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Because of their impact on fibroblast proliferation, treatment with pirfenidone or nintedanib in close proximity to lung transplant raises the theoretical risk of airway anastomotic dehiscence. Small, retrospective single center studies, however, have suggested that the use of antifibrotics is not associated with dehiscence and may be protective from primary graft dysfunction (PGD). We performed a meta-analysis assessing the association between antifibrotics and post-transplant airway dehiscence, PGD, and 30-day mortality. Using a pre-specified search strategy (PROSPERO registration CRD42021240952), we identified all studies between 1/1/2011 and 9/1/2022 assessing the relationship between antifibrotics and at least one of the outcomes. Because several studies had no events, the primary effect measure was risk difference (RD) of antifibrotic medication use on dehiscence, PGD3 at 72 hours, and 30-day mortality. We combined individual statistics using a random effects model, weighted by sample size. We assessed for heterogeneity using a Q statistic and an I2. Twelve studies met inclusion criteria. In aggregate, there were 1345 recipients, 643 of whom were receiving antifibrotics and 702 of whom were not. Patients on antifibrotics were not more likely to have airway dehiscence (RD=0.01, 95% CI=-0.01-0.03, p=0.25) (Figure 1). There was no difference in PGD3 at 72 hours between groups (RD= -0.01, 95% CI=-0.11-0.08, p=0.78), although there was significant heterogeneity between studies (I2 =63.2, Q =16.3, p=0.01). 30-day mortality was not higher in patients on antifibrotics (RD=0.00, 95% CI=-0.02-0.02, p=0.76). The use of antifibrotic medications in close proximity to lung transplant is not associated with increased airway dehiscence, decreased PGD3 at 72 hours, or increased 30-day mortality. [ABSTRACT FROM AUTHOR]

Existing measures of frailty developed in community dwelling older adults may misclassify frailty in lung transplant candidates. We aimed to develop a novel frailty index for lung transplantation with improved performance characteristics compared to existing measures. In a three-center cohort study of lung transplant candidates, we measured the Short Physical Performance Battery (SPPB) and Fried Frailty Phenotype (FFP) measures; body composition by bioelectrical impedance; and serum biomarkers associated with frailty (hemoglobin, albumin, and C-reactive protein). We evaluated individual variable domains to identify those associated with the criterion of candidate delisting for becoming too ill or death. Next, we built composite multidimensional models by testing the addition of domain variables in clusters: (1) performance measures (gait speed, balance, grip strength, low physical activity level); (2) body composition (low skeletal muscle, high % body fat), and (3) biomarkers. Domain cut-points were determined using receiver operating curve analyses. Three threshold selection methods for variable retention were evaluated; where methods differed, we prioritized specificity for delisting/death. Logistic regression analyses then estimated the odds of death/delisting across candidate Lung Transplant Frailty Index models. In 533 participants, we identified two candidate Lung Transplant Frailty Index (LT-FI) measures that maximized specificity, area under the curve, and had stronger associations with delisting and death compared to either the SPPB or FFP (Table). Candidate LT-FI measures that include measures of physical performance, body composition, and serum biomarkers have improved discrimination for candidate delisting or death compared to the SPPB and FFP. Validating these candidate LT-FI measures' capacity to identify people at risk for peri- and post-operative complications and at other centers will help to define the optimal measure of frailty in lung transplantation. [ABSTRACT FROM AUTHOR]

