Sleep Breath (2012) 16:413–417
DOI 10.1007/s11325-011-0517-x
ORIGINAL ARTICLE
Is obstructive sleep apnea syndrome a risk factor
for auditory pathway?
Manuele Casale & Emanuela Vesperini & Massimiliano Potena & Marco Pappacena &
Federica Bressi & Peter Jarden Baptista & Fabrizio Salvinelli
Received: 24 December 2010 / Revised: 18 March 2011 / Accepted: 22 March 2011 / Published online: 9 April 2011
# Springer-Verlag 2011
Abstract
Purpose The transduction mechanism of the inner ear and
the transmission of nerve impulses along the auditory way
are highly dependent upon the cochlear oxygen supply.
Several studies have considered the possibility that obstruc-
tive sleep apnea–hypopneas during sleep can interfere with
these processes, and the results are not uniform. The aim of
the study is to evaluate the auditory function in adult
patients affected by severe obstructive sleep apnea syn-
drome (OSAS).
Methods Thirty-nine patients in this study were included
and divided in OSAS group, with severe OSAS (Apnea–
Hypopnea Index, AHI>30), and control group with snoring
without OSAS (AHI<5). Each patient was subjected to
pure-tone audiogram (PTA), otoacoustic emission (OAE),
and brainstem auditory evoked potentials.
Results The OSAS group showed a PTA significantly higher
than the control group (14.23±6.25 vs. 7.45±2.54; p<0.01), a
lower TEOAE reproducibility (0.57±0.10 vs. 0.92±0.10; p<
0.01) such as a lower signal-to-noise 0atio (p<0,01) and a
lower DPOAE amplitude (5.96±6.34; 13.18±2.97; p<0.01).
The mean latencies of waves I, III, and V were prolonged in
OSAS group as compared to the healthy people, especially
for wave V (p<0.05). The interpeak latency (IPL) of I–V
M. Casale (*) : E. Vesperini : M. Potena : M. Pappacena :
F. Bressi : F. Salvinelli
Area of Otolaryngology, Campus Bio-Medico University,
Via Alvaro del Portillo 21,
00128 Rome, Italy
e-mail: m.casale@unicampus.it
P. J. Baptista
Departamento de Otorrinolaringología,
Clínica Universitaria de Navarra,
Pamplona, Navarra, Spain
was significantly higher (p<0.01) in the OSAS patients
(5.84±0.15) as compared to the control group (5.4±0.12),
such as IPLs I–III and III–V (p<0.05).
Conclusions Our data showed an auditory dysfunction in
patients affected by severe OSAS, suggesting that severe
OSAS could represent a risk factor for auditory pathway.
Keywords Hypoxia . Obstructive sleep apnea syndrome .
Auditory brainstem response . Otoacoustic emissions .
Audiometry
Introduction
The obstructive sleep apnea syndrome (OSAS) is a
potentially disabling condition characterized by excessive
daytime sleepiness, disruptive snoring, recurrent episodes
of apnea or hypopnea, and nocturnal hypoxemia, associated
with episodes of choking or gasping during sleep, recurrent
awakenings, unrefreshing sleep, daytime fatigue, or im-
paired concentration or memory. There are several risk
factors involved in the development of obstructive sleep
apnea, including obesity, age, male sex, and heritable
factors [1, 2].
In populations with cardiovascular diseases, the OSAS
prevalence has been found to be substantially increased,
especially in patients with hypertension [3–5]. It has been
also reported to be increased in patients with stroke, renal
failure [6], and heart failure [7]. Nazzaro et al. assert that
OSAS is associated with reduced basal and functional
capillarity rarefaction with an additional risk of impaired
peripheral perfusion [8].
The mechanisms involved in this relation are most likely
induced by the periodic hypoxia/reoxygenation that char-
acteristically occur in OSAS, which results in oxidative
414
stress, endothelial dysfunction, and activation of the
inflammatory cascade. These noxious stimuli can, in turn,
activate the sympathetic nervous system, depress parasym-
pathetic activity, provoke oxidative stress and systemic
inflammation, activate platelets, and impair vascular endo-
thelial function [9]. On the other hand, the hypoxemia
results in peripheral nerve damage by harming the vasa
nervorum. In the early stages of ischemia, mechanisms to
reduce peripheral neuropathy are activated, but these
become insufficient over time, and obvious neuropathy is
inevitable in chronic hypoxemia [10].
The transduction mechanism of the inner ear and the
