SERUM BIOMARKERS AND NOISE-INDUCED HEARING LOSS.

INTRODUCTION

Noise-induced hearing loss (NIHL) is the most common form of sensori-neural hearing loss caused by exposure to noise. Exposure to high intensity sound (noise) affects the outer hair cell plasma membrane liquidity ¹.

Sensori-neural hearing loss (SNHL) is the commonest type of hearing loss due to damage of hair cells (receptor of hearing), degeneration of neurons & or neuron-hair cell junction ². The most common causes of SNHL are degenerative changes associated with age, noise exposure, drugs that have ototoxic effect & rarely due to genetic changes ³.

It is known that around 1.2 billion cases of hearing disorders are due to exposure to high intensity sound worldwide ⁴. Exposure to high intensity sound levels for long duration, is the cause of about 16% of cases of hearing loss in adults worldwide ^4,5&6.

Exposure to high intensity sound leads to irreversible damage of hair cells by multiple pathological mechanisms. The hair like projection (stereocilia) on hair cells surface are easily damaged by mechanical trauma caused by the high intensity sound, directly affecting the cellular organization of the organ of Corti. Also, the severe and profound types of hearing loss is not only due to mechanical effect of high intensity sound; but also due to other factors such as increase of the free radicals that affect the growth of hair cells ².

The affecting mechanisms primarily involves the contraction of outer hair cells, derived by changes in potential membrane and mediated by prestin ⁷.

Prestin, is a protein in the outer hair cells (OHCs) that is responsible for good electro-motility of the cells and so, any changes in the level of the prestin can affect the electro-motility of the hair cells and lead to hearing disorders ⁸.

Prestin is an essential protein required for good functioning of the inner ear as the noise induced restricted expression of it results in hearing loss. A molecular targeted delivery of polymersomes mediated drug (prestin) in OHC with some degree of hearing loss has led to complete cure or at least some improvement of the hearing disorder ^{9, 10&11}.

Otolin-1 is a glycoprotein specifically secreted in the inner ear ¹². Its mRNA expression is restricted to the vestibular part of the inner ear, in addition to stria vascularis of organ of Corti ¹³. It interacts with prestin to improve the function of the inner ear. Therefore, these two protein can possibly be used as circulatory biomarkers special for NIHL ¹⁴.

The aim of this study is to investigate the relationship between serum Prestin and Otolin-1 levels and noise-induced hearing loss.

PATIENTS AND METHODS

This cross-sectional study was conducted on one hundred (100) patients with NIHL representing the study group.  Another fifty (50) normal healthy adult subjects were selected from relatives accompanying patients representing the control group. The age of both groups ranged from (20-40) years and represented both genders. All patients and controls were recruited from Damietta, Al-Azhar University Hospital, Egypt from May 2018 to December 2020.

This study was approved by the local ethics and research committee of Al-Azhar Faculty of Medicine in New Damietta. An informed consent was taken from all patients before starting the study.

For the control group, the inclusion criteria was the normal otoscopic finding, normal hearing threshold and normal middle ear functions as evidenced by tympanometry and acoustic reflex with no history of ear diseases nor any history of medical systemic diseases such as any rheumatic diseases, diabetes mellitus, hypertension, smoking, renal and cardiovascular diseases. The patients group have the same criteria of the control group except that they are having
a history of noise exposure and/or mobile phone users for more than one hour/day.

Instrumentation:

Sound treated room locally made according to international specifications.

One channel intracoustic audiometer GSI (model AD229b), calibrated according to ANSI standards.

Impedance-meter Interacoustics (model AT235).

Methods:

All individuals participated were subjected to the following:

Full history taken to exclude systemic diseases, noise exposure, ototoxic drug intake, and family history of hearing impairment.

Otological examination.

Basic audiological evaluation, which included the following:

Pure tone audiometry from (250 – 8000 Hz) for air conduction, from (500 – 4000 Hz) for bone conduction in octave steps. The air conduction stimulus was delivered via supra-aural headphone model TDH 39P. The bone conduction was delivered via bone conduction vibrator model B71.

Speech audiometry including:

Speech reception threshold (SRT) using Arabic spondee words.

Speech discrimination scores using phonetically Arab balanced words (PB words).

Impedancemetry included:

Tympanometry done at pressure range from (+200 to –400 mm H₂O).

Acoustic reflex threshold elicited ipsilaterally and contralaterally using frequency range of (500 up to 4000Hz).

Laboratory tests for the assessment of blood prestin & otolin-1 levels were done by ELISA.

Statistical analysis

Statistical analyses were completed using SPSS v23 statistical software (SPSS, Inc, Chicago, Illinois). Descriptive statistics (means, standard deviations, frequencies, and correlation coefficients) were calculated for all measures.  To compare between two groups, a paired t‐test was carried out to determine P values using the Pearson’s correlation test and a χ² test and a one‐sample t‐test and Wilcoxon test were performed when appropriate. In comparison between more than two groups (F) test by Analysis of Variance (ANOVA), p less than 0.05 was considered statistically significant.

RESULTS

The study included 100 NIHL patients (66 males and 34 females) representing the patients’ group with the age ranging from 30 to 50 years (mean ± SD of 41.6 ± 6.12 years). The 50 apparently healthy subjects (30 males and 20 females) represent the control group with age ranging from 26 to 48 years (mean ± SD of 39.7 ± 5.93 years). The two groups were matched in sex and age (P >0.05) as well as smoking habit which was present in 68.0% of patients and 62% of controls as shown in table (1).

Measurement of air conduction hearing thresholds of both right and left ears shows significant decline in NIHL patients compared to control subjects. Bone conduction hearing thresholds of both right and left ears showed significant elevation in NIHL in patients compared to control subjects. Pure tone audiometry (PTA) showed a statistically significant decrease in NIHL compared to controls (P <0.05), Table (2). The level of noise exposure also showed statistically significant values (P <0.05) between the two groups as shown in Table (2).

The serum Otolin-1 and Prestin levels were significantly higher in NIHL group compared to control subjects (P <0.05) as shown in Table (3). Comparison between serum Otolin-1 and Prestin biomarkers regarding their accuracy showed highly significant values in detection of hearing loss as shown in Table (4).

χ² = Chi square test, P >0.05= non-significant.

Table 1: Demographic characteristics of the studied groups.

* P <0.05= significant. PTA: pure tone audiometry, db: decibel.

Table 2: Tests of hearing function and exposure level in both groups.

* P <0.001= highly significant.

Table 3: Serum Prestin and Otolin-1 levels in both groups.

*P < 0.001 = highly significant.

Table 4: Comparison between serum Prestin and Otolin-1 biomarkers regarding their accuracy of hearing loss detection.