Higashi Noritaka, Taniguchi Masami, Mita Haruhisa, Kawagishi Yukio, Ishii Toyota, Higashi Ai, Osame Mitsuhiro, Akiyama Kazuo
Clinical Research Center, National Sagamihara Hospital, Kanagawa, Japan.
J Allergy Clin Immunol. 2004 Feb;113(2):277-83. doi: 10.1016/j.jaci.2003.10.068.
The urinary leukotriene E4 (U-LTE4) concentration is significantly increased in patients with aspirin-intolerant asthma (AIA). However, the relationship between the clinicopathogenetic factors of asthma and the U-LTE4 concentration remains undetermined.
We sought to examine the clinical features of asthmatic patients with increased excretion levels of U-LTE4 (hyperleukotrienuria).
We measured the U-LTE4 concentrations in 137 asthmatic patients (including 64 patients with AIA) who were in clinically stable condition. A U-LTE4 concentration of 150 pg/mg creatinine or greater (mean U-LTE4 + 3 SDs of normal healthy control subjects) was indicative of hyperleukotrienuria.
The basal concentration of U-LTE4 was significantly higher in the patients with AIA than in those with aspirin-tolerant asthma (ATA; median, 227.2 vs 90.3 pg/mg creatinine; P <.01). Compared with normal leukotrienuria in the patients with AIA, hyperleukotrienuria in the patients with AIA was associated with older age and decrease in pulmonary function. On the other hand, compared with normal leukotrienuria in the patients with ATA, hyperleukotrienuria in the patients with ATA was associated with severe asthma and chronic hyperplastic rhinosinusitis with nasal polyposis (CHRS/NP), which are well-known symptoms of the aspirin triad, as well as hypereosinophilia and anosmia. The patients with ATA with CHRS/NP excreted U-LTE4 at significantly high concentrations. There were significant decreases in the U-LTE4 concentrations before and after the sinus surgery in both the AIA and ATA groups (P <.05).
Cysteinyl leukotrienes are not strictly associated with aspirin intolerance itself but rather with clinical features, such as CHRS/NP, that are similar to those seen in AIA. CHRS/NP might be involved in cysteinyl leukotriene overproduction in asthmatic patients.
阿司匹林不耐受性哮喘(AIA)患者的尿白三烯E4(U-LTE4)浓度显著升高。然而,哮喘的临床病理发生因素与U-LTE4浓度之间的关系仍未明确。
我们试图研究U-LTE4排泄水平升高(高白三烯尿症)的哮喘患者的临床特征。
我们测量了137例临床病情稳定的哮喘患者(包括64例AIA患者)的U-LTE4浓度。U-LTE4浓度≥150 pg/mg肌酐(正常健康对照者的平均U-LTE4 + 3个标准差)表明存在高白三烯尿症。
AIA患者的U-LTE4基础浓度显著高于阿司匹林耐受哮喘(ATA)患者(中位数分别为227.2和90.3 pg/mg肌酐;P <.01)。与AIA患者的正常白三烯尿症相比,AIA患者的高白三烯尿症与年龄较大和肺功能下降有关。另一方面,与ATA患者的正常白三烯尿症相比,ATA患者的高白三烯尿症与重度哮喘、伴有鼻息肉的慢性增生性鼻窦炎(CHRS/NP)(阿司匹林三联征的常见症状)、嗜酸性粒细胞增多和嗅觉丧失有关。患有CHRS/NP的ATA患者排泄的U-LTE4浓度显著升高。AIA组和ATA组鼻窦手术后U-LTE4浓度均显著降低(P <.05)。
半胱氨酰白三烯并非严格与阿司匹林不耐受本身相关,而是与CHRS/NP等类似于AIA所见的临床特征相关。CHRS/NP可能参与哮喘患者半胱氨酰白三烯的过度产生。