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Elevated donor lung weight may adversely affect donor lung transplant suitability and post-transplant outcomes. The objective of this study is to investigate the impact of lung weight after procurement and ex vivo lung perfusion (EVLP) on transplant suitability, post-transplant graft dysfunction, and clinical outcomes and define the donor lung weight range most relevant to clinical outcomes.From February 2016 to August 2020, 365 human lung donors to a single transplant center were retrospectively reviewed. 239 were transplanted without EVLP, 74 treated with EVLP (50 went on to transplant), and 52 declined for transplant without EVLP consideration. Donor lung weights were measured immediately after procurement and, when performed, after EVLP. Lung weights were adjusted by donor height and divided into 4 quartiles.Donor lungs in the highest weight quartile at donor hospital had a significantly lower transplant suitability rate after EVLP, higher rates of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay. For lungs treated with lung perfusion, the highest lung weight quartile at the end of lung perfusion was associated with a significantly lower transplant suitability rate, higher incidence of primary graft dysfunction grade 3 at 72 hours, and longer intensive care unit/hospital stay, compared to the other categories.Donor lung weight stratified by quartile categories can assist decision-making regarding need for EVLP at the donor hospital as well as during EVLP evaluation. Caution should be used when considering donor lungs in the highest weight quartile for transplantation.

Purpose Dire c t l ung u ltrasound e valuation (CLUE) technique was proven to be an accurate method for monitoring extravascular lung water in donor lungs during ex-vivo lung perfusion (EVLP) in porcine and human lung models. The aim of this study was to examine the application of CLUE in the clinical setting. Methods Lungs were evaluated in acellular EVLP with standard protocol. Ultrasound images were obtained at each point of 4 lines passing through the anterior, lateral, posterior, and diaphragmatic surfaces of each lung. Images were graded according to the percentage of B-lines and presence of consolidation. CLUE scores were calculated at the beginning (initial) and the end (final) of EVLP for the whole lung, each side and lobe using this equation: CLUE Score = (No. of Grade 1 images x 1 + No. of Grade 2 images x 2 + No. of Grade 3 images x 3 + No. of Grade 4 images x 4 + No. of Consolidation images x 5) / Total No. of images taken. Results In our clinical EVLP program, 36 lungs from 18 donors were evaluated by CLUE. Eighteen lungs were deemed suitable and were transplanted (8 double & 2 single) with no hospital mortality. There were no cases of primary graft dysfunction (PGD) grade 2 observed and one recipient had PGD 3 at 72 hours. Final CLUE score was significantly lower in suitable lungs compared to non-suitable (0.86 ± 0.4 vs 1.80 ± 0.3, p Conclusion CLUE technique shows the highest accuracy in evaluating donor lungs for transplant compared to other parameters used in EVLP. CLUE can help in improving the outcomes of lung transplant by guiding decision making through the whole process of EVLP and providing a comprehensive precise assessment of individual lungs and lobes.

BACKGROUND Extravascular lung water (EVLW) could change in donor lungs in a time-dependent fashion during procurement or ex-vivo lung perfusion (EVLP) and may vary across different zones. Current techniques for EVLW assessment are either subjective, general estimation, or not feasible in the clinical setting. An accurate and non-invasive diagnostic tool for EVLW would be desirable for donor lung assessment and management. Therefore, we studied the feasibility and accuracy of direCt Lung Ultrasound Evaluation (CLUE) technique. METHODS Eleven lungs were utilized for the human model and 6 lungs for the porcine model. Lungs underwent EVLP for 2 hours. In CLUE, ultrasound images were taken directly from the lungs. A scoring system was created for each point based on the percentage of B-lines. Images were graded according to the degree of edema. An equation was used to calculate total lung and lobe scores based on number of images of each grade. RESULTS CLUE point score correlated with wet/dry ratio in human and porcine models (n = 99, r = 0.863, p < 0.001; and n = 31, r = 0.916, p < 0.001, respectively). CLUE total lung score correlated with lung weight (n = 19, r = 0.812, p < 0.001; and n = 12, r = 0.895, p < 0.001, respectively). CLUE lobe score correlated negatively with partial pressure of oxygen/fraction of inspired oxygen ratio in the human model (n = 20, r = -0.775, p < 0.001). CONCLUSIONS EVLW monitoring in donor lungs with CLUE after procurement is feasible and CLUE scores were found to be significantly correlated with lung weight, wet/dry, and PaO2/FIO2 ratio.

