Lung Transplant Outcomes Research Articles

Lung Transplantation Outcomes after Crossing Low Level Donor Specific Antibodies without Augmented Immunosuppression

<h3>Purpose</h3> Lung transplant recipients with pre-transplant donor specific antibodies (DSA) are often treated with augmented immunosuppression. It is unknown whether some DSA can be safely crossed without additional therapies. We implemented a protocol allowing transplant when crossing select low level DSA (defined as mean fluorescence intensity (MFI) 1000-5000) without planned augmented immunosuppression. <h3>Methods</h3> This was a single center retrospective cohort study between 4/1/2015-8/31/2020. All recipients received solumedrol and basiliximab induction without desensitization. Presence of low level pre-transplant DSA was recorded. All post-transplant DSA was monitored within 14 days of transplant and then at routine intervals. The primary study outcomes were overall survival, definite CLAD≥1-free survival, and definite antibody mediated rejection (AMR), all defined according to ISHLT consensus guidelines. <h3>Results</h3> Of the 453 recipients, 36 (7.9%) had a low-level pre-transplant DSA crossed at transplant (Table 1). 13 had Class I antibodies and 26 had Class II. The median historical DSA MFI was 1800 (IQR 1300-2400) and the median most recent MFI was 1200 (IQR 950-2000). Among recipients where pre-transplant DSA was crossed, 17 (47.2%) had persistent post-transplant DSA with a median peak MFI of 7400. Class II antibodies were more likely to be detected post-transplant than Class I (57.7% vs 15.4%, p=0.02). There was no statistical difference in definite AMR in recipients where pre-transplant DSA was and was not crossed (8.3% vs 3.1%, p=0.11). With a median follow-up time of 2.4 years, there were no differences in adjusted overall survival (HR=1.14, 95% CI=0.57-2.32, p=0.71) or CLAD≥1-free survival (HR=0.82, 95% CI=0.44-1.54, p=0.54). <h3>Conclusion</h3> Lung transplantation in the presence of low level DSA without planned augmented immunosuppression was not associated with worse overall or CLAD-free intermediate-term survival but may be associated with increased AMR.

Racial Differences in Immunosuppression and Lung Transplant Outcomes

<h3>Purpose</h3> Maintenance of immunosuppression in lung transplant recipients (LTx) is integral for preventing allograft rejection, with tacrolimus as a mainstay drug. Prior research from our group showed significantly poorer outcomes for Non-European Ancestry patients (Non-EA) as compared to those of European Ancestry (EA) and that donor-derived cell-free DNA (ddcfDNA) predicts molecular allograft injury in LTx. This study examines differences in immunosuppression between EA and Non-EA LTx in the context of disparate outcomes. <h3>Methods</h3> 453 LTx within two multicenter cohorts were analyzed based on self-identified race. Serial post-transplant tacrolimus blood levels and dosages were collected. Tacrolimus trough levels were dichotomized as "therapeutic" or "non-therapeutic" based on goal trough level ranges and were analyzed over 6-month periods up to 18 months post-transplant. Serial plasma samples were assayed for %ddcfDNA by shotgun sequencing and log-transformed to adjust for skewness. <h3>Results</h3> The study cohort was 80.1% EA and 19.9% Non-EA. The odds and mean number of therapeutic trough levels were similar between EA and Non-EA within the 0-6 (OR=0.98 95% CI 0.71 - 1.35, p=0.91), 6-12 (OR=2.25 95% CI 0.93 - 5.45, p=0.07), and 12-18-month (OR= 1.41 95% CI 0.73 - 2.71, p=0.31) intervals. However, non-EA patients required twofold higher median tacrolimus dosages to reach therapeutic trough levels as compared to EA patients (Fig. 1a). Furthermore, non-EA patients had significantly higher ddcfDNA levels as compared to non-EA (Fig. 1b). <h3>Conclusion</h3> Despite disparities in post-transplant outcomes, non-EA achieve similar therapeutic levels of tacrolimus as compared to EA but require significantly higher doses to do so. At a molecular level, non-EA showed significantly higher levels of molecular allograft injury as assessed by ddcfDNA despite equivalent immunosuppression trough levels. Further research is needed to investigate racial outcome disparities and use of ddcfDNA to augment immunosuppressive monitoring in minority LTx.

