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Ear, Nose & Throat Associates |
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May 2008 News Archives
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May 5: NASCAR widow warns of head, neck cancer dangers, CNN
By Judy Fortin
CNN Medical Correspondent
ATLANTA, Georgia (CNN) -- At 33, Lori Hamilton is young and healthy. So what is she doing at an oral, head and neck cancer screening at an Atlanta, Georgia, hospital?
"It's therapeutic for me to talk to patients," Hamilton explained. Her husband, Bobby Hamilton Sr., a champion NASCAR driver, died of neck cancer last year at the age of 49.
"It blindsides you," Hamilton said. "It just completely caught us off guard."
The American Cancer Society estimates 35,000 new cases of oral, head and neck cancer will be diagnosed in the United States this year, accounting for between 3 and 5 percent of all cancers. More than 7,000 people will die.
Nearly a quarter of the cancers occur in the tongue; others develop on the floor of the mouth, lips, salivary glands, gums and tonsils.
Doctors don't know for certain what causes this type of cancer, but they do know that heavy smokers and drinkers are most at risk.
The cancer society reports the disease is twice as common in men compared with women, possibly because more men are likely to drink and smoke.
"It's not just smoking tobacco products," clarified Dr. Michelle Cullen, assistant professor of otolaryngology at Emory School of Medicine. "Chewing tobacco increases risk, especially if you chew in one particular area."
The cancer society revealed another emerging source of oral cancers. The organization said up to 30 percent of new cases may be caused by a common sexually transmitted disease that can be passed along through unprotected oral sex.
"There has been some recent evidence, particularly in the base of the tongue and the tonsils that may be linked to the human papillomavirus or HPV," according to Dr. Amy Chen, director of Health Services Research for the cancer society.
HPV is probably best known as the leading cause of cervical cancer in women.
Researchers at Johns Hopkins University in Baltimore, Maryland, found the number of cases of oral cancers related to HPV nearly doubled between 1973 and 2004. Study authors concluded it may be the result of changing sexual behaviors.
Experts recommend that adults of all ages be screened annually for oral, head and neck cancer. Some of the warning signs may include: red or white patches in the mouth that last more than two weeks, difficultly chewing or swallowing and a change in voice or hoarseness.
Chen added "ear pain, difficultly breathing or spitting up blood" might also be symptoms.
"For someone who is afflicted with head and neck cancer it is a huge problem because it affects speech and swallowing," noted Chen. "If you have a cancer like that it can be quite devastating for someone's appearance."
While the condition can be easily treated if caught early, it can also be fatal.
Lori Hamilton is trying to spread the word about the dangers of oral cancers by visiting screening centers around the country.
One of her target groups hits close to home: NASCAR fans. Hamilton operates her husband's racing team out of Greensboro, North Carolina. She travels the racing circuit urging people to get checked for cancer.
"At a racetrack, we have a captive audience of 80,000 people," Hamilton said. "If we can reach a third of them, maybe it can make a difference."
Hamilton explained her husband was neither a drinker nor a smoker. "He took very good care of himself. I'm not sure why this happened."
He had never been screened for oral cancer before the condition was detected after the removal of an infected wisdom tooth.
He endured chemotherapy, radiation and surgery before succumbing to the disease in January 2007.
"He wasn't aware that head and neck cancer was the fifth-largest cancer out there," Hamilton said. "It's important for people to know it's something that can come out of left field."
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May 5: The story of a father, a daughter, and a fever, The Boston Globe
By Billy Baker
Globe Correspondent
By the time Robbie Stankard was 14 months old, he had been to the emergency room 19 times. Every time the symptom was the same, a fever of 103.8.
The doctors ran tests, scary tests, looking for things like leukemia, things that would make Robbie's mother, Marcia, throw up with worry. The tests were always negative, but the fevers persisted like clockwork, every third Monday.
The Stankard's story ended happily, thanks to coincidence, serendipity, and a doctor willing to take a risk with his own daughter.
The coincidence is that the Stankards live in Westwood, the same town as Greg Licameli, a doctor at Children's Hospital Boston. The serendipity is that Marcia Stankard had heard through the grapevine that Licameli's daughter, Claire, had had the same problem, the same cyclical fevers. And Licameli had figured out how to beat it: removing the child's seemingly healthy tonsils and adenoids.
