Higashi N, Taniguchi M, Mita H, Osame M, Akiyama K
Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, Sagamihara, Kanagwa, Japan.
Clin Exp Allergy. 2002 Oct;32(10):1484-90. doi: 10.1046/j.1365-2745.2002.01507.x.
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.
The purpose of this study was to compare the eicosanoid concentrations in sputum and urine from patients with AIA.
The concentrations of sputum cys-LTs, prostaglandin E2 (PGE2), PGF2alpha, 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 9alpha11betaPGF2, were also measured to corroborate the relationship between the eicosanoid biosynthesis in the whole body and that in lower airways.
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, 9alpha11betaPGF2, 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.
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.
尽管许多研究认为半胱氨酰白三烯（cys-LTs）产生过多以及花生四烯酸代谢失衡可能是阿司匹林不耐受性哮喘（AIA）发病机制的合理原因，但几乎没有实验证据能在AIA患者的下呼吸道证实这一观点。
本研究旨在比较AIA患者痰液和尿液中类花生酸的浓度。
测量AIA患者和阿司匹林耐受型哮喘（ATA）患者痰液中cys-LTs、前列腺素E2（PGE2）、PGF2α、PGD2和血栓素B2的浓度，以评估类花生酸的局部浓度。还测量了两种尿液代谢产物白三烯E4（LTE4）和9α11βPGF2的浓度，以证实全身类花生酸生物合成与下呼吸道类花生酸生物合成之间的关系。
AIA患者痰液中PGD2的浓度显著高于ATA患者（中位数，5.3 pg/mL对3.1 pg/mL，P<0.05），但两组中相应代谢产物9α11βPGF2的浓度无显著差异。两组痰液中其他前列腺素的浓度无差异。尽管观察到AIA患者尿液中LTE4的浓度显著高于ATA患者（中位数，195.2 pg/mg-cre对122.1 pg/mg-cre，P<0.05），但两组痰液中cys-LT的浓度无差异。痰液中cys-LTs的浓度、嗜酸性粒细胞数量和嗜酸性粒细胞衍生神经毒素（EDN）的浓度之间存在显著相关性。
尿液中LTE4的浓度不一定反映下呼吸道中cys-LT的生物合成。AIA患者痰液中PGD2的浓度显著升高表明下呼吸道可能存在肥大细胞持续激活。
