49 AB - 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 chromatography–high-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 (p≤0.05). 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=1.7×10−4). 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. oleoylethanolamide, 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.Mild asthma is metabolically distinct from both moderate and severe asthma, and steroid treatment affects metabolism http://ow.ly/EHo7306DwmN