Lung Transplant Outcomes Research Articles

Short-Term Outcomes of Lung Transplantation for COVID-19 ARDS: A Single Center Experience

PurposeThe outcomes of lung transplant (LTx) for COVID-19 related lung disease are continuing to be examined. This study describes our experience in the first 7 cases.MethodsThis study included all patients received double LTx (DLTx) for COVID-19 acute respiratory distress syndrome (ARDS) between November 2020 and October 2021. Patient pre-LTx and perioperative characteristics as well as post-LTx outcomes are presented.ResultsSeven patients underwent DLTx for COVID-19 ARDS. All required mechanical ventilation (MV) pre-LTx. Six patients were male (85%), 5 Hispanic (71%), with a median age of 48 (IQR 40-53) and median body mass index of 23.6 (IQR 21.7-25.6). Six patients (85%) were on veno-venous extracorporeal membrane oxygenation (VV-ECMO) pre-LTx (one conversion from VV to veno-arterial (VA)). Median duration of MV and ECMO pre-LTx was 140 days (IQR 82-165) and 71.5 days (IQR 58-149), respectively. Two patients developed acute kidney injury pre-LTx requiring continuous renal replacement therapy (CRRT). Median time from listing to transplant was 17 days (IQR 10-24). ECMO was discontinued in all but 1 patient post-LTx. Median length of stay in the hospital post-LTx was 30 days (IQR 15-57). All were discharged from the hospital (43% to rehabilitation facility). Two patients on pre-LTx CRRT remained hemodialysis dependent and had multi-drug resistant (MDR) bacterial infections post-LTx. One readmission occurred for presumed rejection, aspiration and infection with MDR Klebsiella now requiring oxygen. All surgical pathology showed diffuse interstitial fibrosis consistent with the fibrotic sequelae of alveolar damage due to COVID-19. At 3-month follow-up, 6 patients (85%) did not need supplemental oxygen and had good pulmonary function.ConclusionLung transplantation for COVID-ARDS is feasible. However, pre-transplant multi-system involvement may be associated with a protracted post-LTx stay and MDR infection. Further studies are needed to assess the long-term outcomes in this cohort.

Utilization of Distressed Communities Index to Examine the Impact of Socioeconomic Status on Lung Transplant Outcomes

<h3>Purpose</h3> Given an increased interest in the intersection of socioeconomic status (SES) and healthcare, there have been efforts to quantify individual and community factors that influence health outcomes. Distressed Communities Index (DCI) is one effort that assigns a score of 0 (not distressed) to 100 (severely distressed) to a zip code based on several SES determinants. We aimed to evaluate the impact of SES on preoperative characteristics and postoperative outcomes in lung transplantation (LTx) through the utilization of DCI. <h3>Methods</h3> All adult patients (pts) undergoing LTx at a quaternary care hospital between 2017-2019 were eligible for inclusion of this retrospective cohort study. Pts were stratified by their home zip code as being distressed (DS), DCI score > 60, or not distressed (ND), DCI score < 60. Categorical variables were analyzed with Chi-square tests and continuous variables with the median test. Kaplan-Meier method and logrank techniques were utilized. <h3>Results</h3> A total of 73 pts with a median age of 64 [IQR: 59-68] years met criteria for inclusion. The two cohorts consisted of 24 (33%) DS and 49 (67%) ND pts. The majority of pts were male in both cohorts, DS (75%) and ND (67%). Co-morbidities in the DS and ND groups included hypertension, 54% vs 59%, and diabetes, 45% vs 49%. The most common reason for LTx was idiopathic pulmonary fibrosis in the DS (42%) and ND (45%) group. Preoperatively, DS pts had a longer Six Minute Walk Test (274 vs 196m, p=0.05) with lower FEV1% predicted, (31% vs 47%, p=0.03). Median lung allocation score for the DS and NS cohorts was 48.3 and 47.6 respectively. Length of stay following LTx was similar in the DS and ND cohorts, 19 vs 14 days (p=0.28), and the majority of pts were discharged directly home, 58% vs 63% (p=0.73). There was no statistically significant difference between the DS and ND cohorts with regards to complications in the first year postoperatively including rejection (25% vs 18%), re-hospitalization (67% vs 71%), renal insufficiency (38% vs 31%), and pneumonia (58% vs 49%). Thirty-day survival was similar between the DS and ND recipient, 96% vs 98%, as was 30-month survival, 44% vs 59% (p=0.39). <h3>Conclusion</h3> While DCI was associated with differences in baseline clinical profile, it was not associated with differences in survival in pts undergoing LTx. DCI, as a marker of SES, was not indicative of worse outcomes in pts undergoing LTx.

