Multifunctional redox modulator prevents blast-induced loss of cochlear and vestibular hair cells and auditory spiral ganglion neurons.

Blast wave exposure, a leading cause of hearing loss and balance dysfunction among military personnel, arises primarily from direct mechanical damage to the mechanosensory hair cells and supporting structures or indirectly through excessive oxidative stress. We previously reported that HK-2, an orally active, multifunctional redox modulator (MFRM), was highly effective in reducing both hearing loss and hair cells loss in rats exposed to a moderate intensity workday noise that likely damages the cochlea primarily from oxidative stress versus direct mechanical trauma. To determine if HK-2 could also protect cochlear and vestibular cells from damage caused primarily from direct blast-induced mechanical trauma versus oxidative stress, we exposed rats to six blasts of 186 dB peak SPL. The rats were divided into four groups: (B) blast alone, (BEP) blast plus earplugs, (BHK-2) blast plus HK-2 and (BEPHK-2) blast plus earplugs plus HK-2. HK-2 was orally administered at 50 mg/kg/d from 7-days before to 30-day after the blast exposure. Cochlear and vestibular tissues were harvested 60-d post-exposure and evaluated for loss of outer hair cells (OHC), inner hair cells (IHC), auditory nerve fibers (ANF), spiral ganglion neurons (SGN) and vestibular hair cells in the saccule, utricle and semicircular canals. In the untreated blast-exposed group (B), massive losses occurred to OHC, IHC, ANF, SGN and only the vestibular hair cells in the striola region of the saccule. In contrast, rats treated with HK-2 (BHK-2) sustained significantly less OHC (67%) and IHC (57%) loss compared to the B group. OHC and IHC losses were smallest in the BEPHK-2 group, but not significantly different from the BEP group indicating lack of protective synergy between EP and HK-2. There was no loss of ANF, SGN or saccular hair cells in the BHK-2, BEP and BEPHK-2 groups. Thus, HK-2 not only significantly reduced OHC and IHC damage, but completely prevented loss of ANF, SGN and saccule hair cells. The powerful protective effects of this oral MFRM make HK-2 an extremely promising candidate for human clinical trials.

Awareness, attitudes and perceptions of students towards leisure noise in Durban, South Africa.

BACKGROUND:  Young adults are exposed to high noise levels in leisure venues, which increases their risk of hearing loss, and can affect their quality of life. OBJECTIVES:  The aim of this study was to describe the young adults' awareness, attitudes and perceptions towards leisure noise at a university in South Africa. METHOD:  A descriptive cross-sectional study design with quantitative methods of data was considered for this study. Students from first to fourth years in the Education Department of a local university in Durban, South Africa, who were aged 18 years old - 25 years old were invited to participate in an online survey. RESULTS:  Of the 462 participants, most had a general awareness on noise and hearing loss but lacked knowledge on the negative effect of loud noise, with 95.2% using personal listening devices, followed by visiting restaurants and gyms, and 48.3% being unsure if noise can damage hearing permanently. They were unaware of methods to reduce their exposure to noise. A significant relationship between awareness of noise and attitudes (p = 0.029) indicated that the higher the level of awareness regarding leisure noise, the better their attitude and behaviour, thus the lower the risk of hearing loss. CONCLUSION:  The results highlight the need for implementing the World Health Organization (WHO) noise regulations and providing education for this age group to prevent irreversible hearing loss through exposure to leisure noise.Contribution: A national study is recommended to increase research evidence.

[A study on the hearing protection and intervention effects of silicone earplug usage among manufacturing workers].

