Lung Allocation Research Articles

Overly Selective Offer Acceptance is Associated With High Waitlist Mortality for the Most Ill Lung Transplant Candidates

The demand for organs for lung transplantation (LTx) continues to outweigh supply. However, nearly 75% of donor lungs are never transplanted. LTx offer acceptance practices and the effects on waitlist/post-transplant outcomes by candidate clinical acuity are understudied. UNOS was used to identify all LTx candidates, donors, and offers from 2005 to 2019. Candidates were grouped by Lung Allocation Score (LAS; applicable post-2005, ages ≥12 years): LAS<40, 40-60, 61-80, and >80. Offer acceptance patterns, waitlist death/decompensation, and post-transplant survival (PTS) were compared. "Acceptable organ offers" were those from donors whose organs were accepted for transplantation. Approximately 3 million offers to 34,531 candidates were reviewed. Median waitlist durations were: 9 days-(LAS>80), 17 days-(LAS 61-80), 42 days-(LAS 40-60), 125 days-(LAS<40) (P < 0.001 between all). Per waitlist-day, offer rates were: total offers - 0.8/day-(LAS>80), 0.7/day-(LAS 61-80), 0.6/day-(LAS 40-60), 0.4/day-(LAS<40); acceptable offers - 0.34/day-(LAS>80), 0.32/day-(LAS 61-80), 0.24/day-(LAS 40-60), 0.15/day-(LAS<40) (both P < 0.001 between all LAS). Among patients who experienced waitlist mortality/decompensation, ≥1 acceptable offer was declined in 92% (3939/4270) of patients - 78% for LAS >80, 88% for LAS 61-80, 93% for LAS 40-60, and 96% for LAS <40. Thirty-day waitlist mortality/decompensation rates were: 46%-(LAS>80), 24%-(LAS 61-80), 5%-(LAS 40-60), <1%-(LAS<40) (P < 0.001 between all). PTS was equivalent between patients for whom the first/second offer vs later offers were accepted (all LAS P > 0.4). The first offers that LTx candidates receive (including acceptable organs) are declined for nearly all candidates. Healthier candidates can afford offer selectivity but more ill patients (LAS>60) cannot, experiencing exceedingly high 30-day waitlist mortality.

Prolonged Ischemia Increases Complications Among High- and Low-Volume Centers in Lung Transplantation

BackgroundThe effect of prolonged allograft ischemic time on lung transplant outcomes remains controversial, with most studies associating it with increased mortality, but this effect is partly mitigated by center volume. This study sought to evaluate the mechanism of these findings and clarify the impact of ischemic time on short-term outcomes in a national sample. MethodsData on lung transplants (January 2010-Janary 2017) were extracted from the Scientific Registry of Transplant Recipients database. Ischemic time was dichotomized as prolonged ischemic time (PIT) or no PIT (N-PIT) at 6 hours. High-volume centers were defined as the top quintile. The primary outcome was 30-day, 1-year, and 3-year mortality; secondary outcomes included in-hospital complications and 72-hour oxygenation. ResultsAmong 11,809 records, there were significant differences between PIT and N-PIT recipients by demographics, lung allocation score, and donor organ metrics. In a 1:1 propensity score–matched cohort (n = 6422), PIT recipients had reduced survival compared with N-PIT at 3 years (66.5% vs 68.8%, P = .031). On multivariable analysis, this effect persisted among low-volume but not high-volume centers. PIT recipients were more likely to require reintubation, prolonged (>5 days) mechanical ventilation, hemodialysis, longer stay, and acute rejection (all P < .01). Except for reintubation, these disparities were present at both high- and low-volume centers independently. Ischemic time had no effect on 72-hour oxygenation. ConclusionsPIT remains associated with higher rates of postoperative complications and reduced short-term survival. While center volume ameliorated the survival impact, this was not achieved by reducing postoperative complications. Further research is warranted before broadening ischemic time thresholds among low-volume centers.