transmission of nerve impulses along the auditory way are
highly dependent upon the oxygen supply; few studies,
with not uniform results, have considered the possibility
that obstructive apnea–hypopneas at night can interfere
with the processes of generation and transmission of nerve
impulses at the level of auditory system [11–13]. The aim
of the study is to evaluate the auditory function in patients
affected by severe OSAS.
Materials and methods
Subjects
Ninety-seven snoring patients with suspected OSAS under-
went an overnight polysomnography (PSG) from Novem-
ber 2009 to May 2010 at the Department of
Otolaryngology, University Campus Bio-Medico, Rome
(Italy). Patients with a history of drugs able to influence
the vascular reactivity and lung functions, hearing loss, or
any middle or inner ear pathology are excluded from the
study; besides, any medical diseases which affect or are
suspected to affect hearing (e.g., diabetes mellitus, untreat-
ed hypertension, noise exposure, hypercholesterolemia, or
use of ototoxic drug therapy), mild or moderate OSAS are
rule out from the study.
According to exclusion criteria, 39 patients (mean age,
38; range 25–45) study (31 males and 8 females, body mass
index (BMI) 31.3±7.6 kg/m2) were included and divided in
two groups:
OSAS group: eighteen subjects (3 females and 15 males)
with severe OSAS (apnea–hypopnea index, AHI>30),
BMI (kilograms per square meter) 32.1±6.5, mean age 31.
Control group: twenty-one subjects (5 females and 16
males) snoring group, with no OSAS (AHI<5). BMI
(kilograms per square meter) 28.8±5.5, mean age 39.
Each patient enrolled in our study underwent otologic
examination, pure-tone laminar audiometry (PTA), otoa-
coustic emissions (OAE), and brainstem auditory evoked
potentials (BAEP).
Sleep Breath (2012) 16:413–417
Procedures
Sleep studies
Modified portable sleep apnea monitoring was performed in
all patients with a polygraphy Mesam-8 Polymesam, with
recording of abdominal and chest movements, body
position, snoring, oxygen blood saturation, pulse rate, oro-
nasal airflow (nasal air pressure).
According to international guidelines (Roche et al. 2007),
we considered the AHI (apnea+hypopnea per hour of sleep)
<5 suggestive of simple snoring with no OSAS; 5<AHI<15
mild OSAS; 15<AHI<30 moderate OSAS, and AHI>30
suggestive of severe OSAS. We considered the hypoxemia
during sleep through ODI (oxygen desaturation index) (n/h)
and mean nocturnal oxygen saturation (Sat O2%) in both
groups; in OSAS group, we also evaluated the possible
correlations between ODI, Sat O2 and hearing parameters.
Audiological assessment
All patients were subjected to PTA from 250 to 8 KHz
according to international standard. The PTA average from
250 to 8,000 Hz for each ear was calculated.
Otoacoustic emission
Transient-evoked otoacoustic emissions (TEOAEs) were eval-
uated in reproducibility (expressed as the correlation between
two waveforms, namely for responses stored in buffers A and
B, acquired alternately) and amplitude of the signal-to-noise
(S/N) ratio (computed from the sum and differences of the
A and B records), distortion product otoacoustic emissions
(DPOAEs) measured as DP-grams were recorded using an
ILO88 OAE Analyser (Otodynamics) [14–16].
Brainstem auditory evoked potentials
Brainstem auditory evoked potentials (BAEPs) were accom-
plished using an OtoAccess program. The time window was
10 ms, and the filter band pass was set from 30 to 3,000 Hz.
Brainstem auditory evoked potentials (BAEPs) were
accomplished using an OtoAccess program. The time window
was 10 ms, and the filter band pass was set from 30 to
3,000 Hz. The stimulus was an acoustic click created by a
pulse of 0.1 ms duration with alternating polarity to cancel
cochlear microphonic and stimulus artifact in the recording.
The stimulus rate was 21 clicks/s. The intensity level of the
stimulus was 80 dB nHL to allow clear definition of the
waves. The stimulus was presented 2,000 times for each
recording trial, and at least three trials/replications were made
to permit confident identification of the response. Latencies of
waves I, II, III, IV, and V, together with interpeak latencies
Sleep Breath (2012) 16:413–417 415