It's still unclear why a tonsillectomy should cure children of unexplained, recurring fevers. But in the five years since he removed his daughter's tonsils, Licameli, an otolaryngologist, has seen 60 patients suffering from this cyclical fever syndrome, known as PFAFA, and the findings continue to hold up. Robbie Stankard, who is about to turn 6, is one of those successes. In February, Licameli published a paper on 27 of his earliest patients. After having the surgery, 26 of those people remain fever-free.
Now Licameli is hoping to get his findings out to the general public. PFAFA was first described in 1987, but has remained, in Licameli's view, "as low-level background noise," without enough cases to raise it to the surface and make the average doctor aware of the condition.
When his daughter came down with the fevers around her first birthday, Licameli reacted as both a doctor and a father.
"Why is this happening?" he asked himself. "It was frustrating as a parent and as a physician to see your child having an issue and you can't fix it," he said.
They went through the tests, the blood workups, the specialists, each time coming up empty. So Licameli dipped into the medical literature, finding a couple of European studies that pointed toward removing the tonsils and adenoids as a cure.
Licameli's daughter had two seizures as a result of the fevers. Traditional remedies failed to bring her fever down, so she had to be packed in ice. Her development was being affected, he felt, because she was getting knocked down for five days at a time. At the same time, all surgeries come with risk. And there was evidence that many children grow out of the fevers by the time they're 7 or 8. He thought about it, decided he didn't want to put his daughter through the up-and-down for years to come, and went for it.
She turns 6 tomorrow. She's healthy.
The Prendergast family does not live in Westwood. They live in Sterling. Their daughter, Sophia, now 2 1/2, came down with the cyclical fevers when she was 6 months old. But they also had coincidence on their side because they happened to see a pediatrician who had experience with a PFAFA patient, which is uncommon. And the pediatrician knew of Licameli's success.
Because Sophia was so young, the Prendergasts first opted for a steroid treatment, which can help lessen the severity of the fevers but increases their frequency, according to Licameli. In November, she went in for the tonsillectomy on the day she was due for another fever. It never came.
"We used to hope that she would grow out of them," said Melissa Prendergast. "Now, we're just so thankful for Dr. Licameli and Children's Hospital. This whole procedure changed our lives. We're thankful that what she had was a safe, benign thing, but it was agonizing for a parent. She's always been such a happy child, and then every three weeks she would get very sick, she wouldn't eat. And you knew it was coming."
With the publication of the study, which appeared in the "Archives of Otolaryngology and Head and Neck Surgery," Licameli is hoping to remove coincidence, serendipity, and proximity to Children's Hospital from the equation.
"The goal is to make people aware," Licameli said. "We're treating. We're getting a cure. Intellectually, we don't know why. But there's infinitely more that we don't know about medicine than we do."
"And nobody has asked me to put their tonsils back in."
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May 5: Lasers May Treat Cancers of the Larynx, The New York Times
By LAWRENCE K. ALTMAN, M.D.
For people with early cancer of the larynx, the standard treatment can be grueling: a biopsy in an operating room followed by a six-week course of radiation that may lead to permanent hoarseness or speech impairment.
But a team of Harvard doctors is reporting that a new outpatient laser procedure promises to eliminate the need for radiation, preserve speech, shorten treatment time and significantly improve care in other ways for many patients whose cancer is diagnosed early.
The therapy, which uses heat from the laser to destroy the tumor’s blood supply and cancer cells, damages surrounding tissue far less than radiation and different types of lasers.
It has been tested in only 28 patients, all at Massachusetts General Hospital in Boston. Yet the initial findings hold promise because the laser was the patients’ only treatment and none have had a recurrence or needed surgery or radiation after a mean follow-up of 27 months, the team’s leader, Dr. Steven M. Zeitels, said in an interview. The longest is more than five years.
Other experts expressed cautious optimism about the findings from the pilot study, which the Harvard team reported May 1 at a meeting of the American Broncho-Esophagological Association in Orlando. The scientific report involved the first 22 of the 28 patients.
The procedure “represents a radically new approach to treatment of these cancers,” said Dr. Gregory A. Grillone, an otolaryngologist at Boston University School of Medicine. Dr. Grillone, who directs the Center for Voice and Swallowing at Boston Medical Center, spoke in an interview after hearing Dr. Zeitels’s presentation at the meeting.
