Deposition Fraction Research Articles

Numerical simulation of welding fume lung dosimetry

Exposures to airborne particles and toxic gases generated by welding fabrication activities will potentially lead to various diseases. Accurate information on the transport and deposition of such aerosols in the respiratory system is critically needed for precise health risk assessments. To address the data demand mentioned above, a multiscale computational fluid-particle dynamics (CFPD) model was developed in this study. Specifically, a virtual fabrication shop was integrated with a virtual human in the numerical model to evaluate the effects of ventilation condition, particle size, and gas species on the lung uptakes of those welding fume particles and gases. Welding fume particle and gases transmission, transport, and deposition have been simulated and analyzed starting from the emission source to the subject-specific human respiratory system via oral inhalation. Spherical iron particles with diameters of 100, 190, and 830 nm were simulated. The transport and absorption of NOx and CO were predicted too. Steady-state inhalation with 11.87 L/min was applied with two different air filter ventilation conditions. The numerical results indicate that the ventilation condition can significantly influence welding gas transport and deposition. The pulmonary gas absorption rate is much higher at poor ventilation conditions. The air-tissue absorption coefficient is another crucial factor that can impact pulmonary gas absorption. The total particle deposition fractions (TDFs) from mouth/nose to generation 6 (G6) are less than 18.0%, and particles mostly deposit in the oral cavity. Regional and local particle deposition data demonstrate that particles tend to enter the two upper lobes more than the other three lobes. In summary, this study paves the way to build a personalized in silico tool based on CFPD models for noninvasive precise health risk assessments associated with different welding activities.

Laminar-turbulent transition in a constricted tube: Comparison of Reynolds-averaged Navier–Stokes turbulence models and large eddy simulation with experiments

Constricted tubes appear in many engineering as well as biological systems such as blood vessels or pulmonary airways. The aim of this article is to test the ability of different turbulence models to predict the flow field and deposition of particles in a constricted tube. The constricted geometry of Ahmed and Giddens was employed to compare various numerical approaches. Two large eddy simulations and several Reynolds-averaged Navier–Stokes models were used for calculations using the Star-CCM+ commercial solver. The performance of these models was compared with the experiments and other published studies. For selected turbulence models, deposition of particles with different Stokes numbers using Lagrangian multiphase model was enabled. The results show that large eddy simulation best predicts the transition from laminar to turbulent flow in terms of mean axial velocity, and similarly does also standard low-Reynolds k–ε model. The comparison of deposition fractions shows substantial differences among the models, especially for the smallest particles. It was demonstrated that even a simple stenosed smooth tube is a very intricate problem for the present computational fluid dynamics models; therefore, to get reliable results, numerical models need to be validated for the same geometry and similar conditions.

Aerosol depositional characteristics in piping assembly under varying flow conditions

In the event of a nuclear reactor accident, large amount of radioactivity in the form of fission products may get released to the piping assembly of primary heat transport system. These fission products mostly in the form of aerosol particles get deposited on the inner surface of the piping system due to various depositional processes. The removal processes in the complex piping system are controlled to a large extent by the thermal-hydraulic conditions like temperature, pressure and flow rates. These parameters generally vary with time and therefore must be carefully monitored to predict the aerosol behavior in the piping system. Experimental determination of the deposition fraction, interpretation of the role of controlling parameters and development/validation of theoretical models are key areas gaining constant attention among researchers. In the present work, experiments were conducted in a piping assembly consisting of bends and horizontal-vertical orientation at two different carrier gas flow rates. Deposition fractions in the test assembly were estimated and the role of different dynamical processes (thermophoresis, gravitation and bend impaction) was interpreted. The computational fluid dynamics modeling approach is used for theoretical simulation in this work. Aerosol behavior in terms of number concentration, particle size distribution, and particle deposition in the piping system was simulated with the computational fluid dynamics software ANSYS Fluent 16.0 and the results were compared with experimental measurements (wherever applicable).

