Extended Criteria Donor Lungs Research Articles

Extracorporeal cytokine adsorption reduces systemic cytokine storm and improves graft function in lung transplantation

ObjectivesIschemia–reperfusion injury often coincides with a cytokine storm, which can result in primary graft dysfunction following lung transplantation. Our previous research has demonstrated allograft improvement by cytokine adsorption during ex vivo lung perfusion. The aim of this study was to investigate the effect of in vivo extracorporeal cytokine adsorption in a large animal model. Materials and MethodsPig left lung transplantation was performed following 24 hours of cold ischemic storage. Observation period after transplantation was 24 hours. In the treatment group (n = 6), extracorporeal CytoSorb adsorption was started 30 minutes before reperfusion and continued for 6 hours. A control group (n = 3) did not receive adsorber treatment. ResultsDuring adsorption, we consistently noticed a significant decrease in plasma proinflammatory interleukin (IL)-2, trends of less proinflammatory, tumor necrosis factor- α, IL-1α, and granulocyte-macrophage colony-stimulating factor as well as significantly reduced systemic neutrophils. In addition, a significantly lower peak airway pressure was detected during the 6 hours of adsorption. After 24 hours of observation, when evaluating the left lung allograft independently, we observed significantly improved CO2 removal, partial pressure of oxygen/inspired oxygen fraction ratio, and less acidosis in the treatment group. At autopsy, bronchoalveolar lavage results exhibited significantly lower recruitment of cells and less pro-inflammatory IL-1α, IL-1β, IL-6, and IL-8 in the treatment group. Histologically, the treatment group had a strong trend, indicating less neutrophil invasion into the alveolar space. ConclusionsBased on our findings, cytokine adsorption during and after reperfusion is a viable approach to reducing posttransplant inflammation following lung transplantation. CytoSorb may increase the acceptance of extended criteria donor lungs, which are more susceptible to ischemia–reperfusion injury.

Extended criteria donor organ use for heart-lung transplantation in the modern era

BackgroundDemand for donor hearts and lungs exceeds their supply. Extended Criteria Donor (ECD) organs are used to help meet this demand, but their impact on heart-lung transplantation outcomes is poorly characterized. Methods and results: The United Network for Organ Sharing was queried for data on adult heart-lung transplantation recipients (n = 447) from 2005‒2021. Recipients were stratified based on whether they received ECD hearts and/or lungs. Morbidity was analyzed using Kruskal-Wallis, chi-square, and Fisher's exact tests. Mortality was analyzed using Kaplan-Meier estimation, log-rank tests and Cox regression. Sixty-five (14.5%) patients received two ECD organs, 134 (30.0%) received only an ECD lung, and 65 (14.5%) only an ECD heart. Recipients of two ECD organs were older, more likely to have diabetes, and more likely transplanted from 2015‒2021 (p < 0.05). Groups did not differ by pre-transplant diagnosis, intensive care unit disposition, life support use, or hemodynamics. Group five-year survival rates ranged from 54.5% to 63.2% (p = 0.428). Groups did not differ by 30-day mortality, strokes, graft rejection, or hospital length of stay. Conclusions: Using ECD hearts and/or lungs for heart-lung transplantation is not associated with increased mortality and is a safe strategy for increasing donor organ supply in this complex patient population.

Outcome After Lung Transplantation From a Donor With Bacterial Pneumonia Under the Japanese Donor Evaluation System