Objective: To assess the efficacy of silicone earplugs in protecting workers exposed to noise in a typical manufacturing environment, and to provide training interventions for workers who do not achieve the anticipated noise reduction levels, as well as examining the spectral characteristics of earplug attenuation. Methods: From June to August 2022, a total of 294 noise-exposed workers in two manufacturing enterprises equipped with the same type of earplug were studied by cluster sampling method, by conducting questionnaire surveys, collecting data, fitting tests, and providing trainings, the current noise exposure levels of workers in the industry as well as the perception about the earplug were understood. Additionally, the attenuation before and after intervention in workplace were measured, the spectral characteristics of noise reduction were were described and compared. Results: The percentage of workers with Personal Attenuation Rating (PAR) of 0 is 32.7% (96/294), and the baseline pass rates are all below 60%. There were no significant differences in pass rates based on gender, age, noise exposure, education level, or cognition of earplug effectiveness. After adjusting the way that earplugs are worn or changing the type of earplugs, all workers were able to meet their noise reduction requirements. The median PAR improvement for both companies is above 10 dB. The noise attenuation of the earplug vary with frequency, with lower attenuation at 4 000 Hz and higher attenuation at 8 000 Hz, showing some deviation from the nominal values. Conclusion: The difference between the actual sound attenuation value of earplugs and the nominal value is related to the noise frequency. When using silicone earplugs, attention should be paid to the spectral composition of the noise in the workplace.

In silico transcriptome screens identify epidermal growth factor receptor inhibitors as therapeutics for noise-induced hearing loss.

Noise-induced hearing loss (NIHL) is a common sensorineural hearing impairment that lacks U.S. Food and Drug Administration-approved drugs. To fill the gap in effective screening models, we used an in silico transcriptome-based drug screening approach, identifying 22 biological pathways and 64 potential small molecule treatments for NIHL. Two of these, afatinib and zorifertinib [epidermal growth factor receptor (EGFR) inhibitors], showed efficacy in zebrafish and mouse models. Further tests with EGFR knockout mice and EGF-morpholino zebrafish confirmed their protective role against NIHL. Molecular studies in mice highlighted EGFR's crucial involvement in NIHL and the protective effect of zorifertinib. When given orally, zorifertinib was found in the perilymph with favorable pharmacokinetics. In addition, zorifertinib combined with AZD5438 (a cyclin-dependent kinase 2 inhibitor) synergistically prevented NIHL in zebrafish. Our results underscore the potential for in silico transcriptome-based drug screening in diseases lacking efficient models and suggest EGFR inhibitors as potential treatments for NIHL, meriting clinical trials.

A Comprehensive Review of Auditory and Non-Auditory Effects of Noise on Human Health.

OBJECTIVE: Excessive noise is unpleasant and induces several physiological and psychological effects. Noise pollution is a potential threat to humans, particularly those continuously exposed for extended periods throughout the day over many years. This review aims to examine the various auditory and non-auditory outcomes associated with prolonged exposure to noise pollution. MATERIALS AND METHODS: The review utilized a combination of relevant keywords to search the electronic databases. After screening based on the applied selection criteria for title, abstract, and full text, 44 articles were finally selected for critical review. RESULTS: We identified and analyzed research findings related to noise-induced hearing loss, tinnitus, and sleep disturbances along with non-auditory issues such as annoyance, cognitive impairments, and mental stress associated with cardiovascular disorders. Furthermore, the existing studies were compared and collated to highlight the unique challenges and significance of noise pollution as a distinctive environmental concern and to explore the ongoing efforts in its research and prevention, including the early detection and potential reversal of noise-induced hearing loss. CONCLUSION: The fundamental health consequences of noise pollution underscore the need for extensive research encompassing emerging noise sources and technologies to establish a health management system tailored to address noise-related health concerns and reduce noise exposure risk among populations. Finally, further research is warranted to ensure improved measurement of noise exposure and related health outcomes, especially in the context of occupational noise.

Cross-sectional study on the health of workers exposed to occupational noise in China.

