Lung Allocation Score Research Articles

Strategic application of modular risk components to safely increase lung transplantation volume.

Considerable growth of individual lung transplant programs remains challenging. We hypothesized that the systematic implementation of modular risk components to a lung transplantation program would allow for expeditious growth without increasing mortality. All consecutive patients placed on the lung transplantation waitlist were reviewed. Patients were stratified by an 18-month period surrounding the systematic implementation of the modular risk components Era 1 (1/2014-6/2015) and Era 2 (7/2015-12/2016). Modular risk components were separately evaluated for donors, recipients, and perioperative features. One hundred and thirty-two waitlist patients (Era 1: 48 and Era 2: 84) and 100 transplants (Era 1: 32 and Era 2: 68) were identified. There was a trend toward decreased waitlist mortality (P = .07). In Era 2, the use of ex vivo lung perfusion (P = .05) and donor-recipient over-sizing (P = .005) significantly increased. Moreover, transplantation with a lung allocation score greater than 70 (P = .05), extracorporeal support (P = .06), and desensitization (P = .008) were more common. Transplant rate significantly improved from Era 1 to Era 2 (325 vs 535 transplants per 100 patient years, P = .02). While primary graft dysfunction (PGD) grade 3 at 72 hours (P = .05) was significantly higher in Era 2, 1-year freedom from rejection was similar (86% vs 90%, P = .69) and survival (81% vs 95%, P = .02) was significantly greater in Era 2. The systematic implementation of a modular risk components to a lung transplantation program can result in a significant increase in center volume. However, measures to mitigate an expected increase in the incidence of PGD must be undertaken to maintain excellent short and midterm outcomes.

A Simple Prioritization Change to Lung Transplant Allocation May Result in Improved Outcomes

The lung allocation score (LAS) significantly improved outcomes and wait list mortality in lung transplantation. However, mortality remains high for the sickest wait list candidates despite additional changes to allocation distance. Regulatory considerations of overhauling the current lung allocation system have met significant resistance, and changes would require years to implement. This study evaluates whether a modest change to the current system by prioritization of only high-LAS lung transplant candidates would result in lowered wait list mortality. The Thoracic Simulated Allocation Model was used to evaluate all lung transplant candidates and donor lungs recovered between July 1, 2009 and June 30, 2011. Current lung allocation rules (initial offer within a 250-nautical mile radius for ABO-identical then compatible offers) were run. Allocation was then changed for only patients with an LAS of50 or higher (high-LAS) to be prioritized within a 500-nautical mile radius with no stratification between ABO-identical and compatible offers. Ten iterations of each model were run. Primary end points were wait list mortality and posttransplant 1-year survival. A total of 6538 wait list candidates and transplant recipients were evaluated per iteration, for a total of 130,760 simulated patients. Compared with current allocation, the adjusted model had a 23.3% decrease in wait list mortality. Posttransplant 1-year survival was minimally affected. Without overhauling the entire system, simple prioritization changes to the allocation system for high-LAS candidates may lead to decreased wait list mortality and increased organ use. Importantly, these changes do not appear to lead to clinically significant changes in posttransplant 1-year survival.

National Trends in Extended Criteria Donor Utilization and Outcomes for Lung Transplantation

Extended criteria donor (ECD) for lung transplantation (LTx) have been implemented due to the donor organ shortage. The impact on recipient survival is under investigation. We report trends in the use of extended criteria lungs in the modern era and its association with survival outcomes using a large national database. We performed a retrospective analysis of all adult LTx from May 2005 to December 2018 using the United Network for Organ Sharing database. ECD were defined by 2 or more variances from standard criteria: age ≥ 55 years, pO2 ≤ 300, pack years ≥ 20, diabetes, purulent bronchoscopy, blood infection, or abnormal chest radiographs. Transplant centers were dichotomized based on volume. Recipient survival was analyzed using lung allocation score as a covariate. Of 24,888 LTx, 80% had extended criteria; 42% had 2 or more extensions and were deemed ECD in this analysis. Both LTx volume (2005: 1352; 2018: 2495) and use of ECD (2005: 27% ECD, 2018: 50% ECD) have increased over the study period. Survival of LTx recipients has steadily increased (2005: 82% 1-year survival in 2005; 2017: 90% 1-year survival). High-volume centers (>47 annual LTx) utilized ECD in 46% of transplants compared with 40% ECD among other centers. Recipients of ECD and standard criteria organs had no difference in 1-year survival. Donor supply limits the number of LTx performed. Extension of donor criteria has occurred alongside increased overall LTx volume. Use of ECD did not compromise 30-day, 90-day, nor 1-year survival. Further studies are warranted to define long-term outcomes.