Numerical study of the effects of temperature and humidity on the transport and deposition of hygroscopic aerosols in a G3-G6 airway

The hygroscopicity of the aerosols could be utilized to enhance the delivery efficiency of the drug aerosols for pulmonary diseases. In a simple mouth-throat airway model, the heat and mass transfer of the airway boundary, i.e., convection over the mucus layer, evaporation heat of the water vapor evaporated from the mucus layer and the conduction in the mucus-tissue region, have been found to have notable impacts on the transport and deposition of hygroscopic aerosols (Chen et al., 2018). The effect of this coupled heat and mass transfer on the hygroscopic aerosol transport is yet unknown in the deeper lung region in light of the increases of the airway temperature and humidity. This numerical study investigates the transport and deposition of the hygroscopic aerosols in a G3-G6 lung airway under three conditions: (i) constant temperature at 37 °C and constant relative humidity (RH) at 0% in the whole airway, i.e., neglecting hygroscopicity; (ii) more realistic boundary including the mass and heat transfer at the airway boundary; (iii) constant temperature at 37 °C and constant RH at 99.5% in the whole airway. Besides the temperature and RH distributions of the airway, the deposition fractions and deposition patterns of the hygroscopic aerosols as well as the distributions of the escaped aerosols are compared. As the most important outcome, the results show that using the heat and mass transfer of the airway boundary can better predict the aerosol hygroscopic growth and thereby more accurately estimate the deposition fraction of the hygroscopic aerosol. Thus, for the design of a high efficiency pulmonary drug delivery system, including the device and the hygroscopic drug aerosol, on a patient-specific level in future, the heat and mass transfer of the airway boundary should be considered.

Simulation of Airway Deposition of an Aerosol Drug in COPD Patients.

Medical aerosols are key elements of current chronic obstructive pulmonary disease (COPD) therapy. Therapeutic effects are conditioned by the delivery of the right amount of medication to the right place within the airways, that is, to the drug receptors. Deposition of the inhaled drugs is sensitive to the breathing pattern of the patients which is also connected with the patient’s disease severity. The objective of this work was to measure the realistic inhalation profiles of mild, moderate, and severe COPD patients, simulate the deposition patterns of Symbicort® Turbuhaler® dry powder drug and compare them to similar patterns of healthy control subjects. For this purpose, a stochastic airway deposition model has been applied. Our results revealed that the amount of drug depositing within the lungs correlated with the degree of disease severity. While drug deposition fraction in the lungs of mild COPD patients compared with that of healthy subjects (28% versus 31%), lung deposition fraction characteristic of severe COPD patients was lower by a factor of almost two (about 17%). Deposition fraction of moderate COPD patients was in-between (23%). This implies that for the same inhaler dosage severe COPD patients receive a significantly lower lung dose, although, they would need more.

Differences in Particle Deposition Between Members of Imaging-Based Asthma Clusters.

Background: Four computed tomography (CT) imaging-based clusters have been identified in a study of the Severe Asthma Research Program (SARP) cohort and have been significantly correlated with clinical and demographic metrics (J Allergy Clin Immunol 2017; 140:690-700.e8). We used a computational fluid dynamics (CFD) model to investigate air flow and aerosol deposition within imaging archetypes representative of the four clusters. Methods: CFD simulations for air flow and 1-8 μm particle transport were performed using CT-based airway models from two healthy subjects and eight asthma subjects. The subject selection criterion was based on the discriminant imaging-based flow-related variables of J(Total) (average local volume expansion in the total lung) and Dh*(sLLL) (normalized airway hydraulic diameter in the left lower lobe), where reduced J(Total) and Dh*(sLLL) indicate reduced regional ventilation and airway constriction, respectively. The analysis focused on the comparisons between all clusters with respect to healthy subjects, between cluster 2 and cluster 4 (nonsevere and severe asthma clusters with airway constriction) and between cluster 3 and cluster 4 (two severe asthma clusters characterized by normal and constricted airways, respectively). Results: Nonsevere asthma cluster 2 and severe asthma cluster 4 subjects characterized by airway constriction had an increase in the deposition fraction (DF) in the left lower lobe. Constricted flows impinged on distal bifurcations resulting in large depositions. Although both cluster 3 (without constriction) and cluster 4 (with constriction) were severe asthma, they exhibited different particle deposition patterns with increasing particle size. The statistical analysis showed that Dh*(sLLL) plays a more important role in particle deposition than J(Total), and regional flow fraction is correlated with DF among lobes for smaller particles. Conclusions: We demonstrated particle deposition characteristics associated with cluster-specific imaging-based metrics such as airway constriction, which could pertain to the design of future drug delivery improvements.

The Influence of Aerosol Density and Shape Factor on the Assessment of Internal Exposure to 239Pu.

