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Objectives: To determine the impact of older donor age (70+ years) on long-term survival and freedom from chronic lung allograft dysfunction in lung transplant (LTx) recipients., Methods: A retrospective single-center study was performed on all LTx recipients from 2002 to 2017 and a modern subgroup from 2013 to 2017. Recipients were stratified into 4 groups based on donor lung age (<18, 18-55, 56-69, ≥70 years). Donor and recipient characteristics were compared using χ 2 tests for differences in proportions and analysis of variance for differences in means. Univariable and multivariable Cox regression was used to describe differences in long-term survival and freedom from chronic lung allograft dysfunction., Results: Between 2002 and 2017, 1600 LTx were performed, 98 of which were performed from donors aged 70 years or older. Recipients of 70+ years donor lungs were significantly older with a mean age of 55.5 ± 12.9 years old (P = .001) and had more Status 3 (urgent) recipients (37.4%, P = .002). After multivariable regression, there were no significant differences in survival or freedom from chronic lung allograft dysfunction between the 4 strata of recipients., Conclusions: Lung transplantation using donors 70 years old or older can be considered when all other parameters suggest excellent donor lung function without compromising short- or long-term outcomes., (Copyright © 2023 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: Diagnosing lung injury is a challenge in lung transplantation. It has been unclear if a single biopsy specimen is truly representative of the entire organ. Our objective was to investigate lung inflammatory biomarkers using human lung tissue biopsies and ex vivo lung perfusion perfusate., Methods: Eight human donor lungs declined for transplantation were air inflated, flash frozen, and partitioned from apex to base. Biopsies were then sampled throughout the lung. Perfusate was sampled from 4 lung lobes in 8 additional donor lungs subjected to ex vivo lung perfusion. The levels of interleukin-6, interleukin-8, interleukin-10, and interleukin-1β were measured using quantitative reverse transcription polymerase chain reaction from lung biopsies and enzyme-linked immunosorbent assay from ex vivo lung perfusion perfusate., Results: The median intra-biopsy equal-variance P value was .50 for messenger RNA biomarkers in tissue biopsies. The median intra-biopsy coefficient of variance was 18%. In donors with no apparent focal injuries, the biopsies in each donor showed no difference in various lung slices, with a coefficient of variance of 20%. The exception was biopsies from the lingula and injured focal areas that demonstrated larger differences. Cytokines in ex vivo lung perfusion perfusate showed minimal variation among different lobes (coefficient of variance = 4.9%)., Conclusions: Cytokine gene expression in lung biopsies was consistent, and the biopsy analysis reflects the whole lung, except when specimens were collected from the lingula or an area of focal injury. Ex vivo lung perfusion perfusate also provides a representative measurement of lung inflammation from the draining lobe. These results will reassure clinicians that a lung biopsy or an ex vivo lung perfusion perfusate sample can be used to inform donor lung selection., (Copyright © 2023. Published by Elsevier Inc.)

Objective: Our objective was to develop a rapid-onset and durable gene-delivery strategy that is applicable at the time of transplant to determine its effects on both acute rejection and chronic lung allograft fibrosis using a mouse orthotopic lung transplant model., Methods: C57BL/6 mice received an orthotopic left lung transplant from syngeneic donors or C57BL/10 donors. By using syngeneic lung transplantation, we established a novel gene transfer protocol with lentivirus luciferase intrabronchial administration to the donor lung ex vivo before transplantation. This strategy was applied in allogeneic lung transplantation with lentivirus engineering expression of human interleukin-10 or lentivirus luciferase (control)., Results: Bioluminescent imaging revealed that the highest early transgene expression was achieved when lentivirus luciferase was administered both directly into the donor lung graft ex vivo before implantation and subsequently to the recipient in vivo daily on post-transplant days 1 to 4, compared with post-transplant in vivo administration only (days 0 to 4). Our previous work with adenoviral interleukin-10 gene therapy indicates that early interleukin-10 expression in the allograft is desirable. Therefore, we selected the combined protocol for human interleukin-10 encoding lentiviral vector therapy. In the allogeneic transplant setting, ex vivo and in vivo human interleukin-10 encoding lentiviral vector therapy reduced acute rejection grade (2.0 vs 3.0, P < .05) at day 28. The percentage of fibrotic obliterated airways was reduced in the human interleukin-10 encoding lentiviral vector-treated group (10.9% ± 7.7% vs 40.9% ± 9.3%, P < .05)., Conclusions: Delivery of lentiviral interleukin-10 gene therapy, using a novel combined ex vivo and in vivo delivery strategy, significantly improves acute and chronic rejection in the mouse lung transplant model., (Copyright © 2018. Published by Elsevier Inc.)