Purpose Elevated donor lung weight can result from excess extravascular lung water and adversely affect transplant suitability and post-transplant outcomes. We sought to define the impact of lung weight on 1) donor lung suitability and 2) post-transplant graft dysfunction in lungs transplanted with and without ex vivo lung perfusion (EVLP). Methods From Feb 2016 to Aug 2020, 365 human lung donors were reviewed. Of 365, 239 were transplanted without EVLP, 74 treated with acellular EVLP (50 went on to transplant), and 52 declined for transplant without EVLP. Lung weights were measured at two time points: at 0 hr (LW0; after lung explant or start of EVLP), and after EVLP was completed (LWend). LW0 data were divided into 4 quartiles (Category 1=0-25%, Category 2=25-50%, Category 3=50-75%, and Category 4=75-100%) within 3 height groups ( Results For LW0 Category 4, EVLP was utilized more frequently (45 vs. 17%, p Conclusion Donor lungs in the highest quartile of lung weight are associated with increased need for EVLP, but lower transplant suitability rates after EVLP when compared to lungs with lower weight. Donor lungs in the highest quartile are also associated with higher Grade 3 PGD rates and longer ICU/hospital stay. These findings should be taken into account when high weight donor lungs are considered for clinical use.

Purpose Ischemia-reperfusion injury after lung transplantation is associated with worse clinical outcomes including primary graft dysfunction. Previously, microRNA (miR)-223 was shown to regulate the NF-kB pathway in lung injury models. Herein, we aim to examine the microRNA-mRNA interactions during human lung response to cold storage/ex-vivo lung perfusion (CS/EVLP) and identify correlations between miR-223 and the transcriptome. Methods Tissue samples were obtained from 5 human lungs after CS and after 2hrs of EVLP. Control samples were obtained from 5 different donors without CS/EVLP. The NanoString platform was used for miR profiling and mRNA sequencing. Ingenuity Pathway Analysis was used to study network interactions between miR expression and the transcriptome. Validation in vitro experiments were performed in a specialized oxygenation chamber using A549 cells. Results Microarray analysis showed significant differential expression of 44 mRNA & 123 microRNA after cold storage, and 61 mRNA & 157 miR after EVLP compared to control (p 5 fold). Showing in the in-vitro model, miR-223 was down-regulated in A549 cells during reperfusion (20-22°C, 40% O2) after 4 hr of CS (4°C, 100% O2) while it was up-regulated when the experiment repeated under normothermia conditions storage (20-22°C, 100% O2). Conclusion This study provides for the first time evidence for miR-223 targeting NF-kB pathway in human lung response to CS/EVLP which could serve as a novel therapy to mitigate reperfusion injury. The finding that CS modulates miR-223 expression in human lungs is novel and warrant further investigation.

Purpose Lung weight (LW) gain is a typical characteristic of ischemia reperfusion injury in ex-vivo lung perfusion (EVLP). However, LW gain data is available only at the end of EVLP. Additionally, objective physiological parameters useful in EVLP evaluation are limited. The study purpose was to investigate the usefulness of real-time LW measurement to assess pulmonary edema and to predict clinical outcomes. Methods LW at back table was measured before and after EVLP. During acellular EVLP, real-time LW was continuously measured by a scale attached under the organ chamber. The LW change (weight change per time, g/min) was measured during the non-touching period at multiple time points and the estimated LW gain was calculated by LW change and its duration. Transplant suitability was judged based on the standard criteria including trend of physiological parameters and palpation findings. Results Ten lungs were perfused at our institute and 8 lungs were clinically transplanted. All patients survived and primary graft dysfunction (PGD) grade at 72 hours were Grade 0-1, n = 6; Grade 2, n = 2; Grade 3, n = 0. Estimated LW gain during the entire perfusion period significantly correlated with LW gain at the back table (n = 10, r = 0.95, p Conclusion The data suggest that LW gain calculated by real-time LW measurement might be useful to assess pulmonary edema during EVLP. Initial LW gain at 0-60 min of EVLP might be a predictor of transplant suitability and clinical outcomes.

