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. Author manuscript; available in PMC: 2023 Mar 3.
Published in final edited form as: Cleft Palate Craniofac J. 2020 Dec 24;58(10):1242–1250. doi: 10.1177/1055665620982754

Computational Analysis of Olfactory Airspace in Patients with Unilateral Cleft Lip Nasal Deformity

Reanna Shah 1, Jeffrey Marcus 2, Dennis O Frank-Ito 1,3,4
PMCID: PMC9984277  NIHMSID: NIHMS1868119  PMID: 33356511

Abstract

Objectives:

To evaluate the magnitude of olfactory recess opacity in patients with unilateral cleft lip nasal deformity (uCLND).

Design:

Subject-specific three-dimensional reconstruction of the nasal airway anatomy was created from computed tomography images in 11 subjects (4 males and 7 females) with uCLND and 7 normal subjects (3 males, and 4 females). The volume and surface area of each subject’s unilateral and bilateral olfactory airspace was quantified to assess the impact of opacification. Qualitatively speaking, patients with 75%–100% olfactory recess opacification were classified as extreme, 50%–75% as severe, 25%–50% as moderate, and 0%–25% as mild.

Results:

Of the 11 subjects with uCLND, 5 (45%) were classified as having extreme olfactory recess opacification, 3 (27%) subjects had severe opacification, and 3 (27%) subjects had moderate opacification. Mean ( ± standard deviation) bilateral olfactory recess volume was significantly greater in normal subjects than in subjects with uCLND (0.9668 cm3 ± 0.4061 cm3 versus 0.3426 cm3 ± 0.1316 cm3; p<0.001). Furthermore, unilateral olfactory airspace volumes for the cleft and non-cleft sides in subjects with uCLND were considerably less than unilateral olfactory volume in subjects with normal anatomy (uCLND cleft side = 0.1623 cm3 ± 0.0933 cm3; uCLND non-cleft side = 0.1803 cm3 ± 0.0938 cm3; normal = 0.4834 cm3 ± 0.2328 cm3; p<0.001).

Conclusions:

Our findings indicate a high prevalence of olfactory recess opacification among subjects with uCLND when compared to subjects with normal anatomy. The majority of subjects with uCLND had extreme olfactory recess opacity, which will likely influence their sense of smell.

Keywords: Airway obstruction, Craniofacial morphology, Computerized tomography, Nasal morphology, Nasality

Introduction – Opacification of Olfactory Recess

Cleft lip and cleft palate are among the most common craniofacial abnormalities, affecting approximately 1 out of every 1,600 newborns in the United States (Mai et al., 2019). Among individuals with cleft, about 70% experience impaired functional nasal breathing and upward of 80% “mouth-breathe” due to nasal abnormalities (Warren et al., 1992).The nasal deformity in patients with unilateral cleft lip (with or without cleft palate) is a consistent anatomic deformation that results from lateralization of the maxillary prominences, more specifically, the columellar and alar bases, consequent to their failed coalescence (Fisher et al., 2014, Kosowski et al., 2012). This constellation of complex anatomic derangements has been well characterized by our group and others and is associated with multiple sites of nasal airflow obstruction in the nasal functional airway as well as an increased incidence of sleep disordered breathing (Frank-Ito et al., 2019, Marcus et al., 2019). In particular, severity of nasal obstruction is often worse in unilateral cases of cleft lip than for bilateral cases (Sobol et al., 2016). As described in a recent publication by Tse et al. (2020), for patients with unilateral cleft lip nasal deformity (uCLND), the alar base on the non-cleft side is farther from the facial midline relative to the cleft side alar base; which is contrary to the classical opinion that lateral and inferior displacement were on the cleft side alar base. In addition, airway obstruction induced by uCLND may also impact olfactory function (Richman et al., 1988).

