An in vivo and in vitro comparison of inhaled steroid delivery via a novel vortex actuator and a conventional valved holding chamber

Abstract

Valved holding chambers improve delivery of inhaled corticosteroids to the lung but are bulky in design. A novel compact vortex actuator device has therefore been developed. To compare the in vitro and in vivo performance of a novel compact vortex actuator (the Neohaler [NH]) vs a conventional small-volume valve holding chamber (the AeroChamber Plus [AP]. Seventeen asthmatic patients completed the study per protocol, receiving 4 weeks each of 100 microg/d (50-microg formulation) or 400 microg/d (100-microg formulation) of hydrofluoroalkane beclomethasone dipropionate via the NH or AP devices in a randomized crossover, double-blind, double-dummy, placebo-controlled design. The doubling dilution (dd) shift in methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20% (primary outcome) was used to evaluate anti-inflammatory effects and adrenal function to measure systemic exposure. The fine particle (<4.7 tm) dose was evaluated using an Andersen Cascade Impactor. A total of 100 microg of hydrofluoroalkane beclomethasone dipropionate via the NH and AP produced 0.95-dd (95% confidence interval [CI], 0.44-1.45; P = .006) and 0.45-dd (95% CI, -0.16 to 1.06; P = .83) improvements from baseline in methacholine provocation concentration that caused a decrease in forced expiratory volume in 1 second of 20%, respectively, with no statistically significant difference between devices: 0.50 dd (95% CI, -0.25 to 1.24; P = .18). At 400 microg/d, 1.08-dd (95% CI, 0.49-1.67; P = .006) and 0.85-dd (95% CI, 0.32-1.39; P = .02) improvements were found for the NH and AP, respectively, with a 0.23-dd difference (95% CI, -0.28 to 0.74; P = .36) between devices. No adrenal suppression occurred with either device. The in vitro fine particle dose was 39.1 microg for the NH and 39.0 microg for the AP with the 100-microg formulation and 26.0 g and 25.2 microg, respectively, with the 50-microg formulation. Delivering hydrofluoroalkane beclomethasone dipropionate via the NH and AP attenuates asthmatic airway inflammation to a comparable degree and produces a similar in vitro fine particle dose profile.