Purpose Evidence suggests that high grade primary graft dysfunction after lung transplantation (LTx) is a major threat for early and late outcomes. Herein, we aim to examine the risk factors and clinical impact of PGD in a contemporary cohort at a single center. Methods From 1/2008 to 7/2018, 1147 LTx procedures were performed at our institution. Clinical data was prospectively collected and PGD defined according to ISHLT criteria. Median follow up was 3.3 years (interquartile range 1.2 - 7.4). Multi-variable analysis utilizing recipient, donor, and LTx procedure variables was performed to assess risk factors for PGD, acute rejection, chronic lung allograft dysfunction (CLAD), early mortality, and late survival. Results Out of 1147 LTx procedures, 61% were bilateral. The incidence of PGD (grade II & III) was 13% & 15% at 24 hr , 12% & 14% at 48 hr , and 12% & 14% at 72 hr, respectively. Multi-variable analysis identified cardiopulmonary bypass usage/duration, single LTx, recipient pulmonary arterial hypertension, longer ischemic time, earlier year of LTx, older donor, higher Lung Allocation Score, and higher ratio of recipient/donor weight as risk factors for high grade PGD (grade II or III at 48-72 hr). Notably, recipient body mass index, donor smoking history, and diabetes were not significant risk factors for high grade PGD. Further analysis demonstrated that PGD II or III at 48-72 hr were independent significant risk factors for early mortality and higher acute rejection grades, while not significantly associated with CLAD or late survival. PGD grade II or III at 24 hr were not significant risk factors for early mortality, acute rejection, CLAD, or late survival. Conclusion This single-center data analysis of > 1000 contemporary lung transplants identified risk factors for high grade PGD. While high grade PGD at 48-72 hr was associated with higher risk of early mortality and acute rejection, in contrast to previous studies, it was not associated with a higher risk of CLAD or late survival, perhaps due to evolving management strategies.

Purpose Evaluating marginal donor lungs for transplant suitability in acellular ex-vivo lung perfusion (EVLP) can be challenging. Relying on a single parameter for evaluation can be misleading and may result in unfavorable outcomes following lung transplantation (LTx). This study aimed to establish a comprehensive scoring system incorporating important evaluation parameters in a simple reproducible way. Methods The comp rehensive l ung e valua t ion E VLP ( COMPLETE ) score is the composite result of ten evaluation parameters including: lung weight measurement, ultrasound evaluation, airway pressure, lung compliance, P/F ratio, lactate level, deflation, palpation, bronchoscopy, and x-ray. Each parameter is scored from 0 to 3, 3 being the worst, then the COMPLETE score is calculated by the summation of the individual parameter scores. Data was collected prospectively, then analyzed retrospectively utilizing receiver operating characteristic (ROC) analysis to inform the cut off values for each parameter scoring. Results Seventy-three EVLP cases were performed resulting in 48 lung transplants with 100% 30-day survival and 96% 1-year survival. Median time to extubation was 1 day and median ICU stay was 7 days. The incidence of primary graft dysfunction (PGD) grades 0, 1, 2, and 3 at 72 hours were 23%, 61%, 9%, and 7%, respectively. The COMPLETE score was significantly higher in lungs non-suitable for LTx compared to transplanted lungs (17 [15-20] vs 7 [4-8], P Conclusion The COMPLETE scoring system is a comprehensive system that can facilitate decision making in EVLP in a protocolized manner. The COMPLETE score was significantly higher in EVLP lungs deemed non-suitable for transplant and, in those transplanted after EVLP, the COMPLETE score had a significant correlation with time to extubation, ICU stay, and incidence of PGD3. Consideration should be given to the routine use of the COMPLETE score during EVLP evaluation.