Dr. Zeitels agreed with Dr. Grillone and other experts who said the procedure must now be tested on more patients in other hospitals and monitored for a longer period before it could become a standard therapy. Longer studies comparing the new technique with standard therapy are needed to confirm that it is equally effective in curing the cancers.
Even then, only an estimated 2,000 of the 11,300 people, mostly men, who develop laryngeal cancer in this country each year seem likely to be candidates for the laser therapy.
Those eligible would be patients whose cancer was detected when the malignant growth was small and limited to one or both vocal cords in a form known as glottal cancer, which accounts for about 65 percent of new laryngeal cancers. An estimated one-third of glottal tumors are detected in an early stage, Dr. Zeitels said.
If studies confirm the early findings, then researchers must determine which kinds of laryngeal cancers and which patients are appropriate for the laser treatment, said Dr. Andrew Blitzer, a professor of otolaryngology at Columbia and director of the New York Center for Voice and Swallowing Disorders.
The initial clue to cancer of the vocal cords is often persistent hoarseness. The cancer most commonly develops among smokers, who are prone to developing additional types of cancer in the head and neck.
When radiation is used for laryngeal cancer, it cannot ordinarily be used again if other cancers develop nearby. So the laser procedure offers a strong additional advantage, Dr. Zeitels said — preserving radiation as a treatment option for laryngeal cancer patients who later develop head and neck cancers.
Treatment for laryngeal cancer has progressed slowly. Surgery was the only treatment until the advent of radiation in the early 20th century. In 1971, lasers began to be used for a noncancerous vocal cord problem, and different kinds of lasers have followed for vocal cord cancer.
The concept of the laser therapy derives from the work of the late Dr. Judah Folkman, the pioneering Harvard scientist who theorized that tumors could be starved by stopping angiogenesis — the process by which tumors stimulate formation of new blood vessels to feed themselves.
The new procedure relies on a type of laser called the pulsed photoangiolytic KTP. Its green light selectively destroys the blood vessels feeding the tumor without burning the vocal cords. “It’s like sandblasting the surface with light,” Dr. Zeitels said.
Vibration of the vocal cords is essential for good voice and speech. By preserving vocal cord function, the laser treatment allows the cords to vibrate, “not perfectly, but substantially better” than before patients had the procedure, Dr. Zeitels said.
“All the prior laser treatments would burn the vocal cords,” he said, “and when that happens they do not vibrate normally.”
Dr. Zeitels said his team had long used pulsed angiolytic lasers for a variety of benign laryngeal problems, including a precancerous condition called dysplasia.
The pulsed angiolytic laser has allowed ear, nose and throat specialists to treat most laryngeal dysplasias under local anesthesia in an office instead of general anesthesia in an operating room.
But “treating cancer is not the same as treating dysplasia,” he said, and he moved cautiously before using the laser for cancer.
One step was to alter the KTP laser to deliver the light in pulses to the soft tissue of the vocal cords, allowing the tissue to cool between bursts. The cooling prevented significant heat-induced scarring.
The first patient was John Ward, a professor at the Kellogg School of Management at Northwestern University. After several years in which he was hoarse and needed a microphone to give lectures, he said in a recent interview, doctors detected cancers on both vocal cords.
Dr. Ward read up on the disease and consulted with Dr. Zeitels and other specialists about his treatment options. Dr. Zeitels suggested the new laser therapy in extensive discussions, and Dr. Ward agreed.
The two tumors differed in size, so Dr. Zeitels said he aimed at preventing scars that might fuse the cords. He treated the larger cancer with a carbon dioxide laser and the smaller one with the angiolytic laser.
Six weeks later, both tumors had disappeared.
Dr. Ward said the treatment had saved his career — that he now had about 80 percent of his original quality of voice and 90 percent of its strength, and no longer needed a microphone to lecture.
Typically, patients are treated two to three times spaced six weeks apart to reduce the tumor’s size, Dr. Zeitels said. He added that it was generally safe to leave early vocal cord cancers in place for that period of time because they rarely spread at this stage.
Standard acoustic and other tests are performed in a sound-treated room before the procedure and monitored thereafter.