Molecular Phenotypes of Frailty in Lung Transplant Candidates

<h3>Purpose</h3> The potential for heterogenous pathobiology underlying physical frailty might explain the inconsistent associations observed between frailty and poor outcomes in lung transplantation. We hypothesize that molecular phenotyping could refine frailty measurement and ultimately tailor interventions. <h3>Methods</h3> In a three-center cohort of lung transplant candidates, we measured frailty by the Short Physical Performance Battery (SPPB); demographic and clinical variables; body composition by bioelectrical impedance, and 17 serum biomarkers reflecting commonly cited causes of frailty including inflammation, sarcopenia, adiposity, mitochondrial and neurohormonal dysfunction. Among those pre-frail or frail (SPPB <12), we first applied latent class modelling to the baseline data and then followed participants forward in time. The best-fitting model was determined by the Bayesian Information Criteria and the Vuong-Lo-Mendell-Rubin test. We tested predictive validity of these classes with disability by the Lung Transplant Valued Life Activities scale and by candidate delisting for becoming too ill or death. <h3>Results</h3> In 442 participants, a 3 latent class model best fit (p = 0.046; Figure 1A). Type A was characterized by higher serum biomarkers of inflammation and sarcopenia (lower muscle mass [ASMI] and grip strength); Type B by sarcopenia, high adiposity (VFA), and lack of inflammation, and Type C was relatively fit (higher ASMI and grip strength) and without inflammation (Figure 1B). Amongst the Type A endotype, 13% of participants died or were delisted compared to 6% in both Type B and C (p = 0.15). Participants comprising Type A reported worse disability (LT-VLA 1.7) than Types B and C (1.4 and 1.3, respectively) (p < 0.001) and had shorter time to delisting or death (1.4 vs 8.0 and 4.0 months, respectively) (p < 0.001). <h3>Conclusion</h3> We identified distinct biological phenotypes of frailty. A frailty phenotype characterized by systemic inflammation and sarcopenia appears to be associated with worse clinical outcomes.

Malnutrition in Lung Transplant Recipients: Weighing the Outcomes

<h3>Purpose</h3> Malnutrition negatively impacts outcomes post-lung transplantation. Therefore, nutrition status is routinely considered in the selection criteria for lung transplant candidates. Malnourishment is often present in patients with end-stage lung disease, and unfortunately, it cannot always be resolved before surgery. The impact of malnutrition on lung transplant outcomes has been assessed in the literature using a variety of different methods. However, the standard of care used by nutrition experts and Registered Dietitians, the Academy of Nutrition and Dietetics/American Society of Parenteral and Enteral Nutrition (AND/ASPEN) criteria, has not been considered. Here we investigated how malnutrition identified by these criteria can affect outcomes of lung transplant recipients. <h3>Methods</h3> We retrospectively assessed twenty-two patients who met criteria for moderate or severe malnutrition at the time of transplant using the AND/ASPEN criteria between Jan 1st 2018 and June 1st 2021. We used a control group of twenty-two non-malnourished patients that had similar age and transplant type (single vs bilateral) and compared several different outcome measures using a Kruskal-Wallis test. The data was analyzed using R 4.0.2 (The R Foundation for Statistical Computing http://www.R-project.org). <h3>Results</h3> The average age of both groups was 54.4 years, and 50% of the population was female. We found a significant increase in length of stay (LOS) for the malnourished group (p=0.045) as well as an increased need for return to the intensive care unit (ICU) within 60 days of transplant (p=0.021). Interestingly, no differences were found between the two groups regarding days on a ventilator, days in ICU, the number of rejections in the first six months, or the need for acute inpatient rehabilitation (AIR) following the transplant admission. <h3>Conclusion</h3> Malnutrition identified by AND/ASPEN criteria does seem to impact outcomes following lung transplant, specifically overall LOS and the need for return to ICU within 60 days of transplant. However, there were no significant differences with days on a ventilator, days in ICU, number of rejections in the first 6 months, or need for AIR after transplant. If possible, malnutrition should be improved before lung transplantation. Larger studies are needed to better understand the impact of malnutrition on outcomes after lung transplant.

Donor-Derived Cell-Free DNA Plus Tissue Gene Expression Profiling of Lung Allograft Injury

<h3>Purpose</h3> Lung transplantation outcomes are limited by chronic lung allograft dysfunction, of which acute rejection is a significant risk factor. Acute rejection includes acute cellular rejection (ACR) and antibody-mediated rejection (AMR), and historically has been diagnosed through a combination of transbronchial biopsy histopathology, pulmonary function testing, and the presence of serum donor-specific antibodies. Donor-derived cell-free DNA (dd-cfDNA) has recently shown promise as a less invasive biomarker of allograft injury, but, in isolation, dd-cfDNA does not sufficiently delineate ACR from AMR from infection. Here we propose to combine dd-cfDNA analysis of allograft injury with in situ lung tissue gene expression to better characterize different forms of allograft injury following lung transplantation. <h3>Methods</h3> This is a single center retrospective cohort study of at least 20 lung transplant recipients with longitudinally matched plasma and transbronchial biopsies (n=100). All samples have previously been collected and stored. Plasma will be obtained from the institution's Total Transplant Care Protocol (TTCP) Biorepository, while formalin fixed paraffin embedded (FFPE) biopsy specimens will be obtained from the Department of Pathology through the institution's Tissue Archive Service (TAS). Samples will be assigned to specific clinical cohorts based on histopathology, radiology, microbiological studies and pulmonary function tests at the time of sample collection. Plasma dd-cfDNA fractions will be quantified using Allosure Lung (CareDx), and tissue gene expression profiles (GEP) will be captured with the nCounter Gene Expression Assay (Nanostring Technologies). Data will be analyzed with non-parametric tests and multivariate analyses to determine associations between dd-cfDNA levels and tissue gene expression patterns. <h3>Endpoints</h3> 1. Correlate plasma dd-cfDNA levels with acute allograft injury from ACR, AMR, or infection and determine the time course of dd-cfDNA expression during the first year after lung transplantation. 2. Validate the nCounter Gene Expression Assay platform and identify gene(s) associated with different types of acute rejection and/or infection.

