Chem. Senses 27: 831-839,
2002
© Oxford University Press 2002
Intranasal Volume and Olfactory Function
Department of Otorhinolaryngology, University of Cologne, Cologne, Germany 1 Department of Nuclear Medicine, University of Cologne, Cologne, Germany 2 Pharmazentrum Frankfurt, Department of Clinical Pharmacology, University of Frankfurt am Main, Frankfurt am Main, Germany 3 Department of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany
Correspondence to be sent to: Michael Damm, Department of Otorhinolaryngology (HNO), University of Cologne, Joseph Stelzmann Str. 9, D-50924 Köln, Germany. e-mail michael.damm{at}uni-koeln.de
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Abstract |
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The aim of this exploratory study was to identify the volume intranasal segments as they relate to parameters of olfactory function. Fifty healthy male volunteers (age range 22-59 years, mean age 28.5 years) were included. Olfactory function was measured by lateralized phenyl ethyl alcohol odor thresholds and odor discrimination, and by bilateral odor identification. Magnetic resonance imaging of the nasal cavity was performed immediately following olfactometry. To correlate the results of olfactometry with intranasal volume, each nasal cavity was divided into 11 segments. Significant correlations were found between the odor thresholds and volumes of the anterior part of the lower and upper meatus of the right nasal cavity. These results reveal that two nasal segments are important for inter-individual differences of odor thresholds in healthy subjects: (i) the segment in the upper meatus below the cribriform plate and (ii) the anterior segment of the inferior meatus. The latter finding is of special interest for nasal surgery, which allows modification of this volume through resection of the inferior turbinate and/or septoplasty.
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Introduction |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Shape and volume of the nasal cavity influence olfactory function (Masing, 1967
;
Youngentob et al.,
1986; Keyhani et al.,
1997). They have a strong impact on intranasal airflow
(Scherer et al.,
1989; Kelly et al.,
2000) and thus on the number of odorant molecules transported to
the olfactory epithelium (Tonosaki and
Tucker, 1985; Hornung et
al., 1987; Keyhani et
al., 1997). Several studies have focused on the relationship
between the intranasal airflow and olfactory function
(Youngentob et al.,
1986; Eccles et al.,
1989; Hornung et al.,
1997; Damm et al.,
2000).
Only two studies have quantitatively investigated correlations of human
olfactory function and nasal volumetrics
(Leopold, 1988;
Hornung and Leopold, 1999).
Leopold studied the relationship between bilateral human olfaction and nasal
anatomy in 34 hyposomic patients. Olfactory function was assessed with an odor
identification test (odorant confusion matrix, OCM), and nasal anatomy was
evaluated using computed tomography (CT). Leopold identified three areas
influencing olfaction. These areas were located beneath and anterior to the
cribriform plate, and in the space in the posterior portion of the nose and
below the cribriform plate. In a later study
(Hornung and Leopold, 1999)
unilateral measurements confirmed the findings of the first study.
To date, however, no data are available about nasal anatomy and olfactory function in subjects without nasal pathology. The aim of the present exploratory study was to identify intranasal volumes that are related to olfactory function in normosomic subjects.
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Materials and methods |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Study design
The current exploratory study was performed as an open trial in healthy subjects. Analysis of intranasal volumes was observer-blinded.
Subjects
The study was performed according to the ethical principles for medical
research involving human subjects (World
Medical Association, 2000). Informed written consent was obtained
following oral and written explanation of aims and potential risks of the
study. Fifty healthy volunteers (mean age 28.5 years, range 22-59 years)
participated. To exclude gender as a possible source of variation in olfactory
function, only male subjects were recruited
(Doty, 1986).
Procedure
The following procedures were performed in all subjects in chronological
order: (i) medical history; (ii) self-assessment of olfactory sensitivity and
nasal ventilation; (iii) active anterior rhinomanometry; (iv) psychophysical
measurements of olfactory function (odor detection thresholds, odor
discrimination, odor identification); and (v) anatomical measures using
magnetic resonance imaging (MRI). To minimize the potential effects of
variations in nasal airway congestion on olfactory function, 0.15 mg
oxymetazoline (Nasivinetten®, Merck Darmstadt, Germany)
(Hummel et al.,
1998b) were administered to each nostril after the history was
recorded and self-assessments had been made
(Kayser, 1895;
Hasegawa and Kern, 1977;
Eccles, 2001). Oxymetazoline
was shown to have little or no influence on olfactory function in healthy
subjects (Hummel et al.,
1998b; Temmel et al.,
1999). Rhinomanometry, olfactometry and MRI were performed
sequentially, with breaks of <5 min between tests (duration of all
measurements 
2 h). This tight schedule was thought to be necessary as
olfactory function appears to exhibit a certain day-to-day variability, and
can even show fluctuations within a single day
(Stevens et al.,
1988; Lotsch et al.,
1997) [see also (Kendal-Reed
et al., 2001)].