Olfactory dysfunction is characterized by reduced or absent sense of smell, ranging from hyposmia to total anosmia (Guss J, 2009). Loss of the sense of smell negatively impacts patients’ quality of life, both in a practical and social context. In general, practical problems associated with impaired olfactory function can be categorized into three groups: problems with detecting hazardous situations, food-related problems, and problems with managing personal odors. In an online study consisting of 1,000 patients with olfactory dysfunction, 72% of the subjects claimed they were scared of being exposed to dangers. Primary concerns revolved around being unable to detect gas leaks, fires, or exposure to volatile chemicals. In terms of food-related problems, the main consequence of smell loss is the lack of enjoyment when eating. Lastly, individuals with olfactory dysfunction are unable to properly maintain their personal hygiene because they cannot smell their own body odor. This has severe social consequences because individuals with this problem are more likely to become isolated and avoided by their friends and family. Hence, the consequences of uCLND related opacification of the olfactory recess should not be neglected (Keller and Malaspina, 2013).

Unfortunately, there have only been a few articles published addressing the consequences of cleft associated opacification of the olfactory recess, and more specifically, the possible deterioration of the sense of smell in individuals with uCLND (May, 2011). Majority of the investigations conducted on the opacification of the airspace and its effect on sense of smell have focused on diseases such as chronic rhinosinusitis and allergic rhinitis. Analysis of the magnitude of olfactory opacification and relative association to sense of smell is important because it will provide concrete evidence on the impact of uCLND olfactory airspace blockage and provide insight into the need for treatment around the olfactory region.

The purpose of this study is to use three-dimensional (3D) reconstructions of the nasal airway anatomy to evaluate the magnitude of olfactory recess opacity in patients with uCLND, and for comparison with the olfactory recess in subject with healthy normal nasal and olfactory anatomy.

Method

I. Subject Selection

This is a retrospective study approved by the Duke University Health System Institutional Review Board for Clinical Investigations. Eighteen subjects with high resolution computed tomography (CT) scans were selected based on a chart review of medical records from 2010 to 2017. Eleven of these subjects (15–35 years, 4 males, and 7 females; Table 1) had a clinical diagnosis of uCLND with cleft type as unilateral complete cleft lip, alveolus, and palate (Veau 3) or unilateral complete cleft lip alveolus or unilateral incomplete cleft lip. These subjects had not had definitive cleft rhinoplasty or septoplasty for correction of nasal airway obstruction. The other seven subjects (25–70 years, 3 males, and 4 females) have radiographically healthy normal nasal cavity and sinus anatomy, which will serve as the control group. DICOM images from head computed tomographic (CT) scans in all subjects were imported into image analysis software, Avizo Lite 9.5.0 (Thermo Fisher Scientific, Waltham, Massachusetts, USA) for creation of anatomically accurate three-dimensional (3D) reconstructions of the nasal airways and olfactory region.

TABLE 1.

Qualitative assessment of olfactory airspace opacification in subjects with uCLND.

Subject Gender Age Cleft Side Non-Cleft Side Bilateral
uCLND-01 Female 15 Extreme Extreme Extreme
uCLND-02 Male 30 Severe Severe Severe
uCLND-03 Male 15 Moderate Moderate Moderate
uCLND-04 Female 15 Extreme Extreme Extreme
uCLND-05 Female 15 Extreme Moderate Severe
uCLND-06 Female 30 Extreme Moderate Severe
uCLND-07 Female 28 Extreme Extreme Extreme
uCLND-08 Female 32 Severe Extreme Extreme
uCLND-09 Female 25 Moderate Mild Moderate
uCLND-10 Male 17 Extreme Severe Extreme
uCLND-11 Male 22 Mild Moderate Moderate
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II. Qualitative and Quantitative Analyses

To perform qualitative analysis of the olfactory recess, 3D reconstruction of each subject’s unilateral olfactory airspace was delineated. Horizontal delineation of olfactory airspace was from anterior middle turbinate to anterior sphenoid sinus (Holbrook et al., 2011, Leopold et al., 2000, Soler et al., 2015). The vertical height of the olfactory airspace was defined from the roof of the cribriform plate down 10mm inferiorly (Holbrook et al., 2011, Leopold et al., 2000, Soler et al., 2015). In certain cases, the olfactory airspace may be completely occluded, thus impeding such delineation.