Lung Transplantation in the Elderly: How Old is Too Old?

<h3>Purpose</h3> We aim to determine the effect of age on lung transplant outcomes. There is a paucity of single-center data assessing whether there should be an upper age limit for lung transplant candidates. In analyzing our institution's single-center data to assess age-related outcomes we hope to inform future transplant practices. <h3>Methods</h3> We retrospectively analyzed all single and double lung transplants at our institution from Feb-2012 to Aug-2021 (n=868). Patients were grouped by age into those <70 years old and those ≥70. The two groups were compared for total ischemic time, warm ischemic time, gender, CPB time, LAS score, LOS, SLTx vs DLTx, surgical approach, and type of induction therapy. Data were analyzed using JMP Inc. (version 15.0) and p-value less than 0.05 was considered as significant. <h3>Results</h3> Between all groups, ischemic time (p=0.076) and warm ischemic time (p=0.399) were not significantly different. The <70 age group had more males in proportion to females (p<0.01), were more ethnically white (p<0.001), had greater CPB times (p=0.037), greater LAS scores (p=0.009), and longer LOS (p=0.026). The ≥70 age group had predominantly more SLTx (p<0.001), favored the antero-axillary thoracotomy approach (p=0.002), and had a greater majority of simulect induction compared to campath (p<0.001). Kaplan Meier analysis showed no significant 5- year survival difference in the <70 years age group compared to the ≥70 years group within both the SLTx group (p=0.054) and the DLTx group (p=0.063). Cox Regression showed survival was impacted by longer LOS (p<0.001). <h3>Conclusion</h3> Our results suggest that lung transplant recipients ≥70 years old have similar survival outcomes compared to those <70 for both SLTx and DLTx. This data supports the idea that lung transplantation is a safe and promising treatment option for elderly patients.

Extracorporeal Photopheresis in Lung Transplantation - New Frontiers in Infection Immunomodulation - A Case Series

<h3>Purpose</h3> Lung transplantation outcomes are limited by chronic lung allograft dysfunction (CLAD). Infection driven loss of graft function is a common cause of CLAD. Extracorporeal photopheresis (ECP) is a salvage therapy post lung transplantation with the indications broadening as experience and availability increases. The therapeutic role of ECP is yet to be explored in infection driven CLAD. <h3>Methods</h3> A retrospective audit of all lung transplant recipients at a single UK lung transplant centre who received ECP from 2017 to 2021 was performed using electronic records.5 patients with infection driven CLAD treated with ECP were identified. <h3>Results</h3> 40% were male with median(range) age 63(30-70) years. Median duration from lung transplant to ECP was 38(13-53)months and median duration of ECP was 14(10-15) months. All 5 patients were responders at 2 months (defined as less than 20 percent FEV1 fall). Median(range) FEV1 percentage change improved from -17% (-20 to+10%) one year pre-ECP to +1%(-1to+10%) one year post-ECP (Figure1). Mycophenolate mofetil was stopped for all patients on initiation of ECP. 4 patients had a reduction in length of stay in hospital (Figure 2). 3 patients were alive 1 year post ECP whilst 2 patients are still within their first year of follow up. <h3>Conclusion</h3> ECP can help to stabilize graft function in lung transplant recipients with recurrent infections. It allows for modification of conventional immunosuppression regimens and contributes to improved quality of life by decreasing the length of hospital stay and number of antibiotic days.

Standardized Radiographic Evaluation of Human Donor Lungs During Ex Vivo Lung Perfusion Predicts Lung Injury and Lung Transplant Outcomes