Purpose The novel coronavirus (COVID-19) pandemic presented unique challenges to lung transplant (LTx) programs. On the donor side, infection concerns resulted in a dramatic reduction in donor lung offers and raised the specter of viral transmission to procurement team members. On the recipient side, the need for pre-transplant COVID-19 testing and COVID free patient care units presented unprecedented logistical challenges. New indications for ex vivo lung perfusion (EVLP) also emerged, including logistics (e.g. providing adequate time for recipient COVID testing), and donor lung evaluation following 3rd party procurement. In this study, we defined the novel roles of EVLP that our LTx program developed during the COVI-19 pandemic. Methods Retrospective analysis of adult LTx procedures performed at our institute from March 17th (when COVID restrictions began at our institute) through May 31st 2020, compared to LTx performed during the same period in 2019. Results During the study period, 17 LTx were performed. Eight of 17 were performed after EVLP evaluation, and 6 with EVLP back-up. Notably, the number of LTx after EVLP doubled vs. the same period in 2019, and the number of LTx cases with EVLP backup tripled (Figure 1A). Indications for EVLP in 4 LTx cases and 4 cases with EVLP backup were unique to pandemic conditions (Figure 1B). To date, no patients transplanted during this period, or team members tested positive for COVID-19, or are suspected of COVID infection post-LTx. 30-day survival was 100%, and incidence of primary graft dysfunction grades 0, 1, 2, and 3 at 72 hours post-transplant were 39%, 52%, 4%, and 4%, respectively. Median ventilation duration was 1 day. Conclusion Maintaining LTx activity with EVLP was feasible in the early phases of the COVID-19 pandemic. EVLP enabled our team to solve challenges with donor evaluation and logistics. By enabling donor assessment after local procurement, EVLP also increased the procurement team's safety. In the future, these newer EVLP indications may be applicable beyond the COVID-19 pandemic.

Purpose Assessment of marginal donor lungs during asanguineous ex vivo lung perfusion (EVLP) can be challenging due to limited objective parameters. We hypothesized that determination of PaO2/FiO2 (P/F) ratio from each lobar vein can provide valuable information regarding lobar function. The aim of this study is to determine lobar vein P/F ratio during EVLP and correlate with standard EVLP assessment parameters as well as post-transplant outcomes. Methods Data from 139 lungs from 75 donors assessed in asanguineous EVLP from Feb 2016 to April 2020 were analyzed for this study. Transplant suitability of lungs was determined based on standard EVLP parameters. pO2 was assessed from each pulmonary vein at the time of standard evaluation. In transplanted EVLP lungs, primary graft dysfunction (PGD) was assessed at 72 hours. Results In the favorable group (defined as PGD grade 0-1), both P/F ratio at left atrium (P/F LA) and P/F ratio at lower lobe pulmonary vein (P/F LPV) were significantly higher than that of the unfavorable group (non-suitable or PGD grade 2-3) (LA, 496±77 vs. 444±74 mmHg, P Conclusion These results suggest that determination of lobar P/F ratio during EVLP can provide additional, valuable information for lung assessment. Deterioration of lobar function might be masked assessment of only LA P/F ratio and potentially lead to a greater incidence of high-grade PGD after lung transplantation.

