Nasal Irrigation Delivery in Three Post-FESS Models From a Squeeze-bottle Using CFD.

PURPOSE: Nasal saline irrigation is highly recommended in patients following functional endoscopic sinus surgery (FESS) to aid the postoperative recovery. Post-FESS patients have significantly altered anatomy leading to markedly different flow dynamics from those found in pre-op or non-diseased airways, resulting in unknown flow dynamics. METHODS: This work investigated how the liquid stream disperses through altered nasal cavities following surgery using Computational Fluid Dynamics (CFD). A realistic squeeze profile was determined from physical experiments with a 27-year-old male using a squeeze bottle with load sensors. The administration technique involved a head tilt of 45-degrees forward to represent a head position over a sink. After the irrigation event that lasted 4.5 s, the simulation continued for an additional 1.5 s, with the head orientation returning to an upright position. RESULTS: The results demonstrated that a large maxillary sinus ostium on the right side allows saline penetration into this sinus. The increased volume of saline entering the maxillary sinus limits the saline volume available to the rest of the sinonasal cavity and reduces the surface coverage of the other paranasal sinuses. The average wall shear stress was higher on the right side than on the other side for two patients. The results also revealed that head position alters the sinuses' saline residual, especially the frontal sinuses. CONCLUSION: While greater access to sinuses is achieved through FESS surgery, patients without a nasal septum limits posterior sinus penetration due to the liquid crossing over to the contralateral cavity and exiting the nasal cavity early.

Comparison of Sinus Deposition from an Aqueous Nasal Spray and Pressurised MDI in a Post-Endoscopic Sinus Surgery Nasal Replica.

BACKGROUND: Optimising intranasal distribution and retention of topical therapy is essential for effectively managing patients with chronic rhinosinusitis, including those that have had functional endoscopic sinus surgery (FESS). This study presents a new technique for quantifying in vitro experiments of fluticasone propionate deposition within the sinuses of a 3D-printed model from a post-FESS patient. METHODS: Circular filter papers were placed on the sinus surfaces of the model. Deposition of fluticasone on the filter paper was quantified using high-performance liquid chromatography (HPLC) assay-based techniques. The deposition patterns of two nasal drug delivery devices, an aqueous nasal spray (Flixonase) and metered dose inhaler (Flixotide), were compared. The effects of airflow (0 L/min vs. 12 L/min) and administration angle (30° vs. and 45°) were evaluated. RESULTS: Inhaled airflow made little difference to sinus deposition for either device. A 45° administration angle improved frontal sinus deposition with the nasal spray and both ethmoidal and sphenoidal deposition with the inhaler. The inhaler provided significantly better deposition within the ethmoid sinuses (8.5x) and within the maxillary sinuses (3.9x) compared with the nasal spray under the same conditions. CONCLUSION: In the post-FESS model analysed, the inhaler produced better sinus deposition overall compared with the nasal spray. The techniques described can be used and adapted for in vitro performance testing of different drug formulations and intranasal devices under different experimental conditions. They can also help validate computational fluid dynamics modelling and in vivo studies.

Correlation of regional deposition dosage for inhaled nanoparticles in human and rat olfactory.

