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BackgroundWe sought to describe trends in extracorporeal membrane oxygenation (ECMO) use, and define the impact on PGD incidence and early mortality in lung transplantation.MethodsPatients were enrolled from August 2011 to June 2018 at 10 transplant centers in the multi-center Lung Transplant Outcomes Group prospective cohort study. PGD was defined as Grade 3 at 48 or 72 hours, based on the 2016 PGD ISHLT guidelines. Logistic regression and survival models were used to contrast between group effects for event (i.e., PGD and Death) and time-to-event (i.e., death, extubation, discharge) outcomes respectively. Both modeling frameworks accommodate the inclusion of potential confounders.ResultsA total of 1,528 subjects were enrolled with a 25.7% incidence of PGD. Annual PGD incidence (14.3%-38.2%, p=.0002), median LAS (38.0-47.7 p=.009) and the use of ECMO salvage for PGD (5.7%-20.9%, p=.007) increased over the course of the study. PGD was associated with increased 1 year mortality (OR 1.7 [95% C.I. 1.2, 2.3], p=.0001). Bridging strategies were not associated with increased mortality compared to non-bridged patients (p=.66); however, salvage ECMO for PGD was significantly associated with increased mortality (OR 1.9 [1.3, 2.7], p=.0007). Restricted mean survival time comparison at 1-year demonstrated 84.1 days lost in venoarterial salvaged recipients with PGD when compared to those without PGD (ratio 1.3 [1.1, 1.5]) and 27.2 days for venovenous with PGD (ratio 1.1 [1.0, 1.4]).ConclusionsPGD incidence continues to rise in modern transplant practice paralleled by significant increases in recipient severity of illness. Bridging strategies have increased but did not affect PGD incidence or mortality. PGD remains highly associated with mortality and is increasingly treated with salvage ECMO.

Background This study was designed to prospectively evaluate the efficacy of extracorporeal photopheresis (ECP) to attenuate the rate of decline of FEV1 in lung transplant recipients with refractory bronchiolitis obliterans. Due to an observed higher than expected early mortality, a preliminary analysis was performed. Study Design and Methods Subjects from 10 lung transplant centres were assigned to ECP treatment or to observation based on spirometric criteria, with potential crossover for those under observation. The primary endpoint of this study was to assess response to ECP (i.e., greater than a 50% decrease in the rate of FEV1 decline) before and 6 months after initiation of ECP. Mortality was also evaluated 6 and 12 months after enrolment as a secondary endpoint. Results Of 44 enrolled subjects, 31 were assigned to ECP treatment while 13 were initially assigned to observation on a non‐random basis using specific spirometric inclusion criteria (seven of the observation patients subsequently crossed over to receive ECP). Of evaluable patients, 95% of patients initially assigned to treatment responded to ECP with rates of FEV1 decline that were reduced by 93% in evaluable ECP‐treated patients. Mortality rates (percentages) at 6 and 12 months after enrolment was 32% and 41%, respectively. The most common (92%) primary cause of death was respiratory or graft failure. Significantly (p = 0.002) higher rates of FEV1 decline were observed in the non‐survivors (−212 ± 177 ml/month) when compared to the survivors (−95 ± 117 ml/month) 12 months after enrolment. In addition, 18 patients with bronchiolitis obliterans syndrome (BOS) diagnosis within 6 months of enrolment had lost 38% of their baseline lung function at BOS diagnosis and 50% of their lung function at enrolment. Conclusions These analyses suggest that earlier detection and treatment of BOS should be considered to appreciate improved outcomes with ECP.

Background Previous studies have reported similarities in long-term outcomes following lung transplantation for connective tissue disease-associated interstitial lung disease (CTD-ILD) and idiopathic pulmonary fibrosis (IPF). However, it is unknown whether CTD-ILD patients are at increased risk of primary graft dysfunction (PGD), delays in extubation, or longer index hospitalizations following transplant compared to IPF patients. Methods We performed a multicenter retrospective cohort study of CTD-ILD and IPF patients enrolled in the Lung Transplant Outcomes Group registry who underwent lung transplantation between 2012 and 2018. We utilized mixed effects logistic regression and stratified Cox proportional hazards regression to determine whether CTD-ILD was independently associated with increased risk for grade 3 PGD or delays in post-transplant extubation and hospital discharge compared to IPF. Results A total of 32.7% (33/101) of patients with CTD-ILD and 28.9% (145/501) of patients with IPF developed grade 3 PGD 48-72 hours after transplant. There were no significant differences in odds of grade 3 PGD among patients with CTD-ILD compared to those with IPF (adjusted OR 1.12, 95% CI 0.64-1.97, p = 0.69), nor was CTD-ILD independently associated with a longer post-transplant time to extubation (adjusted HR for first extubation 0.87, 95% CI 0.66-1.13, p = 0.30). However, CTD-ILD was independently associated with a longer post-transplant hospital length of stay (median 23 days [IQR 14-35 days] vs17 days [IQR 12-28 days], adjusted HR for hospital discharge 0.68, 95% CI 0.51-0.90, p = 0.008). Conclusion Patients with CTD-ILD experienced significantly longer postoperative hospitalizations compared to IPF patients without an increased risk of grade 3 PGD.