OBJECTIVE: This study aimed to understand the health of workers exposed to occupational noise and explore the influencing factors related to workers' health, especially the impact of noise on workers' hearing. This work can provide a basis for formulating relevant measures for occupational noise prevention and control in the future. METHODS: On the basis of the key occupational disease monitoring project in Chongqing, China, in 2021, the data of 1125 workers exposed to occupational noise were analyzed. Data included demographic information, occupational history, clinical physical examination information, and noise detection information of the working environment. Chi-square test and multifactorial logistic regression were used for statistical analysis. RESULTS: The prevalence rates of abnormal electrocardiogram (ECG), blood pressure (BP), and pure tone audiometry (PTA) were 21.9% (246/1125), 27.8% (313/1125), and 18.0% (202/1125), respectively. Male workers accounted for 78.8%. Compared with male workers, female workers had a lower prevalence of abnormal PTA (OR = 0.28, 95% CI = 0.16-0.50). Workers working in medium enterprises had a lower prevalence of abnormal BP than workers in micro enterprises (OR = 0.36, 95% CI = 0.19-0.66). The prevalence of abnormal BP and PTA of workers increased with age. After adjusting for age, sex, and body mass index, the prevalence of abnormal ECG of mining workers was higher than that of manufacturing workers (OR = 1.54, 95% CI = 1.07-2.24), and the prevalence of abnormal PTA had a rising trend with the increase in noise exposure value. CONCLUSION: Noise-exposed workers have a high prevalence of abnormal ECG, BP, and PTA, and factors such as age, enterprise size, and workplace noise exposure are correlated with the aberrant health of workers. Governments, enterprises, and individuals need to attach great importance to the possible adverse effects of noise. They must also actively adopt various effective measures to protect the occupational safety and health of workers.

ERK1/2 Inhibition via the Oral Administration of Tizaterkib Alleviates Noise-Induced Hearing Loss While Tempering down the Immune Response.

Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to prevent it. Downregulating the mitogen-activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL, but the molecular targets and the mechanism of protection are not fully understood. Here, we tested specifically the role of the kinases ERK1/2 in noise otoprotection using a newly developed, highly specific ERK1/2 inhibitor, tizaterkib, in preclinical animal models. Tizaterkib is currently being tested in phase 1 clinical trials for cancer treatment and has high oral bioavailability and low predicted systemic toxicity in mice and humans. In this study, we performed dose-response measurements of tizaterkib's efficacy against permanent NIHL in adult FVB/NJ mice, and its minimum effective dose (0.5 mg/kg/bw), therapeutic index (>50), and window of opportunity (<48 h) were determined. The drug, administered orally twice daily for 3 days, 24 h after 2 h of 100 dB or 106 dB SPL noise exposure, at a dose equivalent to what is prescribed currently for humans in clinical trials, conferred an average protection of 20-25 dB SPL in both female and male mice. The drug shielded mice from the noise-induced synaptic damage which occurs following loud noise exposure. Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases' inhibition could be a promising strategy for the treatment of NIHL.

ABCC1 deficiency potentiated noise-induced hearing loss in mice by impairing cochlear antioxidant capacity.

The ABCC1 gene belongs to the ATP-binding cassette membrane transporter superfamily, which plays a crucial role in the efflux of various endogenous and exogenous substances. Mutations in ABCC1 can result in autosomal dominant hearing loss. However, the specific roles of ABCC1 in auditory function are not fully understood. Through immunofluorescence, we found that ABCC1 was expressed in microvascular endothelial cells (ECs) of the stria vascularis (StV) in the murine cochlea. Then, an Abcc1 knockout mouse model was established by using CRISPR/Cas9 technology to elucidate the role of ABCC1 in the inner ear. The ABR threshold did not significantly differ between WT and Abcc1-/- mice at any age studied. After noise exposure, the ABR thresholds of the WT and Abcc1-/- mice were significantly elevated. Interestingly, after 14 days of noise exposure, ABR thresholds largely returned to pre-exposure levels in WT mice but not in Abcc1-/- mice. Our subsequent experiments showed that microvascular integrity in the StV was compromised and that the number of outer hair cells and the number of ribbons were significantly decreased in the cochleae of Abcc1-/- mice post-exposure. Besides, the production of ROS and the accumulation of 4-HNE significantly increased. Furthermore, StV microvascular ECs were cultured to elucidate the role of ABCC1 in these cells under glucose oxidase challenge. Notably, 30 U/L glucose oxidase (GO) induced severe oxidative stress damage in Abcc1-/- cells. Compared with WT cells, the ROS and 4-HNE levels and the apoptotic rate were significantly elevated in Abcc1-/- cells. In addition, the reduced GSH/GSSG ratio was significantly decreased in Abcc1-/- cells after GO treatment. Taken together, Abcc1-/- mice are more susceptible to noise-induced hearing loss, possibly because ABCC1 knockdown compromises the GSH antioxidant system of StV ECs. The exogenous antioxidant N-acetylcysteine (NAC) may protect against oxidative damage in Abcc1-/- murine cochleae and ECs.

