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

Abstract

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. We tested the hypothesis that in patients with aspirin‐induced asthma the attacks are triggered by inhibition of COX‐1 and not COX‐2. In twelve asthmatic patients (seven men, five women, average age 39 years) oral aspirin challenge precipitated symptoms of bronchial obstruction with fall in FEV 1 > 20%, and a rise in urinary leukotriene E 4 (LTE 4) excretion; also in five patients the stable metabolite of PGD 2, 9α11βPGF 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 FEV 1 > 20%; mean urinary LTE 4 and 9α11βPGF 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. 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.