Extracorporeal membrane oxygenation (ECMO) is a life‐saving therapy utilized for patients with severe life‐threatening cardiorespiratory failure. Patients treated with ECMO are among the most severely ill encountered in critical care and are at high‐risk of developing multiple organ dysfunction, including acute kidney injury (AKI) and fluid overload. Continuous renal replacement therapy (CRRT) is increasingly utilized inpatients on ECMO to manage AKI and treat fluid overload. The indications for renal replacement therapy for patients on ECMO are similar to those of other critically ill populations; however, there is wide practice variation in how renal supportive therapies are utilized during ECMO. For patients requiring both CRRT and ECMO, CRRT may be connected directly to the ECMO circuit, or CRRT and ECMO may be performed independently. This review will summarize current knowledge of the epidemiology of AKI, indications and timing of CRRT, delivery of CRRT, and the outcomes of patients requiring CRRT with ECMO.

Purpose Limited data are available on venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe hypoxemic respiratory failure from coronavirus disease 2019 (COVID-19). Methods We examined the clinical features and outcomes of 190 patients treated with ECMO within 14 days of ICU admission, using data from a multicenter cohort study of 5122 critically ill adults with COVID-19 admitted to 68 hospitals across the United States. To estimate the effect of ECMO on mortality, we emulated a target trial of ECMO receipt versus no ECMO receipt within 7 days of ICU admission among mechanically ventilated patients with severe hypoxemia (PaO2/FiO2

Rationale: Lung transplant is an effective treatment option providing survival benefit in patients with cystic fibrosis (CF). Several studies have suggested survival benefit in adults compared with pediatric patients with CF undergoing lung transplant. However, it remains unclear whether this age-related disparity persists in adult subjects with CF.Objectives: We investigated the impact of age at transplant on post-transplant outcomes in adult patients with CF.Methods: The United Network of Organ Sharing Registry was queried for all adult patients with CF who underwent lung transplantation between 1992 and 2016. Pertinent baseline characteristics, demographics, clinical parameters, and outcomes were recorded. The patients were divided into two groups based on age at transplant (18-29 yr old and 30 yr or older). The primary endpoint was survival time. Assessment of post-transplant survival was performed using Kaplan-Meier tests and log-rank tests with multivariable Cox proportional hazards analysis to adjust for confounding variables.Results: A total of 3,881 patients with CF underwent lung transplantation between 1992 and 2016; mean age was 31.0 (± 9.3) years. The 18-29-year-old at transplant cohort consisted of 2,002 subjects and the 30 years or older cohort had 1,879 subjects. Survival analysis demonstrated significantly higher survival in subjects in the 30 years or older cohort (9.47 yr; 95% confidence interval [CI], 8.7-10.2) compared with the 18-29-year-old cohort (5.21 yr; 95% CI, 4.6-5.8). After adjusting for confounders, survival remained higher in recipients aged 30 years or older (hazard ratio, 0.44; 95% CI, 0.2-0.9). Mortality due to allograft failure was significantly lower in patients with CF aged 30 years or older (28% vs. 36.5%; odds ratio [OR], 0.7; 95% CI, 0.6-0.8), whereas the incidence of malignancy was higher in the 30 years or older cohort (8% vs. 2.9%; OR, 3.0; 95% CI, 1.9-4.6).Conclusions: Age at transplant influences lung transplant outcomes in recipients with CF. Subjects with CF aged 30 years or older at transplant have superior survival compared with adult subjects with CF transplanted between the ages 18 and 29 years.

Bronchoalveolar lavage (BAL) is a key clinical and research tool in lung transplantation (LTx). However, BAL collection and processing are not standardized across LTx centers. This International Society for Heart and Lung Transplantation-supported consensus document on BAL standardization aims to clarify definitions and propose common approaches to improve clinical and research practice standards. The following 9 areas are covered: (1) bronchoscopy procedure and BAL collection, (2) sample handling, (3) sample processing for microbiology, (4) cytology, (5) research, (6) microbiome, (7) sample inventory/tracking, (8) donor bronchoscopy, and (9) pediatric considerations. This consensus document aims to harmonize clinical and research practices for BAL collection and processing in LTx. The overarching goal is to enhance standardization and multicenter collaboration within the international LTx community and enable improvement and development of new BAL-based diagnostics. ispartof: JOURNAL OF HEART AND LUNG TRANSPLANTATION vol:39 issue:11 pages:1171-1190 ispartof: location:United States status: published

Objectives Paramyxoviruses contribute to morbidity and mortality after lung transplant and are associated with bronchiolitis obliterans syndrome. Oral ribavirin has been used off-label for treatment of paramyxoviruses in immunosuppressed patients; however, data supporting its use for this purpose are lacking. Materials and methods We conducted a retrospective review to evaluate clinical outcomes of lung transplant recipients infected with paramyxoviruses and received treatment with oral ribavirin at 2 tertiary referral centers. Patients who were diagnosed with paramyxovirus infection by polymerase chain reaction testing between January 2011 and December 2014 and who received oral ribavirin were included. Clinical outcomes included pulmonary function testing, infection severity, and adverse events related to treatment. Results Twenty-six patients were diagnosed with a paramyxovirus and received oral ribavirin. The changes in mean forced expiratory volume 1 second from preinfection to infection onset and from infection onset to postinfection were significant (1.79 ± 0.13 to 1.61 ± 0.12 L and 1.61 ± 0.12L to 1.74 ± 0.12 L; P = .0001). Similar results were seen in subgroup analysis when respiratory syncytial virus and parainfluenza infections were evaluated independently. Conclusions Use of oral ribavirin for treatment of paramyxovirus infections in lung transplant recipients was safe and associated with recovery of lung function.

