Controversies involving inhaled beta-agonists and inhaled corticosteroids in the treatment of asthma.

Controversy over the use of inhaled beta-agonists has dated almost from their introduction as a treatment for asthma. Their effectiveness as bronchodilators is not disputed, but there is concern that they may worsen asthma control if used regularly and that excessive use may increase the risk of death from asthma. Five years after the report from Sears and colleagues suggested that regular use of fenoterol worsens asthma control, we do not have definitive corroborative evidence that this effect of fenoterol is real or is shared by other members of the beta-agonist class. It also remains disputed whether the documented association between excessive beta-agonist use and death from asthma is a causal or a spurious association. Undisputed is the fact that excessive beta-agonist use by asthmatics indicates an increased risk of death from asthma and so indicates a need for clinicians to advise anti-inflammatory medications for these patients. Happily, although there are legitimate concerns about the possible implications of the development of tolerance to the non-bronchodilating effects of beta-agonists, there is currently little evidence that treatment with conventional doses of the beta-agonists currently available in the United States, including salmeterol, is harmful to asthmatic patients. The controversies over the use of inhaled corticosteroids revolve around the issue of whether the clinical benefit easily demonstrated with their short-term use is justified in the face of their possible long-term systemic toxicity. Unsettled questions about their therapeutic use include whether dose dependence can be shown for the clinical benefits of inhaled corticosteroids, whether delay in initiating inhaled corticosteroid treatment reduces the benefit that can be achieved, and whether the benefits of even prolonged therapy are short-lasting. The great unsettled question about their toxicity is whether systemic absorption of inhaled corticosteroids increases the risk of long-term systemic complications, like osteoporosis, cataracts, and growth inhibition. Current evidence suggests that significant risk of such toxicity is not likely to be associated with the long-term use of the equivalent of 800 micrograms/d of beclomethasone in adults and 400 micrograms/d in children. If higher doses are used to obtain greater clinical benefit, the answers to these questions may determine the place of new inhaled corticosteroids with high local potency and little systemic activity.