Safety of a specific COX-2 inhibitor in aspirin-induced asthma

Background In a subset of patients with asthma, aspirin and several other non-steroidal anti-inflammatory drugs (NSAID) that inhibit simultaneously cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) precipitate dangerous asthmatic attacks. Objective We tested the hypothesis that in patients with aspirin-induced asthma the attacks are triggered by inhibition of COX-1 and not COX-2. Methods and results In twelve asthmatic patients (seven men, five women, average age 39 years) oral aspirin challenge precipitated symptoms of bronchial obstruction with fall in FEV1 > 20%, and a rise in urinary leukotriene E-4 (LTE4) excretion; also in five patients the stable metabolite of PGD(2), 9 alpha 11 beta PGF(2), increased in urine. The patients then entered a double-blind, placebo-controlled, cross-over study in which they received either placebo or rofecoxib in increasing doses 1.5-25.0 mg for 5 consecutive days, separated by a 1-week wash-out period. No patient on rofecoxib developed dyspnoea or fall in FEV1 > 20%; mean urinary LTE4 and 9 alpha 11 beta PGF(2) urinary levels, measured on each study day for 6 h post-dosing, remained unchanged. Two patients on placebo experienced moderate dyspnoea without alterations in urinary metabolites excretion. At least 2 weeks after completion of the study, all patients received on an open basis 25 mg rofecoxib without any adverse effects. Conclusions NSAID that inhibit COX-1, but not COX-2, trigger asthmatic attacks in patients with asthma and aspirin intolerance. Rofecoxib can be administered to patients with aspirin-induced asthma.