Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation
Prostaglandin E2 and cysteinyl leukotriene concentrations in sputum: association with asthma severity and eosinophilic inflammation
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DOI：
10.1111/j.1365-2222.2009.03386.x
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发表时间：
2010-01-01
影响因子：
6.1
通讯作者：
Misso, N. L.
中科院分区：
文献类型：
--
作者：
Aggarwal, S.;Moodley, Y. P.;Misso, N. L.
P>背景哮喘气道炎症与半胱氨酰白三烯 (cysLT)、前列腺素 (PG)E-2、8-异前列腺素、一氧化氮和其他介质的产生有关。然而，哮喘严重程度或嗜酸性粒细胞炎症与痰中介质浓度之间的关系尚不清楚。 目的评估不同严重程度的哮喘和哮喘患者的痰中PGE(2)、cysLT、8-异前列腺素和硝酸盐浓度，以及尿白三烯(LT)E-4和9α、11β-前列腺素(PG)F-2浓度。方法对 12 名轻度哮喘患者、14 名中度哮喘患者和 12 名重度持续性哮喘患者以及 13 名对照受试者的痰中炎症细胞进行了评估。哮喘患者分为嗜酸性粒细胞性或非嗜酸性粒细胞性气道炎症。在免疫亲和吸附剂上提取痰液PGE(2)、cysLT和8-异前列腺素以及尿液LTE4，并使用酶免疫测定法测量所有介质的浓度。在化学发光分析仪上测量痰液硝酸盐浓度。结果与对照组 (827 pg/mL) 相比，中度哮喘 (1710 pg/mL) 和重度哮喘 (1590 pg/mL) 的痰液 PGE(2) 浓度均较高 (P < 0.05)。与对照组或重度哮喘受试者相比，中度哮喘受试者的 CysLT 浓度较高（P < 0.05）。与非嗜酸性气道炎症患者 (2520 pg/mL) 相比，嗜酸性粒细胞性气道炎症患者的痰 PGE(2) 浓度 (1180 pg/mL) 较低 (P=0.02)。相反，嗜酸性气道炎症患者的痰 cysLT 和尿 LTE4 浓度较高（P < 0.05）。所有哮喘患者1 s用力呼气量与痰嗜酸性粒细胞呈负相关（r(s)=-0.5，P=0.002）。痰中 8-异前列烷或硝酸盐浓度没有显着差异。结论 PGE(2) 气道浓度增加与 PGE(2) 在较严重哮喘患者中具有支气管保护和抗炎作用的假设一致。气道中 PGE(2) 与 cysLT 比率降低可能会对肺功能产生不利影响，并导致嗜酸性粒细胞性气道炎症患者症状持续和气道重塑。引用此为：S. Aggarwal、Y. P. Moodley、P. J. Thompson 和 N. L. Misso，临床与实验过敏，2010 (40) 85-93。
P>BackgroundInflammation of the airways in asthma is associated with the production of cysteinyl leukotrienes (cysLT), prostaglandin (PG)E-2, 8-isoprostane, nitric oxide and other mediators. However, the relationship between asthma severity or eosinophilic inflammation and the concentrations of mediators in sputum is unclear.ObjectiveTo assess sputum PGE(2), cysLT, 8-isoprostane and nitrate concentrations, as well as urinary leukotriene (LT)E-4 and 9 alpha,11 beta-prostaglandin (PG)F-2 concentrations, in patients with differing severities of asthma and eosinophilic or non-eosinophilic airway inflammation.MethodsInflammatory cells in sputum were assessed in 12 patients with mild, 14 with moderate and 12 with severe persistent asthma, as well as in 13 control subjects. Asthmatic patients were categorized into those with eosinophilic or non-eosinophilic airway inflammation. Sputum PGE(2), cysLT and 8-isoprostane, and urinary LTE4 were extracted on immunoaffinity sorbents, and the concentrations of all mediators were measured using enzyme immunoassays. Sputum nitrate concentrations were measured on a chemiluminescence analyzer.ResultsSputum PGE(2) concentrations were higher in both moderate (1710 pg/mL) and severe asthmatic (1590 pg/mL) compared with control subjects (827 pg/mL) (P < 0.05). CysLT concentrations were higher in moderate asthmatic compared with control or severe asthmatic subjects (P < 0.05). Sputum PGE(2) concentrations were lower in patients with eosinophilic (1180 pg/mL) compared with non-eosinophilic airway inflammation (2520 pg/mL) (P=0.02). In contrast, sputum cysLT and urinary LTE4 concentrations were higher in those with eosinophilic airway inflammation (P < 0.05). Forced expiratory volume in 1 s was inversely correlated with sputum eosinophils in all asthmatic patients (r(s)=-0.5, P=0.002). There were no significant differences in sputum 8-isoprostane or nitrate concentrations.ConclusionsIncreased airway concentrations of PGE(2) are consistent with the hypothesis that PGE(2) has a bronchoprotective and anti-inflammatory role in patients with more severe asthma. A reduced PGE(2) to cysLT ratio in the airways may adversely affect lung function and contribute to persistence of symptoms and airway remodelling in patients with eosinophilic airway inflammation.Cite this as: S. Aggarwal, Y. P. Moodley, P. J. Thompson and N. L. Misso, Clinical & Experimental Allergy, 2010 (40) 85-93.