Selective Removal of Neutrophil Extracellular Traps (NETs) Combined with Ex Vivo Lung Perfusion (EVLP): Current Evidence and Future Perspectives.

Severe discrepancy between availability of donor organs suitable for clinical transplantation and the proportion of patients on the waiting list has resulted in several clinical problems. First, waiting times for a suitable organ match have become increasingly long, leading to higher mortality while awaiting transplantation. Second, to address this issue, more "marginal" donor lungs have been used in the last two decades, inevitably leading to higher risk of perioperative and long-term complications. The ex vivo lung perfusion (EVLP) technology has been used to recondition marginal donor organs for clinical transplantation. There remains a further untapped pool of donor organs that are currently deemed too injured even for reconditioning via currently available EVLP strategies and are therefore discarded without reconditioning attempts. As the clinical use of EVLP has reached its full potential, further adjunct technologies, such as selective NET removal, cytokine removal and cell therapy techniques, may improve reconditioning outcomes and lead to increased number of donor organs transplanted. Moreover, NET removal may significantly improve donor organ quality and, therefore, the outcomes of recipients after lung transplantation. Such adjunct technology may also provide short- and longer-term benefits in reduction in early graft failure (primary graft dysfunction, PGD) and longer-term chronic lung allograft dysfunction (CLAD, previously known as chronic rejection) via more favorable early immune priming of organs. In this article we present current evidence and future perspectives on this novel intervention strategy that can be used on human donor lungs with the view to increase the utilization rate in lung transplantation in the near future.