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Volume 12 No. 05
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Accepted Papers





Scientific Investigations

Lowest Oxyhemoglobin Saturation May Be an Independent Factor Influencing Auditory Function in Severe Obstructive Sleep Apnea

Young Joon Seo, MD, PhD1,*; Sang Yoo Park, MD, PhD1,*; Hyo Jin Chung, MD2; Chang-Hoon Kim, MD, PhD2,3; Jeung-Gweon Lee, MD, PhD2; Sung Huhn Kim, MD, PhD2; Hyung-Ju Cho, MD, PhD2,3
1Department of Otorhinolaryngology, Yonsei University Wonju College of Medicine, Seoul, South Korea; 2Department of Otolaryngology, Yonsei University College of Medicine Seoul, South Korea; 3The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, South Korea; *co-first authors

ABSTRACT

Study Objectives:

The aims of this study were to determine if a correlation exists between the level of hypoxia induced by severe obstructive sleep apnea syndrome (OSAS) and the level of auditory dysfunction when verifying such a relationship using polysomnography (PSG).

Methods:

A retrospective review of 41 patients with severe OSAS was performed. Independent risk factors for hearing impairment included parameters of PSG, which were analyzed in two hearing groups at a level ≥ 40 decibels (dB).

Results:

Oxyhemoglobin saturation, especially the lowest oxyhemoglobin saturation level, showed lower thresholds in the hearing impairment group than in the control group (p = 0.039 at NREM stage; p = 0.029 at REM stage; p = 0.001 at total sleep stage). After adjusting for other risk factors, the sole variable that remained significant was lowest oxyhemoglobin saturation (total; p = 0.046). In the correlation analysis, a decreasing lowest oxyhemoglobin saturation (from all subjects, n = 41) correlated with a greater mean hearing threshold (R2 = 0.297; p < 0.001).

Conclusion:

Our results indicated that lowest oxyhemoglobin saturation in PSG is the only variable correlated with the hearing threshold. This finding could be predictive of possible hearing alternation in patients with severe OSAS.

Commentary:

A commentary on this article appears in this issue on page 641.

Citation:

Seo YJ, Park SY, Chung HJ, Kim CH, Lee JG, Kim SH, Cho HJ. Lowest oxyhemoglobin saturation may be an independent factor influencing auditory function in severe obstructive sleep apnea. J Clin Sleep Med 2016;12(5):653–658.


INTRODUCTION

Obstructive sleep apnea syndrome (OSAS) is a common breathing disorder that occurs during sleep. It is characterized by episodic upper airway obstruction that interferes with normal respiratory gas exchange.1 OSAS causes hypoxia, a condition that has a comorbid relationship with cardiovascular and neurological system diseases.24 Chronic periodic hypoxia associated with OSAS can provoke oxidative stress and impaired vascular endothelial function, and it may also harm the vasa nervorum.5 The condition of chronic intermittent hypoxemia as seen in OSAS patients also potentially results in irreversible peripheral neuropathy.6

As the structures of the inner ear and the auditory nerve are highly dependent on a healthy oxygen supply, OSAS may interfere with the processes that generate and transmit nerve impulses within the auditory system.7 Research suggests that severe OSAS could represent a risk of dysfunction across the auditory pathway, particularly due to the resulting hypoxia.8 However, no correlation has been demonstrated between blood oxygen index (oxyhemoglobin saturation) and auditory dysfunction. The aim of this investigation was to verify our hypothesis that a correlation exists between the level of hypoxia induced by severe OSAS and the level of auditory dysfunction using polysomnography (PSG).

BRIEF SUMMARY

Current Knowledge/Study Rationale: To verify our hypothesis that a correlation exists between the level of hypoxia induced by severe OSAS and the level of auditory dysfunction using polysomnography (PSG), We found that the sole variable that remained significant in parameters of PSG was lowest oxyhemoglobin saturation (total; p = 0.046). Oxyhemoglobin saturation, especially the lowest oxyhemoglobin saturation level, showed lower thresholds in the hearing impairment group than in the control group (p = 0.039 at NREM stage; p = 0.029 at REM stage; p = 0.001 at total sleep stage).

