In the fourth decade of clinical practice, lung transplantation (LTx) continues to evolve. This is reflected through the continued increase in the number of transplants performed worldwide and the improving survival rates, despite the increasing complexity of donors and recipients. However, long-term survival after LTx remains poor compared to other solid organ transplants. The main barriers to long-term success are primary graft dysfunction (PGD), which develops during the first days of reperfusion, followed by infections and chronic lung allograft dysfunction (CLAD). Recent evidence suggests there is a link between severe PGD and CLAD development, and therefore there are reduced survival rates in those affected following LTx.

The underlying pathogenesis of PGD is multifactorial, mainly driven by inevitable ischemia-reperfusion (IR) processes. Donor and recipients related factors further alleviate the acute lung injury. Considerable progress has been made with the implementation of ex vivo lung perfusion (EVLP) in donor lung management for the prevention of PGD during the past decade. However, there is no widely accepted treatment options available for patients with PGD in clinical settings.

Using the translational “bench-to-bedside” research concept, in-vitro, in-vivo and ex-vivo models have been utilized to study the underlying mechanisms of IR injury and possible therapeutic options over the last decades. In-vitro models using epithelial and/or endothelial cells in culture medium are utilized as screening tools to identify potential therapeutic targets to guide future in-vivo experiments. Although not simulating all aspects of IR injury related to LTx, hilar clamping models, which are the first in line in in-vivo settings, are utilized to test potential therapeutics due to its simplicity and cost effectivity. Orthotopic LTx, on the other hand, simulates various mechanisms of IR injury including the surgical technique and innate immunity, however, requires surgical expertise and consumes significant time and resources. Small (rodents) and large (ie. pigs) animal models of orthotopic LTx have been frequently utilized to study IR injury both in acute and survival settings. Furthermore, recently popularized EVLP models using lungs originating from small/large animals to humans offer a unique opportunity to study IR injury in ex-vivo settings.

The aim of this research topic is to bring the recent studies related to IR injury in LTx utilizing the bench-to-bedside concept from in-vitro to in-vivo and ex-vivo models not only in preclinical but also in clinical settings. We are pleased to invite you to submit original research articles, case reports, and/or reviews covering, but not limited to, the following topics in the field of LTx:

• Underlying mechanisms of IR injury
• Donor and recipient-related factors related to PGD
• Experimental models of IR injury
• Prevention and/or treatment of IR injury
• EVLP assessment and treatment of donor's lungs
• Biomarkers of PGD
• Long-term impact of PGD

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Frontiers in Immunology

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