Introduction

Tinnitus is a sound perceived in one or both ears even in the absence of a sound stimulus, which directly affects the quality of life of individuals [1-3]. The annoyance caused by tinnitus has negative impacts on the life of affected individuals, reducing concentration and sleep and compromising emotional balance and social life. Patients with complaints of tinnitus indicate the annoyance of the symptom to be distressing. There are reports of attempted suicide as a result of the despair and disability caused by tinnitus. In some cases, tinnitus is more debilitating than hearing loss. About 20% of patients with tinnitus report significant annoyance associated with major impairment of quality of life [4-7].

Tinnitus shows a strong association with hearing loss. However, about 10 to 20% of individuals with normal hearing thresholds have tinnitus in any time of life [8-13]. Several lines of research have been proposed to better understand the auditory pathway in tinnitus patients with normal hearing. One of these lines advocates that changes at central levels of the auditory system and in the efferent pathway, more specifically in the superior olivary complex, are one of the causes of tinnitus in normalhearing individuals, although the role of the efferent system in the etiology of tinnitus remains unclear [14-16].

The human cochlea receives afferent innervation (eighth pair) and innervation of ipsi- and contralateral efferent fibers of the superior olivary complex (olivocochlear bundle). The efferent olivocochlear bundle is composed of two systems: the medial system, which innervates outer hair cells, and the lateral system, which innervates inner hair cells. These two systems influence the modulation of cochlear activity both by exciting and inhibiting it. The function of these systems can be measured through the suppression of evoked otoacoustic emissions [17].

The otoacoustic emission (OAE) suppression test is an audiological test that assesses the efferent auditory system by investigating response amplitude suppression or changes in the latency and in the phase of EOAEs when a contralateral acoustic stimulus is introduced simultaneously to test recordings [14]. Suppression may be absent in cases of tinnitus, but its association with possible dysfunction in the medial efferent tract has not been confirmed.

The annoyance of tinnitus affects individuals in different ways. Thus, two patients may not perceive tinnitus in the same way, but all of them agree that the discomfort caused by it leads to anguish and despair [17-19].

There are no studies in the literature establishing a correlation between the level of annoyance reported by tinnitus patients and the OAE suppression test. Therefore, the aim of the present study was to investigate the occurrence of this association.

Methods

A case-control study was conducted at the Otolaryngology Department of Hospital de Base do Distrito Federal, city of Brasília, Brazil. The study was approved by the institutional Research Ethics Committee (Protocol No. 453.379).

Sample

The study sample was initially based on a population of 80 subjects with tinnitus and normal hearing determined by a hearing test. Next, OAE testing was performed and 20 subjects with normal results for distortion product otoacoustic emissions (DPOAEs) and transient evoked otoacoustic emissions (TEOAEs) were included in the study (tinnitus group). For the purpose of comparison, a control group was formed, which consisted of 17 subjects of both genders with confirmed presence of OAEs and no tinnitus complaints.

Subjects of both genders ranging in age from 20 to 60 years, who suffered from tinnitus, had normal hearing thresholds (up to 25 dB) in all frequency bands tested, type A tympanometric curves and DPOAEs and TEOAEs, and signed the written consent form were included in the study. Exclusion criteria were audiometry tests showed hearing thresholds above 25 dB or abnormal OAEs, the presence of neurological disorders, drug treatment for tinnitus and ototoxic drug use.

Procedures

The participants were submitted to the following assessments: anamnesis and evaluation of tinnitus annoyance by the Tinnitus Handicap Inventory (THI) and on a visual analog scale (VAS). Next, the subjects underwent DPOAE and TEOAE testing.

