title: Aspirin-intolerant asthma (AIA) assessment using the urinary biomarkers, leukotriene E4 (LTE4) and prostaglandin D2 (PGD2) metabolites.
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 E(4) (LTE(4)) and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM), a newly identified metabolite of PGD(2), 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 E(2) and 15-epimer of lipoxin A(4) 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 LTE(4) and PGD(2) 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 PGD(2) biosynthetic pathway, the precise mechanism underlying the PGD(2) 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.
authors.affiliation: Clinical Research Center for Allergy and Rheumatology, National Hospital Organization, Sagamihara National Hospital, 18−1 Sakuradai, Minami-ku, Sagamihara, Kanagawa, Japan. n−higashi@sagamihara−hosp.gr.jp
authors.forename: Noritaka
authors.initials: N
authors.lastname: Higashi
authors.forename: Masami
authors.initials: M
authors.lastname: Taniguchi
authors.forename: Haruhisa
authors.initials: H
authors.lastname: Mita
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Yamaguchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Ono
authors.forename: Kazuo
authors.initials: K
authors.lastname: Akiyama
mesh_terms: D055963:Asthma, Aspirin-Induced / Q000175:diagnosis* / Q000652:urine; D015415:Biomarkers; D006801:Humans; D017999:Leukotriene E4 / Q000652:urine*; D015230:Prostaglandin D2 / Q000652:urine*; D011453:Prostaglandins / Q000378:metabolism / Q000652:urine
chemical_list: D015415:Biomarkers; D011453:Prostaglandins; D017999:Leukotriene E4; D015230:Prostaglandin D2