There is significant variability in induction immunosuppression for sensitized (PRA≥1%) and highly sensitized (PRA>60%) lung transplant recipients. We compared retransplant-free and bronchiolitis obliterans (BOS)-free survival among sensitized recipients based on cytolytic versus interleukin-2 receptor antagonist (IL2-RA) versus corticosteroid only induction. This was a retrospective study sensitized adult lung transplant recipients in SRTR from 5/5/2005-5/31/2019. Subjects were categorized according to cytolytic (ATG, OKT3, alemtuzumab), IL2-RA (daclizumab, basiliximab), or corticosteroid-only induction. Cox proportional-hazard models were used to compare retransplant-free survival and BOS-free survival according to induction, adjusting for clinical covariates. Of the 5696 included recipients, 1281 (22.5%) received cytolytic, 3057 (53.7%) IL2-RA, and 908 (15.9%) corticosteroid-only induction. Compared to IL2-RA, cytolytic induction was associated with improved adjusted retransplant-free survival (HR=0.80, 95% CI=0.05-1.00, p=0.052) and improved adjusted BOS-free survival (HR=0.79, 95% CI=0.88-0.97, p=0.009) (Figure 1). Cytolytic induction was also associated with decreased need for plasmapheresis after index hospitalization (OR=0.47, p=0.04). Among highly sensitized recipients (n=712) cytolytic induction (n=161) was not associated with retransplant-free (p=0.51) or BOS-free survival (p=0.73) compared to IL2-RA (n=551). Among all sensitized recipients, the use of corticosteroid-only induction was associated with worse BOS-free survival (HR=1.19, 95% CI=1.08-1.31, p<0.001). The use of cytolytic induction compared to IL2-RA is associated with a small improvement in retransplant-free and BOS-free survival among sensitized lung transplant recipients. Corticosteroid-only induction is associated with worse BOS-free survival. [ABSTRACT FROM AUTHOR]

Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. We previously developed an easy to use PGD predictive model utilizing the Lung Transplant Outcomes Group (LTOG) cohort. We therefore sought to demonstrate the net benefit of the model at an external site as a measure of model generalizability. We tested external validation in a well-phenotyped lung transplant cohort from Washington University in St. Louis (WashU) for a PGD predictive model based on lung allocation score, body mass index, pulmonary arterial pressure, recipient total lung capacity, donor and recipient age and gender, donor mode of death, and donor distance to transplant center. We primarily employed decision curve analysis (DCA) to quantify the net benefit of the predictive model and also assessed model discrimination using the c-statistic and calibration using the Hosmer-Lemeshow (H-L) test. The incidence of PGD at WashU was lower than in the LTOG cohort (7% vs 25%); the validation model accounts for the differences in PGD incidence. The model demonstrated good discrimination (c-statistic=0.67) and calibration (H-L p=0.2, where non-significant p-value is good calibration). DCA describes whether the model performs better than alternatives of classifying everyone (or no one) as high PGD risk as well as the net benefit of the model across a range of decision thresholds. The DCA (Figure 1) shows that the predictive model demonstrates significant net benefit in the PGD incidence range 2-15%, incorporating the PGD incidence seen in the WashU cohort. Our simple to implement PGD predictive model demonstrates excellent net benefit, even at centers with differing PGD incidence than the discovery cohort centers. This model can be used to identify recipients at high and low risk for PGD across a range of transplant centers, allowing treatment teams to be prepared for post-transplant complications and identify patients for potential enrollment in targeted intervention studies based on patient risk. [ABSTRACT FROM AUTHOR]

To evaluate efficacy and safety of the Janus kinase 1 inhibitor ITA in patients (pts) with BOS following double lung transplantation. Phase 1 of the study is presented. INCB39110-214 (NCT03978637) is an open-label, phase 1/2 study evaluating 3 doses of ITA: 300 mg twice daily (BID), 400 mg once daily (QD) and 600 mg QD. Key inclusion criteria were age ≥18 years; double lung transplantation ≥1 year before screening; and a diagnosis of BOS stage 1-3 in the past year or in the past 2 years with either a ≥200-mL decrease in forced expiratory volume 1 (FEV1) in the past 12 months or a ≥50-mL decrease in FEV1 in the last 2 measurements. Co-primary endpoints were safety and frequency of ≥10% absolute increase in FEV1 vs baseline in 2 consecutive assessments. 23 pts were randomized to ITA 300 mg BID (n=7), 400 mg QD (n=7), 600 mg QD (n=8), or 200 mg QD (n=1; enrolled under previous protocol version). Baseline pt demographics/characteristics were similar across doses. Prior treatment for BOS included azithromycin (n=9), alemtuzumab (n=1), antithymocyte globulin (n=3), corticosteroids (n=7), extracorporeal photophoresis (n=1), and montelukast (n=4). Mean FEV1 was 1.61 L at study enrollment across all doses of ITA (n=23). No clear dose-related trends were seen; therefore, results are reported as pooled across all doses. Post enrollment mean FEV1 increased at subsequent time points (Week 4, 1.69 L [n=19]; Week 8, 1.76 L [n=12]; Week 12, 1.86 L [n=13]). Protocol-defined FEV1 response was observed in 5 pts (21.7%). Overall incidence of treatment-emergent adverse events (AEs) was similar across all doses (87.0% of all pts); grade ≥3 AEs occurred in 60.9% of pts. The most common AEs were cytomegalovirus (CMV) reactivation/viremia (30.4%), diarrhea (21.7%), and fatigue (21.7%). Infections of any cause occurred in 14 pts (60.9%), and grade ≥3 infections were observed in 7 pts (30.4%). One pt discontinued treatment owing to a treatment-related AE (pseudomonas pneumonia). Lung function stabilized or improved in a subset of pts who were treated with ITA following a recent diagnosis with progressive BOS stage 1-3. Although AEs were frequent, they were generally not dose limiting; CMV reactivation/viremia and overall infection rates were high but manageable. Further study in pts after lung transplant is warranted. [ABSTRACT FROM AUTHOR]

