ASTHMA AND THE BETA-AGONIST DEBATE

The association between the use of inhaled β agonists and the risk of death and near death from asthma has previously been reported. It was based on a nested case-control study of 129 cases and 655 control subjects selected from a cohort of 12301 users of asthma drugs followed during the period 1980 through 1987. In this paper, we examine the question of asthma and non-asthma mortality using data from the entire cohort of 12301 asthmatics. There were 46 asthma and 134 non-asthma deaths in this cohort, for which there were 47842 person-years of follow-up. The overall rate of asthma death was 9 6 per 10 000 asthmatics per year. This rate varied significantly according to the use of fenoterol, albuterol, or oral corticosteroids in the prior 12 months and the number of hospitalisations in the prior 2 years. The rate decreased significantly, by 0-6 asthma deaths per 10 000 asthmatics per year over the study period, after controlling for the effect of the four other risk factors. It also increased significantly with the use of all β agonists, and more so for fenoterol than for albuterol, although this difference was partly explained by the dose inequivalence of the two drugs. Change-point dose-response curves showed that the risk of asthma death began to escalate drastically at about 1.4 canisters (of 20 000 μg each) per month of inhaled β agonist, the recommended limit. For non-asthma death, the overall rate of 28 deaths per 10000 asthmatics per year was not related to the use of inhaled β agonists. We conclude that the strong association between the use of inhaled β agonists and asthma mortality is confined primarily to the use of these drugs in excess of recommended limits. Non-asthma mortality, including that from cardiovascular causes, is not associated with the use of inhaled β agonists.