Steady-state Inspiratory Airflow Research Articles

Normative ranges of nasal airflow variables in healthy adults.

Virtual surgery planning based on computational fluid dynamics (CFD) simulations of nasal airflow has the potential to improve surgical outcomes for patients with nasal airway obstruction (NAO). Virtual surgery planning requires normative ranges of airflow variables, but few studies to date have quantified inter-individual variability of nasal airflow among healthy subjects. This study reports CFD simulations of nasal airflow in 47 healthy adults. Anatomically accurate three-dimensional nasal models were reconstructed from cone beam computed tomography scans and used for steady-state inspiratory airflow simulations with a bilateral flowrate of 250ml/s. Normal subjective sensation of nasal patency was confirmed using the nasal obstruction symptom evaluation and visual analog scale. Healthy ranges for several CFD variables known to correlate with subjective nasal patency were computed, including unilateral airflow, nasal resistance, airspace minimal cross-sectional area (mCSA), heat flux (HF), and surface area stimulated by mucosal cooling (defined as the area where HF > 50W/m2). The normative ranges were targeted to contain 95% of the healthy population and computed using a nonparametric method based on order statistics. A wide range of inter-individual variability in nasal airflow was observed among healthy subjects. Unilateral airflow varied from 60 to 191ml/s, airflow partitioning ranged from 23.8 to 76.2%, and unilateral mCSA varied from 0.24 to 1.21cm2. These ranges are in good agreement with rhinomanometry and acoustic rhinometry data from the literature. A key innovation of this study are the normative ranges of flow variables associated with mucosal cooling, which recent research suggests is the primary physiological mechanism of nasal airflow sensation. Unilateral HF ranged from 94 to 281W/m2, while the surface area stimulated by cooling ranged from 27.4 to 64.3cm2. These normative ranges may serve as targets in future virtual surgery planning for patients with NAO.

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

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

A computational fluid dynamics analysis of the effects of size and shape of anterior nasal septal perforations.

Nasal septal perforations (NSPs) often cause bleeding, crusting, obstruction, and/or whistling. The objective was to analyze the impact of anterior NSP size and shape on nasal physiology using computational fluid dynamics (CFD). A 3-dimensional model of the nasal cavity was constructed from a radiologically normal CT scan using imaging software. Anterior NSPs (ovoid (ONSP): 0.5, 1, 2, and 3 cm long anterior-to-posteriorly and round (RNSP, 0.5 and 1 cm)) were virtually created in the model and divided into ventral, dorsal, anterior, and posterior regions. Steady-state inspiratory airflow, heat, and water vapor transport were simulated using Fluent CFD software. Air crossover through the perforation, wall shear, heat flux, water vapor flux, resistance, and humidification were analyzed. Air crossover and wall shear increased with perforation size. Regionally, wall shear and heat and water vapor flux were highest posteriorly and lowest anteriorly, generally increasing with size in those regions. RNSPs had greater heat and water vapor flux compared to corresponding size ONSPs. Resistance decreased by 10% or more from normal only in the 3 cm ONSP. Maximum water content was achieved more posteriorly in larger NSP nasal cavities. High wall shear and heat and water vapor flux in posterior perforation regions may explain the crusting most commonly noted on posterior NSP edges. This preliminary study suggests that larger NSPs have a greater effect on nasal resistance and water content. Decrease in resistance with larger NSP size may be implicated in reported symptomatic improvement following enlargement of NSPs for treatment.

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

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

Simulation of the phase change and deposition of inhaled semi-volatile liquid droplets in the nasal passages of rats and humans

Inhaled airborne droplets may undergo phase change as they travel through the respiratory tract. Droplet evaporation and condensation depends on the physicochemical and thermodynamic properties of the aerosol and will impact deposition in the respiratory airways. The deposition behavior of four fragrance aerosols (d-limonene, linalool, benzaldehyde, and benzyl acetate) with different vapor pressures was simulated in anatomically accurate computational fluid dynamics (CFD) models of the rat and human nasal passages. Steady-state inspiratory airflow was simulated in each species at resting breathing rates. Droplet transport and deposition was simulated using Lagrangian particle tracking. Droplet size evolution due to phase change was governed by molecular diffusion to or from the droplet surface and was driven by the difference in partial pressures between the droplet surface and the surrounding environment. CFD predictions revealed significant evaporation of these fragrance materials in the nasal passages with evaporation rates dependent on the saturation vapor pressures of the substances. In the human nose, complete evaporation was observed for d-limonene droplets with initial diameters ≤6µm, benzaldehyde droplets ≤4µm, and benzyl acetate and linalool droplets <2µm. The minimum droplet size for complete evaporation was smaller in the rat nose due to higher deposition in the anterior nose. Larger droplets did not completely evaporate but decreased in size, thereby reducing deposition by inertial impaction in the nasal passages of each species. Quantification of droplet deposition in the nose has significant implications for lung dosimetry since vapor concentrations and droplet characteristics are altered during transport through the upper respiratory tract.