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. 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. 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). We identified distinct biological phenotypes of frailty. A frailty phenotype characterized by systemic inflammation and sarcopenia appears to be associated with worse clinical outcomes. [ABSTRACT FROM AUTHOR]

Post-transplant frailty is a risk factor for poorer health-related quality of life, rehospitalization, and death. We aimed to evaluate the feasibility, safety, and efficacy of a remote mHealth-supported physical activity pilot intervention to treat frailty in lung transplant recipients following discharge from their index hospitalization. We screened lung transplant recipients for frailty at the time of discharge at the University of Pennsylvania and UC San Francisco. Frailty was defined as a Short Physical Performance Battery (SPPB) score ≤7 and pre-frail as 8-9 (range 0-12, higher scores reflect less frailty). The primary intervention modality was Aidcube, a customizable app-based platform for home-based pulmonary rehabilitation providing personalized exercise prescriptions, for 8 weeks post-discharge. The primary aims included tolerability, feasibility, and acceptability of use of the mHealth platform. Additional outcome measures were changes in SPPB score and in scores of physical activity and disability measured using the DASI and LT-VLA. No adverse events were reported across the 18 study subjects throughout the 152 subject-week study time. Several themes emerged from weekly subject feedback. Subjects reported that the app was easy to use and that usability improved over time. Subjects also found that app use enhanced motivation to engage in post-transplant rehabilitation. Comments also highlighted the complexities of rehabilitation after lung transplant surgery, including level of functional decline, pain, tremor, and fatigue. At the end of the intervention, SPPB scores improved a median of 5 points (IQR 4, 7; p<0.0001) from a baseline of 4 (IQR 0, 7). Physical activity and patient-reported disability also improved. The DASI improved from 4.5 (IQR 0.0, 10.0) to 19.8 (IQR 15.2, 32.3)) (p=0.001) and LT-VLA score improved from 2 (IQR 1.2, 2.53) to 0.59 (IQR 0.14, 1.18) (p=0.001) at closeout. Utilization of a personalized, app-based rehabilitation platform with participant-specific exercise prescriptions was safe and well received by post-lung transplant recipients. Remote rehabilitation was associated with improvements in frailty, physical activity and disability. Future studies should further evaluate mHealth treatment modalities in larger-scale randomized trials of lung transplant recipients. [ABSTRACT FROM AUTHOR]

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. 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). 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). 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. [ABSTRACT FROM AUTHOR]

