Role of Nasal Vestibule Morphological Variations on Olfactory Airflow Dynamics

Abstract

Background:

The conductive mechanisms of olfaction are typically given little priority in the evaluation olfactory function. The objective of this study is to investigate the role of nasal vestibule morphological variations on airflow volume at the olfactory recess in healthy subjects.

Methods:

Anatomically realistic three-dimensional nasal airway models were constructed from computed-tomography scans in five subjects. Each individual’s unilateral nasal cavity (10 total) was classified according to the shape of their nasal vestibule: Standard, Notched, or Elongated. Nasal airflow simulations were performed using computational fluid dynamics modeling at two inspiratory flow rates (15L/min and 30L/min) to reflect resting and moderate breathing rates. Olfactory airflow volume and cross-sectional flow resistance were computed.

Findings:

Average olfactory airflow volumes (and percent airflow in olfactory) were: 0.25L/min to 0.64L/min (3.0% – 7.7%; 15L/min simulations) and 0.53L/min to 1.30L/min (3.2% – 7.8%; 30 L/min simulations) for Standard; 0.13L/min – 0.47L/min (2.0% – 6.8%; 15L/min simulations) and 0.06L/min – 0.82L/min (1.7% – 6.1%; 30L/min simulations) for Notched; and 0.07L/min – 0.39L/min (1.2% – 5.4%; 15L/min simulations) and 0.30L/min – 0.99L/min (2.1% – 6.7%; 30L/min simulations) for Elongated. On average, relative difference in olfactory resistance between left and right sides was 141.5% for patients with different unilateral phenotypes and 82.2% for patients with identical unilateral phenotype.

Interpretation:

Olfactory cleft airflow volume was highest in the Standard nasal vestibule phenotype, followed by Notched phenotype for 15L/min simulations and Elongated phenotype for 30L/min simulations. Further, intra-patient variation in olfactory cleft airflow resistance differs greatly for patients with different unilateral phenotypes compared to patients with identical unilateral phenotype.

INTRODUCTION

Human olfaction is thought to be effective when the combination of sensorineural components and conductive factors function properly; however, the role of conductive factors in olfaction has been given less attention. Instead, much attention to human olfaction has focused on sensorineural components and the interaction between olfactory receptor neurons and odorant molecules, thus ignoring the conductive medium (nasal cavity) where odorant molecules are transported to olfactory receptor neurons. Nonetheless, variations in nasal morphology have traditionally been understood to influence olfactory function.^1,2 Morphologic profiles that have been postulated to be associated with improved olfaction include the dorsal conduit, which delivers inhaled odorant-laden air to the olfaction recess through enhanced olfactory airflow, and an enlarged olfactory recess at the posterior end of the nasal cavity.^2–4 It has also been reported that anatomical changes in the olfactory cleft or the nasal valve region alter odorant transport to the olfactory epithelium.⁵ Since the nasal vestibule lies directly posterior to the nostrils and is the initial point of interface between odorant-laden air and nasal mucosa, it is important to determine the effects of morphologic variations in the nasal vestibule on airflow into the olfactory region.

In addition, evolutionary adaptation of humans to diverse climatic environments is another contributing factor to inter-individual variability in nasal morphology.^6–8 The variabilities that arise from adaptation to varying geographic regions are particularly evident in the ratio of nasal width to nasal height, termed the nasal index.^8–13 In their study, Leong and Eccles ¹⁴ stated that nasal physiology is not significantly different across varying nasal indices. Similarly, the studies by Doddi and Eccles ¹⁵, and Patki and Frank-Ito ¹⁶ also reported a low correlation between nasal index and nasal resistance. Another main feature of normal variations seen in both intra- and inter-individual nasal anatomy are the distinct nasal vestibule morphological phenotypes described by Ramprasad and Frank-Ito ¹⁷, namely Notched, Standard and Elongated (Fig. 1A). The Notched phenotype has a prominent notch at the junction of the ala and sidewall; the Standard phenotype is considered the “typical” formation; and the Elongated phenotype is slightly elongated at the level of the nasal ala.¹⁷ These distinct morphological phenotypes do not affect global airflow dynamics and resistance in the nasal cavity.^17,18 However, local airflow resistance, air conditioning performance, and transport of particulate matter in the nasal cavity were significantly influenced by nasal vestibule morphological phenotypes.^17,19,20

Figure 1.

