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Medline ® Abstract for Reference 79

of 'Laboratory tests to support the clinical diagnosis of anaphylaxis'

Profile of eicosanoid generation in aspirin-intolerant asthma and anaphylaxis assessed by new biomarkers.
Higashi N, Mita H, Ono E, Fukutomi Y, Yamaguchi H, Kajiwara K, Tanimoto H, Sekiya K, Akiyama K, Taniguchi M
J Allergy Clin Immunol. 2010 May;125(5):1084-1091.e6. Epub 2010 Mar 20.
BACKGROUND: It has recently demonstrated that a free radical-mediated pathway generates prostaglandins (PGs) and the corresponding prostaglandin enantiomers (ent-PGs). Aspirin-intolerant asthma and anaphylaxis accompany PGD(2) overproduction, possibly associated with mast cell activation via the COX pathway. However, free radical-mediated PG generation in the pathophysiology of these diseases, which can be demonstrated by measuring urinary ent-PGF(2)alpha, has not been reported.
OBJECTIVES: To evaluate the characteristic profile of eicosanoid generation via the COX and/or free radical-mediated pathway underlying aspirin-intolerant asthma and anaphylaxis.
METHODS: A comparative group analysis consisted of asthma (n = 17) and anaphylaxis (n = 8, none with aspirin-induced anaphylaxis) cases. Urinary eicosanoid concentrations were quantified as follows: 2,3-dinor-9alpha,11beta-PGF(2) by gas chromatography-mass spectrometry; leukotriene E(4), 9alpha,11beta-PGF(2), and PGs by enzyme immunoassay.
RESULTS: 2,3-Dinor-9alpha,11beta-PGF(2) is a more predominant PGD(2) metabolite in urine than 9alpha,11beta-PGF(2). At baseline, the aspirin-intolerant asthma group (n = 10) had significantly higher leukotriene E(4) and lower PGE(2) concentrations in urine than the aspirin-tolerant asthma group. During the reaction, the urinary concentrations of leukotriene E(4) and PGD(2) metabolites correlatively increased, but with markedly different patterns of the mediator release, in the aspirin-intolerant asthma group and the anaphylaxis group, respectively. The urinary PGD(2) metabolites and primary PGs were significantly decreased in the aspirin-tolerant asthma group. Urinary ent-PGF(2)alpha concentrations were significantly increased in the anaphylaxis group but not the aspirin-intolerant asthma group.
CONCLUSIONS: When assessed by urinary 2,3-dinor-9alpha,11beta-PGF(2), PGD(2) overproduction during aspirin-intolerant bronchoconstriction was clearly identified, regardless of COX inhibition. It is evident that free radical-mediated PG generation is involved in the pathophysiology of anaphylaxis.
Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, Sagamihara, Kanagawa 228-8522, Japan. n-higashi@sagamihara-hosp.gr.jp