Purpose The use of cardiopulmonary bypass (CPB) during lung transplantation (LTx) has been linked to higher rates of primary graft dysfunction (PGD) and worse postoperative outcomes. However, the effect of the duration of CPB has not been examined yet. Thus, the aim of our study was to examine the effect of CPB duration on rates of PGD and survival. Methods A retrospective cohort study was performed from a prospective database of adult LTx procedures performed at our institute from 1/2008 to 7/2018 (n = 1039). CPB was utilized in 67% of these procedures. Logistic regression fit model was utilized for univariate analysis of PGD at 72 hours. Nonlinear cumulative logistic mixed model was used in analysis of time related PGD grades and the associated risk factors. The survival rates were evaluated by Kaplan-Meier survival -estimate. Results Longer duration of CPB was found to be an independent risk factor for severe PGD (Odds ratio, 1.0 per 1 minute increase in CPB duration; P 3 hours (55%, 26%, 25%, and 24%, respectively, Figure 1B). Patients with CPB >3 hours had the lowest 1-year survival rates compared with CPB ≤3 hours and no CPB patients (83%, 89% and 90%, respectively; log-rank P = 0.018). Conclusion Analysis of more than 1000 LTx data has shown that longer duration of CPB (>3 hours) is associated with severe PGD and worse survival, while shorter duration of CPB (≤3 hours) and no CPB outcomes remain comparable. These results suggest that duration of CPB is more important rather than using CPB itself. Future studies investigating CPB in LTx should consider the duration as an important factor that might affect results.

Purpose Lung assessment of marginal donor lungs on ex vivo lung perfusion (EVLP) can be challenging due to limited objective parameters. Currently, the significance of isolated differential analysis of blood gas (ABG) from each lobar pulmonary vein is not clear. The aim of this study is to identify the impact of differential ABG (D-ABG) on EVLP evaluation, and compare the D-ABG with the post-transplant outcomes. Methods From Feb 2016 to August 2019, 110 EVLP lungs from 57 donors were analyzed for this study. Donor lungs were perfused with an acellular EVLP protocol, and transplant suitability of lungs was evaluated based on standard EVLP parameters. D-ABGs were taken from each pulmonary vein at the same time of standard evaluation. In transplanted EVLP lungs, primary graft dysfunction (PGD) was assessed at 72 hours. Results In the favorable group (defined as PGD grade 0-1), both PaO2/FiO2 (P/F) ratio at left atrium (P/F LA) and P/F ratio at lower lobe pulmonary vein (P/F LPV) were significantly higher than that of the unfavorable group (non-suitable or PGD grade 2-3) [LA, 526 (466-574) vs. 437 (386-499) mmHg, P Conclusion These results suggest that D-ABG on EVLP could provide additional, valuable information for evaluation. The deterioration of lobe oxygenation might be masked throughout whole lung ABG; however, low D-ABG of the lower lobe may predict a greater incidence of high-grade PGD after lung transplantation.

Purpose Ischemia-reperfusion injury after lung transplantation (LTx) is associated with early graft dysfunction, increased morbidity, and mortality. MicroRNA (miR) are identified as critical regulators of gene expression which could provide potential targets for novel gene therapy. Herein, we aim to examine the feasibility of using the ex vivo lung perfusion (EVLP) platform to study miR expression change in human lungs in response to cold ischemia and ex-vivo reperfusion (CI/EVR). Methods Prior to initiating the clinical EVLP program at our institution, our group has established a biobank of human lung tissue according to an approved (cellular) EVLP research protocol. Twenty-four donor lungs that did not meet the ideal criteria for LTx or did not match to an available recipient were used for this study. Samples were obtained after cold ischemia (median 6, interquartile range 5-13 hrs), and after 2 hrs of EVLP. Control samples were obtained from different 6 donors that were stored directly without cold ischemia or reperfusion. MicroRNA expression profiling of lung tissue was performed using next generation sequencing. MicroRNAs with the most significant fold change were validated and detected in the tissues using In-situ hybridization assay. Results Assessment of inflammatory response of the EVLP model using cytokines array showed significant up-regulation of IL-1β, IL-6, IL-8, IL-10, and TNF-α in the perfusate after 2 hours EVLP. MicroRNA sequencing identified significant expression change of a total of 21 miR after cold ischemia and 47 miR after ex-vivo reperfusion when compared to control group. Validation using quantitative PCR showed significant up-regulation of miR-17 & miR548b after CI/EVR. Downstream analysis identified abundant inflammatory and immunologic targets for miR-17 and miR-548b that are known mediators of lung injury. Expression of miR-17 in the lung tissue had a significant negative correlation with IL-8 levels in the perfusate (R = -0.8, p=0.001). In-situ hybridization assays detected positive expression of miR-17 & miR548b in alveolar epithelial cells after CI/EVR. R. Conclusion In this study, we were able to utilize EVLP model to study miR signature in human lungs after CI/EVR. The finding that alveolar epithelial cells up-regulate miR-17 & miR548b in response to CI/EVT is novel and warrant further investigation.

