title: Metabolomics analysis identifies different metabotypes of asthma severity.
abstract: 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.
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Stacey N
authors.initials: SN
authors.lastname: Reinke
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Héctor
authors.initials: H
authors.lastname: Gallart-Ayala
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.|Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Cristina
authors.initials: C
authors.lastname: Gómez
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.|Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Antonio
authors.initials: A
authors.lastname: Checa
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.|Institute of Environmental Medicine and the Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Alexander
authors.initials: A
authors.lastname: Fauland
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Shama
authors.initials: S
authors.lastname: Naz
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Muhammad Anas
authors.initials: MA
authors.lastname: Kamleh
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK.
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanović
authors.affiliation: Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.|Southampton NIHR Respiratory Biomedical Research Unit, University Hospital Southampton, Southampton, UK.|Dept for Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Australia.
authors.forename: Timothy S C
authors.initials: TS
authors.lastname: Hinks
authors.affiliation: Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden craig.wheelock@ki.se.
authors.forename: Craig E
authors.initials: CE
authors.lastname: Wheelock
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D055442:Metabolome; D055432:Metabolomics; D008875:Middle Aged; D015999:Multivariate Analysis; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones