Prostaglandins, along with thromboxane and prostacy-clin, are products of arachidonic acid cyclooxygenation. Selective inhibitors of cyclooxygenase-2 - coxibs - were introduced to limit the adverse gastro-intestinal effects of non-steroidal anti-inflammatory drugs (NSAIDs). A distinct phenotype of aspirin-induced asthma (AIA) is accompanied by chronic rhinosinusitis and nasal poly-posis. These patients respond to cyclooxygenase inhibitors with bronchospasm but coxibs are well tolerated In the current issue of the Journal, Daham et al.[l] present the results of a small cross-over study, in which asthmatic subjects received a 5-day course of celecoxib or placebo. Major urinary metabolites of the cyclooxygenase pathway were quantified using liquid chromatography and the tandem mass spectrometry method. The authors found that celecoxib inhibited the systemic biosynthesis of prostaglan-din E_2, but failed to inhibit PGD2 production. The latter was elevated in asthmatics vs. healthy controls. As these results were replicated by a decrease in the urinary prostacyclin metabolite, but no change in the thromboxane metabolite, the conclusion is that most systemic PGD2 biosynthesis is catalysed by the constitutive cyclooxygenase-1.
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