Impact of the elimination of the donation service area on United States lung transplant practices and outcomes at high and low competition centers.

In November 2017, the donation service area (DSA) was removed as the primary unit of US donor lung allocation. Our primary objective was to evaluate the effect of this change on recipient characteristics, the use of pretransplant extracorporeal membrane oxygenation (ECMO), and on index hospitalization length of stay (LOS) and early posttransplant complications. We also assessed whether these outcomes differed in high and low competition centers, as defined by the Herfindahl-Hirschman Index. Following DSA removal, there was a 9-day decrease in median waitlist time (P=.001) and an increase in median lung allocation score (40 vs 42, P<.0001) but no difference in the need for pretransplant ECMO (incidence rate ratio=1.16, P=.12). Median LOS increased from 17 to 19days in the post-DSA era (P=.01). There was no difference in posttransplant outcomes, including prolonged ventilation, new dialysis, or early survival, in the general cohort or between competition groups. High competition centers saw an 18.5-minute increase in ischemic time compared to low competition centers (P=.04) but did not differentially increase single lung transplants or pretransplant ECMO utilization. Overall, DSA elimination was associated with increased posttransplant LOS but no significant differences in pretransplant ECMO or other posttransplant outcomes. Effects were largely similar at low and high competition centers.

Acute Kidney Injury in Patients Undergoing Cardiopulmonary Bypass for Lung Transplantation

BackgroundCardiopulmonary bypass (CPB) is often used to support patients undergoing lung transplantation who are intolerant of anatomic manipulation or single lung ventilation during the procedure. However, CPB may be associated with adverse outcomes. We evaluated the hypothesis that CPB is associated with increased acute kidney injury (AKI) and postoperative mortality after lung transplantation. Materials and methodsThis was a retrospective review of our institutional lung transplant database at the University of Texas Southwestern Medical Center from 2012 to 2018. Patients were grouped based on their need for CPB. The primary outcome was AKI within 48 h of transplantation, which was defined as Kidney Disease Improving Global Outcomes stage 1 or greater. Secondary outcomes included all-cause mortality. ResultsA total of 426 patients underwent lung transplantation with 39.0% (n = 166) requiring CPB. There were no differences in demographics and comorbidities, including baseline renal function, between CPB and no CPB. CPB use was higher in recipients with interstitial lung diseases and primary pulmonary hypertension. Median lung allocation score was higher in those needing CPB (47 [interquartile range, 40-59] versus 39 [interquartile range, 35-47]). Patients requiring CPB were significantly more likely to experience AKI (61.44% versus 36.5.3%, P < 0.01) and postoperative hemodialysis (6.6% versus 0.4%, P < 0.01). On multivariable analysis, CPB was significantly associated with postoperative AKI (odds ratio, 1.66; 95% CI, 1.01-2.75; P = 0.04). Thirty-day mortality was higher in patients undergoing CPB (4.2% versus 0.8%, P = 0.03). ConclusionsCPB for lung transplantation is associated with a higher incidence of AKI, renal failure requiring hemodialysis, and 30-d mortality. CPB should be used selectively for lung transplantation.

What Awaits on the Other Side: Post-Lung Transplant Morbidity and Mortality After Pre-Transplant Hospitalization.