In Japan, a unique medical consultant system for donor evaluation and management has been developed in an effort to maximize the use of extended criteria donor lungs. The aim of this study was to investigate the impact of donor pneumonia (DP) on the outcome after lung transplantation under this system. Clinical data of 85 patients who underwent deceased donor lung transplantation (41 single and 44 bilateral lung transplants) between August 2012 and March 2018 were reviewed. DP was defined as the recognition of pneumonia on imaging with positive bacterial culture in the airway at the time of transplantation. Twenty-three transplanted lung grafts were recognized as having DP (27.1%). Serial chest x-rays at the donor hospital did not show deteriorating infiltration or consolidation. The PaO2/FiO2 ratio at brain death evaluations were similar between the donor pneumonia (DP) negative (-) and donor pneumonia (DP) positive (+) groups. Perioperative antibiotics were effective against 94% of isolated bacteria. The duration of postoperative antibiotics therapy was longer in the DP (+) group (P=.02). The incidence of primary graft dysfunction and acute rejection, intensive care unit stay, chronic lung allograft dysfunction-free survival, and overall survival were similar between the DP (+) and DP (-) groups. Transplantation of donor lung grafts harboring pneumonia but having a similar oxygenation level to those without pneumonia was safely performed and did not affect long-term outcome. Appropriate evaluation of serial imaging at donor hospital and suitable perioperative antibiotic management may be reasons for this outcome.

Left Lung Orthotopic Transplantation in a Juvenile Porcine Model for ESLP

Lung transplantation is the gold-standard treatment for end-stage lung disease, with over 4,600 lung transplantations performed worldwide annually. However, lung transplantation is limited by a shortage of available donor organs. As such, there is high waitlist mortality. Ex situ lung perfusion (ESLP) has increased donor lung utilization rates in some centers by 15%-20%. ESLP has been applied as a method to assess and recondition marginal donor lungs and has demonstrated acceptable short- and long-term outcomes following transplantation of extended criteria donor (ECD) lungs. Large animal (in vivo) transplantation models are required to validate ongoing in vitro research findings. Anatomic and physiologic differences between humans and pigs pose significant technical and anesthetic challenges. An easily reproducible transplant model would permit the in vivo validation of current ESLP strategies and the preclinical evaluation of various interventions designed to improve donor lung function. This protocol describes a porcine model of orthotopic left lung allotransplantation. This includes anesthetic and surgical techniques, a customized surgical checklist, troubleshooting, modifications, and the benefits and limitations of the approach.

“Hybrid Lung Transplantation” Combining Living Donor and Cadaveric Lung Transplants: Report of 2 Cases

We present 2 cases of "hybrid lung transplant," which included sequentially implanting a living lobar graft to 1 side and a cadaveric graft to the other side. This procedure was approved by the institutional review board at Okayama University Hospital. The 2 recipients were diagnosed with severe idiopathic pulmonary fibrosis, and living donor lobar lung transplant was considered; however, 2 appropriate donors were not available. Therefore, we accepted extended criteria donor lungs with a partial pressure of oxygen/fraction of inspired oxygen ratio of <251 mm Hg. However, 1 of the 2 patients developed grade 2 primary graft dysfunction. The living donor lobar lung had a low volume but was in good condition, which contributed to the patient's recovery after primary graft dysfunction during the perioperative period. The other patient's status of bronchiolitis obliterans syndrome had gradually progressed to grade 3, and only the living donor lung was functioning at that time. However, both patients are alive 5.5 and 4.2 years after lung transplant, respectively. Hybrid lung transplantation may increase patients' chances of receiving transplants because patients are not likely to survive while waiting for ideal donor lungs to become available.

