An improved numerical model for epidemic transmission and infection risks assessment in indoor environment.

Social distance will remain the key measure to contain COVID-19 before the global widespread vaccination coverage expected in 2024. Containing the virus outbreak in the office is prioritised to relieve socio-economic burdens caused by COVID-19 and potential pandemics in the future. However, "what is the transmissible distance of SARS-CoV-2" and "what are the appropriate ventilation rates in the office" have been under debate. Without quantitative evaluation of the infection risk, some studies challenged the current social distance policies of 1-2 m adopted by most countries and suggested that longer social distance rule is required as the maximum transmission distance of cough ejected droplets could reach 3-10 m. With the emergence of virus variants such as the Delta variant, the applicability of previous social distance rules are also in doubt. To address the above problem, this study conducted transient Computational Fluid Dynamics (CFD) simulations to evaluate the infection risks under calm and wind scenarios. The calculated Social Distance Index (SDI) indicates that lower humidity leads to a higher infection risk due to weaker evaporation. The infection risk in office was found more sensitive to social distance than ventilation rate. In standard ventilation conditions, social distance of 1.7 m-1.8 m is sufficient distances to reach low probability of infection (PI) target in a calm scenario when coughing is the dominant transmission route. However in the wind scenario (0.25 m/s indoor wind), distance of 2.8 m is required to contain the wild virus type and 3 m is insufficient to contain the spread of the Delta variant. The numerical methods developed in this study provide a framework to evaluate the COVID-19 infection risk in indoor environment. The predicted PI will be beneficial for governments and regulators to make appropriate social-distance and ventilation rules in the office.

Deposition features of inhaled viral droplets may lead to rapid secondary transmission of COVID-19.

Inhaled viral droplets may immediately be expelled and cause an escalating re-transmission. Differences in the deposition location of inhaled viral droplets may have a direct impact on the probability of virus expelling. This study develops a numerical model to estimate the region-specific deposition fractions for inhalable droplets (1-50 µ m) in respiratory airways. The results identified a higher deposition fraction in the upper airways than the lower airways. Particularly for droplets larger than 10 µ m, the relatively high deposition fraction in the oral/laryngeal combined region warns of its easy transmission through casual talking/coughing. Moreover, considering droplet sizes' effect on virus loading capacity, we built a correlation model to quantify the potential of virus expelling hazards, which suggests an amplified cascade effect on virus transmission on top of the existing transmission mechanism. It therefore highlights the importance of considering the instant expelling possibilities from inhaled droplets, and also implies potentials in restricting a rapid secondary transmission by measures that can lower down droplet deposition in the upper airways.

Detailed deposition analysis of inertial and diffusive particles in a rat nasal passage.

Rats have been widely used as surrogates for evaluating the health effects of inhaled airborne particulate matter. To provide a thorough understanding of particle transport and deposition mechanisms in the rat nasal airway, this article presents a computational fluid dynamics (CFD) study of particle exposure in a realistic rat nasal passage under a resting flow condition. Particles covering a diameter range from 1 nm to 4 µm were passively released in front of the rat's breathing zone, and the Lagrangian particle tracking approach was used to calculate individual particle trajectories. Detailed particle deposition analysis shows the deposition of inertial particles >2 µm is high in the rat nasal vestibule and more than 70% of all inhaled inertial particles were trapped in this region. While for diffusive nanoparticles, the vestibule filtration effect is reduced, only less than 60% of inhaled nanoparticles were blocked by the anterior nasal structures. The particle exposure in the olfactory region only shows notable deposition for diffusive nanoparticles, which peaks at 9.4% for 5 nm particles. Despite the olfactory deposition remains at a low level, the ratio between the olfactory and the main passage is kept around 30-40% for 10-800 nm particles, which indicates a particle-size-independent distribution pattern in the main nasal passage and olfactory. This study provides a deep understanding of particles deposition features in a rat nasal passage, and the research findings can aid toxicologist in inter-species exposure-response extrapolation study.