BACKGROUND: Nose-to-brain transport of airborne ultrafine particles (UFPs) via the olfactory pathway has been verified as a possible route for particle translocation into the brain. The exact relationship between increased airborne toxicant exposure and neurological deterioration in the human central nervous system, is still unclear. However, the nasal olfactory is undoubtedly a critical junction where the time course and toxicant dose dependency might be inferred. METHOD: Computational fluid-particle dynamics modeling of inhaled nanoparticles (1 to 100 nm) under low to moderate breathing conditions (5 to 14 L/min - human; and 0.14 to 0.40 L/min - rat) were performed in physiologically realistic human and rat nasal airways. The simulation emphasized olfactory deposition, and variations in airflow and particle flux caused by the inter-species airway geometry differences. Empirical equations were developed to predict regional deposition rates of inhaled nanoparticles on human and rat olfactory mucosa in sedentary breathing. Considering, breathing and geometric differences, quantified correlations between human and the rat olfactory deposition dose against a variety of metrics were proposed. RESULTS: Regional deposition of nanoparticles in human and the rat olfactory was extremely low, with the highest deposition (< 3.5 and 8.1%) occurring for high diffusivity particles of 1.5 nm and 5 nm, respectively. Due to significant filtering of extremely small particles (< 2 nm) by abrupt sharp turns at front of the rat nose, only small fractions of the inhaled nanoparticles (in this range) reached rat olfactory than that in human (1.25 to 45%); however, for larger sizes (> 3 nm), significantly higher percentage of the inhaled nanoparticles reached rat nasal olfactory than that in human (2 to 32 folds). Taking into account the physical and geometric features between human and rat, the total deposition rate (#/min) and deposition rate per unit surface area (#/min/mm2) were comparable for particles> 3 nm. However, when body mass was considered, the normalized deposition rate (#/min/kg) in the rat olfactory region exceeded that in the human. Nanoparticles < 1.5 nm were filtered out by rat anterior nasal cavity, and therefore deposition in human olfactory region exceeded that in the rat model. CONCLUSION: Regional deposition dose of inhaled nanoparticles in a human and rat olfactory region was governed by particle size and the breathing rate. Interspecies correlation was determined by combining the effect of deposition dosage, physical\geometric features, and genetic differences. Developed empirical equations provided a tool to quantify inhaled nanoparticle dose in human and rat nasal olfactory regions, which lay the ground work for comprehensive interspecies correlation between the two species. Furthermore, this study contributes to the fields in toxicology, i.e., neurotoxicity evaluation and risk assessment of UFPs, in long-term and low-dose inhalation exposure scenarios.

Computational investigation of dust mite allergens in a realistic human nasal cavity.

Aim: Inhaled allergens from house dust mite (HDM) are a major source of allergic disease such as allergic rhinitis and asthma. It has been a challenge to properly evaluate health risks caused by HDM related allergens including mite bodies, eggs and fecal pellets. This paper presents a numerical study on particle deposition of dust mite allergens in a human nasal cavity. Materials and methods: A realistic nasal cavity model was reconstructed from CT scans and a Computational Fluid Dynamics analysis of steady airflow was simulated. The discrete phase model was used to trace particle trajectories of three dust mite related particles. Results: The flow and particle model were validated by comparing with nasal resistance measurement and previous literature respectively. Aerodynamic characteristics and deposition of dust mite allergens in the nasal cavity were analyzed under different breathing conditions including rest and exercising conditions. Conclusions: The numerical results revealed the roles of different nasal cavity regions in filtering various types of dust mite allergens with consideration of breathing conditions.

Antennal scales improve signal detection efficiency in moths.

The elaborate bipectinate antennae of male moths are thought to increase their sensitivity to female sex pheromones, and so should be favoured by selection. Yet simple filamentous antennae are the most common structure among moths. The stereotypic arrangements of scales on the surface of antennae may resolve this paradox. We use computational fluid dynamics techniques to model how scales on the filamentous antennae of moths affect the passage of different particles in the airflow across the flagellum in both small and large moths. We found that the scales provide an effective solution to improve the efficacy of filamentous antennae, by increasing the concentration of nanoparticles, which resemble pheromones, around the antennae. The smaller moths have a greater increase in antennal efficiency than larger moths. The scales also divert microparticles, which resemble dust, away from the antennal surface, thereby reducing contamination. The positive correlations between antennal scale angles and sensilla number across Heliozelidae moths are consistent with the predictions of our model.

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.

Particle and inhalation exposure in human and monkey computational airway models.