Experimental Measurements and Computational Predictions of Regional Particle Deposition in a Sectional Nasal Model

Knowledge of the regional deposition of inhaled particles in the nose is important for drug delivery and assessment of the toxicity of inhaled materials. In this study, computational fluid dynamics (CFD) predictions and experimental measurements in a nasal replica cast were used to study regional deposition of inhaled microparticles. The replica cast was sectioned into six regions of interest based on nasal anatomy: the nasal vestibule, nasal valve, anterior turbinates, olfactory region, turbinates, and nasopharynx. Monodisperse fluorescein particles with aerodynamic diameters of 2.6-14.3 μm were passed through the assembled cast in the presence of steady inspiratory airflow at 15 L/min. After each experiment, the cast was disassembled and the deposited fluorescein in each region was washed out and quantified with fluorescence spectrometry. A nasal CFD model was developed from the same magnetic resonance imaging scans that were used to construct the replica cast. Steady-state inspiratory airflow and particle deposition calculations were conducted in the CFD model using Fluent(™) at flow rates producing Stokes numbers comparable to experimental conditions. Total and regional particle deposition predictions from the CFD model were compared with experimental measurements from the replica cast. Overall, good agreement was observed between CFD predictions and experimental measurements with similar deposition trends in each region of interest. CFD predictions in central nasal regions demonstrated well-defined maximum values of 15%, 7%, and 12% in the anterior turbinates, olfactory, and turbinates regions, respectively, at particle sizes of 10-11 μm. These results demonstrate the use of a sectioned nasal CFD model based on anatomical regions of interest for nasal drug delivery to elucidate patterns of regional deposition within a human nasal cavity.

Changes in nasal airflow and heat transfer correlate with symptom improvement after surgery for nasal obstruction

Surgeries to correct nasal airway obstruction (NAO) often have less than desirable outcomes, partly due to the absence of an objective tool to select the most appropriate surgical approach for each patient. Computational fluid dynamics (CFD) models can be used to investigate nasal airflow, but variables need to be identified that can detect surgical changes and correlate with patient symptoms. CFD models were constructed from pre- and post-surgery computed tomography scans for 10 NAO patients showing no evidence of nasal cycling. Steady-state inspiratory airflow, nasal resistance, wall shear stress, and heat flux were computed for the main nasal cavity from nostrils to posterior nasal septum both bilaterally and unilaterally. Paired t-tests indicated that all CFD variables were significantly changed by surgery when calculated on the most obstructed side, and that airflow, nasal resistance, and heat flux were significantly changed bilaterally as well. Moderate linear correlations with patient-reported symptoms were found for airflow, heat flux, unilateral allocation of airflow, and unilateral nasal resistance as a fraction of bilateral nasal resistance when calculated on the most obstructed nasal side, suggesting that these variables may be useful for evaluating the efficacy of nasal surgery objectively. Similarity in the strengths of these correlations suggests that patient-reported symptoms may represent a constellation of effects and that these variables should be tracked concurrently during future virtual surgery planning.

Computed nasal resistance compared with patient-reported symptoms in surgically treated nasal airway passages: A preliminary report.