<h3>Purpose</h3> Ex vivo lung perfusion (EVLP) is increasingly used to evaluate marginal donor lungs for transplantation. A commonly used component of donor lung assessment during EVLP is a lung radiograph taken after 1h and 3h of perfusion. The purpose of our study was to systematically evaluate EVLP radiographic findings and define their association with observed lung injury and EVLP outcomes. <h3>Methods</h3> We retrospectively evaluated all EVLP cases from 2020-21 (n=113). Radiographs were scored by a thoracic radiologist blinded to donor lung outcome. Each ex vivo lung lobe was scored for five radiographic features (consolidation, infiltrates, atelectasis, nodules, and interstitial lines) on a scale of 0 to 3 by severity for a maximum radiographic lung score (RLS) of 18 per feature. The RLS was correlated with markers of lung injury (PaO₂/FiO₂ and edema) using Spearman's correlation. Logistic regression was used to generate receiver operating curves to derive the performance of RLS in predicting transplantation outcome following EVLP. <h3>Results</h3> Consolidation and infiltrates after 1h of EVLP were the most frequent findings (RLS 2.5±3.4 and 4.4±4.3). Interstitial lines were less frequent (RLS 1.76±3.53), with nodules and atelectasis being uncommon (RLS 0.60±1.30 and 0.41±0.65). At the first and third hours of perfusion, consolidation (r=-0.536 and -0.608, p<0.0001) and infiltrates (r=-0.492 and -0.616, p<0.0001) were inversely correlated with oxygenation (PaO₂/FiO₂), whereas interstitial lines were correlated with increased perfusate loss in the circuit reflecting increased edema (r=0.244, p=0.019, and r=0.309, p=0.0047). First-hour consolidation, infiltrates, atelectasis, nodules, and interstitial line RLS predicted the decision to transplant the lungs with area under the curve of 87%, 88%, 52%, 58%, and 56%, respectively. First- and third-hour RLS from all five features predicted the decision to transplant with an area under the curve of 90% and 88%, respectively, and when combined, the value increased to 92%. <h3>Conclusion</h3> Consolidation and infiltrates were the most frequent findings in lungs undergoing ex vivo lung perfusion. The Radiographic Lung Score (RLS) predicted the suitability of donor lungs for transplant. Radiographic ex vivo lung images provide key information for the clinical evaluation of donor lungs for transplantation.

Kinetic Modeling of Ex Vivo Lung Perfusion Biomarkers for the Prediction of Lung Transplant Outcomes

<h3>Purpose</h3> Many ex vivo lung perfusion (EVLP) biomarker studies involve hourly perfusate sampling to predict lung transplant outcomes; however, the diagnostic and predictive value of repeated sampling and a biomarker kinetic profile remains unknown. In this study, we constructed mathematical models of protein biomarkers in EVLP perfusate and assessed the predictive value of the kinetic model features. <h3>Methods</h3> Clinical EVLP cases (n=45) were used in this study. Perfusate samples were collected every 15 minutes from 0-180 minutes of perfusion. Seven protein biomarkers were studied: GM-CSF, IL-10, IL-1β, IL-6, IL-8, sTNFR1, and sTREM1. All concentration data were corrected for circuit dilution using the reported standardized perfusate exchanges. Five mathematical models were tested to fit the biomarker time-series data: linear, quadratic, exponential, four- and five-parametric logistic regression. The model features were then used to predict recipient ICU length of stay using the area under the receiver operating characteristic curve (AUROC). <h3>Results</h3> The time-series data showed that GM-CSF (r²=0.92), sTNFR1 (r²=0.95), sTREM1 (r²=0.96) were best described using a linear model, whereas, IL-10 (r²=0.93), IL-1β (r²=0.92), IL-6 (r²=0.95), and IL-8 (r²=0.98) were best described by an exponential growth curve. When biomarker data were corrected for dilution, there was a significant improvement in model fit [p<0.05 (IL-8, GM-CSF); p<0.001 (IL-1β, IL-10, IL-6, sTNFR1, sTREM1)]. For linear models of GM-CSF and sTNFR1, the rate of change (slope) was predictive for ICU length-of-stay (<3days). For exponential models, the rate constant was predictive for IL-1β and IL-8, whereas both the rate constant and starting value were predictive for IL-6. Combining kinetic model features with hourly data resulted in improved diagnostic performance for GM-CSF (AUROC=88% [95%CI:72-99]), IL-10 (AUROC=81% [95%CI:61-99]), and IL-8 (AUROC=72% [95%CI:50-94]). <h3>Conclusion</h3> Kinetic modeling can be utilized to accurately reflect protein biomarker behaviour during EVLP, and features extracted from these models improve the prediction of EVLP outcomes. This study represents an important framework to guide future research to improve the predictive utility of EVLP perfusate-derived biomarkers.

Lung Transplant Outcomes in Patients with Pulmonary Veno-Occlusive Disease

<h3>Purpose</h3> Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension. Prognosis of PVOD is worse than PAH. Most patients need lung transplantation. Previous study showed that PVOD patients had higher waitlist mortality compared to PAH patients. To date, there are no study report outcomes of lung transplant in this population. We would like to study the outcome and compare with IPAH patients. <h3>Methods</h3> This is a retrospective observational study. Patients with a diagnosis of PVOD and PAH underwent lung transplant between 2005 and 2018 were identified from SRTR database. Numerical data were reported in mean and standard deviation. Categorical data were reported in count and percent. T-test and Chi-square test were performed to compare variables between 2 groups. Survival was compared using Kaplan-Meier (K-M) method. <h3>Results</h3> 61 PVOD patients and 970 PAH patients underwent lung transplant were identified. There was no significant difference in age and BMI. Patients with PVOD had significant lower post-transplant systolic, diastolic and mean PA pressure and higher cardiac output. LAS at matching were not significantly different. PVOD patients had shorter time on waiting list (152.7±263.34 vs 337.56±511.14, p<0.01). Proportion of patients requiring ECMO post lung transplant were higher in PVOD group (13.11% vs 4.23%, p<0.01). Proportion of patients developing primary graft dysfunction (PGD) were lower in PVOD group (37.5% vs 61.93%, p=0.056). There was no difference of length of stay, FEV1, FVC, PCO2 post lung transplant and acute rejection between 2 groups. Survivals were not different between 2 groups using K-M method (p=0.33). <h3>Conclusion</h3> We found that PVOD patients who underwent lung transplant had shorter waiting time compared to PAH patients which suggest that disease severity of PVOD is higher than PAH. Despite that more PVOD patients required ECMO support post-operative, patient survival and other long-term outcomes such as lung function or rejection were not different between from PAH patients.