The mechanisms by which environmental exposures contribute to the pathogenesis of lung fibrosis are unclear. Here, we demonstrate an increase in cadmium (Cd) and carbon black (CB), common components of cigarette smoke (CS) and environmental particulate matter (PM), in lung tissue from subjects with idiopathic pulmonary fibrosis (IPF). Cd concentrations were directly proportional to citrullinated vimentin (Cit-Vim) amounts in lung tissue of subjects with IPF. Cit-Vim amounts were higher in subjects with IPF, especially smokers, which correlated with lung function and were associated with disease manifestations. Cd/CB induced the secretion of Cit-Vim in an Akt1- and peptidylarginine deiminase 2 (PAD2)–dependent manner. Cit-Vim mediated fibroblast invasion in a 3D ex vivo model of human pulmospheres that resulted in higher expression of CD26, collagen, and α-SMA. Cit-Vim activated NF-κB in a TLR4-dependent fashion and induced the production of active TGF-β1, CTGF, and IL-8 along with higher surface expression of TLR4 in lung fibroblasts. To corroborate ex vivo findings, mice treated with Cit-Vim, but not Vim, independently developed a similar pattern of fibrotic tissue remodeling, which was TLR4 dependent. Moreover, wild-type mice, but not PAD2(−/−) and TLR4 mutant (MUT) mice, exposed to Cd/CB generated high amounts of Cit-Vim, in both plasma and bronchoalveolar lavage fluid, and developed lung fibrosis in a stereotypic manner. Together, these studies support a role for Cit-Vim as a damage-associated molecular pattern molecule (DAMP) that is generated by lung macrophages in response to environmental Cd/CB exposure. Furthermore, PAD2 might represent a promising target to attenuate Cd/CB-induced fibrosis.

Background Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. Methods We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period. Results We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%). Conclusion Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients.

Continuous renal replacement therapy (CRRT) is the preferred dialysis modality for solute management, acid-base stability, and volume control in critically ill patients with acute kidney injury (AKI) in the intensive care unit (ICU). CRRT offers multiple advantages over conventional hemodialysis in the critically ill population such as greater hemodynamic stability, better fluid management, greater solute control, lower bleeding risk and a more continuous (physiologic) approach of kidney support. Despite its frequent use, several aspects of CRRT delivery are still not fully standardized or do not have solid evidence-based foundations. In this manuscript, we provide a case-based review and recommendations of common scenarios and interventions encountered during the provision of CRRT to critically ill patients. Specific focus is made on initial prescription, CRRT dosing, and adjustments related to severe hyponatremia management, concomitant extracorporeal membrane oxygenation support, dialysis catheter placement, use of regional citrate anticoagulation and antibiotic dosing. This case-driven simulation is made as the clinical status of the patient evolves and is based on step-wise decisions made during the care of this patient according to specific patient9s needs and the logistics available at the corresponding institution.

Background Recent studies suggest that alterations in lung microbiome are associated with occurrence of chronic lung diseases and transplant rejection. To investigate the host-microbiome interactions, we characterized the airway microbiome and metabolome of the allograft (transplanted lung) and native lung of single lung transplant recipients. Methods BAL was collected from the allograft and native lungs of SLTs and healthy controls. 16S rRNA microbiome analysis was performed on BAL bacterial pellets and supernatant used for metabolome, cytokines and acetylated proline-glycine-proline (Ac-PGP) measurement by liquid chromatography-high-resolution mass spectrometry. Results In our cohort, the allograft airway microbiome was distinct with a significantly higher bacterial burden and relative abundance of genera Acinetobacter & Pseudomonas. Likewise, the expression of the pro-inflammatory cytokine VEGF and the neutrophil chemoattractant matrikine Ac-PGP in the allograft was significantly higher. Airway metabolome distinguished the native lung from the allografts and an increased concentration of sphingosine-like metabolites that negatively correlated with abundance of bacteria from phyla Proteobacteria. Conclusions Allograft lungs have a distinct microbiome signature, a higher bacterial biomass and an increased Ac-PGP compared to the native lungs in SLTs compared to the native lungs in SLTs. Airway metabolome distinguishes the allografts from native lungs and is associated with distinct microbial communities, suggesting a functional relationship between the local microbiome and metabolome.

Background Long-term survival of lung transplant recipients (LTRs) is limited by the occurrence of bronchiolitis obliterans syndrome (BOS). Recent evidence suggests a role for microbiome alterations in the occurrence of BOS, although the precise mechanisms are unclear. In this study we evaluated the relationship between the airway microbiome and distinct subsets of immunoregulatory myeloid-derived suppressor cells (MDSCs) in LTRs. Methods Bronchoalveolar lavage (BAL) and simultaneous oral wash and nasal swab samples were collected from adult LTRs. Microbial genomic DNA was isolated, 16S rRNA genes amplified using V4 primers, and polymerase chain reaction (PCR) products sequenced and analyzed. BAL MDSC subsets were enumerated using flow cytometry. Results The oral microbiome signature differs from that of the nasal, proximal and distal airway microbiomes, whereas the nasal microbiome is closer to the airway microbiome. Proximal and distal airway microbiome signatures of individual subjects are distinct. We identified phenotypic subsets of MDSCs in BAL, with a higher proportion of immunosuppressive MDSCs in the proximal airways, in contrast to a preponderance of pro-inflammatory MDSCs in distal airways. Relative abundance of distinct bacterial phyla in proximal and distal airways correlated with particular airway MDSCs. Expression of CCAAT/enhancer binding protein (C/EBP)-homologous protein (CHOP), an endoplasmic (ER) stress sensor, was increased in immunosuppressive MDSCs when compared with pro-inflammatory MDSCs. Conclusions The nasal microbiome closely resembles the microbiome of the proximal and distal airways in LTRs. The association of distinct microbial communities with airway MDSCs suggests a functional relationship between the local microbiome and MDSC phenotype, which may contribute to the pathogenesis of BOS.