BackgroundMorbidity and mortality rates after lung transplantation remain high compared to other solid organ transplants. In the lung allocation score era, patients given the highest priority on the waitlist are those with the greatest severity of illness, who often require preoperative hospitalization.Material/MethodsTo determine the association of pre-transplant hospitalization with post-transplant outcomes, we retrospectively evaluated 448 lung transplant recipients at our center between January 2010 and July 2017 (114 hospitalized; 334 outpatient).ResultsSurvival was similar between the groups (hazard ratio 0.93 [95% CI 0.61 to 1.42], p=0.738). However, hospitalized patients had longer hospital and intensive care unit length of stay compared to outpatients – 25 vs. 18 days, (p<0.001) and 9.5 vs. 6 days, (p<0.001), respectively. Hospitalized patients had higher rates of Grade 3 primary graft dysfunction – 29.8% vs. 9.6%, p<0.001 – and remained mechanically ventilated longer – 6 vs. 3 days, p<0.001. A greater percentage of hospitalized patients needed a tracheostomy and a re-operation within 30 days – 39.5% vs. 15.3% (p<0.001) and 22.8% vs. 12.0% (p=0.005) – respectively. After discharge, 28% of hospitalized patients required acute rehabilitation compared with 12% of outpatients (p=0.001).ConclusionsWhile pre-transplant hospitalization is not associated with mortality, it is associated with significant morbidity after transplant.

Perspectives on donor lung allocation from both sides of the Atlantic: The United States.

Donor lung allocation in the United States focuses on decreasing waitlist mortality and improving recipient outcomes. The implementation of allocation policy to match deceased donor lungs to waitlisted patients occurs through a unique partnership between government and private organizations, namely the Organ Procurement and Transplantation Network under the Department of Health and Human Services and the United Network for Organ Sharing. In 2005, the donor lung allocation algorithm shifted toward the prioritization of medical urgency of waitlisted patients instead of time accrued on the waitlist. This led to the Lung Allocation Score, which weighs over a dozen clinical variables to predict a 1-year estimate of survival benefit, and is used to prioritize waitlisted patients. In 2017, the use of local allocation boundaries was eliminated in favor of a 250 nautical mile radius from the donor hospital as the first unit of distance used in allocation. The next upcoming iteration of donor allocation policy is expected to use a continuous distribution algorithm where all geographic boundaries are eliminated. There are additional opportunities to improve donor lung allocation, such as for patients with high antibody titers with access to a limited number of donors.

Is Extracorporeal Membrane Oxygenation Withdrawal a Safe Option After Double-Lung Transplantation?

Extracorporeal membrane oxygenation (ECMO) is commonly used during double-lung transplantation. ECMO can be planned or unplanned, and used only during the procedure or extended postoperatively (intraoperative or extended). Our practice is to limit its use and duration as much as possible. We conducted this retrospective single-center study to assess prognoses of patients undergoing unplanned-intraoperative ECMO. From among 436 patients who underwent double-lung transplantation from 2012 to 2018, we excluded those who underwent bridge-to-transplantation, multiorgan transplantation, repeated transplantation during the study period, and cardiopulmonary bypass. Unplanned-intraoperative ECMO group was compared with no-ECMO and planned-intraoperative ECMO groups. In our sample, 209 patients did not require ECMO, 77 underwent unplanned-intraoperative ECMO, and 14 underwent planned-intraoperative ECMO. One-year and 3-year survival were lower in unplanned-intraoperative ECMO group than in the no-ECMO group (P= .043 and P= .032, respectively). The only independent protective factor related to 1-year mortality was history of cystic fibrosis (P= .013). Lung allocation score (P= .001), grade 3 pulmonary graft dysfunction at end-surgery status (P= .014), and estimated intraoperative blood loss (P= .031) were risk factors. Patients who underwent unplanned-intraoperative ECMO showed poorer prognoses than patients who did not require ECMO. This finding may be explained by differences in initial condition severity, by long-term consequences of the intraoperative complications leading to ECMO pump implantation, or by flaws in our weaning protocol.

Clinical judgment versus lung allocation score in predicting lung transplant waitlist mortality.