(A) 3D model illustrating the three nasal phenotypes. This figure is reproduced with permission from Ramprasad and Frank-Ito ¹⁷; (B) Olfactory Z-axis cross sections with front facing image of the cross section above; (C) Hybrid tetrahedral-prismatic mesh elements; and (D) Olfactory airspace contour plot colored by velocity magnitude for 15 L/min simulation.

Limitations in the literature to date have been with the difficulty of isolating which air that reaches the olfactory cleft as well as eliminating confounding factors such as nasal inflammation, which has been shown to be highly correlative with olfactory dysfunction.^21,22 Thus, the main objective of this research is to utilize computational fluid dynamics (CFD) modeling techniques to investigate the effects of distinct nasal vestibule morphologies on airflow in different regions across the olfactory cleft. This research may illustrates potential causes of differential olfactory function based on nasal vestibule morphology. Additionally, findings from this work may offer important understanding whether or not certain individuals with particular nasal vestibule morphology may be predisposed to heightened severity of olfactory dysfunction when affected by diseases associated with loss of smell or as they progress in age.

METHODS

Study Subjects

Five adult subjects with high resolution computed tomography (CT) images of the entire nasal cavity and radiographic evidence of normal nasal cavity were selected after study approved by the Duke University Health System Institutional Review Board for Clinical Investigations. The nasal anatomy of all subjects had either no septal deviation or less than five degree septal deviation in any direction including septal spurs, and no substantial aberrant anatomy or significant nasal cycling. Subject “DN001” is a 54-year-old African American female with bilateral Elongated nasal vestibule morphology. Subject “DN002” is 32 years old, a Latin American female with bilateral Notched nasal vestibule morphology. Subject “DN003” is a 26-year-old Caucasian female with bilateral Standard nasal vestibule morphology. Subjects “DN008” and “DN009” are both Caucasian males ages 65 years and 72 years, respectively. Subject “DN008” has the Notched nasal vestibule morphology on the left nasal cavity and Standard nasal vestibule morphology on the right cavity, while Subject “DN009” has Standard and Notched nasal vestibule morphologies on the left side and right side, respectively (Fig. 1A).

Nasal Airway Reconstruction

Each subject’s CT images was imported into the medical imaging software package, Mimics™ 16.1 (Materialise, Inc., Leuven, Belgium) creation of anatomically accurate subject-specific three dimensional (3D) reconstruction of the nasal cavity. Following the creation of subject-specific 3D nasal airway models, the models were exported in stereolithography file format and imported into the CAD and mesh generating software package, ICEM-CFD™ 19.0 (ANSYS, Canonsburg, PA, USA) for creation of planar inlet surfaces around the nostrils and an outlet surface at the nasopharynx. Next, on each unilateral side of the nasal cavity model, the olfactory cleft airspace was defined from the most anterior plane of the middle turbinate to just anterior of the sphenoid sinus.^23–25 The vertical height of the olfactory recess will be defined from the roof of the cribriform plate down 10mm inferiorly (Fig. 1B).^23–25

Nasal Airflow Simulations

In order to simulate airflow in the subject-specific 3D nasal airway models, a hybrid tetrahedral-prismatic mesh elements was generated in the computational domain (nasal cavity) using ICEM-CFD. In brief, approximately 4 million unstructured tetrahedral elements with five-layer prismatic-element of 0.1 mm prism thickness for each layer were created in the models. Mesh quality analysis was done to prevent distorted elements from affecting the accuracy of the numerical simulation (Fig. 1C). The choice of hybrid tetrahedral-prismatic mesh density generated was consistent with a mesh density refinement analysis reported in Frank-Ito, et al. ²⁶; therefore, mesh convergence test to ensure mesh-independent numerical solutions was not done in the present study. For each subject, the same mesh was used for both the 15L/min and 30L/min simulations. Although prism layers may not be necessary for laminar flow simulations, the hybrid tetrahedral-prismatic elements was maintained for consistency of mesh structure in simulating both flow rates and to accurately capture the near wall velocity profile in our models.