Urologists have used angiolytic lasers in a different way to burn prostate tissue, Dr. Zeitels said. For the vocal cords, “the procedure is dead-on easy” and could be performed by any ear, nose and throat specialist who learns to use the $70,000 laser, he said.
He also speculated that the angiolytic laser might eventually be adapted for treatment of cancers of the esophagus, bladder, cervix, windpipe and parts of the lungs.
Dr. Zeitels said that he had not received industry financial support for his research and that his team’s paper would be published in The Annals of Otology, Rhinology and Laryngology in July.
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May 10: Seeking sleep, willing to pay, Chicago Tribune
70 million Americans have fueled a huge industry with a not-so-simple goal: Getting some shut-eye
By John Keilman | Tribune Reporter
Glenn Yunashko has rarely had a restful night in 30 years.
The Chicago computer consultant, 61, said he wakes frequently because of sleep apnea and stress. Neither surgery nor medical devices have ended his problem, setting him on a weary but tenacious quest for new solutions.
His search brought him Friday to the Big Sleep Show, an expo at Rosemont's Donald E. Stephens Convention Center with dozens of purveyors of mattresses, medicine and gizmos holding out the promise of sweet, peaceful slumber.
"I'm positive I will learn something," Yunashko said. "And I stand a 50-50 chance of seeing something that will make a difference in my life."
The show, which organizers say is one of the first of its kind, is the latest sign of a booming, multibillion-dollar industry geared toward the 70 million Americans thought to suffer from sleep problems.
Though scientists say it's not clear whether people's sleep has grown worse in recent years, it has by some accounts become more scarce: A survey by the federal government found that compared with 1985, more people today get by on six hours or less. The average adult needs seven to nine.
At the same time, people are spending as never before in pursuit of rest. The International Sleep Products Association, the trade group for the nearly $7 billion mattress industry, said more than 1 in 4 mattress sets sold in 2007 cost at least $1,000. In 2001, it was 1 in 7.
The king of them all is the Hastens Vividus, a Swedish model pricier than many luxury cars. A concoction of horsehair, cotton, flax and wool, the all-natural handmade mattress costs $60,000.
Mary Pat Wallace, of Chicago's Hastens Passion for Beds, which did not exhibit at the show, said she has sold three of them so far this year. Her typical customer chooses something relatively more modest -- but still in the $10,000 to $12,000 range.
"Our client is not 20 years old," she said. "It's somebody who's definitely accomplished and looks for the best in products."
Dr. Lisa Shives, medical director of Northshore Sleep Medicine in Evanston, paid only $350 for her mattress, but she represents a different part of the sleep boom. Clinics like hers, which specialize in apnea, insomnia and other sleep maladies, have more than tripled nationwide in the last decade, from 417 to 1,432, according to the American Academy of Sleep Medicine.
"What you're witnessing is a growing awareness of the public that they don't have to suffer from sleep problems," she said. "They're pushing doctors to do something."
That something often comes in a pill -- pharmacies dispensed 54 million sleep aid prescriptions last year, according to health care information company IMS Health -- but many patients increasingly are interested in non-pharmaceutical remedies.
Those were well-represented at the Big Sleep Show, from $80 amber-colored eyeglasses that supposedly encourage the production of the sleep-promoting hormone melatonin, to $20 compact discs that promise to soothe the brain with special tones embedded in New Age music.
Ed Zebus, 61, a retired engineer from La Grange, tried a different balm: a "motion lounge" sold by a Schaumburg company.
Virtual Relaxation Solutions claims its $8,000 system offers the equivalent of several hours of rest in just 20 minutes of reclining on a lounge that mildly rocks and rotates. The aim is to simulate the motion of waves while thrumming music vibrates through the cushion.
It's like a massage performed by a subwoofer, and it worked for Zebus.
"It was a really relaxing, calming experience," he said. "I do some meditation myself, and this seemed to bring me down faster."
A New York company called MetroNaps offered a similar experience with its EnergyPod. A lounge chair with a light-blocking hood, it's supposed to recharge workers in 20 minutes.
Co-founder Christopher Lindholst said that while some American hospitals and dot-com companies have rented the pods for $800 a month, companies overseas seem more comfortable with the idea of snoozing employees. "It's harder in the states," he said. "We have a definite 'work for 8 to 10 hours' mentality."
