Targeting leukocytes, neutrophil extracellular traps and cytokines: A conceptual review to prevent primary graft dysfunction after lung transplantation

Even with the advances of perioperative management and surgical techniques, the outcomes of lung transplantation remain inferior to other solid organ transplantations, in part due to the high occurrence of primary graft dysfunction (PGD) which occurs in up to 30-50 % of lung transplant recipients. Ischemia-reperfusion injury (IRI) is one of the main causes of PGD. Neutrophils play an important role in the mechanism of IRI. Recent studies showed that neutrophil extracellular traps (NETs) also play an important role in development of PGD. There are also some studies about the innovative devices which can remove NETs and pathogenic cytokines. In this review, we discuss the effects of a leukocyte-depleting filter, NETs disruption with Deoxyribonuclease, NETs removal with filter (NucleoCapture), cytokine adsorption filter (CytoSorb), and neutrophil elastase inhibitor for the prevention of PGD. All of these techniques have been studied mainly in animal lung transplant models or ex vivo lung perfusion models, and have shown to have a potential to prevent PGD after clinical lung transplantation. However, clinical trials are needed to critically assess these novel therapies.