Keywords
wideband absorbance - wideband tympanometry - cholesteatoma - retraction pockets -
conductive hearing loss
Retraction of the tympanic membrane is caused by a difference in pressure between
the outer ear and middle ear. Retraction pocket (RP) is a special condition, wherein
part of the tympanic membrane is stretched in more than the rest of the tympanic membrane,
forming a distinct second (or multiple) concavity.[1] An RP is a pathological invagination of the tympanic membrane into the middle ear
space[2] that results in a loss of the fibrous layer of the tympanic membrane and the inability
of the tympanic membrane to return to its original strength and position. A chronic
RP can form adhesions with surrounding structures and accumulation of debris and epithelium,
predisposing to the development of cholesteatoma.[3]
[4]
[5]
Longstanding Eustachian tube dysfunction has been linked to the formation of RPs.[6] Although, RPs can be small and self-cleansing, without any symptoms of hearing loss
or otalgia, they can progressively erode the adjacent structures and cause otorrhea,
hearing loss, and otalgia.[7] The incidence rate of retractions involving the pars flaccida and pars tensa of
the tympanic membrane is reported to be 11.23%.[8]
A cholesteatoma is a well demarcated noncancerous cystic lesion derived from the growth
of keratinizing squamous epithelium that originates from the external layer of the
tympanic membrane or ear canal.[9] Cholesteatoma invades the middle ear cleft and is the most common destructive disease
of the ear, affecting both adults and children alike.[10] The annual incidence of acquired cholesteatoma ranges from approximately 9 to 12.6
cases per 100,000 adults and from 3 to 15 cases per 100,000 children.[11]
[12]
[13]
[14] The causes of cholesteatoma are often attributed to recurrent history of otitis
media and long standing negative pressure in the ear.[15] Patients with advanced cholesteatomas may experience feeling of fullness in their
ears, tinnitus, hearing loss, earache, vertigo, and ear discharge.
Based on the site of lesion, RP and cholesteatomas can be classified as (1) epitympanic—arising
from the pars flaccida and progressing upward (2) mesotympanic—arising from the pars
tensa and progressing medially along the lenticular process and stapes superstructure.
Pathological changes associated with middle ear pathologies vary depending on the
nature of the disease and site of lesion, and the management of the disease by an
otolaryngologist also differs depending on the severity of the disease.
Unfortunately, current standard tests including 226-Hz tympanometry and audiometry
fail to detect RP and cholesteatoma with accuracy, resulting in delayed diagnosis
and treatment.[16] Hunter and Margolis[17] reported a single case study of early cholesteatoma wherein serial audiograms and
tympanograms were normal but videotoscopy showed RP filled with debris. Researchers
examining the influence of RPs on the shape and peak of the tympanograms using a middle
ear modelling technique have concluded that tympanometry is not a suitable test for
RPs.[18] As tympanometry fails to detect RPs and cholesteatomas with high accuracy, an alternative
test that can improve the accuracy of detection of these middle ear conditions is
deemed necessary.[17] To date, there are no reported studies that have compared tympanometric and audiometric
findings in ears with RPs and cholesteatomas.
Wideband absorbance (WBA) is an emerging test that is reported to be sensitive to
detecting middle ear disorders in children and adults. WBA, measured at ambient pressure
(WBA) or under pressurized conditions (wideband tympanometry, WBT) performs better
than the single frequency tympanometry in identifying middle ear pathologies such
as otosclerosis, otitis media with effusion (OME), and eustachian tube dysfunction.[12]
[19]
[20]
[21]
[22] To date, there are no studies that have systematically investigated WBA or WBT in
ears with RPs or cholesteatomas. As a sensitive measure of middle ear function, WBA
may shed light on specific pathological changes of RPs and cholesteatomas. An understanding
of WBA findings would aid in better detection and management of RPs and cholesteatomas.
The objective of the present study was to describe and compare WBA and WBT findings
in ears with RPs and cholesteatomas.
Materials and Methods
Participants
Details of subjects including the age groups are provided in [Table 1]. Inclusion criteria for the control group were (1) normal otoscopy findings and
aerated middle ear; (2) negative history of middle ear infections at the time of testing;
(3) type A tympanogram with tympanometric peak pressure (TPP) between +50 and −100
daPa and peak compensated admittance (Y
tm) between 0.3 and 1.6 mmho[23]; (4) air conduction thresholds below 20 dB HL between 0.25 and 8 kHz; (5) air–bone
gap (ABG) of less than l5 dB at frequencies between 0.25 and 4 kHz.
