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On November 24, 2017, US lung transplant policy replaced donor service area with 250-nautical-mile radius as the first unit of allocation. Understanding this policy's economic impact is important, because the United States is poised to adopt the broadest feasible geographic organ distribution. All lung transplant recipients from January 1, 2015, to December 31, 2018, in the Scientific Registry of Transplant Recipients, were included. Recipients before and after November 24, 2017 were in the donor service area-first and 250-nautical-mile donor service area-free periods, respectively. Travel time was estimated using a Google application; mode was assigned as flying when driving time was longer than 60 min. Travel costs were estimated by mode and distance. Travel distance and time for organ procurement increased under the policy change. The estimated proportion of organs traveling by air increased from 61% to 76%. Estimated average costs increased by $14 051 if travel mode changed to flying, resulting in an average increase of $1264 for all transplants. Travel costs were highest for candidates

Efforts are underway to transition the current lung allocation system to a continuous distribution framework whereby multiple factors are simultaneously combined into a Composite Allocation Score (CAS) to prioritize candidates for lung transplant. The purpose of this study was to compare discrete CAS scenarios with the current concentric circle-based allocation system to assess their potential effects on the US lung transplantation system using the Scientific Registry of Transplant Recipients' thoracic simulated allocation model. Six alternative CAS scenarios were compared over 10 simulation runs using data from individuals on the lung transplant waiting list from January 1, 2018, through December 31, 2019. Outcome measures were transplant rate, count, waitlist deaths, posttransplant deaths within 2 years, donor-to-recipient distance, and percentage of organs predicted to have flown. Across scenarios, waitlist deaths decreased by 36% to 47%, with larger decreases in deaths at lower placement efficiency weight and higher weighting of the waitlist outcomes. When waitlist outcomes were equally weighted to posttransplant outcomes, more transplants occurred in individuals with the highest expected posttransplant survival. All CAS scenarios led to improved overall measures of equity compared with the current Lung Allocation Score system, including reduced waitlist deaths, and resulted in similar posttransplant survival.

The number of lung transplants performed continues to increase annually and reached an all-time high in 2019, with decreasing waitlist mortality. These trends are attributable to an increasing number of candidates listed for transplant each year and a continuing increase in the number of donors. Despite these favorable trends, 6.4% of lungs recovered for transplant were not transplanted in 2019, and strategies to optimize use of these available organs may reduce the number of waitlist even further. Time to transplant continued to decrease, as over 50% of candidates waited 3 months or less in 2019, yet regional heterogeneity remained despite policy changes intended to improve allocation equity. Small gains continued in posttransplant survival, with 1-year survival at 88.8%; 3 year, 74.4%; 5 year, 59.2%, and 10 year, 33.1 %.

The primary goal of US lung allocation policy is to ensure that candidates with the highest risk for mortality receive appropriate access to lung transplant. In 2018, 2562 lung transplants were performed in the US, reflecting a 31% increase over the past 5 years. More candidates are being listed for lung transplant, and the number of donors has increased substantially. Despite an increase of 84 lung transplants in 2018, 365 adult candidates died or became too sick to undergo transplant. In 2018, 24 new child (ages 0-11 years) candidates were added to the lung transplant waiting list. Fifteen lung transplants were performed in recipients aged 0-11 years, three in recipients aged younger than 1 year, two in recipients aged 1-5 years, and ten in recipients aged 6-11 years. Of 27 child candidates removed from the waiting list in 2018, 16 (59.3%) were removed due to undergoing transplant, six (22.2%) due to death, one (3.7%) due to improved condition, and one (3.7%) due to becoming too sick to undergo transplant.