Table 1 Auditory threshold in patients with OSA and in control group

Frequency (Hz) 250 500 1,000 2,000 4,000 PTA (pure tone average)

OSAS group 10.76±8.9 11.15±7.9 11.7±6.5 26.3±16.6 14.2±6.2 14.23±6.25

Control group 7±4.04 7.75±3.98 6.25±2.12 7±2.83 9.25±6.56 7.45±2.54
P value 0.22 0.23 0.019 0.074 <0.01 <0.01

(ILs) of I–III, I–V, and III–V, and amplitudes of waves I and V
were measured from recordings [17, 18].
Statistical analyses
Statistical analysis was performed using the Statistical
Package for Social Sciences Software (SPSS 10.0 for
Windows, SPSS Inc., Chicago, IL, USA). Data are shown as
mean and standard deviation or as median and interquartile
range. Parametric (Student's t test) test was used to compare
different values. Our criterion for statistical significance was
set at P values of less than 0.05 (two-tailed).
Results
Sleep data
All OSAS group patients had a severe OSAS characterized
by AHI range 36.2±24.7, ODI values around 52.6±24.2,
and mean Sat O2% of 13.1±32.8 (such as PaO2%<90).
Audiometric data
We found that patients with OSAS had a PTA significantly
higher than the control group (OSAS group, 14.23±6.25;
control group, 7.45±2.54; p<0.01). Analyzing the single
frequencies, OSAS group showed higher thresholds and
was statistically significant at 4 kHz compared with the
control group (p<0.01) as indicated in Table 1.
Otoacoustic emission data
OSAS group showed lower TEOAE reproducibility (0.57±
0.10) compared with the control group (0.92±0.10) that was
statistically significant (p<0.01). The S/N ratio was statisti-
cally significantly lower at each frequency tested (p<0.01) in
OSAS versus control group, as shown in Table 2.
Table 3 shows the value of DPOAE at each frequency
tested in both groups. Analyzing the results obtained with
the DP gram, the OSAS group had significantly lower
amplitude values (5.96±6.34) compared with the control
group (13.18±2.97).
BAEP data
The BAEP results showed that in OSAS patients the
mean latencies of wave I, III, and V were significantly
prolonged as compared to simple snoring (Table 4). The
IPLs of I–V was significantly higher (p<0.01) in the
OSAS patients (5.84±0.15) as compared to the control
group (5.4±0.12); also the IPLs III–V and I–III in OSAS
were higher in OSAS group than in control group, but the
difference was statistically significant only for IPLs III–V
(Table 4). Analyzing the BAEP wave reproducibility, a
statistically significant difference between OSAS and
control group (OSAS, mean 0.66±0.24; control group,
mean 0.92± 0.18; P <0.05) was found. Analyzing the
possible correlations between AHI, mean SatO2 values,
and all hearing index (hearing thresholds, OAE data and
BAEP values) within OSAS group, no significant differ-
ences (p=NS) were found.
Discussion
In our study, we observed an evident auditory dysfunction
in patients affected by severe OSAS in absence of other
auditory risk factors, suggesting that the hypoxia in severe
OSAS could represent a risk factor for auditory pathway
[19, 20]. The otoacoustic emission was significantly lower
in the OSAS patients compared to the control group; if we
consider that it is widely accepted that the otoacoustic
emission is the direct reflection of the cochlear active
mechanisms, attributed to the active process of outer and
inner hair cells, it is possible that the reduction of the OAE

Table 2 TEOAE data about

signal-to-noise (S/N) ratio Frequency (Hz) 1,000 1,400 2,000 2,800 4,000

OSA group 4.36±5.18 7.06±5.97 9.33±5.98 5.5±5.6 1.87±3.9

Control group 13.94±7.22 18.35±8.01 18.06±7.2 14.7±7.22 10.05±6.18
P value <0.01 <0.01 <0.01 <0.01 <0.01
416 Sleep Breath (2012) 16:413–417