Canadian lung transplant centers currently use a subjective and dichotomous "Status" ranking to prioritize waitlisted patients for lung transplantation. The lung allocation score (LAS) is an objective composite score derived from clinical parameters associated with both waitlist and post-transplant survival. We performed a retrospective cohort study to determine whether clinical judgment (Status) or LAS better predicted waitlist mortality. All adult patients listed for lung transplantation between 2007 and 2012 at three Canadian lung transplant programs were included. Status and LAS were compared in their ability to predict waitlist mortality using Cox proportional hazards models and C-statistics. Status and LAS were available for 1122 patients. Status 2 patients had a higher LAS compared to Status 1 patients (mean 40.8 (4.4) vs 34.6 (12.5), P=.0001). Higher LAS was associated with higher risk of waitlist mortality (HR 1.06 per unit LAS, 95% CI 1.05, 1.07, P<.001). LAS predicted waitlist mortality better than Status (C-statistic 0.689 vs 0.674). Patients classified as Status 2 and LAS≥37 had the worst survival awaiting transplant, HR of 8.94 (95% CI 5.97, 13.37). LAS predicted waitlist mortality better than Status; however, the best predictor of waitlist mortality may be a combination of both LAS and clinical judgment.

Urgently listed lung transplant patients have outcomes similar to those of electively listed patients

ObjectivesTo (1) determine outcomes after urgent listing compared with elective listing for lung transplant and (2) compare in-hospital morbidity and mortality, survival, and allograft function in these 2 groups. MethodsFrom January 2006 to September 2017, 201 patients were urgently and 1423 electively listed. Among urgently listed patients, 130 subsequently underwent primary lung transplant as did 995 electively listed patients. Competing-risks analysis for death and transplant after listing and weighted balancing score matching (76 pairs) were used to compare in-hospital morbidity and survival. Mixed-effect longitudinal modeling was used to compare allograft function to 8 years post-transplant. ResultsAt 1 month, mortality was 26% in urgently listed patients, and 58% were transplanted. Risk factors for death included older age, higher bilirubin, and transfer from an outside hospital. At transplantation, urgently listed transplant patients were younger (53 ± 13 vs 55 ± 12 years), had more ventilator and extracorporeal membrane oxygenation support (32/25% vs 20/2.0%), more restrictive lung disease (95/73% vs 509/51%), and a higher lung allocation score (82 ± 13 vs 47 ± 17). In-hospital morbidity and mortality, time-related survival, and longitudinal allograft function were similar between matched groups. ConclusionsUrgent listing more often than not leads to transplantation. Although urgently listed patients are sicker overall, after transplant their perioperative morbidity and mortality, overall survival, and allograft function are similar to those of electively listed patients. Appropriate patient selection and aggressive supportive care allow urgently listed lung transplant patients to achieve these similar post-transplant outcomes.

Sympatho-Vagal Dysfunction in Patients with End-Stage Lung Disease Awaiting Lung Transplantation.

Although the literature demonstrates that cardiac autonomic control (CAC) might be impaired in patients with chronic pulmonary diseases, the interplay between CAC and disease severity in end-stage lung disease has not been studied yet. We investigated the effects of end-stage lung disease on CAC through the analysis of heart rate variability (HRV) among patients awaiting lung transplantation. Forty-nine patients on the waiting list for lung transplantation (LTx; 19 men, age 38 ± 15 years) and 49 healthy non-smoking controls (HC; 22 men, age 40 ± 16 years) were enrolled in a case–control study at Policlinico Hospital in Milan, Italy. LTx patients were divided into two groups, according to disease severity evaluated by the Lung Allocation Score (LAS). To assess CAC, electrocardiogram (ECG) and respiration were recorded at rest for 10 min in supine position and for 10 min during active standing. Spectral analysis identified low and high frequencies (LF, sympathetic, and HF, vagal). Symbolic analysis identified three patterns, i.e., 0V% (sympathetic) and 2UV% and 2LV% (vagal). Compared to HCs, LTx patients showed higher markers of sympathetic modulation and lower markers of vagal modulation. However, more severely affected LTx patients, compared to less severely affected ones, showed an autonomic profile characterized by loss of sympathetic modulation and predominant vagal modulation. This pattern can be due to a loss of sympathetic rhythmic oscillation and a subsequent prevalent respiratory modulation of heart rate in severely affected patients.

The Impact of Donor Asphyxiation or Drowning on Pediatric Lung Transplant Recipients.

