Lung Transplant Survival Research Articles

Prevalence of Clinical COPD Phenotypes in Patients Who Are Candidates for Lung Transplantation, Complications and Post-Transplant Survival

IntroductionThe prevalence of COPD phenotypes that are referred for assessment for lung transplantation is unknown, as well as whether specific phenotype influences post-transplant evolution in those patients who receive it. Material and methodsAmbispective observational study without intervention. The main objective was to know the prevalence of the different COPD phenotypes of the patients referred for the evaluation of a lung transplant. Secondary objective were to compare their clinical characteristics, to perform an analysis of post-transplant survival or complications according to their phenotype. Results502 patients were evaluated for lung transplantation, of which 173 met the study criteria. 31.21% of the patients were discarded for transplantation on a first visit. The final cohort of potential transplant candidates who completed the pre-transplant study was 119 (69%) and 47 finally received a lung transplant (39.5%). The most frequent COPD phenotype evaluated for lung transplantation was the exacerbator (59%), followed by the non-exacerbator (38%) and the Asthma COPD Overlap [ACO] (3%). 59.8% of the exacerbator-phenotype patients assessed did not complete the pre-transplant study. Exacerbator-phenotype patients have a lower post-transplant survival (1115.1 days [standard deviation-DE-587]) vs. ACO: 1432 days [DE 507.5] and Non-exacerbators: 1317.8 days [DE 544.7] p=0.16), although this difference has not been statistically significant. ConclusionsThe most frequent COPD phenotype assessed for lung transplantation is the exacerbator, although more than half of these patients fail to complete the pre-transplant study.

Idiopathic pulmonary fibrosis cluster analysis highlights diagnostic delay and cardiovascular comorbidity association with outcome.

IntroductionIdiopathic pulmonary fibrosis (IPF) prognosis is heterogeneous despite antifibrotic treatment. Cluster analysis has proven to be a useful tool in identifying interstitial lung disease phenotypes, which has yet to be performed in IPF. The aim of this study is to identify phenotypes of IPF with different prognoses and requirements.MethodsObservational retrospective study including 136 IPF patients receiving antifibrotic treatment between 2012 and 2018. Six patients were excluded due to follow-up in other centres. Cluster analysis of 30 variables was performed using approximate singular value-based tensor decomposition method and comparative statistical analysis.ResultsThe cluster analysis identified three different groups of patients according to disease behaviour and clinical features, including mortality, lung transplant and progression-free survival time after 3-year follow-up. Cluster 1 (n=60) was significantly associated (p=0.02) with higher mortality. Diagnostic delay was the most relevant characteristic of this cluster, as 48% of patients had ≥2 years from first respiratory symptoms to antifibrotic treatment initiation. Cluster 2 (n=22) had the longest progression-free survival time and was correlated to subclinical patients evaluated in the context of incidental findings or familial screening. Cluster 3 (n=48) showed the highest percentage of disease progression without cluster 1 mortality, with metabolic syndrome and cardiovascular comorbidities as the main characteristics.ConclusionThis cluster analysis of IPF patients suggests that diagnostic and treatment delay are the most significant factors associated with mortality, while IPF progression was more related to metabolic syndrome and cardiovascular comorbidities.

