The association between beta-agonist use and death from asthma. A meta-analytic integration of case-control studies.

OBJECTIVES: The purpose of this investigation was to provide an empirical summary of the evidence regarding the association between beta-agonist use and death from asthma. This effort integrated the results of case-control studies that examined the use of beta-agonists among asthmatic patients who died and the use of beta-agonists among asthmatic patients who did not die. The possible moderating effects of patient sample age and mode of delivery (oral, metered-dose inhaler, and nebulizer) were also examined. DATA SOURCES: An on-line computer search (using MEDLINE) was conducted using the key words beta-agonist and asthma. This search was supplemented by ancestry and descendency approach searches. Studies that were available as of April 1992 were eligible for inclusion in this integration. STUDY SELECTION: Studies were included if they reported the precise numbers of cases and controls who did and did not use a beta-agonist. A total of six case-control studies comprising 15 separate tests of the relation between beta-agonist use and death from asthma and data for 364 cases and 1388 controls were included. DATA EXTRACTION: The 2 (case vs control) x 2 (did vs did not use beta-agonist) designs allowed for direct derivation of a chi 2 statistic that tested the association between beta-agonist use and death from asthma. Mode of delivery and average age of sample were also coded. DATA SYNTHESIS: Statistical integration revealed a significant, although extremely weak, relation between beta-agonist use and death from asthma (z = 3.996; P = .000075; mean r = .055). This relation emerged only when beta-agonists were administered with a nebulizer (z = 4.481; P = .0000038; mean r = .103). There was no association between beta-agonist use and death when beta-agonists were administered by metered-dose inhaler (z = 1.194; P = .11; mean r = .031) or orally (z = 1.247; P = .1; mean r = .031). Adults were more likely than adolescents to evidence the association between beta-agonist use and death.
CONCLUSIONS: These results document the extremely small magnitude of the relation between beta-agonist use and death from asthma. Furthermore, these results specify that the weak relation between beta-agonist use and death from asthma may really be restricted to the delivery of beta-agonists with a nebulizer. These findings suggest that the headlines that followed the report by Spitzer et al (1992) were misleading.