Imaging the Postdeposition Dispersion of an Inhaled Surfactant Aerosol

Abstract

Aerodynamic forces provide the primary means of distributing aerosol medications within the lungs. Partial airway obstructions can limit both air flow and aerosol penetration into diseased zones. We hypothesize that low surface tension additives may help to disperse aerosol medications after deposition in the airways, improving dose uniformity and drug delivery to underventilated regions. To test this, we performed a pilot scintigraphy study of surfactant and saline deposition and postdeposition dispersion. Because inhaled antibiotics for cystic fibrosis provide an example of where self-dispersing medications may be useful, we administered calfactant and saline aerosols with added Technetium 99m sulfur colloid (Tc-SC; 100 nm filtered) on different days in randomized order to eight cystic fibrosis (CF) subjects (average FEV(1)%, p=85 ± 12%). Nebulized delivery was matched (similar aerosol sizes and volume delivery rates, fixed breathing patterns). Tc-SC distribution in the lungs was imaged continuously for 30 min after delivery. Both aerosols were well tolerated. Aerosol distribution was mostly peripheral (58/42%) and initially similar for saline and surfactant. Changes in whole lung counts after 30 min were also similar. Peripheral lung activity decreased more rapidly on average with calfactant though the difference versus saline was not statistically significant. Central to peripheral count ratio decreased with saline and increased with calfactant and c/p changes approached significance (-0.05 ± 0.16 vs. 0.10 ± 0.10; p=0.07 Wilcoxon). Our results lack statistical significance, but suggest that inhaled calfactant increased peripheral clearance, due to either surfactant-based dispersion or mucociliary effects. Further studies are needed to define the potential for low surface tension carriers to improve drug delivery.