Jinxiang Xi

Effectiveness of Direct Lagrangian Tracking Models for Simulating Nanoparticle Deposition in the Upper Airways

Direct Lagrangian particle tracking may provide an effective method for simulating the deposition of ultrafine aerosols in the upper respiratory airways that can account for finite inertia and slip correction effects. However, use of the Lagrangian approach for simulating ultrafine aerosols has been limited due to computational cost and numerical difficulties. The objective of this study is to evaluate the effectiveness of direct Lagrangian tracking methods for calculating ultrafine aerosol transport and deposition in flow fields consistent with the upper respiratory tract. Representative geometries that have been considered include a straight tubular flow field, a 90° tubular bend, and an idealized replica of the human oral airway. The Lagrangian particle tracking algorithms considered include the Fluent Brownian motion (BM) routine, a user-defined BM model, and a user-defined BM model in conjunction with a near-wall interpolation (NWI) algorithm. Lagrangian deposition results have been compared with a chemical species Eulerian model, which neglects particle inertia, and available experimental data. Results indicate that the Fluent BM routine incorrectly predicts the diffusion-driven deposition of ultrafine aerosols by up to one order of magnitude in all cases considered. For the tubular and 90° bend geometries, Lagrangian model results with a user-defined BM routine agreed well with the Eulerian model, available analytic correlations, and experimental deposition data. Considering the oral airway model, the best match to empirical deposition data over a range of particle sizes from 1 to 120 nm was provided by the Lagrangian model with user-defined BM and NWI routines. Therefore, a direct Lagrangian transport model with appropriate user-defined routines provides an effective approach to accurately predict the deposition of nanoparticles in the respiratory tract.

Effects of the laryngeal jet on nano- and microparticle transport and deposition in an approximate model of the upper tracheobronchial airways

The extent to which laryngeal-induced flow features penetrate into the upper tracheobronchial (TB) airways and their related impact on particle transport and deposition are not well understood. The objective of this study was to evaluate the effects of including the laryngeal jet on the behavior and fate of inhaled aerosols in an approximate model of the upper TB region. The upper TB model was based on a simplified numerical reproduction of a replica cast geometry used in previous in vitro deposition experiments that extended to the sixth respiratory generation along some paths. Simulations with and without an approximate larynx were performed. Particle sizes ranging from 2.5 nm to 12 mum were considered using a well-tested Lagrangian tracking model. The model larynx was observed to significantly affect flow dynamics, including a laryngeal jet skewed toward the right wall of the trachea and a significant reverse flow in the left region of the trachea. Inclusion of the laryngeal model increased the tracheal deposition of nano- and micrometer particles by factors ranging from 2 to 10 and significantly reduced deposition in the first three bronchi of the model. Considering localized conditions, inclusion of the laryngeal approximation decreased deposition at the main carina and produced a maximum in local surface deposition density in the lobar-to-segmental bifurcations (G2-G3) for both 40-nm and 4-microm aerosols. These findings corroborate previous experiments and highlight the need to include a laryngeal representation in future computational and in vitro models of the TB region.

Condensational Growth May Contribute to the Enhanced Deposition of Cigarette Smoke Particles in the Upper Respiratory Tract

Previous experimental studies have shown that concentrated cigarette smoke particles (CSPs) deposit in the upper airways like much larger 6 to 7 μ m aerosols. Based on the frequent assumption that relative humidity (RH) in the lungs does not exceed approximately 99.5%, the hygroscopic growth of initially submicrometer CSPs is expected to be a relatively minor factor. However, the inhalation of mainstream smoke may result in humidity values ranging from sub-saturated through supersaturated conditions. The objective of this study is to evaluate the effect of condensation particle growth on the transport and deposition of CSPs in the upper respiratory tract under various RH and temperature conditions. To achieve this objective, a computational model of transport in the continuous phase surrounding a CSP was developed for a multicomponent aerosol consisting of water soluble and insoluble species. To evaluate the transport and deposition of dilute hygroscopic CSPs in the upper airways, a model of the human mouth-throat (MT) through approximately respiratory generation G6 was considered with four steady inhalation conditions. These inhalation conditions were representative of inhaled ambient cigarette smoke as well as warm and hot saturated smoke. Results indicate that RH conditions above 100% are possible in the upper respiratory tract during the inhalation of a warm or hot saturated airstream. For sub-saturated inhalation conditions, initial evaporation of the CSPs was observed followed by hygroscopic growth and diameter increases less than approximately 50%. In contrast, the inhalation of warm or hot saturated air resulted in significant particle growth in the MT and tracheobronchial regions. For the inhalation of warm saturated air 3°C above body temperature, initially 200 and 400 nm particles were observed to increase in size to above 3 μ m near the trachea inlet. The upper boundary inhalation condition of saturated 47°C air resulted in 7 to 8 μ m droplets entering the trachea. These results do not prove that the enhanced deposition of CSPs in the upper airways is only a result of condensational growth. However, this study does highlight condensational growth as a potentially significant mechanism in the deposition of smoke particles under saturated inhalation conditions.

