Computational modeling and validation of human nasal airflow under various breathing conditions

The human nose serves vital physiological functions, including warming, filtration, humidification, and olfaction. These functions are based on transport phenomena that depend on nasal airflow patterns and turbulence. Accurate prediction of these airflow properties requires careful selection of computational fluid dynamics models and rigorous validation. The validation studies in the past have been limited by poor representations of the complex nasal geometry, lack of detailed airflow comparisons, and restricted ranges of flow rate. The objective of this study is to validate various numerical methods based on an anatomically accurate nasal model against published experimentally measured data under breathing flow rates from 180 to 1100 ml/s. The numerical results of velocity profiles and turbulence intensities were obtained using the laminar model, four widely used Reynolds-averaged Navier-Stokes (RANS) turbulence models (i.e., k-ε, standard k-ω, Shear Stress Transport k-ω, and Reynolds Stress Model), large eddy simulation (LES) model, and direct numerical simulation (DNS). It was found that, despite certain irregularity in the flow field, the laminar model achieved good agreement with experimental results under restful breathing condition (180 ml/s) and performed better than the RANS models. As the breathing flow rate increased, the RANS models achieved more accurate predictions but still performed worse than LES and DNS. As expected, LES and DNS can provide accurate predictions of the nasal airflow under all flow conditions but have an approximately 100-fold higher computational cost. Among all the RANS models tested, the standard k-ω model agrees most closely with the experimental values in terms of velocity profile and turbulence intensity.     

Development of a computational fluid dynamics model for mucociliary clearance in the nasal cavity

Intranasal drug delivery has attracted significant attention because of the opportunity to deliver systemic drugs directly to the blood stream. However, the mucociliary clearance poses a challenge in gaining high efficacy of intranasal drug delivery because cilia continuously carry the mucus blanket towards the laryngeal region. To better understand mucus flow behaviour on the human nasal cavity wall, we present computational model development, and evaluation of mucus motion on a realistic nasal cavity model reconstructed from CT-scans. The model development involved two approaches based on the actual nasal cavity geometry namely: (i) unwrapped-surface model in 2D domain and (ii) 3D-shell model. Conservation equations of fluid motion were applied to the domains, where a mucus production source term was used to initiate the mucus motion. The analysis included mucus flow patterns, virtual saccharin tests and quantitative velocity magnitude analysis, which demonstrated that the 3D-shell model results provided better agreement with experimental data. The unwrapped-surface model also suffered from mesh-deformations during the unwrapping stage and this led to higher mucus velocity compared to experimental data. Therefore, the 3D-shell model was recommended for future mucus flow simulations. As a first step towards mucus motion modelling this study provides important information that accurately simulates a mucus velocity field on a human nasal cavity wall, for assessment of toxicology and efficacy of intranasal drug delivery.     

Comparison between effects of various partial inferior turbinectomy options on nasal airflow: a computer simulation study

Partial inferior turbinectomy is typically performed on patients suffering from chronic nasal obstruction due to hypertrophy of inferior turbinates and is refractory to other more conservative treatments. The effects of the various options of incision performed on the inferior turbinate in terms of the resulting nasal airflow pattern are examined using computational fluid mechanics. The pressure drops across the severely blocked nose and healthy nose models were found to be 32.3 and 12.3 Pa, respectively, whereas the pressure drops across the nasal cavity following one-third turbinate resection, total turbinate resection and front-end resection were obtained as 5.8, 6.1 and 30.5 Pa correspondingly. Based on the total pressure drop results, the one-third resection option seems to be better than the front-end surgery and the total turbinate resection.     

Inspirational airflow patterns in deviated noses: a numerical study

This study attempts to evaluate the effects of deviation of external nose to nasal airflow patterns. Four typical subjects were chosen for model reconstruction based on computed tomography images of undeviated, S-shaped deviated, C-shaped deviated and slanted deviated noses. To study the hypothetical influence of deviation of external nasal wall on nasal airflow (without internal blockage), the collapsed region along the turbinate was artificially reopened in all the three cases with deviated noses. Computational fluid dynamics simulations were carried out in models of undeviated, original deviated and reopened nasal cavities at both flow rates of 167 and 500 ml/s. The shape of the anterior nasal roof was found to be collapsed on one side of the nasal airways in all the deviated noses. High wall shear stress region was found around the collapsed anterior nasal roof. The nasal resistances in cavities with deviated noses were considerably larger than healthy nasal cavity. Patterns of path-line distribution and wall shear stress distribution were similar between original deviated and reopened models. In conclusion, the deviation of an external nose is associated with the collapse of one anterior nasal roof. The crooked external nose induced a larger nasal resistance compared to the undeviated case, while the internal blockage of the airway along the turbinates further increased it.     

