Sound is collected by the external ear and decoded in

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Evaluation of Middle Ear Function by Tympanometry and the Influence of Lower Barometric Pressure

at High Altitude

Tao Jiang, MD, PhD,^1,2,{Liping Zhao, MD, PhD,^1,2,{Yanbo Yin, MD, PhD,^1,2,{

Huiqian Yu, MD, PhD,^1,2and Qingzhong Li, MD, PhD^1,2

Abstract

Jiang, Tao, Liping Zhao, Yanbo Yin, Huiqian Yu, and Qingzhong Li. Evaluation of middle ear function by tympanometry and the influence of lower barometric pressure at high altitude. High Alt Med Biol. 22:70–76, 2021.

Objective: To evaluate middle ear function in residents of high-altitude areas in comparison to sea-level participants.

Design: Prospective observational study.

Setting: All experiments were performed by experienced audiologists with a calibrated tympanometry machine.

Participants: Young adults between the age of 17 and 23 were recruited. Seventy-five participants from Shanghai (altitude 4 m) and 133 participants from the Shigatse area (altitude 4,040 m) were recruited. Any participant with any otological disorder was excluded.

Main Outcome Measure: Four indexes of the tympanogram were evaluated in the two groups from different altitudes.

Results: Our results showed that the peak of static compliance for the participants in Shigatse was smaller, but the absolute compliance of tympanic membrane remained the same. Similarly, the ear canal volume (ECV) from tympanometry was also affected by the elevated altitude in Tibet. In addition, the tympanometric peak pressure was decreased in high-altitude residents, which suggests a slightly declined function of the Eustachian tube at lower barometric pressure. However, no difference was found in the tympanometric width (TW).

Conclusion: Our results indicate that tympanograms were affected by decreased atmospheric pressure at high altitude. Therefore, other than pressure-related indexes, TW is better for evaluating the function of the middle ear in high-altitude regions.

Keywords:high altitude; middle ear; tympanometry

Introduction

Sound is collectedby the external ear and decoded in the inner ear for further perception (Wu and Kelley, 2012;

Jiang et al., 2017). The middle ear is responsible in trans- ducing sound vibrations from air in the external ear canal to fluid in the inner ear (Tucker, 2017). During this process,

proper functioning of the ossicular chain and tympanic membrane are necessary for normal function of the middle ear. The acoustic waves are amplified by the ossicular chain, which is well supported by surrounding muscles and tendons before reaching the inner ear. In addition, opening and closing of the Eustachian tube that connects the middle ear to the nasopharynx is necessary to maintain aeration in the

1ENT Institute and Otorhinolaryngology Department of Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Fudan University, Shanghai, P.R. China.

2NHC Key Laboratory of Hearing Medicine (Fudan University), Shanghai, P.R. China.

{These authors contributed equally to this work.

ª Mary Ann Liebert, Inc.

DOI: 10.1089/ham.2020.0042

70

Downloaded by 134.122.89.123 from www.liebertpub.com at 11/07/21. For personal use only.

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middle ear to ensure ossicular vibration (Bunne et al., 2000).

When the tympanic cavity is filled with effusion or pus, sounds can no longer transduce properly in patients diag- nosed with otitis media (Rovers et al., 2004). Otitis media is one of the most common causes for patients to visit otolar- yngologists. Direct and indirect costs related to otitis media are enormous. Thus, diagnosis and treatment of middle ear dysfunction as early as possible are important for both clinical and financial consideration.