Regional deposition of inhaled aerosols is essential for assessing health risks from toxic exposure. Upper airway physiology plays a significant role in respiratory defense by filtering micrometer particles, whose deposition mechanism is predominantly inertial impaction and is mainly controlled by airflow characteristics. The monkey is commonly used in tests that study inhalation toxicity as well as in preclinical tests as human surrogates due to their anatomical similarities to humans. Therefore, accurate predictions and an understanding of the inhaled particles and their distribution in monkeys are essential for extrapolating laboratory animal data to humans. The study goals were as follows: (1) to predict the particle deposition based on aerodynamic diameters (1-10 µm) and various steady inspiratory flow rates in computational models of monkey and human upper airways; and (2) to investigate potential differences in inhalation flow and particle deposition between humans and monkeys by comparing numerical simulation results with similar in-vitro and in-vivo measurements from recent literature. The deposition fractions of the monkey's numerical airway model agreed well with in-vitro and human model data when equivalent Stokes numbers were compared, based on the minimum cross-sectional area as representative of length scale. Vestibule removal efficiencies were predicted to be higher in the monkey model compared with the human model. Our results revealed that the particle transportations were sensitive to the anatomical structure, airway geometry, airflow rates, inflow boundary conditions and particle size.

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.

A combined experimental and numerical study on upper airway dosimetry of inhaled nanoparticles from an electrical discharge machine shop.

BACKGROUNDS: Exposure to nanoparticles in the workplace is a health concern to occupational workers with increased risk of developing respiratory, cardiovascular, and neurological disorders. Based on animal inhalation study and human lung tumor risk extrapolation, current authoritative recommendations on exposure limits are either on total mass or number concentrations. Effects of particle size distribution and the implication to regional airway dosages are not elaborated. METHODS: Real time production of particle concentration and size distribution in the range from 5.52 to 98.2 nm were recorded in a wire-cut electrical discharge machine shop (WEDM) during a typical working day. Under the realistic exposure condition, human inhalation simulations were performed in a physiologically realistic nasal and upper airway replica. The combined experimental and numerical study is the first to establish a realistic exposure condition, and under which, detailed dose metric studies can be performed. In addition to mass concentration guided exposure limit, inhalation risks to nano-pollutant were reexamined accounting for the actual particle size distribution and deposition statistics. Detailed dosimetries of the inhaled nano-pollutants in human nasal and upper airways with respect to particle number, mass and surface area were discussed, and empirical equations were developed. RESULTS: An astonishing enhancement of human airway dosages were detected by current combined experimental and numerical study in the WEDM machine shop. Up to 33 folds in mass, 27 folds in surface area and 8 folds in number dosages were detected during working hours in comparison to the background dosimetry measured at midnight. The real time particle concentration measurement showed substantial emission of nano-pollutants by WEDM machining activity, and the combined experimental and numerical study provided extraordinary details on human inhalation dosimetry. It was found out that human inhalation dosimetry was extremely sensitive to real time particle concentration and size distribution. Averaged particle concentration over 24-h period will inevitably misrepresent the sensible information critical for realistic inhalation risk assessment. CONCLUSIONS: Particle size distribution carries very important information in determining human airway dosimetry. A pure number or mass concentration recommendation on the exposure limit at workplace is insufficient. A particle size distribution, together with the deposition equations, is critical to recognize the actual exposure risks. In addition, human airway dosimetry in number, mass and surface area varies significantly. A complete inhalation risk assessment requires the knowledge of toxicity mechanisms in response to each individual metric. Further improvements in these areas are needed.

Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition in olfactory mucosa on particle size implies that the occupation deposition of welding fume manganese can be expected to vary with welding method.

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.

High resolution visualization and analysis of nasal spray drug delivery.

PURPOSE: Effective nasal drug delivery of new-generation systemic drugs requires efficient devices that can achieve targeted drug delivery. It has been established that droplet size, spray plume, and droplet velocity are major contributors to drug deposition. Continual effort is needed to better understand and characterise the physical mechanisms underpinning droplet formation from nasal spray devices. METHODS: High speed laser photography combined with an in-house designed automated actuation system, and a highly precise traversing unit, measurements and images magnified in small field-of-view regions within the spray was performed. RESULTS: The qualitative results showed a swirling liquid sheet at the near-nozzle region as the liquid is discharged before ligaments of fluid are separated off the liquid sheet. Droplets are formed and continue to deform as they travel downstream at velocities of up to 20 m/s. Increase in actuation pressure produces more rapid atomization and discharge time where finer droplets are produced. CONCLUSIONS: The results suggest that device designs should consider reducing droplet inertia to penetrate the nasal valve region, but find a way to deposit in the main nasal passage and not escape through to the lungs.