Numerical Comparison of Nasal Aerosol Administration Systems for Efficient Nose-to-Brain Drug Delivery.

PURPOSE: Nose-to-brain drug administration along the olfactory and trigeminal nerve pathways offers an alternative route for the treatment of central nervous system (CNS) disorders. The characterization of particle deposition remains difficult to achieve in experiments. Alternative numerical approach is applied to identify suitable aerosol particle size with maximized inhaled doses. METHODS: This study numerically compared the drug delivery efficiency in a realistic human nasal cavity between two aerosol drug administration systems targeting the olfactory region: the aerosol mask system and the breath-powered bi-directional system. Steady inhalation and exhalation flow rates were applied to both delivery systems. The discrete phase particle tracking method was employed to capture the aerosol drug transport and deposition behaviours in the nasal cavity. Both overall and regional deposition characteristics were analysed in detail. RESULTS: The results demonstrated the breath-powered drug delivery approach can produce superior olfactory deposition with peaking olfactory deposition fractions for diffusive 1 nm particles and inertial 10 µm. While for particles in the range of 10 nm to 2 µm, no significant olfactory deposition can be found, indicating the therapeutic agents should avoid this size range when targeting the olfactory deposition. CONCLUSIONS: The breath-powered bi-directional aerosol delivery approach shows better drug delivery performance globally and locally, and improved drug administration doses can be achieved in targeted olfactory region.

Comparative numerical modeling of inhaled micron-sized particle deposition in human and rat nasal cavities.

Micron-sized particle deposition in anatomically realistic models of a rat and human nasal cavity was numerically investigated. A steady laminar inhalation flow rate was applied and particles were released from the outside air. Particles showing equivalent total particle deposition fractions were classified into low, medium and high inertial particle. Typical particle sizes are 2.5, 9 and 20 µm for the human model and 1, 2 and 3 µm for the rat model, respectively. Using a surface-mapping technique the 3D nasal cavity surface was "unwrapped" into a 2D domain and the particle deposition locations were plotted for complete visual coverage of the domain surface. The total surface area comparison showed that the surface area of the human nasal model was about ten times the size of the rat model. In contrast, the regional surface area percentage analysis revealed the olfactory region of the rat model was significantly larger than all other regions making up ∼55.6% of the total surface area, while that of the human nasal model only occupying 10.5%. Flow pattern comparisons showed rapid airflow acceleration was found at the nasopharynx region and the nostril region for the human and rat model, respectively. For the human model, the main passage is the major deposition region for micro-particles. While for the rat model, it is the vestibule. Through comparing the regional deposition flux between human and rat models, this study can contribute towards better extrapolation approach of inhalation exposure data between inter-subject species.

Numerical and experimental evaluation of nasopharyngeal aerosol administration methods in children with adenoid hypertrophy.

Administering aerosol drugs through the nasal pathway is a common early treatment for children with adenoid hypertrophy (AH). To enhance therapeutic efficacy, a deeper understanding of nasal drug delivery in the nasopharynx is essential. This study uses an integrated experimental, numerical modelling approach to investigate the delivery process of both the aerosol mask delivery system (MDS) and the bi-directional delivery system (BDS) in the pediatric nasal airway with AH. The combined effect of respiratory flow rates and particle size on delivery efficiency was systematically analyzed. The results showed that the nasopharyngeal peak deposition efficiency (DE) for BDS was approximately 2.25-3.73 times higher than that for MDS under low-flow, resting and high-flow respiratory conditions. Overall nasopharyngeal DEs for MDS were at a low level of below 16 %. For each respiratory flow rate, the BDS tended to achieve higher peak DEs (36.36 % vs 9.74 %, 37.80 % vs 14.01 %, 34.58 % vs 15.35 %) at smaller particle sizes (15 µm vs 17 µm, 10 µm vs 14 µm, 6 µm vs 9 µm). An optimal particle size exists for each respiratory flow rate, maximizing the drug delivery efficiency to the nasopharynx. The BDS is more effective in delivering drug aerosols to the nasal cavity and nasopharynx, which is crucial for early intervention in children with AH.