Advancing noise management in aviation: Strategic approaches for preventing noise-induced hearing loss.

As urbanization and population growth escalate, the challenge of noise pollution intensifies, particularly within the aviation industry. This review examines current insights into noise-induced hearing loss (NIHL) in aviation, highlighting the risks to pilots, cabin crew, aircraft maintenance engineers, and ground staff from continuous exposure to high-level noise. It evaluates existing noise management and hearing conservation strategies, identifying key obstacles and exploring new technological solutions. While progress in developing protective devices and noise control technologies is evident, gaps in their widespread implementation persist. The study underscores the need for an integrated strategy combining regulatory compliance, technological advances, and targeted educational efforts. It advocates for global collaboration and policy development to safeguard the auditory health of aviation workers and proposes a strategic framework to enhance hearing conservation practices within the unique challenges of the aviation sector.

Influence of Different Noise Types on Hearing Function in Patients Treated for Mild Otitis Media.

BACKGROUND: Otitis media (OM) refers to a common clinical ear disease. Noise seriously damages human hearing function. This study aimed to investigate the effects of various noise types on the hearing function of patients who have recovered from mild OM. MATERIALS AND METHODS: A total of 160 patients with mild OM treated at our hospital from May 2020 to May 2023 were retrospectively selected for this study. Based on clinical data, the patients were divided into the non-noise group (n = 80) and the noise (n = 80) group. The hearing thresholds of the two groups were compared across various noise types at 500, 1000, and 2000 Hz. In addition, the hearing thresholds of the noise group were compared under the same conditions. RESULTS: The noise group exhibited significantly higher hearing thresholds at 500, 1000, and 2000 Hz than the non-noise group (P < 0.05). Under traffic, urban construction, and industrial noises, the auditory thresholds at 500, 1000, and 2000 Hz in the noise group were significantly higher than those observed under domestic and speech noises (P < 0.05). CONCLUSION: Noise shows a close relationship with the hearing function of patients with OM. Traffic, urban construction, and industrial noises greatly influence the hearing function of patients who have recovered from mild OM.

Oxidative Stress Assessment of Noise Exposure in the Workers Using Hearing Protection in a Pressing Industry.

BACKGROUND AND OBJECTIVE: Exposure to noise by generation of free radicals causes oxidative stress in body. The aim of this study was the evaluation of oxidative stress in workers who have used hearing protection devices during working time. MATERIAL AND METHOD: Pressing workers (n=24) of a home appliance industry were studied using hearing protection devices to reduce noise exposure. Twenty two office staff (without exposure to noise) were considered as a control group. Two groups were matched for age, work experience and smoking. Exposure to noise was measured by dosimeter method at workstations. By obtaining 3 ml blood sample, Malondialdehyde levels, Thiol groups and total antioxidant capacity were evaluated in all subjects. RESULTS: Exposure to sound pressure level in pressing workers by considering the noise reduction factor of the earplug was observed in 77.65 dB with minimum 75.1 dB and Maximum 81.22 dB. Plasma thiol groups (0.076 (0.041-0.119) vs (0.110 (0.076-0.197), mmol/l P =0.0001) and total antioxidant capacity (361.33± 54.65 vs 414.14± 96.82, µmol/ml P = 0.026) in pressing workers significantly decreased than control group. Pearson correlation showed significant results between exposure to noise and oxidative stress parameters. CONCLUSION: Exposure to noise wave cause oxidative stress in different site of body. Oxidative stress is an intermediate way for different disease due to noise exposure. Reducing of noise exposure by earplug in pressing workers is not efficient protection for oxidative stress generation. Therefore, hearing protection devices are not a barrier to the harmful effects of noise in occupational exposure.