Study Impact: With this study, we recommend that lowest oxyhemoglobin saturation in PSG is the only variable correlated with the hearing threshold could be predictive of possible hearing alternation in patients with severe OSAS. Considering that severe OSAS might be a trigger for hearing loss, attention should be given to hearing evaluations in high-risk patients (e.g., obese middle-aged or elderly male) with OSAS screening.

METHODS

Subjects

This retrospective study was performed on patients diagnosed with severe OSAS, as determined by overnight polysomnography (PSG) during the period from 2009 to 2013. The patients underwent an auditory test using pure tone audiometry (PTA) at our department of otorhinolaryngology within 3 months of PSG as part of a regular health check-up (n = 10), based on a doctor's recommendation (n = 11), or due to hearing disturbance (n = 20). Patients with a history that included effective drug treatments that were able to influence vascular reactivity and lung functions, hearing loss, or any middle-or inner-ear pathology were excluded. Patients with mild or moderate OSAS were also excluded, as several reports had already demonstrated a relation between hearing and severe OSAS. As determined by our criteria, 41 patients were included in the experiment. They were subsequently divided into two groups according to their hearing impairment: a “Control” group with no hearing impairment and an “HI” group with hearing impairment. For this experiment, hearing impairment was defined as a level ≥ 40 decibels (dB), measured through pure tone audiometry (PTA) and calculated using the following formula: (5,000 Hz + 2 × 1,000 Hz + 2,000 Hz) / 4.

Sleep Studies

All patients underwent overnight PSG performed by study-certified technicians using a standardized protocol and following the guidelines of the American Academy of Sleep Medicine (AASM). According to these guidelines, as well as the apnea-hypopnea index (AHI), (apnea + hypopnea per hour of sleep) > 30 suggests severe OSAS. We considered the parameters of PSG through a variety of indices and measurements: sleep time (total, stage N1, stage N2, stage N3, and stage R minutes); apnea-hypopnea index (AHI); respiratory disturbance index (RDI), defined as ([respiratory effort-related arousals] + hypopnea + apnea) × 60 / total sleep time (in minutes); snoring index; number of respiration events (index) including numbers of apnea or hypopnea events; average heart rate (pulses/ min); duration below 90% oxyhemoglobin saturation (in min); lowest oxygen desaturation index; average oxyhemoglobin saturation (%); and lowest oxyhemoglobin saturation (%). We evaluated the possible correlations of these parameters with hearing level.

Auditory Evaluation

Pure-tone thresholds were obtained for air conduction at 250 Hz, 500 Hz, 1,000 Hz, 2,000 Hz, 4,000 Hz, and 8,000 Hz. Audiologic data were reported in accordance with the methods recommended by the Hearing Committee of the American Academy of Otolaryngology Head and Neck Surgery.

Statistical Analysis

Statistical analysis was performed using the Statistical Package for Social Sciences Software (SPSS 18.0 for Windows, SPSS Inc., Chicago, IL, USA). Data are presented as mean and standard error of mean (SEM). The comparison of each variable between groups was performed using the Mann-Whitney U Test or the modified Rao-Scott χ2 test. To analyze the strength of the relationship between hearing levels and lowest oxyhemoglobin saturation, we conducted Pearson correlation analysis to determine linear associations between variables. Multivariable linear regression was used to assess associations between mean hearing thresholds and lowest oxyhemoglobin saturation (total), and the results were fitted with increasing degrees of adjustment. We adjusted for age (continuous), BMI (continuous), and sex (men or women). Models were further adjusted for the presence of hypertension (yes or no), diabetes (yes or no), dyslipidemia (yes or no), CKD (yes or no), smoking exposure (never or current), and alcohol intake (never or current). Multicollinearity was considered for predictor variables in the multiple linear model. Any characteristic that was significant at α < 0.20 in the univariate analysis with necessary related factors was entered into the multiple linear model. The final multivariable models for hearing and lowest oxyhemoglobin saturation included all variables identified by the selection procedures (backward, stepwise) that remained simultaneously significant at p < 0.05.