Impact of Pulmonary Artery Pressure on Survival Outcome of Single- and Double-Lung Transplantation in Chronic Obstructive Pulmonary Disease Patients

<h3>Purpose</h3> It remains unclear whether double lung transplantation (DLT) or single lung transplantation (SLT) is preferred for end-stage chronic obstructive pulmonary disease (COPD) patients. The purpose of this study is to examine the interplay between patient age and pulmonary artery pressure on survival after SLT vs DLT for COPD. <h3>Methods</h3> We performed a single-center retrospective study of lung transplantations for COPD between February 2012 to March 2020 (n=186). Demographics and clinical parameters were compared between patients based on their pulmonary artery pressure (PAP; PAP<25 mmHg vs PAP≥25 mmHg) and type of transplantation (single vs. double). Additionally, survival based on age (≤65 vs. >65 years old) and PAP were analyzed using Kaplan-Meier curves and log-rank tests. Cox proportional-hazards regression was also performed. P-value less 0.05 was considered significant. <h3>Results</h3> Of the 186 COPD patients who received lung transplants, 71 (38.2%) received double-lung transplants and 115 (61.8%) received single-lung transplants. Demographics and clinical parameters between the two PAP groups showed significance in: lung allocation score (p=0.002) and BMI at time of transplant (p<0.001). There was no significant difference in survival outcomes between SLT vs. DLT patients (p=0.870). Patients with elevated pulmonary artery pressures (PAP≥25 mmHg) did not have significantly different survival outcomes from patients with normal pressures (PAP<25 mmHg; p=0.16). There was also no difference in survival between the two age groups, ≤65 vs. >65 years (p=0.723). The Cox model itself, also, did not show a statistically significant improvement in evaluating survival outcomes (p=0.126). <h3>Conclusion</h3> Lung transplantation outcomes in end-stage COPD patients demonstrated non-inferior results with SLT compared to DLT. When patients were differentiated based on PA pressure, adopting SLT or DLT did not show any survival differences.

Lung Transplant Outcomes with Concomitant Heart Donation

<h3>Purpose</h3> Concomitant heart and lung donation may adversely affect outcomes in lung transplant recipients. In this study we characterized donor characteristics and examined the outcomes of lung transplantation from donors with concomitant heart donation. <h3>Methods</h3> This retrospective cohort study used the UNOS SRTR database and identified donors as lung only (LO) or heart and lung (HL) donors. Recipients from 5/01/05-03/31/19 were identified and compared. Redo and multi-organ transplants were excluded. Characteristics and outcomes were compared using the Kruskal-Wallis and chi-square tests. Survival was analyzed with Kaplan-Meier analysis and Cox proportional-hazard (CPH) model. <h3>Results</h3> We identified 24,393 lung transplant recipients. 6,412 were in the HL group and 17,981 in the LO donor group. HL recipients were older, male, and had shorter waitlist times (Table, p<0.01 for all). HL donors were younger and had a significantly lower incidence of coronary disease, smoking, diabetes, and hypertension (Table, p<0.01 for all). HL recipients were more likely to be single lung transplants, have shorter ischemic times, and have shorter length of stay (Table, p<0.01 for all). No significant difference in survival was noted with unadjusted analysis (p=0.09), or with the CPH (HL hazard ratio 0.956, 95% confidence interval 0.91-1.00, p=0.06). <h3>Conclusion</h3> No survival difference was noted in recipients of LO and HL donors. Given comparable survival outcomes HL donors should be viewed as equivalent to LO donors. Further investigation should be directed into the reasons behind increased use of single lung transplantation of HL donors and whether both lungs are utilized.

Donor-Recipient Body Mass Index Matching in Lung Transplantation

Purpose Donor-recipient size matching, in terms of height, total lung capacity and chest x-ray measurements, has been studied and is known to affect outcomes. Less is known about the impact of BMI matching which could have equally important implications on outcomes. We analyzed the Scientific Registry of Transplant Recipients (SRTR) database to determine the effects of BMI-matching on patient survival and graft function after lung transplant. Methods We evaluated a national cohort of patients from the SRTR database who underwent single or double lung Tx between 2006-17. Donor and recipient BMI were categorized using the World Health Organization classification: underweight (BMI 14.0-18.49); normal, (18.5-24.99); overweight (25.00-29.99); obese (≥30.00). In addition, donor and recipient BMI categories were used to stratify patients based on donor-recipient BMI matching: same category; donor BMI in a higher category than the recipient; recipient BMI in a higher category than the donor. The association between donor BMI, recipient BMI, as well as donor-recipient BMI similarity and overall risk of death or risk of graft loss were separately evaluated using multivariable Cox regression. Results Among 20,404 patients, median donor BMI was 25.1 [IQR 22.3-28.7] and median recipient BMI was 25.4 [IQR 21.6-28.7]. For donors, 3.5% were underweight, 44.6% were normal weight, 32.7% were overweight, and 19.2% were obese. For recipients, these were 8.5%, 38.8%, 37.2%, and 15.6%, respectively. Donor BMI was not associated with overall risk of death or risk of graft loss. By comparison, relative to normal weight recipients, underweight recipients had a 42% higher risk of death (Hazard Ratio 1.42 [95% CI 1.02-2.00]). Relative to patients receiving organs from a donor in a similar BMI category, donor-recipient differences in BMI category were neither associated with risk of death nor graft loss. Conclusion Consistent with prior reports, recipient BMI was an important factor in lung transplant outcomes, but donor-recipient BMI matching, or lack of, did not have an effect. Neither donor BMI nor donor-recipient size matching based on BMI are associated with improved Tx outcomes.