Sources of noise exposure across Australian workplaces: cross-sectional analysis and modelling the impact of a targeted noise-source reduction initiative.

CONTEXT: Workplace noise regulations and guidance follow the hierarchy of control model that prioritizes eliminating or reducing noise at its source. OBJECTIVES: To determine the main sources of workplace noise exposure in the Australian working population and estimate the reduction of workers exposed over the noise limit (LAeq,8h > 85 dB) if noise levels of specific tools or equipment were reduced by 10 dB. METHODS: Information on the tools used and tasks performed during each participant's last working shift was collected from 4,977 workers via telephone survey. Using a predetermined database of task-based noise levels, partial noise exposures (Pa2h) were determined for each noisy activity performed by the workers and their daily noise exposure level (LAeq,8h) was estimated. Partial exposures were categorized into 15 tool/task groups and the tally, average, and sum (Pa2h) for each group were calculated. The impacts of 5 different scenarios that simulated a reduction of 10 dB in noise emissions for specific tool groups were modelled. RESULTS: Powered tools and equipment were responsible for 59.3% of all noise exposure (Pa2h); vehicles for 10.6%; mining, refineries, and plant equipment for 5.1%; and manufacturing and food processing for 4.2%. Modelling demonstrated that a 10 dBA noise-level reduction of all powered tools and equipment would lead to a 26.4% (95% confidence interval: 22.7% to 30.3%) reduction of workers with an LAeq,8h > 85 dB. This could represent over 350,000 Australian workers no longer exposed above the workplace limit daily. CONCLUSIONS: A universal reduction of 10 dB to power tools and equipment would substantially reduce the future burden of hearing loss, tinnitus, workplace injuries, and other health effects. Initiatives to reduce the noise emissions of specific powered tool groups are warranted.

[Quantitative analysis of the characteristics and influencing factors of hearing loss among workers exposed to noise in Tianjin].

Objective: To analyze the characteristics of high-frequency average hearing loss in both ears of noise exposed workers in Tianjin in 2020, and quantitatively analyze the influencing factors of high-frequency hearing loss in both ears of workers. Methods: In March 2023, Collect and organize basic information about noise-hazardous enterprises and personal information of workers exposed to noise. Data from the Tianjin Occupational Disease and Health Hazard Factors Information Monitoring System from January 2020 to December 2020, and analyze the impact of basic information of employees, enterprise size, regional distribution, industry category, and economic type on the high-frequency average hearing loss of workers during work. Apply logistic regression to quantitatively analyze the influencing factors of abnormal high-frequency average hearing threshold of noise exposed workers. Results: The size, economic type, industry category, and regional distribution of enterprises, as well as the gender, age, length of service of workers, have an impact on the abnormal high-frequency average hearing threshold of noise exposed workers (χ(2)=733.56、3 497、27、1352.84、1197.62、2570.59、22.30、506.60, P<0.001) . Quantitative analysis using a logistic regression model showed that in the basic information of workers, noise exposed workers were male (OR=2.500, P<0.001) and aged 30-39, 40-49, and 50-59 years (OR=1.33, P<0.001; OR=1.68, P<0.001; OR=1.52, P< 0.001) , with a length of service of 4 to<10 years and≥10 years (OR=1.08, P<0.001; OR=1.615, P<0.001) being the influencing factors for high-frequency hearing loss in both ears of noise exposed workers; In terms of enterprise characteristics, medium-sized, small and micro enterprises (OR=1.12, P<0.001; OR=1.75, P<0.001; OR=2.09, P<0.001) , enterprises located in the fourth district around the city (OR=1.268, P<0.001) , and enterprises with economic types of collective economy, other economy, private economy, Hong Kong, Macao and Taiwan investment, shareholding system, and other industry economies (OR are all >1, P<0.001) are all factors affecting high-frequency hearing loss in noise exposed personnel. Conclusion: Noise is a common occupational hazard factor in Tianjin's enterprises, especially for workers in micro enterprises who face a high risk of hearing abnormalities. Therefore, enterprises need to strengthen the management and intervention of noise operations to prevent the occurrence of hearing loss in workers.

