title: Metabolomic analysis identifies potential diagnostic biomarkers for aspirin-exacerbated respiratory disease.
abstract: To date, there has been no reliable in vitro test to diagnose aspirin-exacerbated respiratory disease (AERD).
  
  
  
  To investigate potential diagnostic biomarkers for AERD using metabolomic analysis.
  
  
  
  An untargeted profile of serum from asthmatics in the first cohort (group 1) comprising 45 AERD, 44 patients with aspirin-tolerant asthma (ATA), and 28 normal controls was developed using the ultra-high-performance liquid chromatography (UHPLC)/Q-ToF MS system. Metabolites that discriminate AERD from ATA were quantified in both serum and urine, which were collected before (baseline) and after the lysine-aspirin bronchoprovocation test (Lys-ASA BPT). The serum metabolites were validated in the second cohort (group 2) comprising 50 patients with AERD and 50 patients with ATA.
  
  
  
  A clear discrimination of metabolomes was found between patients with AERD and ATA. In group 1, serum levels of LTE4and LTE4/PGF2α ratio before and after the Lys-ASA BPT were significantly higher in patients with AERD than in patients with ATA (P < 0.05 for each), and urine baseline levels of these two metabolites were significantly higher in patients with AERD. Significant differences of serum metabolite levels between patients with AERD and ATA were replicated in group 2 (P < 0.05 for each). Moreover, serum baseline levels of LTE4and LTE4/PGF2α ratio discriminated AERD from ATA with 70.5%/71.6% sensitivity and 41.5%/62.8% specificity, respectively (AUC = 0.649 and 0.732, respectively P < 0.001 for each). Urine baseline LTE4levels were significantly correlated with the fall in FEV1% after the Lys-ASA BPT in patients with AERD (P = 0.008, r = 0.463).
  
  
  
  Serum metabolite level of LTE4and LTE4/PGF2α ratio was identified as potential in vitro diagnostic biomarkers for AERD using the UHPLC/Q-ToF MS system, which were closely associated with major pathogenetic mechanisms underlying AERD.
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: G-Y
authors.initials: GY
authors.lastname: Ban
authors.affiliation: Department of Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.|Department of Biomedical Science, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: K
authors.initials: K
authors.lastname: Cho
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: M K
authors.initials: MK
authors.lastname: Yoon
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: J-H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Statistics, Clinical Trial Center, Ajou University Medical Center, Suwon, Korea.
authors.forename: H Y
authors.initials: HY
authors.lastname: Lee
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Y S
authors.initials: YS
authors.lastname: Shin
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: Y-M
authors.initials: YM
authors.lastname: Ye
authors.affiliation: Department of Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: J-Y
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors.forename: H-S
authors.initials: HS
authors.lastname: Park
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D055963:Asthma, Aspirin-Induced / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000378:metabolism*; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D008875:Middle Aged; D009504:Neutrophils; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018836:Inflammation Mediators; D007073:Immunoglobulin E
keywords: aspirin-exacerbated respiratory disease; biomarker; serum LTE4