The Inhibitory Effect of Nebulized Albuterol on the Early and Late Asthmatic Reactions and Increase in Airway Responsiveness Provoked by Inhaled Allergen in Asthma

It is widely held that inhaled β2-adrenoceptor agonists inhibit the early asthmatic response (EAR) but not the late response (LAR) or attendant increase in bronchial responsiveness. In this study of 10 atopic asthmatic subjects, we have investigated the effects of a high dose of nebulized albuterol (2.5 mg) on the allergen-provoked EAR, LAR, and increase in histamine responsiveness. In a randomized blinded fashion, study subjects inhaled the following combinations: albuterol followed 10 min later by allergen, placebo followed by allergen, albuterol followed by saline (albuterol, placebo, and control study periods, respectively). Airway caliber was measured as FEV1 and followed at regular intervals for 7.5 h postallergen. Bronchial responsiveness to histamine was measured and recorded as the PC20 value before and at 1.5, 3.5, 5.5, and 7.5 h after allergen or control challenge. During the placebo study period, allergen challenge caused mean 29.6 ± 6.4 and 24.4 ± 6.4% falls in FEV1 at 20 min and 7.5 h, respectively (both p < 0.05), and a progressive decrease in PC20 amounting to a geometric mean of 1.9 doubling dilutions at 7.5 h (p < 0.05). Albuterol followed by allergen resulted in a 13.1 ± 2.2% increase in FEV1 prior to allergen followed by abolition of the EAR and inhibition of the LAR with only a 9.2 ± 3.5% fall in FEV1 at 7.5 h, significantly different from that of placebo at 7.5 h (p = 0.048). Similarly, PC20 histamine fell by only 0.64 doubling dilutions at 7.5 h, not significantly different from baseline values but different from placebo values (p = 0.03). Albuterol during the control study period (sham allergen challenge) produced an increase in both FEV1 and PC20 histamine that lasted less than 7.5 h. Thus, albuterol in the inhaled dose administered in this study protected against the allergen-provoked EAR, LAR, and increase in airways responsiveness by mechanism(s) that cannot be accounted for by bronchodilatation and functional antagonism of bronchoconstriction.