Factors Associated with Long-Term CLAD-Free Survival in Lung Transplantation

<h3>Purpose</h3> Chronic allograft dysfunction (CLAD) limits survival after lung transplantation (LT), affecting 50% by 5-years and 75% by 10 years. Long-term survival (≥10 years) is seen in 35-40% after LT. While 10-15% of patients survive ≥10 years without CLAD, the reasons remain unclear. Our aim was to determine clinical factors that differ between long-term survivors with and without CLAD <h3>Methods</h3> This was a single-center retrospective cohort study of all first LT performed between 1983 and 2010. Re-transplants and those without follow-up data were excluded. CLAD was adjudicated by ISHLT criteria in patients with ≥ 4 pulmonary function tests (PFTs). Associations of clinical variables with CLAD-free status were assessed using univariate logistic regression <h3>Results</h3> 1110 patients underwent primary LT in the study period. 1-year survival was 79.5 (882/1110). 32.2% (357/1110) survived ≥10 years, and of those with sufficient PFTs, 10.6% (118/348) were long-term CLAD-free survivors. 73.7% (87/357) of this cohort are still alive at a median follow-up of 12.49 (IQR 11.3-14.85) years. Among very long-term survivors (≥20 years; n=49) with sufficient PFTs, 83% were CLAD-free at a median of 23.3 (IQR 21.1-25.87) years. Shorter ischemic time, lower donor age, indication for transplant, higher baseline total lung capacity and baseline renal function, and absence of gastroparesis, major infections and treatment for acute rejection were all associated with ≥10-year CLAD-free survival. Compared to long-term survivors without CLAD, those with CLAD had higher mortality (<0.001) and skin cancers on follow-up <h3>Conclusion</h3> We identified clinical variables associated with ≥10-year CLAD-free survival in our cohort. We will perform multiple regression and compare this cohort with those surviving 1 to 5 years post-LT using Cox proportional hazards model. We aim to optimize recipient-allograft matching leading to better long-term CLAD-free survival.

Time from Start of Agonal Phase to Pulmonary Artery Cross Clamp in Donor Cardiac Death Donors Does Not Correlate with Diminished Recipient Lung Function or Survival

Purpose Donor cardiac death (DCD) donors could expand the field of lung donors, but the acceptably safe time interval between the onset of agonal phase and application of the pulmonary artery clamp is controversial. The purpose of this study was to determine if the time from the beginning of the agonal phase to placement of the pulmonary artery cross clamp in DCD donors is associated with worse recipient lung function or long-term survival. Methods The Scientific Registry for Transplant Research database (2008-2019) was queried for lung transplants performed from DCD donors (N=227) excluding pediatric, multi-organ, and redo lung transplants. Time from the beginning of agonal phase to the time of pulmonary artery cross clamp placement was determined, and donor and recipient characteristics and outcomes were examined for 3 groups: 0-30 minutes (N=178), 30-45 minutes (N=25), and over 45 minutes (N=21). Eight DCD donor lungs had an agonal phase to pulmonary artery cross clamp time between 75 and 120 minutes. The primary endpoints were forced expiratory volume in 1 second (FEV1) at 1 and 2 years and overall survival using Kaplan Meier analysis. Results There were no significant differences in donor age, gender or body mass index between the three groups. Recipient characteristics were comparable between the three groups, and there was no difference in recipient FEV1 at 1 (80.47+/-22.45%, 79.81+/-16.60%, and 76.67+/-13.30%, p=0.840) and 2 years (76.23+/-27.13%, 76.11+/-24.31%, 82.17+/-17.58%, p=0.868) for the three groups (0-30 minutes, 30-45 minutes, and over 45 minutes, respectively) . There was no difference in long term survival out to 10 years between the three groups using Kaplan Meier analysis. Conclusion Lung transplant recipient lung function and survival is similar for recipients of DCD donor lungs regardless of the time from start of the agonal phase to application of the pulmonary artery transplant out to and beyond 45 minutes.

Induction of Epithelial-Mesenchymal Transition (EMT) by Neutrophil Extracellular Traps (NETs) as Possible Molecular Mechanism in CLAD