Patients with normal OAE test results were submitted to OAE suppression testing. The ILO USB-V6 Clinical OAE system from Otodynamics Ltd. was used. For analysis of the suppression effect, an ipsilateral linear click presented at an intensity of 65 dB NPS was used as the evoking stimulus. The suppressor noise consisted of contralateral white noise stimulation at intensity of 60 dB NPS. This intensity is safe to prevent the activation of reflex mechanisms in the middle ear. The equipment possesses a semi-automated method in which samplings are presented alternately in the presence or absence of the suppressor noise at an interval of 3 seconds.

After the suppression procedure, the difference in TEOAEs in the presence or absence of the contralateral noise was analyzed for each ear according to specific frequency (1, 1.4, 2, 2.8, and 4 Hz) and overall response (provided by the equipment). A value higher than 0.5 dB was defined as a suppression effect as described by Velenovsky & Glattke [20].

The data were analyzed and correlated using the SPSS 21.0 for Windows software. The results were tabulated and analyzed statistically using descriptive statistics and parametric (Student t-test) and nonparametric tests (Pearson’s chi-square test). Levene’s test was used to assess homogeneity of variances. The following analyses were performed: comparison of DPOAEs and TEOAEs and of the suppression effect of TEOAEs between the tinnitus and control groups; analysis of tinnitus annoyance and comparison with the TEOAE suppression test result, and trend analysis (ANOVA). A level of significance of ≤ 5% (p ≤ 0.05) was adopted.

Results

The tinnitus group consisted of 20 subjects aged 21 to 56 years (mean ± standard deviation: 37.8 ± 10.381 years). Thirty-four ears with tinnitus were studied, including 41.18% (n = 14) of males and 58.82% (n = 20) of females. The control group consisted of 17 subjects aged 22 to 57 years (32.41 ± 7.34 years). Thirty-four ears were studied, including 35.3% (n = 12) of males and 64.7% (n = 22) of females. Since no significant differences were found in the distribution of ears between groups (Levene’s test for homogeneity of variances = 2.74, p = 0.107), the results were reported according to ear.

DPOAE analysis showed higher amplitudes (S/R) in the control group at frequencies of 1, 1.4, 2, 2.8 and 8 kHz. Higher TEOAE amplitudes (S/R) were observed in the tinnitus group compared to control at all frequency bands tested, with a significant difference at the 1-kHz frequency (p = 0.005) (Table 1).

Table 1: Distribution of the amplitudes of transient evoked otoacoustic emissions in the tinnitus and control groups.

The amplitudes of the DPOAE and TEOAE responses were also compared according to gender.

No significant differences were observed; however, the mean response amplitude was higher in females both in the control and tinnitus groups at all frequencies tested.

No significant differences in the overall suppression effect or in the values according to frequency band were observed between the two groups. In the tinnitus group, a suppression effect was present in 47.1% (n = 16) of the subjects and was absent in 52.9% (n = 18), while in the control group a suppression effect was present in 67.6% (n = 23) and absent in 32.4% (n = 11) (Table 2).

Table 2: Analysis of the suppression effect of transient evoked otoacoustic emissions.

Regarding the discomfort caused by tinnitus and assessed by the THI, 38.2% (n = 13) of the participants were classified as having minimal or mild tinnitus and 61.8% (n = 21) as having moderate or severe tinnitus. There was no case of catastrophic tinnitus. Analysis of the discomfort caused by tinnitus on a VAS showed mild discomfort in 8.8% (n = 3) of the subjects, moderate discomfort in 41.2% (n = 14), and severe discomfort in 50% (n = 17).

The correlation between the discomfort caused by tinnitus and the level of TEOAE suppression was also analyzed. Among subjects who reported minimal/ mild discomfort, 38.5% (n = 5) exhibited no suppression effect of TEOAEs. Among subjects with mild/severe tinnitus, 61.9% (n = 13) exhibited no suppression effect of TEOAEs. However, the difference between these two groups was not statistically significant (Table 3).

Table 3: Association between the suppression effect of transient evoked otoacoustic emissions and tinnitus annoyance assessed by the Tinnitus Handicap Inventory in subjects of the tinnitus group.

