Present state of the controversy about regular inhaled β-agonists in asthma

A possible association between the use of β-agonists and mortality from asthma was postulated for the first time during the so-called epidemic of asthma deaths, which was observed in England and Wales in the 1960s [1]. With reference to this epidemic, INMAN and ADELSTEIN [2] reported a rise and fall of asthma mortality paralleling an increase and decrease, respectively, in the use of pressurized aerosols. However, SPEIZER et al. [1], the authors of the first report, pointed out that "Accounts of the excess use of aerosols have been obtained in some cases, but decisive evidence to incriminate them is lacking". Other studies based on the same approach have yielded different results. In New Zealand, from 1979 to 1987, asthma mortality showed a trend to decline, whereas fenoterol and salbutamol use had a further increase [3]. In Sweden, asthma mortality remained quite stable from the beginning of the 1960s, whereas there was a marked increase in the use of inhaled β-agonists [4]. In the UK, prescription of β-agonists increased threefold during the 1980s, without any appreciable change of asthma mortality in this decade [4]. In Italy, no correlation was apparent between asthma mortality in three age classes (5–34, 35–54, and more than 55 yrs) and the number of β-agonist canisters sold in the period 1980– 1989, since against an increase in the sale of metereddose inhalers there was a trend for asthma mortality firstly to level-off and then to decline [5]. Ecological studies of this type, which are based on correlations, at a regional level, between rates of asthma death and sales of inhaled β-agonist bronchodilators, may be used only to generate or support cause-effect hypotheses, which then require other methodological approaches to be tested [6]. Case-control studies