Nasal airway obstruction (NAO) is a common health condition impacting mood, energy, recreation, sleep, and overall quality of life. Nasal surgery often addresses NAO but the results are sometimes unsatisfactory. Evaluating surgical treatment efficacy could be improved if objective tests were available that correlated with patient-reported measures of symptoms. The goal of this study was to develop methods for comparing nasal resistance computed by computational fluid dynamics (CFD) models with patient-reported symptoms of NAO using early data from a 4-year prospective study. Computed tomography (CT) scans and patient-reported scores from the Nasal Obstruction Symptom Evaluation (NOSE) scale and a visual analog scale (VAS) measuring unilateral airflow sensation were obtained pre- and postoperatively in two NAO patients showing no significant mucosal asymmetry who were successfully treated with functional nasal surgery, including septoplasty. Pre- and postsurgery CFD models were created from the CT scans. Numerical simulation of steady-state inspiratory airflow was used to calculate bilateral and unilateral CFD-derived nasal resistance (CFD-NR). In both subjects, NOSE and VAS scores improved after surgery, bilateral CFD-NR decreased, and unilateral CFD-NR decreased on the affected side. In addition, NOSE and VAS scores tracked with unilateral CFD-NR on the affected side. These preliminary results suggest a possible correlation between unilateral NR and patient-reported symptoms and imply that analysis of unilateral obstruction should focus on the affected side. A formal investigation of unilateral CFD-NR and patient-reported symptoms in a series of NAO patients is needed to determine if these variables are correlated.

Deviated nasal septum hinders intranasal sprays: a computer simulation study.

This study investigates how deviated nasal septum affects the quantity and distribution of spray particles, and examines the effects of inspiratory airflow and head position on particle transport. Deposition of spray particles was analysed using a three-dimensional computational fluid dynamics model created from a computed tomography scan of a human nose with leftward septal deviation and a right inferior turbinate hypertrophy. Five simulations were conducted using FluentTM software, with particle sizes ranging from 20-110 &#956;m, a spray speed of 3 m/s, plume angle of 68(deg), and with steady state inspiratory airflow either present (15.7 L/min) or absent at varying head positions. With inspiratory airflow present, posterior deposition on the obstructed side was approximately four times less than the contralateral side, regardless of head position, and was statistically significant. When airflow was absent, predicted deposition beyond the nasal valve on the left and right sides were between 16% and 69% lower and positively influenced by a dependent head position. Simulations predicted that septal deviation significantly diminished drug delivery on the obstructed side. Furthermore, increased particle penetration was associated with presence of nasal airflow. Head position is an important factor in particle deposition patterns when inspiratory airflow is absent.

Effects of Anatomy and Particle Size on Nasal Sprays and Nebulizers

To study the effects of nasal deformity on aerosol penetration past the nasal valve (NV) for varying particle sizes using sprays or nebulizers. Computed mathematical nasal airway model. Department computer lab. Particle deposition was analyzed using a computational fluid dynamics model of the human nose with leftward septal deviation and compensatory right inferior turbinate hypertrophy. Sprays were simulated for 10 µm, 20 µm, 50 µm, or particle sizes following a Rosin Rammler particle size distribution (10-110 µm), at speeds of 1, 3, or 10 meters per second. Nebulization was simulated for 1, 3.2, 6.42, or 10 µm particles. Steady state inspiratory airflow was simulated at 15.7 liters per minute. Sprays predicted higher NV penetration on the right side for particle sizes >10 µm, with comparable penetration on both sides at 10 µm. Nearly 100% deposited in the nasal passages for all spray characteristics. Nebulizer predictions showed nearly 100% of particles <6.42 µm and more than 50% of 6.42 µm bypassing both sides of the nose without depositing. Of the nebulized particles that deposited, penetration was higher on the right at 10 µm, with comparable penetration on both sides at 6.42 µm. Spray penetration was highest at 10 µm, with more than 96% penetrating on both sides at 1 and 3 meters per second. Nebulization penetration was also highest at 10 µm (40% on the left, >90% on the right). In the presence of a septal deviation, sprays or nebulizers containing 10-µm particles may have good penetration beyond the NV. Nebulized particles <10 µm are likely to be respirable. Additionally, spray speeds above 3 meters per second may limit penetration.