Numerical modelling of micron particle inhalation in a realistic nasal airway with pediatric adenoid hypertrophy: A virtual comparison between pre- and postoperative models.

Adenoid hypertrophy (AH) is an obstructive condition due to enlarged adenoids, causing mouth breathing, nasal blockage, snoring and/or restless sleep. While reliable diagnostic techniques, such as lateral soft tissue x-ray imaging or flexible nasopharyngoscopy, have been widely adopted in general practice, the actual impact of airway obstruction on nasal airflow and inhalation exposure to drug aerosols remains largely unknown. In this study, the effects of adenoid hypertrophy on airflow and micron particle inhalation exposure characteristics were analysed by virtually comparing pre- and postoperative models based on a realistic 3-year-old nasal airway with AH. More specifically, detailed comparison focused on anatomical shape variations, overall airflow and olfactory ventilation, associated particle deposition in overall and local regions were conducted. Our results indicate that the enlarged adenoid tissue can significantly alter the airflow fields. By virtually removing the enlarged tissue and restoring the airway, peak velocity and wall shear stress were restored, and olfactory ventilation was considerably improved (with a 16∼63% improvement in terms of local ventilation speed). Furthermore, particle deposition results revealed that nasal airway with AH exhibits higher particle filtration tendency with densely packed deposition hot spots being observed along the floor region and enlarged adenoid tissue area. While for the postoperative model, the deposition curve was shifted to the right. The local deposition efficiency results demonstrated that more particles with larger inertia can be delivered to the targeted affected area following Adenoidectomy (Adenoid Removal). Research findings are expected to provide scientific evidence for adenoidectomy planning and aerosol therapy following Adenoidectomy, which can substantially improve present clinical treatment outcomes.

Total and regional microfiber transport characterization in a 15th - Generation human respiratory airway.

Fiber transport and deposition in the complete respiratory airway is of great significance for human health risk assessment. Thus far, the literature has mainly focused on limited branches of the upper airway and assumes spherical particles by neglecting fiber anisotropy. To fill the gap, this paper utilized an extended realistic respiratory airway from the nasal cavity to the distal bronchial tracts, up to the 15th generation. Fibers with aerodynamic diameters from 2 to 12 µm and aspect ratios of 1, 10, and 50 were released at the inlet of the respiratory airway model, and the coupled translational and rotational motion were computed. Overall and regional fiber deposition fractions, including the nasal cavities, laryngeal airway, and lungs were predicted and compared with earlier numerical results. The study also investigated: 1) secondary flow and distributions of the fibers at the lower respiratory airway entrance; 2) upstream conditions toward fiber deposition efficiencies; 3) fiber deposition patterns and detailed deposition fractions in the five lobes. Utilizing the realistic fiber transport model, the current study found that the upstream airway geometry and the flow condition have a significant impact on the fiber transport and deposition in the downstream airway regions. The fiber depositions in the lower and middle lobes are sensitive to the fiber aerodynamic diameter, but insensitive in the upper lobes. This study expects to generate innovative knowledge on the unique fiber motion characteristics toward potential inhalation health risks.

Evolution Law of Structural Form and Heat Transfer Performance of Thermal Insulation System.