In silico approaches to respiratory nasal flows: A review

The engineering discipline of in silico fluid dynamics delivers quantitative information on airflow behaviour in the nasal regions with unprecedented detail, often beyond the reach of traditional experiments. The ability to provide visualisation and analysis of flow properties such as velocity and pressure fields, as well as wall shear stress, dynamically during the respiratory cycle may give significant insight to clinicians. Yet, there remains ongoing challenges to advance the state-of-the-art further, including for example the lack of comprehensive CFD modelling on varied cohorts of patients. The present article embodies a review of previous and current in silico approaches to simulating nasal airflows. The review discusses specific modelling techniques required to accommodate physiologically- and clinically-relevant findings. It also provides a critical summary of the reported results in the literature followed by an outlook on the challenges and topics anticipated to drive research into the future.     

Numerical modelling of nanoparticle deposition in the nasal cavity and the tracheobronchial airway

Recent advances in nanotechnology have seen the manufacture of engineered nanoparticles for many commercial and medical applications such as targeted drug delivery and gene therapy. Transport of nanoparticles is mainly attributed to the Brownian force which increases as the nanoparticle decreases to 1 nm. This paper first verifies a Lagrangian Brownian model found in the commercial computational fluid dynamics software Fluent before applying the model to the nasal cavity and the tracheobronchial (TB) airway tree with a focus on drug delivery. The average radial dispersion of the nanoparticles was 9x greater for the user-defined function model over the Fluent in-built model. Deposition in the nasal cavity was high for very small nanoparticles. The particle diameter range in which the deposition drops from 80 to 18% is between 1 and 10 nm. From 10 to 150 nm, however, there is only a small change in the deposition curve from 18 to 15%. A similar deposition curve profile was found for the TB airway.     

Computational model of particle deposition in the nasal cavity under steady and dynamic flow

A computational model for flow and particle deposition in a three-dimensional representation of the human nasal cavity is developed. Simulations of steady state and dynamic airflow during inhalation are performed at flow rates of 9–60 l/min. Depositions for particles of size 0.5–20 μm are determined and compared with experimental and simulation results from the literature in terms of deposition efficiencies. The nasal model is validated by comparison with experimental and simulation results from the literature for particle deposition under steady-state flow. The distribution of deposited particles in the nasal cavity is presented in terms of an axial deposition distribution as well as a bivariate axial deposition and particle size distribution. Simulations of dynamic airflow and particle deposition during an inhalation cycle are performed for different nasal cavity outlet pressure variations and different particle injections. The total particle deposition efficiency under dynamic flow is found to depend strongly on the dynamics of airflow as well as the type of particle injection.     

Numerical modeling of turbulent and laminar airflow and odorant transport during sniffing in the human and rat nose

Human sniffing behavior usually involves bouts of short, high flow rate inhalation (>300 ml/s through each nostril) with mostly turbulent airflow. This has often been characterized as a factor enabling higher amounts of odorant to deposit onto olfactory mucosa than for laminar airflow and thereby aid in olfactory detection. Using computational fluid dynamics human nasal cavity models, however, we found essentially no difference in predicted olfactory odorant flux (g/cm2 s) for turbulent versus laminar flow for total nasal flow rates between 300 and 1000 ml/s and for odorants of quite different mucosal solubility. This lack of difference was shown to be due to the much higher resistance to lateral odorant mass transport in the mucosal nasal airway wall than in the air phase. The simulation also revealed that the increase in airflow rate during sniffing can increase odorant uptake flux to the nasal/olfactory mucosa but lower the cumulative total uptake in the olfactory region when the inspired air/odorant volume was held fixed, which is consistent with the observation that sniff duration may be more important than sniff strength for optimizing olfactory detection. In contrast, in rats, sniffing involves high-frequency bouts of both inhalation and exhalation with laminar airflow. In rat nose odorant uptake simulations, it was observed that odorant deposition was highly dependent on solubility and correlated with the locations of different types of receptors.     

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.     

HIV感染患者口咽、鼻腔内真菌分离率的调查

目的了解HIV感染者口咽及鼻腔内真菌分离阳性率。方法用无菌拭子采集口咽腔溃疡、白斑、口角炎等和咽颊区黏膜分泌物,鼻腔取下鼻甲黏膜或中鼻道黏膜分泌物,直接接种于1 mL沙堡弱液体培养基中。取该离心沉淀物作真菌直接镜检,并接种于科玛嘉念珠菌显色培养基置37℃培养48 h后鉴定。如为丝状真菌,转种于察氏琼脂。25℃培养1周后根据菌落形态结合镜下结构鉴定菌种。结果 94例HIV感染者在口咽腔中真菌培养阳性62例(66%),分离出65株真菌,在鼻腔中真菌培养阳性48例(51%),分离出57株真菌。结论 HIV感染者免疫功能低下,易继发真菌机会性感染,口咽及鼻腔真菌的高寄居率是HIV侵袭性真菌感染的先兆症状,真菌菌种以白念珠菌比例为最高,口咽及鼻腔分别61%和33%。     