Use of Ex Vivo Lung Perfusion for Lung Transplantation: Midterm Results

Purpose Ex vivo lung perfusion (EVLP) offers a unique potential in evaluation, optimization and transplantation of lungs that would otherwise potentially be rejected. Between 2016 and 2020 208 lung transplants (LuTx) were performed and 22 donor lungs were evaluated by EVLP of which 16 were transplanted. Aim of the study was to compare mid-term results in LuTx recipients with or without the use of EVLP. Methods In a retrospective single-center analysis data from a prospectively collected database were analysed. The EVLP group (n=16) consisted of donor lungs classified as marginal and were evaluated by EVLP and afterwards transplanted. The non EVLP group (n=16) consisted of conventional LuTx recipients matched for age and pulmonary disease. Both groups were compared for the endpoints survival, primary graft dysfunction, rejection episodes and chronic allograft dysfunction. Results Recipient age was 55 ± 6 years in EVLP group and 57 ± 5 years non EVLP group (n.s.). Female gender was present in 36% EVLP patients and 50% non EVLP (n.s.). The rate PGD grade 1 at 72 h post-LTx was 14% in both groups (each2/16). In non EVLP group 1recipient was PGD 2 (7%). PGD3 was present only in the EVLP group 14% (2/16) vs. 0% in control. At last visit, post-LuTx, forced expiratory volume in 1 s (FEV1%) as percentage of predicted best was similar in the EVLP and non-EVLP group (77% vs. 78%). Chronic lung allograft dysfunction was diagnosed in one non EVLP patient and one EVLP patient during follow up post-LuTx. In the EVLP group 2 patients had rejection episodes subjected to treatment and 6 patients in the non EVLP group (n.s.). Survival at 1 year was 81% for the EVLP group and 94% in non EVLP group (n.s.). Conclusion Recipients transplanted with extended criteria donor lungs, thoroughly evaluated by EVLP show similar mid term outcomes as conventionally transplanted lungs from standard donors. EVLP shall increase the number of acceptable donor lungs. Future clinical trials will bring further evidence; clear guidelines regarding application of machine perfusion have to be developed.

Clinical transplantation using negative pressure ventilation ex situ lung perfusion with extended criteria donor lungs

Lung transplantation remains the best treatment option for end-stage lung disease; however, is limited by a shortage of donor grafts. Ex situ lung perfusion, also known as ex vivo lung perfusion, has been shown to allow for the safe evaluation and reconditioning of extended criteria donor lungs, increasing donor utilization. Negative pressure ventilation ex situ lung perfusion has been shown, preclinically, to result in less ventilator-induced lung injury than positive pressure ventilation. Here we demonstrate that, in a single-arm interventional study (ClinicalTrials.gov number NCT03293043) of 12 extended criteria donor human lungs, negative pressure ventilation ex situ lung perfusion allows for preservation and evaluation of donor lungs with all grafts and patients surviving to 30 days and recovered to discharge from hospital. This trial also demonstrates that ex situ lung perfusion is safe and feasible with no patients demonstrating primary graft dysfunction scores grade 3 at 72 h or requiring post-operative extracorporeal membrane oxygenation.

Impact of extended-criteria donor lungs according to preoperative recipient status and age in lung transplantation.

BackgroundOrgan donor shortage remains as one of the limiting factors for lung transplantation. Given the increase in waiting time, preoperative condition has worsened and affects surgical outcomes. This study aimed to evaluate the immediate postoperative and long-term outcomes of lung transplantation in extended-criteria donor (ECD) lungs compared with standard-criteria donor (SCD) lungs.MethodsA total of 246 patients who had undergone double-lung transplantation during the study period were enrolled. SCD was defined based on the following characteristics age <55 years, <20 pack-years smoking history, and PaO2/fraction of O2 ratio >300 mmHg. Organ donors who do not fulfill these criteria were classified as ECD. Pre- and postoperative data for outcomes and survival data were analyzed.ResultsECD showed significant association with extracorporeal membrane oxygenation weaning in the operating room (hazard ratio [HR], 0.531; 95% confidence interval [CI], 0.291–0.970; P=0.039) considering recipient’s age and status at operation. The ECD group showed comparable survival rate with the SCD group (HR, 1.413; 95% CI, 0.885–2.255; P=0.148), with adjustment of other factors. However, when the recipient had Korean Network for Organ Sharing (KONOS) status 0 at the time of transplantation (HR, 1.662; 95% CI, 1.025–2.568; P=0.039), G3 primary graft dysfunction at 72 hours after surgery (HR, 2.508; 95% CI, 1.416–4.440; P=0.002) was a risk factor that decreased survival.ConclusionsThe outcome of ECD is not inferior to that of SCD. Therefore, ECD lung should be considered a potential donor organ following active donor management rather than a contraindication of transplantation in highly selected recipients.

