A COHORT ANALYSIS OF EXCESS MORTALITY IN ASTHMA AND THE USE OF INHALED BETA-AGONISTS

The association between the use of inhaled beta-agonists and the risk of death and near-death from asthma has previously been reported. It w as based on a nested case-control study of 129 cases and:655 control s ubjects selected from a cohort of 12,301 users of asthma drugs followe d during the period 1980 through 1987. In this paper we examine the qu estion of asthma and non-asthma mortality using data from the entire c ohort of 12,301 asthmatics. There were 46 asthma and 134 non-asthma de aths in this cohort, for which there were 47,842 person-years of follo w-up. The overall rate of asthma death was 9.6 per 10,000 asthmatics p er year. This rate varied significantly according to the use of fenote rol, albuterol, or oral corticosteroids in the prior 12 months and the number of asthma hospitalizations in the prior 2 years. The rate decr eased significantly, by 0.6 asthma deaths per 10,000 asthmatics per ye ar over the study period, after controlling for the effect of the four other risk factors. It also increased significantly with the use of a ll beta-agonists, and more so for fenoterol than for albuterol, althou gh this difference was partly explained by the dose inequivalence of t he two drugs. Change-point dose-response curves showed that the risk o f asthma death began to escalate drastically at about 1.4 canisters (o f 20,000 mu g each) per month of inhaled beta-agonist, the recommended limit. For non-asthma death, the overall rate of 28 deaths per 10,000 asthmatics per year was not related to the use of inhaled beta-agonis ts. We conclude that the strong association between the use of inhaled beta-agonists and asthma mortality is confined primarily to the use o f these drugs in excess of recommended limits. Non-asthma mortality, i ncluding that from cardiovascular causes, is not associated with the u se of inhaled beta-agonists.