The use of beta-agonists and the risk of death and near death from asthma.
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.
Department of Epidemiology and Biostatistics, Montreal General Hospital, Canada.
W O
WO
Spitzer
S
S
Suissa
P
P
Ernst
R I
RI
Horwitz
B
B
Habbick
D
D
Cockcroft
J F
JF
Boivin
M
M
McNutt
A S
AS
Buist
A S
AS
Rebuck
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000009:adverse effects*; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects; D001249:Asthma / Q000401:mortality*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005280:Fenoterol / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007348:Insurance, Health; D008297:Male; D009330:Nebulizers and Vaporizers; D016017:Odds Ratio; D012525:Saskatchewan / Q000453:epidemiology
D000318:Adrenergic beta-Agonists; D005280:Fenoterol; D000420:Albuterol