Unilateral olfactory airspace was analyzed and a qualitative classification was determined based on the magnitude of olfactory recess opacity: [1] unilateral olfactory airspace with 75% – 100% opacification was classified as extreme; [2] 50% – 75% opacification as severe; [3] 25% – 50% opacification as moderate; and [4] 0% – 25% opacification as mild. In addition, bilateral classification was determined for each patient by assessing the combined unilateral olfactory opacity classification assigned to that patient’s cleft and non-cleft sides (Table 1).

Next, in order to calculate the volume (V) and surface area (SA) of each unilateral olfactory recess, the delineated 3D model of the olfactory airway was isolated from the nasal passage using Avizo Lite 9.5.0 and the Computer Aided Design software package ICEM-CFD™ 19.0 (ANSYS, Canonsburg, Pennsylvania, USA). The isolated 3D olfactory airway volume and surface area were calculated in Avizo Lite 9.5.0. Boxplots of calculated anatomical volume and surface area of 11 subjects with uCLND were compared with 7 subjects with normal nasal and olfactory airspace using a two-tailed non-parametric Wilcoxon rank sum test to perform statistical analyses at ∝ = 0.05.

Results

I. Sample Size Justification

Due to the complexity of analyses, detailed sample size calculations as those conducted here are not trivial. Necessary sample size calculations were performed using one-sample t-test for the following variables: [1] uCLND olfactory recess volume; [2] Normal olfactory recess volume; [3] uCLND olfactory recess surface area; [4] Normal olfactory recess surface area; [5] Unilateral Normal olfactory recess volume; [6] Unilateral Normal olfactory recess surface area; [7] Unilateral Normal Nasal Cavity volume; and [8] Unilateral Normal Nasal Cavity surface area. Power of 90% and a type 1 error rate of α=0.05 were set. From data on 11 uCLND patients and 7 Normal subjects, based on computed mean and standard deviation for the aforementioned variables yield maximum sample sizes of 4 and 5 for uCLND and Normal subjects, respectively.

Next, sample size calculations were performed using paired t-test for uCLND cleft and non-cleft sides on the following variables: [1] Difference between cleft and non-cleft olfactory recess volume; [2] Difference between cleft and non-cleft olfactory recess surface area; [3] Difference between cleft and non-cleft nasal cavity volume; and [4] Difference between cleft and non-cleft nasal cavity surface area. Power of 90%, a medium strength correlation of 0.6 between cleft and non-cleft sides, and a type 1 error rate of α=0.05 were set. Computed mean difference and standard deviation difference for the four uCLND variables yield a maximum sample size of 11.

Lastly, sample size calculations were performed using the two-sample t-test difference between uCLND and Normal subjects on the following variables: [1] Normal and uCLND olfactory recess volume; and [2] Normal and uCLND olfactory recess surface area. Power of 90% and a type 1 error rate of α=0.05 were set, as well as pooled standard deviation was calculated for each variable. Computed mean difference and pooled standard deviation resulted in a maximum sample size of 7 subjects per group (Normal and uCLND). Thus, our planned sample sizes of 11 uCLND patients and 7 Normal subjects is sufficient to detect potentially significant differences in all variables of interest. Analyses on sample size were performed using SAS v9.4 (SAS Institute, Inc., Cary, NC, USA).

II. Qualitative Analysis of Olfactory Opacification

Of the 11 subjects with uCLND involved in this study, 5 subjects (45%) were classified as having bilateral extreme olfactory recess opacification, 3 subjects (27%) had bilateral severe opacification, and 3 subjects (27%) had bilateral moderate opacification (Table 1). In this cohort, no subject was classified as having bilateral mild olfactory recess opacification. With regards to unilateral analysis comparing the cleft side versus the non-cleft side, there were 6 subjects (55%) whose cleft side were classified as having extreme olfactory recess opacification, 2 severe opacification (18%), 2 moderate opacification (18%), and 1 mild olfactory recess opacification on the cleft side (9%). In comparison, olfactory recess opacifications on the non-cleft side were classified as extreme in 4 subjects (36%), severe in 2 subjects (18%), moderate in 3 subjects (27%), and mild in 1 subject (9%; Table 1).

