β agonists: What is the evidence that their use increases the risk of asthma morbidity and mortality?

Abstract

In this article, studies that have examined the effects on morbidity and mortality of β-agonist drugs are reviewed. With regard to morbidity, there is considerable evidence that the regular use of β-agonist drugs as a class could potentially lead to worsening asthma control because of the effects on bronchial hyperresponsiveness, the development of tolerance and reduced protection against provoking stimuli, an increased allergen load, and masking of the symptoms of deteriorating asthma. Despite these effects, the short-acting β-agonist drugs albuterol and terbutaline and the long-acting β-agonist drugs salmeterol and formoterol have, in general, not been associated with a significant worsening of asthma control or an increased frequency of severe attacks. In contrast, there is evidence that the regular use of isoproterenol and fenoterol may lead to worsening asthma control. With regard to deaths, available evidence indicates that the high-dose preparations of isoproterenol and fenoterol are associated with increased mortality and were the major causes of the epidemics of asthma mortality observed in some countries. The increased risk of death associated with isoproterenol and fenoterol is probably the result of both long-term effects with their regular use leading to worsening asthma control and acute effects resulting from their overuse in the situation of a life-threatening attack of asthma. In contrast, the use of the short-acting β-agonists albuterol and terbutaline is not associated with an increased risk of mortality. Although this lack of risk may also apply to formoterol and salmeterol, in the absence of sufficient studies specifically addressing the risk of death, this remains uncertain. (J Allergy Clin Immunol 1999;103:S18-30.)