Computational fluid dynamics simulations of submicrometer and micrometer particle deposition in the nasal passages of a Sprague-Dawley rat

Computational fluid dynamics (CFD) simulations were conducted in a model of the complete nasal passages of an adult male Sprague-Dawley rat to predict regional deposition patterns of inhaled particles in the size range of 1 nm to 10 μm. Steady-state inspiratory airflow rates of 185, 369, and 738 ml/min (equal to 50%, 100%, and 200% of the estimated minute volume during resting breathing) were simulated using Fluent™. The Lagrangian particle tracking method was used to calculate trajectories of individual particles that were passively released from the nostrils. Computational predictions of total nasal deposition compared well with experimental data from the literature when deposition fractions were plotted against the Stokes and Peclet numbers for micro- and nanoparticles, respectively. Regional deposition was assessed by computing deposition efficiency curves for major nasal epithelial cell types. For micrometer particles, maximum olfactory deposition was 27% and occurred at the lowest flow rate with a particle diameter of 7 μm. Maximum deposition on mucus-coated non-olfactory epithelium was 27% for 3.25 μm particles at the highest flow rate. For submicrometer particles, olfactory deposition reached a maximum of 20% with a particle size of 5 nm at the highest flow rate, whereas deposition on mucus-coated non-olfactory epithelium reached a peak of approximately 60% for 1–4 nm particles at all flow rates. These simulations show that regional particle deposition patterns are highly dependent on particle size and flow rate, indicating the importance of accurate quantification of deposition in the rat for extrapolation of results to humans.

Effects of surface smoothness on inertial particle deposition in human nasal models

Computational fluid dynamics (CFD) predictions of inertial particle deposition have not compared well with data from nasal replicas due to effects of surface texture and the resolution of tomographic images. To study effects of geometric differences between CFD models and nasal replicas, nasal CFD models with different levels of surface smoothness were reconstructed from the same MRI data used to construct the nasal replica used by Kelly, Asgharian, Kimbell, and Wong (2004a) [ Aerosol Science and Technology, 38,1063–1071]. One CFD model in particular was reconstructed without any surface smoothing to preserve the detailed topology present in the nasal replica. Steady-state inspiratory airflow and Lagrangian particle tracking were simulated using Fluent software. Particle deposition estimates from the smoother models under-predicted nasal deposition from replica casts, which was consistent with previous findings. These discrepancies were overcome by including surface artifacts that were not present in the reduced models and by plotting deposition efficiency versus the Stokes number, where the characteristic diameter was defined in terms of the pressure-flow relationship to account for changes in airflow resistance due to wall roughness. These results indicate that even slight geometric differences have significant effects on nasal deposition and that this information should be taken into account when comparing particle deposition data from CFD models with experimental data from nasal replica casts.

A computational fluid dynamics approach to assess interhuman variability in hydrogen sulfide nasal dosimetry

Human exposure to hydrogen sulfide (H2S) gas occurs from natural and industrial sources and can result in dose-related neurological, respiratory, and cardiovascular effects. Olfactory neuronal loss in H2S-exposed rats has been used to develop occupational and environmental exposure limits. Using nasal computational fluid dynamics (CFD) models, a correlation was found between wall mass flux and olfactory neuronal loss in rodents, suggesting an influence of airflow patterns on lesion locations that may affect interspecies extrapolation of inhaled dose. Human nasal anatomy varies considerably within a population, potentially affecting airflow patterns and dosimetry of inhaled gases. This study investigates interhuman variability of H2S nasal dosimetry using anatomically accurate CFD models of the nasal passages of five adults and two children generated from magnetic resonance imaging (MRI) or computed tomography (CT) scan data. Using allometrically equivalent breathing rates, steady-state inspiratory airflow and H2S uptake were simulated. Approximate locations of olfactory epithelium were mapped in each model to compare air:tissue flux in the olfactory region among individuals. The fraction of total airflow to the olfactory region ranged from 2% to 16%. Despite this wide range in olfactory airflow, H2S dosimetry in the olfactory region was predicted to be similar among individuals. Differences in the 99th percentile and average flux values were <1.2-fold at inhaled concentrations of 1, 5, and 10 ppm. These preliminary results suggest that differences in nasal anatomy and ventilation among adults and children do not have a significant effect on H2S dosimetry in the olfactory region.

