Objective Oxidant stress pathway activation during ischemia reperfusion injury may contribute to the development of primary graft dysfunction (PGD) after lung transplantation. We hypothesized oxidant stress gene variation in recipients and donors is associated with PGD. Methods Donors and recipients from the Lung Transplant Outcomes Group (LTOG) cohort were genotyped using the Illumina IBC chip filtered for oxidant stress pathway genes. Single nucleotide polymorphisms (SNPs) grouped into SNP-sets based on haplotype blocks within 49 oxidant stress genes selected from gene ontology pathways and literature review were tested for PGD association using a sequencing kernel association test. Analyses were adjusted for clinical confounding variables and population stratification. Results 392 donors and 1038 recipients met genetic quality control standards. 30% of subjects developed grade 3 PGD within 72 hours. Donor NADPH Oxidase 3 (NOX3) was associated with PGD (p=0.01) with 5 individual significant loci (p-values between 0.006 and 0.03). In recipients, variation in glutathione peroxidase (GPX1) and NRF-2 (NFE2L2) was significantly associated with PGD (p=0.01 for both). The GPX1 association included 3 individual loci (p-values between 0.006 and 0.049) and the NFE2L2 association included 2 loci (p=0.03 and 0.05). Significant epistatic effects influencing PGD susceptibility were evident between three different donor blocks of NOX3 and recipient NFE2L2 (p=0.026, p=0.017 and p=0.031). Conclusions Our study prioritizes GPX1, NOX3, and NFE2L2 genes for future research in PGD pathogenesis, and highlights a donor-recipient interaction of NOX3 and NFE2L2 that increases PGD risk.

Lung transplantation through controlled donation after circulatory death (cDCD) has slowly gained universal acceptance with reports of equivalent outcomes to those through donation after brain death. In contrast, uncontrolled DCD (uDCD) lung use is controversial and requires ethical, legal and medical complexities to be addressed in a limited time. Consequently, uDCD lung use has not previously been reported in the United States. Despite these potential barriers, we present a case of a patient with multiple gunshot wounds to the head and the body who was unsuccessfully resuscitated and ultimately became an uDCD donor. A cytomegalovirus positive recipient who had previously consented for CDC high-risk, DCD and participation in the NOVEL trial was transplanted from this uDCD donor, following 3 hours of ex vivo lung perfusion. The postoperative course was uneventful and the recipient was discharged home on day 9. While this case represents a “best-case scenario,” it illustrates a method for potential expansion of the lung allograft pool through uDCD after unsuccessful resuscitation in hospitalized patients.

Objective Donor blood transfusion has been identified as a potential risk factor for primary graft dysfunction and by extension early mortality. We sought to define the contributing risk of donor transfusion on early mortality for lung transplant. Methods Donor and recipient data were abstracted from the OPTN database updated through 6/30/14, which included 86,398 potential donors and 16,255 transplants. Using the UNOS 4-level designation of transfusion (no blood, 1–5 units, 6–10 units, and >10 units - massive), all-cause mortality at 30-days was analyzed using logistic regression adjusted for confounders (ischemic time, donor age, recipient diagnosis, LAS and recipient age and recipient BMI). Secondary analyses assessed 90-day, 1-year mortality and hospital length of stay. Results Of the 16,255 recipients transplanted, 8,835 (54.35%) donors received at least one transfusion. Among those transfused, 1,016 (6.25%) received a massive transfusion, defined as >10 units. Those donors with massive transfusion were most commonly young trauma patients. Following adjustment for confounding variables, donor massive transfusion was significantly associated with an increased risk in 30-day (p = .03) and 90-day recipient mortality (p= 0.01) but not 1-year mortality (p = 0.09). There was no significant difference in recipient length of stay or hospital free days with respect to donor transfusion. Conclusions Massive donor blood transfusion (>10 units) was associated with early recipient mortality after lung transplantation. Conversely, sub-massive donor transfusion was not associated with increased recipient mortality. The mechanism of increased early mortality in recipients of lungs from massively transfused donors is unclear and needs further study, but is consistent with excess mortality seen with primary graft dysfunction in the first 90 days post-transplant.

transfusion were most commonly younger trauma patients. Following adjustment for confounding variables, massive transfusion was significantly associated with an increased risk in 30-day (OR = 1.41; CI 1.03, 1.92; p-value = .03) and 90-day mortality (OR = 1.36; CI 1.06, 1.73; p-value = .01) but not 1 year mortality (OR = 1.17; CI 0.97, 1.41; p-value = .11). There was no significant difference in length of stay or hospital free days with respect to donor transfusion. Conclusion: Massive donor blood transfusion (> 10 units) increases early mortality after lung transplantation. Conversely, sub-massive donor transfusion does not increase donor risk. The mechanism of increased early mortality in massively transfused donors is unclear but is consistent with increased mortality risk seen with primary graft dysfunction.

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