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Nonsteroidal anti-inflammatory drugs (NSAIDs) cause bronchospasm in susceptible patients with asthma, often termed aspirin-exacerbated respiratory disease (AERD), with the risk being greatest after acute exposure. Selective NSAIDs that preferentially inhibit COX-2 might be safer.We sought to systematically evaluate changes in symptoms and pulmonary function after acute selective NSAID or COX-2 inhibitor exposure in patients with the AERD phenotype.A systematic review of databases was performed to identify all blinded, placebo-controlled clinical trials evaluating acute selective NSAID or COX-2 inhibitor exposure in patients with AERD. Effect estimates for changes in respiratory function and symptoms were pooled by using fixed-effects meta-analysis, with heterogeneity investigated.No significant difference in respiratory symptoms (risk difference, −0.01; 95% CI, −0.03 to 0.01;P= .57), decrease in FEV1 of 20% or greater (RD, 0.00; 95% CI, −0.02 to 0.02;P= .77), or nasal symptoms (RD, −0.01; 95% CI, −0.04 to 0.02;P= .42) occurred with COX-2 inhibitors (eg, celecoxib). Selective NSAID exposure caused respiratory symptoms in approximately 1 in 13 patients with AERD (RD, 0.08; 95% CI, 0.02 to 0.14;P= .01). No significant differences were found according to leukotriene antagonist exposure or whether NSAIDs were randomly allocated.According to clinical trial evidence in patients with stable mild-to-moderate asthma with AERD, acute exposure to COX-2 inhibitors is safe, and selective NSAIDs exhibit a small risk. Thus COX-2 inhibitors could be used in patients with AERD or in patients with general asthma unwilling to risk nonselective NSAID exposure when oral challenge tests are unavailable.