1.

Introduction
Maintenance of middle ear pressure (MEP) by an appropiately functioning
eusctachian tube (ET) is vital to the health of the middle ear. ET dysfunction resulting
is chronic negative MEP has been implicated in many significant otologic conditions
including hearing loss, tympanic membrane (TM) retraction, and chronic otitis media.
Prior studies evaluating middle ear and ET physiology have been performed on
awake patients with normal or negative MEP [1-3]. To the authors’ knowledge, no
study to date has specifically investigated MEPs during sleep despite the fact that the
average individual sleeps nearly a third of their lifetime. Many organ system have
normal physiologic changes during sleep. In patients without middle ear disease,
studies have shown that MEP is most commonly positive upon waking, but quickly
normalized toward zero after swallowing and chewing maneuvers [1-3]. These
findings suggest that middle ear and ET physiology also change during sleep.
Contionuous positive airway pressure (CPAP) theraphy, a highly effective
treatment for obstructive sleep apnea (OSA), provides a pneumatic stent for the upper
airway and prevents apnea during sleep. It is highly plausible that positive pressure
may be transmitted to the middle ear through the ET during CPAP use. This can
occur during periodic ET opening or when nasopharyngeal airway pressures exceed
the resting pressure keeping the ET closed. A recent study demonstrated a linear
increased in MEP with increasing CPAP levels in awake patients [4]. We
hypothesized that MEP would rise slowly with duration of sleep and that escalating
CPAP levels would cause propotional elevations in MEP during sleep.

2. Materials and methods

Following Institutional Review Board approval (IRB No. 12-005787), adults patients
undergoing polysomnography at a tertiary academic refferal center were
prospectively enrolled. All research subjects were provided informed consent. Study
participation was limited to patients without prior middle ear disease or a history of
otologic surgery. Each eligible participant was further screened using otomicroscopy
and thymphanometry (Madsen OTOflex 100; GN otometrics North America,
Schaumburg, IL), and all patients with evidence of active ET dysfunction, middle ear
disease , TM perforation, or a non-Type A tympanogram were excluded. One subject
was excluded because of ongoing ET dysfunction with TM retraction and a Type C
tympanogram. Each patient was then fitted with a tympanometry probe in one ear that
was sealed in place with polyvonylsiloxane ear impression molding (Oaktree
Products Inc., Chesterfield, MO) using a manual impression gun (Fig. 1).
Tympanometry was performed and MEP was recorded in decapascals (daPa) in
supine subjects. Two additional patients were excluded; one could not tolarate
sleeping with the tympanometry probe in place, and in the other, a seal could not be
kept with the probe in the ear to obtain accurate pressure readings. MEP readings
were taken just before sleep initiation and during the diagnostic portion of the
polysomnogram at 1-hour intervals following sleep onset. Confirmation of sleep was
performed using electroencephalography (EEG). Following diagnostic
polysomnography, if the patient met criteria for OSA with an apnea-hyponea index
(AHI) ≥5 events/hour, they were fitted with a CPAP device. The CPAP level, in
centimeters of waters (cm H2O) was titrated during sleep until the patient’s OSA was
adequately treated. Tympanometry was performed and MEP readings were taken
prior to the initiation of CPAP and at each level of CPAP during the titration. MEP
mean values, standard deviations, and ranges were calculated for each category.
Paired t-tests were used for comparison of MEP with and without CPAP use while
asleep. Spearman’s rank correlation coefficient (r) was utilized to compare MEP with
time asleep and CPAP levels.

3. Results
Ten patients, six men and four women, were included. The mean age at testing
was 57.8 years (range 37.7-74.7 yrs). Monoaural testing was performed in each
patients including six left and four right ears. The mean MEP of all patients before
sleep was +3 daPa [range, -12 to +18 daPa; SD ±10]. The mean MEP at 1,2,3, and 4
hours following sleep onset were +14 daPa (range, -15 to +40 daPa; SD, ±24),
±22daPa (range, -1 to +64 daPa; SD, ±23), +27 daPa (range, -9 to +53 daPa; SD,
±23) and +41 daPa (range =, +12 to +86 daPa; SD, ±26), respectively (Fig. 2). There
was a strong positive relationship between time asleep and MEP (r = 0,52, p < 0,001).
Eight of ten patients met criteria of OSA with a mean AHI of 16 range, 6-40), and
qualified for CPAP titration. One patient was not able to initiate sleep with the CPAP
device and did not undergo titration. The mean MEP before CPAP initiation for the
seven patients that underwent succesful CPAP titration was +14 daPa (range, -4 - +39
daPa; SD, ±13). The mean MEP at a CPAP levels of 5 cm H2O was +54 daPa (range,
+26 to +73 daPa; SD, ±15), (p <0.01). the differences between the mean MEP during
sleep without CPAP and with CPAP became greater as the CPAP pressure was
increased beyond 5 cm H2O (p <0.005).

