CDR Keith S. Wolgemuth, MSC, USN
Naval Submarine Medical Research Laboratory
Groton, CT
I ATTENDED the NOPHER (Noise Protection Health Effects Reduction) 2000 International Symposium on Noise Induced Hearing Loss at Cambridge University, United Kingdom 7-10 July 2000. Wow, TAD assignments like this are not offered on a regular basis so I jumped at the chance to go! My thanks to my former research supervisor, Colonel Richard Kopke, MC, USA, at the Department of Defense Spatial Orientation Laboratory, and the Office of Navy Research, for procuring funding allowing me to go. This was a unique opportunity to hear presentations on cutting edge research related to noise protection and hearing conservation. Scientists from the United Kingdom, Norway, Sweden, Finland, Denmark, Poland, France, the United States, Israel, the Czech Republic, and the Netherlands presented their work. As if the presentations were not enough, Robinson College, at Cambridge, provided very delicious, gourmet meals. Include a Shakespeare performance at a nearby college (Much Ado' About Nothing) and time in cozy, British pubs and you have all the ingredients for a most excellent travel experience.
My goal with this essay is to summarize the work of these international investigators, including some of the Navy's top investigators (Colonel Kopke, Lynn Marshall, Ph.D. and her team at the Navy Sub Lab), to help keep us all up to date with future directions of hearing conservation. Slowly, but steadily, strides are being made to improve how we protect military and non-military personnel from the effects of hazardous noise. NOPHER is a European Commission, concerted action group project devoted to protection against noise. This was their sixth in a series of international meetings focused on the auditory effects of noise exposure. A lot was packed into two and a half days of presentations. I will do my best to highlight what was important and may have practical applications to future hearing conservation practices.
DAY 1 started off with presentations pertaining to the role of the cochlear efferent system in noise-induced hearing loss (NIHL). We know that high noise levels (excluding blast types of injuries that we know also cause mechanical damage) stress out the outer hair cells (OHCs) by causing them to "over metabolize" or work too hard. This results in the OHCs entering into a "death cycle" and they become nonfunctional. Some evidence also exists that noise can also cause swelling and degeneration of the afferent VIIIth nerve terminals that attach below the inner hair cells (IHCs). Some investigators believe that the auditory efferent system, nerves traveling from the medial and lateral olivary regions of the brainstem to the outer hair cells of the cochlea, may play in role a person's susceptibility to NIHL. When sound is processed by the VIIIth nerve and reaches the superior olivary region of the auditory system, signals are then sent down via the efferent system to the OHCs. Then the OHCs exhibit their mechanical movements that enhance basilar membrane movement and allow the IHCs to be more sensitive in processing frequency and intensity properties Otoacoustic emissions, both transient (TEOAEs) and distortion product (DPOAEs) types, involve the measurement of the mechanical movement of the OHCs as driven by the efferent system. Don Henderson, of the State University of New York, Buffalo, Hearing Research Center (This is where CDR Nanci Hight, MSC, USN earned her Ph.D.) presented findings indicating when the chinchilla's efferent auditory system is stimulated with electric shocks, temporary threshold shift (TTS) can be reduced for some noise conditions. TTS was induced in chinchillas placed within two groups, those with the efferent nerves intact and those with their efferent nerves sectioned so signals could not reach the OHCs. Those with the efferent nerves cut developed more hearing loss and greater loss of OHCs than animals whose efferent system was left intact.
Dr.s Jean-Luc Puel and Jerome Ruel of France think they have found a neurochemical basis for a "protective efferent effect." Dopamine (DA) is released by olivary efferent nerves and prevents over neurochemical stimulation of the inner hair cells. Thus, the IHC suffers less damage. CDR Hight could explain this better than I, since her background in bio-chemistry using chemical treatments to restore/protect the inner ear is vastly superior to mine. This is interesting stuff in that it suggests we have some "natural protection" within our auditory nervous system and reminds us of how important a role the efferent "feedback" nervous system and the OHCs both play in auditory processing.
