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Clinical and Experimental Otorhinolaryngology > Volume 10(1); 2017 > Article
Shin, Ahn, Yang, Choi, Cho, Hong, and Kim: The Effect of Sleep Disordered Breathing on Olfactory Functions: Analysis by Apnea-Hypopnea Index

Abstract

Objectives

One hypothesis of obstructive sleep apnea syndrome (OSAS) is that long-standing snoring vibrations and hypoxia of the nerves cause a local neuropathy in the upper airway during sleep. The aim of this study was to investigate olfactory function in subjects comprising snorers and untreated subjects with OSAS, and to correlate data with polysomnographic parameters.

Methods

Sixty-nine patients were evaluated for snoring from January 2010 to December 2013. The mild group (apneahypopnea index [AHI]<15) consisted of 19 subjects, and the moderate-severe group (AHI≥15) consisted of 50 subjects. Exclusion criteria were conductive olfactory dysfunction, previous tonsil or soft palatal surgery, central sleep apnea, and medications that are known to affect peripheral nerves. Nocturnal polysomnography and olfactory function test such as Korean version of Sniffin’s stick test I, II (KVSS I, II) were performed.

Results

There was a significant difference in body mass index, average oxygen saturation (SaO2), lowest SaO2, average snoring duration, and KVSS I, II between the two groups. AHI was related to odor threshold score, and average SaO2 was related to odor discrimination score. But, odor identification score showed no relation with AHI and average SaO2 except for age. Average SaO2 and AHI were closely related to the function of smell.

Conclusion

Hypoxia and low nasal airflow caused by OSAS may have an effect on the olfactory function. On comparison between the two groups, patients with a high AHI, especially those with OSAS, had an olfactory dysfunction. Also, low average oxygen is the main risk factor in determining the olfactory function. In people with OSAS, the possibility of olfactory dysfunction should be considered and an olfactory function test should be performed.

INTRODUCTION

Obstructive sleep apnea syndrome (OSAS) causes excessive daytime sleepiness, mood problems, poor neurocognitive performance, erectile dysfunction, and cardiovascular disorders [1-3].
In general, OSAS seems to be a progressive disorder whose pathogenesis is not fully understood. One hypothesis is that long-standing snoring vibrations and hypoxia of the nerves cause a local neuropathy in the upper airway [4-7], which predisposes to obstructive events during sleep. Poor neurocognitive performance due to OSAS affects well known memory [8], new learning, attention, executive function, and cognitive function [1]. OSA is a risk factor for developing mild cognitive impairment [9] and the adult with severe OSA was more likely present cognitive deficits than those with mild or moderate OSA [10].
Olfaction is one of the special senses, and it plays a critical role in human life [11]. Olfactory function is reportedly influenced by cognitive impairment, as well as other main factors affecting head trauma, post-upper respiratory tract infection and sinonasal disease [11,12]. Olfaction scores were lower in pa-tients with mild cognitive impairment than in healthy comparison subjects [13]. And the other studies also found that olfactory impairment was associated mild cognitive impairment [14,15]. However, few studies had been reported on the relationship between the effect of olfactory function and degree of OSA.
The aim of this study was to determine among the subjects comprising snorers and untreated subjects with OSAS, classified by polysomnographic parameters such as apnea-hypopnea index (AHI), whether the moderate-severe group that has a high AHI (≥15/hr) will have more severe olfactory dysfunction as compared to the mild group that have a low AHI (<15/hr) and to investigate the correlation between the influence of OSA and parameters of olfactory function.

MATERIALS AND METHODS

Subjects

Sixty-nine patients, who underwent a full-night respiratory recording in a sleep research laboratory because of snoring during sleep, were evaluated by an olfactory function test from January 2010 to December 2013. The inclusion criteria were as follows: age above 20 years; absence of neurologic, cardiovascular, pulmonary, or other chronic illness; no history of prior surgery on the nose and palate; no current history of drug intake; and no prior history of treatment of sleep-disordered breathing. Exclusion criteria were as follows: any previous history of treatment for snoring or OSAS, conductive olfactory dysfunction identified by computed tomography and endoscopic findings, sinonasal disease, central sleep apnea, previous history of oropharyngeal surgery excluding remote tonsillectomy, previous history of cerebrovascular accident, diabetes, any neuropathy or active neurologic disease, and a recent history of upper respiratory tract infection at the time of proposed investigation. The moderate-severe group included patients with AHI≥15/hr and the mild group included patients with habitual snoring verified by partners and AHI<15/hr [16].
This study was approved by the Ethics Committee of Konkuk University Hospital (KUH1110018).