For attendees whose problem was waking up, inventor Gauri Nanda offered Clocky, a $50 alarm on wheels. At the appointed hour it drives off the nightstand and skitters around the room, beeping and tweeting like R2-D2 until the groggy sleeper chases it down. "I would always hit the snooze button over and over again," Nanda said. "I needed something that would drag me out of bed."
Janis Bell came to Rosemont in search of something more prosaic. The retired software engineer from Berwyn was told a year ago she had sleep apnea, a narrowing of the airway. Though she treats it with a stream of pressurized air delivered through a mask, she still wakes three or four times a night.
Alerted to the show by a support group, Bell, 67, wanted only to find a mask that was more comfortable, or perhaps a new sleep doctor. Anything more than that seemed too much to hope for.
"I'm still waiting for the miracle people talk about," she said. "I don't think there will be a miracle."
Yunashko, a fellow sleep apnea sufferer, wasn't expecting a magic bullet either, but he was interested in a New York doctor's talk on music therapy. She was looking for research subjects, he said, and he was willing to volunteer.
If it didn't work, he reasoned, he'd be out $1,000 or so in travel expenses. If it did, it might change his life.
"I'm here with an open mind," he said.
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May 12: Virus-Linked Throat Cancer Easier to Treat?, WebMD
Study: HPV-Positive Throat Cancers Respond Better to Treatments Than Cancers Not Associated With HPV
By Kelli Miller Stacy
WebMD Medical News
Reviewed by Louise Chang, MD
Researchers have discovered that throat cancers linked to the human papillomavirus (HPV) respond better to cancer treatments than cancers not associated with HPV, a finding that's being lauded as a promising step toward tailored treatment.
Thomas Carey, PhD, professor and distinguished research scientist at the University of Michigan Kresge Hearing Research Institute and co-director of the head and neck oncology program at the University of Michigan Comprehensive Cancer Center, and colleagues published their results in two papers in the May 12 online issue of Journal of Clinical Oncology.
Most throat cancers, or oropharyngeal cancers, occur in people who smoke or chew tobacco. However, certain strains of HPV, including one known to cause cervical cancer, play a role in the development of some throat cancers. According to the American Cancer Society, people with throat cancers linked to HPV are less likely to smoke and drink, and generally have better survival rates.
"The biggest challenge is how best to treat patients with tumors that stem from tobacco and alcohol use as opposed to tumors linked to HPV. We now know they're two different cancers," study researcher Francis Worden, MD, assistant professor of internal medicine at the University of Michigan Medical School, says in a news release.
Scientists blame HPV infection for a recent rise in throat cancer cases, particularly among younger patients, according to background information in the journal article.
The current study involved 66 patients with advanced throat cancer. Each study participant received an initial round of chemotherapy to determine how well the tumor responded to the cancer-killing medication. If the treatment reduced the tumor by more than half its original size, the patient received radiation and a full course of chemotherapy.
The first round of chemotherapy successfully shrank the tumor in 54 patients, and most of these patients went on to receive additional chemotherapy with radiation. After four years, 62% of those patients were still alive. Most of the patients had surgical treatment of their cancers if their tumor did not respond to the first round of chemotherapy. Only four of the 11 patients who did not respond to the first round of chemotherapy survived.
The researchers' next step was to determine why chemoradiation failed to work in a subset of patients. They looked at tissue samples taken from patients before treatment and found that 64% tested positive for a high-risk strain of HPV (HPV 16). The team's analysis showed that most of the HPV-positive tumors responded to the first round of chemotherapy. Only four patients with HPV-negative tumors survived.
The experiments also revealed that patients with tumors that give off high levels of a certain growth factor receptor called EGFR had the poorest survival rates.
"The combination of markers was an important indicator. Patients whose tumors expressed high levels of EGFR did poorly. But those who had high EGFR and were also HPV-positive had some protection. Patients with high EGFR and low HPV fared the worst," Bhavna Kumar, a research laboratory specialist and study co-author, says in a news release.
Study authors say their findings have large implications for therapy.
"The chemotherapy and radiation therapy we use to treat this type of cancer is very aggressive. If we can identify those patients most likely to respond, we could reduce the intensity of the therapy for those likely to have the best outcomes. At the same time, we hope to identify new treatments that specifically target those tumors that we know are not responding to current therapies," Carey says.
