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A comparative study of eicosanoid concentrations in sputum and urine in patients with aspirin-intolerant asthma


Noritaka Higashi, MD, Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, 18–1 Sakuradai, Sagamihara, Kanagawa 228–8522, Japan. E-mail:


Background Although many studies have assumed that the overproduction of cysteinyl- leukotrienes (cys-LTs) and an imbalance of arachidonic acid metabolism may be plausible causes for the pathogenesis of aspirin-intolerant asthma (AIA), there has been little experimental evidence to substantiate this notion in lower airways of patients with AIA.

Objectives The purpose of this study was to compare the eicosanoid concentrations in sputum and urine from patients with AIA.

Methods The concentrations of sputum cys-LTs, prostaglandin E2 (PGE2), PGF, PGD2 and thromboxane B2 were measured to assess local concentrations of eicosanoids in patients with AIA and in those with aspirin-tolerant asthma (ATA). The concentrations of two urinary metabolites, leukotriene E4 (LTE4) and 9α11βPGF2, were also measured to corroborate the relationship between the eicosanoid biosynthesis in the whole body and that in lower airways.

Results The concentration of PGD2 in sputum was significantly higher in patients with AIA than in those with ATA (median, 5.3 pg/mL vs. 3.1 pg/mL, P < 0.05), but there was no significant difference in the concentration of the corresponding metabolite, 9α11βPGF2, between the two groups. No differences were noted in the concentrations of other prostanoids in sputum between the two groups. The sputum cys-LT concentrations showed no differences between the two groups, in spite of the observation that the concentration of urinary LTE4 was significantly higher in patients with AIA than in those with ATA (median, 195.2 pg/mg-cre vs. 122.1 pg/mg-cre, P < 0.05). There was a significant correlation among the concentration of cys-LTs, the number of eosinophils and the concentration of eosinophil-derived neurotoxin (EDN) in sputum.

Conclusion The urinary concentration of LTE4 does not necessary reflect cys-LT biosynthesis in lower airways. A significantly higher concentration of PGD2 in sputum from patients with AIA suggests the possible ongoing mast cell activation in lower airways.