Polysomnography

All of the subjects with an initial evaluation who met the inclusion criteria underwent nocturnal polysomnography (PSG). PSG study was performed using an Embla N7000 (Embla, Reykjavik, Iceland). The following variables were monitored: electroencephalogram, electrooculogram, chin electromyogram, leg electromyogram, heart rate (modified V2 lead), and body position. Respiration was evaluated with a nasal cannula/pressure transducer system, polygraphic recording with measurement of esophageal pressure (PES), thoracic bands, abdominal bands, pulse oximetry, and neck microphone. Apnea was defined as the complete cessation of airflow for at least 10 seconds, whereas hypopnea was defined as a substantial reduction in airflow (50%) for at least 10 seconds or a moderate reduction in airflow (30%) for at least 10 seconds associated with electroencephalographic arousal or oxygen desaturation (>4%). The AHI was defined as the total number of apneas and hypopneas per hour of sleep [16]. Snoring components included relative snoring time (%), average snoring episode duration (minutes), longest snoring episode duration (minutes), total snoring time (minutes), and number of snoring episodes. These components were automatically calculated during PSG.

Olfactory function test

Olfactory function test included Korean version of Sniffin’s stick test I, II (KVSS I, II), which was performed by the same examiner. KVSS I test is an identification test which is performed with 8 different odorant pens. There are tampons with an odorant substance in each pen so that when the examiner opens the lid and shakes it horizontally, it is set up to make the odor with equal concentration. The KVSS II offers an extensive test of olfactory deficits. It consists of three different sets, namely KVSS II threshold, discrimination, and identification tests. In brief, threshold is defined as the concentration at which n-butanol (highest concentration 4%, 1:2 serial dilutions to 16 steps) is correctly identified four times in a row from two blanks. For discrimination testing, triplets of odorants (two of them are identical, one is different) are presented and subjects have to choose the odd odorant. KVSS II identification test is a 16-item odor identification test [17,18]. All of the odors used in the test are familiar to Koreans. Subjects are supposed to choose one out of the four odors even though they do not know the correct one, and the number of correct answers is recorded. The result of each test is recorded as a score, ranging from 0 to 16, and the sum of the three tests is presented as a composite KVSS II score. Total scores of 0–20 are defined as anosmia, 21–27 as hyposmia, and 28–48 as normosmia [19]. Patients with a KVSS II score <28 were diagnosed as having olfactory dysfunction in this study. PSG and olfactory function test were performed on the same day.

Statistical analysis

Analysis were performed using IBM SPSS ver. 20.0 (IBM Co., Armonk, NY, USA). The Wilcoxon signed rank test and Fisher exact test were used to evaluate the differences between the moderate-severe group and the mild group. Univariate analyses were performed using logistic regression to identify risk factors for olfactory dysfunction. A value of P<0.05 was considered to indicate a statistically significant result.

RESULTS

Demographics

Sixty-nine patients were recruited for this study (56 men, 13 women; mean age, 43.86±14.16 years). The number of patients in the mild group was 19 (28%), and the number of patients in the moderate-severe group was 50 (73%). The variables such as demographic distribution, body mass index (BMI), basic PSG parameters, and olfactory function test are summarized in Table 1. BMI, sex, average oxygen saturation (SaO2), lowest SaO2, average snoring episode duration, and KVSS II score were significantly different between the two groups. Otherwise, no statistically significant difference was observed in age, snoring time, longest snoring duration, and KVSS I. Regarding olfaction, 88% of patients (61/69) demonstrated olfactory dysfunction on testing. Among all patients, 68% of patients in the mild group (13/19) and 96% of patients in the moderate-severe group (48/50) demonstrated olfactory dysfunction on testing.
In KVSS II, odor threshold test and discrimination test scores were significantly worse in moderate-severe group. Otherwise, odor identification score showed no difference between the two groups.

Correlation of olfactory function and OSAS

KVSS I test score was significantly correlated with age (P<0.001). Also, KVSS II test score (threshold, discrimination, identification [TDI]) was significantly associated with AHI (P=0.022) and average SaO2 (P=0.024). We found that AHI and average SaO2 were more closely related to the olfactory function test scores than snoring time and longest snoring episode (Table 2, Fig. 1). Snoring time and longest snoring episode showed no significant association with olfactory function test scores. In KVSS II test, threshold (T) test score was significantly correlated with AHI (P=0.005). Therefore, AHI was more strongly associated with odor threshold score than average SaO2. Discrimination (D) test score was significantly correlated with average SaO2 (P=0.042). Average SaO2 was related to odor discrimination score than AHI. Identification (I) test score was significantly associated with age (P<0.001). Odor identification score showed no significant relation with AHI and average SaO2 (Table 3, Fig. 2).

