Allergology International
Online ISSN : 1440-1592
Print ISSN : 1323-8930
ISSN-L : 1323-8930
Aspirin-Intolerant Asthma (AIA) Assessment Using the Urinary Biomarkers, Leukotriene E4 (LTE4) and Prostaglandin D2 (PGD2) Metabolites
Noritaka HigashiMasami TaniguchiHaruhisa MitaHiromichi YamaguchiEmiko OnoKazuo Akiyama
Author information

2012 Volume 61 Issue 3 Pages 393-403


The clinical syndrome of aspirin-intolerant asthma (AIA) is characterized by aspirin/nonsteroidal anti-inflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E4 (LTE4) and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD2, at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E2 and 15-epimer of lipoxin A4 at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE4 and PGD2 metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD2 biosynthetic pathway, the precise mechanism underlying the PGD2 overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA.

Information related to the author

This article cannot obtain the latest cited-by information.

© 2012 by Japanese Society of Allergology
Previous article Next article