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The Evaluaton of Audtory System in Obstructve Sleep Apnea Syndrome
(Osas) Patents

Mahmut Deniz M.D., Zafer C iftci M.D., Tolga Ersozlu M.D., Erdogan
Gultekin M.D., Recep Alp M.D.

PII: S0196-0709(16)00065-X
DOI: doi: 10.1016/j.amjoto.2016.03.004
Reference: YAJOT 1702

To appear in: American Journal of OtolaryngologyHead and Neck Medicine and Surgery

Received date: 10 February 2016

Please cite this article as: Deniz Mahmut, C


iftci Zafer, Ersozl
u Tolga, G
ultekin Erdo
gan,
Alp Recep, The Evaluaton of Audtory System in Obstructve Sleep Apnea Syndrome
(Osas) Patents, American Journal of OtolaryngologyHead and Neck Medicine and Surgery
(2016), doi: 10.1016/j.amjoto.2016.03.004

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THE EVALUATION OF AUDITORY SYSTEM IN OBSTRUCTIVE SLEEP APNEA


SYNDROME (OSAS) PATIENTS

Mahmut Deniz1, Zafer ifti1, Tolga Erszl1, Erdoan Gltekin1, Recep Alp2

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: Namk Kemal University Medical Faculty Otorhinolaryngology Department

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2
: Namk Kemal University Medical Faculty Neurology Department

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Mahmut Deniz, Assist Prof, M.D. (drmahmutdeniz@hotmail.com)

Zafer ifti, Assist Prof, M.D. (zaferciftci@yahoo.com)

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Tolga Erszl, Assist Prof, M.D. (tolga76@hotmail.com)
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Erdoan Gltekin, Associate Prof, M.D. (erdogangultekin@hotmail.com)

Recep Alp, Associate Prof, M.D. (recep.alp@gmail.com)


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Please address all correspondence to: Assist. Prof. Mahmut Deniz, M.D

Namk Kemal University Medical Faculty Tekirda/TURKEY


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E mail: drmahmutdeniz@hotmail.com

Namk Kemal Universitesi Aratrma Hastanesi Kulak Burun Bogaz Klinigi


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Degirmenalt Kampus

59000 Tekirdag

Turkey

Phone: +905325059507

Telephone number: 0090 282 250 51 88


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ABSTRACT

Objective: The authors of the present study aimed to investigate the impact of hypoxemia on

the auditory functions of OSAS patients and discussed their findings under the scope of the

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existing literature.

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Materials and Methods: 160 patients who underwent a polysomnographic analysis for the

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diagnosis of possible sleep disordered breathing between Jan 2015 and December 2015 were

enrolled in this study. Polysomnography tests were conducted at the sleep laboratory of the

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department of neurology at the same institute. Comprehensive otorhinolaryngological

examinations of all participants were conducted by the same senior otorhinolaryngologist.


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Three study groups and a control group were designated in the study. Each study group was
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designated according to the severity of the apnea hypopnea index (AHI) and blood oxygen

saturation values of the participants. All participants underwent pure tone auditometry and
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otoacoustic emission testing (OAE). Statistical data analysis was performed using SPSS for

Windows, version 17 (SPSS Inc., Chicago, IL, USA).


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Results: Audiological assessment of the patients revealed that all patients in the control group
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and in mild OSAS group had normal hearing thresholds (lower than 26 dB). However, the

patients who had moderate and severe OSAS had varying degrees of sensorineural hearing

losses. As far as body mass indexes are concerned, statisitically significant differences were

observed among the groups (p=0.038).

Conclusion: There is convincing evidence that the risk of progressive dysfunction in vascular

and neural structures of the body is inevitable for the patients who suffer from a chronic

hypoxemic condition secondary to OSAS. The findings of the present study indicated auditory

transduction and transmission mechanisms may also be affected in moderate and severe

OSAS patients. Therefore, via taking necessary steps in preventing hypoxemia at the outset,
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OSAS patients may be protected from the long term detrimental effects of chronic hypoxemia

on the auditory system.

Keywords: Obstructive sleep apnea, hypoxemia, auditory system, sensorineural hearing

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loss, polysomnography test.