Murine cochlear damage models in the context of hair cell regeneration research.

Understanding the complex pathologies associated with hearing loss is a significant motivation for conducting inner ear research. Lifelong exposure to loud noise, ototoxic drugs, genetic diversity, sex, and aging collectively contribute to human hearing loss. Replicating this pathology in research animals is challenging because hearing impairment has varied causes and different manifestations. A central aspect, however, is the loss of sensory hair cells and the inability of the mammalian cochlea to replace them. Researching therapeutic strategies to rekindle regenerative cochlear capacity, therefore, requires the generation of animal models in which cochlear hair cells are eliminated. This review discusses different approaches to ablate cochlear hair cells in adult mice. We inventoried the cochlear cyto- and histo-pathology caused by acoustic overstimulation, systemic and locally applied drugs, and various genetic tools. The focus is not to prescribe a perfect damage model but to highlight the limitations and advantages of existing approaches and identify areas for further refinement of damage models for use in regenerative studies.

White noise use among children undergoing sound field audiometry: A preliminary study.

OBJECTIVE: To describe the prevalence of routine white noise exposure in children who undergo sound field audiometry. METHODS: A retrospective cohort study was conducted at a pediatric otolaryngology clinic affiliated with an academic tertiary care hospital. The medical records of children who underwent sound field audiometry were reviewed and data was collected regarding demographics and audiogram results. The group was divided into two cohorts based on routine exposure to white noise. Children exposed to white noise were tested with warble tones, while those not exposed were tested with narrow-band noise. RESULTS: 127 patients underwent sound field audiometry testing, of which 96 (75.6%) were reported by their parents to use white noise for sleep. The mean age at time of testing was 1.6 years (95% Confidence Interval [CI] 1.5-1.7). 104 (81.9%) children were able to respond to at least four of the sound field thresholds, and there was no significant difference between the children exposed to white noise and those who were not (P = 0.459). Mean pure tone average (PTA) was 26.2 dB (95% CI 25.2-27.2) and mean speech reception threshold (SRT) was 19.2 dB (95% CI 18.2-20.2). The sound field response rate, PTA, and SRT were similar between these two groups. CONCLUSIONS: The routine use of white noise therapy was extremely common in this pediatric population. The use of warble tones as the audiometric stimuli for children exposed to white noise resulted in similar testing success compared to the use of narrow-band noise in children not exposed to white noise.

Hearing protection field attenuation estimation systems and associated training for reducing workers' exposure to noise.

