Mastalerz L, Sanak M, Gawlewicz-Mroczka A, Gielicz A, Cmiel A, Szczeklik A
Jagiellonian University, School of Medicine, Department of Medicine, ul. Skawinska 8, 31-066 Krakow, Poland.
Thorax. 2008 Jan;63(1):27-34. doi: 10.1136/thx.2007.080903. Epub 2007 Jun 21.
A special regulatory role for prostaglandin E2 has been postulated in aspirin-induced asthma. A study was undertaken to investigate the effects of aspirin on the systemic production of prostaglandin E2 and cysteinyl leucotrienes in patients with asthma.
The urinary concentrations were determined of two main prostaglandin E2 metabolites (13,14-dihydro-15keto-PGE2 using a commercial enzyme immunoassay and 9,15-dioxo-11alpha-hydroxy-2,3,4,5-tetranor-prostane-1,20-dioic acid by gas chromatography/mass spectrometry) and leucotriene E4 using an immunoassay. Determinations were performed at baseline and following oral aspirin and celecoxib challenges in two well-defined asthma phenotypes: aspirin-sensitive and aspirin-tolerant patients.
Aspirin precipitated bronchial reactions in all aspirin-sensitive patients but in none of the aspirin-tolerant patients. Celecoxib 400 mg was well tolerated by all patients except for one with aspirin-induced asthma. At baseline, the mean levels of prostaglandin E2 metabolites did not differ between the groups. Following different aspirin provocation doses, the mean levels of the two main prostaglandin E2 metabolites were decreased in the aspirin-tolerant group but remained unchanged in the aspirin-sensitive group. The dose of aspirin had no effect on the magnitude of the response on the prostaglandin E2 metabolites and its duration. In both groups, urinary prostaglandin E2 metabolites decreased following celecoxib challenge. No correlation was found between prostaglandin E2 metabolites and leucotriene E4.
Aspirin-precipitated asthmatic attacks are not associated with changes in the systemic production of prostaglandin E2. In contrast, the systemic production of prostaglandin E2 becomes depressed by aspirin in non-sensitive patients. This different response might indicate COX-1-dependent prostaglandin E2 control of inflammatory cells in aspirin-induced asthma. Thus, PGE2 is released during the clinical reactions to aspirin through an alternative COX-2 pathway. The clinical implications of this finding are in line with current observations of good tolerance of the selective COX-2 inhibitors in aspirin-sensitive patients.
在阿司匹林诱发的哮喘中，有人假定前列腺素E2具有特殊的调节作用。开展了一项研究，以调查阿司匹林对哮喘患者体内前列腺素E2和半胱氨酰白三烯全身生成的影响。
采用商业酶免疫测定法测定两种主要前列腺素E2代谢物（13,14-二氢-15-酮-PGE2）的尿浓度，并通过气相色谱/质谱法测定9,15-二氧代-11α-羟基-2,3,4,5-四去甲前列腺烷-1,20-二酸的尿浓度，同时采用免疫测定法测定白三烯E4的尿浓度。在两种明确的哮喘表型（阿司匹林敏感型和阿司匹林耐受型患者）的基线期以及口服阿司匹林和塞来昔布激发后进行测定。
阿司匹林在所有阿司匹林敏感型患者中引发了支气管反应，但在阿司匹林耐受型患者中均未引发。除一名阿司匹林诱发哮喘患者外，所有患者对400 mg塞来昔布耐受性良好。在基线期，两组间前列腺素E2代谢物的平均水平无差异。在给予不同剂量的阿司匹林激发后，阿司匹林耐受组中两种主要前列腺素E2代谢物的平均水平降低，但阿司匹林敏感组中保持不变。阿司匹林剂量对前列腺素E2代谢物的反应幅度及其持续时间无影响。在两组中，塞来昔布激发后尿中前列腺素E2代谢物均降低。未发现前列腺素E2代谢物与白三烯E4之间存在相关性。
阿司匹林诱发的哮喘发作与前列腺素E2全身生成的变化无关。相反，在非敏感患者中，阿司匹林会使前列腺素E2的全身生成受到抑制。这种不同的反应可能表明在阿司匹林诱发的哮喘中，前列腺素E2通过COX-1依赖途径控制炎症细胞。因此，在对阿司匹林的临床反应过程中，PGE2通过另一种COX-2途径释放。这一发现的临床意义与目前观察到的选择性COX-2抑制剂在阿司匹林敏感型患者中耐受性良好的情况相符。
