Apoptotic vesicles resist oxidative damage in noise-induced hearing loss through activation of FOXO3a-SOD2 pathway.

BACKGROUND: Mesenchymal stem cell (MSC) transplantation is a promising therapeutic approach for noise-induced hearing loss (NIHL). As the indispensable role of apoptosis in MSC transplantation was raised, the benefits of MSC-derived apoptotic vesicles (apoVs) in several disease models have been proved. However, whether apoVs benefit in NIHL have not been studied yet. METHODS: Female CBA/J mice and HEI-OC1 cells were used in this study. Flow cytometry, nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) were used to characterize apoVs. Proteomic analysis was used to identify function proteins in apoVs. Immunofluorescence was used to reveal distribution pattern. Auditory brainstem response (ABR) test was used to measure the effect of apoVs treatment. DCFH-DA staining and MitoSOX staining were used to indicate oxidative damage. Western-blot and qRT-PCR were used to study the signaling pathways. RESULTS: We found that apoVs can be endocytosed by hair cells through systemic administration. Importantly, apoVs administration effectively attenuated NIHL and reduced hair cell loss by resisting oxidative damage in vivo. Further, apoVs application activated forkhead box o3 (FOXO3a)-mitochondrial superoxide dismutase 2(SOD2) pathway, which may relate to signal transduction and activators of transcription 3 (STAT3) in apoVs. CONCLUSIONS: These findings uncovered the role of apoVs in preventing NIHL and resisting oxidative damage, indicating that apoVs is a promising way for inner ear delivery and a prospective cell-free therapy for NIHL.

Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins.

As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.

[Often not considered during Expert opinion: Patients after accidents or noise traumata - A patient-focused, complementary perspective]. / Bei der Begutachtung oft nicht bedacht: Unfallpatienten und Patienten nach einem Lärmtrauma ­ Eine patientenzugewandte, komplementäre Sichtweise.

Patients who have acquired tinnitus in the context of an accident, a noise trauma or other external influences have important distinctive features in treatment. Although their suffering was in general caused by external circumstances or other people and mostly without own fault, they suffer from a permanent damage, difficult to be realized externally. Additionally they must concentrate their remaining resources to deal adequately with their suffering from tinnitus and very often permanent hearing loss. Legal disputes and the assessment processes necessary in this context can have an unfavorable and perpetuating effect. These influences and patient's reception is laid down here.

VEGFA165 gene therapy ameliorates blood-labyrinth barrier breakdown and hearing loss.

Millions of people are affected by hearing loss. Hearing loss is frequently caused by noise or aging and often associated with loss of pericytes. Pericytes populate the small vessels in the adult cochlea. However, their role in different types of hearing loss is largely unknown. Using an inducible and conditional pericyte depletion mouse model and noise-exposed mouse model, we show that loss of pericytes leads to marked changes in vascular structure, in turn leading to vascular degeneration and hearing loss. In vitro, using advanced tissue explants from pericyte fluorescence reporter models combined with exogenous donor pericytes, we show that pericytes, signaled by VEGF isoform A165 (VEGFA165), vigorously drive new vessel growth in both adult and neonatal mouse inner ear tissue. In vivo, the delivery of an adeno-associated virus serotype 1-mediated (AAV1-mediated) VEGFA165 viral vector to pericyte-depleted or noise-exposed animals prevented and regenerated lost pericytes, improved blood supply, and attenuated hearing loss. These studies provide the first clear-cut evidence that pericytes are critical for vascular regeneration, vascular stability, and hearing in adults. The restoration of vascular function in the damaged cochlea, including in noise-exposed animals, suggests that VEGFA165 gene therapy could be a new strategy for ameliorating vascular associated hearing disorders.

Effects of Oxygen Therapies in Experimental Acute Acoustic Trauma.