Trends, Outcomes, and Predictors of Acute In-hospital Stroke after Lung Transplantation: An Analysis of the United Network for Organ Sharing Database

INTRODUCTION: Lung transplantation is the gold standard treatment for end-stage lung failure. We sought to characterize the impact of strokes on mortality and identify factors which were associated with stroke. METHODS: We identified adult (≥18 years old) first-time, isolated lung transplant (LTx) recipients from the United Network for Organ Sharing database between 5/2005 and 12/2020. Stroke was defined as occurring at any time after LTx but prior to discharge. Cox proportional hazards analysis was used to identify predictors of death at 24 months. Freedom from death in stroke vs non-stroke was evaluated with Kaplan-Meier analysis. Multivariable logistic regression was used to identify risk factors for stroke. RESULTS: Of 28,564 patients (median age = 60, 60% male), 653 (2.3%) experienced an acute in-hospital stroke after LTx. Median follow-up was 1.2 (stroke) and 3.0 years (non-stroke). Annual incidence of stroke increased (1.5% in 2005 to 2.4% in 2020, p-trend = 0.007), as did lung allocation score (LAS) and utilization of post-LTx extracorporeal membrane oxygenation (postLTX-ECMO) (p = 0.01 and p < 0.001, respectively). Those with stroke had lower survival at 1-month (84% vs 98%) and 12-months (61% vs 88%) compared to those without (p < 0.001; Figure). In Cox analysis, stroke had the highest hazard of death (HR = 3.05, 95% CI = 2.70-3.44). PostLTx-ECMO was the strongest risk factor of stroke (adjusted odds ratio = 2.76, 95% CI = 2.07-3.68).FigureCONCLUSION: Strokes after LTx have increased over time; this likely corresponds to the transplantation of patients with increasingly higher LAS. Strokes were associated with significant short- and long-term mortality in patients after LTx and postLTx-ECMO was a strong risk factor.

A Matched Survival Analysis of Lung Transplant Recipients With Coronavirus Disease 2019–Related Respiratory Failure

BackgroundLung transplantation is an acceptable and potentially life-saving treatment option for coronavirus disease 2019 (COVID-19)–induced acute respiratory distress syndrome and pulmonary fibrosis. This study was conducted to determine whether recipients of lung transplantation (LT) for COVID-19–related lung disease have comparable outcomes to other recipients with a similar level of lung dysfunction. MethodsThe Organ Procurement and Transplant Network database was queried for adult LT candidates between 2006 and 2021. Recipients with COVID-19–related respiratory failure were matched 1:2 using a nearest-neighbor algorithm. Kaplan-Meier methods with log-rank tests were used to compare long-term survival. A proportional hazards model was used to calculate risk of death. ResultsA total of 37,333 LT candidates from all causes were compared with 334 candidates from COVID-19–related respiratory failure. COVID-19 recipients were more likely to be younger (50 vs 57 years, P < .001), male (79% vs 60%, P < .001), require extracorporeal membrane oxygenation (56.3% vs 4.0%, P < .001), and have worse lung function (lung allocation score, 82.4 vs 47.8; P < .001) at transplantation. Subsequently, 227 COVID-19 recipients were matched with 454 controls. Patients who received a transplant for COVID-19 had similar rates of mechanical ventilation, extracorporeal membrane oxygenation, postoperative complications, and functional status at discharge compared with controls. There was no difference in overall survival or risk of death from COVID-19 (hazard ratio, 0.82; 95% CI, 0.45-1.53; P = .54). ConclusionsSix-month survival for recipients of LT for COVID-19–related respiratory failure was comparable to that of other LT recipients.

Predictors of lung transplant waitlist mortality for sarcoidosis

RationaleUnlike in other chronic lung diseases, criteria for lung transplant referral in sarcoidosis is not well-established. Waitlist mortality may offer clues in identifying clinical factors that warrant early referral. We aim to identify predictors for transplant waitlist mortality to improve referral criteria for patients with sarcoidosis. MethodsWe conducted a retrospective analysis of 1034 sarcoidosis patients listed for lung transplantation from May 2005 to May 2019 in the Scientific Registry of Transplant Recipients (SRTR) database. All patients were listed after the establishment of the Lung Allocation Score (LAS). We compared patients who died on the transplant waitlist to those who survived to transplantation. Potential predictors of waitlist mortality were assessed utilizing univariate and multivariate analysis performed via logistic regression modeling. ResultsOf 1034 candidates listed after LAS implementation, 704 were transplanted and 110 died on the waitlist. Significant predictors of waitlist mortality on multivariate analysis include female gender (OR 2.445; 95% CI 1.513–3.951; p = 0.0003) and severe pulmonary hypertension (OR 1.619; 95% CI 1.067–2.457; p = 0.0236). Taller minimum donor height (OR 0.606; 95% CI 0.379–0.969; p = 0.0365) and blood type B (OR 0.524; 95% CI 0.281–0.975 p = 0.0415) were associated with decreased likelihood of death on the waitlist. ConclusionAmong patients with sarcoidosis on the lung transplant waitlist, taller minimum donor height and blood type B were found to be protective factors against death on the waitlist. Female gender and severe pulmonary hypertension have a higher likelihood of death and earlier referral for transplantation in patients with these characteristics should be considered.

NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

NINTEDANIB CESSATION IN WAITLISTED LUNG TRANSPLANT CANDIDATES IS NOT ASSOCIATED WITH INCREASED WAITLIST MORTALITY OR PERIOPERATIVE COMPLICATIONS

The Lung Allocation Score Remains Inequitable for Patients with Pulmonary Arterial Hypertension, Even after the 2015 Revision.

Rationale: The lung allocation score (LAS) was revised in 2015 to improve waiting list mortality and rate of transplant for patients with pulmonary arterial hypertension (PAH). Objectives: We sought to determine if the 2015 revision achieved its intended goals. Methods: Using the Standard Transplant Analysis and Research file, we assessed the impact of the 2015 LAS revision by comparing the pre- and postrevision eras. Registrants were divided into the LAS diagnostic categories: group A-chronic obstructive pulmonary disease; group B-pulmonary arterial hypertension; group C-cystic fibrosis; and group D-interstitial lung disease. Competing risk regressions were used to assess the two mutually exclusive competing risks of waiting list death and transplant. Cumulative incidence plots were created to visually inspect risks. Measurements and Main Results: The LAS at organ matching increased by 14.2 points for registrants with PAH after the 2015 LAS revision, the greatest increase among diagnostic categories (other LAS categories: Δ, -0.9 to +2.8 points). Before the revision, registrants with PAH had the highest risk of death and lowest likelihood of transplant. After the 2015 revision, registrants with PAH still had the highest risk of death, now similar to those with interstitial lung disease, and the lowest rate of transplant, now similar to those with chronic obstructive pulmonary disease. Conclusions: Although the 2015 LAS revision improved access to transplant and reduced the risk of waitlist death for patients with PAH, it did not go far enough. Significant differences in waitlist mortality and likelihood of transplant persist.

Trends in use and three-year outcomes of hepatitis C virus–viremic donor lung transplants for hepatitis C virus–seronegative recipients

ObjectiveThe feasibility and 6-month outcome safety of lung transplants (LTs) from hepatitis C virus (HCV)-viremic donors for HCV-seronegative recipients (R–) were established in 2019, but longer-term safety and uptake of this practice nationally remain unknown. MethodsWe identified HCV-seronegative LT recipients (R–) 2015-2020 using the Scientific Registry of Transplant Recipients. We classified donors as seronegative (D–) or viremic (D+). We used χ2 testing, rank-sum testing, and Cox regression to compare posttransplant outcomes between HCV D+/R– and D–/R– LT recipients. ResultsHCV D+/R– LT increased from 2 to 97/year; centers performing HCV D+/R– LT increased from 1 to 25. HCV D+/R– versus HCV D–/R– LT recipients had more obstructive disease (35.7% vs 23.3%, P < .001), lower lung allocation score (36.5 vs 41.1, P < .001), and longer waitlist time (P = .002). HCV D+/R– LT had similar risk of acute rejection (adjusted odds ratio [aOR], 0.87; P = .58), extracorporeal membranous oxygenation (aOR, 1.94; P = .10), and tracheostomy (aOR, 0.42; P = .16); similar median hospital stay (P = .07); and lower risk of ventilator > 48 hours (aOR, 0.68; P = .006). Adjusting for donor, recipient, and transplant characteristics, risk of all-cause graft failure and mortality were similar at 30 days, 1 year, and 3 years for HCV D+/R– versus HCV D–/R– LT (all P > .1), as well as for high- (≥20/year) versus low-volume LT centers and high- (≥5/year) versus low-volume HCV D+/R– LT centers (all P > .5). ConclusionsHCV D+/R– and HCV D–/R– LT have similar outcomes at 3 years posttransplant. These results underscore the safety of HCV D+/R– LT and the potential benefit of expanding this practice further.