More patients are waitlisted for solid organs than transplants are performed each year. The COVID-19 pandemic immediately increased waitlist mortality and decreased transplants and listings.To calculate the number of candidate listings after the pandemic began and short-term changes that may affect waiting time, we conducted a Scientific Registry of Transplant Recipients surveillance study from January 1, 2012 to February 28, 2021.The number of candidates on the liver waitlist continued a steady decline that began before the pandemic. Numbers of candidates on the kidney, heart, and lung waitlists decreased dramatically. More than 3000 fewer candidates were awaiting a kidney transplant on March 7, 2021, than on March 8, 2020. Listings and removals decreased for each solid organ beginning in March 2020. The number of heart and lung listings returned to equal or above that of removals. Listings for kidney transplant, which is often less urgent than heart and lung transplant, remain below numbers of removals. Removals due to transplant decreased for all organs, while removals due to death increased for only kidneys.We found no evidence of the predicted surge in listings for solid organ transplant with a plateau or control of the pandemic.

The lung allocation score prioritizes candidates for a lung transplant in the United States. As the country adopts the continuous distribution framework for organ allocation, we must reevaluate lung allocation score assumptions to maximize transplant benefit.We used Scientific Registry of Transplant Recipients data to study the impact of these changes: (1) updating cohorts; (2) transitioning from 1- to 5-year posttransplant survival; (3) using time-varying effects for non-proportional hazards; and (4) weighting waitlist and posttransplant area under the curve differently. Models were compared using Spearman correlations and C-statistics. The thoracic simulation allocation model characterized transplant rates and proportions of recipient subgroups under the current and new systems.Posttransplant areas under the curve models were estimated with recipients aged ≥12 from January 1, 2014, to December 31, 2018. All models had similar C-statistics and Spearman correlations, indicating similar predictive performance and posttransplant area under the curve rankings. Five-year posttransplant area under the curve across age and diagnosis groups varied more than 1-year groups. Using the thoracic simulation allocation model, 1- and 5-year posttransplant model under the curve models showed similar transplant rates and recipient characteristics under the current system, but under continuous distribution, 5-year posttransplant area under the curve resulted in increased transplant rates with more recipients younger and in diagnosis groups B and C.Incorporating equally weighted waitlist and posttransplant models using 5-year posttransplant survival detected the largest variability in survival under the continuous distribution system, which could improve long-term survival in the United States.

Gastroparesis is a debilitating and difficult to manage problem that has been reported in 20% to 90% of lung and heart-lung transplant recipients. The primary objective was to evaluate the safety and clinical effectiveness of per-oral endoscopic pyloromyotomy in relieving gastroparesis after lung transplant. Secondary objectives evaluated the effect of per-oral endoscopic pyloromyotomy on gastroesophageal reflux and allograft function.Fifty-two lung transplant recipients underwent per-oral endoscopic pyloromyotomy for refractory gastroparesis. Gastroparesis was assessed by a pre-per-oral endoscopic pyloromyotomy and post-per-oral endoscopic pyloromyotomy radionuclide gastric emptying test and Gastroparesis Cardinal Symptom Index. Secondary outcomes included 90-day complications, gastroesophageal reflux as measured by pH testing, and longitudinal spirometry measurements.Median time from lung transplant to per-oral endoscopic pyloromyotomy was 10.5 months. Twenty-eight patients had prior pyloric botulinum injection with either no improvement or relapse of symptoms. Post-per-oral endoscopic pyloromyotomy gastric emptying tests were available for 32 patients and showed a decrease in median gastric retention at 4 hours from 63.5% pre-per-oral endoscopic pyloromyotomy to 5.5% post-per-oral endoscopic pyloromyotomy (P .0001). Complete normalization of gastric emptying time was noted in 19 patients. Gastroparesis Cardinal Symptom Index score significantly improved after per-oral endoscopic pyloromyotomy (median, 23-3.5; P .0001). Post-per-oral endoscopic pyloromyotomy pH testing showed improved or stable DeMeester score in all patients except 1. Graft function (forced expiratory volume in 1 second) remained stable 1 year after per-oral endoscopic pyloromyotomy.The improvements in symptom score and radionuclide imaging observed in this uncontrolled study suggest that per-oral endoscopic pyloromyotomy is an effective strategy in the lung transplant population and can be performed with minimal morbidity.

