We hereby declare no financial relationship with any technological and/or pharmaceutical manufacturer that has interest in the subject matter or materials discussed in this manuscript.
Urinary concentrations of 15-epimer of lipoxin A4 are lower in patients with aspirin-intolerant compared with aspirin-tolerant asthma
Article first published online: 22 AUG 2011
© 2011 Blackwell Publishing Ltd
Clinical & Experimental Allergy
Volume 41, Issue 12, pages 1711–1718, December 2011
How to Cite
- Issue published online: 23 NOV 2011
- Article first published online: 22 AUG 2011
- Manuscript Accepted: 22 JUN 2011
- Manuscript Revised: 5 MAY 2011
- Manuscript Received: 17 JAN 2011
- Ministry of Health, Labour and Welfare of Japan
- 15-epimer of lipoxin A4;
- aspirin-intolerant asthma;
- asthma severity;
- leukotriene E4;
- lipoxin A4
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 A4 (LXA4) and the 15-epimer of LXA4 (15-epi-LXA4) in relation to asthma severity in AIA subjects.
The purpose of this study is to estimate urinary LXA4 and the 15-epimer concentrations to investigate lipoxins in AIA.
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 LXA4, 15-epi-LXA4 and leukotriene E4 (LTE4) were quantified using enzyme immunoassay after separating these compounds using high-performance liquid chromatography.
The urinary LXA4 concentration was significantly lower than the 15-epi-LXA4 concentration in the asthmatic subjects. The AIA group showed significantly lower urinary 15-epi-LXA4 (P < 0.01) and higher urinary LTE4 concentrations (P < 0.05) than the ATA group. Comparison of 15-epi-LXA4 concentrations between the severe asthmatic and non-severe asthmatic subjects in the AIA and ATA groups revealed that the decreased 15-epi-LXA4 concentration may be related to aspirin intolerance, but not asthma severity. Receiver operator characteristic curves demonstrated that the concentration ratio of LTE4 to 15-epi-LXA4 was superior to 15-epi-LXA4 concentration and LTE4 concentration as a predictive factor for aspirin intolerance.
Conclusions and Clinical Relevance
We have demonstrated for the first time that urinary 15-epi-LXA4 concentration is significantly higher than LXA4 concentration in both the AIA and ATA groups. 15-Epi-LXA4 concentration was significantly lower in the AIA group with an increased urinary LTE4 concentration than in the ATA group. An imbalance between proinflammatory cysteinyl-leukotrienes and anti-inflammatory 15-epi-LXA4 may be involved in AIA pathogenesis.