An inhaled drug designed to reduce the odds of a new lung being rejected after a transplant may dramatically improve survival afterwards, says a new study from the University of Pittsburgh.¹

The results of the research are published in the January 12 issue of The New England Journal of Medicine.

Inhaled Cyclosporine May be Effective
It was the first double-blind, placebo-controlled trial ever conducted in lung transplant patients. The researchers tested an inhaled form of cyclosporine, a widely used medicine to prevent organ rejection after a transplant procedure. The study was held between 1998 and 2001.

“Inhaled cyclosporine is the first drug ever to show a decline in the incidence of chronic rejection, the leading cause of death following a lung transplant,” explained Aldo Iacono, MD, the study’s lead researcher and an associate professor of Medicine at the University of Maryland.

“In our study, the patients who took the inhaled cyclosporine had a two-thirds reduction in chronic rejection compared to those who had the placebo,” Iacono said. “The risk of death, adjusting for all other variables, was five times greater in the group of patients who took the placebo than among those on the inhaled cyclosporine.”

Traditional Versus Inhaled Treatment Compared
The study included 56 people who had received either a single or double lung transplant. Within a month following the operation, they were assigned at random to receive either the inhaled cyclosporine or an inhalable placebo with traditional anti-rejection treatment. The patients took the inhaled drugs at home three times a week. They were then followed by the researchers for a total of two years.

“The results of this study are exceedingly important for lung transplant patients,” said Bartley Griffith, MD, a professor of Surgery and head of the Division of Cardiac Surgery at the University of Maryland.

“It just makes a lot more sense to give a higher concentration of drug right into the area you are trying to treat,” said Griffith, show was also a senior investigator in the study. “Conventional anti-rejection drugs, which are given orally, do not get into the small air sacs of the lungs where chronic rejection takes place.”

Organ-specific immune suppression is primarily a new way of treating rejection, he added.

Of 26 patients who received the inhaled cyclosporine, 23 were still alive two years later. However of 30 patients in the group given a placebo combined with traditional anti-rejection drugs, only 16 were alive at the two-year point, the investigators reported.

“Our study shows for the first time that inhaled cyclosporine, taken in conjunction with oral anti-rejection medication, can protect patients from chronic rejection, which is the main reason than the average three-year survival rate from lung transplantation is only 55 percent—a much lower rate than for other solid organ transplants,” Iacono said.

Safety Was a Concern
One of the key challenges in the research was adding a substance to the cyclosporine that enables patients to safely inhale the mixture without irritating their throats or lungs. They decided to combine the cyclosporine with propylene glycol, which allowed the drug to be given as an aerosol.  The formula allowed patients to breathe in high doses of the anti-rejection drug without hurting other organs. About half of the people in the study, coming from either group, experienced some respiratory irritation. But they were able to tolerate the therapy after a few subsequent doses, the investigators claimed.

“My hope is that one day soon, our patient swill have access to this therapy,” Iacono said.

1. Iacono AT, Johnson BA, Grgurich WF et al. A randomized trial of inhaled cyclosporine in lung-transplant patients. N Engl J Med 2006 Jan 12;354(2):191-3.

John Martin is a long-time health journalist and an editor for CuraScript. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.