Rationale: Referrals for lung transplant and transplant rates in the United States are lower than in Canada for patients with advanced cystic fibrosis (CF) lung disease. Further study of factors limiting access are needed to optimize referral and transplant for this population. Objectives: To determine the effect of socioeconomic position, while accounting for disease severity, on the likelihood of wait-listing for lung transplant in the United States. Methods: A case–control study of 3,110 patients (1,555 wait-listed, 1,555 never wait-listed) in the linked CF Foundation Patient Registry/Scientific Registry of Transplant Recipients was performed with 1:1 matching for age, forced expiratory volume in 1 second, and year. Logistic regression was performed with univariate and multivariate analyses accounting for eight clinical factors (sex, oxygen use, body mass index, hemoptysis, forced vital capacity, methicillin-resistant Staphylococcus aureus, multidrug-resistant Pseudomonas aeruginosa, and i.v. antibiotic days) and six socioeconomic factors (race, marital status, education, health insurance, median zip code income, and distance to transplant program). The CF Health Score and Socioeconomic Barrier Score were created based on summation of variables. Interactions between scores were calculated. Results: We found an inverse relationship between the probability of wait-listing and CF Health Score and Socioeconomic Barrier Score. As the CF Health Score decreased (less healthy), the probability of wait-listing increased by 69.3% from a score of 7 to 2. As the Socioeconomic Barrier Score decreased (fewer barriers), the probability of wait-listing increased by 31.7% from a score of ≥5 to 1). Regardless of illness severity, socioeconomic barriers presented an impediment to wait-listing. Individuals with higher Socioeconomic Barrier Scores accessed transplant about half as often as those with lower scores at the same level of medical severity. Analysis of interactions demonstrated a higher probability of wait-listing for individuals with moderate health severity and fewer social barriers compared with sicker individuals with more socioeconomic barriers. Conclusions: Accrual of socioeconomic barriers limits access to lung transplant irrespective of disease severity, a finding of substantial concern for patients with CF and for transplant providers. Future interventions can focus on this at-risk population early in the disease course.

In 2016, 2692 candidates aged 12 years or older were added to the lung transplant waiting list; 2345 transplants were performed, the largest number of any prior year. The median waiting time for listed candidates in 2016 was 2.5 months, and waiting times were shortest for group D candidates. The transplant rate increased to 191.9 transplants per 100 waitlist years in 2016, with a slight decrease in waitlist mortality to 15.1 deaths per 100 waitlist years. Short-term survival continued to improve, with a 6-month death rate of 6.6% and a 1-year death rate of 10.8% among recipients in 2015 compared with 8.0% and 13.3%, respectively, among recipients in 2014. Long-term survival rates remained unchanged; 55.6% of recipients were alive at 5 years. In 2016, 23 new candidates aged 0-11 years were added to the waiting list and 16 lung transplants were performed. Incidence of posttransplant mortality for lung transplant recipients aged 0-11 years who underwent transplant in 2014-2015 was 13.8% at 6 months and 19.6% at 1 year. Changes in waitlist and transplant demographic features continued to evolve following implementation of the revised lung allocation score in 2015. Some early trends that may be attributable to the revised LAS are shorter waiting times, stabilization of the number of group D candidates listed for transplant, and convergence of LAS with lower prevalence of extremely high scores.

