The beta-agonist saga and its clinical relevance: on and on it goes.

The decision by the Food and Drug Administration to issue a "black box" warning for long-acting beta-agonists has been followed by a series of pharmacoepidemiological studies focusing on the safety of these drugs. However, these provide the clinician with mixed messages and do not offer clear guidance as to whether adverse responses to beta-agonists are a relevant consideration in individual patients. Simultaneously, there is a growing body of evidence that continuous or high dose-beta-agonist exposure is proinflammatory and that, paradoxically, airway hyperresponsiveness is enhanced, not attenuated. Also, pharmacological theory regarding the pathophysiological function of the beta-adrenoceptor is having to be revised. A recent clinical study has even suggested that beta-blockers rather than beta-agonists may be beneficial in asthma. In practice, there are individuals in whom excessive beta-agonist use contributes adversely to poor asthma control. The recommendation that concomitant use of inhaled steroids will obviate any risks associated with beta-agonists is not in fact fool-proof. Clinicians need to be aware of how to identify and manage patients for whom beta-agonist treatment is a problem rather than a solution. They constitute a small but important subgroup of patients with difficult asthma.