Table 1
Subject details
|
|
C
|
Combined
|
Epitympanic
|
Mesotympanic
|
|
RP
|
Chol
|
RP
|
Chol
|
RP
|
Chol
|
|
Total
|
49
|
23
|
37
|
7
|
22
|
16
|
15
|
|
Subjects
|
Male
|
23
|
11
|
18
|
4
|
12
|
7
|
6
|
|
Female
|
26
|
12
|
19
|
3
|
10
|
9
|
9
|
|
Total
|
49
|
27
|
39
|
8
|
23
|
19
|
16
|
|
Ears
|
Right
|
29
|
13
|
23
|
4
|
12
|
9
|
11
|
|
Left
|
20
|
14
|
16
|
4
|
11
|
10
|
5
|
|
Mean
|
27
|
31.1
|
34.7
|
26.3
|
35.7
|
33.1
|
33.3
|
|
Age (in years)
|
SD
|
18.1
|
23.4
|
21.2
|
27.2
|
22
|
22
|
20.5
|
|
Range
|
6.0–59.1
|
5.1–75.1
|
6.1–77.1
|
16.1–75.1
|
6.1–77.1
|
5.1–65.1
|
6.1–77.1
|
|
Age group (in years)
|
5–10
|
13
|
7
|
7
|
3
|
4
|
4
|
3
|
|
11–20
|
11
|
2
|
5
|
1
|
3
|
1
|
2
|
|
21–30
|
3
|
5
|
3
|
1
|
1
|
4
|
2
|
|
31–40
|
6
|
2
|
7
|
–
|
4
|
2
|
1
|
|
41–50
|
11
|
2
|
5
|
–
|
4
|
2
|
1
|
|
51–60
|
5
|
–
|
6
|
–
|
2
|
–
|
4
|
|
61–70
|
–
|
4
|
–
|
1
|
–
|
3
|
–
|
|
71–80
|
–
|
1
|
4
|
1
|
3
|
–
|
1
|
Abbreviations: C, control group; Chol, cholesteatoma; RP, retraction pocket.
The experimental groups consisted of 27 ears from 23 patients with RPs and 39 ears
from 37 patients with cholesteatomas who were referred to the Audiology clinic at
the Townsville Hospital, Queensland. Diagnosis of RP or cholesteatoma was made by
an experienced otolaryngologist. In the RP group, all patients had otomicroscopic
and otoendoscopic examinations (using a fiberoptic endoscope to diagnose middle ear
conditions), 33% had confirmation of RP through computed tomography (CT) scan and
surgery and 4% had confirmation through CT scan only. Of the 10 (37%) patients with
RP who had confirmation of RP either via CT scan or surgery, one patient had epitympanic
RP (ERP) while nine patients had mesotympanic RP (MRP). About 80% of patients in the
RP group had a history of Eustachian tube dysfunction and/or middle ear infection
and 17% (4/23) of patients had a history of previous grommet insertions. Only one
patient had a grommet in situ and all the other patients had RPs without tympanic
membrane perforations.
In the cholesteatoma group, all patients had otomicroscopy, otoendoscopy, and CT scan,
while 95% of patients had confirmation of cholesteatoma through surgery. In the cholesteatoma
group, 46% (18/37) of patients had a history of ear infections and 18.9% (7/37) of
patients had a history of grommet insertions. Five patients had tympanic membrane
perforation and two patients had grommets at the time of testing. None of the patients
had a history of surgery for treatment of RPs or cholesteatomas prior to enrolling
in this study.
RPs and cholesteatomas were further classified as ERP and epitympanic cholesteatoma
(EC)—arising from the pars flaccida and growing upward, MRP and mesotympanic cholesteatoma
(MC)—arising from the pars tensa and growing medially along the lenticular process
and stapes superstructure. Pathological changes in RP and cholesteatoma vary depending
on the site of lesion. From a medical perspective, the epitympanic and mesotympanic
subgroups indicate the severity of the disease. The management of the disease by an
otolaryngologist differs depending on the site of lesion. Hence, apart from analyzing
RP and cholesteatoma, the results were also analyzed based on the site of lesion.
The first column in [Table 1] illustrates the data for all the participants while second and third columns are
separated into subgroups.
Procedures
Tympanometry, WBA assessment, and pure tone audiometry were performed in the same
order by experienced clinical audiologists. Tympanometry was performed using the Interacoustics
Titan version 3.1 (IMP440, Denmark). TPP and Y
tm were recorded by sweeping a 226-Hz probe tone from +200 to −400 daPa in a positive
to negative sweep direction.
Pure tone audiometry was conducted in a sound-treated room with ambient noise below
30 dBA. An AC-40 clinical audiometer (Interacoustics, Middelfart, Denmark) with TDH-39
earphones was used. Hearing thresholds for air conduction audiometry were determined
for octave frequencies between 0.25 and 8 kHz, while bone conduction thresholds were
determined for octave frequencies between 0.25 and 4 kHz.
A research version of the Titan software with module (IMP440/WBT440) was used for
WBA measurements. An appropriate sized probe was placed in the ear canal and the testing
began when the probe light turned green, suggesting an adequate seal for testing.
To measure WBA at ambient pressure (WBAamb), click stimuli were presented at ambient pressure at 100 dB peSPL (65 dB nHL) at
a rate of 21.5 Hz.[24] For WBT measurements, clicks were presented while ear canal pressure was swept from
+200 to −300 daPa at a rate of 200 daPa/s and the TPP was determined from a wideband
averaged tympanogram across a frequency range of 0.375 to 2 kHz. Titan automatically
generated WBA measured at TPP, and this is denoted as WBA at tympanometric peak pressure
(WBATPP) in this study.