Medical history
A detailed history ascertained the absence of diseases with potential
impact on olfaction, including major head trauma, nasal or sinusoidal disease,
neural or endocrinological disorders, or previous nasal surgery. All subjects
were in excellent health; none of them reported significant olfactory
dysfunction. Normosmia was verified by means of the `Sniffin' Sticks' test
(Hummel et al., 1997;
Kobal et al.,
2000).
Ratings of olfactory sensitivity and nasal ventilation
Ratings of olfactory sensitivity and nasal ventilation were obtained using
visual analogue scales (VAS) of 10 cm length (left-hand end: `no olfactory
sensitivity' or `totally blocked nasal airways', respectively; right-hand end:
`extremely high olfactory sensitivity' or `extremely easy nasal breathing',
respectively).
Active anterior rhinomanometry
A computer-aided rhinomanometer (Rhinodat K, Heinemann, Hamburg, Germany)
was used for measurements of the nasal flow, with a tight-fitting facemask and
integrated flow meter. The inspiratory airflows in cm3/s at 150 Pa
(measured 10 min after decongestion) were subsequently submitted to
statistical analysis.
Measures of olfactory function
Olfactory function was evaluated using the `Sniffin' Sticks' test battery
(Hummel et al., 1997;
Klimek et al., 1998;
Kobal et al., 2000).
This test is based on odor-dispensing devices similar to a felt-tip pen. For
odor presentation, the cap was removed by the experimenter for 3 s and
the tip of the odorized pen was placed 2 cm in front of either
nostril.
Phenyl ethyl alcohol (PEA) odor thresholds and odor discrimination were measured separately for the left and right nostril. Each nostril was sealed with Micropore® tape (3M, Minneapolis, MN). The sequence of the lateralized measurements was randomized across all participants. Odor identification was measured bilaterally. Subjects might have remembered the odor labels when left and right sides would have been tested sequentially, which, in turn, would have impacted on the test results.
PEA odor thresholds were assessed using a single-staircase, triple
forced-choice procedure (Hummel et
al., 1997; Ehrenstein and
Ehrenstein, 1999). Sixteen dilutions were prepared in a geometric
series starting at a 4% solution (dilution ratio 1:2 in propylene glycol). At
each trial, three pens were presented in a randomized order, two of which
contained the solvent only, the other containing the odorant at a certain
dilution. The subject's task was to detect the odor-containing pen, which was
color-coded. Subjects were blindfolded to prevent visual identification of
this pen. Triplets were presented at intervals of 20 s. Reversal of the
staircase was triggered when the odor was correctly identified in two
successive trials. Threshold was defined as the mean of the last four out of
seven staircase reversal points. The subjects' scores ranged between 0 and
16.
In the odor discrimination task, triplets of pens were presented in a
randomized order. Two of them contained the same odorant, while the third
contained a different odorant [for individual odors see Hummel et al.
(Hummel et al.,
1997)]. Subjects had to find out which of the three
odor-containing pens smelled differently. Presentation of triplets was
separated by 20-30 s. The interval between presentations of individual pens of
a triplet was 3 s. The score was determined as the sum of all correct
discriminations; as 16 triplets were tested in total, scores ranged from 0 to
16. The pen with the target odor was color coded for each triplet.
Accordingly, as with assessment of odor thresholds, subjects were blindfolded
to prevent visual identification of this pen.
Odor identification was assessed by means of 16 common odorants. Using a
multiple choice task, identification of individual odorants was performed from
a list of four descriptors each. The interval between odor presentations was
20-30 s. The descriptors used were identified during validation of this test
(Hummel et al.,
1997). Specifically, the odor of each individual descriptor is
known by >90% of healthy subjects. The subject's score was determined as
the sum of all correct identifications, thus allowing ranges between 0 and
16.