Purpose 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. Methods 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 Results 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 Conclusion 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.

Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted.We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity.Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination.A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination.The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination.

Pulmonary hypertension from pulmonary arterial hypertension or parenchymal lung disease is associated with an increased risk for primary graft dysfunction after lung transplantation.We evaluated the clinical determinants of severe primary graft dysfunction in pulmonary hypertension and developed and validated a prognostic model.We conducted a retrospective cohort study of patients in the multicenter Lung Transplant Outcomes Group with pulmonary hypertension at transplant listing. Severe primary graft dysfunction was defined as PaIn the explanatory model of 826 patients with pulmonary hypertension, donor tobacco smoke exposure, higher recipient body mass index, female sex, listing mean pulmonary artery pressure, right atrial pressure and creatinine at transplant, cardiopulmonary bypass use, transfusion volume, and reperfusion fraction of inspired oxygen were associated with primary graft dysfunction. Donor obesity was associated with a lower risk for primary graft dysfunction. Using a 20% threshold for elevated risk, the prognostic model had good negative predictive value in both derivation and validation cohorts (89.1% [95% confidence interval, 85.3-92.8] and 83.3% [95% confidence interval, 78.5-88.2], respectively), but low positive predictive value.Several recipient, donor, and operative characteristics were associated with severe primary graft dysfunction in patients with pulmonary hypertension, including several risk factors not identified in the overall transplant population. A prognostic model with donor and recipient clinical risk factors alone had low positive predictive value, but high negative predictive value, to rule out high risk for primary graft dysfunction.

Purpose ECMO is increasingly used for bridging and salvage therapies in lung transplantation, with favorable short-term results. Mid- to long-term outcomes of ECMO use for bridging and salvage are incompletely understood, as is effect on PGD risk; therefore, we sought to define the effects of these strategies on mortality and PGD. Methods The Lung Transplant Outcomes Group study is a multi-center prospective cohort study designed to identify risk factors for PGD and mortality. Patients were enrolled from August 2011 to June 2018. The effect of pre-operative (bridging) and post-operative (salvage) ECMO on Grade 3 PGD incidence and long-term survival were assessed using time-to-event analyses adjusted for center. Results 1,537 subjects were enrolled with a 17.0% incidence of PGD on day 3 and an 18.9% mortality overall. PGD was associated with mortality (p=0.0001, Fig. 1a). ECMO bridging and salvage strategies increased over time (Fig. 1b). 138 (9%) subjects had bridging ECMO and 275 (17.9%) had salvage ECMO. PGD was associated with bridging strategies (p=0.001). PGD incidence in bridged patients (50.7%) exceeded non-bridged (42.2%). Bridging was not associated with mortality overall (p=0.70, Fig. 1c); however, if PGD developed after transplant using a bridging strategy, there was a significant increase in mortality (HR 1.8 [1.3; 2.61]; p=0.0007). About 45% of patients bridged with ECMO required salvage after transplant. ECMO use for salvage was highly associated with mortality (HR 2.1 [1.6; 2.8]; p Conclusion Use of the ISHLT Revised definition identifies Grade 3 PGD as highly associated with mortality in the ECMO bridging and salvage era. ECMO use is increasing for both bridging and salvage strategies. ECMO bridging strategies do not seem to increase mortality in lung transplant patients unless Grade 3 PGD subsequently develops. ECMO salvage after transplant is associated with increased risk of mortality; however, it is likely used only in the severest cases, thus indication bias is likely present.

Lung transplantation may be considered for patients with a variety of end-stage lung diseases. Improvements in surgical technique, peri-operative management, and immunosuppressive strategies have resulted in better long-term post-transplant outcomes. However, careful candidate selection, including a thorough assessment of cardiac function, is essential for optimizing the likelihood of survival while awaiting transplantation, and improving the chance of a successful outcome. This chapter will review some of the important cardiac considerations for candidates with end-stage lung disease, including coronary artery disease, diastolic dysfunction, atrial arrhythmias, valvular heart disease, and pulmonary hypertension related to lung disease.

BackgroundPulmonary artery (PA) enlargement, defined as pulmonary artery to ascending aorta diameter ratio (PA:A)>1 on computed tomography (CT), is a marker of pulmonary vascular disease in chronic lung diseases. PA enlargement is prevalent in cystic fibrosis (CF), but its relationship to hemodynamics and prognostic utility in severe CF are unknown. We hypothesized that the PA:A would have utility in identifying pulmonary hypertension (PH) in severe CF and that PA enlargement would be associated with reduced transplant-free survival.MethodsWe conducted a retrospective study of adults with CF undergoing lung transplant evaluation at a single center between 2000 and 2015. CT, right heart catheterization (RHC), and clinical data were collected. The PA:A was measured from a single CT slice. We measured associations between PA:A and invasive hemodynamic parameters including PH defined as a mPAP ≥25mmHg using adjusted linear and logistic regression models. Kaplan-Meier and adjusted Cox regression models were used to measure associations between PA:A>1, RHC-defined PH, and transplant-free survival in severe CF.ResultsWe analyzed 78 adults with CF that had CT scans available for review, including 44 that also had RHC. RHC-defined PH defined as a mPAP ≥25mmHg was present in 36% of patients with CF undergoing transplant evaluation. The PA:A correlated with mPAP (r = 0.73; 95% CI 3.87-7.80; p1 was an independent predictor of PH (aOR 4.50; 95% CI 1.05-19.2; p = 0.042). PA:A>1 was independently associated with increased hazards for death or transplant (aHR 2.69; 95% CI 1.41-5.14; P = 0.003). The presence of mPAP ≥25mmHg was independently associated with decreased survival in this cohort.ConclusionsPA enlargement is associated with pulmonary hemodynamics and PH in severe CF. PA enlargement is an independent prognostic indicator of PH and decreased survival in this population.