RESULTS

The HI group included 14 males and 5 females (Table 1). The mean age of the patients was 61.5 ± 3.3 years. The mean age of the Control group was 57.3 ± 1.6 years, and the ratio of males to females was about 3:1. No differences in body mass index (BMI), hypertension, cardiovascular disease, diabetes, or renal function were observed between the two groups. On analyzing the audiometry, the hearing impairment group showed higher thresholds than the Control group, statistically significant at every frequency on both ears (p < 0.05), as indicated in Figure 1.

Baseline characteristics of the study and control groups.

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Table 1

Baseline characteristics of the study and control groups.

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Mean hearing thresholds in pure tone audiometry between study groups.

On analyzing the audiometry, the hearing impairment group showed higher thresholds than the Control group, statistically significant at every frequency on both ears (p < 0.05).

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Figure 1

Mean hearing thresholds in pure tone audiometry between study groups.

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All OSAS patients had severe OSAS characterized by an AHI range > 30 (Control: 39.9 ± 4.9; HI: 39.6 ± 6.3; p = 0.491; Table 2). The sleep time at each stage was not significantly different across groups. Statistical analysis showed no significant differences in the most important factors of the polysomnography, including RDI, snoring index, duration of < 90% oxyhemoglobin saturation, number of respiration events during each sleep stage, and heart rate between the groups. However, oxyhemoglobin saturation, especially the lowest oxyhemoglobin saturation level, showed lower thresholds in the HI group than in the control group (p = 0.039 at NREM stage; p = 0.029 at REM stage; p = 0.001 at total sleep stage).

Polysomnography data of the study and control groups.

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Table 2

Polysomnography data of the study and control groups.

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In the multivariate analysis modeling of hearing and lowest oxyhemoglobin saturation (Table 3), the sole variable that remained significant in parameters of PSG was lowest oxyhemoglobin saturation (total; p = 0.046). The R-squared output of this model, which measured the proportion of the variance of hearing by variables, was 0.892. The β coefficient between the hearing and lowest oxyhemoglobin saturation (total) was –0.361, a negative correlation. There were fewer than 4 variance inflation factors for all variables in the model. In the correlation analysis, Figure 2 shows decreasing lowest oxyhemoglobin saturation (for all subjects, n = 41) correlated with a greater mean hearing threshold (R2 = 0.297; p < 0.001; both ears).

Effects of lowest oxyhemoglobin saturation on auditory function, after adjusting for age, sex, BMI, and other risk factors.

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Table 3

Effects of lowest oxyhemoglobin saturation on auditory function, after adjusting for age, sex, BMI, and other risk factors.

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Graphs of correlation analyses for lowest oxyhemoglobin saturation and mean hearing threshold on both ears.

A decreasing lowest oxyhemoglobin saturation (from all subjects, n = 41) correlated with a greater mean hearing threshold (R2 = 0.297; p < 0.001; both ears).

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Figure 2

Graphs of correlation analyses for lowest oxyhemoglobin saturation and mean hearing threshold on both ears.

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DISCUSSION

Several studies have revealed auditory dysfunction in patients affected by severe OSAS in the absence of other auditory risk factors. This suggests that hypoxia brought on by OSAS could represent a risk to the auditory pathway.810 A study by Fischer et al.11 suggested that sudden deafness may also be an indicator of damage secondary to such risk factors as hypertension, diabetes, and hyperlipidemia, which were highly significant for OSAS patients. Although the effects of chronic intermittent hypoxia during sleep result in alterations to the normal physiology of several organ systems in the body,24 only a small amount of research has been performed to explore the effect of OSAS and its resulting hypoxia on the fragile auditory system.