DR. MARK LUTMAN and associates the University of Southhamptom, U.K., and our very own Dr. Lynn Marshall of the Navy Submarine Medical Research Laboratory, Groton CT, talked about their work in using OAE testing as a screening tool for NIHL. OAEs are dependent on normal outer hair cells for their generation. Since this is the site in the human inner ear that is most susceptible to noise-induced damage, there has been a lot of interest in the application of OAEs to NIHL screening. Mark Lutman compared the test-retest reliability and sensitivity to measuring changes in hearing for TEOAE and DPOAE otoacoustic emissions and pure tone audiometry. He found that both types of OAE tests were twice as sensitive as pure tone audiometry in detecting changes in hearing thresholds. Being objective measures, he suggests they offer the promise of improved monitoring for NIHL. Lynn Marshall and her team have also been examining the sensitivity of OAEs to detect sub-clinical hearing damage (noise-induced changes to the inner ear but no accompanying hearing loss), pre-clinical damage (the damage will eventually turn into actual hearing loss), and whether or not OAE measures can reliably detect temporary threshold shift (TTS), permanent threshold shift (PTS), and susceptibility to TTS and PTS. Lynn and her staff are analyzing longitudinal data from a four year study, doing a study on aircraft carrier personnel in Norfolk, and working with COL Kopke and myself in San Diego assessing the Marine Corps recruit population. So far, it appears that DPOAEs appear to be more sensitive for detecting NIHL in individuals, but the results from the three studies mentioned are not completely analyzed yet.
Dr. Attias from Israel has also been doing some related work and like Dr.s Lutman and Marshall, believes OAEs are more sensitive in revealing subtle cochlear damage before audiometry does. I believe OAEs are going to play a bigger role in hearing conservation programs in the future in conjunction with audiometry. It is a more objective test than audiometry, something that may be an important addition in testing fatigued Marine Corps recruits on processing 1 day in boot camp or flightdeck sailors who worked a 12 hour shift the day and night before! Otoacoustic emission testing is not a replacement for the audiogram. Although emissions do correlate with hearing testing, they do not actually measure hearing.
DR. JAMES KALTENBACH and associates at Wayne State University (Detroit, MI) have been trying to determine a neurophysiological mechanism of noise-induced tinnitus. For years now a lot of us have assumed that tinnitus is related to noise-induced mechanical damage of hair cells. Research now suggests the OHCs are damaged by working too hard to process hazardous noise (e.g., over metabolizing, overdosed with neurochemical transmitters). Dr. Kaltenback suggests intense sound exposure cause increases in spontaneous VIIIth nerve neural activity (hyperactivity) in the cochlear nucleus. It may be that the cause of tinnitus is due to over stimulation of auditory brainstem structures rather than damage just within the cochlea itself. Another theory proposes that OHC damage results in less input getting to the auditory cortex from the cochlea so that the cortex has trouble processing the more limited, "uneven" input. Hence, tinnitus is caused by the auditory cortex trying to "resolve" the fact that it is getting fewer signals coming in from the inner ear. I know, it sounds pretty incredible. Again, it reminds us of just how complex the auditory system is and the fact that damage or over-stimulation can affect any part of the neural auditory system (not just the cochlea).
Dr. Deepak Prasher at University College, London has been investigating objective evidence for tinnitus from spontaneous otoacoustic emission variability. Remember, spontaneous emissions are present without any acoustic stimulation. He measured spontaneous OAEs in Polish mill workers, exposed to 85-95 dB (A) for a mean of twelve and a half years, some of whom (104) reported the presence tinnitus and some of whom (94) did not. His results demonstrated that the incidence of spontaneous OAEs is higher in noise-exposed workers than in previous studies and that the stability of spontaneous emissions is significantly lower in those individuals with subjective tinnitus. The assumption here is that exposure to noise results in instability within the cochlea, which alters spontaneous otoacoustic emission activity.