Scale resolving simulations of the effect of glottis motion and the laryngeal jet on flow dynamics during respiration.

BACKGROUND AND OBJECTIVE: The movement of the respiratory walls has a significant impact on airflow through the respiratory tract. The majority of computational fluid dynamics (CFD) studies assume a static geometry which may not provide a realistic flow field. Furthermore, many studies use Reynolds Averaged Navier-Stokes (RANS) turbulence models that do not resolve turbulence structure. Combining the application of advanced scale-resolving turbulence models with moving respiratory walls using CFD will provide detailed insights into respiratory flow structures. METHODS: This study simulated a complete breathing cycle involving inhalation and exhalation in a nasal cavity to trachea geometry that incorporated moving glottis walls. A second breathing cycle was simulated with static glottis walls for comparison. A recently developed hybrid RANS-LES turbulence model, the Stress-Blended Eddy Simulation (SBES), was incorporated to resolve turbulent flow structures in fine detail for both transient simulations. Transient results were compared with steady-state RANS simulations for the same respiratory geometry. RESULTS: Glottis motion caused substantial effects on flow structure through the complete breathing cycle. Significant flow structure and velocity variations were observed due to glottal motion, primarily in the larynx and trachea. Resolved turbulence structures using SBES showed an intense mixing section in the glottis region during inhalation and in the nasopharynx during expiration, which was not present in the RANS simulations. CONCLUSION: Transient simulations of a realistic breathing cycle uncovered flow structures absent in simulations with a constant flow rate. Furthermore, the incorporation of glottis motion impacted airflow characteristics that suggest rigid respiratory walls do not accurately describe respiratory flow. Future research in respiratory airflow should be conducted using transient scale-resolving models in conjunction with moving respiratory walls to capture flow structures in detail.

Source and trajectories of inhaled particles from a surrounding environment and its deposition in the respiratory airway.

The inhalation exposure to airborne particles is investigated using a newly developed computational model that integrates the human respiratory airway with a human mannequin and at an enclosed room environment. Three free-stream air flow velocities (0.05, 0.20, and 0.35 m s⁻¹) that are in the range of occupational environments are used. Particles are released from different upstream locations and their trajectories are shown, which revealed that the trajectory paths of 80 µm particles that are inhaled are the same from the three different upstream planes evaluated. Smaller particles, 1 and 10 µm, exhibited different inhalation paths when released from different upstream distances. The free-stream velocity also has an effect on the particle trajectory particularly for larger particles. The aspiration efficiency for an extended range of particle sizes was evaluated. Reverse particle tracking matches the deposition in the respiratory airway with its initial particle source location. This can allow better risk assessments, and dosimetry determination due to inhalation exposure to contaminant sources.

Correlation of Nasal Mucosal Temperature and Nasal Patency-A Computational Fluid Dynamics Study.

OBJECTIVES: Recent evidence suggests that detection of nasal mucosal temperature, rather than direct airflow detection, is the primary determinant of subjective nasal patency. This study examines the role of nasal mucosal temperature in the perception of nasal patency using in vivo and computational fluid dynamics (CFD) measurements. METHODS: Healthy adult participants completed Nasal Obstruction Symptom Evaluation (NOSE) and Visual Analogue Scale (VAS) questionnaires. A temperature probe measured nasal mucosal temperature at the vestibule, inferior turbinate, middle turbinate, and nasopharynx bilaterally. Participants underwent a CT scan, used to create a 3D nasal anatomy model to perform CFD analysis of nasal mucosal and inspired air temperature and heat flux along with mucosal surface area where heat flux >50 W/m2 (SAHF50). RESULTS: Eleven participants with a median age of 27 (IQR 24; 48) were recruited. Probe-measured temperature values correlated strongly with CFD-derived values (r = 0.87, p < 0.05). Correlations were seen anteriorly in the vestibule and inferior turbinate regions between nasal mucosal temperature and unilateral VAS (r = 0.42-0.46; p < 0.05), between SAHF50 and unilateral VAS (r = -0.31 to -0.36; p < 0.05) and between nasal mucosal temperature and SAHF50 (r = -0.37 to -0.41; p < 0.05). Subjects with high patency (VAS ≤10) had increased heat flux anteriorly compared with lower patency subjects (VAS >10; p < 0.05). CONCLUSION: Lower nasal mucosal temperature and higher heat flux within the anterior nasal cavity correlates with a perception of improved unilateral nasal patency in healthy individuals. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:1328-1335, 2023.