Although no significant correlation was found between the discomfort caused by tinnitus and OAE suppression effects, the results were analyzed using tests for homogeneity of variances and trends. As can be seen in Figure 1, the absolute values of the suppression effect decreased with increasing discomfort caused by tinnitus.

Figure 1: Trends of suppression effects according to tinnitus intensity assessed by the Tinnitus Handicap Inventory in subjects of the tinnitus group (ANOVA for trend analysis).

Discussion

Tinnitus is a symptom that has major effects on many aspects of the life of affected individuals. The presentation of the symptom and the discomfort caused by it vary from case to case. A recent study published in The Lancet reported that tinnitus is more common in the left ear and usually progresses gradually, but a sudden onset may occur. In the present study, there was a predominance of bilateral tinnitus, and in cases of unilateral tinnitus the left ear was more frequently affected. Most participants of the tinnitus group (70%) reported a sudden onset of the symptom [4].

With respect to tinnitus periodicity, 80% of the subjects studied reported continuous tinnitus and 20% intermittent tinnitus. Sanchez et al. [21] observed continuous tinnitus in 69% of cases and data from the Oregon Hearing Research Center [22] revealed the presence of continuous tinnitus in 85 to 90% of the subjects studied.

Cortina et al. [23] investigated factors that improve and worsen the perception of tinnitus in 300 subjects with chronic tinnitus. Silence was reported to worsen tinnitus by 66% of the subjects, followed by nighttime (61%) and anxiety (54%). In the present study, silence was reported to worsen tinnitus by 70% of the patients and anxiety by 40%. Most participants (90%) reported tinnitus to get worse at night. Regarding factors that improve the symptom, in the study of Cortina et al. [23], noise was mentioned by 38% of the participants and periods of rest by 26%. In the present study, 30% of the patients reported background sounds (radio or TV) and music to improve tinnitus.

Analysis of DPOAEs and TEOAEs in the groups

Otoacoustic emissions are present in individuals with normal hearing thresholds and are no longer produced when the hearing loss is greater than 30 dB. Changes in cochlear function are likely to be detected by the OAE test before the audiogram shows hearing loss [24-26].

The risk of tinnitus is significantly increased in individuals with hearing loss. However, the annoyance caused by the symptom is not associated with the degree of hearing loss [11].

About 10 to 20% of patients with tinnitus have normal hearing thresholds. There are no epidemiological studies investigating the percentage of subjects with tinnitus, normal hearing thresholds and OAE as done in the present study; however, on the basis of important studies such as those of Paglialonga et al.[27] and Granjeiro et al. [28], this number is believed to be small [15].

Alterations in OAEs are more common in individuals with tinnitus compared to those without the symptom. Granjeiro [25], studying a group of subjects with tinnitus and normal hearing, observed altered TEOAEs and DPOAEs in 61.8% of this group, while this percentage was 23.9% in the control group. In a similar study, Paglialonga et al. [27] found altered DPOAE tests in 78% of subjects with tinnitus. The authors emphasized that DPOAEs were more sensitive in detecting outer hair cell dysfunction in individuals with tinnitus than TEOAEs.

The participants in the present study exhibited no changes in the DPOAE and TEOAE tests according to the protocol established in the methods section. Thus, the cochlear mechanism was completely or partly intact in this population.

Although the presence of normal OAEs was used as an inclusion criterion in the present study, the OAE response amplitudes were lower in tinnitus patients than in the control group; however, this difference was not statistically significant in the DPOAE or TEOAE test, in agreement with the findings reported above.

Sato et al. [29] and Miller [30] reported greater OAE response amplitudes in females, a fact that might be due to differences in anatomical configurations between genders. In the present study, although not statistically significant, the amplitudes of the DPOAE and TEOAE responses were also greater in women both in the tinnitus and control groups.

