The Impact of Donor Smoking on Primary Graft Dysfunction and Mortality after Lung Transplantation.

Rationale: Primary graft dysfunction (PGD) is the leading cause of early morbidity and mortality after lung transplantation. Prior studies implicated proxy-defined donor smoking as a risk factor for PGD and mortality. Objectives: We aimed to more accurately assess the impact of donor smoke exposure on PGD and mortality using quantitative smoke exposure biomarkers. Methods: We performed a multicenter prospective cohort study of lung transplant recipients enrolled in the Lung Transplant Outcomes Group cohort between 2012 and 2018. PGD was defined as grade 3 at 48 or 72 hours after lung reperfusion. Donor smoking was defined using accepted thresholds of urinary biomarkers of nicotine exposure (cotinine) and tobacco-specific nitrosamine (4-[methylnitrosamino]-1-[3-pyridyl]-1-butanol [NNAL]) in addition to clinical history. The donor smoking-PGD association was assessed using logistic regression, and survival analysis was performed using inverse probability of exposure weighting according to smoking category. Measurements and Main Results: Active donor smoking prevalence varied by definition, with 34-43% based on urinary cotinine, 28% by urinary NNAL, and 37% by clinical documentation. The standardized risk of PGD associated with active donor smoking was higher across all definitions, with an absolute risk increase of 11.5% (95% confidence interval [CI], 3.8% to 19.2%) by urinary cotinine, 5.7% (95% CI, -3.4% to 14.9%) by urinary NNAL, and 6.5% (95% CI, -2.8% to 15.8%) defined clinically. Donor smoking was not associated with differential post-lung transplant survival using any definition. Conclusions: Donor smoking associates with a modest increase in PGD risk but not with increased recipient mortality. Use of lungs from smokers is likely safe and may increase lung donor availability. Clinical trial registered with www.clinicaltrials.gov (NCT00552357).

Impact of simultaneous heart procurement on outcomes of donation after circulatory death lung transplantation.

Donation after circulatory death (DCD) heart procurement is done using either direct procurement (DP) or thoracoabdominal normothermic machine perfusion (TA-NRP). Both approaches could impact lung transplant outcomes with combined heart and lung procurements from the same donor. The impact of such practice on DCD lung transplant remains unstudied. We performed a retrospective analysis using the United Network for Organ Sharing (UNOS) dataset, identifying DCD lung transplants where the donor also donated the heart (cardia lung donor [CD]). A cohort of noncardiac DCD lung donors (noncardiac lung donor [NCD]) from the same era, matched for donor and recipient characteristics, was used as a comparison group. Both immediate and long-term outcomes were examined. A subanalysis was performed comparing the distinct impact of DP or TA-NRP on DCD lung transplant outcomes. Overall graft survival did not significantly differ between CD and NCD. However, recipients in the CD group trended toward a lower P/F ratio at 72 hours (CD vs NCD: 284 vs 3190; P = .054). In the subanalysis, we identified 40 DP donors and 22 TA-NRP donors. We found the both cohorts had lower P/F ratio at 72 hours than the NCD control (P = .04). Overall, 1-year graft survival was equivalent among the TA-NRP, DP, and NCD cohorts.

Validation of a novel donor lung scoring system based on the updated lung Composite Allocation Score.

Lung transplantation (LTx) continues to have lower rates of long-term graft survival compared with other organs. Additionally, lung utilization rates from brain-dead donors remain substantially lower compared with other solid organs, despite a growing need for LTx and the significant risk of waitlist mortality. This study aims to examine the effects of using a combination of the recently described novel lung donor (LUNDON) acceptability score and the newly adopted recipient lung Composite Allocation Score (CAS) to guide transplantation. We performed a review of nearly 18 000 adult primary lung transplants from 2015-2022 across the US with retroactive calculations of the CAS value. The medium-CAS group (29.6-34.5) had superior 1-year posttransplant survival. Importantly, the combination of high-CAS (> 34.5) recipients with low LUNDON score (≤ 40) donors had the worst survival at 1 year compared with any other combination. Additionally, we constructed a model that predicts 1-year and 3-year survival using the LUNDON acceptability score and CAS values. These results suggest that caution should be exercised when using marginally acceptable donor lungs in high-priority recipients. The use of the LUNDON score with CAS value can potentially guide clinical decision-making for optimal donor-recipient matches for LTx.

A Multi-Center International Analysis of Lung Transplantation Outcomes in Patients With COVID-19.