Building thermal insulation and energy conservation have become urgent problems in the field of civil engineering because they are important for achieving the goal of carbon neutralization. Thermal conductivity is an important index for evaluating the thermal insulation of materials. To study the influence of different porosity levels on the thermal conductivity of materials, this paper established a random distribution model using MATLAB and conducted a comparative analysis using COMSOL finite element software and classical theoretical numerical calculation formulas. The thermal conductivity of composite materials was determined based on a theoretical calculation formula and COMSOL software simulations, and the theoretical calculation results and simulation results were compared with the measured thermal conductivity of the composites. Furthermore, the influence of the width of the gaps between the materials on the heat transfer process was simulated in the fabricated roof structure. The results showed the following: (1) The thermal conductivity values calculated using the Zimmerman model were quite different from those calculated using the Campbell-Allen model and those calculated using the COMSOL software; (2) The thermal conductivity values calculated using the theoretical calculation formula were lower than the measured data, and the maximum relative error was more than 29%. The COMSOL simulation results were in good agreement with the measured data, and the relative error was less than 5%; (3) When the gap width was less than 60 mm, it increased linearly with the heat transfer coefficient. The heat transfer coefficient increased slowly when the gap width was greater than 60 mm. This was mainly due to the thermal bridge effect inside the insulation system. Based on these research results, a thermal insulation system was prepared in a factory.

Numerical investigation of nanoparticle deposition in the olfactory region among pediatric nasal airways with adenoid hypertrophy.

To understand inhaled nanoparticle transport and deposition characteristics in pediatric nasal airways with adenoid hypertrophy (AH), with a specific emphasis on the olfactory region, virtual nanoparticle inhalation studies were conducted on anatomically accurate child nasal airway models. The computational fluid-particle dynamics (CFPD) method was employed, and numerical simulations were performed to compare the airflow and nanoparticle deposition patterns between nasal airways with nasopharyngeal obstruction before adenoidectomy and healthy nasal airways after virtual adenoidectomy. The influence of different inhalation rates and exhalation phase on olfactory regional nanoparticle deposition features was systematically analyzed. We found that nasopharyngeal obstruction resulted in significant uneven airflow distribution in the nasal cavity. The deposited nanoparticles were concentrated in the middle meatus, septum, inferior meatus and nasal vestibule. The deposition efficiency (DE) in the olfactory region decreases with increasing nanoparticle size (1-10 nm) during inhalation. After adenoidectomy, the pediatric olfactory region DE increased significantly while nasopharynx DE dramatically decreased. When the inhalation rate decreased, the deposition pattern in the olfactory region significantly altered, exhibiting an initial rise followed by a subsequent decline, reaching peak deposition at 2 nm. During exhalation, the pediatric olfactory region DE was substantially lower than during inhalation, and the olfactory region DE in the pre-operative models were found to be significantly higher than that of the post-operative models. In conclusions, ventilation and particle deposition in the olfactory region were significantly improved in post-operative models. Inhalation rate and exhalation process can significantly affect nanoparticle deposition in the olfactory region.

Understanding the effects of inhaler resistance on particle deposition behaviour - A computational modelling study.

BACKGROUND AND OBJECTIVE: Understanding the impact of inhaler resistance on particle transport and deposition in the human upper airway is essential for optimizing inhaler designs, thereby contributing to the enhancement of the therapeutic efficacy of inhaled drug delivery. This study demonstrates the potential effects of inhaler resistance on particle deposition characteristics in an anatomically realistic human oropharynx and the United States Pharmacopeia (USP) throat using computational fluid dynamics (CFD). METHOD: Magnetic resonance (MR) imaging was performed on a healthy volunteer biting on a small mockup inhaler mouthpiece. Three-dimensional geometry of the oropharynx and mouthpiece were reconstructed from the MR images. CFD simulations coupled with discrete phase modelling were conducted. Inhaled polydisperse particles under two different transient flow profiles with peak inspiratory flow rates (PIFR) of 30 L/min and 60 L/min were investigated. The effect of inhaler mouthpiece resistance was modelled as a porous medium by varying the initial resistance (Ri) and viscous resistance (Rv). Three resistance values, 0.02 kPa0.5minL-1, 0.035 kPa0.5minL-1 and 0.05 kPa0.5 minL-1, were simulated. The inhaler outlet velocity was set to be consistent across all models for both flow rate conditions to enable a meaningful comparison of models with different inhaler resistances. RESULT: The results from this study demonstrate that investigating the effect of inhaler resistance by solely relying on the USP throat model may yield misleading results. For the geometrically realistic oropharyngeal model, both the pressure and kinetic energy profiles at the mid-sagittal plane of the airway change dramatically when connected to a higher-resistance inhaler. In addition, the geometrically realistic oropharyngeal model appears to have a resistance threshold. When this threshold is surpassed, significant changes in flow dynamics become evident, which is not observed in the USP throat model. Furthermore, this study also reveals that the impact of inhaler resistance in a geometrically realistic throat model extends beyond the oral cavity and affects particle deposition downstream of the oral cavity, including the oropharynx region. CONCLUSION: Results from this study suggest that key mechanisms underpinning the working principles of inhaler resistance are intricately connected to their complex interaction with the pharynx geometry, which affects the local pressure, local variation in velocity and kinetic energy profile in the airway.

