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 Johns Hopkins sinus experts has found that
the gene for the enzyme, acidic mammalian chitinase, known
as 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 Johns 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," said study lead author Andrew Lane, an associate
professor at the Johns Hopkins 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. These genes are dormant in healthy people; when
turned on by so-called ghost parasites, however, 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 make the enzyme a
legitimate target for drug therapies to block its
production and action.
"If we can selectively shut down the anti-parasite
immune response, we could potentially have new treatments
for these airway diseases of the lung and nose," Lane
said.
New therapies are needed, he said, 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 Johns 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 ailment other 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 said, are particularly hard to
treat. 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, and 12 remained symptom-free.
The Johns 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 said.
Lane said 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 said, is to look
for what triggers the anti-parasite response. However, Lane
cautioned 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 said. "But when they are distracted
fighting nonexistent 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.
Funding for this study was provided in part by the
National Institute on Deafness and Other Communication
Disorders, a member of the National Institutes of Health,
and by the American Rhinologic Society.
Other researchers involved in this study, conducted
solely at Johns Hopkins, were Murugappan Ramanathan Jr. and
Won-Kyung Lee.
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