The Association Between β-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 β-agonist use and death from asthma. This effort integrated the results of case-control studies that examined the use of β-agonists among asthmatic patients who died and the use of β-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 β-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 β-agonist. A total of six case-control studies comprising 15 separate tests of the relation between β-agonist use and death from asthma and data for 364 cases and 1388 controls were included. Data Extraction. —The 2 (case vs control) × 2 (did vs did not use β-agonist) designs allowed for direct derivation of a χ 2 statistic that tested the association between β-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 β-agonist use and death from asthma ( z =3.996; P =.000075; mean r =.055). This relation emerged only when β-agonists were administered with a nebulizer ( z =4.481; P =.0000038; mean r =.103). There was no association between β-agonist use and death when β-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 β-agonist use and death. Conclusions. —These results document the extremely small magnitude of the relation between β-agonist use and death from asthma. Furthermore, these results specify that the weak relation between β-agonist use and death from asthma may really be restricted to the delivery of β-agonists with a nebulizer. These findings suggest that the headlines that followed the report by Spitzer et al (1992) were misleading. ( JAMA . 1993;270:1842-1845)