Tympanometry, also known as the acoustic admittance test, is the preliminary examination applied during clinical practice to evaluate middle ear function and to diagnose otitis media (Palmu et al., 1999; Shanks and Shohet, 2009). Two important variables of the tympanogram are the volume on the y axis and the pressure on the x axis (Fig. 1A). During the test, a tip is inserted into the external ear canal to apply a pressure starting from 200 daPa. Under this pressure, the tympanic membrane is presumably tense enough to remain still. The measured volume at this point only represents the space between the tip in the external ear canal and the tympanic membrane, which is defined as ear canal volume (ECV) (Lide´n, 1969; Steele, 2003). With a decrease in applied pressure, the tympanic membrane becomes flexible, and the measured volume increases. The compliance of the tympanic membrane reaches a peak when the pressure outside the middle ear equals that within. After subtracting the ECV from the largest measurement, the volume is defined as the peak of static compliance (SC), which indicates the flexibility of the middle ear cavity. The pressure within the tympanic cavity that is measurable at this point is defined as the tympanometric peak pressure (TPP). An increased SC indicates a possible ossicular chain discontinuity, whereas a decreased SC can be attributed to a middle ear cavity with effusions such as in otitis media ( Jerger, 1970; Duzer et al., 2017). In addition, when the TPP is equivalent to the pressure of the middle ear cavity (around 0 daPa), any significant shift of TPP from 0 (–20 daPa) indicates that the Eustachian tube does not function properly to adjust the tympanic pressure. In summary, the tympanometry is an efficient examination that evaluates middle ear function and diagnoses otitis media easily.

Given the importance of tympanometry, there are some baseline data that need to be addressed beforehand. The function of the middle ear in high-altitude regions is an in- sufficiently explored area. Previous publications have demonstrated that acute hypoxia leads to various neuro-otological disorders, such as headache, hearing disturbance, and even vestibular defects (Dursun and Engin, 2009; Cingi et al., 2010). However, these studies rarely focused on hearing conduction of residents in high-altitude areas. Only one previously published paper investigated the acoustic stapedius reflex in Andean children between 2 and 17 years old in Peru at 2,850 meters (m) and 3,973 m, respectively (Counter et al., 2017). This reflex is controlled by the central nervous system to protect the hair cells from damage, which are due to the stapedius and tensor tympani muscles in the middle ear being activated whenever high-intensity sounds reach the inner ear. Their study found no differences in this hearing response between groups, which indicates that sound trans- duction was not affected by high altitude. Nonetheless, the article only focused on the ossicular chain mediation, but it neglected the possible effects of higher altitudes on other aspects of the middle ear.

In this study, we focused on the basic indexes of tympanometry. With the barometric pressure decreases with the altitude climbing, we hypothesized that lower pressure would affect the tympanic function. We studied tympanometry in residents from both sea-level and high-altitude areas, where the altitudes are 4 and 4,050 m, respectively. In addition, to reduce the influence of development (Roush et al., 1995), we purposely selected college-age young adults whose middle ears were considered as fully developed. Our results suggest that there are differences between tympanogram measurements, but the compliance of the middle ear determined by anatomical features was rarely affected by high altitude.

Moreover, statistically significant decreases in tympanic pressure were observed in the high-altitude group, which indicates a slight decline in function of the Eustachian tube.

Further, since this index is not affected by barometric pressure, it may be a better evaluation of middle ear function independent of altitude differences.

FIG. 1. Age-matched participants who were clear of otologic diseases were recruited from Tibet and Shanghai, respectively. (A). Schematics of the tympanogram. ECV is the volume measured at 200 daPa (orange). The peak of the SC is the SC (yellow). The tympanic pressure when the SC reached is the TPP (gray). TW is defined as the pressure width between the 50% decreased peak of SC (green). (B) College-age participants were recruited. The average age was 19.1 years old in the sea-level group (N= 75), and 18.8 in the high-altitude group (N = 133). No significant difference in age was found between the two groups. (C). Representative pictures of tympanic membranes from both groups. The membranes are transparent without any indication of otitis media. The tympana are clear from effusion or pus. SC, static compliance; TPP, tympanometric peak pressure; TW, tympanometric width.

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Materials and Methods

Participants and group designation

Participants recruited in our experiments were young adults around 17 to 23 years old from high schools or uni- versities. In the sea-level group, 75 participants (35 females and 40 males) were recruited from Shanghai where the altitude is 4 m. In the high-altitude group, 133 participants (85 females and 48 males) were recruited from Shigatse re- gion at the altitude of 4,050 m. None of the participants in- cluded in our experiments had any otological disorders by history or physical examination.

Subjects were enrolled under a protocol approved by the Ethical Committee of the Eye and ENT Hospital of Fudan University. All procedures involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from the participants.