Frailty Measurements are Poor Predictor of Lung Transplantation Outcomes

Purpose Lung transplantation is a lifesaving therapy in patients with advanced lung disease. However, frail lung transplant candidates are more likely to be delisted or die on the waitlist. It is not clear if currently used frailty tools can predict outcomes after lung transplantation. We investigated the correlation between frailty measurements and outcomes after lung transplantation. Methods We prospectively assessed frailty in 25 consecutive lung transplant candidates using the Fried Frailty Phenotype (FFP), Short physical performance battery (SPPB) tools, and the Montreal Cognitive Assessment (MoCA). We evaluated the correlation between frailty measurement and lung transplant outcomes such as death, length of stay in the hospital, number of rejection episodes, and pulmonary function tests (PFT) one year after lung transplantation. The data was analyzed using R 4.0.2 (The R Foundation for Statistical Computing http://www.R-project.org) Packages PerformanceAnalytics and ggplot2 were used in addition to core R. Results We evaluated 25 lung transplant patients with an average age of 56. Both “Frail” and “Pre-frail” frailty phenotypes had 11 (44%) patients. The remaining 3/25 (12%) had a “Robust” phenotype. There was no clear relationship between frailty score and mortality (p=0.23), length of stay (p=0.5), number of rejections episode (p=0.83), and PFT after one year (FVC p=0.71 and FEV1 p=0.78). Age has a strong trend for association with frailty however, it did not reach statistical significance (p=0.16). Among used frailty tools, MOCA had the strongest association with mortality after one year (p=0.17). Conclusion Frailty score, as assigned by three phenotypes pre-frail, frail, and robust, had no significant relationship with outcomes after lung transplantation. Interestingly amongst used frailty instruments, MOCA has the strongest correlation with mortality one year after lung transplantation. Larger studies are needed to understand better if frailty measurements can predict outcomes after lung transplantation.

Histologic Phenotypes and Outcomes in Single vs Double Lung Transplantation among Recipients with Interstitial Lung Disease

<h3>Purpose</h3> The role of single vs double lung transplantation for ILD remains controversial due to heterogeneity within this population. This study elucidates the role of explant histology on outcomes among patients undergoing a single vs double lung transplant. <h3>Methods</h3> A total of 412 patients with ILD transplanted from 2001-2019 at our institution were retrospectively reviewed. Patients were stratified by those who underwent a single (n=239, 58%) or double (n=173, 42%) lung transplant. Explant pathology reports were analyzed to understand the effect of histologic phenotypes and post-transplant outcomes. Primary outcomes of interest included overall and CLAD free survival. Treatment effects were obtained using a multivariable Cox-proportional hazards function. <h3>Results</h3> Of the total population, 41.7% had UIP, 26.5% NSIP, 5.8% mixed NSIP+UIP, 14.8% hypersensitivity pneumonitis (HP), and 11.2% sarcoid on explant pathology. Overall survival was similar between histologic phenotypes. HP and NSIP had earlier development of CLAD compared to sarcoidosis and UIP. A single lung transplant was an independent predictor of mortality among recipients with HP at explant pathology on multivariable analysis. Single lung transplant was also an independent predictor for CLAD among patients with NSIP and HP. The rest of the histologic phenotypes UIP, mixed NSIP+UIP ad sarcoid failed to show a significant difference in any of the outcomes by the use of single vs double lung transplant. <h3>Conclusion</h3> Patients with ILD have distinct pathologic characteristics and related post lung transplant outcomes. Recipients with UIP, mixed NSIP+UIP and sarcoid treated with a single lung transplant had no adverse overall and CLAD-free survival. Recipients with conditions at risk for earlier CLAD, such as HP and NSIP, may benefit from double lung transplantation. Lung biopsies prior to transplantation may aid in donor lung allocation among patients with ILD and optimize organ utilization.