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May 13: A Pot, Short and Squat, To Clear Your Nose Out, The Wall Street Journal
By LAURA JOHANNES
Spring is here, and with it comes misery for allergy sufferers. The neti pot, a small teapot-like device used to irrigate your nose, can help you breathe easier, according to companies that sell them. Physicians say nasal irrigation is a helpful, inexpensive treatment for allergy symptoms, the common cold and many other nasal conditions, but it isn't a cure.
About 50 million Americans suffer from rhinitis, a condition that includes a stuffy nose, sneezing and itchy eyes, mouth and throat, according to the American Academy of Allergy, Asthma & Immunology. It is usually caused by allergies but also can have other causes. Many people suffer chronically from nasal and sinus symptoms, including post-nasal drip, when mucus from the nose runs into the throat.
The neti pot is used to cleanse mucus from the nasal passages, and may also help to rinse out allergens. You fill the pot with salt-water solution, tilt your head to one side and pour water into the top nostril. Gravity takes over and the water pours out the other nostril.
"People say at first that this seems weird and disgusting," says Melissa A. Pynnonen, co-director of the Michigan Sinus Center at the University of Michigan in Ann Arbor. "But generally, if I can get adults to do it once, they don't want to stop since it treats post-nasal drip and mucus better than anything else."
A neti pot, often made of plastic or ceramic, generally costs from $10 to $15. The saline solution can be purchased pre-packaged, or you can mix it at home. Dr. Pynnonen recommends using the pot twice daily, mixing eight ounces of lukewarm tap water with a quarter teaspoon of kosher salt and a quarter teaspoon of baking soda. She tells her patients to make the sound of the letter "k" to prevent the unpleasant sensation of water running into the throat.
Scientific evidence supports nasal irrigation for relief of chronic nasal symptoms. The Cochrane Collaboration, in a 2007 analysis, reviewed eight papers on neti pots and other types of nasal irrigation and concluded there is evidence that it is beneficial for chronic nasal symptoms, either as a sole treatment or in conjunction with standard treatments. A 2006 study on neti pots, by researchers at the University of Wisconsin, found regular use improved quality of life for allergy sufferers.
The neti pot provides at least partial relief for many people, but isn't a miracle cure, physicians say. You still need to try to avoid allergens, and you may need conventional allergy medicine for some symptoms. Also, irrigation helps dislodge mucus but it isn't known if it eases itching in the eyes, which can cause as much misery as nasal symptoms, physicians say.
Also, you don't necessarily need a neti pot to irrigate your nose. Other options include a squeeze bottle, a syringe or a turkey baster, which provide more positive pressure and are likely to dislodge more mucus, physicians say. The neti pot is gentler and less likely to result in fluid traveling into the middle ear and causing temporary loss of hearing, says Bradley Marple, vice chairman of the department of otolaryngology at the University of Texas Southwestern Medical Center in Dallas.
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May 19: Sleep Disorder Raises Heart Risks While Flying, The New York Times
People with obstructive sleep apnea may be at greater risk for heart troubles during air travel, a new study shows.
Sleep apnea is a common condition characterized by temporary breathing interruptions during sleep, often due to an upper airway obstruction. People with sleep apnea often snore loudly and gasp for air during sleep.
In a new study, Australian researchers looked at oxygen levels and breathing patterns in healthy people and in 22 people with severe sleep apnea during a simulated flight. All study subjects were awake, and the conditions in the simulator mimicked oxygen and pressure levels typically found on commercial airline flights.
The researchers found that people with obstructive sleep apnea had lower levels of oxygen in their blood before and during the simulated flight. People with apnea experienced higher heart rates, physiological stress and demand for oxygen than healthy people, according to the findings, presented this weekend at the American Thoracic Society’s 2008 International Conference in Toronto.
“We addressed obstructive sleep apnea because it is becoming so much more common as obesity increases and there are greater numbers of obese passengers on commercial flights,'’ said lead researcher Leigh Seccombe, a senior scientist in the department of thoracic medicine at Concord Repatriation General Hospital in Sydney.
The results suggest patients with obstructive sleep apnea are at higher risk for heart problems during air travel, and raise questions about whether patients with severe apnea should travel with supplemental oxygen, the way patients with lung diseases do.