Anatomical measures using MRI
MRI. MRI was performed on a 1.5 T scanner (Gyroscan 1.0-NT,
Philips Medical Systems, Eindhoven, The Netherlands). Immediately following
olfactometry, T2-weighted turbo spin echo sequences were obtained in the head
coil, with a repetition time of 3000 ms and an echo time of 100 ms in
transverse and coronal planes. Slice thickness was 4 mm, with a 0.4 mm
intersectional gap. The acquisition matrix was 256 x 256 pixel, and the
field of view was 230 mm. Scan percentage was set to 90% of the phase encoding
profiles, resulting in a spatial resolution of 0.9 x 1.0 mm. The
obtained images were transferred to an IBM-compatible workstation.
Measurements were done with reference to a caliper. Final volumetric data were
calculated with correction for the intersectional gap of 10% between slices.
All pixels of one region in one slice were summed up and the sum of the slices
were corrected by 10%. No contrast agent was administered. Subsequently to the
measurements of the nasal airways, MRI scans of the head were performed to
exclude the possible presence of pathologies in the cranium (T1-weighted
transversal, Flair transversal, T2-3D transversal).
Image analysis. The MRI scans were transferred to an
IBM-compatible workstation and converted to a tagged image file format (TIFF)
for digital processing. All data were computed in Image Pro Plus® 1.3
(Media Cybernetics, Silver Spring, MD). This software allows semiautomatic
measurement of a region of interest (ROI)
(Figure 1). A grid was
superimposed on the scans, which divided each nasal cavity into 80 areas
of 10 square pixels each. To contrast the border between air and mucosa, the
image was transformed to a two-color bitmap level. For validation of this
approach we investigated differences between areas measured on 256 grayscale
original images and bitmap level images. Differences between these two
approaches were <1%.
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Nasal segments. To correlate olfactory function and nasal volumes,
the nasal cavity was subdivided into 22 segments (11 segments for the left and
11 segments for the right cavity). Segmentation of the nasal cavity was made
similar to suggestions by Leopold, Hong and others
(Hong et al., 1998;
Hornung and Leopold, 1999;
Leopold, 1988). Borders of the
presently used segments were non-overlapping; these borders were aligned with
respect to the grid mentioned above. Segmentation into 2 x 11 volumes
was orientated on anatomical landmarks, e.g. the nasal meatus, the turbinates
and the nasal septum. The following four regions (A—D) were
distinguished in anterior—posterior direction
(Figure 2): region A, `outer
nose': beginning at the tip of the nose, ending at the maxillary aperture;
region B, `anterior nasal cavity': beginning at the aperture of the maxilla,
ending at the geometrical midline of the nasal cavity; region C, `posterior
nasal cavity': beginning at the geometrical midline, ending with the nasal
septum; region D, `nasopharynx': beginning at the end of the septum, ending at
dorsal pharyngeal mucosa. In the rostro-caudal direction the nasal cavity was
divided into three segments (1-3), using turbinates, the floor and the roof of
the nasal cavity as markers; borders were marked with parallel lines: segment
1, `lower meatus': from the hard palate to the MR slice (transversal
orientation) where the middle turbinate becomes visible; segment 2, `middle
meatus': from the upper border of segment 1 to the MR slice (transversal
orientation) where the anterior insertion of the middle turbinate is still
visible; segment 3, `upper meatus': reaching from the upper border of segment
2 to a line through the top of the roof of the nasal cavity.
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Statistical methods
For statistical analyses, SPSS® for WindowsTM was used (Statistical Package for the Social Sciences, Version 10.0, SPSS Inc. Chicago, IL). Normal distribution of the data was checked with the Kolmogorov—Smirnov test. According to the exploratory character of the study, the relation between olfactory function and volumetric measures of the nasal cavity was evaluated using correlational analyses (Pearson). The alpha-level was set at 0.05.
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Results |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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Descriptive statistics of the acquired parameters are presented in Tables 1 and 2.
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Subjects' self-assessment of olfaction, as well as of bilateral nasal airflow, was relatively high (olfaction, mean 69.2%; right nasal airflow, mean 61.9%; left nasal airflow 62.2%), as would have been expected since inclusion criteria were normosmia and no nasal or sinus disease. These findings were confirmed by anterior rhinomanometry, which revealed inspiratory airflow at 150 Pa of 270.8 cm3/s in the right nasal cavity and 265.9 cm3/s in the left nasal cavity, respectively. Olfactory function was above or within normal limits, resulting in a mean of odor identification of 12.9, threshold right 9.9, threshold left 8.8, discrimination right 12.2, discrimination 11.5 (see Table 1). The slightly better scores for the right nostril throughout all tests may underlie a dominance of the right hemisphere of the brain and the successive olfactory bulb.