Purpose Ex vivo lung perfusion (EVLP) is a technology to evaluate marginal lungs or to preserve standard lungs for logistical reasons. However, the recovery rate for the various indications for EVLP is unknown. The aim of this study is to examine the recovery rate when EVLP is performed for various indications and to evaluate outcomes following transplantation. Methods From Feb 2016 to Sep 2019, 441 lung transplants were performed. During this time, 61 pairs of lungs were perfused using the Toronto-EVLP protocol with intent to transplant. EVLP was broadly utilized for 1) Concerns with lung quality or 2) Logistical restrictions with the transplant. Donation after cardiac death (DCD) lungs were perfused when PaO2/FiO2 (P/F) ratio was less than 300 mmHg or agonal time was 60-120 min. Recovery rate was defined as EVLP cases with lung transplant/ all EVLP cases. Post-operative outcomes of EVLP group were compared to those of recipients receiving lungs meeting standard criteria. Results In the EVLP obtained organs, donor age was median 35 (Interquartile range 26-45) years with 50.8% of lungs from DCD. P/F ratio in intensive care unit was 329 (259-391) mmHg. The indications for EVLP included most commonly a low PF ratio 60 min (18%), the presence of edematous lungs (14%) and question of contusion or pulmonary embolism/infarction (13%). Of the 61 perfused lungs, 39 lungs were clinically utilized in 40 lung transplants (recovery rate = 39/61, 63.9%). The recovery rate varied by indication for EVLP with the highest rate occurring when logistics were the reason for EVLP (92%); followed by extended agonal time >60 min (90%), and then when the extent of contusion or pulmonary embolism was in question (62%). Lower recovery rates from EVLP were found when EVLP was used for P/F ratio Conclusion These data demonstrate that EVLP for marginal or logistical indications can result in a recovery rate of 63% with comparable outcomes to transplants with standard lungs. The data also suggest that the indication for EVLP is an important factor in the recovery rate.

Purpose We previously reported that prone positioning (PP) of porcine lungs during cellular ex vivo lung perfusion (EVLP) diminished inflammatory injury and improved oxygenation and other pulmonary parameters during cellular EVLP. We hypothesized that prone positioning of human lungs during cellular EVLP may diminish injury and improve function, as well. The aim of this study is to validate the previous results with porcine lungs and evaluate the potential benefits of PP EVLP with human rejected donor lungs. Methods Eleven human rejected donor lungs were flushed and stored for 15-16 hours with Perfadex. Lungs were then subjected to 2 hours of cellular EVLP with either maintenance of prone positioning (prone group, n = 6) or supine positioning (control group, n = 5). Lung function was evaluated using blood gas analysis, airway and vascular parameters, visual findings, wet/dry (W/D) ratio and lung weight at 2 hours of EVLP. Results Lung weight (LW) ratio (LW at 2 hours of EVLP/ LW prior to EVLP) was lower in Prone group than in Control group [median (interquartile range)] [1.09 (0.82-1.32) vs. 1.22 (1.01-1.50), p = 0.5] (not statistical significant). The PaO2/FiO2 (P/F) ratio of left atrial blood was significantly higher in Prone group than in Control [335.5 (297.2-392.5) vs. 198.0 (190.5-271.0) mmHg, p Conclusion These results demonstrate that PP during 2 hours of cellular EVLP result in less lung weight gain, and better P/F ratio, especially in the lower lobes. These results were consistent with our previous animal study, and suggest that prone positioning EVLP of rejected human donor lungs also may diminish IRI during EVLP.

