Essentials for aerosol delivery to term and pre-term infants

Effectively delivering pharmaceutical aerosols to the lungs of preterm and term infants represents a considerable technical challenge. Small infants are obligatory nose breathers, they have small airways, low tidal volumes and rapid respiration rates. It is ethically unacceptable to investigate aerosol deposition in vivo in newborns due to ethical concerns about the radiation exposure involved in imaging studies and drug delivery and blood draws in pharmacokinetics studies. The purpose of the work reported in this article was thus to report the use of modeling to develop an understanding of the regional deposition of aerosols in neonates and to build a theoretical basis for choosing an optimum aerosol size to maximize delivery and minimize variability. Recent data on aerosol deposition in the nasal airways of newborn term and preterm infants was coupled to an established, scalable, lung deposition model to investigate the effects of age, aerosol size and ventilation on regional airway deposition. In the term newborn infant lung deposition ranged from 25% to 35% depending on Geometric Standard Deviations (GSDs). Intrasubject variability was minimized for aerosols with larger GSD. However, mean lung deposition is reduced with increasing GSD. A compromise between maximum lung deposition and increased intersubject variability appears to be in the region of GSDs of 1.75. In the 30-week GA preterm infant lung deposition is slightly higher than in the term infant despite smaller airways and lower tidal volumes. This is likely due to the lower inhaled flow rates that are concomitant with lower lung volumes. Finally, when aerosol delivery is directly to the trachea, as it would be if delivered via an endotracheal tube there is a monotonic increase in lung deposition with increasing aerosol size with peripheral deposition peaking at 2 to 3 µm. However, practical limitations of aerosol transport through endotracheal tubes, limiting delivered aerosol size, likely caps lung deposition at around 30% to 30% of the delivered dose.