Donors with drowning or asphyxiation (DA) as a mechanism of death (MOD) are considered high risk in pediatric lung transplantation. We sought to evaluate whether recipients of DA donors had negatively impacted outcomes. Pediatric recipients recorded in the United Network for Organ Sharing registry between 2000 and 2019 were included. Primary stratification was donor MOD. Propensity matching with a 1:1 ratio was performed to balance the DA and non-DA MOD donor cohorts. Cox multivariable regression was used to determine the risk-adjusted impact of donor MOD. A subanalysis of the effect of lung allocation score was also evaluated. A total of 1016 patients underwent bilateral lung transplantation during the study period, including 888 (85.6%) from non-DA donors and 128 (14.4%) from DA donors. Survival at 90 days, 1 year, and 2 years were similar in the matched and unmatched cohorts regardless of the donor MOD. Moreover, separate risk-adjusted analysis of drowning and asphyxiated donors was similar to other MOD donors at 30 days, 1 year, and 5 years. Similar survival findings persisted regardless of pretransplant lung allocation score. Although the rates of posttransplant stroke (1.0% versus 3.1%, P = 0.04) and the length of hospital stay (19 versus 22 d, P = 0.004) were elevated in the unmatched DA MOD recipients, these differences were mitigated after propensity matching. This study evaluated the impact of DA MOD donors in pediatric lung transplant recipients and found similar rates of complications and survival in a propensity-matched cohort. These data collectively support the consideration of DA MOD donors for use in pediatric lung transplantation.

COVID-19: A global transplant perspective on successfully navigating a pandemic.

The COVID‐19 pandemic has rapidly evolved and changed our way of life in an unprecedented manner. The emergence of COVID‐19 has impacted transplantation worldwide. The impact has not been just restricted to issues pertaining to donors or recipients, but also health‐care resource utilization as the intensity of cases in certain jurisdictions exceeds available capacity. Here we provide a personal viewpoint representing different jurisdictions from around the world in order to outline the impact of the current COVID‐19 pandemic on organ transplantation. Based on our collective experience, we discuss mitigation strategies such as donor screening, resource planning, and a staged approach to transplant volume considerations as local resource issues demand. We also discuss issues related to transplant‐related research during the pandemic, the role of transplant infectious diseases, and the influence of transplant societies for education and disseminating current information.

Low Lung Allocation Score Predicts Poor Waitlist Outcomes for Patients on Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation

Extracorporeal membrane oxygenation (ECMO) is increasingly used as a bridge to lung transplantation in the United States. However, ECMO is not separately distinguished from assisted ventilation in the lung allocation score (LAS), and there is a wide range in LAS for candidates on ECMO. In this study, we examined the relationship between LAS and waitlist outcomes in patients on ECMO. This is a retrospective cohort study of lung transplant candidates on ECMO from 5/4/05 until 12/31/18 using data from the United Network for Organ Sharing. We modeled LAS as a continuous variable and as high LAS (top 50% of scores) versus low LAS (bottom 50% of scores). The LAS used was the first one calculated within two days of ECMO initiation. The primary outcomes were transplantation and a composite of death or removal from the waitlist for clinical deterioration. The secondary outcome was post-transplant survival. We used an adjusted competing risk regression model to compare waitlist outcomes and an adjusted Cox regression model to examine post-transplant survival. In total, 954 patients were bridged on ECMO with 594 (62.2%) receiving transplants and 329 (34.4%) dying or being removed from the waitlist. The mean LAS in the low and high LAS cohorts were 78.2 (SD ± 15.6) and 90.7 (SD ± 1.36), respectively. The low LAS cohort had decreased chance of transplant (SHR 0.80, 95% CI 0.67-0.96, p=0.02) and increased risk of death or waitlist removal (SHR 1.34, 95% CI 1.05-1.70, p=0.02) (Figure 1). For every 10 point increase in LAS, the risk of transplant increased by 14% (p<0.01) and the risk of death decreased by 11% (p=0.02). There was no difference in post-transplant survival time between the low and high LAS cohorts (HR 0.82, 95% CI 0.60-1.12, p=0.21). Among patients on ECMO as bridge to transplant, a lower LAS was associated with decreased risk of transplant and increased risk of death or clinical worsening without any difference in post-transplant survival.