Changes in US organ allocation have prioritized lung transplant for sicker, older patients, leading to increased frailty and poorer health-related quality of life (QOL) after lung transplantation. Post-transplant frailty has been associated with rehospitalization and mortality. We sought to evaluate whether use of customized, app based rehabilitation early in the transplant recovery process could improve post-transplant frailty. We are performing a pilot multicenter single arm interventional trial of a digital "app"-based platform (Aidcube) to deliver an 8-week home-based pulmonary rehabilitation program. Transplant recipients are eligible for inclusion if they are deemed to be frail at the time of their incident transplant discharge based on Short Physical Performance Battery testing (SPPB<=9). At the time of discharge, patients undergo in-person training in exercise prescriptions and the Aidcube app is loaded on patients' smart phones. The app contains an individualized prescription for home-based rehabilitation based on in-person physical therapist assessments. The prescription is progressed based on response to exercises and subjective feedback. Our primary outcomes are change in SPPB, incidence of adverse events, and subject and provider app impressions. To date, 13 post-transplant patients have been enrolled in the study. The median SPPB at the time of enrollment was 4 (Interquartile range (IQR) 4, 7). Six patients have completed the full follow-up; the median SPPB at closeout was 9 (IQR 9, 10) with a median within person improvement of 4.5 (IQR 1, 5). To date, no adverse events have been reported with home app use. Patients generally reported positive experiences, including statements such as, " The patient is thrilled about walking. The patient attributes this success to the support of the program." and " 'It's great and easy⋯It keeps me motivated to do what I should be doing." Limitations to app usage included incisional pain, admission to acute rehabilitation, and fatigue. Use of an app based pulmonary rehabilitation program targeting frailty after transplant is safe, generally appreciated by patients, and appears associated with improved frailty scores. Further research is needed to assess the impact of the app on rates of patient reported QOL, re-hospitalization and health care costs. [ABSTRACT FROM AUTHOR]

Pre-transplant antiphospholipid antibodies (aPLab), including anticardiolipin (aCL) and anti-B2 glycoprotein-I (aB2GPI), may be associated with thrombotic complications and graft loss in kidney and liver transplant recipients. The objective of this study was to evaluate the prevalence and impact of aPLab on post-operative thrombotic and bleeding complications in lung transplant recipients. This was a single center retrospective cohort study of patients who were evaluated and transplanted between 1/1/2018-11/30/20. All candidates were screened for aPLab. We compared post-operative arterial and venous thrombotic events, treated as a combined endpoint, in recipients with and without aPLab (Fisher's exact test). Among recipients with aPLab, we recorded major bleeding events—defined as requiring blood transfusion or surgical exploration—while on therapeutic or prophylactic dose anticoagulation (AC). There were 100 patients who were evaluated and transplanted during the study period, 19 (19.0%) of whom had aPLab (Figure 1). Among these, 7 (36.8%) had pre-transplant deep vein thrombosis (DVT) or arterial thrombotic events. After transplant, 7 (36.8%) had new symptomatic DVT or arterial thromboses compared to 20 (24.7%) recipients without aPLab (p=0.39). Ten patients with aPLab were fully anticoagulated post-transplant, either because of prior or new thrombotic events. Of these, 6 (60.0%) had major bleeding. One aPLab patient had major bleeding on prophylactic AC. The majority (85.7%) of patients with major bleeding were on renal replacement therapy or had an eGFR <30. The one-year survival rate among recipients with aPLab was 89.5%. The presence of a pre-transplant aPLab was not associated with an increase in new symptomatic DVT or arterial thrombotic events following lung transplant although the study was underpowered for small or moderate effects. The decision to anticoagulate patients with aPLab should account for other risk factors for bleeding including renal insufficiency. [ABSTRACT FROM AUTHOR]