BARBARA CANLON and colleagues at the Karolinska Institutet, Stockholm, Sweden have studied the physiological process known as "preconditioning". This is an active process found in many neuronal and non-neuronal systems that results in tolerance to subsequent detrimental forms of trauma or stress (i.e., noise). Preconditioning is typically induced by low level, non-damaging stimuli that could result in long-term protective effects. Preconditioning has been demonstrated to increase tolerance to light damage in the retina and ischemia, and noise damage in the cochlea. In animal studies, sound pre-conditioning appears effective in protecting against subsequent noise trauma for both low and high frequency stimuli. Although the basic mechanisms underlying this conditioning protection are not totally understood, Dr. Canlon believes it is related to the "conditioning sound" causing an increase in heat shock proteins, neurotrophins, antioxidants, and reduction of calcium flow. All of these things result in less OHC damage to noise trauma. Dr. Canlon also reported preliminary results indicate a sound conditioner can also be presented after a noise stimulus and still offer some protective effect. The Institutet recently performed a pilot study on young adults and the results demonstrate the feasibility of employing sound conditioning as a clinical therapy. There is still a lot of work that needs to be done in this area, but its encouraging that levels of noise close to, but not at the damage risk criteria of 85 dB (A) may actually protect the ear by stimulating the release of the "right" antioxidants and neurochemicals.
COLONEL Rick Kopke, MC, USA, staff neuro-otologist, Naval Medical Center, San Diego and co-director of the DOD Spatial Orientation Laboratory where I used to work part-time presented an overview of his work and that of others pertaining to hair cell rescue and restoration. Although the armed forces Audiology communities have made great strides in improving hearing conservation programs and reducing occupational hearing loss, hearing protection devices have their limitations. For example, the noise levels on aircraft carrier flightdecks and impulse noise produced by heavy and light artillery are so high that even double hearing protection cannot prevent PTS in all cases. Some data from the Army and the Marine Corps suggest earplugs may not sufficiently protect personnel from the impulse noise produced by M-16 rifles. And then you have the issue of real world hearing protector attenuation not being nearly as effective as fittings in a laboratory setting.
Dr. Kopke and others have noted that noise overexposure leads to the development of reactive oxygen species (ROS) in the cochlea. Think of the ROS as being "thieves" who steal from molecules in the outer hair cells that support healthy functioning. Superoxide, hydrogen peroxide, and hydroxyl radicals are examples of these villains. Noise overexposure makes the OHCs work harder and then the ROS activate and prevent the cells from replenishing their nourishment. Once a certain damage threshold is reached, cell apoptosis (death cycle) is initiated. New understanding has been obtained regarding the cell cycle and molecular mechanisms involved with OHC damage. Colonel Kopke and others have been using antioxidants (something we all have naturally in our bodies) and neurotrophins to combat ROS before the OHC death cycle reaches its threshold of no return. Dr. Kopke's work with chinchillas has suggested that chemical intervention can significantly reduce TTS and PTS when the animals are exposed to hazardous noise levels. In other words, it may be possible to regenerate cochlear sensory cells after sensory cell loss and a PTS.
Josef Miller and Richard Altschuler of the Kresge Hearing Research Institute, University of Michigan and the Karolinska Institutet, Sweden have shown that the ROS prevent the natural antioxidants of the inner ear (glutathione) from doing its thing during noise overexposure, supporting the treatment theory that Dr. Kopke is pursuing. In addition, they have demonstrated that sound conditioning treatments appear to result in the increase of neurotrophins and antioxidant enzymes and direct administration of some neurotrophins can protect the inner ear from damage. Don Henderson, CDR Nanci Hight, MSC, USN, and their associates at State University of New York (SUNY) Buffalo's Center for Hearing and Deafness have also done some great work in this area. They have shown sound conditioning does "toughen" the ear by increasing antioxidant enzymes and that treating the ear with glutathione doses also makes the ear more resistant to noise. Dr. Tom Taggart (Associate Professor, SUNY Buffalo), a geneticist I have been working with for the past year, has demonstrated that genes involved in protein synthesis, cytoskeletal proteins, and calcium binding are all significantly affected by noise exposure. Again, CDR Hight could explain all of this much better than I. I have been struggling to learn some basic concepts in microbiology and chemistry to better understand the "why" and "how" of chemical restoration of the inner ear.