Calculating the Lung Allocation Score Error for ECMO Patients

The use of extracorporeal membranous oxygenation (ECMO) as a bridge to lung transplantation has increased dramatically. However, the Lung Allocation Score (LAS) does not use a dedicated ECMO variable; instead, ECMO is proxied by mechanical ventilation with 100% oxygen. We aimed to determine if this approximation accurately reflects the transplantation urgency for ECMO patients. Lung transplant candidates and recipients greater than 12 years of age between 2008-2014 were selected from the SRTR database. For both the wait-list (WL) and post-transplant (PT) time periods, predicted survival functions were calculated using the LAS model and compared to observed survival functions estimated by Kaplan-Meier. Differences between predicted and observed WL survival and PT survival were calculated for candidates and recipients, stratified by ECMO support at listing or transplant. The errors in WL and PT survival were then combined to estimate the LAS error for each group. During the study period, 16,259 candidates were listed; 236 were on ECMO at listing. A total of 12,169 patients were transplanted; 363 were on ECMO at transplant. Non-ECMO candidates survived a mean of 336 days from listing compared to a LAS prediction of 328 days, leading to a WL error of 9 days. ECMO candidates survived a mean of 199 days from listing compared to a LAS prediction of 123 days, leading to a WL error of 77 days. Non-ECMO recipients survived a mean of 333 days from transplant compared to a LAS prediction of 315 days, leading to a PT error of 17 days. ECMO recipients survived a mean of 296 days from transplant compared to a LAS prediction of 248 days, leading to a PT error of 48 days (Fig 1). ECMO was associated with an overestimation of the LAS by 10 points, compared to a non-ECMO underestimation of 0.04 points. The LAS ECMO correction underestimates both WL and PT one-year survival, leading to an overall upward bias in the LAS compared to non-ECMO candidates. This suggests that ECMO candidates have a lower transplantation urgency than implied by their LAS.

Disparities in the Lung Allocation Score Due to Geography Have Not Changed Since November 2017

Differences in geographic donor lung availability affect waitlist outcomes. We hypothesized that the lung allocation score (LAS) at transplant and waitlist time would vary based on local donor lung availability and that broader geographic sharing since November 2017 would improve these disparities. Using UNOS data, we conducted a retrospective cohort study of 23,414 lung transplant recipients from January 1, 2006 - December 31, 2018. Local lung availability was defined as the ratio of donor lungs to waitlist candidates in the local donation service area. We calculated the local lung availability for candidates prior to November 25, 2017. We used mixed multivariable linear regression and Poisson regression, adjusting for time dependent LAS changes, to examine the relationship between local lung availability, LAS at transplant and waitlist time. We used Wilcoxon rank-sum to compare LAS at transplant before and after November 2017. Compared to recipients in the top quartile with greatest local lung availability, recipients in the lowest quartile were transplanted with a LAS 6.2 points higher (95% CI: 5.6-6.9, p <0.001) and waited significantly longer, 186 days (95% CI: 178-194) compared with 93 days (95%CI: 88-97), p <0.001. This difference varied by transplant type, with single lungs recipients transplanted with a LAS 2.0 points higher in the lowest quartile (95%CI: 0.9-3.0, p < 0.001) compared with the top and double lung recipients transplanted with a LAS 8.8 points higher (95% CI: 8.0-9.6, p<0.001) in the lowest quartile compared with the top. At centers in the lowest quartile of local lung availability, the LAS at transplant did not meaningfully change after November 2017 (44.1 ± 15.2, compared to 45.7± 16.3, p=0.042), however the waitlist time did decrease from 206 days (95%CI: 192-222) to 155 days, (95% CI: 133-176), p <0.001. The LAS at transplant and waitlist time for recipients did not change at high local lung availability centers (50.7 ± 19.6 compared to 51.3 ± 19.6, p=0.38, and 74 days (95%CI: 66-81) compared to 61 days (95%CI: 52-70), p=0.66). Prior to November 2017, low local lung availability was associated with longer waitlist times and higher LAS at transplant that were much more pronounced for double lung recipients. Since expanding allocation to 250 miles, meaningful differences in LAS at transplant have not yet been observed.

