title: 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.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Quality, Safety & Informatics Group, Medical Research Institute, University of Dundee, Dundee, United Kingdom. Electronic address: d.r.z.morales@dundee.ac.uk.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Morales
authors.affiliation: Asthma & Allergy Research Group, Medical Research Institute, University of Dundee, Dundee, United Kingdom.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Lipworth
authors.affiliation: Quality, Safety & Informatics Group, Medical Research Institute, University of Dundee, Dundee, United Kingdom.
authors.forename: Bruce
authors.initials: B
authors.lastname: Guthrie
authors.affiliation: School of Medicine, University of St Andrews, Fife, United Kingdom.
authors.forename: Cathy
authors.initials: C
authors.lastname: Jackson
authors.affiliation: Dundee Epidemiology and Biostatistics Unit, Population Health Sciences, Medical Research Institute, University of Dundee, Dundee, United Kingdom.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Donnan
authors.affiliation: Quality, Safety & Informatics Group, Medical Research Institute, University of Dundee, Dundee, United Kingdom.
authors.forename: Virginia H
authors.initials: VH
authors.lastname: Santiago
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D001986:Bronchial Spasm / Q000139:chemically induced / Q000503:physiopathology; D000068579:Celecoxib; D002986:Clinical Trials as Topic; D052246:Cyclooxygenase 2 Inhibitors / Q000627:therapeutic use*; D004342:Drug Hypersensitivity / Q000503:physiopathology; D006801:Humans; D011720:Pyrazoles / Q000627:therapeutic use*; D012140:Respiratory Tract Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D012306:Risk; D013449:Sulfonamides / Q000627:therapeutic use*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D001241:Aspirin
keywords: Asthma; COX-2 inhibitors; aspirin-exacerbated respiratory disease; aspirin-induced asthma; aspirin-sensitive asthma; meta-analysis; nonsteroidal anti-inflammatory agents; pharmacoepidemiology; systematic review