WBAamb and WBATPP were recorded at 1/24th octave intervals between 0.23 and 8 kHz and then averaged
to 16 frequency bands centered at one-third octave frequencies from 0.25 to 8 kHz.
Visual inspection of the absorbance results was done to determine adequate probe fit.
Absorbance greater than 0.29 in the low frequency band (0.25–0.5 kHz) was indicative
of a probe leak.[25] When probe leakage was suspected, the probe was reinserted, and the test was repeated.
The results were saved into a research folder and then exported into excel for further
analysis.
Statistical Analysis
Statistical analysis was performed using the IBM SPSS software version 23. A mixed
model analysis of variance (ANOVA) was applied to the data wherein group (control,
RP, cholesteatoma) served as a between-subject factor, and frequency (16 levels) and
pressure condition (WBAamb and WBATPP) served as within-subject factor. The Greenhouse and Geisser G-G approach was used
to compensate for the violation of compound symmetry and sphericity.[26] Post hoc analyses were performed using multiple pairwise comparison tests with Bonferroni
adjustments to determine the frequencies at which significant differences existed
between the control and experimental groups.
In view of the small sample size and non-normally distributed data, a Wilcoxon signed
rank test was used to compare mean values of WBAamb and WBATPP of the ERP, EC, MRP, and MC groups. A Mann-Whitney U test was used to analyze the
significance of difference in distribution between the control group and the ERP,
MRP, EC, and MC groups. A p-value of less than 0.05 was considered statistically significant for all analyses.
Receiver operating characteristic (ROC) analysis was used as an objective measure
to determine the test performance of WBA to detect RPs and cholesteatomas. Through
this ROC analysis, the area under the ROC curve (AROC) was determined.
Results
Results for 226-Hz tympanometry, audiometry, and WBA are presented for the RP and
cholesteatoma groups which were subdivided into epitympanic and mesotympanic subgroups.
Tympanometry
Tympanometry results are provided in [Table 2]. The tympanograms were classified as: (1) type A with TPP between +50 and −100 daPa
and Y
tm between 0.3 and 1.6 mmho, (2) type As if the TPP was between +50 and −100 daPa, but
Y
tm was below 0.3 mmho, (3) type Ad if the TPP was between +50 and −100 daPa, but Y
tm was above 1.6 mmho, (4) type B with no identifiable peak, (5) type C with TPP below
−100 daPa and Y
tm between 0.3 and 1.6 mmho, (6) type Cs if the TPP was below −100 daPa and Y
tm was below 0.3 mmho, (7) type Cd if the TPP was below −100 daPa, but Y
tm was greater than 1.6 mmho. All 49 ears in the control group had type A tympanograms.
In the RP group, 25.9 and 33.3% of ears has type A or Ad and C or Cd tympanograms,
respectively, while 40.8% of ears had B type tympanograms. In the cholesteatoma group,
7.7% of ears each had type A or Ad, and C or Cs tympanograms, while 84.6% of ears
had type B tympanograms.
Table 2
Tympanometric results for control group (C) and ears with retraction pocket (RP) and
cholesteatoma (Chol)
|
|
|
Combined
|
Epitympanic
|
Mesotympanic
|
|
Measure
|
C
|
RP
|
Chol
|
RP
|
Chol
|
RP
|
Chol
|
|
Type
|
A
|
49
|
7
|
3
|
4
|
–
|
3
|
3
|
|
B
|
–
|
11
|
33
|
1
|
22
|
10
|
11
|
|
C
|
–
|
9
|
3
|
3
|
1
|
6
|
2
|
|
TPP (daPa)
|
Mean
|
−19
|
−130
|
−124
|
−106
|
−128
|
−142
|
−120
|
|
SD
|
27.34
|
131
|
93
|
152
|
90
|
121
|
100
|
|
Range
|
33 to −90
|
84 to −343
|
8 to −307
|
−21 to −343
|
8 to −307
|
−54 to −324
|
−20 to −277
|
|
Static Compliance (mmho)
|
Mean
|
0.82
|
1.18
|
0.62
|
0.9
|
0.23
|
1.33
|
0.97
|
|
SD
|
0.54
|
0.8
|
0.62
|
0.64
|
0.13
|
0.86
|
0.68
|
|
Range
|
0.31–1.64
|
0.17–3.02
|
0.16–2.12
|
0.19–2.12
|
0.16–0.55
|
0.17–3.02
|
0.16–2.12
|
|
Tympanometric width (daPa)
|
Mean
|
93
|
178
|
245
|
126
|
262
|
202
|
228
|
|
SD
|
40
|
117
|
99
|
63
|
59
|
130
|
135
|
|
Range
|
22–122.4
|
27–417
|
65–386
|
27–220
|
137–332
|
46–417
|
65–386
|
Abbreviations: SD, standard deviation; TPP, tympanometric peak pressure.