So what does all this mean, anyway? It means we are beginning to understand just how hair cell damage occurs in the cochlea. By understanding the mechanisms underlying the damage, we may be able to develop chemical and/or acoustic treatments to prevent it from happening. The idea of chemical treatments for NIHL may seem threatening to some audiologists, e.g. is this going to limit our profession clinically? Are we threatened with losing our jobs? I don't think so. I see this as an opportunity to extend our clinical profession. A professional is needed to perform auditory testing before and after administration of chemical agents to treat noise exposure and "sound conditioning" therapies are right up the audiologist's alley in my opinion. I also do not believe that chemical or acoustical treatments will do away with the use of hearing protective devices. They will still be needed as additional insurance or protection against the harmful effects of high level continuous and impulse noises. The use of chemical agents may not totally prevent the occurrence of NIHL. Magnesium has already been used in clinical trials and we are on the verge of other agents being used as such. We are starting to make the transition from animal trials to human. I believe this line of research will continue to expand and develop and as hearing professionals we need to be a part of it.
Data was also presented by Sliwinska-Kowalska and colleagues (Institute of Occupational Medicine, Poland) showing that exposure to organic solvents (i.e., xylene and toluene, used in paint and lacquer manufacturing) increases NIHL significantly. In the rat, Dr. Campo (Institute of National Research, Vandoeuvre, France) has demonstrated that exposure to the solvent styrene can increase the risk of NIHL, but combined with ethanol its ototoxicity is much worse. I guess alcohol and solvents do not mix, so don't drink when you are using paint thinner around the house! Seriously though, styrene appears to primarily target the OHCs and secondarily the spiral ganglions. Dr. Laurence Fechter (University of Oklahoma Health Sciences Center) showed that although the chemical asphyxiant carbon monoxide (CO) is not by itself ototoxic, in combination with noise releases those deadly reactive oxygen species (ROS) and can end up causing a great deal more NIHL than the noise alone. This is important considering the federal firefighter patients a lot of us evaluate. Firefighters are not exposed to constant noise throughout the week, their exposure is intermittent, but they are exposed to CO in the performance of their duties. For a long time now I have wondered why so many firefighters exhibit what appears to be more than the usual "notch" in the high frequencies.
Dr. ROGER HAMERNIK and associates at SUNY, Plattsburgh, New York suggests we approach the evaluation of hazardous noise exposures in a new way. He suggests energy-based metrics commonly used to evaluate the adverse effects of a noise exposure on hearing (e.g., Leq or the equivalent noise level) are suitable only for Gaussian, random noise while many industrial/military noise environments are non-Gaussian. Gaussian noise is defined as one that has the same averaged spectrum and sound pressure level across its frequency range. A non-Gaussian noise then involves random frequency-specific noise bursts or impulse noises occurring across the averaged spectrum and SPL. In other words, the noise has random spikes occurring over its time period. We typically take our noise measurements, with noise dosimeters and sound level meters, using the A and C frequency weighting networks. Dr. Hamernik proposes we use instead a statistical metric, kurtosis, to more accurately determine for any noise environment its potential for causing NIHL. So what is kurtosis? Well, it's a statistical function that allows for the measurement of the different temporal and peak (impulse) distributions of noises. Noises can have the same arithmetic mean and variance, but can be very different in terms of the actual distribution of energy. When taking our normal noise measurements, we may underestimate the damaging potential of the kurtotic noise on hearing. We may have two noise sources that have similar or the same average noise level or dB (A), but they may be quite different in terms of damage to hearing. By taking kurtotic noise measures (which we cannot do with our current noise measuring equipment in the Navy), we can better assess potential damage to hearing and make better recommendations regarding proper hearing protection for that environment. As we learn more about the value of such measures, we will hopefully see the development of commercial equipment to perform such measures.