Suppression effect of OAEs

The suppression of evoked OAEs is a test that can add value to the diagnosis of different diseases since it is a noninvasive and relatively rapid procedure to evaluate the efferent auditory pathway. We found no studies in the literature providing reference statistics regarding the occurrence of normal OAE suppression in normal-hearing adults, but some studies involving a control group reported data about the presence of a suppression effect.

In the case of individuals with tinnitus, several studies have investigated the correlation between the presence of tinnitus and the absence of suppression of evoked OAEs, but there is still no consensus about this association [6,16,27,31-33].

The difficulty in verifying an association can be explained by the fact that tinnitus is a symptom of variable etiology which, in many cases, is multifactorial. It is therefore difficult for researchers to select a homogenous group of subjects with tinnitus for the development of studies.

Another factor that may have influenced data collection and analysis in studies investigating suppression effects is the lack of a well-established test protocol in terms of the type and intensity of the click and suppressor noise. Hood et al. [34] investigated the suppression of OAEs by testing different intensities of the contralateral noise (50, 55, 60, 65 and 70 dB) and concluded that an association exists between the suppressor noise and active cochlear mechanisms and efferent function. However, it was not the objective of that study to establish protocols for clinical practice.

The protocol adopted in this study was chosen based on its possible reproducibility in future studies and its application with the equipment used for data collection.

Mor & Azevedo [16], studying OAEs and the olivocochlear system in subjects with tinnitus and normal hearing, observed no significant difference in the OAE response amplitudes between the tinnitus and control groups in terms of general responses or according to frequency band. There was also no significant difference in the occurrence of suppression effects between the two groups, although the suppression values were lower in tinnitus patients. A stimulus of about 80 dB and a suppressor noise of 60 dB were used [16]. The results of that study agree with the findings of the present study in which no significant difference was observed; however, suppression effects were less frequent in the tinnitus group (47.1%) compared to the control group (67.6%).

Riga et al. [6] investigated the suppression of OAEs in 18 subjects with tinnitus and normal hearing. The protocol consisted of the evaluation of DPOAEs using a contralateral noise of 55 dB. The authors found lower OAE response amplitudes in the tinnitus group compared to the group without the symptom, but the difference was not significant as observed in the present study.

Chéry-Croze et al. [35] evaluated suppression of DPOAEs using a suppressor noise of 60 dB. In contrast to the present study in which ears were analyzed independently, these authors performed an analysis according to subject and observed that in subjects with unilateral tinnitus the efferent system seemed less efficient on the side of the symptom since OAE suppression was lower in ears with tinnitus [35].

Studying 30 subjects with tinnitus and a control group, Geven et al.[32] observed no significant differences in the overall analysis of OAE suppression. The authors concluded that the amount of contralateral suppression was equal in tinnitus patients and control subjects, except for the 2.0- and 2.8-kHz frequency bands in the right ear for which tinnitus patients presented a lower suppression effect. The protocol consisted of TEOAE analysis using a stimulus of 65 dB and a contralateral noise of 70 dB.

In the present study, no significant differences in the overall suppression effect were observed between groups, but there was a significant difference at the 1-kHz frequency. Fávero et al. [31] found a significant strong association between the absence of suppression and the presence of tinnitus in the frequency range of 1.5 to 4 kHz.

Tinnitus annoyance and TEOAE suppression test

The prevalence of tinnitus is high and this condition is the third worst symptom after severe and intractable pain and dizziness. The annoyance caused by tinnitus severely impairs the quality of life of about 2% of the population. Tinnitus annoyance also has socioeconomic consequences. Patients who require sick leave due to tinnitus are up to three times more likely to receive disability retirement than patients with other diseases [36].

The annoyance caused by tinnitus does not seem to be related to factors such as gender, location of the symptom, age or hearing loss, and affects each individual in a different manner. Studies have reported that the annoyance of tinnitus decreases over time, suggesting that the patient becomes accustomed to the symptom [37,38].