Numerical analysis of airflow and particle deposition in multi-fidelity designs of nasal replicas following nasal administration.

BACKGROUND AND OBJECTIVE: An improved understanding of flow behaviour and particle deposition in the human nasal airway is useful for optimising drug delivery and assessing the implications of pollutants and toxin inhalation. The geometry of the human nasal cavity is inherently complex and presents challenges and manufacturing constraints in creating a geometrically realistic replica. Understanding how anatomical structures of the nasal airway affect flow will shed light on the mechanics underpinning flow regulation in the nasal pharynx and provide a means to interpret flow and particle deposition data conducted in a nasal replica or model that has reduced complexity in terms of their geometries. This study aims to elucidate the effects of sinus and reduced turbinate length on nasal flow and particle deposition efficiencies. METHODS: A complete nasal airway with maxillary sinus was first reconstructed using magnetic resonance imaging (MRI) scans obtained from a healthy human volunteer. The basic model was then modified to produce a model without the sinus, and another with reduced turbinate length. Computational fluid dynamics (CFD) was used to simulate flow in the nasal cavity using transient flow profiles with peak flow rates of 15 L/min, 35 L/min and 55 L/min. Particle deposition was investigated using discrete phase modelling (DPM). RESULTS: Results from this study show that simplifying the nasal cavity by removing the maxillary sinus and curved sections of the meatus only has a minor effect on airflow. By mapping the spatial distribution of monodisperse particles (10 µm) in the three models using a grid map that consists of 30 grids, this work highlights the specific nasal airway locations where deposition efficiencies are highest, as observed within a single grid. It also shows that lower peak flow rates result in higher deposition differences in terms of location and deposition quantity, among the models. The highest difference in particle deposition among the three nasal models is ∼10%, and this is observed at the beginning of the middle meatus and the end of the pharynx, but is only limited to the 15 L/min peak flow rate case. Further work demonstrating how the outcome may be affected by a wider range of particle sizes, less specific to the pharmaceutical industries, is warranted. CONCLUSION: A physical replica manufactured without sections of the middle meatus could still be adequate in producing useful data on the deposition efficiencies associated with an intranasal drug formulation and its delivery device.

Effect of different degrees of adenoid hypertrophy on pediatric upper airway aerodynamics: a computational fluid dynamics study.

To improve the diagnostic accuracy of adenoid hypertrophy (AH) in children and prevent further complications in time, it is important to study and quantify the effects of different degrees of AH on pediatric upper airway (UA) aerodynamics. In this study, based on computed tomography (CT) scans of a child with AH, UA models with different degrees of obstruction (adenoidal-nasopharyngeal (AN) ratio of 0.9, 0.8, 0.7, and 0.6) and no obstruction (AN ratio of 0.5) were constructed through virtual surgery to quantitatively analyze the aerodynamic characteristics of UA with different degrees of obstruction in terms of the peak velocity, pressure drop (△P), and maximum wall shear stress (WSS). We found that two obvious whirlpools are formed in the anterior upper part of the pediatric nasal cavity and in the oropharynx, which is caused by the sudden increase in the nasal cross-section area, resulting in local flow separation and counterflow. In addition, when the AN ratio was ≥ 0.7, the airflow velocity peaked at the protruding area in the nasopharynx, with an increase 1.1-2.7 times greater than that in the nasal valve area; the △P in the nasopharynx was significantly increased, with an increase 1.1-6.8 times greater than that in the nasal cavity; and the maximum WSS of the posterior wall of the nasopharynx was 1.1-4.4 times larger than that of the nasal cavity. The results showed that the size of the adenoid plays an important role in the patency of the pediatric UA.