Pro-IL-1β Is an Early Prognostic Indicator of Severe Donor Lung Injury During Ex Vivo Lung Perfusion.

Ex vivo lung perfusion (EVLP) is used to evaluate and recondition extended criteria donor lungs for transplantation. Interleukin-1β (IL-1β) has been identified as a prognostic indicator of nonrecovery during EVLP. This may be an effect of inflammasome activation or cellular necrosis following donation and graft preservation. Delineating the mechanism of IL-1β release is required. The inactive intracellular precursor molecule, pro-IL-1β, was characterized along with the pro-IL-1β processing enzyme, caspase-1, in the perfusate of n = 20 human lungs that had undergone EVLP (n = 10 lungs that failed to recover and were discarded versus n = 10 lungs that reconditioned and were transplanted). In an experimental porcine model, n = 8 lungs underwent EVLP and were randomized to receive either a specific NLRP3 inflammasome inhibitor or control. Significant increases in pro-IL-1β and caspase-1 were observed in the perfusate from human lungs that did not recondition during EVLP compared with those that successfully reconditioned and were used for transplantation. Within the porcine EVLP, NLRP3 inflammasome inhibition reduced IL-1β within the perfusate compared with controls, but this had no impact on lung function, hemodynamics, or inflammation. Our data suggest that pro-IL-1β is passively released following cellular necrosis of the donor lung.

Initial Successful Clinical Transplantation Using Negative Pressure Ventilation Ex-Situ Lung Perfusion with Extended Criteria Donor Lungs

Ex-situ lung perfusion has been shown to allow for the safe evaluation and reconditioning of extended criteria donor (ECD) lungs. Negative pressure ventilation ex-situ lung perfusion (NPV-ESLP) has been shown, preclinically, to develop less ventilator-induced lung injury than positive pressure ventilation (PPV). We report the first clinical experience utilizing NPV-ESLP for the assessment, preservation, and transplantation of ECD lungs. Twelve patients were transplanted using extended criteria donor lungs. Following standard procurement of ECD lungs the organs underwent assessment and reconditioning using the NPV-ESLP device prior to implantation. Lungs were perfused with Steen solution and red blood cell concentrate. Donor and recipient characteristics including PGD scores at 0, 24, 48, and 72 hours, time to extubation, length of ICU and hospital stay, requirements for extracorporeal membrane oxygenation, and graft and patient survival. Nine out of twelve of the donors involved donation after neurologic determination of death (NDD), while the other three were donation after circulatory determination of death (DCD). The average pre-procurement donor P:F ratio was 234 ± 38 mmHg. Among the nine NDD donors, the average pre-procurement donor P:F ratio was 174 ± 24 mmHg. The average final P:F ratio on the NPV-ESLP device was 540 ± 28 mmHg. The mean duration of ESLP was 182 ± 11 mins. The average recipient P:F ratio at 72 hours post-op was 407 ± 69 mmHg. No patients had a Primary Graft Dysfunction (PGD) Score of 3 at 72 hours and none required post-operative extracorporeal membrane oxygenation. All grafts and patients survived to 30 days and recovered to discharge from hospital. NPV-ESLP demonstrates safe preservation, evaluation, and successful clinical transplantation of extended criteria donor lungs. Further validation of this initial cohort is ongoing and will require large scale pivotal clinical trials to determine overall efficacy.