Development in Lung Transplantation, Organ Shortage, Bronchiolitis Obliterans and Overall Survival in the USA, 2011-2018

Purpose Lung transplantation (LTx) outcome is poor in comparison to other solid organs. Our aim was to review the development in LTx-related procedures and organ availability, survival and leading chronic complications and associated cost in the United States. The time period considered is 2011 to 2018 for LTx. Methods The following parameters from OPTN/SRTR Annual Data Reports for Lung were screened on an annual basis: number of lung transplants, patients on waiting-list at year-end, evolution of 5-year bronchiolitis obliterans syndrome (BOS), and the 5-year overall survival rate. Five-year rates were respectively calculated for a 3-year cluster period. Cost estimates were sourced from the Milliman Research Report 2020. Estimates were based on U.S. average utilization, billed charges, and results per member per month cost. It comprised a 30-day pre- to 180-day post-transplant period, including pre-transplant, organ procurement, hospital transplant, physician during transplant admission, post-transplant discharge, outpatient immunosuppression, and other drugs. Results LTx has registered a growth from 1758 lung transplants in 2011 to 2562 in 2018. This represents an increase of 46%. In the same period, the year-end waiting list has decreased from 1661 to 1419, a decrease of 15%. Although the number of transplant recipients could be increased substantially, the waiting list did not decrease to the same extent. The per patient cost of lung transplantation in the US is estimated at USD $929,600 for single lung and at $1,295,900 for double lung in 2020, an increase of 7.9% and 8.8%, respectively versus 2017 data. In 2018, 5-year overall survival was close to 60% versus 48% in 2011. One-year post-LTx, BOS is the leading cause of death. This remains unchanged during the reporting period: in 2018, 41.8% of lung recipients were reported to suffer from BOS versus 42.4% in 2011. Conclusion The number of lung transplantations has increased since 2011, and overall patient survival improved. The evolution of the waiting list still remains a major issue. Another concern is that the same rate of patients has developed BOS within the time period investigated. Increased investigation and scientific focus are therefore needed to better understand and improve therapeutics outcomes for chronic graft failure and its primary cause, BOS.

Composition of Ex Vivo Lung Perfusion Solutions and Kinetics Define Differential Cytokine and Chemokine Secretion in a Porcine Cardiac Arrest Model of Lung Preservation

Purpose Ex vivo lung perfusion is an innovative technique to evaluate marginal lung organs especially after DCD. Normothermic continuous perfusion should reduce ischemic damage and improve the outcome of lung transplantation. However, the optimal protocol for EVLP has not been defined so far. The aim of our study was to compare cytokine/chemokine concentrations in perfusion solutions using different kinetics and solution compounds of EVLP in a porcine cardiac arrest model and to correlate the inflammatory parameters to oxygenation capacity values (∆pO2). Methods Following cardiac arrest and 1h of warm ischemia, lungs were harvested and flushed. Groups were processed as immediate (I-EVLP) 1h cold static preservation (CSP) and delayed (D-EVLP; 9h CSP). D-EVLP lungs were perfused with different solutions: Steen vs. modified Custodiol-N containing dextran (CD) or dextran/albumin (CDA). Cytokine/chemokine levels were analyzed at baseline (0h), after 1h, 4h using multiplex protein arrays. Results Concentrations of TNF-α, IL-6, CXCL8, IFN-γ, IL-1α and IL-1β increased significantly (p Conclusion In a non-heart beating porcine cardiac arrest model with relevant IRI, lungs were perfused with normothermic EVLP. Longer CSP prior to EVLP did not result in enhanced cytokine secretion, but the first hours of reperfusion seem crucial for tissue damage. CD-solution dampens the cytokine/chemokine secretion probably by iron chelators and, possibly, protecting effects of dextran. Addition of albumin had no further effect on inflammation. Cytokine/chemokine concentrations correlated negatively with the oxygenation capacity, an important parameter for organ acceptance. These finding may help to optimize the ex vivo preservation procedure and possibly, more organs could reach the clinically relevant threshold for transplantation, thus, the pool of marginal donor lungs could be enlarged.

A Single Center Analysis of Increased Risk Donors Utilized in Lung Transplantation

<h3>Purpose</h3> In 2013, the US Public Health Service (PHS) established new guidelines for high risk donor organs and renamed the category "increased risk" (IR). We compared survival outcomes of lung transplant (LTx) patients that received either IR or non-IR donor lungs to determine if IR donor lungs are an underutilized resource. <h3>Methods</h3> This study retrospectively analyzed and compared survival and utilization rates of IR and non-IR donor lung recipients at a single center from Feb-2012 to Mar-2020. LTx recipients were stratified by PHS IR status of the donor lung(s) received. Survival of IR and non-IR donor lung recipients was assessed using Kaplan-Meier (KM) survival analysis and compared by log-rank test. Cox proportional hazards modeling was used to control for variables significantly associated with IR/non-IR status, including recipient race, average warm ischemic time, transplant type, and donor age. <h3>Results</h3> Of 742 LTx patients at the center (Feb-2012 to Mar-2020), there were 193 (26%) recipients of IR organs. In 2012 and 2013, 7% and 0% respectively of the lungs transplanted at the institution were IR labeled. After the PHS guidelines were nationally implemented in Feb-2014, the proportion of IR labeled lung transplants rose to 8% (2014), 26% (2015), 40% (2016), 53% (2017), 38% (2018), and 37% (2019). Median survival times were 1.8 years for IR and 2.0 years for non-IR LTx recipients. KM survival analysis and log-rank test comparison showed no statistically significant difference in survival between IR and non-IR donor lung recipients (p = 0.606) over the 8-year period. Cox regression controlling for significant variables suggested none of the covariates significantly affected survival. <h3>Conclusion</h3> While the 2013 guidelines caused a sharp increase in lungs labeled IR, our survival analysis suggests the criteria may be misleading and of little help when assessing risks and estimating probability of survival. IR designations risk underutilization of viable lungs, a serious concern considering the waitlist demand for donors.