Figure 1 depicts representative images of 3D reconstructed nasal airways for three subjects with uCLND (Figure 1A) and three subjects with normative nasal anatomy (Figure 1B). The olfactory region for each subject is highlighted using an oval outline. The missing space within the olfactory region is greater in subjects with uCLND than in normal subjects. This indicates that there is greater severity of olfactory opacification among subjects with uCLND than in normal subjects. This opacification will likely impede olfactory ability, since olfactory neurons responsible for odor detection are housed within the recess (olfactory epithelium).

FIGURE 1.

FIGURE 1

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Sagittal view of 3D reconstructed nasal airways outlining the olfactory region to depict the magnitude of olfactory opacification for (A) subjects with uCLND, and little to no olfactory opacification in (B) subjects with a normal anatomy.

III. Quantitative Analysis

As indicated in Figure 2, olfactory recess volume (V) was significantly different between both subjects with uCLND and normal cohorts (p < 0.001). Mean ( ± standard deviation) olfactory recess V in subjects with uCLND was (0.3426 cm3 ± 0.1316 cm3) compared to (0.9668 cm3 ± 0.4061 cm3) in those with normal anatomy (Figure 2A). Similarly, differences in olfactory recess surface area (SA) and surface area to volume ratio (SA:V) between both cohorts were statistically significant: p < 0.001 and p < 0.01, respectively. Average olfactory recess SA was smaller in uCLND (9.3774 cm2 ± 2.6949 cm2) than in normal subjects (15.7916 cm2 ± 3.0812 cm2; Figure 2B). Furthermore, mean olfactory recess SA:V ratio was higher in subjects with uCLND (28.2732 cm−1 ± 3.9731 cm−1) than in those with normal anatomy (18.6336 cm−1 ± 6.6851 cm−1; Figure 2C).

FIGURE 2.

FIGURE 2

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Boxplot comparing bilateral olfactory airspace parameters between subjects with uCLND and normal subjects. (A) Olfactory Volume; (B) Olfactory Surface Area; and (C) Olfactory Surface Area to Volume Ratio.

Boxplots of unilaterally computed olfactory airspace parameters (V, SA) on the cleft and non-cleft sides for subjects with uCLND were compared alongside the unilateral left and right olfactory airspace for normal subjects (Fig. 3A for V and 3C for SA). Additionally, nasal cavity parameters (V, SA) were compared between these cohorts (Fig. 3B for V and 3D for SA).

FIGURE 3.

FIGURE 3

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Boxplot comparing unilateral olfactory airspace and entire nasal cavity parameters for cleft side and non-cleft side in subjects with uCLND and the combined unilateral (left-right) sides in normal subjects. (A) Olfactory Volume; (B) Nasal Cavity Volume; (C) Olfactory Surface Area; and (D) Nasal Cavity Surface Area.

Olfactory airspace V was not significantly different between the cleft side and non-cleft side for subjects with uCLND (p = 0.55; Figure 3A). Nonetheless, olfactory airspace V for the cleft side and non-cleft side for subjects with uCLND were respectively different when compared to unilateral olfactory V in subjects with a normal anatomy (p < 0.001 for both comparisons). On average, olfactory recess V was much smaller on the cleft side of subjects with uCLND (0.1623 cm3 ± 0.0933 cm3) than on the non-cleft side of subjects with uCLND (0.1803 cm3 ± 0.0938 cm3), and among subjects with a normal anatomy (0.4834 cm3 ± 0.2328 cm3). In addition, as indicated in Figure 3B, nasal cavity V was not significantly different between the cleft side and non-cleft side for subjects with uCLND (p = 0.10). On the other hand, nasal cavity V comparisons for the cleft side and non-cleft side for uCLND subjects were respectively different when compared to normal subjects (p < 0.001 for cleft side versus normal; p=0.002 for non-cleft side versus normal). Average nasal cavity V was smaller on the cleft side (6.8262 cm3 ± 1.6914 cm3) than on the non-cleft side of subjects with uCLND (7.9297 cm3 ± .1.3046 cm3), and among those with a normal anatomy (11.3891 cm3 ± 2.7311 cm3).

