Biochemical and clinical evidence that aspirin-intolerant asthmatic subjects tolerate the cyclooxygenase 2-selective analgetic drug celecoxib.
BACKGROUND
Subjects with aspirin-intolerant asthma (AIA) respond with bronchoconstriction and extrapulmonary adverse reactions to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) that inhibit the cyclooxygenase (COX) step in the biosynthesis of prostaglandins. Recently, 2 isotypes of COX have been identified, and COX-2-selective NSAIDs have been developed for treatment of inflammatory disorders.


OBJECTIVE
We investigated whether 33 subjects with a typical history of AIA tolerated the new COX-2-selective NSAID celecoxib.


METHODS
All subjects displayed current aspirin sensitivity in oral or inhalation challenge tests. The subjects first underwent a double-blind, randomized, cross-over, increasing-dose challenge with placebo or celecoxib (10, 30, or 100 mg in suspension) on 2 occasions 7 days apart. Thereafter, all subjects were exposed to 400 mg of celecoxib administered during an open challenge session as two 200-mg doses 2 hours apart. Lung function, clinical symptoms, and urinary excretion of leukotriene E(4) (LTE(4)) were monitored, with the latter being a sensitive biochemical marker of aspirin intolerance.


RESULTS
There were no changes in lung function or extrapulmonary symptoms during the double-blind sessions or in urinary excretion of LTE(4). Also, the highest recommended daily dose of celecoxib was well tolerated, with no symptoms, lung function changes, or alterations in urinary LTE(4) levels.


CONCLUSIONS
A group of subjects with clinically well-documented AIA tolerated acute challenge with the selective COX-2 inhibitor celecoxib. The findings indicate that the intolerance reaction in AIA is due to inhibition of COX-1. Large long-term studies of COX-2 inhibitors in AIA should be undertaken.
Division of Respiratory Medicine, Department of Medicine at Karolinska Hospital, Karolinska Institutet, Stockholm, Sweden.
Pär
P
Gyllfors
Grazyna
G
Bochenek
John
J
Overholt
Diane
D
Drupka
Maria
M
Kumlin
James
J
Sheller
Ewa
E
Nizankowska
Peter C
PC
Isakson
Filip
F
Mejza
James B
JB
Lefkowith
Sven-Erik
SE
Dahlén
Andrew
A
Szczeklik
John J
JJ
Murray
Barbro
B
Dahlén
D000328:Adult; D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000276:immunology; D000068579:Celecoxib; D018592:Cross-Over Studies; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D017999:Leukotriene E4 / Q000652:urine; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D011451:Prostaglandin-Endoperoxide Synthases; D011720:Pyrazoles; D013449:Sulfonamides / Q000009:adverse effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D017999:Leukotriene E4; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D000068579:Celecoxib; D001241:Aspirin