title: Urinary concentrations of 15-epimer of lipoxin A(4)  are lower in patients with aspirin-intolerant compared with aspirin-tolerant asthma.
abstract: BACKGROUND
  Although an abnormality in arachidonic acid metabolism may be responsible for aspirin-intolerant asthma (AIA), there is little knowledge about the concentrations of urinary lipoxin A(4) (LXA(4)) and the 15-epimer of LXA(4) (15-epi-LXA(4)) in relation to asthma severity in AIA subjects.
  
  
  OBJECTIVE
  The purpose of this study is to estimate urinary LXA(4) and the 15-epimer concentrations to investigate lipoxins in AIA.
  
  
  METHODS
  In this study, we examined AIA, aspirin-tolerant asthma (ATA) and healthy control groups. The AIA and ATA groups were subdivided into the severe asthma and non-severe asthma subgroups. Urinary LXA(4), 15-epi-LXA(4) and leukotriene E(4) (LTE(4) ) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography.
  
  
  RESULTS
  The urinary LXA(4) concentration was significantly lower than the 15-epi-LXA(4) concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA(4) (P < 0.01) and higher urinary LTE(4) concentrations (P < 0.05) than the ATA group. Comparison of 15-epi-LXA(4) concentrations between the severe asthmatic and non-severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15-epi-LXA(4) concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE(4) to 15-epi-LXA(4) was superior to 15-epi-LXA(4) concentration and LTE(4) concentration as a predictive factor for aspirin intolerance.
  
  
  CONCLUSIONS
  We have demonstrated for the first time that urinary 15-epi-LXA(4) concentration is significantly higher than LXA(4) concentration in both the AIA and ATA groups. 15-Epi-LXA(4) concentration was significantly lower in the AIA group with an increased urinary LTE(4) concentration than in the ATA group. An imbalance between proinflammatory cysteinyl-leukotrienes and anti-inflammatory 15-epi-LXA(4) may be involved in AIA pathogenesis.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, Sagamihara, Kanagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: N
authors.initials: N
authors.lastname: Higashi
authors.forename: H
authors.initials: H
authors.lastname: Mita
authors.forename: E
authors.initials: E
authors.lastname: Ono
authors.forename: Y
authors.initials: Y
authors.lastname: Komase
authors.forename: T
authors.initials: T
authors.lastname: Nakagawa
authors.forename: T
authors.initials: T
authors.lastname: Miyazawa
authors.forename: K
authors.initials: K
authors.lastname: Akiyama
authors.forename: M
authors.initials: M
authors.lastname: Taniguchi
mesh_terms: D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects; D055963:Asthma, Aspirin-Induced / Q000209:etiology / Q000652:urine*; D005260:Female; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine; D044045:Lipoxins / Q000652:urine*; D008297:Male; D008875:Middle Aged; D012372:ROC Curve
chemical_list: D044045:Lipoxins; C040527:lipoxin A4; D017999:Leukotriene E4; D001241:Aspirin