Inspiratory airflow simulations were performed using a steady, incompressible model, at two flow rates (15L/min and 30L/min) by means of the CFD software package, ANSYS Fluent™ 19.0 (ANSYS, Inc., Canonsburg, PA, USA). As 15L/min is considered resting breathing, laminar airflow simulation was performed to target this flow rate. Since flow velocities through the nasal cavity during low to moderate breathing usually have a Mach number $\ll 0.2,$²⁷ the conservation of mass and momentum governing equations for steady, laminar viscous, incompressible flow reduces to

$$\nabla \bullet \overrightarrow{u}=0,\mathrm{ }$$

$$\rho \left(\overrightarrow{u}\bullet \nabla \right)\overrightarrow{u}=-\nabla p+\mu {\nabla }^2\overrightarrow{u},$$

where $\overrightarrow{u}=\overrightarrow{u}(x,y,z)$ is the velocity vector field, $\rho =1.204$ kg/m³ is the fluid density, $\mu =1.825\times {10}^{-5}\mathrm{ }\mathrm{k}\mathrm{g}/\mathrm{m}-\mathrm{s}$ is the dynamic viscosity, and $p$ is the pressure.

The turbulent airflow simulation was implemented using the shear-stress transport k-ω model, with low Reynolds number corrections for 30L/min flow rate.^28,29 The turbulence length scale was set at 1mm, and turbulent intensity to be 5% at the inlet (nostrils). The k-ω model has been reported to accurately predict pressure drop, velocity profiles, and shear stress from transition to turbulent flows.^30–32

To simulate the inspiratory airflow dynamics, “mass flow outlet” boundary condition was specified at the outlet to target 0.0003kg/s (15L/min) and 0.0006kg/s (30L/min), respectively. At the inlet (nostrils), atmospheric conditions were specified with zero gauge pressure. The computational domain (nasal cavity) was considered stationary, with no-slip boundary conditions along the walls (nasal mucosa). A SIMPLEC scheme was used to couple the pressure and velocity fields. SIMPLEC was selected over other schemes to solve the incompressible Navier-Stokes equations due to its lower computational effort requirements.³³ The pressure equation was solved with a second order spatial discretization scheme, and second order upwind for momentum, turbulent kinetic energy and specific dissipation rate.^34–36

RESULTS

Cross-sectional velocity contour plots in the olfactory region are displayed in Fig. 1D for the 15L/min simulations. Olfactory velocity profile was greatest in the cross sections for Subjects DN002 and DN003. In addition, the middle cross sections (Z07 and Z13) for every subject had relatively higher velocity than cross sections Z01 and Z20. Next, the velocity contour plot at each cross section in Subject DN008 were remarkably asymmetrical. At Z01 and Z07, olfactory velocity on the left side was negligible (near 0), with a remarkable switch at cross sections Z13 and Z20 show extremely low olfactory velocity on the right side.

Bilateral and unilateral resistance values calculated from nostril(s) to choana(e) for each patient are presented in Figs. 2A & 2B. Resistance was calculated as $\Delta P/Q$(Pa*s/mL) where $\Delta P$ is bilateral/unilateral pressure drop from nostril(s) to choana(e), and $Q$ is bilateral/unilateral volumetric flow rate. Resistance values calculated from nostril(s) to choana(e) have been reported to capture patients’ symptoms of nasal patency more accurately than those calculated from nostrils to the posterior portion of the nasopharynx.³⁷ Subject DN001 with bilateral Elongated nasal vestibule had the lowest resistance (0.01 Pa*s/mL at 15L/min flow rate and 0.02 Pa*s/mL at 30L/min flow rate), while Subject DN002 with bilateral Notched nasal vestibule had the highest resistance (0.10 Pa*s/mL at 15L/min flow rate and 0.15 Pa*s/mL at 30L/min flow rate). Resistance values for the subject with bilateral Standard nasal vestibule (DN003) were 0.04 Pa*s/mL at 15L/min flow rate (Fig. 2A) and 0.06 Pa*s/mL at 30L/min flow rate (Fig. 2B).

