Epidemiologic Studies of Beta Agonists and Asthma Deaths

From their inception in the modern treatment of asthma, the history of beta agonists has been marked by reports of their undoubted efficacy as bronchodilator drugs, yet dogged by controversy concerning their possible adverse side effects. In particular, two relatively nonselective full agonists, isoprenaline forte and fenoterol, have been associated with epidemics of asthma deaths in six countries during the 1960s (isoprenaline forte) and again in New Zealand during the late 1970s and 1980s (fenoterol). In addition, there has been continuing concern about the possible hazards of beta agonists as a class. In this presentation we review the epidemiologic evidence linking isoprenaline forte with asthma mortality epidemics in six countries during the 1960s, and the evidence linking fenoterol with an epidemic of asthma deaths in New Zealand during the 1970s and 1980s. Finally, we consider the epidemiologic evidence on the possibility of a class effect of beta agonists on asthma mortality. Although we also consider evidence from studies of time trends in beta agonist sales and asthma mortality, we concentrate on analytic (cohort and case-control) studies of beta agonists and asthma deaths, and particularly on the methodological issues involved. In doing so, we have particularly drawn on our experience of involvement in the New Zealand studies of fenoterol and asthma deaths (NP) and on the Scientific Advisory Committee for the Saskatchewan (Canada) study of fenoterol, beta agonists, and asthma death (MJH). We emphasize that there are important pharmacologic differences between beta agonists, and it is therefore essential to distinguish between different beta agonists when considering the epidemiologic evidence.