Acute Interstitial Pneumonia (Hamman–Rich Syndrome) in Lung Transplantation: A Case Series

BackgroundAcute interstitial pneumonia (AIP), also known as Hamman–Rich syndrome, is a rare and rapidly progressive idiopathic interstitial lung disease with a high mortality rate. Treatment is limited to supportive care and empirical high-dose steroids; however, outcomes are generally poor. There are few reports of lung transplantation (LTx) in patients with AIP. MethodsWe retrospectively identified patients with AIP among those who underwent LTx at our center between January 2008 and December 2020. ResultsDuring the study period, 4 patients with AIP underwent bilateral LTx: 3 men and 1 woman, between 30 and 57 years of age. The lung allocation score ranged between 71 and 89. Of the 4 patients, 2 needed extracorporeal membrane oxygenation and mechanical ventilation (MV) and 1 needed MV preoperatively. Time of onset to transplant ranged from 1 to 3 months. None of the patients had primary graft dysfunction after LTx; 2 had acute cellular rejection and 1 had chronic lung allograft dysfunction. The 4 patients are alive with survival ranging between 1 and 12 years after LTx. ConclusionAIP should be considered in patients with acute respiratory failure without a clear etiology. Our study showed that LTx led to good outcomes and should be considered as a treatment option in appropriate candidates.

Experience with intraoperative extracorporeal membrane oxygenation in lung transplantation: intraoperative indicators

Background/Aim: Intraoperative extracorporeal membrane oxygenation (ECMO) is being used with increasing frequency in lung transplantation. However, the factors associated with the use of intraoperative ECMO in lung transplant patients are not yet conclusive. In this study, we aimed to determine the effective factors for providing intraoperative ECMO support in patients undergoing lung transplantation. In addition, we aimed to evaluate the effect of ECMO support on morbidity and mortality. Methods: In this retrospective cohort study evaluating lung transplant patients, patients were divided into two groups: those who received intraoperative ECMO support and those who did not. Demographic data, the lung allocation score (LAS) and pulmonary arterial pressure (PAP), intraoperative data, postoperative complications, duration of mechanical ventilation (MV), length of stay (LOS) in intensive care and hospital, and mortality rates were recorded for both groups. Factors affecting entry to ECMO were analyzed by Multivariate Logistic Regression. Results: In this period, 51.9% of 87 patients who underwent lung transplantation required intraoperative ECMO. The mean age, LAS, and PAP of the ECMO group were significantly higher than the non-ECMO group (P = 0.043, P = 0.007, and P = 0.007, respectively). In multivariate analysis, it was found that lower MAP averages were a predictive parameter in intraoperative ECMO requirements (OR: 1.091; CI: 1.009-1.179; P = 0.028). The ECMO group’s mechanical ventilation time and hospital mortality were significantly higher than the other group (P = 0.004 and P = 0.025, respectively). Conclusion: Preoperative indicators of intraoperative ECMO support were determined as age, LAS, and PAP elevation. In addition, low MAP levels and high lactate levels were always determined as intraoperative indicators in lung transplantation until the transition to ECMO support.

A Conceptual Model for Sources of Differential Selection in Lung Transplant Allocation.

Rationale: In the United States, donor lungs are allocated to transplant candidates on the basis of lung allocation scores (LAS). However, additional factors beyond the LAS can impact who is transplanted, including listing and donor-organ acceptance practices. These factors can result in differential selection, undermining the objectivity of lung allocation. Yet their impact on the lung transplant pathway has been underexplored. Objectives: We sought to systematically examine sources of differential selection in lung transplantation via qualitative methods. Methods: We conducted semistructured qualitative interviews with lung transplant surgeons and pulmonologists in the United States between June 2019 and June 2020 to understand clinician perspectives on differential selection in lung transplantation and the LAS. Results: A total of 51 respondents (30 surgeons and 21 pulmonologists) identified many sources of differential selection arising throughout the pathway from referral to transplantation. We synthesized these sources into a conceptual model with fivethemes: 1) transplant center's degree of risk tolerance andaccountability; 2) successfulness and fairness of the LAS; 3)donor-organ availability and regional competition; 4)patient health versus program health; and 5) access to care versus responsible stewardship of organs. Conclusions: Our conceptual model demonstrates how differential selection can arise throughout lung transplantation and facilitates the further study of such selection. As new organ allocation models are developed, differential selection should be considered carefully to ensure that these models are more equitable.

