NSAID-exacerbated respiratory disease: a meta-analysis evaluating prevalence, mean provocative dose of aspirin and increased asthma morbidity

Allergy. 2015 Jul;70(7):828-35. doi: 10.1111/all.12629. Epub 2015 May 7.


Background: The prevalence and mean provocative dose of oral aspirin (MPDA) triggering respiratory reactions in people with asthma have been inconsistently reported, and the relationship between NSAID-exacerbated respiratory disease (NERD) and asthma morbidity was less well quantified.

Methods: A systematic review was performed by identifying studies diagnosing NERD using blinded, placebo-controlled oral provocation challenge tests (OPCTs) or by self-reported history in people with asthma. Data were extracted, and effect estimates for changes in respiratory function, MPDA and asthma morbidity were pooled using random-effects meta-analysis.

Results: The prevalence of NERD in adults with asthma was 9.0% (95% CI 6-12%) using OPCTs and 9.9% (95% CI 9.4-10.5%) using self-reported history from questionnaires. The MPDA in adults with NERD was 85.8 mg (95% CI 73.9-97.6). In people with NERD, the risk of: uncontrolled asthma was increased twofold (RR 1.96 (95% CI 1.25-3.07)); severe asthma and asthma attacks was increased by 60% (RR 1.58 (95% CI 1.15-2.16) and RR 1.59 (95% CI 1.21-2.09), respectively); emergency room visits was increased by 80% (RR 1.79 (95% CI 1.29-2.49)); and asthma hospitalization was increased by 40% (RR 1.37 (95% CI 1.12-1.67)) compared to people with NSAID-tolerant asthma.

Conclusions: Respiratory reactions triggered by oral aspirin in people with asthma are relatively common. At the population level, the prevalence of NERD was similar when measured using appropriately conducted OPCTs or by self-reported history. On average, respiratory reactions were triggered by clinically relevant doses of oral aspirin. Asthma morbidity was significantly increased in people with NERD who potentially require more intensive monitoring and follow-up.

Keywords: NSAID-exacerbated respiratory disease; aspirin; aspirin-exacerbated respiratory disease; asthma; pharmacoepidemiology.

Publication types

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

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Asthma / epidemiology
  • Asthma / etiology
  • Bronchial Provocation Tests
  • Disease Progression
  • Female
  • Humans
  • Male
  • Morbidity
  • Prevalence
  • Publication Bias
  • Respiratory Tract Diseases / diagnosis*
  • Respiratory Tract Diseases / epidemiology
  • Respiratory Tract Diseases / etiology*
  • Surveys and Questionnaires


  • Anti-Inflammatory Agents, Non-Steroidal
  • Aspirin