BACKGROUND The thoracic simulated allocation model (TSAM) is used by the Scientific Registry of Transplant Recipients to predict the relative effect of organ allocation policy changes. A new lung allocation policy changing the first unit of allocation from donation service area to 250 nautical miles took effect on November 24, 2017. We studied TSAM's ability to correctly predict trends caused by changes in allocation policy. METHODS We compared the population characteristics from the TSAM cohort, 6,386 lung transplant candidates from 2009 to 2011, with the observed cohort of 7,601 candidates from the year before the policy change on November 24, 2017, and the year after. Simulations were run 10 times. Waitlist mortality and transplant rates were calculated and compared with observed mortality and transplant rates in the years before and after the policy change. RESULTS TSAM correctly predicted no change in overall waitlist mortality or transplant rates with the policy change. Observed waitlist mortality values were higher, as were transplant rates, because of increased organ donation and population change. TSAM predicted increased transplant rates for diagnosis group D (idiopathic pulmonary fibrosis), decreased rates for group A (chronic obstructive pulmonary disease), and increased rates for candidates with lung allocation score ≥50, but these changes did not occur in the waitlist and transplant populations after the policy change. CONCLUSIONS TSAM correctly predicted the relative trends caused by a change in allocation policy but smaller sub-group predictions were not seen.

Each year since 2012, the number of lung transplants has increased, reflecting an increase in the number of donors, improved use of recovered organs, and more candidates being listed for transplant. However, the need for organs continues to outpace available donors. Despite an increase of 126 donors in 2017, 1360 candidates remained on the waiting list at the end of the year, and 326 patients died or became too sick to undergo transplant. Approximately 14,000 individuals were living with a lung transplant in 2017; 9492 were aged 50 years or older, 4075 were aged 18-49 years, and 408 were aged younger than 18 years.

US pediatric transplant candidates have limited access to lung transplant due to the small number of donors within current geographic boundaries, leading to assertions that the current lung allocation system does not adequately serve pediatric patients. We hypothesized that broader geographic sharing of pediatric (adolescent, 12-17 years; child

Introduction: Recipient travel distance may be an unrecognized burden in lung transplantation. Design: Retrospective single-center cohort study of all adult (≥18 years) first-time lung-only transplants from January 1, 2010, until February 28, 2017. Recipient distance to transplant center was calculated using the linear distance from the recipient’s home zip code to the Cleveland Clinic in Cleveland, Ohio. Results: 569 recipients met inclusion criteria. Posttransplant graft survival was 85%, 88%, 91%, and 91% at 1 year and 49%, 52%, 57%, and 56% at 5 years posttransplant for recipient travel distances of ≤50, >50 to ≤250, >250 to ≤500, and >500 miles, respectively ( P = .10). Discussion: We found no significant relationship between recipient travel distance and posttransplant graft survival. In carefully selected recipients, travel distance is not a significant barrier to successful posttransplant outcomes which may be important for patient decision-making and donor allocation policy. These data should be validated in a national cohort.

Variation in heart and lung offer acceptance practices may affect numbers of transplanted organs and create variability in waitlist mortality. To investigate these issues, offer acceptance ratios, or adjusted odds ratios, for heart and lung transplant programs individually and for all programs within donation service areas (DSAs) were estimated using offers from donors recovered July 1, 2016-June 30, 2017. Logistic regressions estimated the association of DSA-level offer acceptance ratios with donor yield and local placement of organs recovered in the DSA. Competing risk methodology estimated the association of program-level offer acceptance ratios with incidence and rate of waitlist removals due to death or becoming too sick to undergo transplant. Higher DSA-level offer acceptance was associated with higher yield (odds ratios [ORs]: lung, (1.04)1.11(1.19); heart, (1.09)1.21(1.35)) and more local placement of transplanted organs (ORs: lung, (1.01)1.12(1.24); heart, (1.47)1.69(1.93)). Higher program-level offer acceptance was associated with lower incidence of waitlist removal due to death or becoming too sick to undergo transplant (hazard ratios [HRs]: heart, (0.80)0.86(0.93); lung, (0.67)0.75(0.83)), but not with rate of waitlist removal (HRs: heart, (0.91)0.98(1.06); lung, (0.89)0.99(1.10)). Heart and lung offer acceptance practices affected numbers of transplanted organs and contributed to program-level variability in the probability of waitlist mortality.