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May 19: Immune System Kick-Started in Nasal Lining, Scientists Find, The JHU Gazette
New therapies could help combat inflammation from sinusitis and asthma
By David March
Johns Hopkins Medicine
Scientists at Johns Hopkins have outlined a new path for potential therapies to combat inflammation associated with sinusitis and asthma based on a new understanding of the body's earliest immune response in the nose and sinus cavities.
Researchers say their findings, published in the May edition of The Journal of Allergy and Clinical Immunology, are the first evidence describing how viral agents, such as the rhinovirus responsible for the common cold, can kick-start the body's mobilization of immune white blood cells in the moist, mucous membrane lining of the nasal passages.
While such responses are key to maintaining health in the face of pathogens, they can also become a source of illness due to resulting inflammation. This can lead to potentially lifelong problems, including tissue swelling, nasal polyp formation, sneezing, stuffy and runny nose, sore throat, cough, headache, chills, fever and breathing difficulties.
Thus, blocking these reactions, the re-searchers point out, could interrupt the cascade of feel- awful symptoms that ensue.
The focus of the study is B7-related proteins, called B7 homologs, which trip white blood cell response in a pathogen attack.
Using purified cold virus and its genetic material as bait, the scientists found that production of two B7 homologs spiked in response; levels of B7-H1 jumped almost ninefold, and levels of B7-DC tripled.
Until now, says senior study investigator Jean Kim, viruses were known to reside in and infect the physical epithelium, invading surface membrane cells and revving up the immune system's main blood cell defenses, "but no one knew the major steps involved in or precisely how this immune response was triggered."
"The inside surface of our nose and sinuses is much more than a protective cover, and we have good scientific evidence to show that epithelial cells on these mucosal membranes are very powerful mediators — middlemen — in diseases that result in inflammation," she said. An assistant professor at the School of Medicine and an expert in the molecular origins of inflammation, Kim is also an authority on nasal and sinus infections.
Moreover, she notes, study results demonstrate how the body's immune system is interconnected, where one key part, the physical lining that filters out and captures invading viruses and environmental allergens, can trigger the other key part, which leads to targeted white blood cell action.
"Now that we have a better understanding of the immune pathway, we can start to develop therapies that could potentially block the triggering reactions for sinusitis and asthma, which are both made worse when people are infected with the common cold virus," she said.
Sinusitis is the most common respiratory complaint in the United States. The condition is often linked with asthma, which affects more than 30 million people, 9 million of them children. Each year, 62 million Americans catch a cold.
The study also explains a common failure in current therapy.
According to Kim, nasal and oral steroids are frequently prescribed for many of the 15 percent of the American adult population who suffer from sinusitis, nasal polyps or asthma. Steroids complement drugs taken for symptomatic relief, such as decongestants and pain relievers.
But corticosteroid drugs, she says, do not work for everyone, and their effectiveness often wanes over time.
This may be related to the B7 homolog triggers in the mucous membranes, Kim says, as study results showed that corticosteroid therapy does not fully shut down or prevent their overproduction.
In the study's first set of experiments, researchers found that levels of two of five key proteins tested, B7-H1 and B7-DC, rose sharply after samples of nasal cell concentrate were exposed to genetic material from cold viruses. Spiked production was detected using antibodies chemically tagged to glow when bonded to a specific B7 homolog.
However, when researchers pretreated the cell scrapings with a well-known anti-inflammatory corticosteroid called flucticasone propionate, the drug failed to stop overproduction of either B7-H1 or B7-DC.
In the final set of study experiments, six adult volunteers were infected with the cold virus and monitored for variations in their immune response during infection, which typically lasts a week to 10 days.
Analysis of daily scrapings of surface cells lining the nose showed that production of B7-H1 and B7-DC peaked on the second and third days, when cold symptoms were also at their worst. These protein levels, as a measure of severity of the immune response, dropped quickly afterward, and at the same time as scores of symptom severity went down. It was this evidence, Kim says, that verified the triggering connection between the cold virus and the immune white cell response inside the nose and sinuses.
Kim says that researchers' next steps are to analyze the biological control mechanisms for producing the B7 homologs in the nasal lining, and to map out any chemical interactions that result, to look for ways of breaking the cycle of inflammation involved in sinusitis, asthma and colds.