Effects of Oral Airway Geometry Characteristics on the Diffusional Deposition of Inhaled Nanoparticles

The deposition of ultrafine aerosols in the respiratory tract presents a significant health risk due to the increased cellular-level response that these particles may invoke. However, the effects of geometric simplifications on local and regional nanoparticle depositions remain unknown for the oral airway and throughout the respiratory tract. The objective of this study is to assess the effects of geometric simplifications on diffusional transport and deposition characteristics of inhaled ultrafine aerosols in models of the extrathoracic oral airway. A realistic model of the oral airway with the nasopharynx (NP) included has been constructed based on computed tomography scans of a healthy adult in conjunction with measurements reported in the literature. Three other geometries with descending degrees of physical realism were then constructed with successive geometric simplifications of the realistic model. A validated low Reynolds number k-omega turbulence model was employed to simulate laminar, transitional, and fully turbulent flow regimes for the transport of 1-200 nm particles. Results of this study indicate that the geometric simplifications considered did not significantly affect the total deposition efficiency or maximum local deposition enhancement of nanoparticles. However, particle transport dynamics and the underlying flow characteristics such as separation, turbulence intensity, and secondary motions did show an observable sensitivity to the geometric complexity. The orientation of the upper trachea was shown to be a major factor determining local deposition downstream of the glottis and should be retained in future models of the respiratory tract. In contrast, retaining the NP produced negligible variations in airway dynamics and could be excluded for predominantly oral breathing conditions. Results of this study corroborate the use of existing diffusion correlations based on a circular oral airway model. In comparison to previous studies, an improved correlation for the deposition of nanoparticles was developed based on a wider range of particle sizes and flow rates, which captures the dependence of the Sherwood number on both Reynolds and Schmidt numbers.

Breathing resistance and ultrafine particle deposition in nasal-laryngeal airways of a newborn, an infant, a child, and an adult.

As a human grows from birth to adulthood, both airway anatomy and breathing conditions vary, altering the deposition rate and pattern of inhaled aerosols. However, deposition studies have typically focused on adult subjects, results of which may not be readily extrapolated to children. This study numerically evaluated the age-related effects on the airflow and aerosol dynamics in image-based nose–throat models of a 10-day-old newborn, a 7-month-old infant, a 5-year-old child, and a 53-year-old adult. Differences in airway physiology, breathing resistance, and aerosol filtering efficiency among the four models were quantified and compared. A high-fidelity fluid-particle transport model was employed to simulate the multi-regime airflows and particle transport within the nasal–laryngeal airways. Ultrafine particles were evaluated under breathing conditions ranging from sedentary to heavy activities. Results of this study indicate that the nasal–laryngeal airways at different ages, albeit differ significantly in morphology and dimension, do not significantly affect the total deposition fractions or maximum local deposition enhancement for ultrafine aerosols. Further, the deposition partitioning in the sub-regions of interest is different among the four models. Results of this study corroborate the use of the in vivo-based diffusion parameter (D0.5Q−0.28) over the replica-based parameter in correlating nasal–laryngeal depositions of ultrafine aerosols. Improved correlations have been developed for the four age groups by implementing this in vivo-based diffusion parameter as well as the Cunningham correction factor.

Dynamic growth and deposition of hygroscopic aerosols in the nasal airway of a 5‐year‐old child

Hygroscopic growth within the human respiratory tract can be significant, which may notably alter the behavior and fate of the inhaled aerosols. The objective of this study is to evaluate the hygroscopic effects upon the transport and deposition of nasally inhaled fine-regime aerosols in children. A physiologically realistic nasal-laryngeal airway model was developed based on magnetic resonance imaging of a 5-year-old boy. Temperature and relative humidity field were simulated using the low Reynolds number k - ε turbulence model and chemical specie transport model under a spectrum of four thermo-humidity conditions. Particle growth and transport were simulated using a well validated Lagrangian tracking model coupled with a user-defined hygroscopic growth module. The subsequent aerosol depositions for the four inhalation scenarios were evaluated on a multiscale basis such as total, subregional, and cellular-level depositions. Results of this study show that a supersaturated humid environment is possible in the nasal turbinate region and can lead to significant condensation growth (d / d(0)  > 10) of nasally inhaled aerosols. Depositions in the nasal airway can also be greatly enhanced by condensation growth with appropriate inhalation temperature and humidity. For subsaturated and mild inhalation conditions, the hygroscopic effects were found to be nonsignificant for total depositions, while exerting a large impact upon localized depositions.

