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

Background In a subset of patients with asthma, aspirin and several other n on-steroidal anti-inflammatory drugs (NSAID) that inhibit simultaneously cy clooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) precipitate dangerous a sthmatic attacks. Objective We tested the hypothesis that in patients with aspirin-induced as thma the attacks are triggered by inhibition of COX-1 and not COX-2. Methods and results In twelve asthmatic patients (seven men, five women, av erage age 39 years) oral aspirin challenge precipitated symptoms of bronchi al 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 do uble-blind, placebo-controlled, cross-over study in which they received eit her 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 develo ped dyspnoea or fall in FEV1 > 20%; mean urinary LTE4 and 9 alpha 11 beta P GF(2) urinary levels, measured on each study day for 6 h post-dosing, remai ned unchanged. Two patients on placebo experienced moderate dyspnoea withou t alterations in urinary metabolites excretion. At least 2 weeks after comp letion 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 atta cks in patients with asthma and aspirin intolerance. Rofecoxib can be admin istered to patients with aspirin-induced asthma.