Modeling the Impact of Pediatric Tonsil Size on Aerosol Deposition and Drug Delivery

Current pediatric applications of aerosolized medication consist of off-label prescription of adult medications to scale down the dosage for children; however, studies have shown that there are significant anatomical differences between the airways of pediatric and adult subjects, which could potentially lead to off-target aerosol deposition and decreased drug delivery. In vitro and in silico tools provide innovative ways to model aerosol behavior without the ethical concerns surrounding in vivo testing with pediatric patients. Recent papers from Kolewe et al. study the impacts of this changing anatomy using computational fluid-particle dynamics (CFPD); however, these studies focus on the geometric changes of the airway during development. Other key organs throughout the airway may also have significant impacts on flow development and aerosol transport. The tonsils are one such organ. Tonsil hypertrophy is a common occurrence during early development, whether it is related to tonsillar infections or tissue development. Understanding both flow and transport of aerosols at various levels of tonsil size would allow medications to more effectively target the tonsils or lower lobes of the lung depending on need, leading to maximal bioavailability at the intended tissue. This work aims to extend previous work from the Fromen lab in modeling pediatric aerosol behavior by adding variable tonsil sizes. This consists of 1) creating an anatomically-accurate in vitro model of the pediatric upper airway for each of the four tonsil grades in the Brodsky scale, 2) characterizing nebulized aerosol deposition patterns in the models, and 3) modeling the same aerosol deposition computationally to cross-examine apparent trends. Currently, a 6-year-old airway has been 3D printed using a Carbon 3D digital light synthesis printer, with a focus on modular design for printing and analysis. Pilot studies are also being conducted on using an Aeroneb nebulizer and a next-generation impactor to deliver aerosolized rhodamine b to the model and size the effluent aerosol particles. Thus far, resultant aerosol sizing aligns with the manufacturer-specified particle size, although this procedure is still being refined. Computational data has been recorded for this geometry, which will be used to benchmark the in vitro findings. Future work will include modeling different levels of tonsillar swelling and measuring the impact on deposition, as well as potentially expanding this study to a wider range of patients.