Purpose Chronic Lung Allograft Dysfunction (CLAD) is the main limitation to long term post lung transplant survival and is characterized by interstitial or airway fibrosis. Recruitment and activation of Neutrophils in the graft has been described in CLAD. Neutrophils are an essential component of the innate immune system which can undergo different activation processes, among which NETosis. NETs can drive epithelial cell injury and induce endothelial mesenchymal transition or epithelial mesenchymal transition (EMT) of breast cancer cells. We here aim to investigate whether NETs can induce EMT on a human alveolar basal epithelial cell line (A549) as possible mechanism of fibrosis in CLAD. Methods NETosis was induced on healthy donor-derived neutrophils (Neu) with PMA. EMT was studied on A549 cells in three conditions (PMA-activated Neu (PMA-Neu), purified NETs from PMA-Neu and TGF-β). To study the induction of EMT, we evaluate the expression of two main proteins representative of EMT mechanism (α-SMA and E-cadherin) by western blot of cell lysates. Since it is known that neutrophils activated against NETosis can induce cell damage, we decided to evaluate cell toxicity after treatments with PMA-Neu or NETs by flow cytometry. Results Confocal microscope images confirmed that PMA treatment leads to release NETs by neutrophils. NETs changed the typical epithelial morphology of A549 cells into a mesenchymal phenotype. These morphological changes are also visible after treatment with TGF-β, the best known EMT effector. Morphological changes were confirmed by western blot analysis of EMT markers expression. Both PMA-Neu and purified NETs induced EMT in A549 after 24h, increasing α-SMA (1.21±0.025 and 1.34±0.025, respectively) and decreasing E-Cadherin expression (0.245±0.10 and 0.08±0.002, respectively). Moreover we observed that NETs activate EMT without toxic effects rather than PMA-Neu which induced 33.70 ± 4.37 % cell death compared to control cells. Conclusion This study highlights the contribution NETs as trigger of lung fibrosis, and suggest this mechanism might contribute to CLAD pathogenesis.

Lung Transplantation for Cystic Fibrosis in Turkey: First Report

Lung transplant is the most important treatment approach that improves the life expectancy and quality of life for patients with cystic fibrosis with end-stage lung disease. In this study, we retros-pectively analyzed patients with cystic fibrosis who were referred to our lung transplant program in Turkey. We evaluated 14 patients with cystic fibrosis who were referred to our lung transplant clinic between December 2016 and December 2019. The characteristics of the patients at the time of referral to our lung transplant clinic, survival, and lung transplant results were recorded. Four patients died on the wait list, 3 patients were not eligible for lung transplant, and lung transplant was performed in 7 patients. The mean age of all patients was 22.8 years (range, 11-41 years), and the mean age for patients who underwent lung transplant was 27.5 years (range, 21-41 years). The mean time of suitable donor offer or survival life was 140 days in the patients who were referred for lung transplant. The 1-year mortality rate was 28.6% (2 of 7 patients) after lung transplant. One patient died of chronic lung allograft dysfunction at the 25th month after lung transplant. Four patients were alive without any problems. Lung transplant is the final treatment method for patients with cystic fibrosis with terminal period lung disease. To provide the best benefit, patients should be evaluated for transplant early. Cystic fibrosis care clinics and lung transplant clinics should work in coordination in order to increase the number of lung transplants and improve outcomes.

A new lung donor score to predict short and long-term survival in lung transplantation.

BackgroundDonor selection criteria are crucial for a successful lung transplant outcome. Our objective was to develop a new donor score to predict short- and long-term survival and validate it with five existing lung donor scores (Oto, Eurotransplant, Minnesota, Maryland-UNOS, Louisville-UNOS).MethodsAll 454 adult lung transplants at our center between 1992–2015 were included to develop a new score. Discriminative ability for all scores was calculated by the area under time-dependent receiver operating characteristic curves (time-dependent AUC) at 30-day, 1, 5 and 10-year survival, and their fit compared with Akaike’s information criterion. For the new score, five pre-selected donor risk factors were derived: age, diabetes mellitus, smoking history, pulmonary infection, PaO2/FiO2-ratio, weighed via simplification of a multiple Cox model, and shrinkage used to avoid overfitting. The score sub-weighting resulted in a total of 17 points.ResultsThe existing scores showed predictive accuracy better than chance in prediction of survival of 5-year (AUC 0.58–0.60) to 10-year survival (AUC 0.58–0.64). Our new score had better discriminative ability as the existing scores with regard to 1, 5 and 10-year survival (AUC 0.59, 0.64, 0.66, respectively). Additional adjustment for recipient and surgical procedure variables improved the time-dependent AUC’s slightly. For the secondary outcomes primary graft dysfunction and bronchiolitis obliterans syndrome, the new score showed also a good predictive accuracy.ConclusionsThe proposed Zurich Donor Score is simple, well adapted for the current urge of extended donors use, and shows higher discriminative ability compared to preexisting donor scores regarding short- to long-term survival.