BACKGROUND: Acute acoustic trauma is defined as a sudden sensorineural hearing loss that occurs after an exposure to acoustic overstimulation. Increasing the oxygen in perilymph can be a treatment modality. Our study aims to investigate the influence of normobaric oxygen therapy on the recovery of acute acoustic trauma and to compare it with the hyperbaric oxygen therapy. METHODS: Three groups of rats (5 rats each) were exposed to white noise for 1 hour. Sensorineural hearing loss was identified using distortion product otoacoustic emission. Subsequently, the first group was treated with hyperbaric oxygen therapy, the second group was treated with normobaric oxygen therapy, and the third group did not receive any treatment and was used as a control group. RESULTS: There was a statistically significant difference within time for frequencies of 1, 1.5, and 2 kHz, but there was no statistically significant difference between groups. For frequencies of 3, 4, 5, and 6 kHz, there was a statistically significant difference within time and between groups. Between groups, recovery of distortion product otoacoustic emission values in all frequencies was better in the control group by the third, fifth, and seventh days. Comparing the values of hyperbaric oxygen therapy and normobaric oxygen therapy groups, it was observed that by the third day, the hyperbaric oxygen therapy values were better than those of the normobaric oxygen therapy values. However, by the fifth and seventh days, the normobaric oxygen therapy values were better (except at a frequency of 1 kHz). CONCLUSION: Because there is a high rate of spontaneous recovery, physicians should be more selective to treat patients with oxygen therapies.

Integrated stress response inhibition provides sex-dependent protection against noise-induced cochlear synaptopathy.

Noise-induced hearing loss (NIHL) is a common health concern with significant social, psychological, and cognitive implications. Moderate levels of acoustic overstimulation associated with tinnitus and impaired speech perception cause cochlear synaptopathy, characterized physiologically by reduction in wave I of the suprathreshold auditory brainstem response (ABR) and reduced number of synapses between sensory hair cells and auditory neurons. The unfolded protein response (UPR), an endoplasmic reticulum stress response pathway, has been implicated in the pathogenesis and treatment of NIHL as well as neurodegeneration and synaptic damage in the brain. In this study, we used the small molecule UPR modulator Integrated Stress Response InhiBitor (ISRIB) to treat noise-induced cochlear synaptopathy in a mouse model. Mice pretreated with ISRIB prior to noise-exposure were protected against noise-induced synapse loss. Male, but not female, mice also exhibited ISRIB-mediated protection against noise-induced suprathreshold ABR wave-I amplitude reduction. Female mice had higher baseline wave-I amplitudes but greater sensitivity to noise-induced wave-I reduction. Our results suggest that the UPR is implicated in noise-induced cochlear synaptopathy, and can be targeted for treatment.

Hearing Outcomes of Treatment for Acute Noise-induced Hearing Loss: A Systematic Review and Meta-analysis.

OBJECTIVE: To determine the efficacy of various treatment modalities used for acute noise-induced hearing loss (aNIHL) from acute acoustic trauma (AAT) via a systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane, and Scopus databases. STUDY SELECTION: The scientific literature was searched up to October 2018 for articles evaluating hearing outcomes after treatment of aNIHL. DATA EXTRACTION: The following were extracted: Oxford level of evidence, number of patients, mean age, time to presentation, source of noise exposure, method of treatment/intervention, baseline hearing threshold, posttreatment hearing threshold, hearing gain, proportion of patients with no recovery, partial recovery, or complete recovery, and treatment complications. DATA SYNTHESIS: Sixteen studies with 932 patients met inclusion criteria for systematic review and four studies with 187 patients were included in the meta-analysis. CONCLUSIONS: Treatment modalities identified were steroids, vascular agents, nootropics, antioxidants, vitamins, cell apoptosis inhibitors, and hyperbaric oxygen therapy. Meta-analysis demonstrated significant improvement in mean hearing threshold for patients with high-frequency hearing loss, those treated within 48 hours, and those receiving treatment with a nootropic agent. Significant heterogeneity was present in experimental design among included studies and many were of lower levels of evidence. More prospective, large scale, randomized, double-blinded, placebo-controlled clinical trials are required to determine optimal treatment regimens for patients suffering from aNIHL caused by AAT.

[Noise-induced blood-labyrinth-barrier trauma of guinea pig and the protective effect of matrix metalloproteinase inhibitors].