Multiple Infrequently Used Types of Marginal Donor Lungs are Not Associated with Inferior Survival among Recipients Aged 65+

Though increasing numbers of patients aged 65+ need life-saving lung transplants, these patients are often denied transplantation due to concerns about the scarcity of donor lungs. Using marginal or extended criteria donor lungs could facilitate the transplantation of elderly patients while alleviating concerns about donor scarcity, and may offer elderly patients survival comparable to that with standard criteria donor lungs. Among 4338 U.S. lung transplant recipients aged 65+ from May 2005-August 2016 in the United Network for Organ Sharing (UNOS) dataset, we assessed survival associated with certain marginal donor factors, compared to the absence of each factor. A multivariable Cox regression model generated a Hazard Ratio for each donor factor, adjusted for the other donor factors and over 20 potential confounders, including transplant center performance. Kaplan-Meier methods were used to obtain survival time quartiles for each group. Among recipients aged 65+, marginal donors characterized by: age 55-64 (HR=1.02, p=0.77), ischemic time 6-8 hours (HR=1.05, p=0.48), smoking history 20+ pack-years (HR=1.07, p=0.37), alcohol use 2+ drinks/day (HR=0.91, p=0.16), and history of cancer (HR=0.74, p=0.09), were each not associated with worse survival than donors without the respective marginal factor. These types of marginal donors were used, respectively, in only 11%, 17%, 10%, 15%, and 2% of recipients aged 65+. However, donors with age 65+ (HR=1.48, p=0.01) or ischemic time 8+ hours (HR=1.35, p=0.01) were associated with worse survival. Several types of marginal donor lungs are not associated with worse survival within recipients aged 65+, yet they are hardly used in this population. Widespread acceptance of these donor types could save lives among the growing population of elderly patients who need lung transplants, without expending standard criteria donor lungs, which are commonly preferred to be utilized in younger recipients.

Prolonged extracorporeal preservation and evaluation of human lungs with portable normothermic ex vivo perfusion.

Many lung donor offers are refused despite increasing demand. Portable normothermic ex vivo lung perfusion (EVLP) could increase donor yield by monitoring and reconditioning extended criteria donor (ECD) lungs. We report its use in human lungs declined for clinical transplantation. Ten sets of such lungs were procured from brain-dead donors and underwent 24hours of normothermic EVLP using a perfusate based on donor whole blood. Hemodynamic and ventilatory data and P:F ratios were measured. Advanced donor age and borderline oxygenation (donor mean P:F 228±73) were the most commonly cited reasons for refusal for transplantation. There was no significant worsening of pulmonary hemodynamics or compliance or significant P:F decline during preservation in the overall cohort. Mean P:F ratio in the overall cohort was 315±88mmHg after 24hours EVLP. At EVLP termination 5/10 lung blocks met standard EVLP thresholds for acceptability for transplant. Eventual EVLP performance was poorly predicted by donor P:F ratio but well predicted by data gathered early in EVLP. Portable normothermic EVLP is useful for transportation, monitoring, and reconditioning of ECD lungs. Early EVLP measurements are more effective than preprocurement donor P:F in predicting eventual allograft performance. We advocate an aggressive strategy of evaluation of ECD lungs using blood-based EVLP.

