Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma
Increased levels of cysteinyl-leukotrienes in saliva, induced sputum, urine and blood from patients with aspirin-intolerant asthma
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DOI：
10.1136/thx.2008.101196
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发表时间：
2008-12-01
期刊：
影响因子：
10
通讯作者：
Dahlen, B.
中科院分区：
文献类型：
--
作者：
Gaber, F.;Daham, K.;Dahlen, B.
背景：诊断阿司匹林不耐受哮喘需要在专科诊所服用阿司匹林。尿白三烯E-4 （LTE4）在阿司匹林不耐受哮喘中升高。通过比较阿司匹林不耐受和阿司匹林耐受哮喘患者唾液、痰液和体外刺激血中半胱氨酸-白三烯（CysLTs）和白三烯B-4 （LTB4）的基础水平，研究阿司匹林不耐受的新生物标志物。我们还比较了阿司匹林和过敏原诱导的支气管收缩对唾液和体外刺激血液中白三烯水平的影响，以及刺激对尿介质的影响。方法：采集21例哮喘患者的诱导痰、唾液、尿液和血液。在另一次访问中，11名受试者对赖氨酸-阿司匹林吸入表现出积极反应，10名受试者对阿司匹林耐受。在挑衅当天还采集了唾液、血液和尿液。分析CysLTs、LTB4及前列腺素D-2代谢物9 α、11 β -前列腺素F-2，测定呼出一氧化氮的含量。结果：与阿司匹林耐受哮喘患者相比，阿司匹林不耐受哮喘患者呼出一氧化氮水平较高，唾液、痰、体外血液和尿液中CysLTs的基线水平较高。两组间LTB4水平无差异。在阿司匹林刺激后，尿LTE4和9 α， 11 β -前列腺素F-2水平升高，而唾液和体外刺激血液中的白三烯水平没有升高。结论：这些发现支持阿司匹林不耐受哮喘中CysLT产生的全局性和特异性增加。唾液中CysLTs的测定有可能成为一种新的、方便的、无创的阿司匹林不耐受哮喘生物标志物。
Background: A diagnosis of aspirin-intolerant asthma requires aspirin provocation in specialist clinics. Urinary leukotriene E-4 (LTE4) is increased in aspirin-intolerant asthma. A study was undertaken to investigate new biomarkers of aspirin intolerance by comparing basal levels of cysteinyl-leukotrienes (CysLTs) and leukotriene B-4 (LTB4) in saliva, sputum and ex vivo stimulated blood in subjects with aspirin-intolerant and aspirin-tolerant asthma. The effects of aspirin-and allergen-induced bronchoconstriction on leukotriene levels in saliva and ex vivo stimulated blood were also compared with the effects of the provocations on urinary mediators.Methods: Induced sputum, saliva, urine and blood were obtained at baseline from 21 subjects with asthma. At a separate visit, 11 subjects showed a positive response to lysine-aspirin inhalation and 10 were aspirin tolerant. Saliva, blood and urine were also collected on the provocation day. Analyses of CysLTs and LTB4 and the prostaglandin D-2 metabolite 9 alpha, 11 beta-prostaglandin F-2 were performed and the fraction of exhaled nitric oxide was measured.Results: Subjects with aspirin-intolerant asthma had higher exhaled nitric oxide levels and higher baseline levels of CysLTs in saliva, sputum, blood ex vivo and urine than subjects with aspirin-tolerant asthma. There were no differences in LTB4 levels between the groups. Levels of urinary LTE4 and 9 alpha, 11 beta-prostaglandin F-2 increased after aspirin provocation whereas leukotriene levels in saliva and ex vivo stimulated blood did not increase.Conclusion: These findings support a global and specific increase in CysLT production in aspirin-intolerant asthma. Measurement of CysLTs in saliva has the potential to be a new and convenient non-invasive biomarker of aspirin-intolerant asthma.