Safety risks for patients with aspirin-exacerbated respiratory disease after acute exposure to selective nonsteroidal anti-inflammatory drugs and COX-2 inhibitors: Meta-analysis of controlled clinical trials

J Allergy Clin Immunol. 2014 Jul;134(1):40-5. doi: 10.1016/j.jaci.2013.10.057. Epub 2013 Dec 31.

Abstract

Background: 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.

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Asthma; COX-2 inhibitors; aspirin-exacerbated respiratory disease; aspirin-induced asthma; aspirin-sensitive asthma; meta-analysis; nonsteroidal anti-inflammatory agents; pharmacoepidemiology; systematic review.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Aspirin / adverse effects*
  • Asthma / chemically induced
  • Asthma / complications
  • Asthma / drug therapy*
  • Asthma / physiopathology
  • Bronchial Spasm / chemically induced
  • Bronchial Spasm / physiopathology
  • Celecoxib
  • Clinical Trials as Topic
  • Cyclooxygenase 2 Inhibitors / therapeutic use*
  • Drug Hypersensitivity / physiopathology
  • Humans
  • Pyrazoles / therapeutic use*
  • Respiratory Tract Diseases / chemically induced
  • Respiratory Tract Diseases / complications
  • Respiratory Tract Diseases / drug therapy*
  • Respiratory Tract Diseases / physiopathology
  • Risk
  • Sulfonamides / therapeutic use*

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cyclooxygenase 2 Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Celecoxib
  • Aspirin