4. Disscusion
Using a novel method to record MEP during sleep, our results confirm the
hypothesis that MEP predictably rises during sleep. We found that the mean MEP
after 4 hours of sleep was 41 daPa, which corroborates two earlier studies measuring
an average MEP of 29 and 48 daPa immediately upon waking [1,2]. These values are
significantly higher than the mean awake MEP of 3 daPa in the current study.
The mechanism of increased MEP during sleep is likely multifactorial and may
result, in part from impaired ET ventilation occuring while supine. Hergils et al.
Demonstrated that in awake patients lying supine and performing shallow breathing,
MEP rises slowly with time then decreases quickly swallowing [1]. Swallowing
during sleep has been shown to occur an average of 2.4 times per hour [5,6]. Hergils
and colleagues found that MEP equalization with swallowing was often incomplete
while supine and continued to rise reaching a plateau after approximately 3-4 hours,
paralleling our findings in asleep subjects [1].
Our study confirms a supraphysiologics rise in MEP in patients using CPAP
during sleep. A CPAP setting of 5 cm H2O is typically the lowest level used to treat
OSA. At 5 cm H2O, the mean MEP during sleep was 54 daPa. This is more that=n
double the average MEP during sleep without CPAP. MEP rose steadily with
increasing CPAP levels with a mean MEP of 104 daPa at 10 cm H2O. This is very
similar to that published by Lin et al. in which the mean MEP in awake patients was
47, 82 and 129 daPa at CPAP levels of 5, 10 and 15 cm H2O, respectively [4].
Our study confirms supraphysiologic rise in MEP in patients using CPAP during
sleep. A CPAP setting of 5 cm H2O is typically the lowest level used to treat OSA. At
5 cm H2O, the mean MEP during sleep was 54 daPa. This is more than double the
average MEP during sleep without CPAP. MEP rose steadily with increasing CPAP
levels with a mean MEP of 104 daPa at 10 cm H2O. This is very similar to that
published by Lin et al. in which the mean MEP in awake patients was 47,82, and 129
daPa at CPAP levels of 5, 10 and 15 cm H2O, respectively[4].
The implications of elevated MEP with CPAP use are significant. The upper limit
of normal MEP is considered by many to be between 50 and 100 daPa. These
pressures are easily surpassed by CPAP use. Unfortunately, because the prevalence of
sustained positive MEP is very low and most middle ear disease is associated with
negative pressure, studies evaluating the effects of positive MEP are scarce. Ostegard
et al. identified 13 of 750 (1.7%) patients with ear complaints who had MEP greater
than 49 daPa while awake [7]. In patients with positive MEP, the most common
complaints were otalgia, ear fullness, and pharyngitis. TM erythema and decreased
mobility, as well as otitis media were noted in most of these patients. Only two
patients exhibited a mild conductive hearing loss [7]. A study conducted in guinea
pigs demonstrated that elevating MEP with air up to 250 daPa had no effect on
auditory threshold measured by auditory brainstem response (ABR) [8]. While it
appears that hearing is likely not significantly affected in most individuals, there have
been rare reports of tympanic membrane rupture, pneumocephalus, and tension
pneumocranium with CPAP use [9-12]. Although rare, these findings should prompt
caution with CPAP use following head trauma, rhinologic or otologic surgery, and
particularly following intradural skull base procedures.
 Finally, it is worth discussing the potential therapeutic role of CPAP in patients
with chronic ear disease. ET dysfunction with resultant chronic negative MEP is the
principle mechanism behind chronic otitis media. Two studies have examined the
long-term effects of CPAP on MEP [13,14]. Aksoy et al. compared the awake MEPs
of 51 patients with OSA using CPAP for at least six months to 48 control subjects
that did not use CPAP and found that there no significant difference between groups
[13]. In contrast, Sivri and colleagues compared awake MEPs of 78 patients with
OSA and not using CPAP and found a significant increase in MEP in the group using
CPAP [14]. In addition, the increase in mean MEP in the CPAP group was directly
proportional to the pressure level of CPAP prescribed. There was also a significant
number of patients that converted from a type B or C tympanogram to a type A
configuration, and four of five TM retractions resolved following six month of CPAP
use [14]. Similarly, Yung demonstrated the potential benefit of CPAP for treatment of
TM atelectasis, showing that a single CPAP session at 10 cm H2O reinflated two-
thrids of atelectasis TMs [15].
In closing, we wish to acknowledge several strengths an limitations of current
study. To the author’s knowledge, this is the first study to investigate normal
physiologic MEP during sleep and how this is altered with CPAP use. While middle
ear physiology has been extensively analyzed in awake individuals, studies evaluating
MEP during sleep are lacking despite the fact the average individual sleeps nearly a
third of their lifetime. Second, by performing tympanometry during
polysomnography, the authors could study the effects of duration of sleep on MEP in
a controlled setting, through monitoring of the sleep-wake cycle and arousals. The
primary weakness of the current study is the limited number of patients. Studying
each subjects during overnight polysomnography proved to be costly and time
intesive, which limited prospective enrollment. However even with ten patients, the
primary outcomes of the study were found to be highly statistically significant.
Additionally these data were collected on subjects without a history of ET
dysfunction; therefore our findings may not directly apply to patients with chronic ear
disease. Future studies will be needed to determine if these observations also hold
true for subjects with ET dysfunction.

5. Conclusion
Middle ear pressure rises proportionately with duration of sleep. Furthermore,
increasing CPAP levels result in predictable supraphysiologic elevations in MEP.
Further research is needed to examine the long-term consequences of CPAP use
on the middle ear and the potential therapeutic benefits for patients with tympanic
membrane retraction and chronic ear disease.