The Impact of Geographical Distance on Survival in Adult Cystic Fibrosis Lung Transplant Recipients

<h3>Purpose</h3> Cystic fibrosis (CF) remains one of the most common indications for bilateral lung transplantation (LTx) worldwide. Worse outcomes are seen after other organ transplantations than lung, for those living further from transplant centers. To date, the role of distance in lung transplantation outcomes in the United States (US) among people with CF has not been previously studied. The objective of this study was to assess the association of geographical distance with survival among adult CF LTx recipients in the US. <h3>Methods</h3> A retrospective nationwide cohort study of 2,838 adult CF LTx patients from 2005-2019 was conducted using the Scientific Registry of Transplant Recipients. Geographical distance was determined between the recipients' zip code and their transplant center zip code. Patients were stratified into 3 groups based on their distance (<50, 50-150, and >150 miles). The outcome of interest included time from transplantation to death or re-transplantation. All-cause mortality was examined with multivariable Cox proportional hazard regression, and the Kaplan-Meier method was used to model survival after LTx. <h3>Results</h3> Of the 2,838 CF LTx recipients, 1,218 (42.9%) traveled <50 miles; 814 (28.7%) traveled 50-150 miles; and 806 (28.4%) traveled >150 miles. During the study period, 1,170 (41.2%) patients died. There was a significant difference in survival by distance traveled (log-rank p=0.003). Compared to the recipients living within 50 miles of a transplant center, those traveling 50-150 miles (HR=1.20; 95% CI=1.02-1.41) and >150 miles (HR=1.29; 95% CI=1.10-1.52) had a higher risk of death. Younger age, being African American, having lower BMI, and less education had statistically significant negative associations with patient survival. Health insurance and year of transplantation were also found to have statistically significant associations with patient survival. <h3>Conclusion</h3> This study represents the largest cohort evaluating the effect of distance from transplant center on survival in adult CF LTx recipients. Worse survival was seen in patients living further away from their transplant center. Further investigation of the causes that contribute to this observed disparity may aid in improving survival rates of CF LTx recipients, including evaluating the number of clinic visits, transportation issues, cost of travel, or other financial concerns.

Risks and Outcomes Associated with Pleural Space Infections After Lung Transplantation

<h3>Purpose</h3> Pleural space infections (PSI) are a serious complication after lung transplantation (LT) however there is limited data on the associated risk factors and outcomes of PSI. We examined: 1) risk factors associated with PSI after LT; 2) effect of PSI on LT outcomes. <h3>Methods</h3> This is a retrospective single center cohort study of 74 consecutive LT recipients (1/2018- 6/2020). Patients were divided into infected and non-infected groups, where PSI were defined as post-LT pleural effusions with pathogen(s) isolated from pleural fluid. Data were collected and compared between two groups with two-sample t-test or Fisher-exact. Multivariable logit model was performed with estimations of odds ratio (OR) and its confidence interval [CI]. <h3>Results</h3> Among 74 LT recipients, 38 (51%) developed pleural effusions requiring drainage; of them 16 (42%) had PSI. Baseline demographics were similar in patients with and without PSI (Table). Notably, 88% of PSI group received steroids pre-LT compared to 55% in the non-infected group (p<0.05); 88% of the PSI group had an underlying diagnosis of interstitial lung disease versus 45% of the non-infected group (p<0.01). Overall post-operative complications occurred more frequently in the PSI group vs. non-infected group 77% vs. 25% (p<0.01) and airway complications in 86% vs. 44% (p<0.01). Hospital length of stay was longer in the PSI group with the median of 78 versus 31 days in the non-infected group (p<0.01). Results of logistical modeling showed high risk of PSI with presence of post-LT airway complications (OR =10.8 95% CI 1.7- 72.5) and presence of post operative complications (OR=10.6, 95% CI 1.8-63.5). There was no difference in the incidence of readmissions, acute cellular rejection or 1 year mortality between the two cohorts. <h3>Conclusion</h3> PSI remain a prevalent yet under-studied complication. Airway or post-operative complications after LT were associated with PSI. One-year outcomes were similar in LT recipients with and without PSI.

