Research Round up

Research and new avenues in auditory science are changing the way we look at our ears—and how amplification, drugs, and implants might be applied to them.

Tinnitus Negatively Affects Quality of Life

In the March edition of The Journal of the American Academy of Audiology (JAAA), researchers from the University of Wisconsin at Madison show that tinnitus clearly reduces the quality of life of older adults. Additionally, the most significant negative effects of tinnitus showed up in the domains of physical pain and stress, as opposed to the mental and emotional domains.

More on tinnitus “Low-Pitch Treatment Reported to Alleviate Tinnitus.” February 22, 2007 HR Insider. “Using Open-Ear Hearing Aids in Tinnitus Therapy,” by Luca Del Bo, MSc, et al. August 2006 HR. “TMJD and Tinnitus: What About Pathogenesis?” by Fabrizio Salvinelli, MD, et al. October 2005 HR. “Military Vets Suffer Dramatic Increase in Tinnitus, Other Hearing Damage.” October 11, 2006 HR Insider. “Study Investigates Hearing Loss and High Speed Dental Tools.” August 25, 2006 HR Insider.

In the population-based study, lead-researcher David Nondahl and colleagues looked at self-reported data using the Medical Outcomes Study Short Form Health Survey (SF-36) from 2,800 subjects who were ages 53 to 97, with 669 subjects having mild, moderate, or severe levels of tinnitus.

When looking at the SF-36 data, mean scores for all eight domains (physical functioning, role-physical, bodily pain, general hearing perceptions, vitality, social functioning, role-emotional, and mental health index) worsened with the severity of the subjects’ tinnitus, as did mean scores for the two summary indexes (Physical and Mental Component Summary). A significant (p < .05) linear trend was observed for the role-physical, bodily pain, vitality, and Physical Component Summary index.

Almost 25% of the population had tinnitus, with 9.4% reporting moderate to severe tinnitus. The researchers concluded that “quality of life is diminished in participants with tinnitus, and the effect increases with severity. With improvements in longevity, the number of older adults affected by tinnitus is expected to increase, suggesting that additional efforts to identify effective prevention, diagnosis, and treatment are warranted to increase the quality of life experienced by older adults.”

JAAA Editor-in-Chief James Jerger, PhD, states in his editorial that the study “provides a wealth of data confirming the link between tinnitus and diminished quality of life, an important contribution to the theoretical framework underlying tinnitus intervention therapy.”

The research was supported by grants from the National Institutes of Health (NIH).

Original Article
Nondahl D, Cruickshanks KJ, Dalton DS, Klein BEK, Klein R, Schubert CR, Tweed TS, Wiley TL. The impact of tinnitus on quality of life in older adults. J Am Acad Audiol. 2000;18(3):257-266.

Stem Cell Isolation May Lead to a Hearing Loss Treatment

Members of the National Center for Regenerative Medicine research team, Robert Miller and Kumar Alagramam of Case Western Reserve University School of Medicine, recently published research findings in Developmental Neuroscience that suggest new ways of treating hearing loss. The researchers have isolated “cochlear stem cells” located in the inner ear and already primed for development into ear-related tissue due to their proximity to the ear and expression of certain genes necessary for the development of hearing.

“Previous work in our lab with young-adult mouse cochlear tissue showed expression of genes normally found in stem cells and neural progenitors,” says Alagramam. “This led us to hypothesize that cochlea harbors stem cells and neural precursor cells. Our work in collaboration with Miller’s lab supports our hypothesis.”

They say that, in early life, these precursor cells may be able to regenerate hair cells, but their capacity to do so becomes limited as the ear develops and ages. The team’s research is a major step in devising a therapy to reverse permanent hearing loss, because it may lead to the activation of cochlear stem cells in the inner ear to regenerate new hair cells.

“Clearly, we have miles to go before we reach our end goal, but the exciting part is now we can test compounds that could promote regeneration of hair cells from these precursor cells in vitro, we can study the genes expressed during the transition from stem cells to hair cells, and we can think of developing strategies for cell replacement, ie, transplanting these cochlear stem cells into the adult cochlea to affect hair cell replacement in the mouse, by extension, in humans,” says Alagramam.

In this paper, Miller and Alagramam offer further evidence for the existence of cochlear stem cells in the mouse cochlea by confirming the ability to form “stem cell spheres” in culture, and by characterizing these cells in terms of neural and hair cell development using a panel of stem cell development and hair cell markers. The formation of spheres from early postnatal cochlear tissues and their expression of a wide range of developmental markers unique to hair cells confirm the possibility that self-supporting hair cell precursors exist in or can be derived from the postnatal mammalian cochlea.