Application of Physiological Computational Fluid Dynamics Models to Predict Interspecies Nasal Dosimetry of Inhaled Acrolein

Acrolein is a highly soluble and reactive aldehyde and is a potent upper-respiratory-tract irritant. Acrolein-induced nasal lesions in rodents include olfactory epithelial atrophy and inflammation, epithelial hyperplasia, and squamous metaplasia of the respiratory epithelium. Nasal uptake of inhaled acrolein in rats is moderate to high, and depends on inspiratory flow rate, exposure duration, and concentration. In this study, anatomically accurate three-dimensional computational fluid dynamics (CFD) models were used to simulate steady-state inspiratory airflow and to quantitatively predict acrolein tissue dose in rat and human nasal passages. A multilayered epithelial structure was included in the CFD models to incorporate clearance of inhaled acrolein by diffusion, blood flow, and first-order and saturable metabolic pathways. Kinetic parameters for these pathways were initially estimated by fitting a pharmacokinetic model with a similar epithelial structure to time-averaged acrolein nasal extraction data and were then further adjusted using the CFD model. Predicted air:tissue flux from the rat nasal CFD model compared well with the distribution of acrolein-induced nasal lesions from a subchronic acrolein inhalation study. These correlations were used to estimate a tissue dose-based no-observed-adverse-effect level (NOAEL) for inhaled acrolein. A human nasal CFD model was used to extrapolate effects in laboratory animals to human exposure conditions on the basis of localized tissue dose and tissue responses. Assuming that equivalent tissue dose will induce similar effects across species, a NOAEL human equivalent concentration for inhaled acrolein was estimated to be 8 ppb.

Analysis of Particle Deposition in the Turbinate and Olfactory Regions Using a Human Nasal Computational Fluid Dynamics Model

The human nasal passages effectively filter particles from inhaled air. This prevents harmful pollutants from reaching susceptible pulmonary airways, but may leave the nasal mucosa vulnerable to potentially injurious effects from inhaled toxicants. This filtering property may also be strategically used for aerosolized nasal drug delivery. The nasal route has recently been considered as a means of delivering systemically acting drugs due to the large absorptive surface area available in close proximity to the nostrils. In this study, a computational fluid dynamics (CFD) model of nasal airflow was used with a particle transport and deposition code to predict localized deposition of inhaled particles in human nasal passages. The model geometry was formed from MRI scan tracings of the nasal passages of a healthy adult male. Spherical particles ranging in size from 5 to 50 microm were released from the nostrils. Particle trajectories and deposition sites were calculated in the presence of steady-state inspiratory airflow at volumetric flow rates of 7.5, 15, and 30 L/min. The nasal valve, turbinates, and olfactory region were defined in the CFD model so that particles depositing in these regions could be identified and correlated with their release positions on the nostril surfaces. When plotted against impaction parameter, deposition efficiencies in these regions exhibited maximum values of 53%, 20%, and 3%, respectively. Analysis of preferential deposition patterns and nostril release positions under natural breathing scenarios can be used to determine optimal particle size and flow rate combinations to selectively target drug particles to specific regions of the nose.

Dosimetry modeling of inhaled formaldehyde: binning nasal flux predictions for quantitative risk assessment.

Interspecies extrapolations of tissue dose and tumor response have been a significant source of uncertainty in formaldehyde cancer risk assessment. The ability to account for species-specific variation of dose within the nasal passages would reduce this uncertainty. Three-dimensional, anatomically realistic, computational fluid dynamics (CFD) models of nasal airflow and formaldehyde gas transport in the F344 rat, rhesus monkey, and human were used to predict local patterns of wall mass flux (pmol/[mm(2)-h-ppm]). The nasal surface of each species was partitioned by flux into smaller regions (flux bins), each characterized by surface area and an average flux value. Rat and monkey flux bins were predicted for steady-state inspiratory airflow rates corresponding to the estimated minute volume for each species. Human flux bins were predicted for steady-state inspiratory airflow at 7.4, 15, 18, 25.8, 31.8, and 37 l/min and were extrapolated to 46 and 50 l/min. Flux values higher than half the maximum flux value (flux median) were predicted for nearly 20% of human nasal surfaces at 15 l/min, whereas only 5% of rat and less than 1% of monkey nasal surfaces were associated with fluxes higher than flux medians at 0.576 l/min and 4.8 l/min, respectively. Human nasal flux patterns shifted distally and uptake percentage decreased as inspiratory flow rate increased. Flux binning captures anatomical effects on flux and is thereby a basis for describing the effects of anatomy and airflow on local tissue disposition and distributions of tissue response. Formaldehyde risk models that incorporate flux binning derived from anatomically realistic CFD models will have significantly reduced uncertainty compared with risk estimates based on default methods.