Figure 2.

Average olfactory cleft resistance for each patient at (A) 15L/min and (B) 30 L/min. Average flow rate for each phenotype at (C) 15 L/min and (D) 30 L/min. Average flow partition for each phenotype at (E) 15 L/min and (F) 30 L/min.

Similar to bilateral resistance, unilateral resistance values on the left and right nasal passages were highest and lowest in Subjects DN001 and DN002, respectively. However, in the case of Subjects DN008 and DN009, where the nasal vestibule morphology on one side differed from the contralateral side, unilateral resistance on the Notched side tended to be higher than on the Standard side. For DN008, unilateral resistance values on the Notched (left) side were 0.08 Pa*s/mL (at 15 L/min flow rate; Fig. 2A) and 0.13 Pa*s/mL (at 30 L/min flow rate; Fig. 2B) versus 0.05 Pa*s/mL (at 15 L/min flow rate) and 0.07 Pa*s/mL (at 30 L/min flow rate) on the Standard (right) side. Similar unilateral resistance pattern was observed in DN009. In addition, the relative difference in unilateral resistance between left and right sides revealed a much higher asymmetry in DN008 (50% at 15 L/min and 52% at 30 L/min) and DN009 (73% at 15 L/min and 79% at 30 L/min) compared to DN001 (29% at 15 L/min and 21% at 30 L/min), DN002 (18% at 15 L/min and 19% at 30 L/min), and DN003 (1% at 15 L/min and 1% at 30 L/min).

To effectively describe olfactory cleft airflow volume across the different nasal vestibule morphological phenotypes, olfactory cleft volumetric airflow passing through 20 cross-sectional slices spanning the entire olfactory airspace computed (Figs. 2C & 2D). Average olfactory cleft airflow volume in the airways with Standard nasal vestibule ranged from 0.25L/min to 0.64L/min (for 15 L/min simulations) and 0.53L/min to 1.30L/min (for 30 L/min simulations); average range for Notched nasal vestibule were 0.13L/min – 0.47L/min (for 15 L/min simulations) and 0.06L/min – 0.82L/min (for 30 L/min simulations); and 0.07L/min – 0.39L/min (for 15 L/min simulations) and 0.30L/min – 0.99L/min (for 30 L/min simulations) for Elongated nasal vestibule. This demonstrates that olfactory cleft airflow volume was generally highest in the Standard nasal vestibule, particularly at the anterior region of the olfactory cleft. The Notched and Elongated nasal vestibule phenotypes had considerable overlapping cross-sectional olfactory cleft airflow volume at 15 L/min simulations, while Elongated nasal vestibule had more olfactory cleft airflow volume than Notched nasal vestibule at 30 L/min simulations in 19 of 20 cross-sections (Figs. 2C & 2D).

The plots in Figs. 2E & 2F capture percent of airflow partition going into the olfactory cleft at the different cross-sections. For airways with Standard nasal vestibule phenotype, percent of airflow partition in the olfactory cleft were 3.0% – 7.7% and 3.2% – 7.8% for 15L/min and 30L/min simulations, respectively. In addition, percent airflow partition in the olfactory cleft for Notched phenotype were 2.0% – 6.8% (for 15L/min) and 1.7% – 6.1% (for 30L/min), as well as 1.2% – 5.4% (for 15L/min) and 2.1% – 6.7% (for 30L/min) for Elongated phenotype. In agreement with olfactory cleft airflow volume, the percent of airflow partition in the olfactory cleft was greatest in airways with Standard phenotype. However, notice that although olfactory cleft airflow volume and percent of airflow partition tended to be greatest in Standard phenotype at the anterior region of the olfactory, Notched phenotype had the greatest airflow volume and percent of airflow partition at the posterior end of the olfactory region (Figs. 2E & 2F).

