Safe & SOUND

Sick infants, life-saving helicopter transports, antibiotics that may cause harm. But, these same drugs might actually protect babies’ hearing during their noisy rides.

William W. Clark, PhD, conducts an on-site sound test with members of the St. Lo

William W. Clark, PhD, conducts an on-site sound test with members of the St. Louis Children’s Hospital transport team. A lifelike doll was unfazed during the procedure.

BY Colleen Cotton

A BK-117 HELICOPTER TOUCHES DOWN on the roof of a hospital, its blades still whirling rapidly. A critically ill premature infant is injected with an antibiotic and rushed out to the tarmac in an isolette. The baby waits while the doctor receives last-minute instructions. Then the helicopter is loaded up and lifts off for St. Louis Children’s Hospital.

This seems like an ideal way to quickly and safely transport infants at high risk to a hospital better equipped to meet their needs. But one aspect of this scenario had been overlooked until recently: the danger of hearing loss.

About 26 million Americans suffer from hearing loss caused by loud noises like jet engines, rotating helicopter blades, or even headphones. Certain antibiotics called aminoglycosides, often applied in the emergency setting, are known to cause hearing loss in some patients by damaging sensory cells of the inner ear. But if you put these two together, is hearing loss worse than either alone?

William W. Clark, PhD, professor of otolaryngology and director of the Program in Audiology and Communication Sciences, a division of CID at Washington University School of Medicine, wanted to find out.

“I was contacted by Mary Jude Weathers, a flight nurse at St. Louis Children’s Hospital, who supervised air transport of fragile newborns from remote locations,” says Clark.

Eight hours’ unprotected exposure to this noise level can cause serious hearing damage in adults.

Was this intensity permanently damaging the hearing of infants during their brief journeys to critical medical care?

These infants frequently have a very low birth weight and no immunity to disease. To protect against bacterial infections during transport they often get a dose of an aminoglycoside called gentamicin before being taken from the hospital’s sterile environment. As an expert on noise-induced hearing loss, Clark knew that this could be a problem.

“There is good evidence from studies in animals that gentamicin would exacerbate potential noise damage,” Clark says. “So it seemed logical to assume that people on gentamicin would be more susceptible to noise-induced hearing loss, and we were especially concerned for these babies.”

Weathers and Clark measured noise levels that infants were exposed to during transport. While waiting on the tarmac, the infants experienced sound levels of almost 100 decibels for an average of 12 minutes. This is equivalent to standing next to a running lawn mower or chainsaw without hearing protection. This much noise can cause permanent hearing loss in adults exposed for a few hours, but Clark thought the effect could be much greater in infants with gentamicin in their system.

It was impossible to conduct a clinical study without risking the babies’ health. The solution was to turn to the laboratory of Kevin K. Ohlemiller, PhD, research associate professor in otolaryngology, who studies the genetics of hearing loss in mice.

“Both humans and mice are particularly vulnerable to noise- and drug-induced hearing loss at young ages,” Ohlemiller says. “The laboratory mouse is a well-established model for human hearing. They possess similar inner-ear anatomy and physiology and similar patterns of age-related, noise-induced and drug-related hearing loss.”

Ohlemiller and Clark selected Elizabeth A. Fernandez, then a doctoral student in the Program in Audiology and Communication Sciences (PACS), to structure a research project around this question of hearing loss. The idea was simple: examine how noise, young age and kanamycin (another aminoglycoside like gentamicin) might work together to aggravate hearing loss. Based on previous studies, the researchers fully expected to find dangerous interactions between the different factors.

“At the time, I was doing newborn hearing screenings at Missouri Baptist Hospital, testing babies that were often exposed to gentamicin, Fernandez says. “I was very interested to see if there was a combined effect with these drugs and noise.”

Before they began the study, Ohlemiller and Fernandez tried to come up with levels of noise and kanamycin that by themselves would have no effect on young mice, but together might cause hearing loss. They based their initial guesses on data from a strain of mice closely related to the one they had chosen. But eight minutes of noise ended up causing permanent hearing loss. So did four minutes, and two minutes, and one minute.

PACS graduate Elizabeth A. Fernandez, AuD, CCC-A, with her mentor, Kevin K. Ohlemiller, PhD, in his CID laboratory. Fernandez discovered that a low-level dose of the drug kanamycin was 100 percent effective in protecting against noise-induced hearing loss.

While it was anticipated that young mice would be highly vulnerable to noise, this was an unprecedented level of vulnerability. Ohlemiller was at a loss.

“These mice kept having huge noise-induced hearing losses, much larger than anything the data would have predicted,” he says. “When we got down to 30 seconds of noise, we were running out of time and mice. I had Beth begin her study with that interval, which was essentially a guess of mine.”

As the data began to come in, it was clear that 30 seconds was still too long; the mice continued to show hearing loss. Ohlemiller worried that his judgment error had threatened the study. But instead of the massive hearing loss expected, animals that received a regular, low dose of kanamycin before noise exposure were fine. Like flipping a switch, kanamycin was fully protective against noise that otherwise would have caused permanent hearing damage. Examination of the mouse inner ears by microscopy showed that kanamycin had protected the sensory cells most often killed by noise.

Protection of a mouse cochlea organ of Corti from the effects of noise by kanamycin administration. Several types of cells are missing in the unprotected (saline plus noise) cochlea, but are present in the kanamycin plus noise cochlea.

“The initially unpleasant surprise of Beth’s study, that a supposedly safe level of noise caused hearing loss, led to two new discoveries,” Ohlemiller says. “First, the strain of mice that we were working with was phenomenally sensitive to noise, more so than I would have ever predicted. And second, a low level of kanamycin was 100 percent effective in protecting against noise-induced hearing loss.”

All PACS students must carry out a capstone research project, though the results aren’t usually this stunning. Fernandez was able to present her findings at the American Academy of Audiology, where she was one of five recipients of the Student Research Forum Award. The study was published in the Jan. 22, 2010 online edition of the Journal of the Association for Research in Otolaryngology.

“I’m a coal miner’s daughter, so I have family members with noise-induced hearing loss,” says Fernandez. “The goal is to one day have a pharmacologic solution to the problem of noise exposure.”

While the scientists stress that their findings do not mean that kanamycin — still an ototoxin — should now be used to protect people from noise, their study does show that protective actions of kanamycin may affect outcomes in infants during transport, as well as in other people who are receiving antibiotics and are exposed to noise. Learning exactly how kanamycin protects the ear’s sensory cells could lead to the development of drugs that imitate its effects. Medications that protect the ears from damaging noise are presently missing from the toolbox of clinicians, and they could benefit a wide range of groups, from coal miners to babies. Scientists also can now use the newly recognized “noise sensitive” strain of mice to find genes that may make some humans more vulnerable to noise.

According to Ohlemiller, several new projects are now building on Fernandez’ findings. Two are being conducted by PACS students and another will be led by a medical student this summer.

“These results not only energize laboratory scientists and begin new lines of research, they also have implications for clinical practice,” Clark says. “This has been an amazing sequence of events, to start a project in a helicopter and end up under a microscope.”

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