The ERP group demonstrated greater prevalence of A and C type tympanograms compared
with the EC group. However, 95.6% of ears with EC and 12.5% of ears with ERP had B
type tympanograms. Furthermore, 68.8% of ears with MC and 52.6% of ears with MRP had
B type tympanograms.
As shown in [Table 2], when compared with the control group, mean Y
tm was higher in the RP group and lower in the cholesteatoma group. An ANOVA was performed
with Y
tm as a dependent variable and group as the between-group factor. Results revealed a
significant difference in Y
tm among the three groups [F (2, 112) = 10.39, p = 0.001, ŋp
2 = 0.16]. Post hoc analysis with Bonferroni adjustments revealed a significant difference
in Y
tm between the control and cholesteatoma groups (p < 0.01) and between the RP and cholesteatoma groups (p = 0.01). There was no significant difference in mean Y
tm between the control and RP groups.
Further as illustrated in [Table 2], mean tympanometric width (TW) of the RP and cholesteatoma groups was also higher
than that of the control group. An ANOVA was performed with TW as a dependent variable
and group as the between-group factor. Results revealed a significant difference in
mean TW among the three groups [F (2, 85) = 26.92, p = 0.001, ŋp
2 = 0.40]. Post hoc analysis with Bonferroni adjustments revealed a significant difference
in mean TW between the control and RP group (p < 0.01) and between the control and cholesteatoma groups (p < 0.01). There was no significant difference in TW between the RP and cholesteatoma
groups.
Audiometry
Mean air and bone conduction thresholds for the control group and the cholesteatoma
groups are illustrated in [Fig. 1]. Mean bone conduction thresholds for the control group were within 10 dB HL, while
the mean bone conduction thresholds for the cholesteatoma groups were within 20 dB
HL. Air conduction thresholds of the cholesteatoma group were 4 to 8 dB worse than
that of the RP group. In comparison, air conduction thresholds of the EC group were
7 to 17 dB worse than that of the ERP group, while air conduction thresholds of the
MC group were 0 to 4 dB worse than that of the MRP group.
Fig. 1 Mean air–bone gap in control and experimental groups; (A) control, retraction pocket, and cholesteatoma; (B) control, epitympanic RP, and cholesteatoma; (C) control, mesotympanic RP, and cholesteatoma; Error bars indicate ± 1 standard error
of mean. RP, retraction pocket.
ABGs for the subjects in each group are presented in [Fig. 2]. Mean ABG in the control group was less than 10 dB. In the frequency region between
0.25 and 4 kHz, the RP group demonstrated a mild degree of conductive hearing loss
with an average ABG of 11 to 25 dB, while the cholesteatoma group demonstrated a mild
to moderate degree of conductive hearing loss with an average ABG of 11 to 34 dB.
Repeated measures ANOVA with ABG as a dependent variable and group as the between-group
factor revealed a significant difference in mean ABG among the three groups [F (2, 108) = 43.20 p = 0.001, ŋp
2 = 0.44]. Post hoc analysis with Bonferroni adjustments revealed a significant difference
in mean ABG between the control and RP group (p < 0.001) and between the control and cholesteatoma groups (p = 0.001) at octave frequencies between 0.25 and 4 kHz. There was no significant difference
in mean ABG between the RP and cholesteatoma groups.
Fig. 2 Mean air–bone gap in control and experimental groups; (A) control, retraction pocket, and cholesteatoma; (B) control, epitympanic RP, and cholesteatoma; (C) control, mesotympanic RP, and cholesteatoma; Error bars indicate ± 1 standard error
of mean. RP, retraction pocket.
WBA at Ambient Pressure
As illustrated in [Fig. 3A], mean WBAamb of both RP and cholesteatoma groups was reduced between 1 and 5 kHz when compared
with the control group. Maximum reductions of 0.31 and 0.36 were observed at 1.5 kHz
for the RP group and cholesteatoma group, respectively. Mean WBAamb of cholesteatoma group was 0.01 to 0.05 lower than that of the RP group between 1.25
and 4 kHz.
Fig. 3 WBA at ambient and tympanic peak pressures in control and experimental groups. (A) WBAamb in all participants in control, retraction pocket and cholesteatoma, (B) WBATPP in all participants in control, retraction pocket and cholesteatoma, (C) WBAamb in control, epitympanic retraction pocket and epitympanic cholesteatoma, (D) WBATPP control, epitympanic retraction pocket and epitympanic cholesteatoma, (E) WBAamb in control, mesoympanic retraction pocket and mesotympanic cholesteatoma, (F) WBATPP in control, mesotympanic retraction pocket and mesotympanic cholesteatoma.
Results of repeated measures ANOVA revealed a significant group effect [F (2,112) = 1,747, p < 0.01, ŋp
2 = 0.24]. [Fig. 3A] shows the frequencies at which the difference in mean WBAamb was significant between the three groups. Mean WBAamb was significantly different between the control and RP groups from 0.8 to 4 kHz and
between the control and cholesteatoma groups from 0.8 to 2 kHz and 4 to 5 kHz. There
was no significant difference in mean WBAamb between the RP and cholesteatoma groups.