New Clue: Prediction from Cell-Free DNA

The main challenge for a positive long-term outcome in lung transplantation is the lack of early detection for chronic lung allograft dysfunction (CLAD). With advancements in technology, an increasing number of studies demonstrate that cell-free DNA (cfDNA) in body fluids could be used as a marker for disease diagnosis, prognosis or monitoring response to treatment. A previous report from this journal found the joint assessment of cfDNA and CXCL10 from brochoalveolar lavage (BAL) could determine the subphenotypes of CLAD and predict lung transplant survival. This is an exciting attempt in monitoring the progress for lung transplant recipients. More studies and better understanding of cfDNA are needed to develop an accessible and reliable biomarker to monitor the progress of CLAD to improve the long-term survival for lung transplant recipients.

Predictors for the Bronchiolitis Obliterans Syndrome in Lung Transplant Patient

肺移植是治疗终末期肺病的有效方法。目前，肺移植术后1年生存率已达到80%，由于闭塞性细支气管炎综合症（bronchiolitis obliterans syndrome, BOS）的发生，5年生存率维持在50%左右。BOS是一个纤维化的过程，最终导致不可逆的气道闭塞。缺血-再灌注损伤、感染、氧化应激以及急性排斥反应等多个因素参与了BOS的发生。研究证实BOS的早期诊断与预后良好相关。因此，寻找灵敏、特异的BOS预测标记物对于提高肺移植患者长期生存具有重要的科学和临床意义。本文就与BOS发生发展相关的免疫调节细胞、分泌性蛋白质、细胞膜蛋白等指标的变化在BOS早期诊断中的作用进行综述。

Survival in adult lung transplantation: where are we in 2020?

In this article, an overview of the survival after lung transplantation will be given, with a focus on factors affecting outcome and differences in survival determined by underlying disease. Lung transplantation is an established treatment modality for patients with various end-stage lung diseases. The most recent International Society for Heart and Lung Transplantation Registry reports a 1 and 5-year survival of 85 and 59%, respectively, for adult lung transplant recipients transplanted since 2010. Over the past decades, significant improvements in patient outcomes have been achieved related to changes in donor selection, organ preservation, perioperative management and better treatment of postoperative complications. However, long-term graft and patient outcomes still lag behind that of other solid organ transplantations. Chronic lung allograft dysfunction (CLAD) a condition which develops in about 50% of recipients 5 year after lung transplantation, remains the major barrier for long-term survival, although development of solid organ cancer is nowadays also an increasing cause of late mortality. Lung transplantation offers a survival benefit in well chosen patients with end-stage lung diseases. However, CLAD, side effects of immunosuppressive therapy and solid organ cancer remain important challenges impairing long-term survival. Advances in prevention and treatment of chronic rejection are critical to further improve outcome.

Survival benefit of lung transplantation compared with medical management and pulmonary rehabilitation for patients with end-stage COPD.

BackgroundCOPD patients account for a large proportion of lung transplants; lung transplantation survival benefit for COPD patients is not well established.MethodsWe identified 4521 COPD patients in the United Network for Organ Sharing (UNOS) dataset transplanted from May 2005 to August 2016, and 604 patients assigned to receive pulmonary rehabilitation and medical management in the National Emphysema Treatment Trial (NETT). After trimming the populations for NETT eligibility criteria and data completeness, 1337 UNOS and 596 NETT patients remained. Kaplan–Meier estimates of transplant-free survival from transplantation for UNOS, and NETT randomisation, were compared between propensity score-matched UNOS (n=401) and NETT (n=262) patients.ResultsIn propensity-matched analyses, transplanted patients had better survival compared to medically managed patients in NETT (p=0.003). Stratifying on 6 min walk distance (6 MWD) and FEV1, UNOS patients with 6 MWD <1000 ft (∼300 m) or FEV1 <20% of predicted had better survival than NETT counterparts (median survival 5.0 years UNOS versus 3.4 years NETT; log-rank p<0.0001), while UNOS patients with 6 MWD ≥1000 ft (∼300 m) and FEV1 ≥20% had similar survival to NETT counterparts (median survival, 5.4 years UNOS versus 4.9 years NETT; log-rank p=0.73), interaction p=0.01.ConclusionsOverall survival is better for matched lung transplant patients compared with medical management alone. Patients who derive maximum benefit are those with 6 MWD <1000 ft (∼300 m) or FEV1 <20% of predicted, compared with pulmonary rehabilitation and medical management.

