Soluble Adhesion Molecules During Ex Vivo Lung Perfusion Are Associated With Posttransplant Primary Graft Dysfunction.

Ex vivo lung perfusion (EVLP) enables assessment of marginal donor lungs for transplantation. We aimed to discover biomarkers in EVLP perfusate that could predict development of primary graft dysfunction (PGD). From September 2008 to August 2013, 100 clinical EVLPs were performed. Eleven patients developed PGD grade 3 within 72 h after transplant. The non-PGD group consisted of 34 patients without PGD grade 3. Nonbilateral lung transplants or transplant after extracorporeal life support were excluded from analyses. Soluble intercellular adhesion molecule 1 (sICAM-1), soluble VCAM-1 (sVCAM-1), and soluble E selectin (sE-selectin) levels, as markers of endothelial activation, were measured in the perfusate of EVLP by enzyme-linked immunosorbent assay and were correlated with clinical outcome. Levels of sICAM-1 at 1 h and sVCAM-1 at 1 and 4 h were significantly higher in the PGD group compared with the non-PGD group. The sE selectin levels were not statistically different between the study groups. Higher levels of sVCAM-1 at 1 and 4 h were statistically significantly associated with PGD either alone or after adjustment for other PGD risk factors. These adhesion molecules may help identify donor lungs at higher risk of PGD during EVLP.

Ex Vivo Perfusion Treatment of Infection in Human Donor Lungs.

Ex vivo lung perfusion (EVLP) is a platform to treat infected donor lungs with antibiotic therapy before lung transplantation. Human donor lungs that were rejected for transplantation because of clinical concern regarding infection were randomly assigned to two groups. In the antibiotic group (n = 8), lungs underwent EVLP for 12 h with high-dose antibiotics (ciprofloxacin 400 mg or azithromycin 500 mg, vancomycin 15 mg/kg, and meropenem 2 g). In the control group (n = 7), lungs underwent EVLP for 12 h without antibiotics. A quantitative decrease in bacterial counts in bronchoalveolar lavage (BAL) was found in all antibiotic-treated cases but in only two control cases. Perfusate endotoxin levels at 12 h were significantly lower in the antibiotic group compared with the control group. EVLP with broad-spectrum antibiotic therapy significantly improved pulmonary oxygenation and compliance and reduced pulmonary vascular resistance. Perfusate endotoxin levels at 12 h were strongly correlated with levels of perfusates tumor necrosis factor α, IL-1ß and macrophage inflammatory proteins 1α and 1ß at 12 h. In conclusion, EVLP treatment of infected donor lungs with broad-spectrum antibiotics significantly reduced BAL bacterial counts and endotoxin levels and improved donor lung function.

Lung transplantation with donation after circulatory determination of death donors and the impact of ex vivo lung perfusion.

The growing demand for suitable lungs for transplantation drives the quest for alternative strategies to expand the donor pool. The aim of this study is to evaluate the outcomes of lung transplantation (LTx) with donation after circulatory determination of death (DCDD) and the impact of selective ex vivo lung perfusion (EVLP). From 2007 to 2013, 673 LTx were performed, with 62 (9.2%) of them using DCDDs (seven bridged cases). Cases bridged with mechanical ventilation/extracorporeal life support were excluded. From 55 DCDDs, 28 (51%) underwent EVLP. Outcomes for LTx using DCDDs and donation after neurological determination of death (DNDD) donors were similar, with 1 and 5-year survivals of 85% and 54% versus 86% and 62%, respectively (p = 0.43). Although comparison of survival curves between DCDD + EVLP versus DCDD-no EVLP showed no significant difference, DCDD + EVLP cases presented shorter hospital stay (median 18 vs. 23 days, p = 0.047) and a trend toward shorter length of mechanical ventilation (2 vs. 3 days, p = 0.059). DCDDs represent a valuable source of lungs for transplantation, providing similar results to DNDDs. EVLP seems an important technique in the armamentarium to safely increase lung utilization from DCDDs; however, further studies are necessary to better define the role of EVLP in this context.

Distinct expression patterns of alveolar "alarmins" in subtypes of chronic lung allograft dysfunction.