DISCUSSION

In this study, we found that olfactory dysfunction was much more frequent in the moderate-severe group than in the mild group and the AHI had a significant negative correlation with odor threshold and TDI scores; otherwise, average SaO2 had a significant positive correlation with odor discrimination and TDI scores.
The comparison of baseline variables showed that the parameters of PSG, BMI, SaO2 level (average and lowest), and snoring duration showed a significant difference between the moderate-severe group and mild group. The figures obtained from this study correspond with those from other recent reports [20].
This study showed the negative effect of OSA on olfactory testing. We assessed olfactory function by the KVSS-I and KVSS-II. KVSS II score (TDI score), and not KVSS I score, showed a significant difference between the two groups. Results of the present study confirm the findings of earlier studies, which reported that TDI scores were significantly decreased with increasing severity of OSA [20]. On comparison between the parameters of PSG and olfactory function test, AHI showed a negative correlation with KVSS II score (TDI score). Average SaO2 level had a significant positive correlation with KVSS II score (TDI scores). Snoring time and longest snoring episode had no significant effects on olfactory function in OSA patients. Our findings imply that olfactory dysfunction in OSAS patients is influenced by apnea-hypopnea and blood oxygen level than long-standing vibration.
Among the TDI scores, odor threshold score had a significant negative correlation with AHI. Otherwise, odor discrimination score had a significant positive correlation with average SaO2. Odor identification score had no effects on the parameters of PSG in OSA patients. Previous reports showed a negative correlation between AHI and TDI scores and a positive correlation between mean SaO2 and odor threshold and discrimination scores. In contrast to a previous study, we found that AHI had a negative correlation with odor threshold score and average SaO2 had a positive correlation with odor discrimination score [20].
Although the mechanism underlying the correlation between OSAS and olfactory function is unclear, the previous study had proposed that intermittent hypoxia and sleep fragmentation can lead to neuronal loss in the hippocampus and prefrontal cortex, areas that are closely associated with memory function and executive function [20,21]. The effect of impairment of cognitive function on olfaction may produce a decrease in discrimination and identification function [22]. But, we found that AHI had no effect on the discrimination and identification tests. These results suggest that these tests used suprathreshold concentration of odorants [23].
It is well known that OSA is characterized by breathing cessation (apnea) or reduction of airflow (hypopnea) during sleep. The increase in AHI was related to the decrease in nasal airflow. Recently, Fu et al. [24] reported that alteration of nasal airflow affected the olfactory function, especially odor threshold. Therefore, negative correlations between AHI and odor threshold seem to indicate the alteration of nasal airflow in OSA patients.
This study has several limitations; first, the sample size was limited (e.g., few female patients) and analyses were done without a healthy control group. Second, this study was a retrospective study on hospital based-subjects and not the general population. Hence, future studies are needed to assess the effect of OSA treatment on olfactory function. Indeed, OSA is associated with olfactory functions. Olfactory dysfunctions were associated with intermittent hypoxia and alteration of airflow.
In conclusion, the current study demonstrated that low nasal airflow and hypoxia caused by OSAS may have an effect on the olfactory function. On comparing between the moderate-severe group and mild group, patients with a high AHI, especially those with OSAS, had negative effects on olfactory dysfunction, especially on threshold, and patients with a high SaO2 had positive effects on olfactory discrimination function.

HIGHLIGHTS

▪ Objective olfactory function (KVSS II) score was significantly associated with apnea-hypopnea index (AHI) and average SaO2.
▪ Threshold (T) and discrimination (D) test scores were significantly correlated with AHI and average SaO2, respectively.
▪ Decreased olfactory function was more frequently seen in patients with moderate-to severe AHI.

CONFLICT OF INTEREST

No potential conflict of interest relevant to this article was reported.

ACKNOWLEDGMENTS

This research was supported by Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (2013R1A1A2009589).