Outcomes of Flow Cytometry Crossmatch-Positive Lung Transplants Using Peri-Operative Desensitization

<h3>Purpose</h3> Successful outcomes among virtual crossmatch (VXM)-positive lung transplant recipients (LTRs) following peri-operative desensitization have been previously reported. However, the subset of flow cytometry crossmatch (FCXM)-positive LTRs, who may be at higher immunologic risk, has not been studied specifically. We conducted a retrospective cohort study to determine the impact of a positive FCXM on allograft survival (death/re-transplant) and chronic lung allograft dysfunction (CLAD)-free survival among LTRs in our program. <h3>Methods</h3> All adult, first-time LTRs from January 2014 to December 2019 with complete crossmatch data were divided into 3 cohorts based on sensitization status at the time of transplant: VXM-negative, VXM-positive/FCXM-negative, and VXM-positive/FCXM-positive. Patients were followed until October 2021. VXM-positive LTRs were routinely desensitized using plasma exchange, intravenous immune globulin, and anti-thymocyte globulin peri-operatively. Patient characteristics were compared using the chi-square test, and Kaplan Meier estimates of allograft survival and CLAD-free survival were compared using the log-rank test. <h3>Results</h3> A total of 902 LTRs were included: 765 (85%) VXM-negative, 63 (7%) VXM-positive/FCXM-negative, and 74 (8%) VXM-positive/FCXM-positive. VXM-positive/FCXM-positive LTRs were more likely to be female (p<0.001) and less likely to have cystic fibrosis/bronchiectasis (p=0.022), but age and urgency status at listing did not differ from the other cohorts. There was no significant difference in allograft survival (p=0.9805) or CLAD-free survival (p=0.9306) among VXM-negative, VXM-positive/FCXM-negative, and VXM-positive/FCXM-positive LTRs (Figure 1). <h3>Conclusion</h3> In the largest study to date of FCXM-positive LTRs, we demonstrate that with our peri-operative desensitization protocol, outcomes are equivalent to other LTRs. Our protocol may be used to facilitate VXM-positive and FCXM-positive lung transplants safely.

Mid-Term Outcome of Lobar Lung Transplantation: Hamburg Experience

<h3>Purpose</h3> Recipients with small chest cavities, especially female patients with lung fibrosis, receive just few opportunities for size-matched organs dedicated for lung transplantation. Lobar lung transplantation (LLuTx) is a reasonable option for these candidates. We compared early complications, long-term lung function and survival with conventional bilateral lung transplantation (CLuTx). <h3>Methods</h3> A retrospective review of patients who underwent lung transplantation at our institution between January 2009 and July 2021 was performed. The Long-term survival and early surgical complications in 12 patients (9 women, 46±13),who received LLuTx, were analyzed. <h3>Results</h3> The underlying diseases were cystic fibrosis (n=6), idiopathic pulmonary fibrosis (n=5) and pulmonary hypertension (n=1) with a mean waiting time of 241±210 days, which was comparable with CLuTx (p=0.333). The mean predicted total lung capacity ratio (donor/recipient) was 1.5±0.3. The postoperative complications included bronchus insufficiency (n=1), bleeding (n=2), kinking of pulmonary artery (n=1) bronchus intermedius stenosis (n=1), lung edema (n=1) and ISHLT Grade 3 primary graft dysfunction (n=3). The 30-day survival (92% vs 91%, p=0.324), one year survival (70% vs 71%, p=1.000) and the Kaplan-Meier curve (p=0.587) is comparable to patients who received CLuTx in the same period (n=91)(Figure 1). <h3>Conclusion</h3> This study suggests that LLuTx is a valuable option for patients with small chests and yields a low complication rate with acceptable Long-term survival when compared to CLuTX. LLuTx warrants consideration of acceptable organs for these patients in a reasonable time frame.

Comparing Outcomes of Single versus Double Lung Transplantation for COPD Patients in a Single-Center Setting

<h3>Purpose</h3> There is conflicting data whether single (SLT) or double (DLT) lung transplant is preferred for end-stage chronic obstructive pulmonary disease (COPD) patients. While national data shows that DLT is the method of choice, it is important re-assess this stance considering the current national organ shortage. The purpose of this study is to investigate whether SLT patients perform similarly to DLT patients in a single center setting. <h3>Methods</h3> We retrospectively identified COPD patients who underwent lung transplantation from 02/2012-05/2021 at our center (n=228). Clinical parameters were compared between the patients based on the type of transplant. Survival outcomes between the cohorts were compared using Kaplan Meier, as well as Cox proportional hazard regression. P-value <0.05 was significant. <h3>Results</h3> Of the 228 COPD patients, 81 (35.5%) received DLTs and 147 (64.5%) received SLTs. The difference in survival outcomes between patients receiving SLTs and DLTs was not significant (P = 0.265). The Cox model also did not show a significant difference in survival (P = 0.298). There was no significance in the distribution of transplant type by recipient body mass index, serum creatinine, serum albumin, or forced expiration volume at time of transplant. There was significance in the distribution of transplant type by recipient age (P = 0.017), recipient sex (P<0.001), recipient race (P = 0.049), lung allocation score (P<0.001), recipient height (P<0.001), mean pulmonary artery pressure (P = 0.002), surgical approach (P<0.001), induction (P = 0.043), donor sex (P = 0.030), donor height (P = 0.005), length of stay (P = 0.008), and forced vital capacity at transplant (P = 0.014). Patient age was the only variable to affect survival (HR = 5.60; P = 0.048). <h3>Conclusion</h3> Patients who received SLTs at our center did not show a significant difference in survival outcomes when compared to patients who received DLTs. This could suggest that SLT's may be the preferred method bearing in mind the current organ shortage.