Lungs are allocated to adult and adolescent transplant candidates (aged ⩾ 12 years) on the basis of age, geography, blood type compatibility, and the lung allocation score (LAS), which reflects risk of waitlist mortality and probability of posttransplant survival. In 2013, the most adult candidates, 2394, of any year were added to the list. Overall median waiting time for candidates listed in 2013 was 4.0 months. The preferred procedure remained bilateral lung transplant, representing approximately 70% of lung transplants in 2013. Measures of short-term and longterm survival have plateaued since the implementation of the LAS in 2005. The number of new child candidates (aged 0-11 years) added to the lung transplant waiting list increased to 39 in 2013. A total of 28 lung transplants were performed in child recipients, 3 for ages younger than 1 year, 9 for ages 1 to 5 years, and 16 for ages 6 to 11 years. The diagnosis of pulmonary hypertension was associated with higher survival rates than cystic fibrosis or other diagnosis (pulmonary fibrosis, bronchiolitis obliterans, bronchopulmonary dysplasia). For child candidates, infection was the leading cause of death in year 1 posttransplant and graft failure in years 2 to 5.

In 2015, 2409 active candidates aged 12 years or older were added to the lung transplant waiting list; 2072 transplants were performed, the most of any year. The median waiting time for candidates listed in 2015 was 3.4 months; the shortest waiting time was for diagnosis group D. Despite the highest recorded transplant rate of 157 per 100 waitlist years, waitlist mortality continued a steady decade-long rise to a high of 16.5 deaths per 100 waitlist years. Measures of short- and long-term survival showed no trend toward improved overall survival in the past 5 years, except that 6-month death rates decreased from 9.4% in 2005 to 7.9% in 2014. At 5 years posttransplant, 55.5% of recipients remained alive. In 2015, 23 new child (ages 0-11 years) candidates were added to the list; 17 transplants were performed. Incidence of death was 6.1% at 6 months and 8.2% at 1 year for transplants in 2013-2014. Important policy changes will affect access to transplant. In February 2015, OPTN implemented a comprehensive revision of the lung allocation score to better reflect mortality risk. Broader geographic sharing of donor lungs for pediatric candidates and allowance for selected transplants across blood types for candidates aged younger than 2 years have been approved and are expected to improve pediatric access to transplant. The impact of these changes on lung transplant trends will be observed in the coming years.

Donation after circulatory determination of death (DCDD) has the potential to increase the number of organs available for transplantation. Because consent and management of potential donors must occur before death, DCDD raises unique ethical and policy issues.To develop an ethics and health policy statement on adult and pediatric DCDD relevant to critical care and transplantation stakeholders.A multidisciplinary panel of stakeholders was convened to develop an ethics and health policy statement. The panel consisted of representatives from the American Thoracic Society, Society of Critical Care Medicine, International Society for Heart and Lung Transplantation, Association of Organ Procurement Organizations, and the United Network of Organ Sharing. The panel reviewed the literature, discussed important ethics and health policy considerations, and developed a guiding framework for decision making by stakeholders.A framework to guide ethics and health policy statement was established, which addressed the consent process, pre- and post mortem interventions, the determination of death, provisions of end-of-life care, and pediatric DCDD.The information presented in this Statement is based on the current evidence, experience, and clinical rationale. New clinical research and the development and dissemination of new technologies will eventually necessitate an update of this Statement.

Lungs are allocated in part based on the Lung Allocation Score (LAS), which considers risk of death without transplant and posttransplant. Wait-list additions have been increasing steadily after an initial decline following LAS implementation. In 2011, the largest number of adult candidates were added to the waiting list in a single year since 1998; donation and transplant rates have been unable to keep pace with wait-list additions. Candidates aged 65 years or older have been added faster than candidates in other age groups. After an initial decline following LAS implementation, wait-list mortality increased to 15.7 per 100 wait-list years in 2011. Short- and long-term graft survival improved in 2011; 10-year graft failure fell to an all-time low. Since 1998, the number of new pediatric (aged 0-11 years) candidates added yearly to the waiting list has declined. In 2011, 19 pediatric lung transplants were performed, a transplant rate of 34.7 per 100 wait-list years. The percentage of patients hospitalized before transplant has not changed. Both graft and patient survival have continued to improve over the past decade. Posttransplant complications for pediatric lung transplant recipients, similar to complications for adult recipients, include hypertension, renal dysfunction, diabetes, bronchiolitis obliterans syndrome, and malignancy.