Clinical Characteristics of Patients with Chronic Lung Allograft Dysfunction Listed for Lung Re-Transplant

<h3>Purpose</h3> Chronic lung allograft dysfunction(CLAD) is the barrier to improve long term outcome of lung transplantation. This study aims to examine prevalence and characteristics of patients with CLAD who were listed for lung re-transplant. <h3>Methods</h3> This is a retrospective observational study. Adult patients (>18 YO) listed for lung re-transplant due to bronchiolitis obliterans syndrome(BOS) or restrictive allograft syndrome(RAS) 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 2 groups. <h3>Results</h3> 1546 adult CLAD patients were included. 85.51% of these patients have BOS phenotype. Mean age was 42.79. There was no significant difference in age, mPAP, history of smoking, previous malignancy, or pan-resistant infection between BOS and RAS groups. Oxygen requirement at listing time was significantly higher in RAS group (5.64±6.33 vs 2.93±3.31, p < 0.01). Proportion of patients who were on ECMO at listing time is significantly higher in RAS group (4.02% vs 0.91%, p<0.01). LAS of RAS group was significantly higher(52.07±18.71 vs 43.60±17.71, p < 0.01). 67.86% of RAS group received re-transplant compared to 59.15% of BOS group (p = 0.014). <h3>Conclusion</h3> RAS patients have worse clinical condition at listing time compared to BOS patients. They required higher FO2 supplement and have higher LAS. More proportion of patients with RAS received re-transplant compared to patients with BOS which reflects the above findings.

Rising PGD Incidence Parallels Increased Recipient Disease Severity

<h3>Purpose</h3> Priority on waitlist urgency over post-transplant survival has decreased waitlist mortality with no appreciable change in short to mid-term survival. We sought to define the effects of increased pressure to transplant sicker candidates on PGD incidence and mortality as a leading indicator for long-term effects. <h3>Methods</h3> We used the multi-center prospective Lung Transplant Outcomes Group cohort study, designed to identify risk factors for PGD and mortality. Patients were enrolled from August 2011 to June 2018 at 10 centers. PGD was graded based on the 2016 PGD consensus ISHLT guidelines. Specifically, PGD was defined as grade 3 PGD (PaO2 /FiO2 ratio <200) at 48 or 72 hours after allograft reperfusion. Patients on ECMO post-transplant were graded as PGD only if there was evidence of parenchymal infiltrates on chest radiograph. <h3>Results</h3> 1,528 subjects were enrolled with a 25.6% incidence of PGD overall. PGD incidence increased from 14.3% to 38.2% over the course of the study. From 2012 to 2018, the median LAS increased from 38.7 to 42.9 and the use of ECMO salvage increased from 5.7% to 20.9% (Fig.1a). PGD was associated with mortality overall (p=0.0001, Fig.1b). Bridging strategies were not associated with mortality (p=0.66); however, salvage ECMO for PGD was significantly associated with mortality (HR 2.1 [1.6; 2.8]; p<0.0001). Restricted mean survival time comparison at 1-year demonstrated 101 days lost in VA salvaged recipients when compared to those without PGD and 29 days for VV. Effects on mortality increased over time (Fig1c). <h3>Conclusion</h3> Severity of illness continues to rise in modern surgical practice paralleled by significant increases in PGD incidence. Bridging strategies have increased but appear safe. PGD is highly associated with mortality and is increasingly treated with salvage ECMO. Though early mortality associated with salvage strategies is low, 1-year survival is significantly reduced. Given the increase in use of salvage ECMO, further work is needed on evaluating 2016 PGD definition.