BACKGROUND: Global Burden of Disease studies identify hearing loss as the third leading cause of years lived with a disability. Their estimates point to large societal and individual costs from unaddressed hearing difficulties. Workplace noise is an important modifiable risk factor; if addressed, it could significantly reduce the global burden of disease. In practice, providing hearing protection devices (HPDs) is the most common intervention to reduce noise exposure at work. However, lack of fit of HPDs, especially earplugs, can greatly limit their effectiveness. This may be the case for 40% of users. Testing the fit and providing instructions to improve noise attenuation might be effective. In the past two decades, hearing protection fit-test systems have been developed and evaluated in the field. They are called field attenuation estimation systems. They measure the noise attenuation obtained by individual workers using HPDs. If there is a lack of fit, instruction for better fit is provided, and may lead to better noise attenuation obtained by HPDs. OBJECTIVES: To assess: (1) the effects of field attenuation estimation systems and associated training on the noise attenuation obtained by HPDs compared to no instruction or to less instruction in workers exposed to noise; and (2) whether these interventions promote adherence to HPD use. SEARCH METHODS: We used CENTRAL, MEDLINE, five other databases, and two trial registers, together with reference checking, citation searching, and contact with study authors to identify studies. We imposed no language or date restrictions. The latest search date was February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs), cluster-RCTs, controlled before-after studies (CBAs), and interrupted time-series studies (ITSs) exploring HPD fit testing in workers exposed to noise levels of more than 80 A-weighted decibels (or dBA) who use hearing protection devices. The unit 'dBA' reports on the use of a frequency-weighting filter to adjust sound measurement results to better reflect how human ears process sound. The outcome noise attenuation had to be measured either as a personal attenuation rating (PAR), PAR pass rate, or both. PAR pass rate is the percentage of workers who passed a pre-established level of sufficient attenuation from their HPDs, identified on the basis of their individual noise exposure. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed study eligibility, risk of bias, and extracted data. We categorised interventions as fit testing of HPDs with instructions at different levels (no instructions, simple instructions, and extensive instructions). MAIN RESULTS: We included three RCTs (756 participants). We did not find any studies that examined whether fit testing and training contributed to hearing protector use, nor any studies that examined whether age, gender, or HPD experience influenced attenuation. We would have included any adverse effects if mentioned by the trial authors, but none reported them. None of the included studies blinded participants; two studies blinded those who delivered the intervention. Effects of fit testing of HPDs with instructions (simple or extensive) versus fit testing of HPDs without instructions Testing the fit of foam and premoulded earplugs accompanied by simple instructions probably does not improve their noise attenuation in the short term after the test (1-month follow-up: mean difference (MD) 1.62 decibels (dB), 95% confidence interval (CI) -0.93 to 4.17; 1 study, 209 participants; 4-month follow-up: MD 0.40 dB, 95% CI -2.28 to 3.08; 1 study, 197 participants; both moderate-certainty evidence). The intervention probably does not improve noise attenuation in the long term (MD 0.15 dB, 95% CI -3.44 to 3.74; 1 study, 103 participants; moderate-certainty evidence). Fit testing of premoulded earplugs with extensive instructions on the fit of the earplugs may improve their noise attenuation at the immediate retest when compared to fit testing without instructions (MD 8.34 dB, 95% CI 7.32 to 9.36; 1 study, 100 participants; low-certainty evidence). Effects of fit testing of HPDs with extensive instructions versus fit testing of HPDs with simple instructions Fit testing of foam earplugs with extensive instructions probably improves their attenuation (MD 8.62 dB, 95% CI 6.31 to 10.93; 1 study, 321 participants; moderate-certainty evidence) and also the pass rate of sufficient attenuation (risk ratio (RR) 1.75, 95% CI 1.44 to 2.11; 1 study, 321 participants; moderate-certainty evidence) when compared to fit testing with simple instructions immediately after the test. This is significant because every 3 dB decrease in noise exposure level halves the sound energy entering the ear. No RCTs reported on the long-term effectiveness of the HPD fit testing with extensive instructions. AUTHORS' CONCLUSIONS: HPD fit testing accompanied by simple instructions probably does not improve noise attenuation from foam and premoulded earplugs. Testing the fit of foam and premoulded earplugs with extensive instructions probably improves attenuation and PAR pass rate immediately after the test. The effects of fit testing associated with training to improve attenuation may vary with types of HPDs and training methods. Better-designed trials with larger sample sizes are required to increase the certainty of the evidence.

Effects of age and noise exposure history on auditory nerve response amplitudes: A systematic review, study, and meta-analysis.

