Clinical concerns with inhaled beta2-agonists: adult asthma.

Inhaled beta2-agonists, when used regularly, cause subtle but significant worsening of asthma control. Overuse of inhaled beta2-agonists is associated with increased risk of death from asthma in a dose-response fashion. beta2-Agonists enhance airway responses to allergens, including induced airway hyperresponsiveness and induced airway inflammation. This is a plausible explanation for beta2-agonist-worsened asthma control. These direct effects of inhaled beta2-agonists, including increased airway response to allergen, tolerance, etc., may partially explain the association of overuse with asthma death. However, it is probable that the major reason for the association of beta2-agonists overuse and asthma mortality is an indirect effect. Inhaled beta2-agonists are effective relievers and preventers of bronchoconstriction and asthma symptoms but fail to treat the underlying pathogenesis, namely the airway inflammation. Thus, overuse may mask the true asthma severity and result in both an underappreciation and undertreatment of the disease. This would provide a rational explanation for the relationship of inhaled beta2-agonist use and mortality and also would fit the dose-response pattern. Inhaled beta2-agonists should be used exclusively as needed for relief of symptoms and their requirement should be infrequent: the need for excessive doses of beta2-agonists provides a useful marker of asthma (lack of) control.