The study, which ran from 2003 to 2007, was funded by the National Institutes of Health and the Flight Attendant Medical Research Institute. Sinusitis afflicts thousands of fight attendants who were exposed to secondhand smoke before smoking was banned on airlines in the late 1980s.
In addition to Kim, Johns Hopkins investigators involved in this research were Lowella Heinecke and Scherer Sanders. Further assistance was provided by David Proud, of the University of Calgary; and Robert Schleimer, of Northwestern University's Feinberg School of Medicine.
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May 20: Esophageal Therapy You Can Stomach, The Wall Street Journal
Got heartburn? Several times a week for five or more years? Then you're at increased risk for a form of esophageal cancer that, though rare, is the fastest-growing cancer in the U.S., particularly in white men over 50. It's also one of the most deadly, with a five-year survival rate of just 17%.
Doctors can sometimes see the cancer coming years earlier when acid reflux causes cells in the esophagus to mutate to become more like stomach tissue, a condition called Barrett's esophagus. In adenocarcinoma, the Barrett's cells keep mutating into cancer.
The standard treatment for Barrett's has been to watch for precancerous changes called dysplasia, and in some cases remove the patient's esophagus. But a new outpatient procedure that lets doctors zap Barrett's tissue with radiofrequency ablation (RFA) is showing promise.
At a conference of gastroenterologists in San Diego on Monday, researchers presented interim results from a multi-center trial showing that among patients treated with RFA, 85% were free of dysplasia, and 74% were free of all signs of Barrett's, 12 months later. None of the treated patients progressed to high-grade dysplasia or cancer. In the control group, several patients got worse, and none was free of Barrett's.
Other studies showed that RFA caused few side effects and that genetic changes in the esophagus returned to normal afterward.
"It's way cool. It's far and away the most effective endoscopic treatment that we've ever had," says Nicholas Shaheen, director of the Center for Esophageal Disease and Swallowing at the University of North Carolina-Chapel Hill School of Medicine and the lead investigator.
The RFA procedure involves no incisions, but the patient is sedated. A gastroenterologist inserts a tiny camera, along with a sizing balloon, down the patient's esophagus. A second balloon delivers a short burst of energy that burns out the Barrett's tissue, which appears rough and red in contrast to healthy pink tissue. The technology, called the HALO Ablation System, is made by BÂRRX Medical Inc., a privately held company in Sunnyvale, Calif.
The RFA procedure is usually repeated a few months later, with a smaller HALO device. "It's like removing old wallpaper -- you do a big stripping and then go back and remove any bits that are left," says Charles Lightdale, a gastroenterologist at NewYork-Presbyterian Hospital/Columbia, who also consults for BÂRRX.
To date, about 16,000 RFA procedures have been performed since 2001; it's available at about 200 centers in the U.S., and covered by Medicare and most insurers. It's too soon to know whether the Barrett's will return in the long run. Patients are usually kept on acid-blocking drugs.
No one knows why adenocarcinoma of the esophagus is rising so fast -- up sixfold in the U.S. since 1975. It appears to be related to obesity, especially belly fat, which puts pressure on the abdomen. Another form of esophageal cancer, squamous cell, linked to alcohol and tobacco use, is declining in the U.S.
An estimated 3.3 million Americans have Barrett's. Only about 1 in every 200 of them will develop esophageal cancer. But people with high-grade dysplasia have a much higher risk.
For them, RFA appears to be a good alternative to an esophagectomy, a grueling operation that severely restricts eating. A big question now is whether people with earlier stages of Barrett's should be treated with RFA, which is still new and costly, or just watched with endoscopes and biopsies.
"This is very safe and effective therapy," says Dr. Shaheen, who gets no remuneration from BÂRRX. "But as we move from high-risk to lower-risk patients, the calculus changes."
Some patients are eager to eliminate the cancer risk. Louis Plzak, a retired thoracic surgeon from Philadelphia, had monitored his Barrett's for several years when he learned about RFA at a surgical conference and decided to have it done preventatively. "This will allow me to start living without the fear of Barrett's," says Dr. Plzak, age 74.
If you're having reflux several times a week, if you need medicine to control it or if you had it in the past, see a gastroenterologist. Chronic heartburn may stop once Barrett's sets in, since the mutated tissue isn't as sensitive to reflux. Controlling your weight will also help cut your risk of esophageal cancer.
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