The role of intrinsic efficacy in determining response to a β₂-agonist in acute severe asthma

Background: Current guidelines recommend repeated doses of albuterol for the emergency treatment of acute asthma. However, approximately one-third of patients show little or no initial response to this partial β₂-agonist. Methods: We conducted a randomized, double-blind, proof-of-concept study to investigate whether a full β₂-agonist, isoproterenol, offers a therapeutic advantage in adults presenting with acute severe asthma (FEV₁<50%) who fail to respond to an initial treatment of the partial β₂-agonist, albuterol. Study subjects were randomized to receive a 2-h continuous nebulization of either albuterol (7.5 mg/h) (n=10, mean FEV₁=37% predicted) or isoproterenol (7.5 mg/h) (n=9, mean FEV₁=33% predicted). Respiratory symptoms, vital signs and pulmonary function measures were collected. Results: Subjects from both treatment groups had similar baseline characteristics. The percent improvements from baseline FEV₁ at 60 and 120 min were significantly higher in subjects receiving isoproterenol than those receiving albuterol (44 vs. 17% and 63 vs. 24%, respectively, P<0.05). The change in symptoms measured by the modified Borg score was also significantly greater in subjects receiving isoproterenol (P<0.01). Both treatments were well tolerated, though the mean increase in pulse rate at 60 and 120 min (21 vs. 1 and 23 vs. 6 beats/min, respectively, P<0.05) and the mean change in serum potassium at 120 min (-0.52 vs. -0.07 meq/L, P<0.05) from baseline were significantly greater in the isoproterenol group. Conclusions: Our data suggest that in subjects presenting with acute severe asthma who fail to show an initial response to albuterol, the use of a β₂-agonist of higher intrinsic efficacy can be more effective in improving lung function and symptoms.