Internal exposure due to inhalation of aerosols depends on the ratio of aerodynamic shape factor (χ) to aerosol mass density (ρ). Inhaled aerosol parameters may differ from the default ρ and χ values provided by the International Commission on Radiological Protection, which are adopted for the assessment of internal exposures. This paper focuses on the influences of χ/ρ on the assessment of internal exposure to Pu for reference workers. Regional deposition fractions are found to decrease with increasing χ/ρ, and larger decreases are observed with smaller activity median aerodynamic diameter aerosols, while the slow clearance fractions (fs) in the tracheobronchial region are more sensitive for larger activity median aerodynamic diameter aerosols. Results from biokinetics calculations reveal that both the time-dependent content (excretion) and cumulative activities are determined mainly for particles initially deposited in the alveolar-interstitial region, while fs affects the local cumulative activities in the tracheobronchial region. χ/ρ is proven to have different influences for aerosols with different activity median aerodynamic diameters. The default χ/ρ values can be used when activity median aerodynamic diameters are greater than 1 μm, while one should pay attention to the value of χ/ρ when activity median aerodynamic diameters are less than 1 μm, where significant influence may be anticipated.

Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients

Topical intranasal drugs are widely prescribed for chronic rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of 3 subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-µm to 120-µm sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-µm to 30-µm droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. Among nebulized droplet sizes, 11-µm to 14-µm droplets achieved at least 50% of MSDF in all 6 sinonasal cavities. Four of 6 sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement.

Evaluation of Bio-relevant Mouth-Throat Models for Characterization of Metered Dose Inhalers.

For inhalation drug characterization, the traditionally used USP induction port provides limited in vivo predictive capability because it does not adequately mimic airway geometry. In this study, various bio-relevant mouth-throat (MT) models, including Alberta Idealized Throat (AIT), and 3D printed large/medium/small-sized VCU (Virginia Commonwealth University) models were evaluated using two metered dose inhaler (MDI) drug products: a solution MDI containing beclomethasone dipropionate (BDP-MDI) and a suspension MDI containing fluticasone propionate (FP-MDI). For BDP-MDI, use of VCU large and small MT models resulted in a significantly higher MT deposition and lower fine particle fraction (FPF) compared with the other MT models. In the case of FP-MDI, the three VCU models resulted in higher MT deposition and lower FPF compared with the USP induction port and AIT. Overall, the in vitro testing results for the suspension MDI were more sensitive to geometric differences of the MT models than those for the solution MDI. Our results suggest that in vitro characterization of MDI products can be influenced by many factors, including the type of formulation, the MT geometry, shape, internal space volume, and the material used to make the MT models.

Study of particle deposition on the complex components of environmental control systems

As most airplanes do not have HEPA filters for filtering outside air, particulate matter in the outdoor air can deposit on the environmental control systems (ECS) of the airplanes. The particles that accumulate on the various surfaces of the ECS components can affect their thermal performance and may lead to component failures. This study experimentally and numerically investigated the particle deposition on a heat exchanger and a turbocharger, which are key components of ECS with complex geometry. A test rig was built to obtain the monodisperse particle deposition fractions by measuring the particle concentration upstream and downstream of the components with the weighing method. The tested particles ranged from 1 to 8 μm in diameter. Different Reynolds-averaged Navier-Stokes (RANS) models, together with a modified Lagrangian method, were used to predict the total particle deposition fractions in the tested components. The computed particle deposition was compared with the experimental data. The results showed that the RNG k-ε model with near-wall correction provided the most accurate prediction of the particle deposition fraction on the heat exchanger and turbocharger. The particle deposition fraction increased significantly with the particle size. CFD simulation provided detailed information about the particle deposition distribution inside the heat exchanger and turbocharger. The location and number of deposited particles depended mainly on the particle size and air velocity. This investigation identified a suitable tool for studying particle deposition in the ECS of commercial airplanes.

Modeling the particle deposition in the respiratory system during successive respiratory cycles

In this study, using a 5-lobe symmetric model, total, lobar and generational particle deposition in the lungs during successive cycles is investigated. It has been found that for the particle size between 0.05 and 2 μm and the tidal volumes greater than 1000 ml, considering the effect of successive cycles predicted more deposition fraction per cycle compared to a single cycle up to about 16 percent. The mentioned range of tidal volume is related to light or heavy physical activities. So, it can be understood that people exposed to particulate matter within the mentioned size range, when acting physically, are at more health risk compared not only to the resting state, but also to the same state calculations based on a single cycle. Finally, total and generational remaining mass fraction suspended in the respiratory tract after the completion of each cycle is calculated. This remaining mass fraction turned out to be negligible except for particles between 0.05 and 2 μm.

