Correspondence

Celecoxib in Patients with Asthma and Aspirin Intolerance

N Engl J Med 2001; 344:142January 11, 2001

Article

To the Editor:

In some patients with asthma, the administration of aspirin and other nonsteroidal antiinflammatory drugs (NSAIDs) leads to bronchospasm.1 The reaction is related to inhibition of the cyclooxygenase (COX) enzyme that catalyzes prostaglandin production. Two isoforms of the enzyme (COX-1 and COX-2) have been identified, but it is not known which isoform is involved in the intolerance of NSAIDs. We examined 27 patients for bronchospasm after the administration of celecoxib,2 a selective COX-2 inhibitor recently introduced as an antiinflammatory treatment for arthritis in patients with asthma and aspirin intolerance.

The patients (17 women and 10 men with a mean [±SD] age of 46±15 years) had stable chronic asthma, with no exacerbations and with stable medication use during the prior three months. Before each study visit, leukotriene antagonists and long-acting bronchodilators were withheld for at least two days, and short-acting bronchodilators for at least six hours. A criterion for inclusion in the trial was a 20 percent drop in the forced expiratory volume in one second after the inhalation of lysine aspirin3 on the first visit. The patients did not have bronchoconstriction or extrapulmonary reactions after a graded oral challenge with increasing doses of celecoxib (suspensions of 10, 30, and 100 mg), given every second hour. On the final day of the study, each patient initially ingested 200 mg of celecoxib suspension, followed two hours later by the commercially available 200-mg capsule, without pulmonary or systemic reactions (Figure 1Figure 1Mean (±SD) Change in the Forced Expiratory Volume in One Second (FEV₁) after the Administration of Celecoxib in 27 Patients with Asthma and Aspirin Intolerance.). Challenges were performed at intervals of at least one week to avoid desensitization.

We conclude that celecoxib, a selective COX-2 NSAID, did not induce bronchospasm in patients with the syndrome of asthma and aspirin intolerance. Thus, inhibition of COX-1 is the likely link between NSAID ingestion and this syndrome. Despite the absence of adverse reactions in our patients, selective COX-2 inhibitors should be given to patients with asthma and aspirin intolerance only in the context of research. However, should our findings be corroborated in larger, long-term studies, patients with asthma may in the future be advised to use selective COX-2 inhibitors when analgesic and antiinflammatory treatment is required.

Barbro Dahlén, M.D., Ph.D.
Karolinska Hospital, SE-17176 Stockholm, Sweden

Andrew Szczeklik, M.D., Ph.D.
Jagellonian University, 31-006 Krakow, Poland

John J. Murray, M.D., Ph.D.
Vanderbilt University Medical Center, Nashville, TN 37203

for the Celecoxib in Aspirin-Intolerant Asthma Study Group

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