Values of the descriptive statistics of segmental nasal volumes are depicted in Table 2. Volumes of the right nasal segments are slightly larger than those of the left, which might contribute to the better performance of the right nostril in olfactometry. Largest volumes were found in the lower meatus, decreasing gradually to the superior meatus.
Correlational analyses were performed separately for structural and functional measures of the left and the right part of the nose with the exception of odor identification scores, which had been obtained bilaterally.
The results of the correlational analysis are depicted in Table 3. For the right part of the nose only, significant correlations were found between PEA odor thresholds and areas B1 (anterior nose, inferior meatus; r = 0.31, P < 0.027), and B3 (anterior nose, upper meatus; r = 0.38, P < 0.012), respectively (Figure 3). No significant correlations were found between nasal volumetrics in the left part of the nose and measures of odor discrimination, respectively.
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Odor identification scores (Figure 4) exhibited a correlation to the left (r = 0.39, P = 0.012) and the right (r = 0.38, P = 0.02) area C3, which indicates an area in the posterior portion of the nose in the upper meatus. However, when outliers were removed the correlations were no longer significant.
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Discussion |
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TopAbstractIntroductionMaterials and methodsResultsDiscussionReferences |
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To our knowledge, this is the first study that identified nasal volumes of significance for olfactory function (assessed by PEA odor detection thresholds, odor discrimination and odor identification) in healthy subjects using correlations between functional analyses and MRI-based volumetric measures. Results of this exploratory study indicated that PEA odor threshold, but not odor discrimination or odor identification ability, is correlated with certain volumes in the anterior portion of the nasal cavity.
The correlations of the right PEA threshold with area B3 is consistent with
the significance of inflammatory processes for olfactory function. Considering
(i) that area B3 encompass a large portion of the olfactory epithelium
(von Brunn 1892;
Leopold et al., 2000)
and (ii) that the average volume of area B3 is only 198 mm3, it is
easily conceivable that minute changes of mucosal thickness (e.g. mucosal
edema by vasodilatation or inflammation) may lead to drastic changes in
olfactory abilities. In terms of the therapy of olfactory dysfunction due to
inflammation with self-administered nasal sprays, it also becomes clear that
only small, if not negligible, amounts of corticosteroids reach the assumed
site of action. In fact, it has been shown repeatedly that only small
quantities of nasally applied sprays reach the area above the middle turbinate
(Hardy et al., 1985;
Newman et al., 1987;
McGarry and Swan, 1992). While
this can be improved by the administration of sprays in `head-down forward'
position (Mott and Leopold,
1991), systemic steroids are usually more effective than locally
administered steroids (Mott and Leopold,
1991; Ikeda et al.,
1995).
The correlation of PEA thresholds with area B1 (anterior nose, inferior
meatus) indicated that this olfactory function might be modified by the volume
of the anterior part of the nasal cavity. Specifically, the present data
suggest that odor thresholds are affected by inter-individual differences in
volumes of the inferior meatus remote from the olfactory cleft. From a
clinical point of view this finding is extremely interesting. It helps to
explain results from previous studies showing that postoperative olfactory
function (Ophir et al.,
1986; Damm et al.,
2002) is changed by surgery which alters spaces in the inferior
meatus (e.g. septoplasty, partial inferior resection of turbinates). However,
this interaction should be evaluated by a new experiment using the methods
presented here for anatomical measurements and odor threshold and
identification to evaluate the intra-individual changes before and after nasal
surgery.
Correlations were not found for odor discrimination or odor identification,
both of which are suprathreshold tests of olfactory function. Importantly, the
presently obtained tests of olfactory function (PEA threshold, odor
discrimination and odor identification) have a similar test—retest
reliability (Hummel et al.,
1997). One possible explanation for this discrepancy may be that
nasal airflow has a weaker impact on `higher' olfactory functions such as odor
discrimination (Zatorre and Jones-Gotman,
1991; Hummel et al.,
1998a). Functions like odor discrimination appear to involve
cognitive factors to a greater degree than odor thresholds. In turn, odor
thresholds appear to be more closely related to peripheral olfactory input
(Jones-Gotman and Zatorre,
1988; Hornung et al.,
1998) [but see also (Doty
et al., 1994)]. Thus, other than odor thresholds, odor
discrimination and odor identification seem to be less directly dependent on
the physical conditions that accompany odorous stimulations. This may partly
depend on cognitive processes involved in the discrimination or identification
of odors.