The Effectiveness of An Averaged Airway Model in Predicting the Airflow and Particle Transport Through the Airway.

Background: In this study, we proposed an averaged airway model design based on four healthy subjects and numerically evaluated its effectiveness for predicting the airflow and particle transport through an airway. Methods: Direct-averaged models of the conducting airways of four subjects were restored by averaging the three-dimensional (3D) skeletons of four healthy airways, which were calculated using an inverse 3D thinning algorithm. We simulated the airflow and particle transport in the individual and the averaged airway models using computational fluid dynamics. Results: The bifurcation geometry differs even among healthy subjects, but the averaged model retains the typical geometrical characteristics of the airways. The Reynolds number of the averaged model varied within the range found in the individual subject models, and the averaged model had similar inspiratory flow characteristics as the individual subject models. The deposition fractions at almost all individual lobes ranged within the variation observed in the subjects, however, the deposition fraction was higher in only one lobe. The deposition distribution at the main bifurcation point differed among the healthy subjects, but the characteristics of the averaged model fell within the variation observed in the individual subject models. On the contrary, the deposition fraction of the averaged model was higher than that of the average of the individual subject models and deviated from the range observed in the subject models. Conclusion: These results indicate that the direct-averaged model may be useful for predicting the individual airflow and particle transport on a macroscopic scale.

Evaluation of particulate matter deposition in the human respiratory tract during winter in Nanjing using size and chemically resolved ambient measurements

Size-segregated ambient aerosols were collected by a five-stage impactor at a suburban Nanjing site during the winter of 2016–2017 to estimate the chemical composition and size distribution of particles deposited in different parts of the human respiratory tract. Chemical compositions of carbonaceous aerosols, water-soluble ions, and trace heavy metals were measured. Particulate matter (PM) mass deposited in nasopharyngeal (NOPL), tracheobronchial (TB), and pulmonary (P) was obtained by integrating the size-dependent deposition fractions. During the sampling period, the average PM10 and PM2.5 concentrations were 108.8 ± 30.8 and 77.2 ± 24.2 μg/m3, respectively. Organic matter and water-soluble ions were major components in fine particles. The fine particles had a significant contribution to the particulate pollution in winter Nanjing. The mass concentration of particles increases significantly from the clean days to the pollution days, especially for particles in 1–2.5 μm. The proportion of NO3− and undetected components in particulate matter increases on pollution days, while the proportion of elemental carbon (EC), SO42−, and NH4+ decreases. During the study period, the total particulate matter deposit per minute in the NOPL, TB, and P was 1.06 ± 0.35, 0.10 ± 0.03, and 0.42 ± 0.14 μg, respectively, assuming normal respiration of tidal volumes of 1450 cm3 per breath and 15 breaths per minute. Particles in 2.5–10 μm had the highest deposition mass in NOPL of 0.57 ± 0.16 μg, while particles in < 0.5 μm had the highest deposition mass in TB (0.03 ± 0.01 μg), and particles in 1–2.5 μm had the highest deposition mass in P (0.14 ± 0.06 μg). The total particulate matter deposited in the NOPL, TB, and P increased from 0.79 ± 0.25, 0.08 ± 0.02, and 0.30 ± 0.09 μg on the clean days to 1.23 ± 0.29 μg, 0.12 ± 0.03 μg, and 0.49 ± 0.11 μg on the pollution days. More secondary inorganic aerosol (SNA) and metals (especially Zn, Cr, and Cu) were in the PM deposited in TB and P than in the ambient PM, while more undetected components in the PM deposited in NOPL. The chemical composition fractions deposited in a specific region were different from those measured in the ambient atmosphere, indicating that health effect studies of PM should consider the deposition rates of PM in the human respiratory tract, in addition to the ambient size and chemical characteristics of ambient PM.

Variability in oropharyngeal airflow and aerosol deposition due to changing tongue positions

Human tongue is a highly compliant entity and its position has significant effects on the delivery efficiency of orally inhaled pharmaceuticals. However, studies of tongue postures on aerosol transport and deposition are rare due to technical challenges in developing such models. This study presents a computational oropharyngeal model with varying tongue shapes, which are representative of the positions a subject takes during pulmonary drug delivery. The affected airflow and aerosol behaviors were simulated using a well-validated computational fluid-particle tracking model. Results show that, depending on the extent of the morphology variations, tongue position can significantly alter the airflow pattern and particle behaviors in the oral cavity and the subsequent pharyngeal airway. The variability in the total oropharyngeal filtering rate was 6%–25% and varied with particles sizes and breathing conditions. Much higher differences were observed in the compartmental deposition fractions, with the most pronounced variations in the oral cavity. The effects from tongue positioning were also observed in the particle distributions that entered the lungs, which might further cause differences in the pulmonary deposition distributions. Results of this study indicate that the tongue position can be a key factor in administering therapeutic agents to conducting airways (e.g., bronchial asthma).