This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.

Background: Dysregulated expression of IL-4 has been linked with allergic diseases. IL-4 expression is controlled at the level of gene transcription by the coordinated action of multiple factors that bind regulatory promoter elements. In addition, alterations in chromatin structure are thought to play a role in regulating the expression of cytokines in the T H 2 gene cluster, although the biochemical basis for these alterations in human T cells is not well understood. Objective: We sought to define the role of histone acetylation in the regulation of IL4 gene expression in human T cells. Methods: IL-4 protein production was measured by means of ELISA. IL-4 promoter activity was measured with luciferase-based reporter constructs transiently transfected into Jurkat T cells. The acetylation status of histones associated with the IL4 gene was analyzed with chromatin immunoprecipitation assays. Results: IL-4 production from activated peripheral blood T cells was enhanced by the histone deacetylase inhibitor trichostatin A. Overexpression of the type 1 histone deacetylases 1, 2, and 3 inhibited transcription driven by the IL-4 promoter in Jurkat T cells, whereas cotransfection of the histone acetyltransferase CREB-binding protein potentiated IL-4 promoter activity. Using chromatin immunoprecipitation assays, we show that nucleosomes in the proximal IL-4 promoter are acetylated on T-cell activation. Conclusion: Our results demonstrate that the acetylation state of histones associated with the IL-4 promoter is a key regulator of IL4 gene expression. (J Allergy Clin Immunol 2002;109:238-45.)

Lung transplants are increasingly used as treatment for end-stage lung diseases not amenable to other medical and surgical therapies. Lungs are allocated to adult and adolescent transplant candidates on the basis of age, geography, blood type compatibility, and the Lung Allocation Score, which reflects risk of wait-list mortality and probability of posttransplant survival. The overall median waiting time in 2012 was 4 months, and 65.3% of candidates underwent transplant within 1 year of listing; however, this proportion varied greatly by donation service area. Unadjusted median survival of lung transplant recipients was 5.3 years in 2012, and median survival conditional on living for 1 year posttransplant was 6.7 years. Among pediatric lung candidates in 2012, 32.1% were wait-listed for less than 1 year, 17.9% for 1 to less than 2 years, 16.7% for 2 to less than 4 years, and 33.3% for 4 or more years. Both graft and patient survival have continued to improve; survival rates for recipients aged 6-11 years are better than for younger recipients. Compared with recipients of other solid organ transplants, lung transplant recipients experienced the highest rates of rehospitalization for transplant complications: 43.7 per 100 patients in year 1 and 36.0 in year 2.

Publication is one of the primary rewards in the academic research community and is the first step in the dissemination of a new discovery that could lead to recognition and opportunity. Because of this, the publication of research can serve as a tacit endorsement of the methodology behind the science. This becomes a problem when vulnerable populations that are incapable of giving legitimate informed consent, such as prisoners, are used in research. The problem is especially critical in the field of transplant research, in which unverified consent can enable research that exploits the vulnerabilities of prisoners, especially those awaiting execution. Because the doctrine of informed consent is central to the protection of vulnerable populations, we have performed a historical analysis of the standards of informed consent in codes of international human subject protections to form the foundation for our limit and ban recommendations: (1) limit the publication of transplant research involving prisoners in general and (2) ban the publication of transplant research involving executed prisoners in particular.

Live organ donors represent nearly 50% of the solid organ donors in the United States. This unique population of individuals accepts risk for the benefit of another. The main justification by the medical community for permitting such risk to live donors has been respect for their autonomy, realized through the practice of informed consent. This article examines the key criteria of informed consent--understanding and non-control (voluntariness)--in the context of live organ donation. It concludes that more prospective studies are needed to improve the process of informed consent in this population.