More on stem cells “UK Stem Cell Research on Deafness Making Rapid Progress.” January 1, 2007 HR Insider. “Stem Cell Research Showing Great Promise for Curing Deafness.” February 22, 2007 HR Insider. “Promising Research on Hair Cell Regeneration.” By Edwin W. Rubel, PhD. October 2004 HR.

Currently, there are no clinical treatments to repair these hair cells vital to normal hearing. In the United States, 30% of people over the age 65 have a handicapping hearing loss, and of those, one in 500 people become deaf before reaching adulthood. In most cases, the target is the highly specialized hair cells. Docked inside the spiral duct of the human cochlea are about 15,000 hair cells, which are highly specialized neuroepithelial cells. These hair cells differ in length by minuscule amounts and are set in motion by specific frequencies of sound. We hear this sound because this motion induces the hair cell to release an electrical impulse, which passes along the auditory nerve to the brain. If the sound is too loud, the hair cells are damaged and no longer send signals to the brain. Severely damaged hair cells do not repair themselves, nor do they regenerate naturally.

While further research is necessary, the researchers believe these precursor cells have the potential to regenerate the damaged hair cells and restore normal hearing. The team has already begun animal studies to explore the use of cochlear stem cells in well-established hair cell ablation models and in deaf mouse mutants with predictable patterns of early hair cell loss. This line of research will evaluate the in-vivo survival and differentiation of self-renewing cochlear cell populations and potentially lead to new therapies for the numerous individuals who are going to suffer from noise-induced hearing loss in the near future. Source: American Association for the Advancement of Science.

Original Article
Yerukhimovich MV, Bai L, Chen DH-C, Miller RH, Alagramam KN. Identification and characterization of mouse cochlear stem cells. Dev Neurosci. 2007;29:251-260.

Effects of “Doubling Up” on Hearing Protection Explored

Will doubling up or wearing dual protection—an earmuff in addition to earplugs—provide added protection against extreme noise levels? The answer is yes, according to a recent Sound Source bulletin by the Bacou-Dalloz Hearing Safety Group.

But perhaps not as much as one may think. According to Brad Witt, who is audiology and regulatory affairs manager for the Hearing Safety Group, dual protection is not required by OSHA regulations for general industry in the United States, but is required for mining operations governed by the Mine Safety & Health Administration (MSHA) for noise exposures over 105 dBA (8-hour time-weighted average). Similarly, NIOSH recommends dual protection for any exposures over 100 dBA, and some companies require it for employees with progressive noise-induced hearing loss despite normal protective measures.

However, Witt cautions, there are also risks associated with dual protection. “Using earplugs and earmuffs concurrently seriously isolates the wearer,” he writes, “so it is warranted only in extreme noise levels.” He also suggests dual protection is overused. “When a high-attenuation earplug or earmuff is properly fitted and the user is motivated to use it correctly, some hearing professionals say the need for dual protection is rare.”

More on ONIHL “Earmuffs: A Primer.” By Brad Witt, MA. March 2007 HR. “Firearms and Hearing Protection.” By William J. Murphy, PhD, David C. Byrne, MS, and John R. Franks, PhD. March 2007 HR. “Hearing Protection for Musicians.” By Patty Niquette, MA. March 2006 HR. “Hearing Conservation for Audio Industry Professionals.” By Rachel Cruz, MA, and Marilee Potthoff. October 2005 HR.

So how much protection will doubling up provide? That depends on the fit, says Witt, but it “is not simply the combined ratings of the earplug and earmuff. There is a ceiling effect that limits the amount of combined protection. Even if wearing a perfectly fitted earplug and earmuff with ideal attenuation, we would still hear sound transmitted through our bodies and bones to the inner ear.”

The maximum attenuation that can be attained by most people is 35 to 50 dB, depending on the frequency of the sound. As a rule of thumb for estimating the effects of dual protection, OSHA recommends adding 5 dB to the NRR of the higher rated device. But this, says Witt, “sacrifices some accuracy. An earmuff typically adds about 4 dB to the NRR of a well-fitted foam earplug, and about 7 dB to a well-fitted premolded earplug.” He also says that an earmuff with moderate attenuation provides the same effect as a high-attenuation earmuff when either is worn over a well-fitted earplug.

“The key to obtaining maximum benefit from dual protection is proper fit,” Witt writes, “especially the fit of the earplug. When a poorly fitted earplug is worn with an earmuff, the resulting dual protection is little more than the earmuff alone.” Witt and Marshall Chasin, AuD, guest-edited the March 2007 HR that had as its focus occupational noise-induced hearing loss (ONIHL).