Figure 3C shows that SA of olfactory airspace was not significantly different between the cleft side and non-cleft side for subjects with uCLND (p = 0.43), but the SA of olfactory airspace for each respective side was significantly different when compared to normal subjects (p < 0.001 for cleft side versus normal; p=0.002 for non-cleft side versus normal). Average olfactory SA on the cleft side was 4.4433 cm2 ± 1.5138 cm2 and 4.9342 cm2 ± 1.8950 cm2 on the noncleft side of subjects with uCLND, and 7.8958 cm2 ± 1.9477 cm2 for unilateral sides among subjects with normal anatomy. Furthermore, the SA of the nasal cavity for subjects with uCLND was significantly different between the cleft side and non-cleft side (p < 0.001), with a lower mean unilateral SA on the cleft side (72.8115 cm2 ± 11.5348 cm2) than on the non-cleft side (85.6101 cm2 ± 9.1292 cm2; Figure 3D). Similarly, nasal cavity SA comparisons for the cleft side and non-cleft side in subjects with uCLND were significantly different from that of normal subjects: p < 0.001 and p < 0.01, respectively. On average, olfactory recess SA was lowest on the cleft side, followed by the non-cleft side when compared with normal anatomy.

The fraction of olfactory-to-nasal cavity V was not significantly different between the cleft and non-cleft side for subjects with uCLND (p = 0.8438), as is evidenced by the boxplot in Figure 4A. On the contrary, nasal cavity V comparisons for cleft side versus unilateral sides in normal subjects and non-cleft side versus unilateral sides in normal subjects were significantly different, p < 0.001 and p < 0.01, respectively. Mean olfactory recess V was 2.3737 cm3 ± 1.1483 cm3 on the cleft side and 2.2277 cm3 ± 0.9958 cm3 on the non-cleft side, and 4.1813 cm3 ± 1.6345 cm3 among subjects with a normal anatomy. Additionally, as depicted in Figure 4B, the fraction of olfactory-to-nasal cavity SA was not significantly different between the cleft and non-cleft side for subjects with uCLND (p = 0.6458). In the same vein, SA was not significantly different between the cleft side for subjects with uCLND and normal subjects (p = 0.2392), and between the non-cleft side for uCLND subjects and normal subjects (p = 0.0846). In agreement with Figure 4, Table 2 shows that the volumes of the olfactory airspace among normal subjects occupy a larger proportion of the entire nasal airspace compared to subjects with uCLND.

FIGURE 4.

FIGURE 4

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Boxplot comparing proportion of olfactory airspace to nasal cavity for unilateral cleft side and non-cleft side in subjects with uCLND and the combined unilateral (left-right) sides in normal subjects. (A) Olfactory-to-Nasal Cavity Volume; (B) Olfactory-to-Nasal Cavity Surface Area.

TABLE 2.

Ratio of olfactory to entire nasal passage and relative difference between unilateral left and right olfactory volume.