Objectives Lung transplantation is a well-established treatment for selected patients with advanced cystic fibrosis (CF)- and non-cystic fibrosis (non-CF)--related bronchiectasis. Because the number of lung transplants performed for patients with non-CF bronchiectasis is much smaller than for patients with CF, little data is available regarding patient selection, choice of procedure, and outcomes. Methods Between November 1997 and December 2013, 42 patients with CF and 33 patients with non-CF bronchiectasis underwent lung transplantation at the Rabin Medical Center, Israel. We analyzed and compared pretransplant evaluation data and short- and long-term results in both groups. Results Median survival for the CF group in our study was 8.4 years, compared with 7.1 years for the non-CF group (P = .098), similarly to that reported by the International Society for Heart and Lung Transplantation Registry data. The main survival difference between groups was in the early postoperative period. Both groups achieved similar peak forced expiratory volume in 1 second values and had stable lung function at the 3-year follow-up. Biopsy-proven rates of acute cellular rejection were low for both groups. Rates of chronic lung allograft dysfunction development did not differ between CF and non-CF recipients. Conclusion Our institutional experience confirms that lung transplantation is feasible for non-CF bronchiectasis, and results are comparable to our CF cohort. The increased early mortality in this study occurred from 1999 to 2008 and was probably related to surgical techniques used at the time. Overall, 3-year and 5-year survival were comparable with the International Society for Heart and Lung Transplantation Registry data. Non-CF bronchiectasis patients achieved and maintained satisfactory lung function.

Purpose 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. Methods 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). Results 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). Conclusion 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.

The authors previously identified plasma plasminogen activator inhibitor-1 (PAI-1) level as a quantitative lung injury biomarker in primary graft dysfunction (PGD). They hypothesized that plasma levels of PAI-1 used as a quantitative trait could facilitate discovery of genetic loci important in PGD pathogenesis. A two-stage cohort study was performed. In stage 1, they tested associations of loci with PAI-1 plasma level using linear modeling. Genotyping was performed using the Illumina CVD Bead Chip v2. Loci meeting a p < 5 × 10(-4) cutoff were carried forward and tested in stage 2 for association with PGD. Two hundred ninety-seven enrollees were evaluated in stage 1. Six loci, associated with PAI-1, were carried forward to stage 2 and evaluated in 728 patients. rs3168046 (Toll interacting protein [TOLLIP]) was significantly associated with PGD (p = 0.006). The increased risk of PGD for carrying at least one copy of this variant was 11.7% (95% confidence interval 4.9-18.5%). The false-positive rate for individuals with this genotype who did not have PGD was 6.1%. Variants in the TOLLIP gene are associated with higher circulating PAI-1 plasma levels and validate for association with clinical PGD. A protein quantitative trait analysis for PGD risk prioritizes genetic variations in TOLLIP and supports a role for Toll-like receptors in PGD pathogenesis.

Primary graft dysfunction (PGD) is a major cause of early mortality after lung transplant. We aimed to define objective estimates of PGD risk based on readily available clinical variables, using a prospective study of 11 centers in the Lung Transplant Outcomes Group (LTOG). Derivation included 1255 subjects from 2002 to 2010; with separate validation in 382 subjects accrued from 2011 to 2012. We used logistic regression to identify predictors of grade 3 PGD at 48/72 h, and decision curve methods to assess impact on clinical decisions. 211/1255 subjects in the derivation and 56/382 subjects in the validation developed PGD. We developed three prediction models, where low-risk recipients had a normal BMI (18.5-25 kg/m(2) ), chronic obstructive pulmonary disease/cystic fibrosis, and absent or mild pulmonary hypertension (mPAP

Background Donor-to-recipient lung size matching at lung transplantation (LTx) can be estimated by the predicted total lung capacity (pTLC) ratio (donor pTLC/recipient pTLC). We aimed to determine whether the pTLC ratio is associated with the risk of primary graft dysfunction (PGD) after bilateral LTx (BLT). Methods We calculated the pTLC ratio for 812 adult BLTs from the Lung Transplant Outcomes Group between March 2002 to December 2010. Patients were stratified by pTLC ratio >1.0 ("oversized") and pTLC ratio ≤1.0 ("undersized"). PGD was defined as any ISHLT Grade 3 PGD (PGD3) within 72 hours of reperfusion. We analyzed the association between risk factors and PGD using multivariable conditional logistic regression. As transplant diagnoses can influence the size-matching decisions and also modulate the risk for PGD, we performed pre-specified analyses by assessing the impact of lung size mismatch within diagnostic categories. Results In univariate analyses oversizing was associated with a 39% lower odds of PGD3 (OR 0.61, 95% CI, 0.45-0.85, p = 0.003). In a multivariate model accounting for center-effects and known PGD risks, oversizing remained independently associated with a decreased odds of PGD3 (OR 0.58, 95% CI 0.38 to 0.88, p = 0.01). The risk-adjusted point estimate was similar for the non-COPD diagnosis groups (OR 0.52, 95% CI 0.32 to 0.86, p = 0.01); however, there was no detected association within the COPD group (OR 0.72, 95% CI 0.29 to 1.78, p = 0.5). Conclusion Oversized allografts are associated with a decreased risk of PGD3 after BLT; this effect appears most apparent in non-COPD patients.

