Spatial aerosol deposition correlated to anatomic feature development in 6-year-old upper airway computational models

Abstract

The upper airways of children undergo developmental changes around age 6, yielding differences between adult and pediatric anatomies. These differences include the cricoid ring area shape, the location of narrowest constriction, and the angle of the epiglottis, all of which are expected to alter local fluid dynamic profiles and subsequent upper airway deposition and downstream aerosol delivery of inhaled therapeutics. In this work, we quantify "pediatric"-like and "adult"-like geometric and fluid dynamic features of two computed tomography (CT)-scan derived models of 6-year-old upper airways in healthy subjects and compare to an idealized model. The two CT-scan models had a mixture of "adult"- and "pediatric"-like anatomic features, with Subject B exhibiting more "pediatric"-like features than Subject A, while the idealized model exhibited entirely "adult"-like features. By computational fluid-particle dynamics, these differences in anatomical features yielded distinct local fluid profiles with altered aerosol deposition between models. Notably, the idealized model better predicted deposition characteristics of Subject A, the more "adult"-like model, including the relationship between the impaction parameter, d_p²Q and the fraction of deposition across a range of flow rates and particle diameters, as well as deposition of an approximate pharmaceutical particle size distribution model. Our results with even this limited dataset suggest that there are key personalized metrics that are influenced by anatomical development, which should be considered when developing pediatric inhalable therapeutics. Quantifying anatomical development and correlating to aerosol deposition has the potential for high-throughput developmental characterization and informing desired aerosol characteristics for pediatric applications.

Keywords: Airway; Anatomy; CFPD; Development; Pediatric.