Therefore, we attempted to study the consequence of OSAS on the hearing of severe OSAS patients, excluding those already known to have hearing loss and non-OSAS subjects without hearing loss. However, it is also important to further evaluate various factors potentially related to preserved or worsened hearing in severe OSAS. Such results could be predictive of possible hearing alternation in patients with severe OSAS.

After adjustment for risk factors such as sex, age, BMI, HTN, DM, dyslipidemia, and CKD using the multiple linear regression model, we found that lowest oxyhemoglobin saturation was the only variable to affect the hearing threshold (p = 0.046 during total sleep stage). Furthermore, there was a negative linear correlation between the mean hearing threshold (p < 0.001) and lowest oxyhemoglobin saturation (total). Chronic intermittent hypoxemia is one of the major symptoms of OSAS, and the level of lowest oxyhemoglobin saturation correlates with OSAS severity.12,13 A recent, large, cross-sectional study of healthy, middle-aged and older adults found a direct, dose-dependent correlation between sleep time below 90% oxyhemoglobin saturation and the odds of systemic disease.14 Dziewas et al. showed that recurrent intermittent hypoxemia may be considered a risk factor for peripheral sensory nerve dysfunction and suggested that treatment for OSAS might result in improved function of these nerves.15 A low level of oxygen perfusion may act alone or in concert with other ailments to negatively influence the neuronal or vascular function of the auditory pathway.

In Figure 2, decreasing lowest oxyhemoglobin saturation corresponds with a higher hearing threshold. Hearing at higher frequencies has larger gaps between the two groups. This finding is consistent with the theory that a higher susceptibility of hair cells in the basal turn to the damage caused by free radicals.1619 We were unable to analyze the exact relation to hearing according to graded groups of lowest oxyhemoglobin saturation (below 90%, 85%, or 75%), as the groups contained too few patients. However, our results demonstrated a relation between hearing and lowest oxyhemoglobin saturation in the correlation graphs. A decreasing lowest oxyhemoglobin saturation (from all subjects, n = 41) correlated with a greater mean hearing threshold (R2 = 0.297; p < 0.001; both ears).

Our study was limited due to the small sample size. As such, it was difficult to rule out the effects of the multiple variables, even with a multiple linear regression test. However, the sample groups did exhibit similarities in this set of variables, and no correlation was found to hearing loss within the set. We were unable to consider the risk factors for snoring noise level and their effects on decreased hearing, as we did not check for noise in this retrospective study. We intend to proceed with a randomized case-controlled study that tests the hearing of patients who are diagnosed for OSAS and have PSG test results, which may clarify whether the auditory system can be altered by OSAS. This further research may ultimately suggest that effective treatment of OSAS may also improve auditory function.

In conclusion, this result that lowest oxyhemoglobin saturation in PSG is the only variable correlated with the hearing threshold could be predictive of possible hearing alternation in patients with severe OSAS. Considering that severe OSAS might be a trigger for hearing loss, attention should be given to hearing evaluations in high-risk patients (e.g., obese middle-aged or elderly male) with OSAS screening.

DISCLOSURE STATEMENT

This was not an industry supported study. This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF), funded by the Ministry of Science, ICT & Future Planning (2013M3A9D5072551) to C.H. Kim. This research was supported (in part) by the Yonsei University Future-leading Research Initiative of 2014 (2014-22-0131) to C.H. Kim. This research was supported (in part) by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (NRF-2013R1A1A1010151) to H. J. Cho. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have indicated no financial conflicts of interest.

ABBREVIATIONS

AASM

American Academy of Sleep Medicine

AHI

apnea-hypopnea index

BMI

body mass index

CKD

chronic kidney diseas

dB

decibel

ESS

Epworth sleepiness scale

HI group

hearing impairment group

MSQ

mini sleep questionnaire items

OSAS

obstructive sleep apnea syndrome

PTA

pure tone audiometry

PSG

polysomnography

RDI

respiratory disturbance index

REM

rapid eye movement

SEM

standard error of mean

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