INTRODUCTION: Lung transplantation has become increasingly utilized in patients with COVID-19. While several single-center and UNOS database studies have been published on lung transplants (LTs) for end-stage lung disease (ESLD) from Coronavirus disease 2019 (COVID-19), there is a lack of multi-center and international data. METHODS: This is a multicenter analysis from 11 high-volume lung transplant centers in the United States and Europe. Data were collected through the Multi-Institutional ECLS Registry and stratified by ESLD due to COVID-19 versus other etiologies. Demographics and clinical variables were compared using Chi-square test and Fisher's exact test. Survival was assessed by Kaplan-Meier curves and compared by log-rank test with propensity score matching. RESULTS: Of 1606 lung transplant recipients, 46 (2.9%) were transplanted for ESLD from COVID-19 compared to 1560 (97.1%) without a history of COVID-19. Among COVID-19 patients, 30 (65.2%) had COVID-19-associated ARDS and 16 (34.8%) had post-COVID-19 fibrosis. COVID-19 patients had higher lung allocation scores (78.0 vs. 44.4, p < 0.0001), had severely limited functional status (37.0% vs. 2.9%, p < 0.0001), had higher preoperative ECMO usage (65.2% vs. 5.4%, p < 0.0001), and spent less time on the waitlist (32 vs. 137 days, p < 0.0001). A 30-day survival was comparable between COVID-19 and non-COVID-19 patients before (100% vs. 98.7%, p = 0.39) and after propensity matching (p = 0.15). CONCLUSIONS: Patients who received LTs due to COVID-19 had short-term survival comparable to that of patients without COVID-19. Our findings support the idea that lung transplantation should be considered for select patients with ESLD due to COVID-19.

Addressing sex-based disparities in solid organ transplantation in the United States - a conference report.

Solid organ transplantation provides the best treatment for end-stage organ failure, but significant sex-based disparities in transplant access exist. On June 25, 2021, a virtual multidisciplinary conference was convened to address sex-based disparities in transplantation. Common themes contributing to sex-based disparities were noted across kidney, liver, heart, and lung transplantation, specifically the existence of barriers to referral and wait listing for women, the pitfalls of using serum creatinine, the issue of donor/recipient size mismatch, approaches to frailty and a higher prevalence of allosensitization among women. In addition, actionable solutions to improve access to transplantation were identified, including alterations to the current allocation system, surgical interventions on donor organs, and the incorporation of objective frailty metrics into the evaluation process. Key knowledge gaps and high-priority areas for future investigation were also discussed.

Textbook Outcome: Definition and Analysis of a Novel Quality Measure in Lung Transplantation.

OBJECTIVE: To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. SUMMARY BACKGROUND DATA: TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. METHODS: Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. RESULTS: Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.

Utilization Trends and Volume-outcomes Relationship of Endoscopic Resection for Early Stage Esophageal Cancer.

OBJECTIVES: We describe utilization trends and center volume-outcomes relationship of ER of early stage esophageal cancer using a large hospitalbased registry. SUMMARY OF BACKGROUND DATA: ER is increasingly accepted as the preferred treatment for early stage esophageal cancer, however its utilization and the center volume-outcomes relationship in the United States is unknown. METHODS: The National Cancer Database was used to identify patients with cT1N0M0 esophageal cancer treated with ER or esophagectomy between 2004 and 2015. Relative frequencies were plotted over time. Restricted cubic splines and maximally selected rank statistics were used to identify an inflection point of center volume and survival. RESULTS: A total of 1136 patients underwent ER and 2829 patients underwent esophagectomy during the study period. Overall utilization of ER, and relative use compared to esophagectomy, increased throughout the study period. Median annualized center ER volume was 1.9 cases per year (interquartile range 0.5-5.8). Multivariable Cox regression showed increasing annualized center volume by 1 case per year was associated with improved survival. Postoperative 30- or 90-day mortality, 30-day readmission, and pathologic T upstaging rates were similar irrespective of center volume. CONCLUSIONS: Utilization of ER compared to esophagectomy for stage I esophageal cancer has increased over the past decade, though many individual centers perform fewer than 1 case annually. increasing annualized center volume by one procedure per year was associated with improved survival. increased volume beyond this was not associated with survival benefit. Referral to higher volume centers for treatment of superficial esophageal cancer should be considered.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: An Analysis of 5721 Cases.