[Effect of nasal swell body on nasal airflow and Artemisia pollen deposition].

Objective:The nasal swell body（NSB） consists of the nasal septal cartilage, nasal bone, and swollen soft tissue, all of which are visible during endoscopic and imaging examinations. Although the function of the NSB remains uncertain, there is evidence to suggest that it plays a vital role in regulating nasal airflow and filtering inhaled air. Based on anatomical and histological evidence, it is hypothesized that the NSB is indispensable in these processes. This study aims to investigate the impact of NSB on nasal aerodynamics and the deposition of allergen particles under physiological conditions. Methods:The three-dimensional （3D） nasal models were reconstructed from computed tomography （CT） scans of the paranasal sinus and nasal cavity in 30 healthy adult volunteers from Northwest China, providing basis for the construction of models without NSB following virtual NSB-removal surgery. To analyze the distribution of airflow in the nasal cavity, nasal resistance, heating and humidification efficiency, and pollen particle deposition rate at various anatomical sites, we employed the computed fluid dynamics（CFD） method for numerical simulation and quantitative analysis. In addition, we created fully transparent segmented nasal cavity models through 3D printing, which were used to conduct bionic experiments to measure nasal resistance and allergen particle deposition. Results:①The average width and length of the NSB in healthy adults in Northwest China were （12.85±1.74） mm and （28.30±1.92） mm, respectively. ②After NSB removal, there was no significant change in total nasal resistance, and cross-sectional airflow velocity remained essentially unaltered except for a decrease in topical airflow velocity in the NSB plane. ③There was no discernible difference in the nasal heating and humidification function following the removal of the NSB; ④After NSB removal, the deposition fraction（DF） of Artemisia pollen in the nasal septum decreased, and the DFs post-and pre-NSB removal were（22.79±6.61）% vs （30.70±12.27）%, respectively; the DF in the lower airway increased, and the DFs post-and pre-NSB removal were（24.12±6.59）% vs （17.00±5.57）%, respectively. Conclusion:This study is the first to explore the effects of NSB on nasal airflow, heating and humidification, and allergen particle deposition in a healthy population. After NSB removal from the healthy nasal cavities: ①nasal airflow distribution was mildly altered while nasal resistance showed no significantly changed; ②nasal heating and humidification were not significantly changed; ③the nasal septum's ability to filter out Artemisia pollen was diminished, which could lead to increased deposition of Artemisia pollen in the lower airway.

Uniqueness of inspiratory airflow patterns in a realistic rat nasal cavity.

In this study, we present a detailed flow analysis using an anatomically accurate rat nasal cavity model, in which the anatomy and physiology of the nasal airway was thoroughly examined. Special efforts were given to the swirling flow structures in the nasal vestibule (anterior section of the nose, lined by squamous epithelium), fractional flow patterns in the olfactory (posterior superior section of the rat nose, lined by olfactory epithelium), and a designated method to precisely quantify flow apportionment in the olfactory region was developed. Results revealed distinct inspiratory flow patterns in the anterior vestibule region, where the accelerated airflow undergoes two sharp turns as traveling through the tortuous airway, making a route in a shape of 8. Besides this, exceptionally large flow apportionment was observed at the interface of the olfactory recess, which can be as much as 15 times greater than that in the human nose. The thorough understanding of the airflow dynamics in the rat nasal cavity is necessary to avoid potential misinterpretation of rat-derived inhalation toxicity results. Research findings are expected to play a fundamental role in developing unbiased rat to human interspecies data extrapolation schemes.

