(688d) Computational Fluid Particle Dynamics Illuminates Developmental Anatomical Feature Influence on Aerosol Deposition Patterns in 6-Year-Old Upper Airway CT-Scan Models

Aerosol therapeutics are influenced by airway geometry and it is known that there are geometric differences between adult and pediatric subjects; the quantification and characterization of anatomical features and their resultant influence on airflow and aerosol deposition patterns has been identified as a needed area of research.¹ Generally, at age 6 there are anatomical developments occurring in the cricoid ring area shape and size, whether the glottis or subglottis is the narrowest point, and epiglottic angle.² These geometry variations are thought to influence fluid dynamic metrics, such as turbulence intensity, glottal length, and Reynolds number, as well as the resultant aerosol deposition patterns. This work characterizes “pediatric”- and “adult”-like anatomical geometric and fluid dynamic features of two healthy 6-year-old subject CT scan derived models and an idealized pediatric airways model, the pediatric Alberta Idealized Throat (AIT).³ The female 6-year-old subject displayed a mixture of “adult”- and “pediatric”-like features, the male 6-year-old subject displayed mostly “pediatric”-like features, and the AIT displayed entirely “adult”-like features. The mixture of features within one model and between the two CT-scan models demonstrates the transient development and geometry of these features at this age and the difficulties in representing these changes in a generalized or idealized model.

In addition to these characterizations, the resultant aerosol deposition pattern and metrics of interest were evaluated for idealized model particles and an Advair® Diskus® aerosol mimic model.⁴ Some aerosol deposition trends were consistent among all three models, such as a significant increase in deposition as a function of particle size (100 nm -10 μm) and an insignificant relationship across flow rates (10 Lpm – 120 Lpm). For both the impaction parameter (d²Q) and the Advair® Diskus® mass median aerodynamic diameter (MMAD) there was agreement between the AIT and the female CT-scan model, both of which presented with predominantly “adult”-like features. This suggests that the AIT would be better at predicting subjects with a more developed upper airway displaying more “adult”-like features. This work demonstrates the transient development of upper airways in pediatric subjects and the resultant variation in aerosol deposition patterns and metrics that can be uniform across subjects, independent of development, or predictable from “adult”-like idealized models. We have quantified and demonstrated differences between adult and pediatric upper airways that highlight the need to recognize and integrate pediatric aerosol requirements into inhalable therapeutics.

REFERENCES:

1. Ahookhosh, K.; Pourmehran, O.; Aminfar, H.; Mohammadpourfard, M.; Sarafraz, M. M.; Hamishehkar, H., Development of human respiratory airway models: A review. European Journal of Pharmaceutical Sciences 2020, 145, 105233.
2. Di Cicco, M.; Kantar, A.; Masini, B.; Nuzzi, G.; Ragazzo, V.; Peroni, D., Structural and functional development in airways throughout childhood: Children are not small adults. Pediatric Pulmonology 2021, 56 (1), 240-251.
3. Golshahi, L.; Finlay, W., An idealized child throat that mimics average pediatric oropharyngeal deposition. Aerosol Science and Technology 2012, 46 (5), i-iv.
4. Weers, J.; Clark, A., The impact of inspiratory flow rate on drug delivery to the lungs with dry powder inhalers. Pharmaceutical research 2017, 34 (3), 507-528.