The use of beta-agonists and the risk of death and near death from asthma

N Engl J Med. 1992 Feb 20;326(8):501-6. doi: 10.1056/NEJM199202203260801.


Background: Morbidity and mortality from asthma appear to be increasing, and it has been suggested that medications used to treat asthma are contributing to this trend. We investigated a possible association between death or near death from asthma and the regular use of beta 2-agonist bronchodilators.

Methods: Using linked health insurance data bases from Saskatchewan, Canada, we conducted a matched case-control study of subjects drawn from a cohort of 12,301 patients for whom asthma medications had been prescribed between 1978 and 1987. We matched 129 case patients who had fatal or near-fatal asthma with 655 controls (who had received medications for asthma but had not had fatal or near-fatal events) with respect to region of residence, age, receipt of social assistance, and previous hospitalization for asthma.

Results: The use of beta-agonists administered by a metered-dose inhaler was associated with an increased risk of death from asthma (odds ratio, 2.6 per canister per month; 95 percent confidence interval, 1.7 to 3.9) and of death or near death from asthma, considered together (odds ratio, 1.9; 95 percent confidence interval, 1.6 to 2.4). For death from asthma, use of the beta-agonist fenoterol was associated with an odds ratio of 5.4 per canister, as compared with 2.4 for the beta-agonist albuterol. On a microgram-equivalent basis, the odds ratio for this outcome with fenoterol was 2.3, as compared with 2.4 with albuterol.

Conclusions: An increased risk of death or near death from asthma was associated with the regular use of inhaled beta 2-agonist bronchodilators, especially fenoterol. Regardless of whether beta-agonists are directly responsible for these adverse effects or are simply a marker for more severe asthma, heavy use of these agents should alert clinicians that it is necessary to reevaluate the patient's condition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / adverse effects*
  • Adult
  • Albuterol / administration & dosage
  • Albuterol / adverse effects
  • Asthma / mortality*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Fenoterol / administration & dosage
  • Fenoterol / adverse effects
  • Humans
  • Insurance, Health
  • Male
  • Nebulizers and Vaporizers
  • Odds Ratio
  • Saskatchewan / epidemiology


  • Adrenergic beta-Agonists
  • Fenoterol
  • Albuterol