Hearing loss and deafness are the most common sensory deficits in babies, affecting between two and three per 1,000 newborns. But hearing loss and deafness affect one in 10 people in the general population, or some 36 million people overall in the United States. What causes this 200-fold increase in acquired hearing loss and deafness as people age?
One major source of the exponential increase is noise trauma: exposure to blasts (e.g., explosions, gunfire), chronic noise in the workplace and recreational activities such as listening to loud music and hunting. Indeed, 50 million individuals in the U.S. complain of tinnitus (ringing in the ears), often a precursor to hearing loss.
A second major source of acquired hearing loss is aging. And lastly there is hearing loss due to drugs toxic to hearing, such as those used to treat cancer and bacterial infections like meningitis. Unfortunately, these life-saving drugs are ototoxic, that is, they have side-effects that damage or
kill hearing and balance system sensory cells. After birth, when sensory cells in the inner ear die, they cannot be replaced, and the result is varying degrees of deafness and balance problems. Ototoxicity affects up to 120,000 people in the U.S. each year, most of whom are either older persons receiving treatment for cancer, or children undergoing treatment for bacterial sepsis or cancer. Yet, for people facing lifethreatening illnesses, their stark options are often reduced to either hearing loss or death. Ototoxic drugs save their lives at the expense of their hearing.
The loss of auditory and vestibular sensation in adults is not only distressing, it is also associated with a loss of income and deteriorating social, familial and intimate relationships. The economic cost of losing one’s hearing as an adult has been calculated at approximately $250,000 over the adult’s
remaining life. For infants who become deaf, the lifetime costs can reach as high as $1 million, reflecting the expenses caused by delays in developing verbal language ability, along with more psychosocial and academic challenges. These costs include auditory rehabilitation, such as digital hearing aids, cochlear implants, language development and special education. Hearing loss is and will increasingly become a major economic, societal and healthcare burden, both in the U.S. and around the world.
There are signifi cant research efforts underway to understand and reverse the mechanisms that induce deafness and vestibular deficits, primarily funded by the Deafness Research Foundation and the National Institutes of Health. While we await breakthroughs in treating hearing loss, it is possible to prevent the loss of hearing and balance sensation in many cases.
Earplugs — Noise’s Nemesis
The most immediate step we can take is to educate ourselves and our children about the dangers of exposure to loud sounds, along with chronic exposure to moderate levels of sounds. Programs like Dangerous Decibels® (www.dangerousdecibels.org) help encourage us to wear hearing protection like muffl ers or earplugs in situations of hazardous exposure to sound, such as orchestra pits, construction zones and commercial airplanes.
A strategy to preserve hearing prior to the onset of noise-induced hearing loss is being extensively researched for applications in the military. Pharmaceuticals such as D-methionine, ebselen and N-acetylcysteine have been shown to boost endogenous production of the antioxidant glutathione, which protects hearing before, during and after toxic noise exposure. The development of an effective dosing strategy for each of these otoprotective drugs is the remaining critical step. If accomplished, these otoprotective compounds may become commercially available in pill form within the next 10 years to help protect the hearing of our troops as well as civilians in noisy environments. However, it will still be essential to use external hearing protection, as otoprotectants are most effective against lower levels of noise trauma which produce less oxidative stress.
Combatting Ototoxic Medications
Sometimes external protection is not applicable to preserving hearing. Such is the case with ototoxic medications like aminoglycoside antibiotics (gentamicin) or platinum-based cancer drugs, like cisplatin, that damage hearing from within. Each of these drugs generates toxic levels of free oxygen
radicals that overwhelm intra-cellular antioxidant defenses and kill sensory cells in the inner ear, causing deafness and balance disorders.
But can we prevent ototoxic drugs from damaging our hearing and balance sensory systems? In recent years, several antioxidants, mimetics or stimulants of antioxidant production have been tested before, during and after exposure to an ototoxic drug. These otoprotectants, and others like dihydroxybenzoate, a precursor of aspirin, also preserve hearing in animals that received ototoxic doses of aminoglycosides and cisplatin. Importantly, these otoprotectants do their job without reducing the therapeutic effect of aminoglycosides, which is to kill bacteria, or cisplatin, which is to kill cancer cells.
Two clinical trials are underway to verify that otoprotectants indeed reduce cisplatin-induced ototoxicity in cancer patients. However, the use of otoprotectants to maintain healthy hearing and to protect hearing during aminoglycoside administration has not been commercially developed beyond
the laboratory because the cost of obtaining federal approval far outweighs the potential for commercial profit. Furthermore, otoprotectants would have to be inexpensive, easily available and without significant side-effects at their effective dose,like the 81mg low-dose aspirin used to maintain healthy heart function, if it were to be used widely to maintain healthy hearing and vestibular function.
Another potential strategy to protect hearing and balance from ototoxic drugs is to disrupt the trafficking of ototoxic drugs into the inner ear. If practical, otoprotectants that keep drugs from moving from the bloodstream to the inner ear could be used in combination with antioxidant otoprotectants and external hearing protective devices to best preserve inner ear function. Unfortunately, the mechanisms by which ototoxic drugs cross the blood-labyrinth barrier into the inner ear are poorly understood. This is an emerging area of research.
Another challenge is that simultaneous exposure to two or more ototoxic infl uences can synergistically induce greater hearing loss than if presented separately. For example, a person could be exposed simultaneously to noise and harmful solvents (such as jet fuel or aerosol propellants), or a person could take aminoglycosides and cisplatin at the same time. Fortunately, it seems antioxidant-based otoprotectants work against multiple forms of ototoxic infl uences since their basic function is rounding up free oxygen radicals that are common to different forms of ototoxicity. Again, it must be stressed that using hearing protection, such as earplugs or masks to prevent inhaling ototoxins, will enhance the efficacy of otoprotectants in preserving hearing and vestibular function.
Although chemoprotective strategies to preserve hearing and balance function during exposure to ototoxic drugs are just now in clinical trials, prospects are bright for future generations of cancer survivors, among others who could benefit. Everyone can take action now to protect hearing and
balance by using hearing protection, being informed about which ototoxic drugs can do permanent damage and by supporting research on otoprotectants. To learn more, visit National Institute of Deafness and Other Communication Disorders (www.nidcd.nih.gov) or the Deafness Research Foundation (www.drf.org).
Peter Steyger, Ph.D., is associate professor of otolaryngology – head and neck surgery at the Oregon Health & Sciences University. He is also scientific director for the Deafness Research Foundation, and serves on the boards of the Alexander Graham Bell Association for the Deaf and Hard of Hearing (www.agbell.org), and Tucker-Maxon Oral School (www.tmos.org), where deaf children learn to talk. Steyger became deaf at the age of 14 months through the treatment of meningitis with ototoxic aminoglycoside antibiotics. His research program at the Oregon Hearing Research Center (www.ohsu.edu/ohrc) investigates the mechanisms by which drugs cross the blood-labyrinth barrier into the cochlea where they can then exert their ototoxic effect.