Long-term Outcomes of Lung Transplant With Ex Vivo Lung Perfusion

The mortality rate for individuals on the wait list for lung transplant is 15% to 25%, and still only 20% of lungs from multiorgan donors are used for lung transplant. The lung donor pool may be increased by assessing and reconditioning high-risk extended criteria donor lungs with ex vivo lung perfusion (EVLP), with similar short-term outcomes. To assess the long-term outcomes of transplant recipients of donor lungs treated with EVLP. This retrospective cohort single-center study was conducted from August 1, 2008, to February 28, 2017, among 706 recipients of donor lungs not undergoing EVLP and 230 recipients of donor lungs undergoing EVLP. Donor lungs undergoing EVLP. The incidence of chronic lung allograft dysfunction and allograft survival during the 10-year EVLP era were the primary outcome measures. Secondary outcomes included donor characteristics, maximum predicted percentage of forced expiratory volume in 1 second, acute cellular rejection, and de novo donor-specific antibody development. This study included 706 patients (311 women and 395 men; median age, 50 years [interquartile range, 34-61 years]) in the non-EVLP group and 230 patients (85 women and 145 men; median age, 46 years [interquartile range, 32-55 years]) in the EVLP group. The EVLP group donors had a significantly lower mean (SD) Pao2:fraction of inspired oxygen ratio than the non-EVLP group donors (348 [108] vs 422 [88] mm Hg; P < .001), higher prevalence of abnormal chest radiography results (135 of 230 [58.7%] vs 349 of 706 [49.4%]; P = .02), and higher proportion of smoking history (125 of 204 [61.3%] vs 322 of 650 [49.5%]; P = .007). More recipients in the EVLP group received single-lung transplants (62 of 230 [27.0%] vs 100 of 706 [14.2%]; P < .001). There was no significant difference in time to chronic lung allograft dysfunction between the EVLP and non-EVLP group (70% vs 72% at 3 years; 56% vs 56% at 5 years; and 53% vs 36% at 9 years; log-rank P = .68) or allograft survival between the EVLP and non-EVLP groups (73% vs 72% at 3 years; 62% vs 58% at 5 years; and 50% vs 44% at 9 years; log-rank P = .97) between the 2 groups. All secondary outcomes were similar between the 2 groups. Since 2008, 230 of 936 lung transplants (24.6%) in the Toronto Lung Transplant Program were performed after EVLP assessment and treatment. Use of EVLP-treated lungs led to an increase in the number of patients undergoing transplantation, with comparable long-term outcomes.

New Technique Which Was Combined Living Donor Lower Lobe with Cadaveric Marginal Lung as Called “Hybrid Lung Transplant”

Purpose When extended criteria donor was transplanted to reduce on waitlist time and mortality for severe donor shortage, it had a potential risk to cause worse outcome. Furthermore, using marginal donor for single lung transplant (LT) was more difficult than double LT. In case of adult male recipients, living donor lobar lung transplant (LDLLT) might not be established due to the lung volume and function after LT. We reported good outcome due to new technique which was combined merits of LDLLT with cadaveric LT as called “hybrid LT”. Methods The relatively high-quality cadaveric single lung was choose and transplanted to unilateral chest, living donor lower lobe was transplanted to the other when extended criteria donor lung was allocated for severe illness recipient. Results Both of recipients were diagnosed idiopathic pulmonary fibrosis . They were registered on waiting list. However, they were considered no survive on the list for their severe illness, because long waiting time, approximately 3 years, was needed in Japan for severe donor shortage. On the other hand, donors were rejected by all other transplant centers because of the lungs on the basis of the initial conventional assessments. PaO2/FiO2 ratio of case 1 was at less than 250 and case 2 was at less than 188. Left cadaveric and right living donor lower robe was transplanted on case 1. The recipient experienced grade 2 primary graft dysfunction (PGD) but rapidly recovered. The other was transplanted right cadaveric and left living donor lower robe on case 2 and had no severe PGD. Both of them returned to their normal daily life and is doing well for 2 years after lung transplantation. Conclusion Hybrid LT using unilateral cadaveric lung and living donor lower lobe is feasible and reasonable option for a high-risk recipient when using marginal lung grafts. Hybrid LT reduce perioperative risk due to overcome lung volume, function and quality at the same time and have merit of bilateral LT at the long term outcome.

Extended criteria donor lungs do not impact recipient outcomes in pediatric transplantation