Detailed comparison of anatomy and airflow dynamics in human and cynomolgus monkey nasal cavity.

Nonhuman primates are occasionally used as laboratory models for sophisticated medical research as they bear the closest resemblance to humans in morphometry and physiological functions. A range of nonhuman primate species have been employed in the inhalation toxicity, nasal drug delivery and respiratory viral infection studies, and they provided valuable insight to disease pathogenesis while other laboratory animals such as rodents cannot recapitulate due to the lesser degree of similarity in metabolism, anatomy and cellular response to that of humans. It is anticipated that nonhuman primate models of respiratory diseases will continue to be instrumental for translating biomedical research for improvement of human health, and the confidence in laboratory data extrapolation between species will play a pivotal role. From the morphometry and flow dynamics point of view, this study performed a detailed comparative analysis between human and a cynomolgus monkey nasal airway, with intention to provide high-fidelity qualitative and quantitative linkage between the two species for more effective laboratory data extrapolation. The study revealed that cynomolgus monkey could be a good human surrogate in nasal inhalation studies; however, care should be given for interspecies data extrapolation as subtle differences in anatomy and airflow dynamics were present between the two species.

Interspecies comparison of heat and mass transfer characteristics in monkey and human nasal cavities.

Air conditioning in the nasal airways plays an important role in regulating ambient atmospheric temperature and humidity conditions of the inhaled air. Inevitably, it may alter the behaviour and fate of inhaled ambient aerosols within the human respiratory airways due to hygroscopic growth and droplet evaporation, which is a phenomena of variations in particle sizes due to physical and chemical reactions on particle surfaces in different temperature and humidity fields. Although laboratory animals have been widely used to predict health effects of human exposure to ambient substances, the nasal temperature and humidity responses in animal surrogates and human nasal cavities are still less-investigated. This paper provides a comparative study between two monkey and two human nasal subjects under the same ambient temperature and humidity conditions, where nasal models were reconstructed from CT images and the heat and mass transfer process incorporating with the intricate nose anatomy were modelled by the computational fluid dynamics (CFD) approach. Present model comparison revealed that the monkey nasal models can reach equilibrium temperature and moisture state for inhaled ambient air in a much shorter distance compared to the human models. This indicate that heat transfer in the monkey models is more effective compared to the human models due to having a higher complexity coefficient and a smaller hydraulic radius. Hence, in order to achieve comparable or similar inhalation exposure patterns in animal surrogates, corresponding adjustments such as changing the size of released particles, or the inhalation flow rates, to achieve comparable particle Stokes number are needed. The outcomes of this study would provide informative insights for future inhalation toxicology studies related to hygroscopic materials and targeted drug delivery through nasal airways.

Numerical comparison of inspiratory airflow patterns in human nasal cavities with distinct age differences.

As a primary determinant of nasal physiological functions, the nasal morphology and its effects on the airflow dynamics have been extensively studied in literature. However, gross flow features reported in literature are mostly obtained from subjects at similar ages, while studies focusing on nasal subjects with distinct age differences are significantly less. To advance current understandings of nasal airflow dynamics in the context of age diversity, this study employed three anatomically accurate nasal cavity models with distinct age features (5-, 24- and 77-year-old models) and numerically compared the physiological nasal airflow fields within these nasal cavity models. To demonstrate the validity of the present numerical models, in vivo rhinomanometry measurement was conducted on the 24-year-old female nasal model, and key anatomical features and pressure-flow curves of all three models were compared with models with similar age features in literature work. Apart from results comparison based on conventional velocity flow fields and wall shear stress distributions, a method for quantifying flow partitions in confined airway spaces was developed to reveal the proportions of fractional flow that enters the olfactory region. Our results revealed dramatic intersubject discrepancies between considered nasal cavity models, especially for the fractional flow that enters the olfactory region. Specifically, the 5-year-old girl nasal model received the highest proportion of fractional flow, which accounts for 13.3% ~ 15% of overall inhalation flow rates under different activity levels. For the 24-year-old female model, on the contrary, the olfactory fractional flow was dramatically reduced (with a local to overall percentage around 4.3%-7.7%). Finally, for the elderly subject-77-year-old male model, minimum level of olfactory flux was observed with a local to overall percentage ranging between 3.1% and 4.9% for considered wide range of inhalation flow rates. Therefore, the local flow intersubject variation can reach nearly fourfold. The vast local flow difference is mainly due to the inherent anatomical features (e.g., immature nasal turbinate structure in the child model, the partial narrowing superior nasal valve in the elder model). The results may further lead to discrepant health effects associated with inhalation exposure to airborne particles.

