REVIEW ARTICLE
Aspirin-Intolerant Asthma (AIA) Assessment Using the Urinary Biomarkers, Leukotriene E4 (LTE4) and Prostaglandin D2 (PGD2) Metabolites
doi:10.2332/allergolint.11-RA-0403
Noritaka Higashi, Masami Taniguchi, Haruhisa Mita, Hiromichi Yamaguchi, Emiko Ono and Kazuo Akiyama [About this authors]
 ABSTRACT
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.
KEY WORDS:
aspirin, asthma, biomarker, cysteinyl-leukotriene, mast cell, prostaglandin D2, urine
ABBREVIATIONS:
AIA, Aspirin-intolerant asthma; NSAID, Nonsteroidal anti-inflammatory drug; CRSwNP, Chronic rhinosinusitis with nasal polyposis; COX, Cyclooxygenase; CysLT, Cysteinyl-leukotriene; PGD2, Prostaglandin D2; LTE4, Leukotriene E4; HPLC, High-performance liquid chromatography; ATA, Aspirin-tolerant asthma; 15-epi-LXA4, 15-Epimer of lipoxin A4; IgE, Immunoglobulin E; LXA4, Lipoxin A4; 9α,11β-PGF2, 9α,11β-Prostaglandin F2; 2,3-Dinor-9α,11β-PGF2, 2,3-Dinor-9α,11β-prostaglandin F2; Tetranor-PGDM, 11,15-Dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid; EIA, Enzyme immunoassay; ent-PGF2α, Prostaglandin F2α enantiomer; GPCR, G-protein coupled receptors; PPAR-γ, Peroxisome proliferator activated receptor γ; BMMC, Bone marrow-derived mast cell; 15R-PGD2, 15R-methyl-prostaglandin D2; DP2, Prostaglandin D2 receptor 2; GSH, Glutathione.
Received: 22 November 2011.
Accepted: 7 February 2012.
Allergology International : In Press
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