Cleft Subject CLEFT SIDE NON-CLEFT SIDE Olfactory Volume Relative Difference Normal Subject LEFT SIDE RIGHT SIDE Olfactory Volume Relative Difference
Volume Surface Area Volume Surface Area Volume Surface Area Volume Surface Area
uCLND-01 1.5% 5.0% 2.3% 5.6% 28% Normal-01 3.6% 6.2% 3.0% 5.9% 28%
uCLND-02 3.8% 6.9% 1.4% 4.4% 87% Normal-02 4.2% 9.3% 3.0% 9.1% 20%
uCLND-03 4.6% 9.4% 3.3% 6.4% 33% Normal-03 3.9% 7.0% 7.0% 3.8% 63%
uCLND-04 1.5% 5.9% 2.3% 5.6% 83% Normal-04 3.5% 7.1% 4.0% 7.5% 10%
uCLND-05 1.5% 5.4% 3.1% 8.0% 78% Normal-05 3.7% 8.4% 4.0% 7.9% 15%
uCLND-06 1.0% 2.7% 1.7% 6.3% 87% Normal-06 2.8% 6.8% 2.9% 6.8% 20%
uCLND-07 1.5% 3.7% 0.8% 2.0% 68% Normal-07 8.6% 4.8% 4.2% 8.7% 59%
uCLND-08 3.2% 7.9% 0.7% 3.1% 127%
uCLND-09 2.6% 6.4% 2.7% 8.1% 88%
uCLND-10 2.0% 8.4% 3.8% 7.8% 86%
uCLND-11 3.0% 6.1% 2.5% 5.9% 29%
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Lastly, the relative difference in unilateral volume between left and right olfactory airspace regions for each subject with uCLND and for each normal subject is also presented in Table 2. Among normal subjects, the minimum and maximum relative differences between left and right olfactory volumes were 10% (Normal-04) and 63% (Normal-03), respectively, with an average (± standard deviation) difference of 31% ± 21%. Among subjects with uCLND, the average relative difference was 72% ± 31%, while minimum and maximum differences were 28% (uCLND-01) and 127% (uCLND-08), respectively. The results in this table reveal a statistically significant (p<0.01) higher asymmetry in intra-subject olfactory airspace volume among subjects with uCLND compared to normal subjects.

Discussion

The results obtained from this preliminary study present a strong association between unilateral cleft lip nasal deformity and opacification of the olfactory recess. The deficits of the entire olfactory region were previously examined by Richman et al. (1988) In their study, olfactory responses of boys and girls with cleft lip were compared to subjects without cleft palate. It was found that cleft palates in boys are more strongly associated with olfactory deficits, as their olfactory scores were much lower than boys without cleft palate. On the other hand, the study Grossmann et al. (2005) conducted had somewhat contrasting discoveries. Grossmann et al. (2005) found that although there was a significant difference in the smell threshold psychophysical test between the cleft cohort and control group, there was no difference between both groups regarding the odor identification psychophysical test. The study also found an inverse correlation between airflow and smell threshold. It should be noted that in both of these studies, a small number of common household odors were tested at relatively high concentrations.

Similar to work by Grossmann et al. (2005), Mani et al. (2010) also concluded that low airflow was related to a high smell threshold. They found that the less airflow that reaches the olfactory region, the higher the concentration level of the odor must be in order to properly detect it. Additionally, the study objectively showed that the nasal function of patients with unilateral cleft lip and palate (UCLP) is significantly compromised compared to patients without UCLP. The study also noted that ability to identify correct odor was severely impaired in patients with UCLP when compared to the control group. Furthermore, similar to the findings in the present study, the nasal volume, cross-sectional area, and resistance were significantly different between the cleft side and non-cleft side.

Several explanations are possible for the presence of impaired olfaction in the UCLP population. Roosenboom and colleagues explored the olfactory function and facial endophenotypes of non-affected first-degree relatives of persons with non-syndromic cleft lip and/or palate (NSCL/P) compared to persons without CL/P family history (Roosenboom et al., 2018, Roosenboom et al., 2015). These authors detected a reduced smell capacity in non-affected first-degree relatives of patients with NSCL/P, compared to a control group with negative familial history for NSCL/P. They also found that the relatives with olfactory dysfunction had a smaller central olfactory region. Similarly, May (2011) found that unaffected first-degree relatives of subjects with orofacial cleft had a higher frequency of deficits in odor discrimination as compared with matched controls. Furthermore, May (2011) discovered that individuals with orofacial cleft have significantly more deficits in olfactory discrimination compared to matched controls, and unaffected first-degree relatives. Both of these studies were examining the potential connection between cleft olfactory dysfunction in cleft individuals and their unaffected relatives, highlighting a possible genetic component in reduced olfactory function in individuals with cleft-related deformity.