Purpose Normothermic cellular ex-vivo lung perfusion (EVLP) can provide a platform for studying ischemia-reperfusion injury (IRI), with the donor lungs being the only source of cytokine appearance in the perfusate. The inflammatory effects of cellular EVLP on lungs are inadequately explored. Herein, we aimed to examine the reperfusion inflammatory state during cellular EVLP in relation to donor factors and impact on lung function. Methods For research purposes, 42 clinically rejected donor lungs underwent normothermic cellular EVLP with open left atrium and flow equivalent to 100% of cardiac output for 2 hours. Reasons for rejection were donor old age, smoking history, low PO2/FiO2 (P/F) ratio, or unavailability of a matched recipient. Perfusate samples were collected at the beginning of EVLP (0 hours), then at 1 and 2 hours of EVLP. Lung weight was measured at the end of EVLP as an indicator for the degree of edema. Data were presented as median (interquartile range). Results Interleukin (IL)-6, IL-8, IL-10, IL-1β, and tumor necrosis factor (TNF)-α were significantly up-regulated in the EVLP perfusate at 1 and 2 hours compared to baseline 0 hours (p Conclusion Cytokine array has shown that cellular EVLP is associated with reperfusion inflammatory state in human lungs. IL-1β and IL-10 were mostly affected by donor factors, while IL-6, IL-8, and TNF-α had the most effect on lung function during EVLP. These results suggest that cellular EVLP can be utilized to study human lung IRI and develop therapeutic targets.

Purpose Anatomical regions of marginal donor lungs display significant heterogeneity in function raising the possibility that good functioning regions might be suitable for transplantation. The aim of this study was to compare gas exchange of upper lobes, which are possibly less susceptible to injury, with whole lungs using ex vivo lung perfusion (EVLP). Methods Nine rejected donor lungs were perfused for 2 hours of cellular EVLP utilizing the Swedish protocol. Transplant suitability was evaluated based on blood gas analysis, hemodynamics, ventilator parameters, palpation, visual findings, and lung weight. In order to assess upper lobe gas exchange, blood samples from upper lobe pulmonary vein (ULPV) were taken selectively at 2 hours of EVLP. PaO2/FiO2 (P/F) ratio, shunt fraction (SF), and A-a gradient in ULPV samples were compared with those of left atrium (LA). Results Upper lobes demonstrated a significantly higher P/F ratio [median (minimum - maximum)] [396 (315-583) vs. 284 (104-415), mmHg, p = 0.02, Figure A] and lower SF [21.8 (7.3-34.6) vs. 29.1 (22.7-73.9), %, p = 0.04] than whole lungs. Based on evaluation at 2 hours of EVLP, 6 of 9 lungs were deemed to be non-suitable for transplantation. In non-suitable group, P/F ratio in ULPV was significantly higher than that in LA [439 (315-583) vs. 245 (104-415) mmHg, p = 0.02, Figure B], whereas SF and A-a gradient of ULPV were significantly lower than those of LA [SF, 18.5 (7.3-34.6) vs. 34.8 (22.7-73.9) %, p = 0.04; A-a gradient, 224.9 (83.5-347.9) vs. 418.4 (246.2-569.6) mmHg, p = 0.02]. In contrast, no difference was found between the ULPV and LA parameters in lungs deemed suitable for transplant. Conclusion These results demonstrate that in marginal donor lungs judged to be non-suitable for transplant at 2 hours of EVLP, the majority of lungs have well-functioning upper lobes. These findings suggest that, in this setting, upper lobes may be suitable for lobar transplantation which could help reduce wait-list mortality.

