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Background: The role of the circulating leukocytes in lungs and their relationship with circulating proinflammatory cytokines during ischemia-reperfusion injury is not well understood. Using ex vivo lung perfusion (EVLP) to investigate the pathophysiology of isolated lungs, we aimed to identify a therapeutic target to optimize lung preservation leading to successful lung transplantation., Methods: Rat heart-lung blocks were placed on EVLP for 4 hours with or without a leukocyte-depleting filter (LF). After EVLP, lung grafts were transplanted, and posttransplant outcomes were compared., Results: Lung function was significantly better in lung grafts on EVLP with a LF than in lungs on EVLP without a LF. The interleukin (IL)-6 levels in the lung grafts and EVLP perfusate were also significantly lower after EVLP with a LF. Interestingly, IL-6 levels in the perfusate did not increase after the lungs were removed from the EVLP circuit, indicating that the cells trapped by the LF were not secreting IL-6. The trapped cells were analyzed with flow cytometry to detect apoptosis and pyroptosis; 26% were pyroptotic (Caspase-1-positive). After transplantation, there was better graft function and less inflammatory response if a LF was used or a caspase-1 inhibitor was administered during EVLP., Conclusions: Our data demonstrated that circulating leukocytes derived from donor lungs, and not circulating proinflammatory cytokines substantially impaired the quality of lung grafts through caspase-1-induced pyroptotic cell death during EVLP. Removing these cells with a LF and/or inhibiting pyroptosis of the cells can be a new therapeutic approach leading to long-term success after lung transplantation.

Background: Accumulating evidence supports an increasing role of ex vivo lung perfusion (EVLP) in clinical lung transplantation. However, EVLP has adverse effects on the quality of lung grafts, which have rarely been discussed. Careful optimization of current EVLP protocols might improve outcomes. This study examined effects of different levels of oxygenation of the perfusate circulated through the lungs during EVLP and the impact on post-transplant functional outcomes., Methods: We compared results of 4 different oxygenation levels in the perfusate during EVLP: 6% oxygen (O 2 ), 40% O 2 , 60% O 2 , and 100% O 2 . We evaluated lung function, compliance, and vascular resistance and levels of glucose and other markers in the perfusate. After EVLP, lung grafts were transplanted, and post-transplant outcomes were compared., Results: Lungs perfused with 40% O 2 on EVLP had the lowest glucose consumption compared with the other perfusates. Lungs treated with 40% O 2 or 60% O 2 exhibited significantly less inflammation, as indicated by reduced pro-inflammatory cytokine messenger RNA levels compared with lungs perfused with 6% O 2 or 100% O 2 . Significantly more oxidative damage was noted after 4 hours of EVLP perfused with 100% O 2 . After transplantation, lungs perfused with 40% O 2 during EVLP had the best post-transplant functional outcomes., Conclusions: Optimization of O 2 levels in the perfusate during EVLP improved outcomes in this rat model. Deoxygenated perfusate, the current standard during EVLP, exhibited significantly more inflammation with compromised cellular metabolic activity and compromised post-transplant outcomes., (Copyright © 2017 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Adult lung transplant recipients with small chests have traditionally received lungs from pediatric donors, placing an additional strain on the already restricted pediatric donor pool. Performing lobar lung transplantation (LLT) can circumvent issues with donor-recipient size mismatch; however, LLT imparts additional risks. Here, we review our experience using LLT and standard lung transplantation using a pediatric donor (PDLT) for adults with small chests., Methods: We retrospectively reviewed consecutive patients with end-stage lung disease and a height of 65 inches or less who underwent LLT (n = 15) or PDLT (n = 15) between 2006 and 2012 at our institution, a high-volume lung transplant center., Results: Lobar lung transplantation recipients were older (54 ± 10 vs 48 ± 8 years) and had higher pulmonary pressure (57 ± 11 vs 52 ± 27 mmHg) and higher lung allocation scores (70 ± 9 vs 51 ± 8) than PDLT recipients (all P < 0.05). Mean waiting time was 62 days for PDLT and 9 days for LLT. Postoperatively, the incidence of severe primary graft dysfunction and the incidence of acute renal insufficiency were higher, and the mean intensive care unit stay was longer in the LLT group, but the incidence of bronchial anastomotic complications was higher in the PDLT group because of significant size discrepancy in the main bronchus (P < 0.05). Interestingly, long-term functional outcomes and survival rates were similar between the groups., Conclusions: Both LLT and PDLT are viable surgical options for adult patients with small chests. Because of the potential impact on posttransplant outcomes, the technical complexity of transplantation, decisions regarding the best surgical approach should be made by experienced surgeons.