Numerical Simulation of Transport and Deposition of Dust Particles in Human Tracheobronchial Airways

Dust is a common pollutant of the air we breath. If dust particles are inhaled and deposited in human airways, they can cause a variety of respiratory disorders. The inhaled dust particles motion in human airways goes along with the airflow. The transport process can be considered as a two-phase flow of a gas phase and a particle phase. In this study, we investigated the airflow and dust particles transport and deposition in human tracheobronchial airways using computational fluid dynamics (CFD) techniques. A steady simulation was performed in asymmetric tracheobronchial airway mode consisting of 19 outlets to observe the characteristics of airflow fields. The discrete phase model (DPM) was employed to predict the particle trajectories and deposition in the airway model. Deposition resulted from inertial impaction and gravitational sedimentation was considered. In the simulation, the airflow characteristics differences in the right and left bronchial trees were observed. The influence of secondary flow on dust particles motion was great. More dust particles were deposited in the right bronchial tree than in the left. The deposition fraction of dust particles in human tracheobronchial airways was high. This study can provide awareness on deposition of dust particles passing beyond the larynx and enhance prevention of their entry into the respiratory system. It can also contribute a convenient way on the location of deposition of particles of a given type in human respiratory tract to be used for respiratory disease preventions.

Magnetic aerosol drug targeting in lung cancer therapy using permanent magnet

Primary bronchial cancer accounts for almost 20% of all cancer death worldwide. One of the emerging techniques with tremendous power for lung cancer therapy is magnetic aerosol drug targeting (MADT). The use of a permanent magnet for effective drug delivery in a desired location throughout the lung requires extensive optimization, but it has not been addressed yet. In the present study, the possibility of using a permanent magnet for trapping the particles on a lung tumor is evaluated numerically in the Weibel's model from G0 to G3. The effect of different parameters is considered on the efficiency of particle deposition in a tumor located on a distant position of the lung bronchi and bronchioles. Also, the effective position of the magnetic source, tumor size, and location are the objectives for particle deposition. The results show that a limited particle deposition occurs on the lung branches in passive targeting. However, the incorporation of a permanent magnet next to the tumor enhanced the particle deposition fraction on G2 to up to 49% for the particles of 7 µm diameter. Optimizing the magnet size could also improve the particle deposition fraction by 68%. It was also shown that the utilization of MADT is essential for effective drug delivery to the tumors located on the lower wall of airway branches given the dominance of the air velocity and resultant drag force in this region. The results demonstrated the high competence and necessity of MADT as a noninvasive drug delivery method for lung cancer therapy.

Environmental inhalants from tobacco burning: Tar and particulate emissions

Abstract Cigarette smoking is credited for decreasing the world population annually by about 1%. This paper therefore explores the carcinogenic and mutagenic residue (tar), and particulate matter from the thermal degradation of tobacco cigarettes coded, SPM and ES1, at a residence time of 2.0 s at 1 atm. This study was carried out in the temperature range 200–600 °C with nitrogen as the pyrolysis gas. Field emission gun scanning electron microscope was used to image the nature of particulate emissions from tobacco smoke. It was shown that tobacco smoke particulates are ultrafine; ∼22 and 28 nm for SPM and ES1 cigarettes respectively. Particle deposition fraction in the human lung and pulmonary lobes was simulated using the Multipath Particle Deposition (MPPD) model. The ultrafine particulates if inhaled are grave precursors for various respiratory health ailments. Maximum tar yield was produced at ∼400 °C. Thus, designing cigarettes that may be smoked at temperatures lower than 400 °C may be beneficial to the tobacco smoking community. From MPPD model runs, it was found that the pulmonary tissue retained the highest fraction (0.448) of particles of 22 nm geometric diameter in comparison to 0.418 fraction of the slightly larger particles of 28 nm geometric diameter from ES1 cigarette. This implies that the respiratory system has a poor clearance of particles of smaller geometric diameter. Thus, extremely ultrafine particulates are of grave concern to cigarette smokers.