Characteristics, Survival, and Outcomes of Lung and Heart-Lung Transplantation for Pulmonary Sarcoidosis in a Multicenter European Study Characteristics, Survival, and Outcomes of Lung and Heart-Lung Transplantation for Pulmonary Sarcoidosis in a Multicenter European Study

In the context of sarcoidosis, lung transplantation is often performed in patients with irreversible advanced lung disease unresponsive to medical therapy. The clinical phenotypes and posttransplant survival remain unclear, due primarily to the recurring nature of the disease and extrapulmonary involvement. The objective of this study in a large multicenter European cohort was to describe the clinical characteristics and outcomes of patients with pulmonary sarcoidosis treated by lung transplantation. We retrospectively reviewed the data of 147 patients with pulmonary sarcoidosis who underwent lung or heart-lung transplantation between 1990 and 2019 at 15 European centers. Inclusion criteria were sarcoidosis meeting international diagnostic criteria and availability of data from pretransplantation right heart catheterization, lung function testing, and chest computed tomography (CT) staged using a standardized system. At transplantation, mean age was 50±8 years, 62% were male, and 20% had extrapulmonary manifestations. Mean values before transplantation were as follows: FVC (%pred), 46±17%; FEV1 (%pred), 38±19; FVC/FEV1 (%), 55±32; DLCO (%pred), 31±13; mPAP (mmHg), 36±13; PCWP (mmHg), 10±5; cardiac index (L/min/m²), 3.0±0.8; and pulmonary vascular resistance (dyn·s·cm-5), 480±340; furthermore, 60% of patients had severe pulmonary hypertension. Posttransplant survival rates after 1, 3, and 5 years were 85%, 69%, and 63%, respectively. During the median [range] follow-up of 43 [17-79] months, 38% of patients developed chronic lung allograft dysfunction. Factors significantly associated with outcomes were high emergency transplantation, era of transplantation, preoperative extrapulmonary sarcoidosis, and extent of fibrosis by CT. Posttransplant survival rates and freedom from chronic lung allograft dysfunction in patients with pulmonary sarcoidosis were similar to those in patients with other reasons for lung transplantation. Factors associated with worse outcomes were high emergency transplantation, earlier transplantation era, preoperative extrapulmonary sarcoidosis, and greater burden of fibrosis by CT.

Wait or No Wait for Reducing Body Weight before Lung Transplant

Lung transplant (LTx) candidates may have both high and low body-mass index (BMI). We investigated the effects of BMI in lung transplantation outcome and survival. Patients from our center (Feb-2012 to Jul-2019) were divided into 5 BMI groups: <18.5, <25, <30, <35, ≥35 kg/m2 using WHO's nutritional standards. Using Cox proportional hazard regression, we examined any differences between these groups in age, gender, race, length of stay (LOS), lung allocation score (LAS), single, and double LTx type. Kaplan-Meier curve showed survival outcomes between the groups compared by Log-rank test. Data were presented as Mean ± Standard deviation and p<0.05 was considered significant. Out of 609 LTx recipients, etiology was 63.1% IPF, 24.3% COPD, and 12.6% others. Furthermore, 28.2% of patients were either underweight or normal weight, 36.9% were overweight, and 34.7% were obese as measured by BMI. Demographically, the patient population was 66% male, mean age 64±9, race 78% white 15% black, and 7% others, median LOS (17 days) and mean LAS 49±19. Kaplan-Meier graph (figure 1) showed no significant differences in 1,3,5 year survival among all the BMI groups (p=0.57). There were also no significant differences among all the groups with regard to LOS (p=0.91) and LAS (p=0.42). Despite larger numbers of overweight patients, there was no evidence of negative effect in survival outcome after LTx. Additionally, LOS and LAS did not have any effect in survival among five groups of BMI. This outcome suggests lung transplantation could be expanded to a wider variety of BMI patients.

