Noise-induced hearing loss and its prevention: current issues in mammalian hearing
Introduction
Noise-induced hearing loss (NIHL) is a major world-wide public health issue. A substantial proportion of disabling hearing has been attributed to occupational noise exposure [1,2]. In addition, there is a significant population of individuals with notched audiometric configurations consistent with noise-induced cochlear injury even in adults who do not have disabling hearing loss. For example, among participants in the 2011–2012 National Health and Nutrition Examination Survey, unilateral or bilateral audiometric notches were detected in 23.5% of those who self-reported good or excellent hearing and 28.3% of those with who self-reported little, moderate, or a lot of trouble hearing [3]. The finding that noise-induced synaptic pathology (‘cochlear synaptopathy’) does not affect the pure-tone audiogram suggests the possibility that there are many more individuals with noise-induced pathology and dysfunction than are currently diagnosed using threshold-based criteria [4••]. Two of the most exposed, and most at-risk, populations are workers exposed to occupational noise [5••], and service members and veterans [6•,7]. Music industry professionals are also at-risk [8] and there is increasing attention to the potential risks for those exposed to loud recreational sound (‘leisure noise’) [9••,10,11••].
It is generally agreed that as noise exposure increases (via longer exposure and/or higher sound levels), risk for cochlear injury and hearing loss increases. The most systematic description of relationships between noise exposure and hearing loss is that of the International Standard Organization [12]. Unfortunately, the patterns of occupational NIHL described in several historic reports and other more recently assessed worker populations deviate from that predicted [13,14]. Such discrepancies might be related to differences between the ethnicity and sex of workers contributing data in the 1950′s and 1960s and those working in loud jobs today, as there is significant variation in NIHL as a function of ethnicity and sex [14, 15, 16, 17].
National regulations, such as that of the Occupational Safety and Health Administration [18] and national guidance documents, such as that of the National Institute on Occupational Safety and Health [19], are based not only on assumptions about the levels at which occupational exposure becomes hazardous, but also public health decisions about how much hearing loss is ‘acceptable’ and in what proportion of the population this hearing loss is ‘acceptable’. Recent reviews discussing prevention of NIHL in adults and children suggest that an exposure limit of 80 dB-A LEX (with LEX being the 8-hour equivalent continuous average sound pressure level) would protect all but the most vulnerable individuals against NIHL, and that 75 dB-A LEX limits would be necessary if the goal were to protect even the most vulnerable individuals [9••,10] . Given the much higher sound levels in many workplaces and during many recreational activities, NIHL is, unfortunately, likely to remain a major public health issue. Animal models and mechanisms of injury are thus of high scientific interest and pharmaceutical intervention has become a commercial goal. Significant current interest also includes the identification of damage-risk criteria for cochlear synaptopathy, the diagnostic tests and corresponding functional deficits associated with synaptopathy, and the relevance of this pathology to workers exposed to occupational noise. This review briefly addresses each of these ‘hot’ topics in which future developments are likely to occur.
Section snippets
Animal models of noise-induced hearing loss
Comprehensive review of noise injury in rodent models was recently provided for the mouse [20], rat [21,22], chinchilla [23,24], and Guinea pig [25]. Although data directly establishing differences in vulnerability across mammalian species are extremely limited, a recent review of hearing loss induced by octave band noise exposures revealed the chinchilla is more vulnerable than both Guinea pig and rat, with the rat being intermediate to the Guinea pig and chinchilla [26]. The chinchilla, and
Mechanisms of injury
There is a wealth of information on the effects of noise on the inner ear. Much of the early investigation of noise-induced pathology focused on mechanical damage to hair cells, the reticular lamina, and other physical elements composing the organ of Corti [see for example, Ref. [31•]. As the understanding of both apoptotic and necrotic cell death in the cochlea increased, the important role of metabolic stress in apoptosis emerged and there are now multiple comprehensive reviews of mechanical
Occupational noise injury
There is significant evidence of OHC injury in workers exposed to occupational noise. OHC damage is commonly inferred based on evidence of permanent threshold shift (PTS), but data revealing reduced or absent DPOAEs also have been used to infer OHC loss or dysfunction in noise-exposed workers [50]. The potential for occupational noise to cause cochlear synaptopathy was suggested by data from rodents subjected to exposures ranging from a longer-duration lower-level noise exposure (7 days, 84 dB
Suprathreshold deficits
While there is significant speculation regarding the specific functional deficits that are associated with cochlear synaptopathy, there is little direct evidence of functional deficits in work with rodents to date. A single study assessing the perceptual consequences of ABR Wave I amplitude deficits in a rat model reported decreases in the detection of masked signals, with deficits limited to the poorest signal to noise ratios at signal frequencies that evoked decreased ABR amplitudes [56].
