Dataset Information

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

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.

SUBMITTER: Das P

PROVIDER: S-EPMC6245749 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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

Das Prashant P Nof Eliram E Amirav Israel I Kassinos Stavros C SC Sznitman Josué J

PloS one 20181120 11

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. ...[more]

PMID: 30458054

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Project description:Existing in vivo experiments show significantly decreased acrolein uptake in rats with increasing inhaled acrolein concentrations. Considering that high-polarity chemicals are prone to bond with each other, it is hypothesized that molecular binding between acrolein and water will contribute to the experimentally observed deposition decrease by decreasing the effective diffusivity. The objective of this study is to quantify the probability of molecular binding for acrolein, as well as its effects on acrolein deposition, using multiscale simulations. An image-based rat airway geometry was used to predict the transport and deposition of acrolein using the chemical species model. The low Reynolds number turbulence model was used to simulate the airflows. Molecular dynamic (MD) simulations were used to study the molecular binding of acrolein in different media and at different acrolein concentrations. MD results show that significant molecular binding can happen between acrolein and water molecules in human and rat airways. With 72 acrolein embedded in 800 water molecules, about 48% of acrolein compounds contain one hydrogen bond and 10% contain two hydrogen bonds, which agreed favorably with previous MD results. The percentage of hydrogen-bonded acrolein compounds is higher at higher acrolein concentrations or in a medium with higher polarity. Computational dosimetry results show that the size increase caused by the molecular binding reduces the effective diffusivity of acrolein and lowers the chemical deposition onto the airway surfaces. This result is consistent with the experimentally observed deposition decrease at higher concentrations. However, this size increase can only explain part of the concentration-dependent variation of the acrolein uptake and acts as a concurrent mechanism with the uptake-limiting tissue ration rate. Intermolecular interactions and associated variation in diffusivity should be considered in future dosimetry modeling of high-polarity chemicals such as acrolein.

Project description:In order to reduce the hemodialysis cost and duration, an investigation of the effect of dialyzer design and process variables on the solute clearance rate is required. It is not easy to translate the in vivo transfer process with in vitro experiments, as it involves a high cost to produce various designs and membranes for the dialyzer. The primary objective of this study was the design and development of a computational tool for a dialyzer by using a computational fluid dynamic (CFD) model. Due to their complexity, only researchers with expertise in computational analysis can use dialyzer models. Therefore, COMSOL Inc. (Stockholm, Sweden) has made an application on membrane dialysis to study the impact of different design and process parameters on dialyzed liquid concentration. Still, membrane mathematical modeling is not considered in this application. This void hinders an investigation of the impact of membrane characteristics on the solute clearance rate. This study has developed a stand-alone computational tool in COMSOL Multiphysics 5.4 to fill this void. A review of the literature conducted shows that there are no suitable stand-alone computational tools for kidney dialysis. Very little work has been undertaken to validate the stand-alone computational tool. Medical staff in the hospitals require a computational tool that can be installed quickly and provide results with limited knowledge of dialysis. This work aims to construct a user-friendly computational tool to solve this problem. The development of a user-friendly stand-alone computational tool for the dialyzer is described thoroughly. This application simulates a mathematical model with the Finite Element Method using the COMSOL Multiphysics solver. The software tool is converted to a stand-alone version with the COMSOL compiler. The stand-alone computational tool provides the clearance rate of six different toxins and module packing density. Compared with the previous application, the stand-alone computational tool of membrane dialysis enables the user to investigate the impact of membrane characteristics and process parameters on the clearance rate of different solutes. The results are also inconsistent with the literature data, and the differences ranges are 0.09-6.35% and 0.22-2.63% for urea clearance rate and glucose clearance rate, respectively. Statistical analysis of the results is presented as mean with 95% confidence intervals (CIs) and p values 0.9472 and 0.833 of the urea and glucose clearance rates, respectively.

Dataset Information

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

Publications

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

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