Survival Outcomes of Lung Transplant Recipients from Donors with High Body Mass Index

Aim of this study is to assess lung utilization from donors with high Body Mass Index (BMI) and outcomes of lung transplant recipients from these donors. We reviewed United Network for Organ Sharing (UNOS) registry for first-time adult lung transplant recipients and donors from 06/2005 to 03/2017. Donors were stratified into 4 groups according to their BMI: normal 18.5-29.9, underweight <18.5, obese 30-34.9 and moderately/severely obese >35 kg/m2. Percentage lung utilization for each group was compared using Chi square test. Recipient survival was estimated with Kaplan-Meier curves and compared using multivariate Cox regression model. Of 20380 donors, 15765 (77.3%) donors had normal BMI, 916 (4.5%) were underweight, 2406 (11.8%) were obese and 1262 (6%) were moderately/severely obese. No significant difference was seen among 4 groups in terms of lung transplant survival (adjusted p=0.59, multivariate cox regression model, Figure 1). The 1, 3 and 5 year recipient survival rates were: 85.8 %, 68.9% and 55.1% in normal donor BMI group, 85.4%, 68.8% and 57.1% in underweight donor group, 86.3%, 67.6% and 56.0 % in the obese donor group and 86.7%, 67.1%, and 54.2 %in moderately/severely obese donor group, respectively. When donors with normal BMI were used as reference, the hazard ratio (95% confidence interval) for donors with obesity was 0.97 (0.88-1.07), donors with moderate/severe obesity was 1.03 (0.96-1.10) and for underweight donors was 1.05 (0.95-1.17). The lung utilization from donors with normal BMI was 31.1% and from donors with BMI >30 was 17% (p<0.0001). There is no significant difference in lung transplant recipient survival among the 4 donor BMI groups but there is lower organ utilization in the obese groups. Lungs from donors with high BMI should be considered more carefully before turning them down.

CF Lung Transplant Survival by Surrogate Markers for Socioeconomic Status

Studies have shown that markers of socioeconomic status (SES) such as education level and non-private insurance status associate with decreased medical adherence in patients with Cystic Fibrosis (CF), as well as increased CF mortality. Further, patients with lower SES are less likely to be referred for lung transplantation (Ltx) by their longitudinal providers. However, little is known about whether the presence of such factors is indeed associated with worse outcomes after Ltx. This study aims to evaluate the hypothesis that education and insurance status are associated with CF-patient survival following Ltx. We retrospectively reviewed the Scientific Registry of Transplant Recipients (SRTR) database for 2,697 adult CF LTx patients from 2005 through 2019. Patients were stratified by insurance status (private, Medicaid, Medicare, and other- including VA/CHIP), and educational attainment (grade school, high school, any college). All-cause mortality was examined with Cox proportional hazard regression (adjusted for age, sex, disease severity, center volume, and CMV mismatch), and the Kaplan-Meier method was used to model survival. Of 2,697 CF LTx recipients, 1,522 (56.4%) had private insurance; 410 (15.2%) had Medicaid; 666 (24.7%) had Medicare; and 97(3.6%) had other types. 20 (0.7%) patients had less than a high school education, 839 (31.1%) completed only high school, and 1,701 (63.1%) had any college or above. During the study period, there were 942 patient deaths (34.9%). Educational attainment of high school (or less) and non-private insurance status were strongly associated with lower survival rates at 2-years, 5 years, and 10 years. In multivariate analyses, non-private insurance and non-post-secondary education increased the risk of death with a hazard ratio 1.33 (95% CI 1.11 to 1.60, p=0.002) and 1.31(95% CI 1.08 to 1.59, p=0.006) respectively. This study represents the largest cohort with longest follow-up evaluating the effect of two separate SES surrogates on survival in CF LTx recipients. Improved survival associated with private insurance and post-secondary education. Further investigation must be taken to understand the nuanced social determinants of health affecting this observation.