As illustrated in [Fig. 3C], mean WBAamb of the ERP subgroup was 0.07 to 0.25 lower than the control group between 1 and 4 kHz.
Mean WBAamb of the EC subgroup was 0.10 to 0.38 lower than the control group between 0.8 and
5 kHz. Mean WBAamb of the EC subgroup showed greater reduction than that of ERP subgroup between 1.5
and 5 kHz. The largest reduction of 0.25 and 0.38 was observed at 1.5 kHz for the
ERP and EC subgroups, respectively.
Results of Mann-Whitney U tests applied to the data revealed no significant difference
in mean WBAamb between the control and ERP subgroup at any of the frequencies. There was a significant
difference in mean WBAamb from 0.8 to 5 kHz between the control and the EC subgroup. There was no significant
difference in mean WBAamb between the ERP and EC groups throughout the frequency range from 0.25 to 8 kHz.
As seen in [Fig. 3E], when compared with the control group, mean WBAamb of the MRP group was 0.11 to 0.34 lower between 0.8 and 5 kHz, while mean WBAamb of the MC group was 0.08 to 0.33 lower. Results of Mann-Whitney U tests revealed
a significant difference in mean WBAamb between the control and MRP subgroup from 0.8 to 5 kHz, and between the control and
MC subgroup from 1 to 5 kHz. There was no significant difference in mean WBAamb between the MRP and MC subgroups.
WBA at TPP
As shown in [Fig. 3B], mean WBATPP of the RP group was 0.07 to 0.10 lower between 1 and 5 kHz compared with the control
group. Mean WBATPP of the cholesteatoma group was 0.09 to 0.19 lower between 1 and 5 kHz compared with
the control group. Mean WBATPP of the cholesteatoma group was 0.03 to 0.10 lower between 0.8 and 1.5 kHz compared
with the RP group.
Results of repeated measures ANOVA revealed a significant group effect [F (2, 112) = 3.34, p = 0.04, ŋp
2 = 0.06]. Further analysis with Bonferroni adjustments revealed no significant difference
in mean WBATPP between the control and RP groups, and between the RP and cholesteatoma groups at
any of the frequencies. However, there was a significant difference in mean WBATPP between the control and cholesteatoma groups at 0.8, 1, 1.25, 2, 4, and 5 kHz ([Fig. 3B]).
As seen in the [Fig. 3D], mean WBATPP of the ERP group was only 0.01 to 0.07 higher between 1 and 4 kHz and 0.08 to 0.09
lower between 6 and 8 kHz compared with the control group. In comparison, mean WBATPP of the cholesteatoma group was 0.06 to 0.21 lower between 1 and 5 kHz compared with
the control group. Mean WBATPP of the cholesteatoma group was 0.07 to 0.28 lower than the RP group at frequencies
between 0.8 and 5 kHz.
Results of a Mann-Whitney U test presented in [Fig. 3D], show that there was no significant difference in mean WBATPP between the control and ERP groups at any of the frequencies. However, the difference
in mean WBATPP between the control and EC groups was significant at 0.8, 1, 1.25, 1.5, 4, and 5 kHz.
There was a significant difference in mean WBATPP between the ERP and EC subgroups at 0.8, 1, and 1.25 kHz only.
As shown in [Fig. 3F], compared with the control group, mean WBATPP of the MRP and MC subgroups was 0.12 to 0.18 lower between 1 and 5 kHz. Mean WBATPP of the MC subgroup was only 0.01 to 0.05 lower than that of the MRP subgroup between
0.25 and 8 kHz. Analysis using Mann-Whitney U tests revealed that the difference in
mean WBATPP between the control and MRP subgroup was significant at 1.25, 1.5, 2.5, and 4 kHz.
Similarly, the difference in mean WBATPP between the control and MC subgroup was significant at 1.25, 1.5, 2, 2.5, 4, and
5 kHz. However, mean WBATPP of the MRP subgroup was not significantly different from that of the MC subgroup
at any frequency.
Comparison between WBAamb and WBATPP
An ANOVA was performed on WBA data with pressure condition (ambient vs. TPP) as the
within group factor and ear condition (control, RP, and cholesteatoma) as between
group factor. The results showed that WBATPP was higher than WBAamb up to 3 kHz for all three ear conditions. The difference between WBAamb and WBATPP was significantly different between 0.5 and 1.5 kHz for the control, between 0.25
and 1.5 kHz and 4 and 8 kHz for the RP, and between 0.4 and 2.5 kHz except at 1 kHz
for the cholesteatoma.
Further, WBA under the pressure conditions was also compared between the epitympanic
and mesotympanic subgroups using a Wilcoxon signed rank test. The showed that the
difference between WBAamb and WBATPP was significant from 0.25 to 2 kHz and 4kHz for the ERP group, from 0.8 to 3 kHz
for the EC group, from 0.3 to 1.5 kHz and 8 kHz for the MRP group, and from 0.6 to
1 kHz for the MC group.
