Targeting inhaled aerosol delivery to upper airways in children: Insight from computational fluid dynamics (CFD)

Prashant Das, Eliram Nof, Israel Amirav, Stavros C. Kassinos, Josué Sznitman

Research output: Contribution to journalArticlepeer-review

44 Scopus citations

Abstract

Despite the prevalence of inhalation therapy in the treatment of pediatric respiratory disorders, most prominently asthma, the fraction of inhaled drugs reaching the lungs for maximal efficacy remains adversely low. By and large drug delivery devices and their inhalation guidelines are typically derived from adult studies with child dosages adapted according to body weight. While it has long been recognized that physiological (e.g. airway sizes, breathing maneuvers) and physical transport (e.g. aerosol dynamics) characteristics are critical in governing deposition outcomes, such knowledge has yet to be extensively adapted to younger populations. Motivated by such shortcomings, the present work leverages in a first step in silico computational fluid dynamics (CFD) to explore opportunities for augmenting aerosol deposition in children based on respiratory physiological and physical transport determinants. Using an idealized, anatomically-faithful upper airway geometry, airflow and aerosol motion are simulated as a function of age, spanning a five year old to an adult. Breathing conditions mimic realistic age-specific inhalation maneuvers representative of Dry Powder Inhalers (DPI) and nebulizer inhalation. Our findings point to the existence of a single dimensionless curve governing deposition in the conductive airways via the dimensionless Stokes number (Stk). Most significantly, we uncover the existence of a distinct deposition peak irrespective of age. For the DPI simulations, this peak ( 80%) occurs at Stk 0.06 whereas for nebulizer simulations, the corresponding peak ( 45%) occurs in the range of Stk between 0.03-0.04. Such dimensionless findings hence translate to an optimal window of micron-sized aerosols that evolves with age and varies with inhalation device. The existence of such deposition optima advocates revisiting design guidelines for optimizing deposition outcomes in pediatric inhalation therapy.

Original languageEnglish
Article numbere0207711
JournalPLoS ONE
Volume13
Issue number11
DOIs
StatePublished - Nov 2018
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2018 Das et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

This work was supported by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 677772). The authors acknowledge COST Action MP1404 SimInhale ‘Simulation and pharmaceutical technologies for advanced patient-tailored inhaled medicines’, supported by the European Cooperation in Science and Technology (COST).

FundersFunder number
Horizon 2020 Framework Programme677772
European Research Council
European Cooperation in Science and Technology

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