Clinical features and outcomes of unplanned single lung transplants

ObjectiveThe decision to perform single lung transplants or double lung transplants is usually made before the operation. We have previously reported that a proportion of single lung transplants were unexpectedly performed in the setting of an aborted double lung transplant, and these patients may be at a higher risk of worse short-term outcomes. Long-term outcomes in unplanned single lung transplants remain unknown. MethodsWe analyzed a single-center database of lung transplants from 2000 to 2020. Single lung transplants were classified into planned and unplanned groups after reviewing operative notes. Root cause analysis was performed for unplanned single lung transplants. ResultsOf the 1326 lung transplants, 1265 (95%) were double lung transplants and 61 (5%) were single lung transplants (22 planned [36%], 39 unplanned [64%]). Underlying indications for transplant were significantly different; planned single lung transplant: chronic obstructive pulmonary disease (55%) and idiopathic pulmonary fibrosis (45%); unplanned single lung transplants: chronic obstructive pulmonary disease (23%), idiopathic pulmonary fibrosis (39%), and bronchiolitis obliterans syndrome (13%). The primary reasons for unplanned single lung transplant were donor-related (3, 7.7%), recipient-related (31, 80%), and donor and recipient-related factors (5, 13%). Unplanned single lung transplants were more likely to require cardiopulmonary bypass during the operation (planned: 4/22, 18% vs unplanned: 20/39, 51%) but had shorter ischemic times (planned: 251 ± 58 minutes vs unplanned: 221 ± 48 minutes). The 5-year overall survival was 53% in the planned and 58% in the unplanned groups, respectively (P = .323). No difference in chronic lung allograft dysfunction–free survival (P = .995) was observed. ConclusionsUnplanned single lung transplants in the setting of aborted double lung transplant may be associated with acceptable long-term outcomes.

A Simple Scoring System for Lung Transplant Waitlist Mortality Risk Factors

<h3>Purpose</h3> Current lung allocation score (LAS) waitlist mortality prediction models are complex and incorporate correlated predictors. This study identified and evaluated three multidimensional indices of correlated risk factors. This approach could enable more efficient use of risk factor information and improve dynamic models of end-stage lung disease and transplant outcomes. <h3>Methods</h3> We analyzed 2015-2020 data on U.S. lung transplant candidates on the waiting list, obtained from the Scientific Registry for Transplant Recipients (N=13990). We used hierarchical clustering to identify distinct respiratory support groups based on supplemental oxygen device, rate and frequency of use; steroid use and extracorporeal membrane oxygenation. We used confirmatory factor analysis (CFA) to derive indices of i) airway function (forced expiratory volume, forced vital capacity, and partial pressure of carbon dioxide [PCO₂]) and ii) oxygen function (partial pressures of oxygen (PO₂), PO₂/FiO₂ ratio, and mean pulmonary artery pressure). Cox proportional hazards regression was used to characterize relationships between the developed constructs and waitlist mortality (or removal) after adjusting for disease group, age and sex. <h3>Results</h3> Four respiratory support clusters were identified (see the panel labels in the <b>Figure</b>). Contours of predicted 6-month waitlist mortality risk are displayed for a sample 63-year-old patient with idiopathic pulmonary fibrosis in the Figure. The area under the receiver-operating characteristic curve [95% confidence interval] for 1-year predictions from the fitted Cox model was 0.75 [0.71, 0.79], which was marginally lower than that of the full LAS waitlist mortality model (AUC = 0.79 [0.75, 0.83]). <h3>Conclusion</h3> The three developed constructs of respiratory support, oxygen function and airway function distilled information in 11 correlated risk factors for waitlist mortality, facilitating interpretation of risk profiles without adversely impacting model accuracy. <h3>Funding</h3> NIH R01HL15375

There is No Smoking Gun: LongTerm Lung Transplant (LTx) Outcomes Using Smoking Donors

<h3>Purpose</h3> Lung transplant (LTx) is limited by a supply of donor lungs. Donor lungs from smokers are known to have adverse effects on early post-LTx outcomes (Oto et al, 2004). As long-term survival outcomes remains under assessed we investigated the effect of donor smoking on long-term LTx survival and death from chronic lung allograft dysfunction (CLAD) using the cohort described by Oto et al. <h3>Methods</h3> 173 bilateral LTx recipient records between 1995-2002 were retrospectively reviewed. 97 (56.1%) of LTx donors had ceased or never smoked and 76 (43.9%) were current smokers. Kaplan-Meir models were used to assess long-term survival. Smoking donors were divided into two groups: 1-15 pack years (PY) (n=35) and >16 PY (n=21). 20 recipients received donors with a smoking history but unknown amount. Hazard ratios (HR) were used to assess survival outcomes between known smoking groups. <h3>Results</h3> No significant survival difference was found between LTx recipients for never/ ceased smokers and smokers (Figure 1) or between smoking dose cohorts (Figure 2). HR for smokers compared to never/ ceased smokers: 1.25, 95% CI 0.70 to 2.25, p=0.439. HR for 1-15 PY compared to never or ceased smokers: 1.21, 95% CI 0.57 to 2.53, p=0.615. HR for >16 PY compared to never/ ceased smokers: 0.83, 95% CI 0.28 to 2.41, p=0.721. There was no significant difference in death from CLAD between groups. <h3>Conclusion</h3> This study suggests that a smoking history in LTx donors does not significantly affect long-term survival or increase death from CLAD. This may have implications for expanding donor criteria, enabling LTx opportunities for more patients.

