Researchers at the San Francisco VA Medical Center (SFVAMC) and the University of California, San Francisco (UCSF) have identified six genes associated with lymphocytic bronchitis, which is thought to lead to obliterative bronchitis (OB), the most common cause of long-term failure of transplanted lungs.
The researchers hope their results will lead to an earlier, more sensitive, and more accurate standard test for chronic lung rejection, as well as greater understanding of the rejection process.
The study is being published in the September 2005 issue of the Journal of Heart and Lung Transplantation, currently available online.
In obliterative bronchitis, scar tissue forms in breathing passages of the transplanted lung, narrowing them and eventually making it impossible for the recipient to breathe. The exact cause is unknown, but it is believed to be related to rejection of the lung by the recipient's body.
"For lung transplant patients, the biggest barrier to long-term survival is control of rejection," says principal investigator George Caughey, MD, head of Pulmonary and Critical Care Medicine at SFVAMC. "If we know rejection is occurring, we can adjust the patient's medication to try and prevent it. But the problem with lung transplants is that it's hard to detect chronic rejection." Currently, he says, OB is best detected through a breathing test--but by the time the disease has a perceptible impact on the patient's ability to breathe, it's often too late to treat effectively.
Caughey and his fellow researchers studied lung biopsy samples from 22 lung transplant patients, with the goal of detecting genes and gene products associated with inflammation and formation of scar tissue in breathing passages. Using a customized version of a conventional laboratory technique, they found that they were able to look at hundreds of gene products simultaneously in lung tissue samples only a few millimeters across. "That was our first achievement: being able to accurately measure that many genes in small samples," notes Caughey, who is also a professor of medicine at UCSF. "We succeeded way beyond our expectations."