Increased Risk Donors Utilized in Lung Transplantation At A Single Center.

Introduction: In 2013, the US Public Health Service (PHS) updated guidelines for high-risk donor organs and renamed the category increased risk. Project Aims: We compared survival of patients who received increased risk or non-increased risk donor lungs to determine if PHS designated increased risk donor lungs were an underutilized resource. Design: This retrospective cohort analysis compared survival and utilization rates of increased-risk and non-increased-risk donor lungs used in lung transplantation at a single institution over a period of 8 years (Feb-2012 through Mar-2020). Survival was assessed using Kaplan-Meier analysis and compared by log-rank test. Cox proportional hazards modeling was used to analyze impact on survival of variables significantly associated with risk status, including recipient ethnicity, lung allocation score (LAS), donor age, year of transplant procedure, and lung transplant type. Results: Of 744 lung transplant recipients from February 2012 through March 2020, there were 192 (26%) recipients of increased risk designated lungs. In 2012 and 2013, 6% and 0% respectively of the lungs transplanted were increased risk labeled. After the PHS guidelines were nationally implemented in February 2014, the proportion of increased risk lung transplants rose to 7% (2014), 21% (2015), 27% (2016), 35% (2017), 28% (2018), 27% (2019), and 40% (January-March 2020). Kaplan-Meier analysis and log-rank test comparison showed no significant difference in survival between patients that received increased risk versus non-increased risk labeled lungs (P = 0.47). Conclusions: Our analysis suggested the 2013 PHS increased risk designation threatened underutilization of viable donor lungs, providing further support for the 2020 PHS changes.

Refining the Lung Allocation Score Models Fails to Improve Discrimination Performance

As broader geographic sharing is implemented in lung transplant allocation through the Composite Allocation Score (CAS) system, models predicting waitlist and posttransplant (PT) survival will become more important in determining access to organs. How well do CAS survival models perform, and can discrimination performance be improved with alternative statistical models or machine learning approaches? Scientific Registry for Transplant Recipients (SRTR) data from 2015-2020 were used to build seven waitlist (WL) and data from 2010-2020 to build similar PT models. These included the (I) current lung allocation score (LAS)/CAS model; (II) re-estimated WL-LAS/CAS model; (III) model II incorporating nonlinear relationships; (IV) random survival forests model; (V) logistic model; (VI) linear discriminant analysis; and (VII) gradient-boosted tree model. Discrimination performance was evaluated at 1, 3, and 6months on the waiting list and 1, 3, and 5 years PT. Area under the curve (AUC) values were estimated across subgroups. WL model performance was similar across models with the greatest discrimination in the baseline cohort (AUC 0.93) and declined to 0.87-0.89 for 3-month and 0.84-0.85 for 6-month predictions and further diminished for residual cohorts. Discrimination performance for PT models ranged from AUC 0.58-0.61 and remained stable with increasing forecasting times but was slightly worse for residual cohorts. WL and PT variability in AUC was greatest for individuals with Medicaid insurance. Use of alternative modeling strategies and contemporary cohorts did not improve performance of models determining access to lung transplant.

Lung Transplantation for COVID-19-related Lung Disease: Clinical Experience and Call for a Global Registry.

Lung Transplantation for COVID-19-related Lung Disease: Clinical Experience and Call for a Global Registry.

Donor and Recipient Hepatitis C Status Does Not Affect Rejection in Thoracic Transplantation