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INTRODUCTION

Hypoxemia is known to have a significant negative impact on the biochemical and

hemodynamical regulatory mechanisms located in the central and peripheral nervous system.
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In response to chronic hypoxemia a number of pathologies including but not limited to

dysfunctions in neural mediator turnover and a decrease in the adenosine levels in the central

nervous system can be observed (1-3). Furthermore, repetitive oxidative stress secondary to

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chronic hypoxemia was found to be associated with endothelial dysfunction in

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microcirculation. This condition, in turn, was proposed to compromise the vascular supply of

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the peripheral nerves and lead to an inevitable loss in neural function (4, 5).

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From an otorhinolaryngological point of view, patients with obstructive sleep apnea

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syndrome (OSAS) usually suffer from such a serious hypoxemic state as a consequence of

repetitive apneic episodes (6- 8). Patients are known to exhibit decreased oxygen (02)
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concentrations in the bloodstream during their sleep. In addition, significant fluctuations in 02

levels may persist even during the day time in OSAS patients (9).
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Chronic hypoxemia and the fluctuations in blood oxygen concentration observed in


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OSAS patients may be detrimental for the auditory transduction and transmission

mechanisms. The sense of hearing is accomplished by the peripheral and central auditory
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mechanisms, which are both vulnerable to the effects of hypoxemia. Flawlesss generation

and conduction of the neural signals from the cochlea to the auditory cortex necessitate the
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presence of an adequate and uninterrrupted supply of oxygen to the components of this neural

circuit (9). The authors of the present study aimed to investigate the impact of hypoxemia on

the auditory functions of OSAS patients and discussed their findings under the scope of the

existing literature.

MATERIALS AND METHODS

The study was conducted in a tertiary referral center in Turkey. Approval was granted

from the local ethics committee (2015/72/06/04) and all patients were asked to fill in an
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informed consent form. Patients who underwent a polysomnographic analysis for the

diagnosis of possible sleep disordered breathing between Jan 2015 and December 2015 were

enrolled in this study. Polysomnography tests were conducted at the sleep laboratory of the

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department of neurology at the same institute. Comprehensive otorhinolaryngological

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examinations of all participants were conducted by the same senior otorhinolaryngologist.

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Patients who had an acute or chronic otorhinolaryngological disease which may have a

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negative impact on hearing mechanism (otitis media, eustachian tube problems, sino-nasal

disorders and etc.) and other co-morbid chronic systemic conditions that are well known to be

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associated with hypoxemia and disturbances in the microvascular circulation, including
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diabetes mellitus (DM), hypertension (HT) and chronic obstructive pulmonary disease

(COPD) were excluded from the study. Three study groups and a control group were

designated in the study. Each study group was designated according to the severity of the
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apnea hypopnea index (AHI) and blood oxygen saturation values (SpO2) of the participants.
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The blood oxygen saturation levels were measured by a pulse oximeter (Beijing Safe Heart

Technology Ltd, China). The first, second and third groups were comprised of patients having
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mild (AHI: 5-15, SpO2 > 85%), moderate (AHI: 15-30, SpO2 = 65-84%) and severe OSAS
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(AHI > 30, SpO2<65%), respectively. Each group consisted of randomly selected 40 patients.

The control group was comprised of individuals who had an AHI < 5.

All participants also underwent pure tone auditometry and otoacoustic emission testing

(OAE). Pure tone audiometry (PTA) was conducted by the same audiometrist in accordance

to the international standards using a two channel audiometer (Interacoustics A/S, Denmark).

Hearing thresholds at 250 to 8 kHz for each ear were determined. Average PTA thresholds

was calculated by using threshold levels at 500, 100, and 2000 Hz. Patients who had a hearing

threshold greater than 25 dBHL were accepted to have auditory dysfunction. The degree of

hearing loss was accepted as mild (26 to 40 dBHL), moderate (41 to 55 dBHL), moderately
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severe (56 to 70 dBHL), severe (71 to 90 dBHL), and profound (91+ dBHL). For OAE

testing, Madsen AccuScreen TE device was used (Otometrics, Denmark). Normal outer hair

cell function was determined by a Pass/Clear Response result. Individuals with a Refer/No

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Clear Response result were re-tested. Upon retesting, individuals with a persistent Refer/No

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Clear Response result were accepted as having a sensorineural hearing loss.