Metabolism-dependent activation and toxicity of chemicals in nasal glands

The mucosae of the nasal passages contain a large amount of glands which express secretory proteins as well as phase I and phase II biotransformation enzymes. In this review the metabolic activation, covalent binding and toxicity of chemicals in the Bowman's glands in the olfactory mucosa, in the sero-mucous glands in the nasal septum and in the lateral nasal glands and maxillary glands around the maxillary sinuses are discussed. Light microscopic autoradiographic studies have demonstrated a selective covalent binding of nasal toxicants and carcinogens such as halogenated hydrocarbons and N-nitrosamines, especially in the Bowman's glands following a single systemic exposure, suggesting a high rate of metabolic activation of chemicals in these glands. Special attention is put on the herbicide dichlobenil which induces necrosis in the olfactory mucosa following a cytochrome-P450-mediated metabolic activation and covalent binding in the Bowman's glands.     

Modeling inspiratory and expiratory steady-state velocity fields in the Sprague-Dawley rat nasal cavity

Distribution patterns of odorant molecules in the rat nasal olfactory region depend in large part on the detailed airflow patterns in the nasal cavity, which in turn depend on the anatomical structure. To investigate these flow patterns, we constructed an anatomically accurate finite element model of the right nasal cavity of the Sprague-Dawley rat based on horizontal (anterior-posterior) nasal cast cross sections. By numerically solving the fluid mechanical momentum and continuity equations using the finite element method, we studied the flow distribution and the complete velocity field for both inspiration and expiration throughout the nasal cavity under physiological flow rates of resting breathing and sniffing. Detailed velocity profiles, volumetric flow distributions, and streamline patterns for quasi-steady airflow are presented. S-shaped streamlines passing through the olfactory region are found to be less prevalent during expiratory than inspiratory flow leading to trapping and an increase in odorant molecule retention in the olfactory region during sniffing. The rat nasal velocity calculations will be used to study the distribution of odorant uptake onto the rat olfactory mucosa and compare it with the known anatomic location of some types of rat olfactory receptors.     

Critical factors in assessing risk from exposure to nasal carcinogens

Anatomical, physiological, biochemical and molecular factors that contribute to chemical-induced nasal carcinogenesis are either largely divergent between test species and humans, or we know very little of them. These factors, let alone the uncertainty associated with our knowledge gap, present a risk assessor with the formidable task of making judgments about risks to human health from exposure to chemicals that have been identified in rodent studies to be nasal carcinogens. This paper summarizes some of the critical attributes of the hazard identification and dose–response aspects of risk assessments for nasal carcinogens that must be accounted for by risk assessors in order to make informed decisions. Data on two example compounds, dimethyl sulfate and hexamethylphosphoramide, are discussed to illustrate the diversity of information that can be used to develop informed hypotheses about mode of action and decisions on appropriate dosimeters for interspecies extrapolation. Default approaches to interspecies dosimetry extrapolation are described briefly and are followed by a discussion of a generalized physiologically based pharmacokinetic model that, unlike default approaches, is flexible and capable of incorporating many of the critical species-specific factors. Recent advancements in interspecies nasal dosimetry modeling are remarkable. However, it is concluded that without the development of research programs aimed at understanding carcinogenic susceptibility factors in human and rodent nasal tissues, development of plausible modes of action will lag behind the advancements made in dosimetry modeling.     

A preliminary 3D computed tomography study of the human maxillary sinus and nasal cavity

Despite centuries of investigation, the function of the maxillary sinus (MS) and underlying patterns governing its form remain elusive. In this study, we articulate a methodology for collecting volumetric data for the MS and nasal cavity (NC) from computed tomography (CT) scans and report details for a small sample of 39 dried human crania of known ecogeographic provenience useful for assessing variation in MS size and shape. We use scaling analyses to preliminarily test the hypothesis that volumes of the nasal cavity (NCV) and maxillary sinus (MSV) are inversely correlated such that the NC covaries with size of the face, whereas the MS "fills in" the leftover space [proposed by Shea: Am J Phys Anthropol 47 (1977):289-300]. Against expectation, MSV is not significantly correlated with NCV or any cranial size variable. NCV, on the other hand, scales isometrically with facial size. The results of this pilot study suggest that NCV covaries with facial size, but that the MS does not simply fill in the leftover space in the face. The role, if any, of the MSs in midfacial function and architecture remains unclear. Larger sample sizes, additional environmental variables, and assessment of MS and NC shape are necessary to resolve this issue.     