BackgroundDonors with hepatitis C virus (HCV) have expanded the donor pool for heart and lung transplantation, but concerns have arisen about rejection. We examined the incidence of rejection after heart and lung transplantation in recipients of HCV-positive donors as well as HCV-positive recipients. MethodsAdults undergoing heart and lung transplantation from March 31, 2015 to December 31, 2019 were identified in the United Network for Organ Sharing/Organ Transplantation and Procurement Network Standard Transplant Analysis and Research file. Patients were stratified as donor–recipient HCV negative, donor positive, and recipient positive. Comparative statistics and a multilevel logistic regression model were used. ResultsMeeting the criteria were 10 624 heart transplant recipients. Donor-positive recipients were significantly associated with older age, blood group O, and shorter waitlist time. No significant differences existed with regards to treatment for rejection in the first year (negative, 19.5%; donor positive, 22.3%; recipient positive, 19.5%; P = .45) or other outcomes. On regression analysis HCV status was not associated with treated rejection; however center variability was significantly associated with treated rejection (median odds ratio, 2.18). Similarly, 9917 lung transplant recipients were identified. Donor-positive recipients were more commonly White and had obstructive disease and lower lung allocation scores. Both unadjusted (negative, 22.1%; donor positive, 23.0%; recipient positive, 18.6%; P = .43) and adjusted analyses failed to demonstrate a significant association between HCV status and treatment for rejection, whereas center variability remained significantly associated with treatment for rejection (median odds ratio, 2.41). ConclusionsUse of HCV donors has expanded the donor pool for heart and lung transplantation. HCV donor status was not associated with treatment for rejection in the first year, but center variability played a role in the incidence and treatment of rejection.

Allocation of Donor Lungs in Korea

The expansion of indications for lung transplantation, the growth of the waiting list, and donor shortages are increasing the waiting list mortality rate in Korea. The current lung allocation system in Korea is based mainly on urgency, but outcomes should also be considered to avoid futile transplantation. This review describes the current status of, and issues with, the lung allocation system in Korea including donors, the waiting list, and transplant outcomes in the context of an aging society, in which the frequency of end-stage pulmonary disease is increasing.

The lung allocation score and other available models lack predictive accuracy for post-lung transplant survival.

Improved predictive models are needed in lung transplantation in the setting of a proposed allocation system that incorporates longer-term post-transplant survival in the United States. Allocation systems require accurate mortality predictions to justly allocate organs. Utilizing the United Network for Organ Sharing database (2005-2017), we fit models to predict 1-year mortality based on the Lung Allocation Score (LAS), the Chan, etal, 2019 model, a novel "clinician" model (a priori clinician selection of pre-transplant covariates), and two machine learning models (Least Absolute Shrinkage and Selection Operator; LASSO and Random Forests) for predicting 1-year and 3-year post-transplant mortality. We compared predictive accuracy among models. We evaluated the calibration of models by comparing average predicted probability vs observed outcome per decile. We repeated analyses fit for 3-year mortality, disease category, including donor covariates, and LAS era. The area under the cure for all models was low, ranging from 0.55 to 0.62. All exhibited reasonable negative predictive values (0.87-0.90), but the positive predictive value for was poor (all <0.25). Evaluating LAS calibration found 1-year post-transplant estimates consistently overestimated risk of mortality, with greater differences in higher deciles. LASSO, Random Forests, and clinician models showed no improvement when evaluated by disease category or with the addition of donor covariates and performed worse for 3-year outcomes. The LAS overestimated patients' risk of post-transplant death, thus underestimating transplant benefit in the sickest candidates. Novel models based on pre-transplant recipient covariates failed to improve prediction. There should be wariness in post-transplant survival predictions from available models.

Dynamic Thiol-Disulfide Homeostasis as a Marker for Oxidative Stress in Lung Transplant Candidates.

Oxidative stress developing due to oxidant/antioxidant imbalance plays a crucial role in the etiopathogenesis of chronic progressive lung diseases.The condition is typically more severe in lung transplant candidates with end-stage lung disease. Here, we investigated dynamic thiol-disulfide homeostasis as a marker for oxidative stress in lung transplant candidates. The study included 40 patients with end-stage lung disease with indications for lung transplant (candidate group) and 40 healthy controls. Patient demographic data, laboratory results, and thiol-disulfide homeostasis values were recorded. We categorized patients according to their primary diseases and noted clinical measurements of forced expiratory volume in 1 second, forced vital capacity, 6-minute walk test, systolic pulmonary artery pressure, and lung allocation scores.Thiol-disulfide homeostasis parameters were compared before and after transplant. Demographic characteristics were similar in the candidate and control groups. In the candidate group, native thiol and total thiol levels (antioxidant parameters of thiol-disulfide homeostasis) were significantly lower, whereas disulfide-to-native thiol and disulfide-to-total thiol ratios (oxidant parameters of thiol-disulfide homeostasis) were significantly higher. We observed no significant differences between the disease subgroups in terms of thioldisulfide homeostasis parameters. Moderately significant correlations were shown between the antioxidant markers ofthiol-disulfide homeostasis and the clinical measurements, including the lung allocation scores. Our multiple regression analyses showed that native thiol and total thiol were significant predictive factors to estimate the lung allocation score. During the study period, 6 patients (15%)received lung transplant. There were significant differences in antioxidant parameters ofthiol-disulfide homeostasis in the pre- versus posttransplant periods. In patients with end-stage lung disease, the dynamic thiol-disulfide homeostasis status is altered in favor of oxidants. Thus, thiol-disulfide homeostasis parameters can be used to detect oxidative stress and estimate lung allocation scores in these patients. Lung transplant may have positive effects on oxidative stress.