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Statistical data analysis was performed using SPSS for Windows, version 17 (SPSS

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Inc., Chicago, IL, USA). The chi-square (2) test was used to compare qualitative data. The

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Kruskal-Wallis test (KW) was used to compare the groups. Dunns multiple comparison test

and the Tukeys range test were used to compare the subgroups. Results were considered
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significant for p<0.05.
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RESULTS
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The ages of the 160 participants (120 OSAS patients and 40 control subjects) were
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found to range between 23 and 55 years (mean age= 42.4 years). Of these, 76 were female

and 84 were male. The mean age for mild, moderate, and severe OSAS groups, and the
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control group was 42.6413.8, 41.3513.7, 43.14 11.6 and 42.3212.4 years, respectively.

No statistically significant difference was observed among the groups in terms of

demographic characteristics (p= 0.763).

As far as body mass indexes (BMI) are concerned, statisitically significant differences

were observed among the groups (p=0.038, odds ratio 1.52; 95% confidence intervals 1.11

2.39). In the control group and the first study group, BMI was within the normal range (18.5

24.9 kg/m2) while it was found to be >30 kg/m2 in the second and third study groups (Figure

1).
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40

35

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30

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25

20

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15

10

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5

0
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Control group (BMI Group 1(mild OSAS) Group 2 (moderate Group 3 (severe
kg/m2) (BMI kg/m2) OSAS) (BMI kg/m2) OSAS)(BMI kg/m2)
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Figure 1: Body mass indexes in groups (kg/m2).


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Audiological assessment of the patients revealed that all patients in the control group

and in mild OSAS group had normal hearing thresholds (lower than 26 dB). Mean hearing
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thresholds for control group, mild (AHI: 5-15, SpO2 > 85%), moderate (AHI: 15-30, SpO2 =

65-84%) and severe OSAS (AHI > 30, SpO2<65%) groups were 16.356.7 dBHL, 17.244.8
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dBHL, 33.245.6 dBHL, and 36.354.2 dBHL, respectively (Figure 2).


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Hearing Levels (dB)

40
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25 Control group

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20 Mild OSAS
15 Moderate OSAS

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10 Severe OSAS
5
0

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Control group Mild OSAS Moderate Severe OSAS
OSAS
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Figure 2: Hearing thresholds in all groups (dBHL).
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However, the patients who had moderate and severe OSAS had varying degrees of

sensorineural hearing losses. 9 of 40 patients in the second group and 16 of 40 patients in the
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third goup had mild sensorineural hearing loss (hearing levels were more than 25 dB) (Figure

3). Moderate and severe OSAS patients showed statistically significant difference with
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control group in terms of hearing levels (KW = 22.34, p = 0.0416, p < 0.05). Despite a slight

increase in the hearing thresholds of the patients at higher frequencies, the difference between

the hearing thresholds across the frequencies in all groups (i.e. lower vs. middle vs. high

frequencies) were not statistically significant (p= 0.618, p > 0.05).


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16

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Control group

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Group 1
Group 2
Group 3
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Figure 3: Number of patient having sensorineural hearing loss more than 25 dB
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Otoacoustic emission testing results revealed that all patients in the control and mild

OSAS groups have passed the test. On the contrary, 9 of 40 patients in the moderate OSAS
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group and 16 of 40 patients in the severe OSAS group have failed the OAE testing.
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DISCUSSION

The findings of the present study pointed out that moderate and severe OSAS may be

associated with a mild sensorineural hearing loss. This finding was in consistence with the

previous literature proposing that OSAS induced hypoxemia may have a negative impact on

the auditory function (1, 2, and 10).

Despite the abundance of the studies analyzing the impact of OSAS on certain aspects

of human functions including memory (11) cognition (12) and cardiac aoutonomic functions

(13, 14), OSAS induced alterations in the auditory system and their mechanisms of action yet

need to be further investigated.


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OSAS induced hypoxemia falls into one of the two broad patterns of hypoxemia

described in the literature. The first pattern is low frequency or sustained hypoxemia and

represents a chronic continuous hypoxemia as observed in high altitudes or chronic

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obstructive pulmonary disease. The second pattern of hypoxemia is characterized by short

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episodes of intermittent and high frequency hypoxemia that is encountered in OSAS patients.

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The decreases in oxygen saturation usually last for 15-60 seconds and this cyclic pattern may

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occcur during the sleep period. The episodic hypoxemia is followed by a reoxygenation or

reperfusion state after each episode (15). Literature review revealed that, the negative impacts

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of OSAS on vascular function and tissue oxygenation were extensively studied. Hypoxemia
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induced chemoreflex stimulation and consequent vasoconstriction which persists even during

normoxic daytime wakefullness in OSAS patients were well documented in previous

researches (16, 17).