Additionally, resonance frequency (RF) was obtained from WBATPP measurements for the RP and cholesteatoma groups. Mean RF of the RP group was 623 Hz
(standard deviation = 211 Hz; range = 333–997 Hz), while the mean RF of the cholesteatoma
group was 592 Hz (standard deviation = 372 Hz; range = 242–1567 Hz). An ANOVA applied
to the RF data revealed no significant difference in RF between the RP and cholesteatoma
groups [F = (1, 42) = 0.74, p > 0.05].
Of the 10 patients who were referred for CT scan or surgery, one patient had ERP while
nine patients had MRP. Patients were referred for CT or surgery when the boundaries
of the RP were not very clear and cholesteatoma had to be ruled out. WBAamb and WBATPP of patients with MRP who had confirmation of RP through CT scan or surgery were compared
with those diagnosed with MRP by otomicroscopy only. The WBATPP of patients with confirmation of MRP through CT scan or surgery was only 0.04 to
0.07 higher than the corresponding WBAamb between 1.25 and 2kHz and similar to WBAamb at all other frequencies. In comparison, the WBATPP of the MRP patients diagnosed through otomicroscopy only was 0.06 to 0.23 higher
than the corresponding WBAamb. The difference between WBATPP and WBAamb in the MRP group diagnosed with otomicroscopy only was highest (0.19–0.23) between
0.5 and 1.25 kHz.
Test Performance
ROC analyses were applied to the WBA data.[27] ROC curves showing test sensitivity against one minus specificity, are standard
procedures to evaluate the test performance of a diagnostic test. They show to what
extent two distributions (e.g., pass and fail) overlap. The further apart the distributions,
greater will be the AROC, which is an overall indication of the diagnostic accuracy
of WBA.[28] An AROC value of 1.0 indicates that the test measure reliably distinguishes between
two mutually exclusive distributions, for instance, “normal” and “disease” conditions.
On the other hand, an AROC value of 0.5 indicates that the predictor is no better
than chance to distinguish between the conditions. For the present work, we regard
an AROC of at least 0.8 as an acceptable level because AROC < 0.7 is regarded as less
accurate and AROC ≥ 0.9 is regarded as highly accurate.[29] The 10th percentile of the WBA for the control group was used as the cut off for
distinguishing cholesteatomas and RP from healthy ears.
Given this cutoff value for the various measures below which a fail outcome was expected
to occur, a comparison with the standard yielded a specific set of hit rate (HR) and
false alarm (FA) rate. By varying the WBA cutoff values, many sets of HR and FA rates
were determined. A plot of the ROC curve (HR against FA) was obtained for each measure.
The point on the ROC curve closest to the top left corner (HR = 1 and FA = 0) was
taken as the optimal point to determine the sensitivity and specificity. Furthermore,
the AROC was determined for TW and Y
tm, and WBA. The cut off values for TW and Y
tm were determined based on the American Speech Language Hearing Association guidelines
(ASHA).[30] The 10th percentile of the TW and Y
tm for the control group was used as the cut off for distinguishing cholesteatomas from
healthy ears.
The AROC for Y
tm for distinguishing between the control and RP group was 0.60, and between the control
and cholesteatoma groups was 0.75. Further, the AROC for distinguishing between the
RP and cholesteatoma groups was 0.65.
Similarly, the AROC for TW for distinguishing between the control and RP group was
0.67, and between the control and cholesteatoma groups was 0.83. The AROC for distinguishing
between the RP and cholesteatoma groups was 0.66.
The test performance of the WBA test was evaluated at one-third octave frequencies
between 0.25 and 8 kHz. The AROC values of WBAamb for distinguishing between control and RP groups ranged between 0.47 and 0.68 across
the frequency range. AROC was highest between 1.5 and 2 kHz, with values of 0.64 to
0.68, while AROC values were less than 0.60 below 1.5 kHz and above 2 kHz. The AROC
values of WBATPP for distinguishing between the control and RP groups ranged between 0.48 and 0.55
across the frequency range.
Similarly, the AROC values of WBATPP for distinguishing between control and cholesteatoma groups ranged between 0.47 and
0.65 across the frequency range with the highest AROC obtained at 1.5 kHz. The AROC
values of WBATPP for distinguishing between the control and cholesteatoma groups ranged between 0.47
and 0.61 across the frequency range. Likewise, the AROC of WBATPP for distinguishing between RP and cholesteatoma groups ranged between 0.44 and 0.60,
while AROC of WBATPP varied between 0.45 and 0.56.
Comparison with Other Middle Ear Pathologies
The results of the present study were compared with the results from other studies
that have investigated WBA in ears with middle ear disorders. [Fig. 4] compares the WBA results of the present study with that of Voss et al's[31] study on cadaveric ears with ossicular chain dysfunction and fluid in middle ear.
The results demonstrated that the results in ears with RP and cholesteatoma were different
from the other middle ear disorders. Nevertheless, this is a comparison of the pattern
of WBA and further quantitative studies are required to compare the difference between
RP, cholesteatoma, and other middle ear disorders.