We calculated the atmospheric pressure from the different altitudes based on the equation P= antilog10 [(53012.2-H)/

18401.8] (Roush et al., 1995; Palmu et al., 1999). At sea level, the pressure equals to 1.01· 10⁴daPa, whereas it is 6.08· 10³ daPa at the altitude of 4,050 m.

Tympanometry examination

The device used for tympanometry test was the MADSEN OTOflex 100. They were calibrated and maintained routinely in both areas following the manufacturer’s requirements.

Only qualified audiologists with at least 5 years of clinical experience operated these devices.

Statistics

We used the Grad-graph to perform statistics. The Stu- dent’s t-test was applied to perform the statistical analysis.

Statistical significance was taken with a p-value<0.05.

Results

Age-matched participants without otological diseases were recruited

The existing literature has shown that the tympanometry results change significantly during the development of the middle ear (Roup et al., 1998). Hence, to minimize the var- iances due to development, we recruited young adults of college age from Shanghai and Tibet, respectively. The age of the participants in the high-altitude group was 18.8 years old (SD= 1.37), similar to 19.1 years old (SD = 1.26) in the sea-level group (Fig. 1B).

We screened tympanic membranes with an electric auriscope to exclude any participant with otological diseases. Then, the endoscope was inserted to evaluate the tympanic membrane and middle ear condition of each participant after tests. Representative pictures of the tympanic membranes from both groups are shown in Figure 1C. No pus, inflammation, or hydrops in the middle ears from either group was detected.

A lower peak of SC was identified in high-altitude group Our data confirm what has been reported in the literature that the average volume of the peak of SC in the sea-level

group was around 0.52 ml (SD= 0.45) (Fig. 2) (Lide´n, 1969; Steele, 2003). No difference was detected between opposite ears (data not shown). However, with the sea- level group serving as the control for the high-altitude group, SC was significantly lower with an average of 0.34 ml (SD= 0.21).

Studies have suggested that females generally have lower SC compared with males (Roup et al., 1998). To eliminate any gender bias, we compared the SC data between males and females within each altitude group. Our data indicate that there is little difference between women and men in each altitude group (Supplementary Fig. S1).

However, when we separately compared males and females across the two groups, significant disparity was found. In this case, gender bias of the SC value can be disregarded.

Absolute compliances of tympanic membrane were comparable between groups

The acoustic compliance of the middle ear depends on the size of the tympanum and the compressibility of the air within. The decrease in barometric pressure of high altitude changes the compressibility of the air. Thus, in this case, SCs at different altitudes would not directly reflect the absolute compliance of tympanic membrane. Thus, we further calculated the absolute compliance in different groups, which is directly related to the ratio between change of volume and

FIG. 2. The high-altitude group has lower SC. The average of SC was 0.52 ml in the sea-level group (blue dots), and 0.34 ml in the high-altitude group (red dots). Boxplots dis- played the minimum, first quantile, median, third quantile, and the maximum data from bottom up. Each dot represents the result from one participant. ***p< 0.05.

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change of pressure (Compliance¼ DVolume=DPressure). To calibrate the absolute compliance of tympanic membrane under different conditions, we normalized the volume results of ‘‘SC’’ we obtained from tympanometry to the adjusted atmospheric pressure. In the sea-level group, the average of absolute compliances was 0.51· 10^-4ml/daPa (SD= 0.45), which was not statistically different from the high-altitude group whose absolute compliances was around 0.56· 10^-4ml/daPa (SD= 0.34) (Fig. 3). Differently from SC, we found that the absolute compliance was more stable between the two groups after eliminating the influence of atmospheric pressure. As such, the SC value we collected from the tympanograms at high altitude was relatively lower, but the absolute compliance of the middle ear cavity was not affected by higher altitude.

Lower atmospheric pressure led to decreased volume of external ear canal

The next index of tympanometry we compared between the two groups was the ear canal volume (ECV). To em- phasize here, the ECV of tympanometry is defined as the volume measured at 200 daPa, rather than the real size of

the external canal. In our data, participants from sea level had an average ECV of 1.32 ml (SD= 0.3) (Fig. 4). By comparison, the averaged ECV in the high-altitude group was 0.99 ml (SD= 0.21), which was significantly lower compared with the controls. Previous literature has suggested that women have smaller ECVs compared with men.

