Novel strategies to increase the number and quality of donor lungs for transplantation

Lung transplantation is a lifesaving treatment option in well-selected patient with end-stage lung disease. Due to the successes of lung transplantation, transplant programs are expanding rapidly worldwide. However, two major problems impede optimal outcome early after lung transplantation. First, 10 to 30% of all lung recipients develop primary graft dysfunction, which is the leading cause of early morbidity and mortality after lung transplantation. PGD is a form of organ failure, and is the end-result of an injurious process that already starts in the donor, continues during preservation of the donor organ and peaks upon reperfusion in the recipient. This results in accumulation of lung water and impaired oxygen transport. Secondly, many donors do not match the strict criteria of lung donation. Therefore, there are more patients listed for lung transplantation than there are donor lungs available, and consequently 12% of listed patients die while waiting in Europe. In addition, those lungs that are available or often of limited quality which again leads to a higher incidence of graft failure and limited early outcome.

This PhD project focusses on two separate time intervals prior to the lung transplant procedure that influence the number and quality of donor lungs. During the donor phase, a suitable donor organ is selected after careful evaluation by the transplant team to obtain optimal organ quality. Secondly, preservation of the donor organ largely determines the organ quality.

In this project, we commented that more donor organs can be made available for lung transplantation when more retrieval teams are send out to inspect the organ quality inside the donor rather than making a selection on medical donor information only. Also, we are the first to provide evidence to support the current clinical practice of administrating corticosteroids to donors who die of circulatory arrest, since this results in improved organ function after lung transplantation.

To evaluate graft function prior to transplantation, ex-vivo lung perfusion (EVLP) was developed. With this technique, a preservation solution is pumped through the lung while it is ventilated so we can evaluate the organ physiologically outside the body. It also offers the opportunity to treat the donor organ and evaluate the effect or the treatment prior to transplantation.

By analyzing data of all donor organs that were not used for transplantation, we could show that there is a large potential for EVLP to make more donor lungs available for transplantation by carefully evaluating them and improve them prior to transplantation. We also published our experience of a pediatric combined liver-lung transplantation where the lungs were kept on EVLP before they were transplanted. We showed that EVLP is also possible in unique cases such as this one and stimulated anesthesiologists to be more involved in research of optimal preservation methods of donor organs to improve their quality.

We investigated the effect of administrating noble gases and multipotent adult progenitor cells (MAPCs, bone marrow stem cells) on our EVLP device to improve lung quality. While we could not detect a beneficial effect of noble gases on the lung, we did show that the inflammatory process that follows lung injury was less pronounced when MAPCs were administered in the airways of donor lungs. The impact of this effect will have to be clarified in future experiments.