Fig. 4 Comparison of wideband absorbance results at ambient pressure from the present study
with various middle ear pathologies from study by Voss et al.[31]
Discussion
The present study is the first attempt to describe the characteristic WBA findings
in patients with RPs and cholesteatomas. The results indicated that both RP and cholesteatoma
groups showed slightly different audiometry, tympanometry, and WBA results.
The RP group demonstrated a mild conductive hearing loss, while the cholesteatoma
group demonstrated a mild to moderate conductive loss. Nevertheless, there was no
significant difference in mean ABG between the two groups. These results hold true
regardless of the sites of lesion, indicating that pure tone audiometry findings alone
cannot distinguish between RPs and cholesteatomas.
Tympanometry results revealed that the cholesteatoma group had twice the prevalence
of type B tympanograms than the RP group. Similar pattern of results was seen with
MRP and MC subgroups while ERP and EC subgroups had A, B, and C type tympanograms.
Nevertheless, irrespective of the site of lesion, there was no significant difference
in Y
tm, TW, and RF between the RP and cholesteatoma groups. Further, the test performance
of Y
tm and TW in distinguishing between RP and cholesteatoma was low. These results suggest
that tympanometry alone cannot differentiate between RPs and cholesteatomas.
The RP and cholesteatomas groups showed similar WBAamb and WBATPP configuration of results, indicating that WBA cannot distinguish between the two
middle ear conditions ([Fig. 2A, B]). Results of ROC analyses also suggested that both WBAamb and WBATPP cannot differentiate between the RP and cholesteatoma groups. Nevertheless, when
the mean WBAamb and WBATPP were compared within each group, the RP group showed greater WBATPP than WBAamb between 0.5 and 1.5 kHz, whereas the cholesteatoma group demonstrated an increase
in absorbance between 1.5 and 3 kHz. The difference between WBAamb and WBATPP was slightly higher for the RP group (0.05–0.16) than for the cholesteatoma group
(0.03–0.11). This result is probably due to the compensatory pressure effect for the
RP patients whose WBA results were more affected by negative middle ear pressures.
When the WBA results were analyzed according to the site of lesion of the RPs and
cholesteatomas, differential WBA patterns were observed ([Fig. 2C–F]). With the epitympanic lesion, both ERP and EC subgroups demonstrated an increase
in WBA at TPP relative to ambient pressure between 0.8 and 4 kHz. Mean WBA of the
ERP subgroup increased to normal levels at TPP compared with ambient pressure, while
WBA of the EC subgroup remained significantly lower than the control group at frequencies
0.8 to 1.5 kHz and 4 to 5 kHz. In contrast, with the mesotympanic lesion, similar
WBAamb and WBATPP results were obtained for both MRP and MC subgroups.
Changes in middle ear function associated with pathologies vary depending on the nature
of the disease and this is reflected in changes in WBA. As illustrated in [Fig. 4], significantly reduced WBA between 0.8 and 5 kHz demonstrated in ears with cholesteatoma
and RP in the present study is different from the pattern of WBA reported for other
middle ear pathologies. For instance, otosclerosis is associated with reduced WBA
at frequencies of 1 kHz and lower.[22]
[32] Voss et al[31] detailed the effects of various sized perforations on WBA using cadaveric specimens
and demonstrated increased absorbance in the low frequencies below 1 kHz for small
sized tympanic membrane perforations, and WBA findings similar to that in normal ears
at frequencies less than 2.5 kHz for large perforations. Significantly higher absorbance
between 0.4 and 1 kHz has been reported in ears with tympanosclerosis.[33]
[34] Several studies have shown a reduced WBA pattern across the frequency range in ears
with OME.[20]
[33]
[35] A sharp WBA peak at around 0.4 to 0.8 kHz has been reported in ears with ossicular
chain discontinuity,[31]
[32]
[33] while a peak around 1 kHz is reported for ears with superior semicircular canal
dehiscence.[32]
Pathological changes associated with the disease process are different for the RP
and cholesteatomas conditions. Clinically, RP is associated with a persistent negative
middle ear pressure and changes in the structure of the tympanic membrane.[36]
[37] The process of retraction is accompanied by irreversible changes in the tympanic
membrane structure. Hence, the weakened parts of pars tensa come into contact with
the underlying ossicles (the long crux of the incus, the incudostapedial articulation).
In contrast, pathological changes in cholesteatoma can be due to the presence of the
cholesteatoma matrix within the middle ear, erosion of ossicles (through chronic inflammation
and pressure necrosis), disruption of the ossicular chain, direct impingement on an
intact ossicle, decreased aeration of the middle ear, and reduced vibratory capacity
of the tympanic membrane.[38]
[39]
The ERP group showed the presence of negative middle ear pressure with pathogenesis
likely related to the dysfunction of the Eustachian tube, inflammation, and pneumatization
of mastoid.[40] Absorbance results of the present study are in agreement with other studies that
reported absorbance being reduced at ambient pressure and returning to normal levels
at TPP in ears with negative middle ear pressure.[19]
[41] Using an experimental model, Pau et al[18] reported that tympanometry in ears with RPs or atelectasis does not measure middle
ear pressure correctly. The TPP depends on the size of the RP and the remaining gas
volume in the middle ear.