Pharmaceutical intervention
Decades of research using animal models to assess mechanisms of noise injury and therapeutic interventions at the selected targets have advanced into clinical trials for a variety of agents [for recent review see Ref. 35] despite the many challenges associated with development of drugs for auditory indications [see Ref. 60]. Indeed, there are now more than 40 companies with pharmaceutical interventions in various stages ranging from pre-clinical to Phase I or even Phase II clinical trials [61••
Summary and conclusions
NIHL is likely to remain a major public health issue given the high levels of environmental, recreational, and occupational noise exposure. Animal models evaluating mechanisms of injury have provided significant insight into the vulnerability of both OHCs and cochlear synapses to noise injury. Related research identifying drugs that alleviate metabolic stress has allowed pharmaceutical intervention for NIHL prevention to become a major commercial goal. With greater understanding of cochlear
Conflict of interest statement
Nothing declared.
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
CGL is currently supported by USAMRAAW81XWH-19-C-0054, JPC-8/SRMRPW81XWH1820014, N.I.H.-NIDCD1R01DC014088, 3M Inc., and the Emilie and Phil Schepps Professorship in Hearing Science. CGL has previously received contract funding and/or clinical trial material from industry partners including Sound Pharmaceuticals, Inc., Edison Pharmaceuticals, Inc., and Hearing Health Science, Inc. RR and TAH are currently partially supported by NIH-NIDCD R01DC015988 and by contract funding from Akouos Inc.
References (67)
- et al.
Human exposures and their associated hearing loss profiles: music industry professionals
J Acoust Soc Am
(2019) - et al.
Noise exposure limit for children in recreational settings: review of available evidence
J Acoust Soc Am
(2019) - et al.
Oxidative stress in the cochlea: an update
Curr Med Chem
(2010) Otoprotectants: from research to clinical application
Semin Hear
(2019)- et al.
Primary neural degeneration in the human cochlea: evidence for hidden hearing loss in the aging ear
Neuroscience
(2019) - et al.
Translating animal models to human therapeutics in noise-induced and age-related hearing loss
Hear Res
(2019) Effects of noise exposure on auditory brainstem response and speech-in-noise tasks: a review of the literature
Int J Audiol
(2019)- et al.
Auditory function in normal-hearing, noise-exposed human ears
Ear Hear
(2015) - et al.
Evidence for age-related cochlear synaptopathy in humans unconnected to speech-in-noise intelligibility deficits
Hear Res
(2019) - et al.
Multivariate DPOAE metrics for identifying changes in hearing: perspectives from ototoxicity monitoring
Int J Audiol
(2012)
Synaptopathy in the noise-exposed and aging cochlea: primary neural degeneration in acquired sensorineural hearing loss
Hear Res
Commentary on the regulatory implications of noise-induced cochlear neuropathy
Int J Audiol
Auditory brainstem response altered in humans with noise exposure despite normal outer hair cell function
Ear Hear
Hearing protection, restoration, and regeneration: an overview of emerging therapeutics for inner ear and central hearing disorders
Otol Neurotol
Neurotrophin-3 regulates ribbon synapse density in the cochlea and induces synapse regeneration after acoustic trauma
eLife
BDNF, NT-3 and Trk receptor agonist monoclonal antibodies promote neuron survival, neurite extension, and synapse restoration in rat cochlea ex vivo models relevant for hidden hearing loss
PLoS One
The global burden of occupational noise-induced hearing loss
Am J Ind Med
Global burden of hearing impairment and ear disease
J Laryngol Otol
Vital signs: noise-induced hearing loss among adults - United States 2011-2012
MMWR Morb Mortal Wkly Rep
Adding insult to injury: cochlear nerve degeneration after "temporary" noise-induced hearing loss
J Neurosci
Review: occupational noise exposure and hearing loss
J Acoust Soc Am
Prelude: noise-induced tinnitus and hearing loss in the military
Hear Res
Audiologic characteristics in a sample of recently-separated military veterans: the Noise Outcomes in Servicemembers Epidemiology Study (NOISE Study)
Hear Res
Risk of noise-induced hearing loss due to recreational sound: review and recommendations
J Acoust Soc Am
The leisure-noise dilemma: hearing loss or hearsay? What does the literature tell us?
Ear Hear
Acoustics: Estimation of Noise-induced Hearing Loss (ISO-1999)
ISO estimates of noise-induced hearing impairment
J Acoust Soc Am
Noise-induced hearing loss and its prevention: integration of data from animal models and human clinical trials
J Acoust Soc Am
Is this STS work-related? ISO 1999 predictions as an adjunct to clinical judgment
Am J Ind Med
Hearing loss among world trade center firefighters and emergency medical service workers
J Occup Environ Med
Sex differences in hearing: probing the role of estrogen signaling
J Acoust Soc Am
Occupational Noise Exposure; Hearing Conservation Amendment; Final Rule
Criteria for a Recommended Standard, Occupational Noise Exposure, DHHS (NIOSH) Publication No. 98-126
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