Characterization of Submicrometer Aerosol Deposition in Extrathoracic Airways during Nasal Exhalation

Submicrometer and especially fine aerosols that enter the respiratory tract are largely exhaled. However, the deposition of these aerosols under expiratory conditions is not well characterized. In this study, expiratory deposition patterns of both ultrafine (<100 nm) and fine (100–1000 nm) respiratory aerosols were numerically modeled in a realistic nasal-laryngeal airway geometry. Particle sizes ranging from 1 through 1000 nm and exhalation flow rates from 4 through 45 L/min were considered. Under these conditions, turbulence only appeared significant in the laryngeal and pharyngeal regions, whereas the nasal passages were primarily in the laminar regime. Exhaled particles were simulated with both a continuous-phase drift flux velocity correction (DF-VC) model and a discrete Lagrangian tracking approach. For the deposition of ultrafine particles, both models provided a good match to existing experimental values, and simulation results corroborated an existing in vivo–based diffusion parameter (i.e., D 0.5 Q −0.28). For fine particles, inertia-based deposition was found to have a greater dependence on the Reynolds number than on the Stokes number (i.e., St0.1 kRe0.9), indicating that secondary flows may significantly influence aerosol deposition in the nasal-laryngeal geometry. A new correlation was proposed for deposition in the extrathoracic airways that is applicable for both ultrafine and fine aerosols over a broad range of nasal exhalation conditions. Results of this study indicate that physical realism of the airway model is crucial in determining particle behavior and fate and that the laryngeal and pharyngeal regions should be retained in future studies of expiratory deposition in the nasal region.

Electrophoretic Particle Guidance Significantly Enhances Olfactory Drug Delivery: A Feasibility Study

Background Intranasal olfactory drug delivery provides a non-invasive method that bypasses the Blood-Brain-Barrier and directly delivers medication to the brain and spinal cord. However, a device designed specifically for olfactory delivery has not yet been found. Methods In this study, a new delivery method was proposed that utilized electrophoretic forces to guide drug particles to the olfactory region. The feasibility of this method was numerically evaluated in both idealized 2-D and anatomically accurate 3-D nose models. The influence of nasal airflow, electrode strength, and drug release position were also studied on the olfactory delivery efficiency. Findings Results showed that by applying electrophoretic forces, the dosage to the olfactory region was significantly enhanced. In both 2-D and 3-D cases, electrophoretic-guided delivery achieved olfactory dosages nearly two orders of magnitude higher than that without electrophoretic forces. Furthermore, releasing drugs into the upper half of the nostril (i.e., partial release) led to olfactory dosages two times higher than releasing drugs over the entire area of the nostril. By combining the advantages of pointed drug release and appropriate electrophoretic guidance, olfactory dosages of more than 90% were observed as compared to the extremely low olfactory dosage (<1%) with conventional inhaler devices. Conclusion Results of this study have important implications in developing personalized olfactory delivery protocols for the treatment of neurological disorders. Moreover, a high sensitivity of olfactory dosage was observed in relation to different pointed release positions, indicating the importance of precise particle guidance for effective olfactory delivery.

Aerosol Deposition in a Nasopharyngolaryngeal Replica of a 5-Year-Old Child

Particle deposition in a childs nasal cavity is much different than that in the nasal airway of an adult because of the differences in geometry and breathing patterns. However, most deposition studies have focused on adults, and only a limited number of studies have been reported in a childs nasal cavity. This study was conducted as an in vitro test and computational fluid dynamics (CFD) analysis of particle deposition in the nasal replica of a 5-year-old child; both total and regional depositions were evaluated. The geometry of the nasal replica was based on magnetic resonance images of the head of the child. The replica was made by a rapid-prototyping machine. Monodisperse oleic acid and polystyrene latex aerosols ranging in size between 1 and 20 μm were delivered into the replica at flow rates of 10 and 20 L/min. Results showed that the total deposition from the in vitro experiments and CFD predictions matched to a high degree. Good agreement was also obtained when results were compared to existing in vitro deposition data from children having comparable nasal geometries. For regional depositions, patterns between the replica and CFD data were similar in trend and magnitude for all four regions considered, although some regions deviated slightly. More tests in nasal replicas of different aged children will be carried out. Copyright 2013 American Association for Aerosol Research

In Vitro Evaluation of Aerosols Delivered via the Nasal Route.

BACKGROUND: Infants and young children are obligate nose breathers; therefore, a transnasal route seems the logical delivery method of inhaled aerosols. The efficiency of aerosol delivery depends on several factors, such as interface, type of nebulizer, and patient age and breathing pattern. We hypothesized that the use of a vibrating mesh nebulizer, a tight-fitting face mask, and a head model and breathing pattern of an older child would result in a higher lung dose. We also hypothesized that the use of an anatomically correct model would more accurately reflect lung dose than models that do not include airways. METHODS: A model comprising a breathing simulator and an anatomically correct model of a 7-month-old infant and a 5-y-old child with an interposed collection filter (lung dose) were used. Breathing patterns of a newborn, infant, and child were used with 7 interfaces. A continuous output and a vibrating mesh nebulizer were loaded with albuterol sulfate solution (5 mg/3.5 mL) and operated for 5 min. Albuterol mass was determined via spectrophotometer (276 nm). RESULTS: Lung dose varied between 0 and 3%. The jet nebulizer was more efficient than the vibrating mesh nebulizer. The front-loaded mask was the most efficient interface. We also found that higher tidal volumes were associated with higher lung doses and that the use of a larger airway model resulted in a lower lung dose. Finally, the model showed a good correlation with in vivo data and rendered lung doses severalfold lower than previous data obtained with oral models. CONCLUSIONS: Careful pairing of the aerosol generator and interface is very important during transnasal aerosol delivery.