Lung Transplantation Research
Our transplant research group conducts basic, translational, and clinical research to improve the care of lung transplant recipients and to optimize utilization of donor lungs. Our longstanding collaboration with Tennessee Donor Services facilitates many of these research projects.
Ex vivo isolated perfused human lung model systems
We have developed an ex vivo human lung perfusion system to allow mechanistic investigation into lung injury in an intact human lung and for testing of novel therapeutic agents. Using this system, we identified that intravascular cell-free hemoglobin causes lung endothelial injury and that acetaminophen can prevent this. When used with a cross circulation platform, this technique can be extended over several days to allow for investigations into mechanisms of lung repair.
Donor lung research
Approximately 60-70% of potential donor lungs are declined for transplantation. We have several projects underway to try to improve lung suitability for transplant and to better understand which lungs are appropriate for transplant. In our HME study, heat moisture exchange filters are collected from the ventilator circuits of potential organ donors from Vanderbilt to collect condensed fluid from the airspaces for biomarker and proteomic studies of donor lung injury. The GOLD clinical trial is comparing the effect of two ventilation strategies on organ acceptance for transplant. In the GOLD trial, one group is managed with high PEEP and lower tidal volume ventilation and the other with lower PEEP and standard tidal volume ventilation.
Impact on other acute and chronic lung disease
Access to human lungs that have been declined for transplantation is an invaluable tool for a wide variety of research programs. Single cell gene expression analysis of declined donors lungs forms the backbone reference sample for studies of COPD, IPF, CF, and other smoking related disease. Declined donor lungs can also facilitate research on mechanisms of acute lung injury and ARDS.
A lung transplant biorepository is maintained by Dr. Shaver. This includes all explanted human lungs as well as bronchoalveolar lavage and plasma samples at multiple timepoints at the time of and after transplantation from all post-transplant bronchoscopy procedures. These samples are available to coinvestigators for collaborative research. Current projects include studies on biomarkers of acute rejection and microbiome assessment after lung transplantation.
The Vanderbilt Lung Transplant Program is an active participant in clinical studies in lung transplantation. Studies include ongoing assessment of quality of life in lung transplant recipients, optimization of pulmonary rehabilitation programs before and after lung transplantation, treatment options for chronic lung allograft dysfunction, and evaluation of cell free DNA and microRNA in lung transplant patients. We have an excellent research infrastructure allowing for ready participation in interventional clinical trials.