How do the present results in healthy volunteers compare to previous work
in subjects with olfactory disorders? While only looking at areas above the
middle turbinate, Leopold (Leopold,
1988) identified three regions to be most important for
non-lateralized measurements of olfactory function, namely (i) `the space
anterior to, and no more than 5 mm below, the cribriform plate' (region 1,
Figure 5b); (ii) `the space
between 10 and 15 mm below the cribriform plate' (region 8,
Figure 5b); and (iii) `the
space posterior to and between 10 and 15 mm below the cribriform plate'
(region 9, Figure 5b). The
first of the three regions exhibits considerable overlap with area B3
identified in the present study to be of importance to PEA thresholds (see
Figure
5a,b).
It is important to note, though, that the volume of Leopold's region 1
correlated negatively with the OCM. The second area identified by Leopold was
a volume which would have accounted in the present investigation for a portion
of segment C2, and the third region for a portion of segment D2, respectively.
Hornung and Leopold (Hornung and Leopold,
1999) evaluated CT scans of 19 subjects presenting with olfactory
dysfunction, largely confirming the results of the previous study by Leopold
(Leopold, 1988). In addition
to previous work, Hornung and Leopold reported numerous and complex
interactions between different volumes of the nasal cavity, indicating that
`the relationship between olfactory ability and nasal structure is complex and
that changing a structure in one part of the nose far removed from the
olfactory area can have dramatic effects on olfactory ability'.
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Thus, previous and present studies indicate that the volume in the upper
meatus is a major determinant of olfactory function, both in subjects with
sino-nasal disease (SND) and healthy volunteers. However, Leopold's region 1
(Leopold, 1988) may reach
special significance in SND subjects. In addition, in line with findings of
Hornung and Leopold (Hornung and Leopold,
1999), the present study identified an area in the anterior nose
(B1, the lower meatus) as a determinant of olfactory function. The lower
meatus has also been shown to be involved in respiratory hyposmia
(Bonfils et al.,
1999).
Although the results of previous work and the present data exhibit numerous
similarities and support each other in many ways, it should be noted that the
decongestant oxymetazoline was used in the present study to minimize potential
effects of, for example, the nasal cycle
(Kayser, 1895;
Hasegawa and Kern, 1977).
While there is evidence that oxymetazoline has little effect on olfactory
function (Hummel et al.,
1998b) [compare (Temmel et
al., 1999)], it may be that oxymetazoline may have a
differential influence on the volumes of the 22 defined areas in the nasal
cavity, also depending on their functional state
(Williams and Eccles, 1992).
Thus, while it appeared necessary to reduce possible effects of mucosal
congestion, it must be kept in mind that this manipulation certainly had a
strong effect on the correlations obtained. In other words, the described
significance might change in relation to the use of oxymetazoline.
Although not focused on in the present investigation, it was interesting to
note that there was no significant correlation between rhinomanometric
measures and intranasal volumes. While the reasons for this finding are
unclear, it may be that the rhinomanometric measures would correlate to the
diameter of the smallest area of the nasal cavity
(Adema and Motserrat, 1982),
which was not obtained in this investigation.
It is difficult how to explain the different outcomes for the right and
left nostrils. One possible explanation might be hemispheric dominancy in
relation to olfactory function (Zatorre
and Jones-Gotman, 1990;
Zatorre et al., 1992;
Hummel et al., 1995;
Doty et al., 1997). In
terms of laterality, the present results partly contradict the findings of
Hong et al. (Hong et
al., 1998), who found correlations only between left-sided
anatomic structures and both right and left sense of smell. Their study,
however, did not actually measure olfactory ability, but the patients
estimated their sense of smell as excellent, diminished or absent, and two
otolaryngologists and three neuroradiologists assessed radiological findings.
This might explain different results in the qualitatively measured study to
the present quantitatively evaluated study. In this context, it may be
interesting to note that the right nasal cavity was found to be wider than the
left nasal cavity [factor side: F(1,47) = 6.0, P = 0.018].
This difference may have had a major effect on the statistical significance of
the shown results. It may also partly explain the differences between the
findings of Hong et al. and this paper.
Taken together, it appears as if nasal volumes of significance to olfactory function are similar in subjects with olfactory dysfunction and healthy volunteers. Intranasal volumes below the cribriform plate and in the anterior, lower meatus appear to be especially important to the sense of smell. Future studies will specifically investigate these correlations.
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Acknowledgments |
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This study was supported by the Deutsche Forschungsgemeinschaft (DFG) under the auspices of the Collaborative Research Center SFB 419 at the University of Cologne.
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Accepted September 2, 2002
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