To understand the influence of gender, we compared the ECV between women and men of the different groups.

Congruent with previous studies, women had smaller ECV compared with men (Supplementary Fig. S2). However, the ECV differences within the same gender from the two groups were also significant. Therefore, residents in high- altitude areas have a smaller ECV value during tympanometric evaluation, and this requires additional attention in clinical practice.

Lower TPP was found at high altitude

Given that the atmospheric pressure affects SC results of tympanometry, we further investigated whether lower pressure of a higher altitude can affect the tympanic pressure. The Eustachian tube opens and closes frequently to adjust the pressure of the tympanic cavity to ensure that atelectasis does not develop in the tympanum. If the function of the Eu- stachian tube is not affected at high altitude, then TPP should be the same. In the sea-level group, the average of TPP was 4.21 daPa (SD= 8.88) (Fig. 5). However, in the high-altitude group, the average pressure was -3.87 daPa (SD = 14.42).

Although TPP values measured in participants at high altitude were statistically significantly lower than those in

FIG. 3. Absolute compliances were similar in between the two altitude groups. After normalizing the SC gained from the tympanometry machine to the local atmosphere pressure, we got the absolute compliance of the tympanic membrane. In the sea-level group (blue dots), there is an average compliance of 0.52 ml, which has little statistical difference, whereas the high-altitude group (red dots) has an average compliance of 0.56 ml.

FIG. 4. A relatively smaller ear canal volume (ECV) was found in the high-altitude group. The average of ECV in the sea-level group (blue dots) was 1.32 ml. Differently, in the high-altitude group (red dots), the average was 0.99 ml, which showed a significant difference. ***p< 0.05.

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Shanghai, indicating possible worse performance of the Eustachian tube, all results were still within the normal clinical range.

No significant differences of tympanometric width were identified in the two groups

While assessing the tympanogram, the tympanometric width (TW) is considered a stable factor that is not affected by development, pump speed, or the value of the SC (Shanks and Shohet, 2009). The TW evaluates the chang- ing slope of compliance along the pressure axis, which is defined as the width between the 50% decreased peak of SC. Increased TW and decreased steepness of the tympanogram can be observed in patients with otitis media ( Jerger, 1970). Independent of the cavity compliance, TW provides a complementary index to assess middle ear function. To exclude any systematic bias in how barometric pressure affects the middle ear, we further evaluated the TW in the two groups. As expected, the TW between the two groups did not display any significant statistical difference. The average TW was 82.35 daPa (SD= 23.21) for the sea-level group and 83.26 daPa (SD= 25.99) in the high-altitude group (Fig. 6). These results indicate that even though SC is lower at high altitude, the sharpness of tympanogram remained the same. Thus, higher altitude affects atmospheric-pressure-related factors of the middle ear but not the TW.

Discussion

Understanding how higher altitude affects body func- tions, especially hearing, is important for both physicians and scientists. However, limited studies have been published that focus on hearing function of the residents at high altitude. A previous paper demonstrated that the acoustic stapedius reflexes of Andean children living at the altitudes of 2,850 and 3,973 m were within the normal range, which indicated that higher altitude has no effect on hearing conduction (Counter et al., 2017). In contrast to that study, our article focused on the basic indexes of tympanometry that evaluated the compliance and pressure of tympanic cavity. This previous study selected their participants within 2–17 years of age, which covers a wide developmental spectrum of middle ear anatomical development. In their case, the influence of altitudes could be obscured by developmental differences. In our study, we carefully selected age-matched young adults to reduce the potential developmental disparity in middle ear performance. Fur- ther, we chose two regions with a 4,000 m altitudinal difference instead of only a 1,000 m elevation difference, allowing us to better identify factors that are strongly affected by altitude.

Our results suggest that SC measured by tympanometry was reduced at high altitude. To exclude any gender bias, we also selectively compared SC of the same gender from the two groups and found little difference, which agrees with the previous data (Wan and Wong, 2002). After normalizing the peak volume to pressure change, we found that the absolute compliance of the tympanic membrane was similar between the two groups. These results are consistent with FIG. 5. The participants in the high-altitude group had

lower TPP. The TPP in the sea-level group (blue dots) were 4.21 daPa. In contrast, in the high-altitude group (red dots), TPP were -3.87 dapa, which were significantly lower than controls. ***p< 0.05.