Average cross-sectional resistance of airflow (defined as the pressure at a given cross-section divided by the flow rate at that cross-section) in the olfactory cleft for each nasal vestibule phenotype is presented in Table 1A. Without exception of cross-sections Z11 to Z15, cross-sectional resistance of airflow in the olfactory region was generally lowest in Elongated phenotype and highest in the Notched phenotype. The resistance values in cross-sections Z11 to Z15 were astronomically high in the Standard phenotype, thus will be considered outliers. Other than these outliers, olfactory cross-sectional resistance the Standard phenotype was generally lower anteriorly and higher posteriorly. In the Notched phenotype, cross-sectional resistance was significantly elevated in the anterior olfactory region, which gradually tailed off posteriorly. In the case of Elongated nasal vestibule phenotype, cross-sectional resistance was lowest in the middle region of the olfactory cleft and elevated at both anterior and posterior olfactory regions.

Table 1.

(A) Individual olfactory cross-section resistance averages for each morphology at 15 L/min and 30 L/min.

Flow Rate (l/m)	Morphology	Olfactory Cross-Section Resistance (Pa*s/ml)
		Z01	Z02	Z03	Z04	Z05	Z06	Z07	Z08	Z09	Z10	Z11	Z12	Z13	Z14	Z15	Z16	Z17	Z18	Z19	Z20
15	Elongated	13.66	1.10	0.54	0.39	0.34	0.32	0.31	0.31	0.31	0.32	0.33	0.34	0.35	0.36	0.39	0.42	0.45	0.50	0.54	0.61
	Notched	27.89	32.75	36.87	20.70	13.53	9.26	7.83	8.68	9.91	3.41	2.63	2.37	2.89	3.00	3.15	3.30	3.37	6.66	10.89	6.00
	Standard	0.57	0.55	0.53	0.54	0.58	0.59	0.62	0.69	0.76	1.17	51.17	11974.35	11493.44	788376.14	571077.09	4.84	1.63	1.88	2.34	2.71
30	Elongated	1.19	0.77	0.58	0.48	0.44	0.41	0.40	0.41	0.40	0.42	0.42	0.44	0.44	0.45	0.47	0.49	0.50	0.53	0.56	0.61
	Notched	34.51	35.18	37.92	35.72	31.08	27.17	23.91	21.71	19.77	32.02	27.61	9.95	7.58	6.20	6.06	6.11	5.76	10.10	16.23	8.79
	Standard	0.90	0.86	0.82	0.81	0.85	0.86	0.92	1.02	1.15	1.83	26.35	2842.37	5283.36	31086.07	172085.69	15.43	2.66	2.95	3.72	4.41

As depicted in Table 1B, airflow Reynolds numbers (Re) in the nasal cavity across all subjects were calculated at the nostril and choana for 15 L/min and 30 L/min flow rates. The Reynolds number (Re) was calculated as $Re=Q{D}_H/vA=4Q/Pv$ where $Q$ is the volumetric flow rate, $D_H$ is the hydraulic diameter defined as $D_H=4A/P,\mathrm{ }A$ is the cross-sectional area at nostril/choana, $v$ is the kinematic viscosity, and $P$ is the perimeter at the nostril/choana. At 15L/min flow rates, Re ranged from 2109 to 941, and from 4219 to 1883 at 30L/min flow rate. For both flow rates, maximum Re occurred at the left nostril of Subject DN002 and minimum Re at the left nostril of Subject DN003. In addition, the nostril Re was generally higher than choana Re. For Subjects DN008 and DN009, where the nasal vestibule morphology on one side differed from the contralateral side, the Re values on the side with Standard phenotype were higher than on the side with Notched phenotype.

Table 1.