Pediatric lung transplantation remains the only curative treatment option for some end-stage lung diseases in childhood. Recipient numbers outnumber potential donor organs, and therefore a broader group of donor organs must be considered for pediatric lung transplantation. Herein we describe the outcome of utilizing extended criteria donor organs in pediatric lung transplantation. A retrospective analysis was performed on all pediatric lung transplantations performed at the Hannover Medical School between April 2010 and December 2016. Donors were assigned to a group fulfilling standard donor criteria (International Society for Heart and Lung Transplantation [ISHLT] 2003) or not. Recipients' early- and mid-term morbidity and mortality were recorded. A total of 57 pediatric lung transplantations were performed: 27 donors fulfilled standard donor criteria (standard criteria donor [SCD] group) and 30 donors were extended criteria donors not fulfilling standard donor criteria (extended criteria donor [ECD] group). Pre-operative recipient characteristics, including age (median [IQR]: 14 [10‒15] vs 13 [10.8‒15] years, p = 0.71), underlying disease, admission to intensive care unit (37.0% vs 50%, p = 0.42), mechanical ventilation (14.8% vs 10.0%, p = 0.70), and extracorporeal membrane oxygenation (ECMO) support (11.1% vs 23.3%, p = 0.30) of both groups were similar. In the ECD group, more atypical volume reductions of the allograft were performed (0% vs 16.7%, p = 0.05), yet incidence of post-operative ECMO support was similar for the 2 groups. ECD recipients spent significantly less time on mechanical ventilation (median [IQR]: 2 [1‒2] vs 1 [1‒2] days, p = 0.04)] after surgery, but total intensive care unit stay and total hospital stay were similar between groups. Pulmonaryfunction testing results at discharge from initial hospital stay, after 1 year, and at last assessment were also similar. Freedom from chronic lung allograft dysfunction at 1 and 5years after transplantation showed no significant differences between groups. Survival rates up to 5years (67.9% vs 90.5%, p = 0.35) after transplantation were comparable between groups, yet, counterintuitively, long-term survival in the ECD group showed superior trends compared with the SCD group. ECD lungs can be used safely for pediatric lung transplantation without compromising short- and mid-term results.

Extended criteria donor lung reconditioning with the organ care system lung: a single institution experience.

Lung transplantation is a life-saving procedure limited by donor's availability. Lung reconditioning by exvivo lung perfusion represents a tool to expand the donor pool. In this study, we describe our experience with the OCS™ Lung to assess and recondition extended criteria lungs. From January 2014 to October 2016, of 86 on-site donors evaluated, eight lungs have been identified as potentially treatable with OCS™ Lung. We analyzed data from these donors and the recipient outcomes after transplantation. All donor lungs improved during OCS perfusion in particular regarding the PaO2 /FiO2 ratio (from 340mmHg in donor to 537mmHg in OCS) leading to lung transplantation in all cases. Concerning postoperative results, primary graft dysfunction score 3 at 72h was observed in one patient, while median mechanical ventilation time, ICU, and hospital stay were 60h, 14 and 36days respectively. One in-hospital death was recorded (12.5%), while other two patients died during follow-up leading to 1-year survival of 62.5%. The remaining five patients are alive and in good conditions. This case series demonstrates the feasibility and value of lung reconditioning with the OCS™ Lung; a prospective trial is underway to validate its role to safely increase the number of donor lungs.

Lung transplant after prolonged ex vivo lung perfusion: predictors of allograft function in swine

Portable normothermic EVLP has been evaluated in clinical trials using standard and extended-criteria donor lungs. We describe a swine model of lung transplant following donation after circulatory death using prolonged normothermic EVLP to assess the relationship between EVLP data and acute lung allograft function. Adult swine were anesthetized and heparinized. In the control group (n=4), lungs were procured, flushed, and transplanted. Treatment swine underwent either standard procurement (n=3) or agonal hypoxia followed by 1 (n=4) or 2hours (H) (n=4) of ventilated warm ischemia. Lungs were preserved for 24H using normothermic blood-based EVLP then transplanted. Recipients were monitored for 4H. After 24H of preservation, mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and dynamic compliance (Cdyn ) were improved in all EVLP groups. After transplant, EVLP groups showed similar allograft oxygenation. EVLP PVR, mPAP, and lung block weights had significant negative correlations with post-transplant allograft oxygenation. EVLP P:F ratio did not correlate with acute post-transplant allograft function until 24H of preservation. Data measured in the first 8H of EVLP were sufficient for predicting acute post-transplant allograft function. This study provides a benchmark and platform for evaluation of therapies for donor-related allograft injury in injured lungs treated with prolonged normothermic EVLP.

One-year experience with ex vivo lung perfusion: Preliminary results from a single center.