Objective: The research is to study the expression and distribution of matrix metalloproteinase (MMPs)-2 and -9 in the guinea pig cochlea after noise exposure, and to explore the role of MMPs in the blood-labyrinth-barrier (BLB). In addition, the role of MMPs inhibitor doxycycline in noise-induced BLB trauma was studied as well, which provides the basis for further studies and prophylaxis of noise-induced hearing loss. Methods: A total of 45 healthy adult guinea pigs were randomly divided into the control group (15 received intraperitoneal injection of 0.9% saline for 4 consecutive days), the noise-exposure group (15 exposed by 120 dB SPL white noise for 4 h per day for continuous 2 d, intraperitoneal injection of normal saline for 4 consecutive days) and the noise-exposure + doxycycline group (15 exposed by 120 dB SPL white noise exposure for 4 h per day for 2 consecutive days, and intraperitoneal injection of doxycycline 50 mg/kg/d for 4 consecutive days), respectively. Immunofluorescence staining, western blot, and real-time quantitative PCR were used to analyze the distribution and differential expression of MMP-2 and -9 in the stria vascularis of guinea pigs in comparison with the normal control group, noise only group, and noise & doxycycline treatment group. Immunofluorescence staining was used to observe the changes in tight junction (TJ) protein ZO-1 in stria vascularis in three groups and to investigate the effect of acoustic injury on TJs. And ABR tests were utilized to detect the hearing function of guinea pigs in the three groups. Intravenous Evans blue was administrated intravenously as an indicator of vascular leakage among three groups to study the changes in BLB permeability in context of acoustic injury. SPSS 22.0 was used for statistical analysis. Results: There was no significant difference in hearing function between the noise-exposure group and the noise & doxycycline group two hours after noise exposure. After seven, 14 and 28 days noise exposure, the hearing recovery of the noise & doxycycline treatment group was significantly greater than that of the noise-exposure group (P<0.05) . Immunofluorescence staining showed that there was only a small amount of MMP-2 and -9 in the stria vascular in the normal control group, and ZO-1 showed dense linear expression. While, in the noise-explore group, MMP-2 and -9 in the stria vascular was significantly elevated (P<0.05), and the configuration of ZO-1 became loose and discontinuous. However, the MMP-2 and -9 in the noise & doxycycline treatment group were not significantly different from the normal control group (P>0.05), which were significantly less than that in the noise-exposure group, and just a little break of ZO-1 was observed, however, the overall structure remained dense. The leakage of Evans blue from stria vascular capillary in the noise-exposure group was significantly increased, and the difference between the other two groups did not show any statistical significance (P>0.05). Conclusions: The damage of tight junction structure induced by MMP-2 and -9 may play an important role in BLB destruction. In addition, doxycycline can inhibit MMPs secretion, thereby, to some extent, protecting the integrity of BLB from acoustic injury, and contributing to the long-term hearing recovery.

Recent advances in hearing conservation programmes: A systematic review.

BACKGROUND: Current evidence from low- and middle-income (LAMI) countries, such as South Africa, indicates that occupational noise-induced hearing loss (ONIHL) continues to be a health and safety challenge for the mining industry. There is also evidence of hearing conservation programmes (HCPs) being implemented with limited success. OBJECTIVES: The aim of this study was to explore and document current evidence reflecting recent advances in HCPs in order to identify gaps within the South African HCPs. METHOD: A systematic literature review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Electronic databases including Sage, Science Direct, PubMed, Scopus MEDLINE, ProQuest and Google Scholar were searched for potential studies published in English between 2010 and 2019 reporting on recent advances in HCPs within the mining industry. RESULTS: The study findings revealed a number of important recent advances internationally, which require deliberation for possible implementation within the South African HCPs context. These advances have been presented under seven themes: (1) the use of metrics, (2) pharmacological interventions and hair cell regeneration, (3) artificial neural network, (4) audiology assessment measures, (5) noise monitoring advances, (6) conceptual approaches to HCPs and (7) buying quiet. CONCLUSION: The study findings raise important advances that may have significant implications for HCPs in LAMI countries where ONIHL remains a highly prevalent occupational health challenge. Establishing feasibility and efficacy of these advances in these contexts to ensure contextual relevance and responsiveness is one of the recommendations to facilitate the success of HCPs targets.