Table 3 Average and standard

deviation of DPOAE amplitude Frequency (Hz) 1,001 2,002 3,003 4,004 6,006
in dB SPL (p<0.01)
OSAS group 2.42±2.44 10.6±9.77 5.64±7.42 7.53±12.3 4.31±5.72
Control group 8.99±2.72 12.9±3.78 14.4±5.33 11.6±2.86 17±8.17
P value <0.01 <0.01 <0.01 <0.01 <0.01

levels can be attributed to a vulnerability of the hair cells to
an oxygen blood level [21, 22].
Analyzing our data, we can see that the damage of the
hair cells extends to the whole cochlea, but it is major at the
cochlear basis, where the higher frequencies are codified
according to the theory of tonotopicity; it is known that the
hair cells of basal turn are more sensitive to trauma than the
apex as seen in noise exposure and ototoxic drugs. Sha et
al. [23] demonstrated that the level of natural glutathione
was significantly lower in basal outer hair cells than apical
outer hair cells, supporting a higher susceptibility of basal
cell population to free-radical damage.
Fischer et al. in our study have analyzed the prevalence of
sleep apnea in patients with sudden hearing loss, compared to
subjects with normal hearing. Their results suggested that the
sudden deafness may also be an indicator of damage secondary
to such risk factors as hypertension, diabetes, and hyperlipid-
emia, which were highly significant for the OSAS patient [24].
In our study, we found the higher thresholds (p<0.01) at
4 kHz in OSAS compared with the control group that could
be attributed to impact of vasospasm, thrombosis, embolism,
hypercoagulation owed to the effects of long period of sleep
disease, as demonstrated in a recent study Chung S. et al. [9,
25, 26]. Also the central auditory ways seem to be affected
by OSAS, as suggested by previous studies.
The increased latencies of BAEP waves, IPLs I–III (p=ns)
and III–V (p<0.05) latencies, such as the lower auditory
brainstem response (ABR) reproducibility showed an altered
conduction in the retrocochlear auditory pathways, especially
in higher brainstem at the level of the inferior colliculus [27,
28]. Regional blood flow has been reported to decrease in
the brainstem of apneics and this would be expected to
aggravate the adverse effects of apnea on auditory brainstem
structures [29].
The chronic hypoxia could lead to a dysfunction of the
brainstem centers resulting in an alteration of ABR tracks
and a further worsening of the sleep apnea due to damage
of the respiratory centers, creating a vicious circle also with
repercussions on the auditory system, which could explain
the central apnoea in OSAS [30]. Dziewas et al. [31] in a
study performed in 2007 showed how the recurrent
intermittent hypoxaemia may be considered a risk factor
for peripheral sensory nerve dysfunction and suggested that
the treatment for OSA might result in an improved function
of these nerves [32]. The lack of correlation between blood
oxygen index (ODI and Sat O2) and audiological param-
eters could be attributed to a small sample of OSAS
patients, or it is possible that the audiological damages from
intermittent hypoxaemia takes place over a longer period of
illness. In our sample study, no correlation was found
between age, BMI, and audiological parameters.
Further studies could clarify whether the alteration of the
auditory system represents an early marker of vascular
dysfunction, due to sensitivity of auditory pathway to
hypoxia. The severity and the duration of the OSAS alone
or together can contribute to the development of the decline of
the neuronal and vascular function of the auditory pathway.
Larger studies will further help confirm the association and
elucidate the auditory benefit of OSAS therapy.
Conflict of interest The authors declare that they have no conflict of
interest.
Appendix
Definition of abbreviations used in the text
OSAS Obstructive sleep apnea syndrome
ODI Oxygen desaturation index
SAT. O2 Mean oxygen saturation
AHI Apnea/hypopnea index
BMI Body mass index [kg/m2]
PSG Polysomnography
PTA Pure-tone audiometry
OAE Otoacoustic emission
ABR Auditory brainstem response
BAEP Brainstem auditory evoked potentials

Table 4 Wave latency and IPLs

of BAEP dB nHL Wave I Wave III Wave V IPL I–V IPL I–III IPL III–V

OSAS 1.59±0.27 3.73±0.23 5.84±0.15 4.25±0.16 2.11±0.24 2.11±0.14

CTRL 1.44±0.07 3.5±0.13 5.4±0.12 3.84±0.27 1.77±0.18 1.77±0.18
P value 0.03 0.05 <0.01 <0.01 ns <0.01
Sleep Breath (2012) 16:413–417
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