Trends in marginal lung allograft survival: Advanced‐age donors improve

Although lung demand continues to outpace supply, 75% of potential donor lungs are discarded without being transplanted in the United States. To identify the discarded cohorts best suited to alleviate the lung shortage and reduce waitlist mortality, we explored changes in survival over time for five marginal donor definitions: age>60 years, smoking history>20 pack-years, PaO2 /FiO2 <300mmHg, purulent bronchoscopic secretions, and chest radiograph infiltrates. Our retrospective cohort study separated 27803 lung recipients in the UNOS Database into three 5-year eras by transplant date: 2005-2009, 2010-2014, and 2015-2019. Multivariable Cox proportional hazards regression and Kaplan-Meier analysis with log-rank test were used to compare survival across the eras. Three definitions-low PaO2 /FiO2 , purulent bronchoscopic secretions, and abnormal chest radiographs-did not bear out as truly marginal, demonstrating lack of significantly elevated risk. Advanced donor age demonstrated considerable survival improvement (HR (95% CI): 1.47 (1.26-1.72) in 2005-2009 down to 1.14 (.97-1.35) for 2015-2019), with protective factors being recipients <60 years, moderate recipient BMI, and low Lung Allocation Score (LAS). Donors with smoking history failed to demonstrate any significant improvement (HR (95% CI): 1.09 (1.01-1.17) in 2005-2009 increasing to 1.22 (1.08-1.38) in 2015-2019). Advanced donor age, previously the most significant risk factor, has improved to near-benchmark levels, demonstrating the possibility for matching older donors to healthier non-elderly recipients in selected circumstances. Low PaO2 /FiO2 , bronchoscopic secretions, and abnormal radiographs demonstrated survival on par with standard donors. Significant donor smoking history, a moderate risk factor, has failed to improve.

Limitations of the dichotomized 6-minute walk distance when computing lung allocation score for cystic fibrosis: a 16-year retrospective cohort study

Purpose The 2010 Lung Allocation Score (LAS) version considers the estimated survival benefit offered by lung transplantation (LTx) and uses 6-minute Walk Test (6MWT) distance as a dichotomous covariate of whether an individual can walk more than 150 ft or 45.7 m in 6 min. This study aimed to provide evidence that 6MWT gives no clinically meaningful information to be used in the current LAS for candidates to LTx with cystic fibrosis (CF). Materials and methods We collected data from 6MWTs performed since 2003 at our CF centre. A joint model was fitted to describe the effect of changes in walked distance on the hazard of LTx or death. Results Up to 2019, 552 6MWTs were performed on 163 individuals with CF. None of the individuals included walked for less than 45.7 m during the 6MWT. Based on the joint modelling, the association of walked distance with the hazard ratio (HR) of LTx or death was significant (HR 0.99, 95% Credible Interval [CI]: 0.99 to 1.00). Conclusions When adopted dichotomously for LAS calculation, walked distance does not add any useful information about exercise capacity. Longitudinal trajectories of walked distance may provide complementary information about prognosis in individuals with CF. Implications for rehabilitation Dichotomized walked distance does not contribute to lung allocation score in candidates to lung transplantation with cystic fibrosis Changes in the longitudinal trajectory of walked distance can be clinically meaningful for prognostication. Sensitive outcomes to be incorporated in the lung allocation scoring system for individuals with CF are yet needed to catch rapid falls in functional capacity.