Esophageal Motility Disorders Associated With Death or Allograft Dysfunction After Lung Transplantation? Results of a Retrospective Monocentric Study.

OBJECTIVES:Pathological gastroesophageal reflux (GER) is a known risk factor for bronchiolitis obliterans syndrome (BOS) after lung transplantation. This study aimed at determining whether functional esophageal evaluation might predict BOS occurrence and survival in this setting.METHODS:Ninety-three patients who underwent esophageal high-resolution manometry and 24-hour pH-impedance monitoring within the first year after lung transplantation were retrospectively included. A univariable analysis was performed to evaluate the parameters associated with GER disease and BOS occurrence. The Cox regression model was used to identify the prognostic factors of death or retransplantation.RESULTS:Thirteen percent of patients exhibited major esophageal motility disorders and 20% pathological GER. GER occurrence was associated with younger age, cystic fibrosis, and hypotensive esophagogastric junction. Within a median follow-up of 62 months, 10 patients (11%) developed BOS, and no predictive factors were identified. At the end of the follow-up, 10 patients died and 1 underwent retransplantation. The 5-year cumulative survival rate without retransplantation was lower in patients with major esophageal motility disorders compared with that in those without (75% vs 90%, P = 0.01) and in patients who developed BOS compared with that in those without (66% vs 91%; P = 0.005). However, in multivariable analysis, major esophageal motility disorders and BOS were no longer significant predictors of survival without retransplantation.DISCUSSION:Major esophageal motility disorders and BOS were associated with allograft survival in lung transplantation in the univariable analysis. Although the causes of this association remain to be determined, this observation confirms that esophageal motor dysfunction should be evaluated in the context of lung transplantation.

Prior and Perioperative Revascularization Does Not Affect Survival in Lung Transplant Patients

Coronary artery disease is common in lung transplant patients and has historically been viewed as a contraindication to the procedure. Although this mindset is changing, the effect of prior or perioperative revascularization on lung transplant survival outcomes is not adequately established. We performed a single-center retrospective analysis of all single and double lung transplant patients from 2012 to 2018 (n= 468). Patients were split into 4 groups: (1) patients who received a preoperative percutaneous coronary intervention (n= 34), (2) those who received coronary artery bypass grafting (CABG) before transplantation (n= 25), (3) those that received concomitant CABG during transplantation (n= 29), and (4) those who had lung transplantation with no need for revascularization (n= 380). Groups were compared for demographics, surgical procedure, and survival outcomes. The no-revascularization group was statistically younger than the rest (P= .001). The lung allocation score trended toward being higher in the concomitant coronary artery bypass group (P= .03). All groups were predominantly diagnosed with idiopathic pulmonary fibrosis. The proportion of patients with chronic obstructive pulmonary disease was greatest in the group not requiring revascularization (P= .001). Patients with previous CABG were more likely to receive a single lung transplant than a double one (21 versus 4; P= .054). Length of stay, posttransplant survival, and postoperative adverse events were similar among all groups. Results suggest that preoperative or intraoperative revascularization does not negatively affect survival in lung transplant patients; lung recipients with coronary artery disease have comparable survival when adequately revascularized.

Patient Travel Distance and Post Lung Transplant Survival in the United States: A Cohort Study.