OBJECTIVE: The aim of this study was to analyze outcomes of open lobectomy (OL), VATS, and robotic-assisted lobectomy (RL). SUMMARY BACKGROUND DATA: Robotic-assisted lobectomy has seen increasing adoption for treatment of early-stage lung cancer. Comparative data regarding these approaches is largely from single-institution case series or administrative datasets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. All consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Neoadjuvant cases were excluded. Propensity-score matching (1:1) was based on age, sex, race, smoking-status, FEV1%, Zubrod score, American Society of Anesthesiologists score, tumor size, and clinical T and N stage. RESULTS: A total of 2391 RL, 2174 VATS, and 1156 OL cases were included. After propensity-score matching there were 885 pairs of RL vs OL, 1,711 pairs of RL vs VATS, and 952 pairs of VATS vs OL. Operative time for RL was shorter than VATS ( P < 0.0001) and OL ( P = 0.0004). Compared to OL, RL and VATS had less overall postoperative complications, shorter hospital stay (LOS), and lower transfusion rates (all P <0.02). Compared to VATS, RL had lower conversion rate ( P <0.0001), shorter hospital stay ( P <0.0001) and a lower postoperative transfusion rate ( P =0.01). RL and VATS cohorts had comparable postoperative complication rates. In-hospital mortality was comparable between all groups. CONCLUSIONS: RL and VATS approaches were associated with favorable perioperative outcomes compared to OL. Robotic-assisted lobectomy was also associated with a reduced length of stay and decreased conversion rate when compared to VATS.

Pulmonary Open, Robotic, and Thoracoscopic Lobectomy (PORTaL) Study: Survival Analysis of 6646 Cases.

OBJECTIVE: The aim of this study was to analyze overall survival (OS) of robotic-assisted lobectomy (RL), video-assisted thoracoscopic lobectomy (VATS), and open lobectomy (OL) performed by experienced thoracic surgeons across multiple institutions. SUMMARY BACKGROUND DATA: Surgeons have increasingly adopted RL for resection of early-stage lung cancer. Comparative survival data following these approaches is largely from single-institution case series or administrative data sets. METHODS: Retrospective data was collected from 21 institutions from 2013 to 2019. Consecutive cases performed for clinical stage IA-IIIA lung cancer were included. Induction therapy patients were excluded. The propensity-score method of inverse-probability of treatment weighting was used to balance baseline characteristics. OS was estimated using the Kaplan-Meier method. Multivariable Cox proportional hazard models were used to evaluate association among OS and relevant risk factors. RESULTS: A total of 2789 RL, 2661 VATS, and 1196 OL cases were included. The unadjusted 5-year OS rate was highest for OL (84%) followed by RL (81%) and VATS (74%); P =0.008. Similar trends were also observed after inverse-probability of treatment weighting adjustment (RL 81%; VATS 73%, OL 85%, P =0.001). Multivariable Cox regression analyses revealed that OL and RL were associated with significantly higher OS compared with VATS (OL vs. VATS: hazard ratio=0.64, P <0.001 and RL vs. VATS: hazard ratio=0.79; P =0.007). CONCLUSIONS: Our finding from this large multicenter study suggests that patients undergoing RL and OL have statistically similar OS, while the VATS group was associated with shorter OS. Further studies with longer follow-up are necessary to help evaluate these observations.

Acid exposure time is sensitive for detecting gastroesophageal reflux disease and is associated with long-term survival after lung transplant.

Gastroesophageal reflux disease (GERD) is common in patients who have undergone lung transplantation and is associated with poorer outcomes, but guidelines are lacking to direct management strategies in this population. We assessed the diagnostic yield of impedance metrics compared to pH-metry alone for detecting GERD among lung transplant recipients and evaluated their association with clinical outcomes. We performed a retrospective cohort study of consecutive patients who underwent lung transplantation. Demographic data, acid exposure time (AET), number of reflux episodes, mean nocturnal baseline impedance (MNBI), post-reflux swallowing-induced peristaltic wave index (PSPWI), and clinical outcomes including mortality were collected. The relationship between GERD metrics and clinical outcomes was assessed using Wilcoxon signed-rank test and Fisher's exact test as appropriate. Of the 76 patients studied, 29 (38%) had GERD based on abnormal AET after lung transplantation. One (1.3%) patient had GERD based on elevated number of reflux episodes and abnormal distal MNBI detected GERD in 19 (26%) patients, resulting in 62% sensitivity and 94% specificity. Two (2.6%) patients had normal PSPWI. Patients with low distal MNBI had significantly decreased forced expiratory volume in 1 second (FEV1) at 3-year posttransplant compared to those without low distal MNBI (P = 0.03). Three-year survival was significantly worse among patients with elevated AET (66.7% vs. 89.1%, P = 0.03) but not with low distal MNBI (68.4% vs. 84.3%, P = 0.18). Abnormal AET is more sensitive for detecting GERD than other reflux metrics studied and is associated with survival, suggesting pH-metry alone may be sufficient to guide GERD management after lung transplant.