Detailed comparative analysis of environmental microparticle deposition characteristics between human and monkey nasal cavities using a surface mapping technique.

Inhaled particulate matter is associated with nasal diseases such as allergic rhinitis, rhinosinusitis and neural disorders. Its health risks on humans are usually evaluated by measurements on monkeys as they share close phylogenetic relationship. However, the reliability of cross-species toxicological extrapolation is in doubt due to physiological and anatomical variations, which greatly undermine the reliability of these expensive human surrogate models. This study numerically investigated in-depth microparticle transport and deposition characteristics on human and monkey (Macaca fuscata) nasal cavities that were reconstructed from CT-images. Deposition characteristics of 1-30µm particles were investigated under resting and active breathing conditions. Similar trends were observed for total deposition efficiencies and a single correlation using Stokes Number was fitted for both species and both breathing conditions, which is convenient for monkey-human extrapolation. Regional deposition patterns were carefully compared using the surface mapping technique. Deposition patterns of low, medium and high inertial particles, classified based on their total deposition efficiencies, were further analyzed in the 3D view and the mapped 2D view, which allows locating particle depositions on specific nasal regions. According to the particle intensity contours and regional deposition profiles, the major differences were observed at the vestibule and the floor of the nasal cavity, where higher deposition intensities of medium and high inertial particles were shown in the monkey case than the human case. Comparisons of airflow streamlines indicated that the cross-species variations of microparticle deposition patterns are mainly contributed by two factors. First, the more oblique directions of monkey nostrils result in a sharper airflow turn in the vestibule region. Second, the monkey's relatively narrower nasal valves lead to higher impaction of medium and high inertial particles on the nasal cavity floor. The methods and findings in this study would contribute to an improved cross-species toxicological extrapolation between human and monkey nasal cavities.

Transport and deposition of ultrafine particles in the upper tracheobronchial tree: a comparative study between approximate and realistic respiratory tract models.

This paper presents a computational fluid dynamics (CFD) study of air-particle flows in the upper tracheobronchial tree. Two respiratory tract models, including a parametrically controlled approximate airway model developed by Kitaoka (KG model) and a CT-based patient specific airway (realistic model) were used. Assuming laminar, quasi-steady, three-dimensional air flow and spherical non-interacting ultrafine particles in sequentially bifurcating rigid bronchial airways, airflow patterns and particle transport/deposition in these two airway models were evaluated and compared. Overall deposition efficiency data was compared with the widely adopted ICRP data published by The International Commission on Radiological Protection. Good deposition efficiency agreements were observed between the present respiratory tract models and the ICRP data, which validated the numerical prediction accuracy of the present computational fluid-particle dynamics (CFPD) model. For the two respiratory models, the comparison showed both difference and similarity between the approximate KG model and the realistic model. Specifically, the realistic model showed more complicated airflow patterns due to the increased surface irregularity. The deposition efficiency data revealed a deposition preference in the first-generation airways compared to the rest regions. For ultrafine particles smaller than 10 nm, Brownian diffusion remains the dominant particle deposition mechanism. However, for ultrafine particles with size ranging from 10 nm to 100 nm, the deposition efficiency decreased dramatically with the 100 nm particles approaching to zero deposition in the present bronchial tree scope. The generation-by-generation deposition data presented in this paper is indispensable to the formulation of new lung inhalation exposure models.