title: Urinary Leukotriene E4 to Determine Aspirin Intolerance in Asthma: A Systematic Review and Meta-Analysis.
abstract: BACKGROUND
  Urinary leukotriene E4 (ULTE4) may be a biomarker that distinguishes aspirin-intolerant asthma from other asthma subtypes.
  
  
  OBJECTIVE
  To estimate the diagnostic testing accuracy of ULTE4 as a marker of aspirin intolerance in patients with asthma using previously published studies.
  
  
  METHODS
  We identified relevant clinical studies from a systematic review of English and non-English articles using MEDLINE, EMBASE, and CENTRAL (inception to February 10, 2015). Articles were screened at the abstract and full-text level by 2 independent reviewers. We included previously published studies that analyzed ULTE4 in human subjects with asthma characterized as having or not having aspirin intolerance on the basis of a specified definition: convincing history of aspirin intolerance, positive aspirin challenge, or both as the criterion standard. Individual-level data points from all included studies were obtained and analyzed.
  
  
  RESULTS
  The search strategy identified 867 potential articles, of which 86 were reviewed at the full-text level and 10 met criteria for inclusion. The sensitivity, specificity, positive predictive value, and negative predictive values of ULTE4 to determine aspirin intolerance in subjects with asthma were 0.55, 0.82, 0.75, and 0.66 (Amersham-enzyme immunoassay); 0.76, 0.77, 0.70, and 0.78 (Cayman-enzyme immunoassay); 0.70, 0.81, 0.86, and 0.79 (mass spectrometry); and 0.81,0.79, 0.65, and 0.88 (radioimmunoassay) at optimal thresholds of 192, 510, 167 to 173, and 66 to 69 pg/mg Cr, respectively. The diagnostic odds ratio for each methodology was 6.0, 11.9, 10.5, and 19.1, respectively.
  
  
  CONCLUSIONS
  ULTE4 is a marker for aspirin-intolerant asthma and could potentially be used as a clinical test to identify the risk of aspirin intolerance in subjects with asthma.
authors.affiliation: Division of Allergic Diseases, Mayo Clinic, Rochester, Minn. Electronic address: hagan.john@mayo.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Hagan
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Mass.
authors.forename: Tanya M
authors.initials: TM
authors.lastname: Laidlaw
authors.affiliation: Division of Allergic Diseases, Mayo Clinic, Rochester, Minn.
authors.forename: Rohit
authors.initials: R
authors.lastname: Divekar
authors.affiliation: Otorhinolaryngology, Head and Neck Surgery, Mayo Clinic, Rochester, Minn.
authors.forename: Erin K
authors.initials: EK
authors.lastname: O'Brien
authors.affiliation: Division of Allergic Diseases, Mayo Clinic, Rochester, Minn; Department of Immunology, Mayo Clinic, Rochester, Minn.
authors.forename: Hirohito
authors.initials: H
authors.lastname: Kita
authors.affiliation: Division of Allergic Diseases, Mayo Clinic, Rochester, Minn.
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Volcheck
authors.affiliation: Department of Biology, Baylor University, Waco, Texas.
authors.forename: Christina R
authors.initials: CR
authors.lastname: Hagan
authors.affiliation: Otorhinolaryngology, Mayo Clinic, Scottsdale, Ariz.
authors.forename: Devyani
authors.initials: D
authors.lastname: Lal
authors.affiliation: Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Ariz.
authors.forename: Harry G
authors.initials: HG
authors.lastname: Teaford
authors.affiliation: Mayo Medical Library, Mayo Clinic, Rochester, Minn.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Erwin
authors.affiliation: Research Biostatistics, Mayo Clinic, Scottsdale, Ariz.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic, Scottsdale, Ariz.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Rank
mesh_terms: D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004342:Drug Hypersensitivity / Q000652:urine*; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*
chemical_list: D015415:Biomarkers; D016861:Cyclooxygenase Inhibitors; D017999:Leukotriene E4; D001241:Aspirin
keywords: Aspirin intolerance; Aspirin-exacerbated respiratory disease; Asthma; Chronic rhinosinusitis; Corticosteroids; Nasal polyps; Urinary leukotriene E4