Background: With an increasing number of potential recipients and a comparatively static number of donors, lung transplantation (LT) in the elderly has come under significant scrutiny. Previous studies have been limited by single-center experiences with small population sizes and often mixed results. Using a national registry, we sought to evaluate the following: (1) differences in survival outcomes in septuagenarians compared with sexagenarians; and (2) the effect of temporal trends on the development of other comorbidities in this population., Methods: We analyzed the Scientific Registry of Transplant Recipients (SRTR) data files from the United Network for Organ Sharing (UNOS) database to identify recipients who underwent LT between the years 2000 and 2013. The study period was divided into two equal eras. Using Kaplan-Meier analysis, we compared the 30-day, 3-month, 1-year, 3-year and 5-year patient survival between septuagenarians and sexagenarians in both eras. Separate multivariate analyses were performed to estimate the risk of renal failure, risk of rejection and length of hospital stay (LOS) post-LT in each of these time periods., Results: A total of 6,596 patients were identified comprising 1,726 (26.2%) during 2000 to 2005 and 4,870 (73.8%) during 2006 to 2012. In the "early era," 32 (1.9%) septuagenarians and 1,694 (98.1%) sexagenarians underwent LT, whereas 543 (11.1%) septuagenarians and 4,327 (88.9%) sexagenarians underwent transplantation in the "latter era." A comparison of patient survival between the two groups in the early era revealed no difference at 30 days (95.7% vs 93.8%, p = 0.65). However, 3-month (91.2% vs 75%, p = 0.04) and 1-year patient survival (79.5% vs 62.5%, p = 0.048) were both lower in the septuagenarian group. In the later era, however, there were no differences in 30-day (96.2% vs 96.8, p = 0.5), 3-month (92.7% vs 91.9%, p = 0.56) or 1-year (81.7% vs 78.6%, p = 0.12) patient survival between the two age groups. Survival rates at 3 years (63.7% vs 49.3%, p < 0.001) and 5 years (47.5% vs 28.2%, p < 0.001) were each significantly lower in the septuagenarian group., Conclusion: Overall, LT outcomes for the elderly have improved significantly over time and early outcomes in the modern era rival those found in younger recipients., (Copyright © 2015 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objective: Improvements in technology have led to a resurgence in the use of extracorporeal membrane oxygenation as a bridge to lung transplantation. By using a national registry, we sought to evaluate how short-term survival has evolved using this strategy., Methods: With the use of the United Network for Organ Sharing database, we analyzed data from 12,458 adults who underwent lung transplantation between 2000 and 2011. Patients were categorized into 2 cohorts: 119 patients who were bridged to transplantation using extracorporeal membrane oxygenation and 12,339 patients who were not. The study period was divided into four 3-year intervals: 2000 to 2002, 2003 to 2005, 2006 to 2008, and 2009 to 2011. With Kaplan-Meier analysis, 1-year survival was compared for the 2 cohorts of patients in each of the time periods. A propensity score-adjusted Cox regression model was used to estimate the risk of 1-year mortality., Results: Of the total number of recipients, 4 (3.4%) were bridged between 2000 and 2002, 17 (14.3%) were bridged between 2003 and 2005, 31 (26.1%) were bridged between 2006 and 2008, and 67 were bridged (56.3%) between 2009 and 2011. Recipients bridged using extracorporeal membrane oxygenation were more likely to be younger and diabetic and to have higher serum creatinine and bilirubin levels. The 1-year survival for those bridged with extracorporeal membrane oxygenation was significantly lower in subsequent periods: 25.0% versus 81.0% (2000-2002), 47.1% versus 84.2% (2006-2008), and 74.4% versus 85.7% (2009-2011). However, this survival progressively increased with each period, as did the number of patients bridged using extracorporeal membrane oxygenation., Conclusions: Short-term survival with the use of extracorporeal membrane oxygenation as a bridge to lung transplantation has significantly improved over the past few years., (Copyright © 2015 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)