The key to that success is reducing the risk of chronic rejection, also called bronchiolitis obliterans syndrome, a condition in which the lung tissue deteriorates over time. There are currently no medications to treat chronic rejection.
Laurie Snyder, MD, MHS, assistant professor of medicine (Pulmonary, Allergy and Critical Care Medicine) and one of the associate medical directors of the Duke Lung Transplant Program, says she and her colleagues are pursuing several avenues to address chronic rejection. One of the most exciting pursuits is a new assay to identify patients at risk for infection with cytomegalovirus (CMV). “If you have CMV after lung transplant, you’re at higher risk for chronic rejection,” Snyder says, “so we’re very interested in trying to prevent CMV.”
The current strategy is to treat all lung transplant patients for a year with medicine that prevents CMV, but the medicine has side effects. Furthermore, it’s a one-size-fits-all treatment, because some patients are more susceptible to CMV and may need longer treatment.
Snyder and her colleagues have developed an assay using a blood sample and a CMV peptide to determine which patients are relatively immune to CMV and which ones are more at risk of infection. In a small study, they found the assay was effective at identifying patients who were likely to develop CMV after going off the preventative medicine. “Rather than just taking everybody off the medicine after a fixed period of time, we can individualize their prophylaxis length,” Snyder says. “Some people need more than a year; some people less than a year.”
Snyder says that project, which was funded by the Biomarker Factory, was a “really nice multidisciplinary collaboration.” She worked with Kent Weinhold, PhD, professor of surgery and immunology, in the DTRI Immune Monitoring Lab to develop the assay. Cliburn Chan, MBBS, PhD, MS, assistant professor in the department of biostatistics and bioinformatics in the School of Medicine, helped with data analysis. Scott Palmer, MD, MHS, associate professor of medicine (Pulmonary, Allergy and Critical Care Medicine), also worked on the project. The group is now seeking funding for a large, prospective, randomized multicenter trial of the assay.
There are also ongoing clinical trials testing various drugs. “We have an active clinical trial going on right now using inhaled aztreonam in patients with early stage chronic rejection,” Snyder says.
Aztreonam is already FDA-approved for use in cystic fibrosis and treating pulmonary infections. “We’re enrolling patients in a multicenter study to see if this inhaled drug is tolerable for lung transplant patients as well as to prevent chronic rejection or decline in lung function,” Snyder says.
On the basic science side, Snyder says her colleagues are working on developing rat and mouse models for chronic rejection. These models will make it easier to study potential treatments.