Auditory nerve (AN) function has been hypothesized to deteriorate with age and noise exposure. Here, we perform a systematic review of published studies and find that the evidence for age-related deficits in AN function is largely consistent across the literature, but there are inconsistent findings among studies of noise exposure history. Further, evidence from animal studies suggests that the greatest deficits in AN response amplitudes are found in noise-exposed aged mice, but a test of the interaction between effects of age and noise exposure on AN function has not been conducted in humans. We report a study of our own examining differences in the response amplitude of the compound action potential N1 (CAP N1) between younger and older adults with and without a self-reported history of noise exposure in a large sample of human participants (63 younger adults 18-30 years of age, 103 older adults 50-86 years of age). CAP N1 response amplitudes were smaller in older than younger adults. Noise exposure history did not appear to predict CAP N1 response amplitudes, nor did the effect of noise exposure history interact with age. We then incorporated our results into two meta-analyses of published studies of age and noise exposure history effects on AN response amplitudes in neurotypical human samples. The meta-analyses found that age effects across studies are robust (r = -0.407), but noise exposure effects are weak (r = -0.152). We conclude that noise exposure effects may be highly variable depending on sample characteristics, study design, and statistical approach, and researchers should be cautious when interpreting results. The underlying pathology of age-related and noise-induced changes in AN function are difficult to determine in living humans, creating a need for longitudinal studies of changes in AN function across the lifespan and histological examination of the AN from temporal bones collected post-mortem.

Noise-induced hearing loss alters potassium-chloride cotransporter KCC2 and GABA inhibition in the auditory centers.

Homeostatic plasticity, the ability of neurons to maintain their averaged activity constant around a set point value, is thought to account for the central hyperactivity after hearing loss. Here, we investigated the putative role of GABAergic neurotransmission in this mechanism after a noise-induced hearing loss larger than 50 dB in high frequencies in guinea pigs. The effect of GABAergic inhibition is linked to the normal functioning of K + -Cl- co-transporter isoform 2 (KCC2) which maintains a low intracellular concentration of chloride. The expression of membrane KCC2 were investigated before and after noise trauma in the ventral and dorsal cochlear nucleus (VCN and DCN, respectively) and in the inferior colliculus (IC). Moreover, the effect of gabazine (GBZ), a GABA antagonist, was also studied on the neural activity in IC. We show that KCC2 is downregulated in VCN, DCN and IC 3 days after noise trauma, and in DCN and IC 30 days after the trauma. As expected, GBZ application in the IC of control animals resulted in an increase of spontaneous and stimulus-evoked activity. In the noise exposed animals, on the other hand, GBZ application decreased the stimulus-evoked activity in IC neurons. The functional implications of these central changes are discussed.

Perceptual Consequences of Cochlear Deafferentation in Humans.

Cochlear synaptopathy, a form of cochlear deafferentation, has been demonstrated in a number of animal species, including non-human primates. Both age and noise exposure contribute to synaptopathy in animal models, indicating that it may be a common type of auditory dysfunction in humans. Temporal bone and auditory physiological data suggest that age and occupational/military noise exposure also lead to synaptopathy in humans. The predicted perceptual consequences of synaptopathy include tinnitus, hyperacusis, and difficulty with speech-in-noise perception. However, confirming the perceptual impacts of this form of cochlear deafferentation presents a particular challenge because synaptopathy can only be confirmed through post-mortem temporal bone analysis and auditory perception is difficult to evaluate in animals. Animal data suggest that deafferentation leads to increased central gain, signs of tinnitus and abnormal loudness perception, and deficits in temporal processing and signal-in-noise detection. If equivalent changes occur in humans following deafferentation, this would be expected to increase the likelihood of developing tinnitus, hyperacusis, and difficulty with speech-in-noise perception. Physiological data from humans is consistent with the hypothesis that deafferentation is associated with increased central gain and a greater likelihood of tinnitus perception, while human data on the relationship between deafferentation and hyperacusis is extremely limited. Many human studies have investigated the relationship between physiological correlates of deafferentation and difficulty with speech-in-noise perception, with mixed findings. A non-linear relationship between deafferentation and speech perception may have contributed to the mixed results. When differences in sample characteristics and study measurements are considered, the findings may be more consistent.