Survival After Lung Transplantation in Europe - Clad as Major Cause of Death

<h3>Purpose</h3> Lung transplantation (LTX) outcomes are poor in comparison to other solid organ transplantations. Our aim was to review survival, leading chronic complications, and major causes of death in Europe. A particular focus is put on Chronic Lung Allograft Dysfunction (CLAD) and its trends. <h3>Methods</h3> There is no dedicated European registry on lung transplantation, outcomes, and complications. Therefore, accessible data from ISHLT registry with focus on the European continent, European Registries and German Quality report were screened for lung transplantation survival data. Furthermore, a dedicated literature research on chronic complications following LTX and particularly CLAD was performed with focus on Europe. In a further step, clinical trial registries were screened for advanced trials addressing the leading form of CLAD - obstructive phenotype - Bronchiolitis Obliterans Syndrome (CLAD-BOS). <h3>Results</h3> Survival rate for LTX reaches 83.2% and 71% at 1 and 3 years, based on 3502 cases included between 2013 and 2016 in the ISHLT registry - European Continent, under exclusion of retransplant. Eurotransplant data from 2012 to 2016 comprising 3053 LTX from Austria, Belgium, Germany, and the Netherlands state survival rates of 83.5%, 76.8% and 62.5% at year 1, 2 and 5. Yet, pan-European data are lacking. Some large monocentric European studies report CLAD rates ranging from 38% at 3 years to 44% at longer follow-up. These findings are in line with US data. CLAD-BOS represented consistently the most prevalent phenotype, up to 80% of all CLAD cases. Although no dedicated European registry data are available, monocentric studies pinpoint CLAD as the single largest cause of death post-LTX. Within CLAD, BOS phenotype accounts for two-thirds of deaths based on reported autopsy analysis. Currently, two substances targeting CLAD-BOS are in phase 3 clinical investigation in Europe. <h3>Conclusion</h3> In Europe, 3-year post-lung transplantation survival is around 70% and 5-year survival at 63%. CLAD is consistently the most prevalent and fatal complication in lung transplant recipients. CLAD-BOS is the most frequent phenotype. New treatments to address chronic graft failure and primary cause of death in LTX, namely CLAD-BOS, are needed. Currently two therapeutic approaches are under investigation in phase 3 clinical trials aiming at CLAD-BOS in Europe.

The Complete Score for Comprehensive Evaluation of Donor Lungs in Ex-Vivo Lung Perfusion: An Approach for Optimizing the Outcomes of Transplantation

<h3>Purpose</h3> The imperfection of the currently utilized tools for assessing graft function in acellular ex-vivo lung perfusion (EVLP) has led our team to develop a comprehensive evaluation scoring system. This study aimed to validate this scoring system in our clinical EVLP program. <h3>Methods</h3> One hundred twelve EVLP cases were performed in our program since 2018. Data from the first 73 cases (derivation cohort) were retrospectively analyzed to identify the included evaluation parameters and to inform the cutoff values in the scoring system using Youden index. The scoring system was then prospectively applied in the remaining 39 cases (validation cohort). The comprehensive lung evaluation EVLP (COMPLETE) score included ultrasound evaluation, lung weight measurement, compliance, airway pressure, deflation, oxygenation, lactate level, bronchoscopy, and x-ray. <h3>Results</h3> Out of 112 EVLP cases, 75 (67%) were transplanted with 98.7% 30-day survival. The incidence of primary graft dysfunction (PGD) grades 0, 1, 2, and 3 at 72 hours post-transplant were 21, 63, 8, and 8 %, respectively. The COMPLETE score cutoff value for transplant suitability identified by the derivation cohort was 12 (AUC 1, 100% sensitivity & specificity) which was then applied in the validation cohort. Only two recipients in the validation cohort had PGD3 (which appeared to be related to intraoperative factors, not donor factors). The COMPLETE score had a significant correlation with IL-1β perfusate levels (r = 0.44, <i>p</i> < .001). Nine cases did not meet the standard criteria (FDA approved) for transplant suitability on EVLP but were transplanted based on their COMPLETE scores with 100% 30-day survival. Of those, 1 had PGD0, 7 had PGD1, and 1 had PGD3. On the other hand, 10 cases met the standard criteria for transplant suitability but were deemed non-suitable based on their COMPLETE scores and the post-EVLP pathological examination showed significant edema in 4 cases, acute lung injury in 4 cases, and pulmonary embolism in 2 cases. <h3>Conclusion</h3> Our novel COMPLETE scoring system provides a protocolized comprehensive evaluation of donor lungs on EVLP. It can be used to optimize the outcomes of lung transplantation by increasing utilization rates after EVLP and by identifying donor factors that might lead to unfavorable outcomes following transplantation.