Numerical investigation of deposition mechanism in three mouth–throat models

Understanding the deposition mechanisms of pharmaceutical aerosol in the mouth-throat (MT) is crucial to developing an in vitro method which aims to better predict in vivo lung deposition. This paper investigated the effect of geometrical variation, particle size and airflow rate on the fine particle deposition in the US pharmacopeia throat (USP), idealized mouth-throat (IMT) and realistic mouth-throat (RMT) models. The flow-field equations were solved with the SST model by computational fluid dynamics (CFD) and monodispersed particles in the size range of 1–30 μm were tracked with discrete phase method (DPM). The results indicated that the deposition fraction and spatial distribution were highly sensitive to the geometrical variation and respiratory conditions such as the inhalation airflow rate and particle size. Moreover, the effect of geometrical variation on the particle escape pattern was more dominant. Comparing to the IMT model, more uniformly distribution of escape particles was observed at the outlet of RMT. While the total deposition fractions in IMT and RMT were similar, the spatial distributions of deposited particles were significantly different. In the RMT model, fewer particles were deposited in mouth and trachea, but the depositions in the pharyngeal and laryngeal regions were more uniform. These conclusions could help study the in vitro-in vivo correlation of dry powder inhaler systems.

Mice-to-men comparison of inhaled drug-aerosol deposition and clearance

Part of the effective prediction of the pharmacokinetics of drugs (or toxic particles) requires extrapolation of experimental data sets from animal studies to humans. As the respiratory tracts of rodents and humans are anatomically very different, there is a need to study airflow and drug-aerosol deposition patterns in lung airways of these laboratory animals and compare them to those of human lungs. As a first step, interspecies computational comparison modeling of inhaled nano-to-micron size drugs (50 nm < d<15μm) was performed using mouse and human upper airway models under realistic breathing conditions. Critical species-specific differences in lung physiology of the upper airways and subsequently in local drug deposition were simulated and analyzed. In addition, a hybrid modeling methodology, combining Computational Fluid-Particle Dynamics (CF-PD) simulations with deterministic lung deposition models, was developed and predicted total and regional drug-aerosol depositions in lung airways of both mouse and man were compared, accounting for the geometric, kinematic and dynamic differences. Interestingly, our results indicate that the total particle deposition fractions, especially for submicron particles, are comparable in rodent and human respiratory models for corresponding breathing conditions. However, care must be taken when extrapolating a given dosage as considerable differences were noted in the regional particle deposition pattern. Combined with the deposition model, the particle retention and clearance kinetics of deposited nanoparticles indicates that the clearance rate from the mouse lung is higher than that in the human lung. In summary, the presented computer simulation models provide detailed fluid-particle dynamics results for upper lung airways of representative human and mouse models with a comparative analysis of particle lung deposition data, including a novel mice-to-men correlation as well as a particle-clearance analysis both useful for pharmacokinetic and toxicokinetic studies.

Comparative study of simulated nebulized and spray particle deposition in chronic rhinosinusitis patients

Introduction: Topical intranasal drugs are widely prescribed for Chronic Rhinosinusitis (CRS), although delivery can vary with device type and droplet size. The study objective was to compare nebulized and sprayed droplet deposition in the paranasal sinuses and ostiomeatal complex (OMC) across multiple droplet sizes in CRS patients using computational fluid dynamics (CFD). Methods: Three-dimensional models of sinonasal cavities were constructed from computed tomography (CT) scans of three subjects with CRS refractory to medical therapy using imaging software. Assuming steady-state inspiratory airflow at resting rate, CFD was used to simulate 1-120 {\mu}m sprayed droplet deposition in the left and right sinuses and OMC with spray nozzle positioning as in current nasal spray use instructions. Zero-velocity nebulization simulations were performed for 1-30 {\mu}m droplet sizes, maximal sinus and OMC deposition fractions (MSDF) were obtained, and sizes that achieved at least 50% of MSDF were identified. Nebulized MSDF was compared to sprayed droplet deposition. We also validated CFD framework through in vitro experiments. Results: Among nebulized droplet sizes, 11-14 {\mu}m droplets achieved at least 50% of MSDF in all six sinonasal cavities. Five of six sinonasal cavities had greater sinus and OMC deposition with nebulized droplets than with sprayed droplets at optimal sizes. Conclusions: Nebulized droplets may target the sinuses and OMC more effectively than sprayed particles at sizes achieving best deposition. Further studies are needed to confirm our preliminary findings. Several commercial nasal nebulizers have average particle sizes outside the optimal nebulized droplet size range found here, suggesting potential for product enhancement.