Abstract

Background: 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.

Methods: 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-11α-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.

Results: 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.

Conclusions: 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.