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WASHINGTON -- Duke University Medical Center researchers
have found that a surgical procedure used to treat chronic
heartburn appears to not only improve the functioning of
transplanted lungs, but also has a positive effect on an
untreatable form of chronic rejection in lung transplant
recipients.

The procedure, known as fundoplication, creates a
super-competent sphincter at the point where the esophagus
meets the stomach. Surgeons create this sphincter by wrapping
the top portion of the stomach around the base of the
esophagus, preventing gastric acids, enzymes and other stomach
contents from splashing up the esophagus and potentially into
the lungs.

"Reflux occurs in about one-third of patients with end-stage
lung disease, and after lung transplantation, two-thirds of
patients will experience reflux," said transplant surgeon R.
Duane Davis, M.D., surgical director of Duke's lung transplant
program. "Lung transplant patients in our study who received
the surgery had an average 24 percent increase in their lung
functions."

Additionally, the fundoplication surgery seemed to have a
positive effect on bronchiolitis obliterans syndrome (BOS), a
progressive disorder in which tiny airways known as bronchioles
become replaced with fibrous scar tissue. BOS is considered to
be the main reason why the five-year survival rate for lung
transplant patients is only 40 percent. It is little understood
and for that reason, there are no effective treatments, Davis
said.

Davis presented the results of the Duke study, which was
funded by Duke's department of surgery, at the annual meeting
of the American Association for Thoracic Surgery.

Chronic heartburn, also known as gastroesophageal reflex
disease (GERD), occurs when contents of the stomach back up, or
reflux, into the esophagus, the tube that allows food to pass
from the mouth to the stomach. In some cases, the stomach
contents can reflux up the esophagus and into the lungs, a
condition known as aspiration.

For his analysis, Davis prospectively reviewed the records
of 108 Duke lung transplant patients. Of those patients, 70 (65
percent) had documented cases of GERD, and 34 of those went on
to receive the fundoplication surgery. Of those receiving the
surgery, 21 had signs of BOS, which is rated on a scale of
BOS-0 to BOS-3, depending on the seriousness of the damage.
BOS-3 is the most advanced stage.

Of those 21 patients, 11 showed improvements in their BOS
scores, with two improving two grades (from BOS-2 to BOS-0),"
Davis said. "It appears that we now have a potential treatment
for an untreatable condition that seems to work. What we still
need to determine is the timing of the surgery."

Davis said that it is seems logical the patients with
documented GERD should receive the surgery earlier rather than
later.

"Earlier detection and treatment may prevent irreversible
damage to the transplanted lung caused by the aspiration of
gastric contents," he said.

While the study showed a clear benefit of the fundoplication
surgery for lung transplant patients, what is still not clear
is the mechanism by which GERD impacts the BOS, Davis said.

One theory is straightforward -- the caustic gastric
contents actually damage or destroy cells lining the lung,
Davis said. Since the process of transplantation severs all
nerves, transplant patients do not have the normal cough
reflex, so any aspiration materials are not quickly cleared.
Also, the tiny hairs known as cilia that line lung passages do
not function properly in transplant patients.

Another explanation, according to Davis, is that the acid
causes cells on the transplanted lungs to slough off, causing
more donor materials to be presented to the immune system,
causing inflammation.

"A more intriguing explanation revolves not so much on how
the immune system responds to the transplanted organ itself,
but how it responds to some other event," Davis said. "If
something, like reflux for example, causes inflammation to
occur, the immune cells that respond could create a robust
response to the injury, leading to BOS. If there wasn't a
trigger like reflux, the immune cells would not respond to the
transplanted lung alone."

Duke surgeons performed their first lung transplant in 1992.
In the ensuing 10 years, the Duke program has become the
largest in the country, having performed more of the surgeries
than any other program in each of the past two years.

Other members of the Duke team included Christine Lau, M.D.,
W. Steve Eubanks, M.D., Theodore N. Pappas, M.D., Dennis
Hadjiladis, M.D., Robert Messier, M.D. and Scott Palmer,
M.D.

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