Rates of deep vein thrombosis (DVT) range from 20-60% in patients undergoing extracorporeal membrane oxygenation (ECMO) for acute respiratory distress syndrome. Data on the rates of DVT in lung transplant recipients bridged with ECMO is limited. The objective of this study was to report incidence and outcomes, including use of anticoagulation and subsequent bleeding rates, of DVT in ECMO-bridged transplant recipients. This was a single center retrospective cohort study of all adult ECMO-bridged lung transplant recipients from 5/1/15 to 9/30/19. Recipients underwent routine ultrasound screening for upper extremity (UE) and lower extremity (LE) DVT following ECMO decannulation. Of the 45 ECMO-bridged recipients, 3 died before ECMO decannulation and 4 did not have screening ultrasounds, leaving 38 patients in the cohort. The majority (81.5%) were bridged using venovenous ECMO and most (63%) were decannulated immediately following transplant (Table 1). Among remaining recipients, mean time to decannulation was 4 days. Among recipients with adequate studies, the incidence of LE DVT was 26.4% and the incidence of UE DVT was 63.6%. Neither total time on ECMO, cannula size, nor need for femoral vein cannulation was associated with LE or UE DVT. All of the recipients with LE DVT but two, were anticoagulated. Three needed an inferior vena cava filter placed. Of recipients with UE DVT only, 43.75% were anticoagulated. Among all anticoagulated recipients, five (31.25%) had significant bleeding during their initial hospitalization requiring cessation of anticoagulation. DVTs are common in patients bridged to lung transplantation with ECMO, particularly in the upper extremity. Bleeding poses further challenges for systemic anticoagulation in this high risk population. Additional studies are needed to identify risk factors for both LE DVT and for bleeding to help guide decisions for systemic anticoagulation in this population. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygen (ECMO) is increasingly used as a bridge to lung transplantation. Although other mechanical circulatory support devices have been associated with a transfusion-independent increase in calculated panel reactive antibodies (CPRA), it is unknown whether ECMO is a sensitizing exposure. In this single center retrospective cohort study of lung transplant candidates between 5/1/2015-6/30/2021, antibodies against human leukocyte antigens (HLA-Ab) were evaluated at the time of ECMO initiation and weekly thereafter. Multivariate logistic regression was used to evaluate associations between CPRA increase and ECMO exposure adjusting for a history of any packed red blood cell (PRBC) transfusion and female gender. Sixty-two candidates were placed on ECMO as a bridge to transplant. Of these, 39 (62.9%) either had available HLA-Ab screens from pre- and post-ECMO initiation or multiple HLA-Ab screens post-ECMO. Of the 250 non-ECMO exposed recipients, 224 (89.6%) had multiple pre-transplant screens and served as the comparison cohort. Nine (23.1%) ECMO bridged recipients had an increase in CPRA, compared to 16 (7.1%) of non-ECMO exposed recipients (Fisher's exact p=0.005). Among those with increased CPRA, the median increase was 6% in ECMO bridge patients and 9% in non-ECMO exposed patients. After adjusting for covariates, however, ECMO bridge was not an independent risk factor for increased CPRA (OR=1.85, 95% CI 0.58-5.95, p=0.30). A history of PRBC transfusion trended toward an association with increased CPRA (OR=2.93, 95% CI 0.98-8.78, p=0.06). Pre-lung transplant ECMO was not independently associated with an increase in CPRA when adjusting for PRBC transfusion, although the study was underpowered for small or moderate effect sizes. Where clinically appropriate, PRBC transfusions should be limited in these patients. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Primary Graft Dysfunction (PGD) is a risk factor for Chronic Lung Allograft Dysfunction (CLAD). However, this association requires further examination for better risk stratification of PGD patients. Donor-derived cell-free DNA (%ddcfDNA) is a biomarker for lung allograft injury and early post-transplant %ddcfDNA levels may predict long-term outcomes. This study leverages %ddcfDNA to assess the association of PGD and allograft injury, as well as the ability of %ddcfDNA to identify PGD patients who are at greater risk of developing long-term complications. Lung Transplant recipients (n=52) enrolled in two prospective cohort studies were included. Serial post-transplant clinical data and plasma samples were obtained. Endpoints: An adjudication committee reviewed Day 3 chest x-rays and arterial blood gases and used standard ISHLT definitions to categorize patients as PGD or non PGD. Other endpoints, such as CLAD were also defined by ISHLT standards. Measures : Plasma %ddcfDNA on Day 1, Day 3, Day 7 were quantified by shotgun sequencing. Within subject mean values for Day 1-7 were computed. Analysis : %ddcfDNA levels were compared between PGD versus non PGD patients. In the PGD subgroup, %ddcfDNA levels were also compared between PGD patients who subsequently developed CLAD vs PGD patients who did not develop CLAD. Median post-transplant follow-up was 38.3 months. %ddcfDNA levels were higher in PGD than in non PGD patients; Day 1 (27.5% vs 20.0% p =0.043), Day 3 (11.2% vs 6.6 %, p=0.003), mean Day 1-7 (17.83% vs 10.58%, p=0.008). PGD patients who developed CLAD had higher within-subject Day 1-7 mean %ddcfDNA levels than PGD patients who did not develop CLAD (22.6% vs 15.2%, p = 0.0438). PGD patients demonstrated increased early post-transplant allograft injury, as measured by %ddcfDNA, than non PGD patients. In addition, early post-transplant %ddcfDNA levels may serve as a predictor for the development of CLAD in patients who experience PGD. [ABSTRACT FROM AUTHOR]