Predicting PGD after Lung Transplantation

<h3>Purpose</h3> Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies highlight the role of donor smoking in poor post-transplant outcomes. We therefore aimed to identify clinical risk factors for PGD after lung transplantation, more accurately assess the impact of donor smoking, and develop an accurate, generalizable PGD prediction model. <h3>Methods</h3> We performed a 10-center prospective cohort study of patients in the Lung Transplant Outcomes Group from 2012-2018. PGD was defined as grade 3 PGD at 48 or 72 hours after lung reperfusion. We defined donor smoking history by clinical documentation, UNOS-reported donor smoking, or donor cotinine >9 mg/ml from urine collected at organ procurement. Building on our prior PGD prediction models, multivariable logistic regression was used to identify PGD risk factors and develop regularized predictive models with a simple user interface (R shiny). <h3>Results</h3> Of 1180 patients, 26% developed PGD and 633 (53%) received an organ from a previously smoking donor. The PGD predictive model included novel predictors of center and donor distance plus recipient age, lung allocation score (LAS), body mass index, pulmonary artery pressure, sex, and indication for transplant; donor age, sex, mechanism of death, and donor distance; and interaction terms for LAS and donor distance. The interface allows for real-time assessment of PGD risk for any donor/recipient combination. The predictive model offers decision making benefit in the PGD risk range of 0.15-0.5. Donor smoking was associated with increased risk of PGD but not patient mortality (Figure 1). <h3>Conclusion</h3> We developed a clinically applicable PGD predictive algorithm based on modern lung transplant practices to aid in transplant decision making, post-transplant care, and to facilitate development of enriched PGD treatment trials. Donor smoking is a risk factor for PGD development but is not associated with increased mortality, potentially because of a lower risk phenotype of PGD occurring in smoking donor recipients.

Lung Transplant Outcomes Based on Immunosuppressive Regimen at Discharge: Data from the US Scientific Registry of Transplant Recipients (SRTR)

<h3>Purpose</h3> There is currently no FDA approved immunosuppressive regimen for lung transplant (Tx) recipients; however, patients routinely receive a CNI-based regimen. The SRTR database was analyzed to provide real-world evidence of the efficacy and safety of tacrolimus-based immunosuppressive regimens post lung Tx. <h3>Methods</h3> Adult and pediatric recipients of a primary deceased donor lung Tx between January 1, 1999 and December 31, 2017 were followed for 3 years post-transplant based on immunosuppressive regimen at discharge: immediate-release tacrolimus (TAC IR)+mycophenolate mofetil (MMF), TAC IR+azathioprine (AZA), cyclosporine (CYA)+MMF, or CYA+AZA. The primary outcome was the composite endpoint of graft failure or death (all cause) at 1 year post-transplant. Cox proportional hazard models were used to test for baseline characteristics associated with a greater risk of graft failure or death in adults. <h3>Results</h3> Data were available for 26,080 lung Tx recipients (25,355 adults and 725 pediatric patients). The most common discharge immunosuppressive regimen was TAC IR+MMF in both groups. Post-transplant outcomes are shown in Tables 1 (adults) and 2 (pediatrics). Factors associated with a greater risk of graft failure or death in adults on TAC IR+MMF included: recipient age ≥65 years, single lung transplant, hospital stay >24 days, BMI <18.5 kg/m², serum creatinine ≥1.0 mg/dL, donor age ≥55 years, and donor race (Black). The risk of graft failure or death was significantly greater in adults receiving CYA+MMF or CYA+AZA compared to TAC IR+MMF. <h3>Conclusion</h3> Discharge immunosuppressive regimens in lung Tx recipients changed over the period from 1999-2017, with a substantial increase in the use of TAC IR+MMF. Adult and pediatric lung Tx recipients receiving TAC IR+MMF had a cumulative incidence of graft failure or death at 1 year post transplant less than 9% (graft survival >91%) and had the lowest rejection rates without increased risks of infection or malignancy.

Incidence of Infection during the First Year after Lung Transplant in a Colombian Center between 2007 and 2019