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Although there is satisfying evidence that points out the association between OSAS
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and decreased tissue oxygenation, the literature review revealed that there are conflicting
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studies regarding the role of OSAS in auditory dysfunction. In a recent study, the authors

concluded that OSAS does not seem to affect the cortical processing of auditory afferent
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stimuli during sleep (18). However, the results of another study showed that severe OSAS

patients had abnormal auditory evoked potentials which persisted despite having an optimal

continuous positive airway pressure treatment for three months (19). Another issue that needs

to be further investigated is the possible association between the degree of hearing loss and

the severity of OSAS. In one study an apnea-hypopnea index value equal or greater than 10

was found to be associated with impaired cochlear function (20), whereas others proposed

that auditory dysfunction could be observed only in severe OSAS patients (10).

The findings of the present study indicated that OSAS patients with an AHI value less

than 15 did not have an auditory dysfunction. On the contrary, a mild sensorineural hearing
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loss was observed in both moderate and severe OSAS patients. Comparison of these two

groups of patients in terms of the severity of the hearing loss, however, yielded that the

difference between the groups was statistically insignificant. Further clinical researches

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should be conducted to delineate the association between AHI value and the degree of hearing

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loss in OSAS patients.

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Obesity and increased body mass index were reported to be important risk factors for

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OSAS in the literature (21-23). In our study a similar correlation between the increased body

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mass index and severity of OSAS was found. The body mass indices of the patients in

moderate and severe OSAS groups in which a mild sensorineural hearing loss was observed
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were greater than 30/m2. As the body mass index increased, the severity of OSAS seemed to

be increased. Therefore, weight gain control should be recommended for these patients for the
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prevention of possible OSAS induced auditory dysfunction.


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In conclusion, there is convincing evidence that the risk of progressive dysfunction in

vascular and neural structures of the body is inevitable for the patients who suffer from a
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chronic hypoxemic condition secondary to OSAS. The findings of the present study indicated

auditory transduction and transmission mechanisms may also be affected in moderate and
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severe OSAS patients. The authors of this research are of the opinion that, via taking

necessary steps in preventing hypoxemia at the outset, OSAS patients may and should be

protected from the long term detrimental effects of chronic hypoxemia on the auditory

system.

Financial Disclosure: No financial disclosures.

Conflicts of Interest: The other authors have no conflicts of interest to disclose.


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REFERENCES

1) Mazurek B, Haupt H, Georgiewa P, Klapp BF, Reisshauer A. A model of peripherally

developing hearing loss and tinnitus based on the role of hypoxia and ischemia.

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MedHypotheses. 2006; 67(4):892-9. Epub 2006 Jun 6. PubMed PMID:16757123.

P
RI
2) Carlile S, Paterson DJ (1992) The effects of chronic hypoxia on human auditory system

SC
sensitivity. Aviat Space Environ Med 63:10931097.

3) Davis JN, Giron LT Jr, Stanton E, Maury W. Theeffect of hypoxia on

NU
brainneurotransmittersystems. Adv Neurol.1979; 26:219-23. PubMed PMID: 42284.
MA
4) Rohit Budhiraja, M.D.; Sairam Parthasarathy, M.D.; Stuart F. Quan, M.D.Endothelial

Dysfunction in Obstructive Sleep Apnea J Clin Sleep Med. 2007 Jun 15;3(4):409-15. Review.
ED

5) Schwarz EI, Puhan MA, Schlatzer C, Stradling JR, Kohler M. Effect of CPAP therapy on
PT

endothelial function in obstructive sleep apnoea: A systematic review and meta-analysis.

Respirology. 2015 Aug; 20(6):889-95. doi: 10.1111/resp.12573.


CE

6) Oldenburg O, Wellmann B, Buchholz A, Bitter T, Fox H, Thiem U, Horstkotte D,


AC

Wegscheider K. Nocturnal hypoxaemia is associated with increased mortality instable

heartfailure patients. Eur Heart J. 2015 Nov 26. pii: ehv624. PubMed PMID: 26612581.

7) Gozal D, Kheirandish-Gozal L. Cardio vascular morbidity in obstructive sleep apnea:

oxidative stress, inflammation, andmuchmore. Am J Respir Crit Care Med. 2008 Feb 15;

177(4):369-75.