To enlarge the donor pool for lung transplantation, an increasing number of extended criteria donor lungs are used. However, in more than 50% of multi-organ donors the lungs are not used. Ex vivo lung perfusion offers a unique possibility to evaluate and eventually recondition the injured donor lungs. The aim of our study was to assess the enlargement of the donor pool and the outcome with extended criteria donor lungs after ex vivo lung perfusion. Data were prospectively collected in our lung transplant database. We compared the results of lung transplants after ex vivo lung perfusion with those after conventional cold static preservation. In total, 11 extended criteria donor lungs processed with ex vivo lung perfusion and 41 cold static preservation lungs transplanted consecutively between May 2016 and May 2017 were evaluated. Normothermic ex vivo lung perfusion was performed according to the Toronto protocol for 4 h. Cold static preservation lungs were stored in low-potassium dextran solution. Ex vivo lung perfusion lungs before procurement had significantly lower PaO2/FiO2 (P/F) ratios and more X-ray abnormalities. There were no statistically significant differences for pre-donation ventilation time, smoking history, or sex. After reconditioning with ex vivo lung perfusion, 9 out of 11 processed lungs were considered suitable and successfully transplanted. The mean postoperative ventilation time and in-hospital stay were not significantly different in ex vivo lung perfusion and cold static preservation recipients. Ex vivo lung perfusion can safely be used in the evaluation of lungs initially considered not suitable for transplantation. The primary outcome was not negatively affected and normothermic ex vivo lung perfusion is a useful tool to increase the usage of potentially transplantable lungs.

Long Term Outcomes of Ex Vivo Lung Perfusion: A Single Center 10 Year Experience

Waiting list mortality for lung transplantation is 15-25%, while only 20% of lungs from multiorgan donors are deemed suitable for transplantation. Ex vivo lung perfusion (EVLP) is a technique to increase the donor pool by reassessing and reconditioning extended criteria donor lungs (ED) that would otherwise be rejected. Previous studies have shown non-inferior short- and mid-term outcomes in EVLP lung transplantation using these lungs. Here, we report the long-term follow-up of our EVLP recipients.

Lung transplantation in the elderly: Influence of age, comorbidities, underlying disease, and extended criteria donor lungs

ObjectiveAs large registries show an increased risk for lung transplant recipients aged 60 years or more, few single centers report favorable outcomes for carefully selected older recipients without providing essential details. The purpose of our study was to determine variables that influence survival in the elderly. MethodsAll adult bilateral first lung transplants between January 2000 and December 2014 were divided in 2 groups: those aged less than 60 years (N = 223) and those aged 60 years or more (N = 83). The Charlson-Deyo Index determined recipient comorbidities. The Oto Donor Score assessed donor lung quality. ResultsRecipients aged 60 years or more had a significant lower median survival compared with their younger counterparts (48 vs 112 months, respectively, P < .001). Recipient age was as an exponentially increasing univariate risk factor for mortality. By adjusting for variables in multivariate analysis, this trend was nonsignificant. The displacing variables were idiopathic pulmonary fibrosis (hazard ratio [HR], 1.5; 95% confidence interval [CI], 1.0-2.2), Charlson-Deyo Index 2 or greater (HR, 1.3; 95% CI, 1.0-1.8), systemic hypertension (HR, 1.7; 95% CI, 1.2-2.6), gastroesophageal reflux (HR, 1.9; 95% CI, 1.1-3.1), diverticulosis (HR, 1.7; 95% CI, 1.0-2.7), and an Oto Donor Score 8 or greater (HR, 1.5; 95% CI, 1.1-2.0). All of these risk factors were significantly more likely to occur in recipients aged 60 years or more, except for a tendency for high Charlson-Deyo Index. ConclusionsThe comorbidity profile, underlying disease, and donor lung quality appear to be more important than age in reducing long-term survival. Older age serves as a marker for a complex constellation of factors that might be considered the relative or absolute contraindication to lung transplantation rather than age, per se.