Purpose Infections are of great concern in lung transplant recipients due to multiple factors. Few studies have evaluated its prevalence and etiology in these patients. Our objective was to characterize infections in the first year after transplant, emphasizing on healthcare-associated infections (HAI), in a program in Colombia Methods Descriptive, retrospective and longitudinal study. We included lung transplant recipients between 2007-2019 in a Colombian institution. Variables were taken from patient's medical records. Analysis was made in SPSS v21®. Results 85 patients were included. 5 (5.9%) patients were excluded due to perioperative demise and 4 (4.7%) due to incomplete medical record. 52.6% (n=40) were male, median age at transplant was 51 (IQR 38-59), and COPD (40.8%) was the main transplant reason. 96% and 92% of the patients received prophylaxis against CMV and fungi, respectively; and 91% received post-transplant trimethoprim sulfamethoxazole. 185 infections were reported in 65 (85.5%) patients in the first year, and pneumonia was the leading infection, causing 40.5% of cases (n=75). Infections distribution was 35.7%, 42.2% and 22.2% in months 1, 2 to 6 and 7 to 12, respectively; and etiology varied between bacterial (35.7%), fungal (15.1%), viral (9.7%), and parasitic (1.6%). Most isolated microorganisms were P. aeruginosa (8.7%), citomegalovirus (6.5%), Candida spp. (6.5%), K. pneumoniae (5.9%) and Aspergillus spp. (5.4%). 15 infections (8.1%) were polymicrobial, and there was no microbial isolation in 55 cases (29.7%). 60 HAI were reported in 30 patients in the first year, 16.6% were polymicrobial and no microorganism was found in 10%. 70% of HAI (n=42) took place in ICU, and 23 were attributable to invasive devices. 13 (21.6%) HAI happened in general ward inpatients, where pneumonia was the most frequent infection (21.6%). 5 HAI were due to surgical site infection (8.6%). Between 2015 and 2019 HAI decreased 50% compared to 2009-2014. 25/76 patients died (32.8%), and infection-attributable mortality was 68%. Conclusion Infections impact lung transplant outcomes significantly in our setting. Institutional protocols must be adjusted according to local microbiology and infection prevalence, emphasizing on healthcare-associated infections.

Panel Reactive Antibody and Donor-Recipient Sex Differences Do Not Affect Long-Term Lung Transplant Outcomes

PurposePatients with elevated panel reactive antibody (PRA) experience delayed transplant and higher waitlist mortality than minimally sensitized patients. If transplanted, the importance of elevated PRA observed with donor-recipient sex differences on long-term outcomes remain unknown.MethodsThe United Network for Organ Sharing database was reviewed for all adult patients who underwent isolated lung transplantation between 2005 and 2015. All patients without known BOS status on follow up were excluded. The date of first BOS diagnosis, if present, was used for analysis. All remaining patients were censored at time of last follow up in absence of BOS, graft dysfunction, or death. Baseline and post-transplant outcomes were reviewed using descriptive and Kaplan-Meier analyses.ResultsBetween 2005 and 2015, 15596 lung transplant recipients with known BOS status were included in analysis and divided into donor-recipient subgroups: male to male (M-M; n=6846, 44%), male to female (M-F: n=2581, 16%), female to male (F-M: n=2347, 15%), and female to female (F-F: n=3822, 25%) - Table 1. The time between listing and transplant was highest among M-F, 263 (95% CI [246-280]), and F-F, 275 days (95% CI [261-289]), subgroups. Female recipients also had higher pre-transplant PRA%, 13.7 (F-F) and 15.0 (M-F), compared to males (p < 0.001 between groups). Overall, there were no differences in freedom from BOS (p=0.282) or graft dysfunction (p=0.602) when adjusted for single or double transplant and donor-recipient subgroup. Composite survival differed between groups (p < 0.001 by log rank test); however, this was unaffected by subgroup PRA% when analyzed continuously or stratified by quartiles.ConclusionDonor-recipient sex differences are associated with elevated pre-transplant PRA levels in female recipients; however, pre-transplant PRA had no observed impact on graft and survival outcomes in all disease groups. The clinical significance of PRA after transplant selection, if any, remains unclear. Patients with elevated panel reactive antibody (PRA) experience delayed transplant and higher waitlist mortality than minimally sensitized patients. If transplanted, the importance of elevated PRA observed with donor-recipient sex differences on long-term outcomes remain unknown. The United Network for Organ Sharing database was reviewed for all adult patients who underwent isolated lung transplantation between 2005 and 2015. All patients without known BOS status on follow up were excluded. The date of first BOS diagnosis, if present, was used for analysis. All remaining patients were censored at time of last follow up in absence of BOS, graft dysfunction, or death. Baseline and post-transplant outcomes were reviewed using descriptive and Kaplan-Meier analyses. Between 2005 and 2015, 15596 lung transplant recipients with known BOS status were included in analysis and divided into donor-recipient subgroups: male to male (M-M; n=6846, 44%), male to female (M-F: n=2581, 16%), female to male (F-M: n=2347, 15%), and female to female (F-F: n=3822, 25%) - Table 1. The time between listing and transplant was highest among M-F, 263 (95% CI [246-280]), and F-F, 275 days (95% CI [261-289]), subgroups. Female recipients also had higher pre-transplant PRA%, 13.7 (F-F) and 15.0 (M-F), compared to males (p < 0.001 between groups). Overall, there were no differences in freedom from BOS (p=0.282) or graft dysfunction (p=0.602) when adjusted for single or double transplant and donor-recipient subgroup. Composite survival differed between groups (p < 0.001 by log rank test); however, this was unaffected by subgroup PRA% when analyzed continuously or stratified by quartiles. Donor-recipient sex differences are associated with elevated pre-transplant PRA levels in female recipients; however, pre-transplant PRA had no observed impact on graft and survival outcomes in all disease groups. The clinical significance of PRA after transplant selection, if any, remains unclear.