Extracorporeal membrane oxygenation (ECMO) has been used to provide "lung rest" through the use of low tidal volume (6 ml/kg) and ultralow tidal volume (

Primary graft dysfunction (PGD) is acute lung injury within 72 hours of lung transplantation. We hypothesized that cell-free hemoglobin (CFH) contributes to PGD by increasing lung microvascular permeability and tested this in patients, ex vivo human lungs, and cultured human lung microvascular endothelial cells. In a nested case control study of 40 patients with severe PGD at 72 hours and 80 matched controls without PGD, elevated preoperative CFH was independently associated with increased PGD risk (odds ratio [OR] 2.75, 95%CI, 1.23–6.16, P = 0.014). The effect of CFH on PGD was magnified by reperfusion fraction of inspired oxygen (FiO2) ≥ 0.40 (OR 3.41, P = 0.031). Isolated perfused human lungs exposed to intravascular CFH (100 mg/dl) developed increased vascular permeability as measured by lung weight (CFH 14.4% vs. control 0.65%, P = 0.047) and extravasation of Evans blue–labeled albumin dye (EBD) into the airspace (P = 0.027). CFH (1 mg/dl) also increased paracellular permeability of human pulmonary microvascular endothelial cell monolayers (hPMVECs). Hyperoxia (FiO2 = 0.95) increased human lung and hPMVEC permeability compared with normoxia (FiO2 = 0.21). Treatment with acetaminophen (15 μg/ml), a specific hemoprotein reductant, prevented CFH-dependent permeability in human lungs (P = 0.046) and hPMVECs (P = 0.037). In summary, CFH may mediate PGD through oxidative effects on microvascular permeability, which are augmented by hyperoxia and abrogated by acetaminophen.

Lung transplantation is an established treatment modality for patients with end-stage lung disease and can improve both quality of life (QOL) and survival. Over 6400 lung transplants have been performed since the first successful operation in the early 1980s. According to the International Society for Heart and Lung Transplantation Registry, between January 1995 and June 2015, there were 24.5% lung transplants performed worldwide for interstitial lung disease (ILD) idiopathic interstitial pneumonia (IIP), 5.2% for ILD non-IIP, and 36.4% for chronic obstructive pulmonary disease (COPD). Median survival after lung transplantation is currently 5.5 years, and long-term outcomes are limited mainly by primary graft dysfunction, infection, and allograft rejection. When considering candidates for transplantation, the expected posttransplant survival is carefully weighed against the prognosis of the underlying disease and expected survival if transplant is not performed. The aim of lung transplantation is to improve survival and quality of life, and these goals can be achieved for selected patients with idiopathic pulmonary fibrosis and pulmonary fibrosis associated with connective tissue disease. This chapter will summarize the clinical features of the interstitial lung diseases, such as IPF, connective tissue diseases, systemic sclerosis, rheumatoid arthritis, sarcoidosis, and other rare interstitial lung diseases. Comorbid conditions associated with the ILDs will be discussed, and guidelines for lung transplant candidacy and referral will be presented.

The management of patients with severe acute kidney injury (AKI) is largely supportive and includes renal replacement therapy (RRT). Available RRT modalities are intermittent hemodialysis (IHD); continuous renal replacement therapy (CRRT); hybrid therapies, known as prolonged intermittent renal replacement therapy (PIRRT); and peritoneal dialysis (PD). This chapter briefly reviews these dialytic options and the current evidence regarding the timing of RRT initiation, modality selection, and the practical considerations of the RRT prescription for AKI.

Background. Patients with acute decompensated heart failure (ADHF) and cardiorenal syndrome (CRS) 1 have poor outcomes. Ultrafiltration (UF) is used to mechanically remove salt and water in ADHF patients with diuretic resistance. However, little is known about the outcomes of ADHF patients on inotropes and/or vasopressors who require continuous renal replacement therapy (CRRT) for both UFand solute clearance in severe acute kidney injury. Methods. We retrospectively analyzed 37 consecutive critically ill patients who were admitted for ADHF from 2005–13 and were on inotropes and/or vasopressors at the time of CRRT initiation. The primary outcome was in-hospital mortality. Results. In-hospital mortality rate was 62%. Median survival was 15.5 days after CRRT initiation, and 10 months following hospital discharge. When comparing renal and cardiovascular variables for survivors and non-survivors at baseline, admission and CRRT initiation, survivors were less likely to need vasopressors. After controlling for multiple predictors, vasopressor use remained associated with time to death (HR 9.9; 95% CI 2.3–43.3; P = 0.002). Patients with isolated right ventricular dysfunction had an in-hospital mortality of 45% compared with 69% in those with left ventricular dysfunction (P = 0.27). Age of >70 years was associated with 100% in-hospital mortality. Conclusions. Rescue therapy using CRRT in refractory CRS1 was associated with high in-hospital mortality, especially when vasopressors were used and when patient age exceeded 70 years. Additionally, survivors had a poor long-term prognosis.