FIG. 6. Similar TW were found from both groups. The TW calculated from either sea-level group (blue dots) or high-altitude group (red dots) were similar. With 82.35 daPa in the sea-level group as controls, the average of TW for high-altitude groups was 83.26 daPa. There was no statistical difference identified.

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previous literature that middle ear compliance is mainly affected by structural features at low frequency, such as the ossicular chain and tympanic membrane (Mason, 2016).

Similarly, lower ECV at high altitude can also be explained by the reduced compressibility of air in the external ears.

However, ECV may also be influenced by other factors. It is possible that the disparity of external canal size contributed to the changed ECV, even though no obvious distinc- tion was noticed. Thus, our experiments indicate that the pressure-related indexes of tympanometry should be considered in light of the barometric pressure to avoid mistakes in diagnosis.

The TW, on the other hand, emerged as a reliable index for assessing middle ear conditions that are independent from the pump speed and barometric pressure (Shanks and Shohet, 2009). Considered as a valuable measurement in identifying otitis media, TW is a not only a complementary value, but also an underestimated index of tympanometry to evaluate the tympanum (Fiellau-Nikolajsen, 1983). As barometric pressure decreases at higher altitude, any pressure-related index loses accuracy unless a local atmospheric pressure adjustment is made. In this case, the TW becomes a better indication of the middle-ear trans- mission system.

The pressure within the middle ear decreases slightly, but with statistical significance at high altitude. Our results indicated that the Eustachian tube might not perform as well at high altitude. The opening of the Eustachian tube is closely related to the nasopharyngeal pressure. Thus, there is a pos- sibility that increased breathing effort at lower atmospheric pressure leads to decreased nasopharyngeal pressure, which can cause stiffness of the Eustachian tube opening. However, we must point out that even though the TPP at high altitude was statistically different from that at sea level, it was still within the normal range, and thus no adjustment is needed in clinical practice.

Although we have addressed several major factors that may influence the SC during tympanometry studies, we cannot completely rule out other parameters that may affect the outcomes, such as body temperature and body mass of each participant (Shahnaz and Davies, 2006). Moreover, our experiments were only performed on residents from two different altitudes. Thus, a comparison among larger groups of participants at multiple altitudes in future experiments could provide more insight on how lower barometric pressure affects the middle ear.

Conclusion

In conclusion, our experiments demonstrate that SC is lower during tympanometry measurements at high altitude, and it might be affected by lower barometric pressure.

However, the absolute compliance that is influenced by the structural compliance of middle ear remains the same. Hence, we propose that TW might be a more reliable index when evaluating the function of the tympanum in high-altitude regions.

Authors’ Contributions

Q.L. and H.Y. conceived and designed the work. T.J. and L.Z. collected the data from Shigatse. T.J. and Y.Y. per-

formed the examinations. T.J., L.Z., and H.Y. analyzed and interpreted the data. T.J., H.Y., and Q.L. wrote the article. All authors reviewed the article.

Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author on rea- sonable request.

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This work was supported by grants from the National Key Research and Development Program of China (2017YFA0103900, 2015CB965000), the National Natural Science Foundation of China (81300825), the National Natural Science Foundation of China Young Investigator program (81800907), the Nature Science Foundation of Tibet (ZX2017ZR-ZYZ17), and the National Science and Tech- nology Cooperation Program 2018 (18695840700). The authors thank Dr. Loksum Wong for reading their article and for the comments she provided.

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Address correspondence to:

Qingzhong Li, MD, PhD ENT Institute and Otorhinolaryngology Department Affiliated Eye and ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University 83 Fenyang Road Shanghai 200031 China

E-mail: [email protected] Huiqian Yu, MD, PhD ENT Institute and Otorhinolaryngology Department Affiliated Eye and ENT Hospital State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan University 83 Fenyang Road Shanghai 200031 China E-mail: [email protected]