Fig. 1.
(A) Scatter plot showing a significant negative association of apnea-hypopnea index (AHI) with Korean version of Sniffin’s stick test II (KVSS II) score (Spearman rank correlation, –0.275; P=0.022). Regression line and lines for the 95% confidence interval (CI) are shown. (B) Scatter plot showing a significant positive association of average oxygen saturation with KVSS II score (Spearman rank correlation, 0.271; P=0.024). Regression line and lines for the 95% CI are shown.
ceo-2015-01438f1.tif
Fig. 2.
(A) Scatter plot showing a significant negative association of apnea-hypopnea index (AHI) with threshold test score (Spearman rank correlation, –0.336; P<0.01). Regression line and lines for the 95% confidence interval (CI) are shown. (B) Scatter plot showing a significant positive association of average oxygen saturation with discrimination test score (Spearman rank correlation, 0.246; P=0.042). Regression line and lines for the 95% CI are shown.
ceo-2015-01438f2.tif
Table 1.
Comparison of baseline variables between the moderate-severe group and the mild group
Variable Moderate-severe group (n=50) Mild group (n=19) P-valuea)
Age (yr) 44.6±13.8 41.8±15.4 0.267
Sex (female:male) 6:44 7:12 0.037b,c)
Body mass index (kg/m2) 29.1±5.7 24.6±2.3 <0.001c)
Average oxygen saturation (%) 94.5±2.2 96.6±1.4 <0.001c)
Low oxygen saturation (%) 79.8±7.3 85.3±9.1 <0.001c)
Snoring time (min) 98.1±69.6 68.0±37.1 0.094
Average snoring duration (min) 0.7±0.5 2.6±3.7 0.034c)
Longest snoring duration (min) 10.8±10.3 10.5±8.3 0.773
KVSS I 5.1±1.6 5.5±1.6 0.334
KVSS II 21.4±4.6 25.5±5.8 0.021c)
Threshold 3.6±2.1 5.4±3.2 0.013c)
Discrimination 8.4±3.1 10.4±3.0 0.030c)
Identification 9.5±2.5 10.2±1.8 0.300

KVSS, Korean version of Sniffin's stick test.

a) Wilcoxon rank-sum test.

b) Fisher exact test.

c) Statistically significant.

Table 2.
Correlation between polysomnographic parameters and olfactory function test score
Variable KVSS I
KVSS II
ra) P-valueb) ra) P-valueb)
Age (yr) –0.408 <0.001c) –0.216 0.075
Apnea-hypopnea index (/hr) 0.151 0.214 –0.275 0.022c)
Average oxygen saturation (%) –0.019 0.878 0.271 0.024c)
Snoring time (min) –0.078 0.526 0.078 0.527
Longest snoring episode (min) –0.150 0.216 0.065 0.598

KVSS, Korean version of Sniffin's stick test.

a) Pearson correlation coefficient.

b) Univariate regression test.

c) Statistically significant.

Table 3.
Correlation between polysomnographic parameters and threshold, discrimination, identification test score
Variable Threshold
Discrimination
Identification
ra) P-valueb) ra) P-valueb) ra) P-valueb)
Age (yr) 0.040 0.744 –0.123 0.313 –0.475 <0.001
Apnea-hypopnea index (/hr) –0.336 0.005c) –0.226 0.062 0.009 0.939
Average oxygen saturation (%) 0.218 0.071 0.246 0.042c) 0.106 0.388
Snoring time (min) 0.020 0.872 –0.013 0.918 0.095 0.438
Longest snoring episode (min) 0.003 0.979 0.022 0.859 0.056 0.650

a) Pearson correlation coefficient.

b) Univariate regression test.

c) Statistically significant.