Cytomegalovirus in Lung Transplant

Lung transplantation is a therapeutic option for patients with advanced lung diseases. Lung transplant outcomes have improved over time with improvements in the management of these complex patients. Cytomegalovirus is a common opportunistic organism affecting all solid organ transplant recipients. Characteristics unique to lung transplantation can make this virus difficult to manage, with myriad complications including graft failure and death. Ongoing research into and understanding of cytomegalovirus has opened exciting new avenues of management. We discuss the various manifestations of CMV related pathologies in the lung transplant recipient. We discuss current mainstays of risk stratification, diagnosis, and treatment, as well as present new and evolving concepts. Current medications are highly effective at preventing and treating CMV manifestations, but may be poorly tolerated. A new generation of therapies carry the promise of efficacy, with a greater safety profile and improved tolerance of adverse effects. We discuss host-virus immune interactions, specifically how these can be utilized in clinical practice to individualize the cytomegalovirus related care of lung transplant recipients. Finally, we turn our attention to the near horizon as we continue to evolve the care of this unique population.

Post-transplant outcomes of standard and extended criteria donation after circulatory death donor lungs categorized by donation after brain death lung criteria.

Most transplant centres use donation after brain death (DBD) criteria to assess the quality of controlled donation after circulatory death (cDCD) lungs. However, research on the relationship between DBD extended criteria and cDCD lung transplantation outcomes is limited. We investigated the outcomes of using DBD extended criteria donor organs in cDCD lung transplantation, compared to the standard criteria cDCD lung transplantation. A retrospective chart review of consecutive cDCD lung referrals to Hospital Universitario Puerta de Hierro-Majadahonda from June 2013 to December 2019 was undertaken. Donors were divided into standard and extended criteria groups. Early outcomes after lung transplant were compared between these groups using the Kaplan-Meier method and log-rank test. Thirty out of 91 cDCD donor lung offers were accepted for transplantation, of which 11 were from standard criteria donors and 19 were extended criteria donors. The baseline characteristics of the 2 recipient groups were similar. There were no differences in the rates of grade 3 primary graft dysfunction at 72 h after lung transplantation (21% vs 18%), duration of mechanical ventilation (48 h vs 36 h), total intensive care unit stay (10 days vs 7 days) and 1-year survival (89% vs 90%). Carefully selecting cDCD lungs from outside the standard acceptability criteria may expand the existing donor pool with no detrimental effects on lung transplantation outcomes.

Lung Transplantation for Pleuroparenchymal Fibroelastosis.

Pleuroparenchymal fibroelastosis (PPFE), a new disease entity associated with interstitial pneumonia, is characterized by fibrosis and elastosis involving the pleura and subpleural lung parenchyma, predominantly in the upper lobe. As the awareness of this disease entity has increased, many studies have revealed the prevalence and incidence, clinical and pathological characteristics, and disease course of PPFE. Patients with PPFE reportedly have several unique clinical characteristics—including an extremely low body mass index with a slender body and chest wall deformity, known as “flat chest”. As this disease progresses, shrinking of the lungs often causes life-threatening complications, such as pneumothorax, and associated air leak syndrome. Lung transplantation is considered the only effective treatment for patients with advanced PPFE; however, little is known about the influences of the characteristics of PPFE on the outcome of lung transplantation. This review focuses on the unique clinicopathologic characteristics of PPFE and associated outcomes of lung transplantation for these patients.

The prognostic nutritional index is correlated negatively with the lung allocation score and predicts survival after both cadaveric and living-donor lobar lung transplantation.

The prognostic nutritional index (PNI), calculated based on the serum albumin levels and the total lymphocyte count, has been identified as a predictor of clinical outcomes in various fields of surgery. In this study, we investigated the relationship between the PNI and the lung allocation score (LAS) as well as the impact of the PNI on the outcomes of both cadaveric lung transplantation (CLT) and living-donor lobar lung transplantation (LDLLT). We reviewed retrospective data for 127 recipients of lung transplantation (LT), including 71 recipients of CLT and 56 recipients of LDLLT. The PNI was correlated significantly and negatively with the LAS (r = -0.40, P = 0.0000037). Multivariate analysis revealed that age (P = 0.00093), BMI (P = 0.00087), and PNI (P = 0.0046) were independent prognostic factors of a worse outcome after LT. In a subgroup analysis, survival after both CLT (P = 0.015) and LDLLT (P = 0.041) was significantly worse in the low PNI group than in the high PNI group. Preoperative nutritional evaluations using the PNI can assist with the assessment of disease severity in LT recipients and may predict survival after both CLT and LDLLT.