[Study protocol of the monocentric prospective randomized placebo-controlled double-blind phase II study to explore the protective effects of the ginkgo biloba extract EGb 761® from temporary noise-induced hearing loss]. / Prüfplan für die monozentrische prospektive randomisierte placebokontrollierte doppelblinde Phase-II-Studie zur Exploration protektiver Effekte des Ginkgo-biloba-Spezialextrakts EGb 761® vor einer vorübergehenden Hörschädigung durch Lärm.

BACKGROUND: Hearing loss is frequently induced by occupational noise exposure and leads to rising hearing thresholds as well as reduced otoacoustic emissions (OAE), mostly caused by metabolic hair cell decompensation. OBJECTIVE: Primary endpoint is the increase in average pure tone thresholds after noise exposure, secondary endpoints are loss of distortion product and click-evoked OAE as well as reduction of their contralateral suppression. PARTICIPANTS AND METHODS: The present study design describes the verification of the anti-oxidant and neuroprotective properties of EGb 761® by evaluation of cochlear protection from noise impact as well as its safety and tolerance in 202 healthy male participants distributed equally to verum and placebo groups in a double-blind manner. Participants were assessed, medicated, exposed to noise, and then examined at timepoints up to 10 min and 4 weeks thereafter. CONCLUSION: This summary of the verification study protocol highlights the complexity of diligent and precise planning according to the European Medicines Agency criteria for controlled trials (EudraCT). Key points are the intervention rationale, definitions of in- and exclusion criteria, estimation of subject numbers, and examination method setting in terms of optimum endpoint description.

Recent Advancements in Gene and Stem Cell-Based Treatment Modalities: Potential Implications in Noise-Induced Hearing Loss.

Noise-induced hearing loss (NIHL) poses a significant burden on not only the economics of health care but also the quality of life of an individual, as we approach an unprecedented age of longevity. In this article, we will delineate the current landscape of management of NIHL. We discuss the most recent results from in vitro and in vivo studies that determine the effectiveness of established pharmacotherapy such as corticosteroid and potential emerging therapies like N-acetyl cysteine and neurotrophins (NTs), as well as highlight ongoing clinical trials for these therapeutic agents. We present an overview of how the recent advancements in the field of gene-based and stem cell-based therapies can help in developing effective therapeutic strategies for NIHL. Gene-based therapies have shown exciting results demonstrating cochlear cellular regeneration using Atoh1, NRF2 as well as NT gene therapy employing viral vectors. In addition, we will discuss the recent advancements in genome-editing technologies, such as CRISPR/Cas9, and its potential role in NIHL therapy. We will further discuss the current state of stem cell therapy as it pertains to treating neurodegenerative conditions including NIHL. Embryonic stem cells, adult-derived stem cells, and induced pluripotent stem cells all represent an enticing reservoir of replacing damaged cells as a result of NIHL. Finally, we will discuss the barriers that need to be overcome to translate these promising treatment modalities to the clinical practice in pursuit of improving quality of life of patients having NIHL. Anat Rec, 303:516-526, 2020. © 2019 American Association for Anatomy.

The use of nonhuman primates in studies of noise injury and treatment.

Exposure to prolonged or high intensity noise increases the risk for permanent hearing impairment. Over several decades, researchers characterized the nature of harmful noise exposures and worked to establish guidelines for effective protection. Recent laboratory studies, primarily conducted in rodent models, indicate that the auditory system may be more vulnerable to noise-induced hearing loss (NIHL) than previously thought, driving renewed inquiries into the harmful effects of noise in humans. To bridge the translational gaps between rodents and humans, nonhuman primates (NHPs) may serve as key animal models. The phylogenetic proximity of NHPs to humans underlies tremendous similarity in many features of the auditory system (genomic, anatomical, physiological, behavioral), all of which are important considerations in the assessment and treatment of NIHL. This review summarizes the literature pertaining to NHPs as models of hearing and noise-induced hearing loss, discusses factors relevant to the translation of diagnostics and therapeutics from animals to humans, and concludes with some of the practical considerations involved in conducting NHP research.