To the Editor: Primary graft dysfunction (PGD) is a form of acute lung injury occurring within 72 hours of lung transplantation (1, 2). We have previously demonstrated an increase in early mortality in subjects with PGD (2). Understanding of the mechanisms leading to PGD and early mortality is important in identifying potential therapeutic targets and interventions. The complement system defines a group of plasma and cell membrane proteins that play a key role in innate immunity as well as regulating adaptive immune response. C3a, C4a, and C5a, downstream products of the activated complement cascade, are potent neutrophil and lymphocyte chemoattractants (3–5). In animal models, activation of the complement system during lung ischemia and reperfusion can lead to cellular injury and lung allograft failure (6, 7). Based on the relationship between complement activation and ischemia reperfusion injury in the lung allograft, we hypothesized that plasma levels of C3a, C4a, and C5a would be associated with both PGD and mortality after lung transplantation. We performed a prospective cohort study of 190 lung transplant recipients from 10 centers enrolled between 2008 and 2010 in the Lung Transplant Outcomes Group (LTOG) cohort. We included consecutive subjects who had plasma samples available at the preoperative, 6-hour, and 24-hour time points (see Figure E1 in the online supplement). Clinical and mortality data were collected as described elsewhere (2). Informed consent was obtained from each subject. The Investigational Review Board at each center approved our study. The primary outcome was grade 3 PGD within 72 hours after transplantation, which has demonstrated construct validity for survival (8). Grade 3 PGD at 24 hours was used to evaluate the relationship between concurrent lung injury, and grade 3 PGD at 48 or 72 hours was used to evaluate a severe lung injury phenotype (2). We evaluated all-cause mortality as an additional end point. Plasma C3a, C4a, and C5a concentrations were measured using a commercially available cytometric bead array (BD Biosciences, San Jose, CA) in a manner devised to ensure stability of complement (see online supplement). We evaluated absolute differences in levels between each time point to assess changes during the early transplant period. The association between complement and PGD was determined using Wilcoxon rank sum testing. We used Cox regression to evaluate associations between complement levels and time to death, conditioned on 90-day survival, to exclude bias from the effect of PGD and sepsis on early mortality. We adjusted for recipient, donor, and surgical variables (see online supplement). Of the 190 subjects enrolled, 82 developed PGD (43%) within 72 hours post-transplant, and 33 had PGD at 48 or 72 hours (17%). Demographics of the cohort are in Table E1. There were no differences between subjects enrolled with blood samples at all three time points and other subjects enrolled in LTOG (Table E2). The median change in plasma C5a levels between 6 and 24 hours post transplantation was significantly greater in subjects with PGD than in those without (867 vs. −156 pg/ml, P = 0.01) (Figure 1A). The median change in plasma C4a levels between preoperative and 6 hours was greater in subjects with PGD (72,075 vs. −79,501, P = 0.01) (Figure 1B). There was no significant difference in change in plasma C3a levels between the PGD and non-PGD group at any individual time point (Table E3). In sensitivity analyses, there was no difference in complement levels using grade 3 PGD at 24 hours (Table E4). However, there was a similar relationship between change in plasma C5a levels between 6 and 24 hours (1,164 vs.113, P = 0.24) and change in plasma C4a levels between preoperative and 6 hours (109,654 vs. −8,185, P = 0.04) using grade 3 PGD at 48 or 72 hours. Figure 1. (A) Plasma C5a concentration at each time point in subjects without primary graft dysfunction (PGD) (dashed line) and with grade 3 PGD (solid line). The P value indicates that the difference in C5a concentration (represented by the slope of the line) ... Of 175 patients with available mortality data, 32 died (17%). The change in C5a levels from 6 to 24 hours was associated with an increased risk of death (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16, 2.83; P = 0.01). C5a levels measured preoperatively and 24 hours after transplantation were also associated with an increased risk of death (HR, 1.64; 95% CI, 1.29, 2.09; P < 0.01; and HR, 1.94; 95% CI, 1.39, 2.72; P < 0.01; respectively). C3a levels measured at 6 hours were associated with an increased risk of death (HR, 1.68; 95% CI, 1.04, 2.71; P = 0.03). There was no association between change in C3a or C4a levels and mortality (Tables E5 and E6). These associations were independent of adjustment for all tested confounders, including PGD (Table 1). Table 1. Association of C3a and C5a at Different Time Points with Mortality Our study demonstrates that early changes in plasma C4a and C5a are associated with PGD, and there is an association between C3a and C5a levels with mortality, independent of PGD. Collectively, these data suggest that systemic complement activation is important in both short- and long-term outcomes after transplantation. The increase in C5a between 6 and 24 hours is associated with both PGD and mortality. This suggests a role for an early systemic complement response in both early and late outcomes. Prior work has implicated complement activation in lung ischemia–reperfusion injury (9). The change in C5a level was observed early after transplant and was not associated with concurrent lung injury (grade 3 at 24 h), indicating it may be driving lung injury and not just a marker of injury. Complement may be important in the pathogenesis PGD by attracting neutrophils and accelerating both the innate and adaptive immune responses within the first 24 hours after injury (10, 11). The association of complement with mortality was independent of PGD. Prior work found an association between C3a, C5a, and obliterative bronchiolitis in a mouse model (12). Our findings in humans suggest a role for complement activation that continues after the early reperfusion period, potentially a signal of chronic immune activation starting in the early post-transplant period and leading to formation of autoantibodies, leading to chronic graft dysfunction and mortality. These findings support the study of blockade of complement activation to improve clinical outcomes after transplantation. Our study had limitations. We were unable to measure complement levels in bronchoalveolar lavage; therefore, we could not link the plasma and lung compartments. The incidence of PGD in this study was 40%, which is higher than previous reports; however, we observed a similar trend in sensitivity analyses using a more restrictive definition of PGD. Finally, we were unable to adjust for center effect given small numbers. In conclusion, our study suggests a role for early, systemic activation of the complement pathway in development of severe PGD and mortality after lung transplantation.

