Controversies in Management: Adverse effects are not proved

doi:10.1136/bmj.309.6957.795

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R W Fuller

Glaxo Group Research and Development Limited, Stockway Park West, Middlesex UB11 1BT.

Use of ß2 agonists in asthma: much ado about nothing?

Inhaled ß2 agonists are widely accepted as the most appropriate bronchodilator therapy for asthma. So why is there a question over their safety? The possibility that ß2 agonists may increase asthma mortality stems from two increases in death rates from asthma that occurred at the same time as sales of high dose inhaled isoprenaline and fenoterol.1,2 The explanation that the increased death rate was due to ß agonists ignores, firstly, epidemics before the discovery of inhaled ß2 agonists3; secondly, the lack of epidemics in other countries where the drugs were used; and, thirdly, that the New Zealand asthma deaths were also associated with other drugs (theophylline and prednisolone).2 It is accepted that cause and effect cannot be established by the retrospective analysis of these epidemics and that the relation is weak.2

Explanation for causal association

The hypothesis of a causal link between ß2 agonists and death from asthma relies on showing that the use of inhaled ß2 agonists can worsen asthma control. Some studies have reported decreased lung function, increased bronchial reactivity, and more attacks with ß agonists, but most have had a small sample size and no placebo control.4 A placebo controlled study was done by Sears …