Noise-induced hearing loss: Translating risk from animal models to real-world environments.

Noise-induced hearing loss (NIHL) is a common injury for service members and civilians. Effective prevention of NIHL with drug agents would reduce the prevalence of NIHL. There are a host of challenges in translation of investigational new drug agents from animals into human clinical testing, however. Initial articles in this special issue describe common pre-clinical (animal) testing paradigms used to assess potential otoprotective drug agents and design-related factors that impact translation of promising agents into human clinical trials. Additional articles describe populations in which NIHL has a high incidence and factors that affect individual vulnerability. While otoprotective drugs will ultimately be developed for use by specific noise-exposed populations, there has been little effort to develop pre-clinical (animal) models that accurately model exposure hazards across diverse human populations. To facilitate advances in the translational framework for NIHL otoprotection in pre-clinical and clinical testing, the overarching goals of the current series are to (1) review the animal models that have been used, highlighting the relevance to the human populations of interest, (2) provide insight into the populations for whom pharmaceutical interventions might, or might not, be appropriate, and (3) highlight the factors that drive the significant individual variability observed in humans.

Utility of Hyperbaric Oxygen Therapy for Acute Acoustic Trauma: 20 years' Experience at the Japan Maritime Self-Defense Force Undersea Medical Center

Introduction: Acute acoustic trauma, which is a kind of sensorineural hearing loss, is caused by acoustic overstimulation. Hyperbaric oxygen therapy (HBOT) is reported to be effective against acute acoustic trauma. Objective: We aimed to evaluate the efficacy of HBOT against acoustic hearing loss based on our 20 years of experience with such cases. Methods: Patients who were treated with HBOT for acute acoustic trauma between April 1997 and August 2017 were evaluated in this study. Thirty-five patients with a mean age of 25.7 ± 9.2 (range: 16­48) years were included. Thirty-nine out of 70 ears (35 patients) were damaged. We investigated the initial level of hearing loss; the extent to which hearing recovered; subjective symptoms, such as tinnitus and aural fullness; and the treatment administered. Results: The planned HBOT was completed in 37 of 39 ears. Twenty-six of the 37 ears (70.2%) displayed improved hearing, and 31 of the 37 ears (83.9%) exhibited symptom improvement. Twenty-three (76.7%) and 26 (86.7%) of the 30 ears treated with steroids demonstrated improvements in hearing and subjective symptoms, respectively. Conclusion: A combination of HBOT and steroids should be considered as a treatment for acute acoustic trauma in cases involving symptoms such as tinnitus and aural fullness (AU)

What is noise-induced hearing loss?

Noise-induced hearing loss is sensory deafness caused by long-term exposure of the auditory system to a noisy environment. Auditory fatigue is an early symptom of noise-induced hearing loss, and hearing can gradually recover after people leave a noisy environment. However, if people remain in a noisy environment for a prolonged period of time, their hearing will be permanently impaired. Societal changes mean that people are more likely to be exposed to noise. The hearing loss and tinnitus caused by noise seriously affect people's quality of life and lead to huge economic loss. The pathogenesis of noise-induced hearing loss is complex. Various theories try to explain this, such as the oxidative stress theory, but none perfectly explains the occurrence of noise-induced hearing loss. There is no treatment which can completely reverse the damage. More research is required to explore the pathogenesis and to better guide clinical practice. Preventative strategies, such as educating the public about hearing health, should be adopted to reduce the harm of noise-induced hearing loss.

An unusual case of sudden sensorineural hearing loss after cycling class.

