Safety of a specific COX-2 inhibitor in aspirin-induced asthma.
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 FEV1 > 20%, and a rise in urinary leukotriene E4 (LTE4) excretion; also in five patients the stable metabolite of PGD2, 9alpha11betaPGF2, 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 9alpha11betaPGF2 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.
Department of Medicine, Jagellonian University School of Medicine, 8 Skawinska Street, 31-066 Cracow, Poland. mmszczek@cyf-kr.edu.pl
A
A
Szczeklik
E
E
Nizankowska
G
G
Bochenek
K
K
Nagraba
F
F
Mejza
M
M
Swierczynska
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects*; D001241:Aspirin / Q000494:pharmacology*; D001249:Asthma / Q000139:chemically induced* / Q000201:enzymology / Q000503:physiopathology; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007783:Lactones / Q000008:administration & dosage / Q000009:adverse effects*; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D015230:Prostaglandin D2 / Q000652:urine; D011451:Prostaglandin-Endoperoxide Synthases; D013450:Sulfones
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D017999:Leukotriene E4; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D015230:Prostaglandin D2