On November 24, 2017, the DSA was removed as the primary unit of lung transplant allocation in the United States. We sought to examine the effects of center competition on recipient demographics, resource utilization, and outcomes before and after this change. This was a retrospective cohort study of adults in the SRTR database who underwent lung transplant in the year before or after DSA elimination. Pre- and post-DSA groups were compared using standard analytic tests. The Herfindahl Hirschman Index (HHI), a measure of market competition, was calculated, and centers in the lowest and highest HHI tertiles were identified. A difference-in-differences analysis was performed to assess the relative effects of the DSA change at these centers. The cohort included 4771 recipients (Table 1). In the post era recipients were less likely to have Group A diseases (31.0% vs 27.9%, p=0.02), and median waitlist times were shorter (p<0.001). There was no significant difference in pre-transplant ECMO, post-transplant length of stay (LOS), or prolonged ventilation between eras. Ischemic times increased with competition, but there was no increase in single lung transplants or ECMO use at high competition centers (Table 2). There was no difference in complication rates, including prolonged ventilation, post-transplant dialysis or airway dehiscence between low and high competition centers. Eliminating the DSA did not significantly affect pre-transplant resource utilization, LOS, or important complications. Effects were similar at low and high competition centers. [ABSTRACT FROM AUTHOR]

Purpose The primary driver of poor outcomes in the early stages of lung transplantation is primary graft dysfunction (PGD). Patients with cystic fibrosis (CF) have unique physiology and demographics compared to other lung transplant recipients. Therefore, we sought to identify risk factors for PGD in the CF patient population undergoing lung transplantation. Methods We utilized clinical data on lung transplant recipients with CF and their donors from the Lung Transplant Outcomes Group cohort, a multi-center prospective cohort study of PGD pathogenesis. The primary outcome was grade 3 PGD within the first 72 hours after transplantation. Potential covariates were identified in univariate analysis and assessed for collinearity. Independent PGD risk factors were identified using multivariate logistic regression. A sensitivity analysis was performed using grade 3 PGD 48 to 72 hours after transplantation. Results We identified 195 patients with CF who received lung transplants between August 2014 and June 2018 across ten centers. Grade 3 PGD developed in 80 subjects (41%). Risk factors for PGD in CF patients based on the multivariable model were white donor race (odds ratio [OR]: 2.6, 95% confidence interval [CI]: 1.4-5.1), any positive panel reactive antibodies (PRA) (OR: 2.2, 95% CI: 1.0-4.7), recipient female gender (OR: 2.1, 95% CI: 1.1-3.9), intraoperative cardiopulmonary bypass use (OR: 2.2, 95% CI: 1.2-4.2), increasing lung allocation score (LAS) (OR: 1.2 per 10 point increase in LAS, 95% CI: 1.0-1.4), and ECMO (extracorporeal membrane oxygenation) bridge to transplant (OR: 2.7, 95% CI: 1.1-6.7). LAS and ECMO were assessed in separate models due to their collinearity. Mean pulmonary artery pressure at the time of transplant was included as a potential confounder. Similar findings were seen in a more severe phenotype of PGD that developed 48 to 72 hours after transplant. Conclusion The CF population is often considered to be at low risk of PGD, however we observed a relatively high rate of PGD in this study. Any positive PRA, female recipient gender, intraoperative bypass, increasing LAS, and ECMO are PGD risk factors that have been identified non-CF transplant populations. We validated these risk factors in recipients with CF. White donor race is a novel risk factor that has not been previously identified in lung transplant recipients with another primary diagnosis. [ABSTRACT FROM AUTHOR]