Effect of anatomy on human nasal air flow and odorant transport patterns: implications for olfaction

Recent studies that have compared CT or MRI images of an individual's nasal anatomy and measures of their olfactory sensitivity have found a correlation between specific anatomical areas and performance on olfactory assessments. Using computational fluid dynamics (CFD) techniques, we have developed a method to quickly (相似文献   

Distribution of trace elements within bones in nasal cavity and labyrinth in humans

Measurements of trace element concentrations within bones in nasal cavity and labyrinth have shown large variations, both with a single bone and between different bones of a same individual. Factors that influence trace element levels include: metabolic activity, environmental effects, sex, and age. Detection of characteristic X-rays has been shown to be a convenient method for the measurement of concentration profiles, micropixe for micrometer variations, and X-ray centration profiles, micropixe for micrometer variations, and X-ray fluorescence for millimeter variations.     

The ontogeny of nasal floor shape variation in extant humans

Variation in nasal floor topography has generated both neontological and paleontological interest. Three categories of nasal floor shape (Franciscus: J Hum Evol 44 (2003) 699–727) have been used when analyzing this trait in extant humans and fossil Homo: flat, sloped, and depressed (or “bi‐level”). Variation in the frequency of these configurations within and among extant and fossil humans has been well‐documented (Franciscus: J Hum Evol 44 (2003) 699–727; Wu et al.: Anthropol Sci 120 (2012) 217–226). However, variation in this trait in Homo has been observed primarily in adults, with comparatively small subadult sample sizes and/or large age gradients that may not sufficiently track key ontogenetic changes. In this study, we investigate the ontogeny of nasal floor shape in a relatively large cross‐sectional age sample of extant humans (n = 382) ranging from 4.0 months fetal to 21 years post‐natal. Results indicate that no fetal or young infant individuals possess a depressed nasal floor, and that a depressed nasal floor, when present (ca. 21% of the sample), does not occur until 3.0 years postnatal. A canonical variates analysis of maxillary shape revealed that individuals with depressed nasal floors were also characterized by relatively taller anterior alveolar regions. This suggests that palate remodeling at about 3.0–3.5 years after birth, under the influence of tooth development, strongly influences nasal floor variation, and that various aspects of dental development, including larger crown/root size, may contribute to the development of a depressed nasal floor. These results in extant humans may help explain the high frequency of this trait found in Neandertal and other archaic Homo maxillae. Am J Phys Anthropol 155:369–378, 2014. © 2014 Wiley Periodicals, Inc.     

Normal nasal cavity and paranasal sinuses in brown lemurs Eulemur fulvus: computed tomography and cross-sectional anatomy

Background Far less is known about the normal anatomy of the nasal cavity of Eulemur fulvus; no computed tomography (CT) scan has ever been published. Methods Relevant CT scans were taken in the transverse, dorsal and longitudinal planes. These scans were compared with anatomical sections of heads. Results Computed tomography scans revealed almost all nasal structures, but cannot differentiate between the various layers of the nasal mucosa. Results show a double‐scroll arrangement of the ventral nasal concha. The dorsal nasal concha protrudes into the maxillary sinus, but no protrusion into the frontal sinus was observed. The ethmoturbinate I is completely closed back on itself and rostrally voluminous. Conclusions This work shows that at a clinical level, the integrity of the different turbinates can easily be appreciated from a simple CT scan. It will assist clinicians to evaluate pathological conditions that affect the nasal region.     

Identification of human nasal mucous proteins using proteomics

The determination of possible biomarkers in nasal secretion of healthy subjects can have a role in early diagnosis of diseases such as rhinosinusitis. For this purpose, nasal lavage fluids (NLFs) from ten volunteers, collected before and after they had been submitted to nasal provocations, were investigated. Separation and analysis of proteins present in this complex matrix was performed using a capillary liquid chromatography-electrospray-quadrupole-time of flight mass spectrometry equipment. From among a total of 111 proteins found (89 known and two unknown proteins), 42 of which had never been previously described in this fluid, such as Deleted in Malignant Brain Tumors 1 isoform a precursors, and cytoskeletal proteins were identified with high statistical score. Three proteins of palate lung nasal epithelial clone (PLUNC) family: SPLUNC1, LPLUNC1, and LPLUNC2 were identified. Proteins involved in innate (27%) and acquired immunity (21%) systems were major components of NLF. Cellular (52% of all proteins identified) such as cytoskeletal (33%), functional (15%), and regulatory (4%) proteins, normally present in the nasal cavity, have also been identified. The proteomic approach presented here allowed us to identify the proteins involved in acquired and innate immune response in the nose against microbial infections and unclean inhaled air.