In this case report, our patient developed sudden sensorineural hearing loss (SSNHL) after loud noise exposure during a popular cardiovascular group exercise cycling class. To increase awareness among all healthcare professionals of the effects of these modern-day group fitness classes on hearing loss, we describe this case and review the current literature on SSNHL and its management. A 35-year old man developed SSNHL in the setting of loud noise exposure during a high intensity aerobic exercise class. After a short course of oral steroids with no improvement, intratympanic steroids were administered weekly for three weeks. The patient showed minimal improvement; thus, hyperbaric oxygen therapy was conducted. Serial audiograms continued to show severe to profound mixed hearing loss in the right ear. In conclusion, individuals who participate in loud, high-intensity aerobic group-exercise classes should be careful of the potential for noise-induced hearing loss. Aerobic exercise may make these individuals more susceptible to noise-induced hearing loss. Early intervention is critical for any chance of recovery.

Effects of oral zinc supplementation on patients with noise-induced hearing loss associated tinnitus: A clinical trial.

BACKGROUND: Zinc plays a vital antioxidant role in human metabolism. Recent studies have demonstrated a correlation between noise-induced hearing loss (NIHL) and oxidative injury; however, no investigation has focused specifically on the subgroup of NIHL associated tinnitus patients. We aimed to evaluate the effectiveness of zinc supplementation in treating NIHL associated tinnitus. METHODS: Twenty patients with tinnitus and a typical NIHL audiogram (38 ears) were included in this study. Another 20 healthy subjects were used as the control group. A full medical history assessment was performed, and each subject underwent an otoscopic examination, basic audiologic evaluation, distortion product otoacoustic emissions (DPOAEs), tinnitus-match testing, Tinnitus Handicap Inventory (THI) and serum zinc level analyses. After 2 months of treatment with zinc, all tests were repeated. RESULTS: There was a significant difference between pretreatment and post-treatment within the tinnitus group (73.6 vs. 84.6 µg/dl). The pre- and post-treatment difference in serum zinc was significantly higher in the young group (≦50 years) compared to the old group (19.4 ± 11.4 vs. 2.6 ± 9.2 µg/dl, respectively; p = 0.002). There were no statistically significant differences in hearing thresholds, speech reception thresholds, or tinnitus frequency and loudness results before and after treatment. In addition, 17 patients (85%) showed statistically significant improvement of THI-total scores post-treatment, from 38.3 to 30 (p = 0.024). CONCLUSIONS: Zinc oral supplementation elevated serum zinc levels, especially in younger patients. THI scores improved significantly following zinc treatment in patients with NIHL associated tinnitus. However, no improvements in objective hearing parameters were observed.

Translating animal models to human therapeutics in noise-induced and age-related hearing loss.

Acquired sensorineural hearing loss is one of the most prevalent chronic diseases, and aging and acoustic overexposure are common contributors. Decades of study in animals and humans have clarified the cellular targets and perceptual consequences of these forms of hearing loss, and preclinical studies have led to the development of therapeutics designed to slow, prevent or reverse them. Here, we review the histopathological changes underlying age-related and noise-induced hearing loss and the functional consequences of these pathologies. Based on these relations, we consider the ambiguities that arise in diagnosing underlying pathology from minimally invasive tests of auditory function, and how those ambiguities present challenges in the design and interpretation of clinical trials.

Aural Blast Injury/Acoustic Trauma and Hearing Loss.

Hearing is a critical sense to military performance. The ability to detect, identify, and localize sounds, the ability to maintain spatial awareness on the battlefield and the awareness to control one's own noise production can be vital to troop's stealth, survivability, and lethality. Hazardous noise is an environmental public health threat encountered in training at war, and in many off-duty activities. The risk to hearing and the resultant damage from any of these hazardous exposures is generally invisible, insidious and cumulative. Regardless of the source of injury, hearing loss degrades the sensor that integrates Service Members with their environment, provides for unity of effort, and ensures command and control.Acoustic trauma-induced hear loss and tinnitus are the two most prevalent disabilities in veterans, with over 765,000 cases in the Gulf War era alone. To counter this threat, it is necessary to push for early identification and early intervention through a trusted surveillance system. Success will require advocacy, education, and encouragement of self-reporting for evaluation following symptomatic noise exposures. This Clinical Practice Guideline (CPG) is a step to ensure the hearing health, readiness, protection, and care of Service Members. This will in turn optimize troop performance and minimize injury risk and mishap.