(B) Calculated Reynolds numbers for all subjects at the nostril and choana for 15 L/min and 30 L/min flow rates

SUBJECT	NASAL CAVITY PLANE	Reynolds number at 15L/min		Reynolds number at 30L/min
		Left Side	Right Side	Left Side	Right Side
DN001	Nostril	1817	1663	3634	3326
	Choana	1347	1224	2695	2448
DN002	Nostril	2109	2095	4219	4189
	Choana	1534	1532	3067	3063
DN003	Nostril	1847	1877	3694	3754
	Choana	941	1054	1883	2107
DN008	Nostril	1616	1741	3232	3482
	Choana	1183	1194	2367	2387
DN009	Nostril	1895	1865	3790	3730
	Choana	1189	1104	2378	2208

Relative difference in intra-subject olfactory airflow volume between left and right olfactory cleft regions shows that DN008 had the largest variation in cross-sectional olfactory airflow volume between both sides (14 of 20 cross-sections had relative difference >185%; Figs. 3A & 3B). This is followed by DN009 for 15L/min simulations (10 of 20 cross-sections with relative difference >90%; Fig. 3A), and DN002 for 30L/min simulations (13 of 20 cross-sections with relative difference >140%; Fig. 3B). Similarly, Fig. 3C depicts relative difference in intra-subject olfactory cleft cross-sectional resistance for 15L/min simulations. In agreement with olfactory airflow relative difference, DN008 had the largest variation in resistance between the left and right olfactory cleft regions, which is followed by DN009. In contrast to Fig. 3C, DN002 had the largest variation in relative difference in olfactory cleft cross-sectional resistance for 30L/min simulations, next to DN009 (Fig. 3D).

Figure 3.

Average flow rate for each phenotype at (A) 15 L/min and (B) 30 L/min. Average flow partition for each phenotype at (C) 15 L/min and (D) 30 L/min.

Fig. 4 shows nasal and olfactory airflow streamline pattern from 200 equally spaced and randomly generated points from the nostril. Airflow pattern in the Elongated phenotype contains anterior superior flow recirculation reaching the anterior olfactory airspace on the left side (DN001). Next, the Notched phenotype (DN002 left and right, DN008 right, and DN009 left) revealed a larger magnitude of anterior superior flow recirculation reaching the anterior olfactory airspace. Both Elongated and Notched phenotypes show more posterior flow passing through the posterior region of the olfactory cleft than the anterior olfactory region. In the case of Standard nasal vestibule phenotype ((DN003 left and right, DN008 left, and DN009 right), there appears to be increased airflow volume passing through the anterior olfactory window compared to the other nasal vestibule phenotypes. These airflow visualization images provide important insights into the variabilities noted above with computed values of olfactory cleft airflow volume, airflow partition and resistance.

Figure 4.

Nasal and olfactory airflow streamlines colored by velocity magnitude for each patient 15 L/min simulation.

Contour plots of turbulent kinetic energy (TKE) at the nasal cavity for the 30L/min simulations are presented in Fig. 5. The results show that Subject DN002 had the most regions with highest TKE. For Subjects DN008 and DN009, where the nasal vestibule morphology on one side differed from the contralateral side, the side with Standard phenotype had several regions with increased TKE; this is a remarkable contrast with the contralateral Notched side where increased TKE values were limited to a tiny portion of the nasal cavity.

Figure 5.

Contour plot of turbulent kinetic energy at the nasal cavity for 30L/min simulation.

DISCUSSION

The typical human nasal cavity is characterized by a number of normal intra- and inter-individual morphological variabilities that can confound concise characterization of a normal nasal airflow profile. ^{14,16,17,38–49} The nasal vestibule is the portal of entry where inhaled ambient air enters the respiratory tract. Inhaled air flowing in the notched nasal vestibule twist and swirl through to the nasal valve, while lateral flow tend to be smoother, less contorted, and have higher velocities.¹⁸ In certain scenarios, depending on nasal anatomical variation, the vortex formed can extend posteriorly to the anterior end of the middle turbinate and beyond; this recirculating zone increases residence time of inhaled air in the anterior superior region.^17,49–53 Ramprasad and Frank-Ito ¹⁷ suggest that local airflow patterns to the superior region of the nasal cavity were significantly influenced by nasal vestibule type (Notched, Standard, and Elongated). This implies that nasal vestibule morphology plays a role in the transportation of odorant-laden air to the olfactory recess. Knowledge of the relationship between nasal vestibule anatomy and olfactory function may advance understanding of whether individuals with certain nasal vestibule morphology are predisposed to heightened severity of olfactory dysfunction when affected by diseases associated with loss of smell or as they progress in age.