In the present study, the RP group exhibited a greater increase in absorbance at TPP
compared with ambient pressure than the cholesteatoma group. This suggests that in
ears with RP, pressurization of ear canal to TPP increased absorbance of the middle
ear. Further, in patients with ERP, absorbance returned to normal levels at TPP. An
increase in absorbance at TPP in ears with ERP may suggest an apparently intact middle
ear system with tympanic membrane retraction only. Normal absorbance at TPP suggests
that normal tympanic membrane mobility could be restored when pressure in the external
ear canal is equalized on either side of the tympanic membrane. This may suggest a
relatively intact ossicular chain with limited vibratory capacity either due to decreased
aeration of the middle ear or decreased vibratory capacity of the tympanic membrane.
In contrast, no such patterns were observed between the MRP and MC subgroups. The
audiometric, tympanometric, and WBA patterns of RP and cholesteatoma were similar
at ambient pressure and TPP with the mesotympanic site of lesion. While the mechanisms
in which MRP and MC affect the middle ear are different, they both involve the middle
ear space and ossicular chain. With MRP, it is possible that the mobility of the ossicular
chain was also affected as the retracted tympanic membrane drapes over the ossicular
chain when it is retracted toward the promontory. The audiological assessment findings
of the MC group are influenced by the presence of the cholesteatoma matrix within
the middle ear, erosion of ossicles (through chronic inflammation and pressure necrosis),
disruption of ossicular chain, direct impingement on an intact ossicle, decreased
aeration of the middle ear, and reduced vibratory capacity of the tympanic membrane.[38]
[39]
The WBATPP of the patients with MRP who had confirmation of RP through CT scan or surgery was
similar to WBAamb across the frequency range except between 1.25 and 2 kHz. In comparison, the WBATPP of patients diagnosed with MRP with otomicroscopy only was 0.09 to 0.23 higher than
WBAamb. One possible reason for this could be that the severity of the condition was different
between the two subgroups. The MRP of patients with CT scan or surgical confirmation
had either stage SADE III or IV retractions while the patients diagnosed with otomicroscopy
only ranged from stage SADE I to IV retraction.[4] Therefore, instead of describing the WBA in MRP as a single group, further research
is needed to explore the patterns of WBA based on staging of the RP.
Differentiating between ERP and EC has implications on the management. Some ears with
ERP heal spontaneously, while others continue to advance to the EC condition. Although
ECs are always managed surgically, the decision on the procedure to be used in the
treatment of ERP depends on the functional and anatomical condition of the ear.[2] The difficulties in decision making about surgical treatment of ERP are also related
to the fact that the symptoms in ERP can be minimal in both early and advanced stages
of the condition. While the decision about surgical management of the ERP is not difficult
in patients with significant conductive hearing loss, it can be difficult in ERP patients
with a lesser degree of hearing loss. With patients wherein a “wait and see” approach
is recommended, WBA can be used to monitor the middle ear condition and alert the
clinician to changes in the middle ear status and hence warrant further investigation
and management.
Limitations
Although the present study has demonstrated different patterns of WBA in ears with
RP and cholesteatoma, there are limitations. First, the sample size was small. Further,
both pediatric and adult participants with an age range of 5 to 77 years were included
in the control and experimental groups. Although there are differences in WBA due
to developmental effects, these differences are too small to be of clinical significance.[42] Second, although the acoustic measures are dependent on the status of the middle
ear ossicles, staging of each ossicle was not considered in the present study. Staging
of ossicular chain can be used to quantify the extent of erosion of each ossicle.
For instance, Martins et al[38] developed a rating scale wherein ratings were assigned to each ossicle as follows:
1 indicates completely normal; 2, cholesteatoma abuts the ossicle but the ossicle
is still intact; 3, the ossicle is partially eroded by cholesteatoma; and 4, the ossicle
is completely absent (for the malleus and incus) or if the superstructure is eroded
(for the stapes). Future studies investigating RP and cholesteatomas need to consider
radiological results of staging of each ossicle and relate it to WBA results. Such
staging would enable exploring the relationship between ossicular destruction and
WBA in detail. Finally, the present study included only one commonly used measure
of wideband acoustic immittance, namely, WBA. Further research is needed to incorporate
additional immittance measures such as admittance and phase to develop objective measures
to improve the identification of RPs and cholesteatomas.
Conclusion
Overall, the present study demonstrated no significant differences in WBAamb and WBATPP results between RP and cholesteatoma. However, when comparing between the WBAamb and WBATPP results for each of the subgroups, it may be possible to distinguish between the
ERP and EC subgroups, but not between the MRP and MC subgroups. Further research is
required to determine the sensitivity and specificity of WBA to differentiate individuals
with EC versus those with ERP.
