Enhanced response to aerosolized bronchodilator therapy in asthma using respiratory maneuvers

To determine if respiratory maneuvers may enhance the response to inhaled bronchodilator drugs, we evaluated the bronchodilator responses when isoproterenol was: inhaled as a bolus at high (80 percent VC) compared to low (20 percent VC) lung volumes, and inhaled as a single 800 μg dose compared to four 200 μg doses given 20 min apart. Nine asthmatic subjects inhaled isoproterenol sequentially at high and low lung volumes on two separate days; 15 other inhaled single doses of 200, 400, 600, and 800 μg isoproterenol on four separate days. FEV₁, specific conductance (Gaw/V(L)), Vmax50%, and the slope of phase 3 of the single-breath nitrogen test (ΔN₂/L) were measured 10 min after each dose. FEV₁ and Gaw/V(L) increased and ΔN₂/L decreased more following inhalation at high compared to low lung volume (P < 0.05). Gaw/V(L) increased more in the group given 800 μg in divided doses than the group given a single dose (P < 0.05). These findings suggest that the bronchodilator response to isoproterenol may be enhanced by inhaling the drug in divided doses sequentially and by delivering the drug near maximal inspiration. An enhanced response after the latter maneuver may be due to more uniform distribution of the drug to airway receptor sites.