In-silico decongested trial effects on the impaired breathing function of a bulldog suffering from severe brachycephalic obstructive airway syndrome.

BACKGROUND AND OBJECTIVE: Brachycephalic obstructive airway syndrome (BOAS) susceptible dogs (e.g., French bulldog), suffer health complications related to deficient breathing primarily due to anatomical airway geometry. Surgical interventions are known to provide acceptable functional and cosmetic results; however, the long-term post-surgery outcome is not well known. In silico analysis provides an objective measure to quantify the respiratory function in postoperative dogs which is critical for successful long-term outcomes. A virtual surgery to open the airway can explore the ability for improved breathing in an obstructed airway of a patient dog, thus supporting surgeons in pre-surgery planning using computational fluid dynamics. METHODS: In this study five surgical interventions were generated with a gradual increment of decongested levels in a bulldog based on computed tomography images. The effects of the decongested airways on the breathing function of a patient bulldog, i.e., airflow characteristics, pressure drop, wall shear stress, and air-conditioning capacity, were quantified by benchmarking against a clinically healthy bulldog using computational fluid dynamics (CFD) method. RESULTS: Our findings demonstrated a promising decrease in excessive airstream velocity, pressure drop, and wall shear stress in virtual surgical scenarios, while constantly preserving adequate air-conditioning efficiency. A linear fit curve was proposed to correlate the reduction in the pressure drop and decongested level. CONCLUSIONS: The in silico analysis is a viable tool providing visual and quantitative insight into new unexplored surgical techniques.

Targeted drug delivery with polydisperse particle transport and deposition in patient-specific upper airway during inhalation and exhalation.

Identifying the deposition pattern of inhaled pharmaceutical aerosols in the human respiratory system and understanding the effective parameters in this process is vital for more efficient drug delivery to this region. This study investigated aerosol deposition in a patient-specific upper respiratory airway and determined the deposition fraction (DF) and pressure drop across the airway. An experimental setup was developed to measure the pressure drop in the same realistic geometry printed from the patient-specific geometry. The unsteady simulations were performed with a flow rate of 15 L/min and different particle diameters ranging from 2 to 30 µm. The results revealed significant flow circulation after the nasal valve in the upper and oropharynx regions, and a maximum local velocity observed in the nasopharynx. Transient cumulative deposition fraction showed that after 2 s of the simulation, all particles deposit or escape the computational domain. About 30 % of the injected large particles (dp ≥ 20 µm) deposited in the first 1 cm away from the nostril and more than 95 % deposited in the nasal airway before entering the oropharynx region. While almost 94 % deposition in trachea was composed of particles smaller than 5 µm. Approximately 20 % of inhaled fine particles (2-5 µm) deposited in the upper airway and the rest deposited in oropharynx, larynx and trachea.

The Impact of Adhesions on Nasal Airflow: A Quantitative Analysis Using Computational Fluid Dynamics.

