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

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

doi:10.1371/journal.pone.0207711

Prashant Das, Stavros C Kassinos + Show 4 more

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https://doi.org/10.1371/journal.pone.0207711

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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.

Highlights

Inhalation therapy is a hallmark in the treatment of pediatric respiratory disorders, including foremost asthma [1,2,3]
While peak inspiratory flow rate (PIFR) increases with age, the mouth inlet area increases as well (Table 1) such that we observe comparatively larger inlet flow velocities for the younger ages (Fig 2a)
Numerical simulations have shown that the larynx is an important anatomical element that influences aerosol deposition outcomes [84]: flow acceleration due to the constriction coupled with directional changes due to anatomy contribute to enhanced aerosol deposition near the larynx [83]

Summary

Introduction

Inhalation therapy is a hallmark in the treatment of pediatric respiratory disorders, including foremost asthma [1,2,3]. Is asthma the leading chronic disease globally [4], recent studies depict a rise in childhood prevalence over the past decade [5,6,7,8] In this context, inhaled corticosteroids are recognized as effective drugs to suppress airway inflammation [9] and the regular use of such therapeutics at low dose is acknowledged to reduce the risk of morbidity and mortality [10, 11]. Past in vivo studies report deposition efficiencies typically ranging between 0.5% and 12% for nebulizers [17], whereas DPIs and pMDIs yield efficiencies nearing 40% in the best of cases [17,18,19] Such shortfalls call for increased efforts in achieving improved, if not optimal, therapeutic delivery in pediatric populations [20]

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