Results from our preliminary data suggest that the amount of air flowing through the unilateral olfactory region ranged between 1% and 5% (median=4.5%), between 2% and 7% (median=5.6%), and between 3% and 8% (median=6.4%) for patients with the Elongated, Notched, and Standard morphologies, respectively, at 15L/min. These ranges are in line with reported values in the literature, Keyhani, et al. ⁵⁴ noted that about 10% of flow volume passes through the olfactory region; while Segal, et al. ⁵⁵ reported 3%−18% (median=6%) of flow volume passing through the superior region of the nasal cavity. In a recent study involving 47 healthy adults, Borojeni and colleagues⁴² computed unilateral airflow allocation across 5 coronal cross-sections, average unilateral airflow through the superior nasal region was 12%±8%; Zhao and Jiang ⁵² reported approximately 16%±10% in corresponding region among 22 healthy subjects, including about 6%±4% in the olfactory recess; and in the 10 healthy nasal cavities studied by Hazeri, et al. ⁵⁶ the amount of airflow passing through the olfactory was 4.1%±2.1%;.

In addition, our findings show that Standard phenotypes have the greatest amount of flow towards the anterior part of the olfactory cleft. Elongated phenotypes have the greatest amount of flow towards the medial part of the olfactory cleft, and Notched phenotypes have the greatest amount of flow in the posterior region of the olfactory cleft. Nonetheless, further research needs to be done to determine if these varying olfactory flow profiles across Standard, Elongated and Notched may have implications for the ability of patients with different phenotypes to better detect particular compounds based on the location of receptors in the olfactory region. The preliminary results presented here also indicate that intra-patient flow variation differs greatly through the olfactory region for patients with different unilateral phenotypes compared to patients with identical unilateral phenotype on the left and right nasal cavities. This is evidenced by the fact that DN008 had the greatest amount of olfactory variation in the anterior three quarters of the olfactory region while DN009 had the greatest amount of variation in the posterior quarter of the olfactory region. Of the patients identical morphologies, the patient with bilateral elongated phenotype (DN001) had the lowest amount of variation in flow for the posterior three quarters of the olfactory region. In the anterior three quarters, the patient with bilateral standard phenotype (DN003) had lower amounts of variation than the patient with bilateral notched nostrils (DN002).

Another important factor of note is the fact that while studies have reported associations between nasal anatomical variations and olfaction,^1–5,57 effects of age-related structural changes in the nasal cavity and breathing techniques on olfactory abilities have been given little attention. Paik, et al. ⁵⁸, Yousem, et al. ⁵⁹, and Buschhüter, et al. ⁵⁷ reported evidence of structural changes in the nasal anatomy with aging, such as age associated decrease in surface/volume of the olfactory epithelium/bulb. Loftus, et al. ⁶⁰ reported an age-related increase in the nasal cavity volume. With respect to aging and the respiratory system, many studies have reported a statistically significant decrease in maximal inspiratory pressure and respiratory muscle strength. ^61–64 Despite this knowledge about age-related changes in inspiration and nasal anatomy, it remains unknown how these changes inhibit olfactory abilities. Thus, understanding of the full impact of conductive factors on human olfaction remains an open question that will benefit from further studies by researchers in this field.

In conclusion, this study uses computational modeling to provide important insights into the effects of nasal vestibule morphological variabilities on olfactory airflow profile, which has a direct impact on the transport of odorant-laden air to the olfactory epithelium. Our results showed that average olfactory cleft airflow volume was highest in the Standard nasal vestibule phenotype, followed by Notched phenotype for 15L/min simulations and Elongated phenotype for 30L/min simulations. Lastly, it is important to note that this study uses twenty cross-sectional planes in the olfactory region to make general assessment of olfactory flow and resistance values. In reality, local airflow in the olfactory usually flows in and out of the olfactory airspace from different points of the airspace below the olfactory region. Nonetheless, the authors are confident that our use of twenty discretized cross-sectional olfactory planes to estimate olfactory flow and resistance values represent a good approximation of the true olfactory flow and resistance values.