BACKGROUND: Nasal adhesions (NAs) are a known complication of nasal airway surgery. Even minor NAs can lead to significant postoperative nasal airway obstruction (NAO). Division of such NAs often provides much greater relief than anticipated. OBJECTIVE: We examine the impact of NAs at various anatomical sites on nasal airflow and mucosal cooling using computational fluid dynamics (CFD) and multiple test subjects. METHODS: CT scans of healthy adult subjects were used to construct three-dimensional nasal airway computational models. A single virtual 2.5 mm diameter NA was placed at one of five sites commonly seen following NAO surgery within each nasal cavity bilaterally, resulting in 10 NA models and 1 NA-free control for each subject. CFD analysis was performed on each NA model and compared with the subject's NA-free control model. RESULTS: 4 subjects were recruited to create 44 computational models. The NAs caused the airflow streamlines to separate, leading to a statistically significant increase in mucosal temperature immediately downstream to the NAs (wake region). Changes in the mucosal temperature in the wake region of the NAs were most prominent in anteriorly located NAs with a mean increase of 1.62 °C for the anterior inferior turbinate NAs (P < .001) and 0.63 °C for the internal valve NAs (P < .001). CONCLUSION: NAs result in marked disruption to airflow patterns and reduced mucosal cooling on critical surfaces, particularly in the wake region. Reduced wake region mucosal cooling may be a contributing factor to the exaggerated perception of nasal obstruction experienced by patients with NAs.

Machine learning and sensitivity analysis for predicting nasal drug delivery for targeted deposition.

Targeted nasal drug delivery can provide improved efficacy for drug formulations to be delivered at high efficacy rates. Some parameters that influence drug delivery have a dependency on the patient's technique of administration and the spray device itself. When the different parameters, each having a specific range of values are combined, the combinatory permutations for studying its effects on particle deposition become large. In this study, we combine six input spray parameters (the spray half-cone angle, the mean spray exit velocity, the breakup length from the nozzle exit, the diameter of the nozzle spray device, the particle size, and the sagittal angle of the spray) with a range of values to produce 384 combinations of spray characteristics. This was repeated for three inhalation flow rates of 20, 40, and 60 L/min. To reduce the computational costs of a full transient Large Eddy Simulation flow field, we create a time-averaged frozen field and perform the time integration of particle trajectories through the flow field to determine the particle deposition in four anatomical regions of the nasal cavity (anterior, middle, olfactory and posterior) for each of the 384 spray field. A sensitivity analysis determined the significance of each input variable on the deposition. It was found the particle size distribution significantly affected deposition in the olfactory and posterior regions, while the spray device insertion angle was significant for deposition in the anterior and middle regions. Five machine learning models were evaluated based on 384 cases and it was found that despite the small sample dataset the simulation data was sufficient to provide accurate machine-learning predictions.

Numerical and Experimental Analysis of Drug Inhalation in Realistic Human Upper Airway Model.

The demand for a more efficient and targeted method for intranasal drug delivery has led to sophisticated device design, delivery methods, and aerosol properties. Due to the complex nasal geometry and measurement limitations, numerical modeling is an appropriate approach to simulate the airflow, aerosol dispersion, and deposition for the initial assessment of novel methodologies for better drug delivery. In this study, a CT-based, 3D-printed model of a realistic nasal airway was reconstructed, and airflow pressure, velocity, turbulent kinetic energy (TKE), and aerosol deposition patterns were simultaneously investigated. Different inhalation flowrates (5, 10, 15, 30, and 45 L/min) and aerosol sizes (1, 1.5, 2.5, 3, 6, 15, and 30 µm) were simulated using laminar and SST viscous models, with the results compared and verified by experimental data. The results revealed that from the vestibule to the nasopharynx, the pressure drop was negligible for flow rates of 5, 10, and 15 L/min, while for flow rates of 30 and 40 L/min, a considerable pressure drop was observed by approximately 14 and 10%, respectively. However, from the nasopharynx and trachea, this reduction was approximately 70%. The aerosol deposition fraction alongside the nasal cavities and upper airway showed a significant difference in pattern, dependent on particle size. More than 90% of the initiated particles were deposited in the anterior region, while just under 20% of the injected ultrafine particles were deposited in this area. The turbulent and laminar models showed slightly different values for the deposition fraction and efficiency of drug delivery for ultrafine particles (about 5%); however, the deposition pattern for ultrafine particles was very different.