HELLSTROM AND DENGERINK of the Swedish Armed Forces performed an interesting study where individuals were either exposed to noise centered at 200 Hz, to noise centered at 2K Hz, or to both noise bands. They wanted to study the assumption we make performing noise measures using the dB (A) and (C) scales, which assume harmful effects of noise to vary with the frequency of the noise exposure. They found the TTS after exposure to 2K Hz centered noise was significantly greater than to 200 Hz centered noise. The TTS seen after exposure to the 200 Hz and 2K Hz noise in combination was significantly less than the shift after exposure to the 2K Hz noise only. They concluded that low frequency noise exposure might protect against NIHL from high frequency noise exposure. This implies that some type of sound conditioning may have noise protective effects, but needs further study to confirm and better understand. It also raises the issue of whether or not the dB (A) scale is the most relevant for calculating the risk of NIHL, as it does not measure the low frequency region to the same degree as the dB (C) scale.
Captain Jonathan Clark, MC, USN, of the NASA Johnson Space Center, Houston, TX gave an interesting presentation concerning noise issues in human space flight. NASA is concerned about the acute effect of sound on crew performance on the International Space Station (ISS) and is looking at strategies to evaluate and reduce acute, chronic, and delayed effects of sound. Crewmembers have complained that noise levels on the ISS have caused impaired speech intelligibility of non-native language (Russian Cosmonauts also work on the ISS.) and often complain of sore throat from talking loudly in noisy environments. On the space shuttle, acoustic dosimetry revealed maximum noise levels to be around 70 dB (A). No hearing loss occurred, but the crew reported significant effects on performance and communication. TTS and PTS have not been observed in the U.S. shuttle program. TTS has been reported for 100% of Russian Cosmonauts and PTS has been identified in 27 of 33 Cosmonauts (82%). Long-term space flight has produced 30-50 dB HL of NIHL in the 4K-6K Hz range. On the International Space Station, there is constant background noise in the 56-60 dB (A) range. There is concern that the Astronauts and Cosmonauts are not able to obtain "auditory rest." NASA recommends hearing protection when noise exceeds 60 dB 24 hour Leq. The use of insert earplugs and passive or active noise reduction headsets are recommended. Captain Clark recommends longitudinal studies are needed to address what co-morbidity factors, i.e. radiation, toxicology, microgravity effects (fluid shift), and aging are involved with hearing loss in space. Wow, who would like to be the first audiologist in space!?
I know a lot of this must sound very "theoretical" and "futuristic." Well, some of it is. The notion of using moderate levels of noise to protect the ear against NIHL from higher noise levels, performing noise measurements using spectrum analyzers and statistical tests to better predict the harmful effects, using chemical agents to stop outer and inner hair cell death so hearing abilities lost can be restored, are new concepts that require further research. The use of otoacoustic emissions to better identify NIHL and assist in monitoring individuals in the HCP is not so far fetched, and neither is the use of chemical agents to protect or restore hearing. The thing that impressed me the most about the conference was that so many people, from so many different countries (acoustic scientists, physicians, audiologists) are working so diligently to better protect people from the harmful effects of noise. I was fortunate to be there, to listen and soak up all of that knowledge. I also gained a greater appreciation of what hearing conservation is all about and why it is so important to me as a Navy audiologist. We should pat ourselves on the back a little, we have made significant improvements in the effectiveness of the Navy's HCP and DOEHRS-HC will add to those improvements. However, we need to keep up with new advances in research that could affect future clinical and HCP practice. We can continue to do better in our fight against NIHL. I would like to see Navy Audiology, all of us, become part of future treatments for this occupational disorder. After all, thirty years ago tympanometry was not thought so highly of when first introduced, nor was the otoacoustic emission test when first introduced by David Kemp in the late 70's. I hope you all got something out of my rambling summary of the meeting. It was fun meeting so many of these people and also a real blast to actually get to visit the Tower of London, London Bridge, Big Ben, and Buckingham Palace. And then there was that British ale...
CDR Keith S. Wolgemuth, MSC, USN
Naval Submarine Medical Research Laboratory
Box 900, Diving Bio-effects/Hearing Conservation
Groton, CT 06340
E-mail: wolgemuth@nsmrl.navy.mil
(860)-694-4680