The long-term success of lung transplantation is limited by chronic lung allograft dysfunction (CLAD). The purpose of this study was to investigate the alveolar alarmin profiles in CLAD subtypes, restrictive allograft syndrome (RAS) and bronchiolitis obliterans syndrome (BOS). Bronchoalveolar lavage (BAL) samples were collected from 53 recipients who underwent double lung or heart-lung transplantation, including patients with RAS (n = 10), BOS (n = 18) and No CLAD (n = 25). Protein levels of alarmins such as S100A8, S100A9, S100A8/A9, S100A12, S100P, high-mobility group box 1 (HMGB1) and soluble receptor for advanced glycation end products (sRAGE) in BAL fluid were measured. RAS and BOS showed higher expressions of S100A8, S100A8/A9 and S100A12 compared with No CLAD (p < 0.0001, p < 0.0001, p < 0.0001 in RAS vs. No CLAD, p = 0.0006, p = 0.0044, p = 0.0086 in BOS vs. No CLAD, respectively). Moreover, RAS showed greater up-regulation of S100A9, S100A8/A9, S100A12, S100P and HMGB1 compared with BOS (p = 0.0094, p = 0.038, p = 0.041, p = 0.035 and p = 0.010, respectively). sRAGE did not show significant difference among the three groups (p = 0.174). Our results demonstrate distinct expression patterns of alveolar alarmins in RAS and BOS, suggesting that RAS and BOS may represent biologically different subtypes. Further refinements in biologic profiling will lead to a better understanding of CLAD.

Lung transplantation for patients older than 65 years: is it a feasible option?

BACKGROUND: Advanced age has been a relative contraindication to lung transplantation. However, the exact age limit for this procedure has not yet been established. The aim of this work is to present our experience with this particular group. METHODS: This retrospective review included medical charts of patients who underwent lung transplantation at our institution from January 2004 to February 2009: namely, 112 cadaveric lung transplants with 12 patients (10.7%) >65 years old. RESULTS: There were 9 male patients and the overall mean age was 68 years (range 66-72). The indications were pulmonary fibrosis in 8 and emphysema in 4 cases. Four patients had mild coronary artery disease and 4 systemic hypertension. All of the procedures were unilateral and only 2 required extracorporeal circulation. Only 5 patients received blood product transfusions intraoperatively; the mean ischemic time was 222 minutes. Four patients developed primary graft dysfunction, the mean requirement for mechanical ventilation was 30 hours, and the mean intensive care unit stay, 11 days. Postoperative complications were respiratory infections (n = 8), catheter-related infection (n = 1), atrial fibrillation (n = 2). The mean hospital stay was 28 days and the 1-year survival was 75%. CONCLUSION: Lung transplantation is a feasible option for well-selected patients with end-stage pulmonary disease who are >65 years old. Our study reinforces the modern trend for unilateral procedures in this situation.

Lung transplantation for lymphangioleiomyomatosis: single-center Brazilian experience with no chylothorax.

BACKGROUND: Lymphangioleiomyomatosis (LAM), a rare cystic disease characterized by proliferation of smooth muscle cells in the lung interstitium, almost exclusively affects females in their reproductive years. Lung transplantation has been established as effective therapy for end-stage pulmonary LAM. METHODS: This retrospective study includes lung transplantation patients with LAM at a single institution between 1989 and 2009. RESULTS: During the study period we performed 300 lung transplantations, and in 10 cases the recipients had LAM. All patients were females with a mean age of 43.8 years. The mean time from the diagnosis to lung transplantation was 5 years. Seven patients had experienced previous pneumothoraces, five of whom were treated with pleurodesis. In all patients we performed a single-lung transplantation (left-sided = 9 and right-sided = 1). In three cases, the pleurodesis was on the same side as the transplantation, with great intraoperative bleeding in one subject (left pleurectomy). There was one early death due to infective endocarditis at posttransplant day 19. The median length of mechanical ventilation was 13 hours, while the mean hospital stay was 16.75 days. There was no case of chylothorax. Late complications included one case of native lung pneumothorax, one diaphragmatic hernia, one posttransplant lymphoproliferative disease, one respiratory sepsis, and one mycobacterial infection. The 1- and 3-year survival rates were 90% and 80%, respectively. CONCLUSION: Lung transplantation is a feasible therapeutic option for patients with LAM, despite previous ipsilateral pleurodesis. The left-sided predilection for our procedures may have been responsible for the absence of chylothorax in this series.

Multiple synchronous bronchial carcinoid tumors: report of a case.

Peripheral bronchial carcinoids are uncommon. Their presentation as synchronous tumors is rare and limited to anecdotal cases.We report the case of a 62-year-old female with the radiological finding of multiple bilateral nodular lesions. Bilateral sequential thoracotomies were performed and all three nodules were treated by sublobar resections. Pathological examination revealed all specimens to be carcinoid tumors and subsequent investigation confirmed the lung as the primary site. A review of previous cases of multiple carcinoids is presented and the particularities of their management are discussed.