Exceptional LAS Requests in Eurotransplant: Analysis of an 8-year Effort to Improve Lung Allocation for Precarious Patients

Following introduction of the lung allocation score (LAS) in 2011, Eurotransplant member centers can apply for an exceptional LAS (eLAS) if the calculated LAS insufficiently reflects the perceived transplant benefit for a patient, specifically in case of primary pulmonary hypertension group 1 and 4; combined lung+non-renal transplantation; rare diseases; or extracorporeal support. Each eLAS proposal is evaluated by a LAS Review Board, consisting of ≥3 lung transplant experts, which subsequently declines or approves the eLAS request in consensus of ≥3 votes. In case of a lower than accepted score, predefined business rules to assign LAS percentiles are used. A retrospective analysis of all eLAS requests in Eurotransplant from December 2011 until September 2019. Overall, 5183 lung transplants (deceased donors) were performed and 420 eLAS requests were made (Germany 52%, Netherlands 18%, Austria 18%, Belgium 13%), of which 116 (28%) were approved. Most eLAS requests concerned group B/Pulmonary vascular disease (44%), followed by group C/Cystic fibrosis or immunodeficiency disorder (28%), then group D/Restrictive lung disease (15%) and finally group A/Obstructive lung disease (11%); whereas 10 patients (2%) were not classified. The proportion of accepted eLAS requests significantly differed between countries (Germany 25%, Netherlands 37%, Austria 20%, Belgium 36%) (p=0.042). eLAS requests decreased in the Netherlands following its LAS introduction in 2014 (2011-2014 mean 13/yr vs. 2015-2019 mean 4.6/yr; p=0.060). However, since 2015 an overall annual increasing number of eLAS requests is seen, with doubling of the eLAS requests in 2018 vs. 2015, but no difference in acceptance rate (2015-2018: 22.4%) (Figure). Acceptance rates were 38% for Group B, 21% for Group C, 20% for Group D and 11% for Group A. The observed variations require further investigation to optimize lung allocation for specific patient populations in Eurotransplant.

Accuracy of the US Lung Allocation Score (LAS) Waitlist Mortality Risk Estimates

The US LAS is used to preferentially allocate donor lungs based on calculated benefit - the difference between recipient estimated risk of mortality without a transplant and survival after transplant. However, the LAS does not account for changing risk of mortality with time which may lead to prediction errors in the waitlist (WL) component of the LAS model and ultimately that of transplant benefit. Cohorts included active lung transplant candidates (at 0, 3, 6, 9, and 12 WL m) between Jan 1, 2015-Sept 1, 2018 in the US Scientific Registry of Transplant Recipients database. The primary outcome was 1-year WL mortality - a composite of 1) all-cause mortality and 2) WL removal due to being too sick. The accuracy of the WL survival model and an internally re-estimated model for WL survival was evaluated at each time point. Analyses of WL survival model performance - discrimination (ability to discriminate between survivors and decedents) and calibration (concordance between predicted and observed mortality) were performed for each cohort. Of 10,329 candidates, 1008 died or were removed from WL for being too sick.1-year cumulative mortality incidence estimates were comparable between the baseline (9.7%) and 3 m residual cohort (9.8%), while estimates for subsequent residual cohorts (6, 9, 12 m) were slightly higher (10.7%, 11.6%, 11.0%). The LAS WL model mis-calibrates, overpredicting risk of mortality by 3-4 fold with moderate discrimination performance (concordance indices: 0.66-0.73). The re-estimated model initially had good calibration but under-estimated risk in residual cohorts. The relationship between disease characteristics and WL mortality dynamically evolves over time. However, the current LAS calculation models are based on static risk estimates that lead to over-estimation of WL mortality as time on WL increased. This may result in miscalculation of transplant benefit on an individual patient level undermining the stated allocation priority of the LAS system.