Purpose Antibody-mediated rejection (AMR) affects survival and incidence of chronic lung allograft dysfunction (CLAD) after lung transplantation, however, the impact has not been adequately assessed. The aim of this study was to investigate the survival of AMR patients based on new criteria established by International Society of Heart and Lung Transplantation (ISHLT) committee and to assess the risk ratio for CLAD including bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). Methods We performed a retrospective, single center cohort study and identified cases who developed AMR based on the new ISHLT-criteria. Risk factors including AMR as a time varying covariate for death and incidence of CLAD were assessed with multivariate analysis. Results Between Jan 2012 and Dec 2016, 489 adult lung transplants were performed. Follow up was completed through Jun 2018. The mean ± SD of age was 58 ± 13 yo, and there were 140 (29%) females. Mean overall follow-up time was 3.5 ± 1.5 years. There were 328 cases with AMR (clinical definite, 4; clinical probable, 29; clinical possible, 26; subclinical definite, 3; subclinical probable, 47; subclinical possible 219). Class II donor specific antibodies (DSA) (hazard ratio; 3.64 ± 0.29, p Conclusion Our study demonstrated that subclinical, definite, probable or possible AMR did not significantly associated with death or CLAD after lung transplantation, although clinical AMR independently affected transplant survival and incidence of CLAD. Further study is necessary to investigate the reliability of the criteria.

Purpose Extravascular lung water (EVLW) could change in donor lungs in a time-dependent fashion during procurement or Ex-Vivo Lung Perfusion (EVLP) and may vary across different zones. Current techniques for EVLW assessment are either subjective or not feasible in the clinical setting. An accurate and non-invasive diagnostic tool for monitoring EVLW would be desirable for donor lung assessment and management. Therefore, we studied the accuracy and reliability of direCt Lung Ultrasound Evaluation (CLUE) technique for the quantification of EVLW. Methods Eleven clinically rejected donor lungs underwent cellular EVLP for 2 hours. In CLUE, ultrasound images were taken directly from the lung surface. A scoring system was created for each point based on the percentage of B-lines. Images were graded according to the degree of edema. The following equation was used to calculate total lung and lobe scores using the number of images of each grade. CLUE total Score = (No. of Grade 1 images x 1 + No. of Grade 2 images x 2 + No. of Grade 3 images x 3 + No. of Grade 4 images x 4 + No. of Consolidation images x 5) / Total No. of images taken The images were reviewed by four blinded raters. CLUE scores and lung weight were measured before and after EVLP. Wet/dry (W/D) ratio was measured from tissue samples taken after EVLP. Results CLUE point score correlated with W/D ratio measured from tissue samples taken from the same location (n = 99, r = 0.86, p (P/F) ratio measured at a sample taken from the corresponding pulmonary vein (n = 20, r = -0.78, p Conclusion CLUE technique showed a substantial inter-rater reliability. CLUE scores were significantly correlated with lung weight, W/D, and P/F ratio. These findings demonstrate the reliability and accuracy of CLUE in quantifying EVLW, which can be applied to donor lung clinical assessment and management.

Purpose Currently, pulmonary edema in donor lungs is evaluated via surgical inspection and palpation at procurement with no quantitative, standard diagnostic tool in use. The purpose of this study was to investigate the significance of lung weight at the donor hospital (LW0) as an indicator of pulmonary edema and predictor of transplant suitability in ex vivo lung perfusion (EVLP). Methods LW0 was recorded in standard donors (n = 53) and rejected donors (n = 69). Twenty-one rejected lungs were perfused in cellular EVLP and transplant suitability evaluated at 2 hours. Results There was a significant difference in LW0 between standard and rejected donors (814.7 ± 185.9 vs. 956.1 ± 275.1 g, p Conclusion Our findings demonstrate that donor lung weight could be a predictor of P/F ratio and transplant suitability during EVLP. The prospect for recovery of EVLP treated rejected donor lungs improved significantly if they weighed less than 1280 g.