Original Article
Witt B. Dual protection. Dallas: Bacou-Dalloz Hearing Safety Group. Sound Source. 2007;11.

Combination of Nutrients Might Prevent Hearing Loss

In a new study in animals, University of Michigan researchers report that a combination of high doses of vitamins A, C, E, and magnesium, taken 1 hour before noise exposure and continued as a once-daily treatment for 5 days, was very effective in preventing permanent noise-induced hearing loss. The animals had prolonged exposure to sounds as loud as a jet engine at takeoff at close range.

Clinical trials of a hearing-protection tablet or snack bar for people could begin soon, and if successful such a product could be available in as little as 2 years, says Josef M. Miller, PhD, the senior author of the study, which is published online in the journal Free Radical Biology and Medicine. Miller is a professor in the Department of Otolaryngology at the U-M Medical School, and former director of the U-M Health System’s Kresge Hearing Research Institute, where the study was performed.

Convinced by emerging evidence that nutrients effectively block one major factor in hearing loss after noise trauma—inner ear damage caused by excessive free radical activity—Miller has launched a U-M startup company, OtoMedicine, that is developing the vitamin-and-magnesium formulation.

“These agents have been used for many years, but not for hearing loss,” says Miller. “We know they’re safe, so that opens the door to push ahead with clinical trials with confidence we’re not going to do any harm.”

The formulation the researchers used built on earlier animal studies showing that single-antioxidant vitamins were somewhat effective in preventing hearing loss, and on studies of Israeli soldiers given magnesium many days prior to exposure, who gained relatively mimimal protective effects.

In the U-M study, noise-induced hearing loss was measured in four groups of guinea pigs treated with the antioxidant vitamins A, C, E, and magnesium alone, an ACE-magnesium combination, or a placebo. The treatments began 1 hour before a 5-hour exposure to 120 dBSPL noise, and continued once daily for 5 days. The group given the combined treatments of vitamins A, C, and E and magnesium showed significantly less noise-induced hearing loss than all of the other groups.

“Vitamins A, C, and E and magnesium worked in synergy to prevent cell damage,” explains Colleen G. Le Prell, PhD, the study’s lead author. According to the researchers, pre-treatment presumably reduced free radicals that form during and after noise exposure and noise-induced constriction of blood flow to the inner ear, and may have also reduced neural excitotoxicity, or the damage to auditory neurons that can occur due to over-stimulation. The post-noise nutrient doses apparently “scavenged” free radicals that continue to form long after this noise exposure ends.

In the past 10 years, scientists have learned that noise-induced hearing loss occurs in part because cell mitochondria in the ear churn out damaging free radicals in response to loud sounds. “Free radical formation bursts initially, then peaks again during the days after exposure,” says Le Prell.

More on nutrition “American Biohealth Group Offers the Hearing Pill.” November 23, 2006 HR Insider. “Hearing Protection Drug Completes Phase I of Clinical Testing.” January 18, 2007 HR Insider. “Exercise Promotes Hearing Health.” By Helaine Alessio, PhD, and Kathleen Hutchinson, PhD. April 2004 HR.

The antioxidant vitamins and magnesium used in the study are widely used dietary supplements, and don’t require the extensive safety tests required for new drug entities prior to use in clinical trials. The doses to be used in proposed human trials will be within the ranges considered safe according to the Institute of Medicine and federal nutrition guidelines.

“Ultimately, we envision soldiers would have a nutritional bar with meals and it would give them adequate daily protection,” says Miller. Similar bars with other formulations are already given to soldiers to help them withstand hot weather and other war zone conditions.

“Other people would likely benefit by consuming a pill or nutritional bar before going to work in noisy environments, or attending noisy events like NASCAR races or rock concerts, or even using an iPod or other music player,” says Le Prell. “Based on an earlier study with other antioxidant agents, we think this micronutrient combination will work even post-noise.”

That study suggested a “morning after” treatment that might minimize hearing damage. If effective, such treatments could have far-reaching effects. About 30 million Americans regularly experience hazardous noise levels at work and at home, according to the NIDCD. About 31.5 million Americans have some degree of hearing loss, and for about a third of them, noise accounts at least in part for their loss. Source: Anne Rueter, University of Michigan Health System.

Original Article
Le Prell CG, Hughes LF, Miller JM. Free radical scavengers vitamins A, C, and E plus magnesium reduce noise trauma. Free Radic Biol Med. 2007; 42(9):1454-1463.