The objective of the present study was to verify the existence of a possible relationship between annoyance reported by patients with tinnitus and normal hearing and the TEOAE suppression test. Tinnitus patients exhibited a lower overall suppression effect and suppression according to frequency than control subjects. However, the difference between the overall results showed no significant association. The value of OAE suppression of tended to decrease as the level of annoyance caused by tinnitus increased. This finding provides further evidence of involvement of the efferent system in the generation of tinnitus.

Since tinnitus is a symptom of multifactorial origin and is often associated with other conditions, psychiatric aspects should also be taken into consideration. A large proportion of patients with tinnitus have anxiety and depression disorders associated with the symptom. The clinical evaluation of patients reporting annoyance of tinnitus should also include the assessment of mental state. Patients with tinnitus are more likely to develop symptoms of depression than those without tinnitus [28].

In another study, Granjeiro et al.[25] demonstrated that tinnitus annoyance was not correlated with outer hair cell function when normal and altered TEOAEs and DPOAEs were evaluated. The authors suggested that, although cochlear dysfunction is a possible cause of tinnitus, it is not associated with the annoyance caused by the symptom. In that study, a significant association was found between the discomfort reported by tinnitus patients and anxiety and depression scores [25].

The objective of the present study was to evaluate the relationship between tinnitus annoyance and suppression of OAEs, but not related psychiatric aspects. Studies in the literature have reported an association between tinnitus annoyance, anxiety, and depression.

Kehrle [39] evaluated the level of annoyance in tinnitus patients with normal hearing thresholds and compared it to the results of the brainstem auditory evoked response test and to anxiety and depression scores. The authors concluded that tinnitus annoyance is not associated with normal or abnormal brainstem auditory evoked potentials (BAEPs), suggesting that dysfunction at the brainstem level is not related to annoyance. However, the authors found statistically significant results when anxiety and depression were analyzed. The results of that study demonstrated that the severity of tinnitus annoyance is associated with the severity of anxiety and depression disorders and not the auditory causes themselves [39].

The present study and the studies of Granjeiro et al. [28] and Kehrle [39] suggest that the annoyance caused by tinnitus is not associated with outer hair cell function or BAEPs, and also does not seem to be related to dysfunction of the medial efferent system

In summary, suppression effects were absent in a considerable proportion of the tinnitus patients studied. However, this finding was also common in control subjects, with no significant difference between groups. The OAE suppression test only evaluates a small part of the efferent system, i.e., the medial olivocochlear system. The present study suggests that, although dysfunction of the medial efferent system is one of the theories accepted as an etiology of tinnitus, the changes found in this system do not seem to be related to the annoyance reported by the patients of this study.

It should be noted that there was a statistical trend indicating a decrease in the value of OAE suppression as the level of tinnitus annoyance increased.

It is possible that the protocol used in this study or even the OAE suppression test does not present adequate sensitivity and specificity to differentiate patients with tinnitus and controls. Further studies involving a larger sample of tinnitus patients with normal hearing in each annoyance category are needed, despite the difficulty in obtaining a homogeneous group of subjects with tinnitus and normal hearing thresholds and OAE tests.

The present results showed the lack of a significant correlation between the annoyance reported by tinnitus patients with normal hearing thresholds and the TEOAE suppression test result.

Most participants classified the discomfort caused by tinnitus as moderate/severe and none of the patients reported catastrophic tinnitus.

The TEOAE suppression test results were more frequently altered in tinnitus patients compared to control subjects, but the difference was not significant. The effect of supression tends to be less important as the annoyance increases.

This study did not receive any financial support.

Acknowledgments

We thank Dr. Julival Fagundes Ribeiro, Director of Hospital de Base do Distrito Federal (HBDF), and Dr. Jader Reis Rebouças Filho, Head of the Otorhinolaryngology Service, HBDF, for permitting this study on the premises of the Hospital.

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