In response to a longstanding Federal mandate to minimize the role of geography in access to transplant in the United States, we assessed whether patient travel distance was associated with lung transplant outcomes. We focused on the posttransplant time period, when the majority of patient visits to a transplant center occur. We present a cohort study of lung transplants in the United States between January 1, 2006, and May 31, 2017. Travel distance was measured from the patient's permanent home zip code to the transplant center using SAS URL access to GoogleMaps. We leveraged data from the US Census, US Department of Agriculture, and the Economic Innovations Group to assess socioeconomic status. Multivariable Cox models were used to assess graft survival. We included 18 128 patients who met the inclusion criteria. Median distance was 69.6 miles. Among patients who traveled >60 miles to reach a transplant center, 41.8% bypassed a closer center and sought care at a more distant center. Patients traveling longer distances sought care at centers with a higher annual transplant volume. In the adjusted Cox Model, patients who traveled >360 miles had a slightly higher risk for posttransplant graft failure than patients traveling ≤60 miles (hazard ratio 1.09; 95% CI, 1.01-1.18), and a higher risk for treated acute rejection (hazard ratio, 1.63; 95% CI, 1.43-1.86). Travel distance was significantly associated with post lung transplant survival. However, this effect was relatively modest. Patient travel distance is an important component of access to lung transplant care.

Variability in donor organ offer acceptance and lung transplantation survival

Lung transplantation offers a survival benefit for patients with end-stage lung disease. When suitable donors are identified, centers must accept or decline the offer for a matched candidate on their waitlist. The degree to which variability in per-center offer acceptance practices impacts candidate survival is not established. The purpose of this study was to determine the degree of variability in per-center rates of lung transplantation offer acceptance and to ascertain the associated contribution to observed differences in per-center waitlist mortality. We performed a retrospective cohort study of candidates waitlisted for lung transplantation in the US using registry data. Logistic regression was fit to assess the relationship of offer acceptance with donor, candidate, and geographic factors. Listing center was evaluated as a fixed effect to determine the adjusted per-center acceptance rate. Competing risks analysis employing the Fine-Gray model was undertaken to establish the relationship between adjusted per-center acceptance and waitlist mortality. Of 15,847 unique organ offers, 4,735 (29.9%) were accepted for first-ranked candidates. After adjustment for important covariates, transplant centers varied markedly in acceptance rate (9%-67%). Higher cumulative incidence of 1-year waitlist mortality was associated with lower acceptance rate. For every 10% increase in adjusted center acceptance rate, the risk of waitlist mortality decreased by 36.3% (sub-distribution hazard ratio 0.637; 95% confidence interval 0.592-0.685). Variability in center-level behavior represents a modifiable risk factor for waitlist mortality in lung transplantation. Further intervention is needed to standardize center-level offer acceptance practices and minimize waitlist mortality.

Donor surfactant protein A2 polymorphism and lung transplant survival

Gene polymorphisms of surfactant proteins, key players in lung innate immunity, have been associated with various lung diseases. The aim of this study was to investigate the potential association between variations within the surfactant protein (SP)-A gene of the donor lung allograft and recipient post-transplant outcome. Lung-transplant patients (n=192) were prospectively followed-up with pulmonary function tests, bronchoscopies with bronchoalveolar lavage and biopsies. Donor lungs were assayed for SP-A1 (6An) and SP-A2 (1An) gene polymorphism using the pyrosequencing method. Unadjusted and adjusted stratified Cox survival models are reported. SP-A1 and SP-A2 genotype frequency and lung transplant recipient and donor characteristics as well as cause of death are noted. Recipients were grouped per donor SP-A2 variants. Individuals that received lungs from donors with the SP-A2 1A0 (n=102) versus 1A1 variant (n=68) or SP-A2 genotype 1A01A0 (n=54) versus 1A0A1 (n=38) had greater survival at 1 year (log-rank p<0.025). No significant association was noted for SP-A1 variants. Stratified adjusted survival models for 1-year survival and diagnosis showed a reduced survival for 1A1 variant and the 1A01A1 genotype. Furthermore, when survival was conditional on 1-year survival no significance was observed, indicating that the survival difference was due to the first year's outcome associated with the 1A1 variant. Donor lung SP-A gene polymorphisms are associated with post-transplant clinical outcome. Lungs from donors with the SP-A2 variant 1A1 had a reduced survival at 1 year. The observed donor genetic differences, via innate immunity relate to the post-transplant clinical outcome.