Study: Inhalant Helps in Lung Transplants

Monday, April 26th 2004, 12:00 am

By: News On 6

WASHINGTON (AP) _ Scientists have created a way for transplant recipients to inhale an anti-rejection drug deep into their new lungs _ and a study unveiled Saturday suggests the therapy may increase patients' chances of survival four-fold.

Organ-specific anti-rejection therapy is a novel approach, and this inhaled version of cyclosporine remains experimental. Its creators at the University of Pittsburgh are working with a drug company to seek government approval for its sale.

Doctors say the new approach holds promise in battling a huge problem for lung transplantation _ a type of rejection that makes it a particularly perilous organ transplant.

``It makes good sense to apply the immuno-suppressive agent right to the location where the problem exists,'' said Dr. Ed Garrity, director of lung transplants at Loyola University Medical Center.

Reviewing Pitt's research, ``it looks like it works,'' Garrity said.

Lung transplants are among the riskiest of organ transplants, and patients' odds haven't improved significantly in over a decade.

About 45 percent of lung recipients survive five years, compared with 75 percent of recipients of hearts, livers and kidneys, said Dr. Aldo Iacono, lung-transplant chief at the University of Pittsburgh Medical Center.

The main reason: A newly implanted lung is particularly vulnerable to chronic rejection, a gradual scarring called ``bronchiolitis obliterans'' that eventually destroys it.

``This is the Achilles heel of the lung transplantation process,'' Iacono said.

Organ recipients take a cocktail of immune-suppressing pills, often including cyclosporine, to ward off both immediate and chronic forms of rejection.

But Iacono theorized that getting anti-rejection therapy directly into the lungs might provide greater protection for those patients, by fending off immune cells' attack of the delicate tissue right at the source.

So Pitt researchers dissolved powdered cyclosporine, donated by Novartis Pharmaceutials, into another chemical so it can be inhaled as a mist using a nebulizer, much like certain asthma medications are.

Then, in a study funded by the National Institutes of Health, they divided 56 new lung recipients into two groups. Everyone got standard anti-rejection treatment. But half also were given the inhalable cyclosporine and half a dummy nebulizer, to use three days a week for two years after their transplant.

Patients were tracked for two to five years. Eleven percent who inhaled cyclosporine died in that time period _ compared with 47 percent who got the placebo, Iacono told a meeting of the International Society for Heart and Lung Transplantation on Saturday.

A mixture of lung biopsies and lung-function tests showed the cyclosporine prevented chronic rejection, he added. Signs of rejection ranged from 19 percent to 39 percent of cyclosporine patients, depending on the test used, compared with 60 percent to 70 percent of placebo patients.

``This may offer hope to a group of patients that basically has no hope,'' Iacono said.

Pitt researchers since the 1990s have used inhaled cyclosporine in about 150 patients already suffering severe rejection, saying it can buy them some time. But other lung specialists have been skeptical because, unlike the new prevention research, that treatment hasn't been offered in a strictly controlled study.

The new study was done well enough to suggest ``this kind of approach may be one whose time has come,'' said Loyola's Garrity.

Pitt has licensed the treatment to Chiron Corp., and provided the study results to the Food and Drug Administration, Iacono said. Chiron and Pitt researchers soon will meet with the FDA to discuss what steps are needed to seek approval of the drug for lung transplants.

But it may have ``fairly dramatic implications'' for other lung diseases that also involve immune cells called T cells, Iacono said. ``This is a new venue in therapeutics.''