Current Status and Future Perspectives on Machine Perfusion: A Treatment Platform to Restore and Regenerate Injured Lungs Using Cell and Cytokine Adsorption Therapy

Since its advent in the 1990′s, ex vivo lung perfusion (EVLP) has been studied and implemented as a tool to evaluate the quality of a donor organ prior to transplantation. It provides an invaluable window of opportunity for therapeutic intervention to render marginal lungs viable for transplantation. This ultimately aligns with the need of the lung transplant field to increase the number of available donor organs given critical shortages. As transplantation is the only option for patients with end-stage lung disease, advancements in technology are needed to decrease wait-list time and mortality. This review summarizes the results from the application of EVLP as a therapeutic intervention and focuses on the use of the platform with regard to cell therapies, cell product therapies, and cytokine filtration among other technologies. This review will summarize both the clinical and translational science being conducted in these aspects and will highlight the opportunities for EVLP to be developed as a powerful tool to increase the donor lung supply.

Ex Vivo Lung Perfusion: A Platform for Donor Lung Assessment, Treatment and Recovery

Lung transplantation offers a lifesaving therapy for patients with end-stage lung disease but its availability is presently limited by low organ utilization rates with donor lungs frequently excluded due to unsuitability at assessment. When transplantation does occur, recipients are then vulnerable to primary graft dysfunction (PGD), multitudinous short-term complications, and chronic lung allograft dysfunction. The decision whether to use donor lungs is made rapidly and subjectively with limited information and means many lungs that might have been suitable are lost to the transplant pathway. Compared to static cold storage (SCS), ex vivo lung perfusion (EVLP) offers clinicians unrivalled opportunity for rigorous objective assessment of donor lungs in conditions replicating normal physiology, thus allowing for better informed decision-making in suitability assessments. EVLP additionally offers a platform for the delivery of intravascular or intrabronchial therapies to metabolically active tissue aiming to treat existing lung injuries. In the future, EVLP may be employed to provide a pre-transplant environment optimized to prevent negative outcomes such as primary graft dysfunction (PGD) or rejection post-transplant.

Imaging Findings for Identifying and Evaluating Complications after Lung Transplantation in Patients with Advanced COVID-19: Two Case Reports

Background: Lung transplantation might be a viable alternative for patients with irreversible lung injury secondary to coronavirus disease 2019 (COVID-19). Here, we describe two patients with end-stage COVID-19 that received lung transplantations, the clinical-radiologic manifestations of post-operative complications, and the imaging features of allograft rejection. Case presentation: Case 1, a 66-year-old woman presented severe hypoxia after lung transplantation. Chest imaging revealed diffuse homogeneous infiltration in the donor lung. Dramatic resolution of the imaging abnormalities after intravenous administration of methylprednisolone favored a diagnosis of hyperacute rejection. The second is a 70-year-old man, who was infected with bacterial postoperatively. During the empiric antibiotic therapy, chest CT showed newly developed ground glass opacities with septal thickening, suggesting a diagnosis of acute rejection. High-dose corticosteroids therapy was initiated, and the patient recovered gradually. Conclusion: This is the first report describing post-operative complications of lung transplantation in patients with advanced COVID-19. We presumed that imaging procedures could be a useful tool in early detecting lung transplant complications and selecting specific interventions for patients with COVID-19.

Evaluation of the efficacy of a novel perfusion solution for normothermic ex vivo lung perfusion compared with Steen solution™ (animal experimental study)

Respiratory diseases, together with infectious complications and hereditary lung diseases, rank third in international mortality statistics. Today, lung transplantation is a recognized method of treating end-stage lung diseases. However, the number of transplant surgeries performed is not much. This is down to the high requirements on the condition of a potential lung donor and directly on the quality of the donor lung. This has significantly limited the number of optimal donors. Rehabilitation of donor lungs to optimal gas exchange indicators can be achieved and objectively assessed in the course of ex vivo lung perfusion (EVLP). The EVLP procedure is widespread in leading transplantation centers in Europe and North America. It allows to significantly expand the pool of donor lungs, thereby serving a greater number of patients in need of lung transplantation. The possibility of EVLP procedure using publicly available perfusion equipment was demonstrated. The optimized protocol fully demonstrated its reliability and efficiency. The developed perfusion solution had no statistically significant differences in comparison with the Steen SolutionTM, which in the future will serve as an alternative for EVLP procedure.

Reliability of Donor Lung Sampling in Lung Transplantation

Introduction: Ex vivo lung perfusion (EVLP) is a normothermic platform used to assess donor lungs. Many have studied biomarkers in lung injury, but it is unclear whether samples taken from one location are representative of the organ. Our objective was to investigate the uniformity of cytokine expression in tissue biopsies and in EVLP perfusates from various locations. Methods: In the tissue study, eight donor lungs were partitioned from apex to base. In each lung, three biopsies were taken from the third, sixth, and ninth slices, while two were taken from the lingula and an injury site. In the perfusate study, four samples were taken from four lobes in eight donors during EVLP. Expressions of IL-6, IL-8, IL-10, and IL-1β were measured using qPCR and ELISA. Results: In the tissue study, the mean intra-biopsy equal-variance F-value was 0.53. The median intra-biopsy coefficient of variation (CV) was 18%. In donors without gross focal injury, the mean comparisons of biopsies in each donor showed that the three consistent slices showed no differences and had a CV of 20%, which was similar to the intra-biopsy CV (p=0.80). Both the lingula and injury biopsies demonstrated larger differences from the rest. The median intra-lung CV of perfusates from different lobes was 4.9%. Conclusion: Intra-biopsy variances were consistent across biopsies. Lungs without gross focal injury demonstrated more consistent gene expression. The lingula is not a representative site due to high signal variability. The consistent measurements in EVLP perfusates provided a uniform picture of the inflammation.