Acidic mammalian chitinase gene linked to recurrent sinusitis
By Johns Hopkins Medical Institutions
Sep 7, 2006, 00:39
Although it's unclear why it's so, scientists at Johns Hopkins have linked a gene that allows for the chemical breakdown of the tough, protective casing that houses insects and worms to the severe congestion and polyp formation typical of chronic sinusitis.
A team of Hopkins sinus experts has found that the gene for the enzyme, acidic mammalian chitinase (AMCase), is up to 250 times more active in people with severe sinus inflammation that persists even after surgery when compared to patients in whom surgery is successful. Sinus surgery is usually the treatment of last resort for those who do not respond to drug therapy. But nearly one in 10 of those treated see symptoms return within weeks or months after surgery fails to keep open the nasal passages, scientists say.
The Hopkins report, published in the July issue of the American Journal of Rhinology, is believed to be the first to identify the enzyme's presence in the nose and confirm its link to sinusitis.
"This finding does not mean that there are actually parasites in the nose causing sinusitis, but our study does lend support to the concept that really severe and persistent sinusitis may be a case of a misplaced immune response directed against parasites that are not really there," says study lead author Andrew Lane, M.D., an associate professor at The Johns Hopkins University School of Medicine and director of its rhinology and sinus surgery center.
Previous research by other scientists had looked at the enzyme's tie-ins to asthma, which, like nasal polyps, is an inflammatory response of the body's immune system. The theory, Lane says, is that allergies and asthma result from genes that control the body's defenses against parasites, but these genes are dormant in healthy people. However, when turned on by so-called ghost parasites, the potent inflammatory response is medically very difficult to control.
Researchers say that although chitin, a rigid chemical compound common to fungi, insects and roundworms, is not naturally found in the human body, the presence of its corresponding enzyme and its role in the buildup of mucus and fluids, and polyp formation makes the enzyme a legitimate target for drug therapies to block its production and action.
"If we can selectively shut down the antiparasite immune response, we could potentially have new treatments for these airway diseases of the lung and nose," says Lane.
New therapies are needed, he says, as an alternative to long-term steroids, which block the inflammatory chemical pathway but also have debilitating side effects, including loss of bone density, cataracts in the eye and weight gain.
An estimated 32 million Americans suffer from persistent inflammation of the tissue that lines the nasal and sinus cavities, according to the United States Centers for Disease Control and Prevention.
Thirty-three men and women participated in the two-year study at Hopkins, designed to find out if any of the genetic traits already known to be common in asthmatics were as active in patients with sinusitis. Twenty-two were scheduled to have surgery for sinusitis, while the remaining 11 served as study controls, having surgery for some other ailment than sinusitis.
All those who underwent sinus surgery did so after standard therapy using antibiotics, decongestants and steroids had failed to stop their symptoms and keep their sinus inflammation from coming back. They also had nasal polyps, or tissue outgrowths resulting from the inflammation, which, Lane says, are particularly hard to treat.
In the surgery, a thin, tube-like endoscope is inserted into the nose, with a camera attached to provide a close-up view of the nasal and sinus passages. Slender surgical instruments placed alongside the endoscope allow surgeons to cut away inflamed tissue and polyps, clearing a path for the sinuses to drain normally. Lane says that if left untreated, polyps can lead to severe blockage and recurring infections.
All patients were monitored for a minimum of nine months to see if polyps and their resulting symptoms returned. Ten in the surgery group had their polyps return within six months, while 12 remained symptom free.
The Hopkins team took samples during surgery of the mucous membrane lining the nose, and using real-time polymerase chain reaction tests, analyzed the samples for any genetic differences between the groups.
When researchers initially compared all the nasal tissue samples, they found that half had the gene for AMCase turned on, or expressed, to make the chitinase protein. During follow up, they found that the 10 patients who had their polyps return had exceedingly higher levels of AMCase expression than the other sinusitis patients and controls. Gene expression of another inflammatory protein, called interleukin-13, already known to be high in asthmatics, was also found to be elevated in those with polyps, but the levels of interleukin-13 did not have the same predictive value as the elevated expression of AMCase, researchers say.
Lane adds that future research will have to determine if high genetic expression of AMCase is an underlying cause of inflammation or if AMCase is simply one of many chemicals produced by cells in the nose in response to chronic inflammation.
The next phase of their research, he says, is to look for what triggers the anti-parasite response. However, Lane cautions that this reaction against parasites may come at the expense of the nose's ability to ward off other invaders, such as bacteria, viruses or fungi.
"The epithelial cells lining the nasal and sinus cavities play an important role as first responders of the immune system," he says. "But when they are distracted fighting non-existent parasites, they cannot deal well with the very real microbes continuously coming into the nose."
This, Lane notes, may promote growth of bacteria and fungi in the nose, which is a common finding in those with chronic sinusitis with polyps.
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