Prognostic Nutritional Index Negatively Correlates with Lung Allocation Score and Predicts Survival after Both Cadaveric and Living-Donor Lobar Lung Transplantation

The preoperative nutritional status affects the clinical outcome of surgery. To predict the clinical outcome, a prognostic nutritional index (PNI) calculated using serum albumin levels (ALB) and total lymphocyte count (TLC) has been shown to be valuable in various fields of surgery. In this study, we investigated the relationship between PNI and lung allocation score (LAS) as well as the impact of PNI on outcomes of lung transplantation (LT), including cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). Between June 2003 and August 2016, a total of 127 patients underwent LT at Okayama University Hospital, including 71 recipients of CLT and 56 recipients of LDLLT. The PNI was calculated by the following equation: PNI = (10 × ALB(g/dl)+(0.005 × TLC(/mm3)). The overall survival was evaluated by univariate analysis (the log rank test) and multivariate analysis (the Cox proportional hazard regression model) using preoperative factors, including sex, age, BMI, diagnosis, oxygen concentration, mechanical ventilation, tracheostomy, ECMO support, use of glucocorticoids, serum creatinine level, diabetes mellitus, LAS, and PNI. PNI was significantly negatively correlated with LAS (r=-0.3, P=0.00062) (Fig. 1A). The univariate analysis revealed that the overall survival was significantly worse in the patients with age>28 (P=0.047), BMI<24.2 (P=0.0098), LAS>58.04 (P=0.000072), PNI<46.35 (P=0.018) (Fig. 1B). The multivariate analysis demonstrated that age (P=0.00093), BMI (P=0.0024), and PNI (P=0.0047) were independent prognostic factors of worse outcome. In the subgroup analysis, low PNI is a significant prognostic factor of worse survival after CLT (P=0.015) (Fig. 1C) and LDLLT (P=0.041) (Fig. 1D). Preoperative nutritional evaluation using PNI could contribute to the assessment of LT recipient's severity and predict survival after both CLT and LDLLT.

Lung Volume Reduction Surgery Prior to Lung Transplantation: A Propensity-Matched Analysis

Lung volume reduction surgery (LVRS) is a therapeutic option in the treatment of chronic obstructive pulmonary disease (COPD), the most common indication for lung transplantation (LTx). LVRS prior to LTx is controversial. Single institution studies report contradicting results, and the impact of undergoing LVRS prior to LTx on outcomes after LTx is unclear. We performed a propensity-matched analysis of outcomes after LTx in patients who underwent LVRS using a national database of LTx. We reviewed the Scientific Registry of Transplant Recipients for all adults (age>18) who underwent first-time LTx for COPD in the Lung Allocation Score (LAS) era. We used patient demographics and LAS to match patients who did and did not undergo LVRS. The primary exposure was prior LVRS. We used multivariate logistic regression modeling to evaluate the primary outcome, one-year mortality, and secondary outcomes, chronic rejection by one year requiring treatment and prolonged ventilation (>5 days). Long-term survival was compared using Kaplan Meier testing. A total of 5,061 patients underwent LTx between January 2005 and March 2017. The average patient age at transplant was 60.7±6.0 years, and 2,591 (51.2%) patients were male. The mean LAS at transplant was 34.9±6.1. A total of 111 (2.2%) patients underwent LVRS prior to LTx. Propensity matching generated 111 matches. Multivariate logistic regression modeling in this group revealed a 16% increased risk of mortality at one year among patients who underwent LVRS prior to LTx (OR: 1.16, 95% CI: 1.01-1.32, p=0.03). There was no statistically significant difference in risk of chronic rejection by one year requiring treatment (p=0.5) or prolonged ventilator support (p=0.5) among the two groups. The Kaplan Meier survival analysis demonstrated a significant survival deficit between patients who received LVRS and those who did not at five years post-transplant (52.3% vs. 66.3% p=0.01). In this national, propensity matched analysis of LVRS prior to LTx, we show that LVRS is associated with a significantly increased risk of mortality. Patients who undergo LVRS and remain in need of LTx should be carefully assessed and followed post-operatively. Further studies are necessary to identify why these patients may be at increased risk of adverse outcomes after LTx.