Introduction Regional citrate anticoagulation (RCA) is used as an anticoagulant for continuous renal replacement therapy (CRRT). A systemic calcium (Ca2+) infusion is required to replace Ca2+ lost in the effluent. The shortage of intravenous Ca2+ in the United States has limited RCA use. We describe a continuous veno-venous hemofiltration (CVVH) protocol with RCA using 2.2% anticoagulant citrate dextrose formula-A (ACD-A) and a commercial dialysate containing Ca2+ 1.5 mmol/l (N × Stage) as post-filter replacement fluid (RF), without need for Ca2+ infusion. Methods We prospectively evaluated five patients on CRRT who had at least three episodes of filter clotting within 24 h. Patients were switched to CVVH using ACD-A infused pre-blood pump and titrated to achieve a post-filter ionized calcium (iCa2+) level 2+ -containing dialysate was delivered post-filter as RF. Results Steady state mean serum chemistries were: Na+: 140.8 ± 2.3 meq/l, K+: 4.2 ± 0.4 meq/l, HCO3–: 30.9 ± 3.7 meq/l, pH: 7.42 ± 0.07, CO2: 47.9 ± 8.3 mmHg, total Ca2+: 8.08 ± 1.09 mg/dL. Post-filter iCa2+ ranged 0.27-0.36 mmol/l, and patient iCa2+ ranged 0.81-1.24 mmol/l. Mean post-filter RF rate: 3086 ± 164 ml/h, mean ACD-A rate: 298 ± 21 ml/h. Mean blood flow rate: 200 ± 17 ml/min, mean filtration fraction: 39.6 ± 7.2%. Mean effluent flow rate: 38.6 ± 6.7 ml/kg/h (range 28.7-55.8). Mean filter survival was 7 h without anticoagulation, compared to 42.6 h in the ACD-A group (pConclusions In this pilot study, CVVH using ACD-A for RCA and a Ca2+ -containing RF was safely and effectively used without a continuous Ca2+ infusion. This protocol is a promising solution for maintaining effective CRRT when intravenous calcium is in short supply.

Rationale: Biologic pathways with significant genetic conservation across human populations have been implicated in the pathogenesis of primary graft dysfunction (PGD). The evaluation of the role of recipient genetic variation in PGD has thus far been limited to single, candidate gene analyses. Objectives: We sought to identify genetic variants in lung transplant recipients that are responsible for increased risk of PGD using a two-phase large-scale genotyping approach. Methods: Phase 1 was a large-scale candidate gene association study of the multicenter, prospective Lung Transplant Outcomes Group cohort. Phase 2 included functional evaluation of selected variants and a bioinformatics screening of variants identified in phase 1. Measurements and Main Results: After genetic data quality control, 680 lung transplant recipients were included in the analysis. In phase 1, a total of 17 variants were significantly associated with PGD, four of which were in the prostaglandin E2 family of genes. Among these were a coding variant in the gene encoding prostaglandin E2 synthase (PTGES2; P = 9.3 × 10−5) resulting in an arginine to histidine substitution at amino acid position 298, and three variants in a block containing the 5′ promoter and first intron of the PTGER4 gene (encoding prostaglandin E2 receptor subtype 4; all P < 5 × 10−5). Functional evaluation in regulatory T cells identified that rs4434423A in the PTGER4 gene was associated with differential suppressive function of regulatory T cells. Conclusions: Further research aimed at replication and additional functional insight into the role played by genetic variation in prostaglandin E2 synthetic and signaling pathways in PGD is warranted.

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.

In May 2005, the Lung Allocation Score (LAS) became the primary method for determining allocation of lungs for organ transplantation for those at least 12 years of age in the United States. During the pre-LAS period, black patients were more likely than white patients to become too sick or die while awaiting transplant. The association between gender and lung transplant outcomes has not been widely studied.Black and white patients aged ≥ 18 years registered on the United Network for Organ Sharing (UNOS) lung transplantation waiting list from January 1, 2000, to May 3, 2005 (pre-LAS, n = 8,765), and from May 4, 2005, to September 4, 2010 (LAS, n = 8,806), were included. Logistic regression analyses were based on smaller cohorts derived from patients listed in the first 2 years of each era (2,350 pre-LAS, and 2,446 LAS) to allow for follow-up time. Lung transplantation was the primary outcome measure. Multivariable analyses were performed within each interval to determine the odds that a patient would die or receive a lung transplant within 3 years of listing.In the pre-LAS era, black patients were more likely than white patients to become too sick for transplantation or die within 3 years of waiting list registration (43.8% vs 30.8%; odds ratio [OR], 1.84; p0.001). Race was not associated with death or becoming too sick while listed for transplantation in the LAS era (14.0% vs 13.3%; OR, 0.93; p = 0.74). Black patients were less likely to undergo transplantation in the pre-LAS era (56.3% vs 69.2%; OR, 0.54; p0.001) but not in the LAS era (86.0% vs 86.7%; OR, 1.07; p = 0.74). Women were more likely than men to die or become too sick for transplantation within 3 years of listing in the LAS era (16.1% vs 11.3%; OR, 1.58; p0.001) compared with the pre-LAS era (33.4% vs 30.7%; OR, 1.19; p = 0.08).Racial disparities in lung transplantation have decreased with the implementation of LAS as the method of organ allocation; however, gender disparities may have actually increased in the LAS era.