8) Matthias F. Kramer, MD, Richard de la Chaux, MD, Rose Fintelmann, MD, and Gerd

Rasp, MD.NARES: A Risk Factor for Obstructive Sleep Apnea? AmJ Otolaryngol. 2004

May-Jun; 25(3):173-7.
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9) Papandreou C. Levels of TBARS are inversely associated with lowest oxygen saturation in

obese patients with OSAS. Sleep Breath. 2013 Dec; 17(4):1319-22.doi: 10.1007/s11325-013-

0819-2.

T
10) Casale M, Vesperini E, Potena M, Pappacena M, Bressi F, Baptista PJ, Salvinelli F. Is

P
obstructive sleep apnea syndrome a risk factor for auditory pathway? Sleep Breath. 2012 Jun;

RI
16(2):413-7. doi: 10.1007/s11325-011-0517-x.

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11) Farnik M, Pierzchaa W.Analysis of memory dysfunction in OSAS patients. Pneumonol

NU
Alergol Pol. 2007; 75(4):349-54.
MA
12) 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.
ED

Neuromolecular Med. 2012 Sep; 14(3):180-93. doi: 10.1007/s12017-012-8182-1. Epub 2012

May 9. Review.
PT

13) Erdem A, Dogan OT, Yontar OC, Epozturk K, Ozlu MF, Ozturk S, Ayhan SS, Erdem FH,
CE

Yazici M, Akkurt I, Talay F. The pure effects of obstructive sleep apnea syndrome on cardiac

autonomic functions: heart rate turbulence analysis. Eur Rev Med Pharmacol Sci. 2013 Oct;
AC

17(20):2778-83.

14) Larrier DR, Huang ZJ, Zhang W, McHugh CH, Brock L, Reddy SC. Is routine pre-

operative cardiac evaluation necessary in obese children undergoing adenotonsillectomy for

OSA? Am J Otolaryngol. 2015 Nov-Dec;36(6):744-7. doi: 10.1016/j.amjoto.2015.05.007.

15) Dewan NA, Nieto FJ, Somers VK. Intermittent hypoxemia and OSA: implications for

comorbidities. Chest. 2015 Jan; 147(1):266-74. doi: 10.1378/chest.14-0500.


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16) Somers VK, Mark AL, Zavala DC, Abboud FM. Influence of ventilation and hypocapnia

on sympathetic nerve responses to hypoxia in normal humans. J Appl Physiol (1985). 1989;

67 (5): 2095 - 2100.

T
17) Somers VK, Dyken ME, Clary MP, Abboud FM. Sympathetic neural mechanisms in

P
obstructive sleep apnea. J Clin Invest. 1995; 96 (4): 1897 1904.

RI
SC
18) Huang J, Marcus CL, Davenport PW, Colrain IM, Gallagher PR, Tapia IE. Respiratory

and auditory cortical processing in children with obstructive sleep apnea syndrome. Am J

NU
Respir Crit Care Med. 2013 Oct 1; 188(7):852-7. doi: 10.1164/rccm.201307-1257OC.
MA
19) Vakulin A1, Catcheside PG, Baulk SD, Antic NA, van den Heuvel CJ, Banks S, McEvoy

RD. Auditory evoked potentials remain abnormal after CPAP treatment in patients with
ED

severe obstructive sleep apnoea. Clin Neurophysiol. 2012 Feb; 123(2):310-7. doi:

10.1016/j.clinph.2011.07.004.
PT

20) Xu Y, He X, Cai Q, Liang X, Zheng Y, Zhang S, Ji S. Influence of childhood obstructive


CE

sleep apnea-hypopnea syndrome on hearing. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za

Zhi. 2008 May; 22(10):436-8.


AC

21) Deegan, PC, McNicholas, WT Predictive value of clinical features for the obstructive

sleep apnoea syndrome. Eur Respir J. 1996; 9,117-124.

22) Schafer, H, Pauleit, D, Sudhop, T, et al Body fat distribution, serum leptin, and

cardiovascular risk factors in men with obstructive sleep apnea. Chest.2002; 122, 829-839.

23) Richman, RM, Elliott, LM, Burns, CM, et al The prevalence of obstructive sleep apnoea

in an obese female population. Int J Obes Relat Metab Disord.1994; 18, 173-177.