REFERENCES

1. Beebe DW, Gozal D. Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits. J Sleep Res. 2002 Mar;11(1):1–16.
crossref
2. Arruda-Olson AM, Olson LJ, Nehra A, Somers VK. Sleep apnea and cardiovascular disease: implications for understanding erectile dysfunction. Herz. 2003 Jun;28(4):298–303.
crossref pmid
3. Shin HW, Rha YC, Han DH, Chung S, Yoon IY, Rhee CS, et al. Erectile dysfunction and disease-specific quality of life in patients with obstructive sleep apnea. Int J Impot Res. 2008 Nov-Dec;20(6):549–53.
crossref pmid
4. Saboisky JP, Butler JE, Gandevia SC, Eckert DJ. Functional role of neural injury in obstructive sleep apnea. Front Neurol. 2012 Jun;3:95.
crossref pmid pmc
5. Sunnergren O, Brostrom A, Svanborg E. Soft palate sensory neuropathy in the pathogenesis of obstructive sleep apnea. Laryngoscope. 2011 Feb;121(2):451–6.
crossref pmid
6. Dziewas R, Schilling M, Engel P, Boentert M, Hor H, Okegwo A, et al. Treatment for obstructive sleep apnoea: effect on peripheral nerve function. J Neurol Neurosurg Psychiatry. 2007 Mar;78(3):295–7.
crossref pmid pmc
7. Jang HU, Park KS, Cheon SM, Lee HW, Kim SW, Lee SH, et al. Development of the korean version of the sleep apnea quality of life index. Clin Exp Otorhinolaryngol. 2014 Mar;7(1):24–9.
crossref pmid pmc
8. Kang IG, Jung JH, Kim ST. The effect of obstructive sleep apnea on DNA damage and oxidative stress. Clin Exp Otorhinolaryngol. 2013 Jun;6(2):68–72.
crossref pmid pmc
9. Gagnon K, Baril AA, Gagnon JF, Fortin M, Decary A, Lafond C, et al. Cognitive impairment in obstructive sleep apnea. Pathol Biol (Paris). 2014 Oct;62(5):233–40.
crossref pmid
10. Kielb SA, Ancoli-Israel S, Rebok GW, Spira AP. Cognition in obstructive sleep apnea-hypopnea syndrome (OSAS): current clinical knowledge and the impact of treatment. Neuromolecular Med. 2012 Sep;14(3):180–93.
crossref pmid pmc
11. Croy I, Nordin S, Hummel T. Olfactory disorders and quality of life: an updated review. Chem Senses. 2014 Mar;39(3):185–94.
crossref pmid
12. Hedner M, Larsson M, Arnold N, Zucco GM, Hummel T. Cognitive factors in odor detection, odor discrimination, and odor identification tasks. J Clin Exp Neuropsychol. 2010 Dec;32(10):1062–7.
crossref pmid
13. Devanand Dp, Michaels-marston Ks, Liu X, Pelton Gh, Padilla M, Marder K, Et Al. Olfactory Deficits In Patients With Mild Cognitive Impairment Predict Alzheimer’s Disease At Follow-up. Am J Psychiatry. 2000 Sep;157(9):1399–405.
crossref pmid
14. Roberts RO, Christianson TJ, Kremers WK, Mielke MM, Machulda MM, Vassilaki M, et al. Association between olfactory dysfunction and amnestic mild cognitive impairment and alzheimer disease dementia. JAMA Neurol. 2016 Jan;73(1):93–101.
crossref pmid pmc
15. Kirkpatrick MA, Combest W, Newton M, Teske Y, Cavendish J, McGee R, et al. Combining olfaction and cognition measures to screen for mild cognitive impairment. Neuropsychiatr Dis Treat. 2006 Dec;2(4):565–70.
crossref pmid pmc
16. American Academy of Sleep Medicine. The international classification of sleep disorders. 2nd ed. Westchester, IL: American Academy of Sleep Medicine; 2005.

17. Kim JM, Jeong MS, Shin DH, Seol JH, Hong SC, Cho JH, et al. Olfactory identification test using familiar distracters for Koreans. Clin Exp Otorhinolaryngol. 2014 Mar;7(1):19–23.
crossref pmid pmc
18. Hong SM, Park IH, Kim KM, Shin JM, Lee HM. Relationship between the Korean version of the Sniffin’ stick test and the T&T olfactometer in the Korean population. Clin Exp Otorhinolaryngol. 2011 Dec;4(4):184–7.
crossref pmid pmc
19. Cho JH, Jeong YS, Lee YJ, Hong SC, Yoon JH, Kim JK. The Korean version of the Sniffin’ stick (KVSS) test and its validity in comparison with the cross-cultural smell identification test (CC-SIT). Auris Nasus Larynx. 2009 Jun;36(3):280–6.
crossref pmid
20. Salihoglu M, Kendirli MT, Altundag A, Tekeli H, Saglam M, Cayonu M, et al. The effect of obstructive sleep apnea on olfactory functions. Laryngoscope. 2014 Sep;124(9):2190–4.
crossref pmid
21. Daurat A, Foret J, Bret-Dibat JL, Fureix C, Tiberge M. Spatial and temporal memories are affected by sleep fragmentation in obstructive sleep apnea syndrome. J Clin Exp Neuropsychol. 2008 Jan;30(1):91–101.
crossref pmid
22. Dulay Mf, Gesteland Rc, Shear Pk, Ritchey Pn, Frank Ra. Assessment Of The Influence Of Cognition And Cognitive Processing Speed On Three Tests Of Olfaction. J Clin Exp Neuropsychol. 2008 Apr;30(3):327–37.
crossref pmid
23. Eibenstein A, Fioretti AB, Lena C, Rosati N, Amabile G, Fusetti M. Modern psychophysical tests to assess olfactory function. Neurol Sci. 2005 Jul;26(3):147–55.
crossref pmid
24. Fu D, Pinto JM, Wang L, Chen G, Zhan X, Wei Y. The effect of nasal structure on olfactory function in patients with OSA. Eur Arch Otorhinolaryngol. 2015 Feb;272(2):357–62.
crossref pmid
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