From the limited number of published articles on cleft-induced olfactory dysfunction, no study thus far has examined the effect of opacification of the olfactory recess in subjects with cleft in relation to reduced sense of smell. This study demonstrated a clear relationship between individuals with uCLND and increased opacification in the olfactory recess. From our qualitative analysis, it was observed that individuals with uCLND had greater opacification in the olfactory recess compared to subjects with a normal anatomy. In addition, as indicated in Table 2, the ratio of olfactory surface area to the surface area of the entire nasal passage is comparable in both subjects with uCLND and normal subjects, but the ratio of olfactory volume to the volume of the entire nasal passage in subjects with uCLND is statistically significant lower when compared with normal subjects. With surface area held constant, the larger proportions of volume in normal subjects suggest that there is a greater amount of obstruction in subjects with uCLND than in normal subjects. Thus, it is logical to postulate that reduced olfactory airspace volume due to increased opacification can contribute to a diminished sense of smell, transport of odorant laden-air particles to the olfactory may be unable to reach the olfactory receptors, which is necessary for smell identification and detection (Eiting et al., 2015). This theory can further be supported by Gopalaswamy (2019) who reported in her Master thesis that over 50% of cleft subjects had some evidence of a smell deficit compared to only 24% of the controls. Furthermore, our quantitative analysis revealed a statistically significant reduction in olfactory volume and surface area among subjects with uCLND relative to normal subjects. And subjects with uCLND had significantly greater asymmetry in unilateral (left-to-right) olfactory volume and surface area than normal subjects.

The findings in the present study raise several unanswered questions: Are olfactory defects due to alteration of airflow to the olfactory cleft from opacification, i.e. obstructive hyposmia? If so, does standard surgical repair improve air flow to the olfactory cleft, resulting in improved olfactory function? Or, are cleft deformities also associated with histologic changes in the olfactory mucosa, such that olfactory dysfunction has a sensorineural component? The implications of olfactory dysfunction are significant; impaired olfactory ability is often associated with decreased enjoyment of food (Schiffman and Zervakis, 2002), changes in emotional and sexual behavior (Nordin et al., 2011, Raviv and Kern, 2004, Temmel et al., 2002), and higher incidence of accidental death from gas poisonings and explosions or unintended exposure to hazardous chemicals/environment (Chalke et al., 1958, Santos et al., 2004, Stevens et al., 1987). Notwithstanding the aforementioned speculation about the fundamental cause of olfactory dysfunction in subjects with uCLND, the results of this study provide important information that will be beneficial to clinicians. Surgeries to correct nasal obstruction do not attempt to directly address any abnormality in the olfactory region. Further, there is no evidence to support whether contemporary surgical correction of the functional nasal airway would result in any change in the opacification of the olfactory recesses. In the absence of any such change, patients with uCLND may continue to experience a diminished sense of smell (olfactory function) postoperatively. However, further studies may be needed to determine the impact of functional nasal surgery in improving olfactory outcomes in patients with uCLND. It must be understood whether or not traditional functional airway surgery has any effect at all on olfactory function. With this knowledge, it would then be crucial to determine if any such surgery is associated with changes in the opacification of the olfactory recess. A relationship between changes in opacification with functional improvement in olfaction would not be definitive for cause-effect, but it could be further evidence in support of this theory.

In conclusion, this study investigated the magnitude of olfactory opacification in patients with uCLND using three-dimensional reconstructions of the nasal airway anatomy from seven normal subjects and eleven cleft subjects. Analyses to characterize the olfactory airspace differences between the two groups were conducted. This study shows that olfactory opacification appears to increase in subjects with uCLND than those with a normal anatomy. To our knowledge, this is the first study to use three-dimensional techniques to quantify the degree of opacification in the olfactory recess in subjects with uCLND and compared with normal subjects.

Acknowledgement

Research reported in this publication was supported by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number R01DE028554. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. In addition, special thanks to ANSYS, ANSYS Global Academic Program, and Dr. Paolo Maccarini (Duke University), for support and strategic donation. All authors gave final approval for publication.

Financial Disclosure Statement:

This research was supported by the National Institute of Dental & Craniofacial Research of the National Institutes of Health under Award Number R01DE028554.

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