Background: A special regulatory role for prostaglandin E 2 has been postulated in aspirin-induced asthma. A study was undertaken to investigate the effects of aspirin on the systemic production of prostaglandin E 2 and cysteinyl leucotrienes in patients with asthma. Methods: The urinary concentrations were determined of two main prostaglandin E 2 metabolites (13,14-dihydro15keto-PGE 2 using a commercial enzyme immunoassay and 9,15-dioxo-11a-hydroxy-2,3,4,5-tetranor-prostane-1,20-dioic acid by gas chromatography/mass spectrometry) and leucotriene E 4 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.Results: Aspirin precipitated bronchial reactions in all aspirin-sensitive patients but in none of the aspirintolerant patients. Celecoxib 400 mg was well tolerated by all patients except for one with aspirin-induced asthma. At baseline, the mean levels of prostaglandin E 2 metabolites did not differ between the groups. Following different aspirin provocation doses, the mean levels of the two main prostaglandin E 2 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 E 2 metabolites and its duration. In both groups, urinary prostaglandin E 2 metabolites decreased following celecoxib challenge. No correlation was found between prostaglandin E 2 metabolites and leucotriene E 4 . Conclusions: Aspirin-precipitated asthmatic attacks are not associated with changes in the systemic production of prostaglandin E 2 . In contrast, the systemic production of prostaglandin E 2 becomes depressed by aspirin in nonsensitive patients. This different response might indicate COX-1-dependent prostaglandin E 2 control of inflammatory cells in aspirin-induced asthma. Thus, PGE 2 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 aspirinsensitive patients.Prostaglandin E 2 (PGE 2 ) is a bioactive compound formed by actions of cyclooxygenase (COX) and specific PGE synthases.1 In human airways PGE 2 is produced by many cells including epithelium, smooth muscle, alveolar cells, macrophages, phagocytes and lymphocytes.1 2 In vitro, PGE 2 relaxes smooth muscle and displays a number of inhibitory effects on mast cell degranulation, synthesis of leucotriene B 4 , activation of granulocytes and T cells.3-5 PGE 2 elicits a large number of biological effects acting through four receptors: EP1, EP2, EP3 and EP4. [6][7][8] The response of target cells to PGE 2 varies according to the spectrum of receptors they express.PGE 2 might be of special importance in aspirininduced asthma. This is a distinct clinical syndrome affecting 5-10% of adults with asthma. Asthma attacks trigge...

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Background. Special regulatory role of eicosanoids has been postulated in aspirin-induced asthma. Objective. To investigate effects of aspirin on exhaled breath condensate (EBC) levels of eicosanoids in patients with asthma. Methods. We determined EBC eicosanoid concentrations using gas chromatography/mass spectrometry (GC-MS) and high-performance liquid chromatography/mass spectrometry (HPLC-MS2) or both. Determinations were performed at baseline and following bronchial aspirin challenge, in two well-defined phenotypes of asthma: aspirin-sensitive and aspirin-tolerant patients. Results. Aspirin precipitated bronchial reactions in all aspirin-sensitive, but in none of aspirin-tolerant patients (ATAs). At baseline, eicosanoids profile did not differ between both asthma groups except for lipoxygenation products: 5- and 15-hydroxyeicosatetraenoic acid (5-, 15-HETE) which were higher in aspirin-induced asthma (AIA) than inaspirin-tolerant subjects. Following aspirin challenge the total levels of cysteinyl-leukotrienes (cys-LTs) remained unchanged in both groups. The dose of aspirin had an effect on magnitude of the response of the exhaled cys-LTs and prostanoids levels only in AIA subjects. Conclusion. The high baseline eicosanoid profiling of lipoxygenation products 5- and 15-HETE in EBC makes it possible to detect alterations in aspirin-sensitive asthma. Cysteinyl-leukotrienes, and eoxins levels in EBC after bronchial aspirin administration in stable asthma patients cannot be used as a reliable diagnostic index for aspirin hypersensitivity.

Patients with AIA and ATA react similarly to exercise challenge and obtain similar protection against EIB by montelukast.

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