Waiting List For Lung Transplantation Research Articles

Improved waitlist and transplant outcomes for pediatric lung transplantation after implementation of the lung allocation score

Although the lung allocation score (LAS) has not been considered valid for lung allocation to children, several additional policy changes for pediatric lung allocation have been adopted since its implementation. We compared changes in waitlist and transplant outcomes for pediatric and adult lung transplant candidates since LAS implementation. The United Network for Organ Sharing database was reviewed for all lung transplant listings during the period 1995 to June 2014. Outcomes were analyzed based on date of listing (pre-LAS vs post-LAS) and candidate age at listing (adults >18 years, adolescents 12 to 17 years, children 0 to 11 years). Of the 39,962 total listings, 2,096 (5%) were for pediatric candidates. Median waiting time decreased after LAS implementation for all age groups (adults: 379 vs 83 days; adolescents: 414 vs 104 days; children: 211 vs 109 days; p < 0.001). The proportion of candidates reaching transplant increased after LAS (adults: 52.6% vs 71.6%, p < 0.001; adolescents: 40.3% vs 61.6%, p < 0.001; children: 42.4% vs 50.9%, p = 0.014), whereas deaths on the waitlist decreased (adults: 28.0% vs 14.4%, p < 0.001; adolescents: 33.1% vs 20.9%, p < 0.001; children: 32.2% vs 25.0%; p = 0.025), despite more critically ill candidates in all groups. Median recipient survival increased after LAS for adults and children (adults: 5.1 vs 5.5 years, p < 0.001; children: 6.5 vs 7.6 years, p = 0.047), but not for adolescents (3.6 vs 4.3 years, p = 0.295). Improvements in waiting time, mortality and post-transplant survival have occurred in children after LAS implementation. Continued refinement of urgency-based allocation to children and broader sharing of pediatric donor lungs may help to maximize these benefits.

Patient factors associated with lung transplant referral and waitlist for patients with cystic fibrosis and pulmonary fibrosis

Since 2005, the Lung Allocation Score (LAS) has prioritized patient benefit and post-transplant survival, reducing waitlist to transplant time to <200 days and decreasing mortality on the waitlist. A current challenge is the wait for the waitlist-the time between the patient's transplant-eligible diagnosis and waitlist registration. We investigated whether sociodemographic (age, sex, race, insurance, marital status, median household income) and clinical (forced expiratory volume in 1 second [FEV1] percent of predicted, body mass index, depression/anxiety, alcohol/substance misuse, absolute/relative contraindications) factors influenced referral and waitlist registration. We conducted a retrospective cohort study through chart review of hospitalized patients on the University of Chicago general medicine service from 2006 to 2014 who met transplant-eligible criteria and ICD-9 billing codes for cystic fibrosis (CF) and pulmonary fibrosis (PF). We analyzed the times from transplant eligibility to referral, work-up and waitlisting using Kaplan-Meier curves and log-rank tests. Overall, the referral rate for transplant-eligible patients was 64%. Of those referred, approximately 36% reach the lung transplant waitlist. Referred CF patients were significantly more likely to reach the transplant waitlist than PF patients (CF 60% vs PF 22%, p < 0.05). In addition, CF patients had a shorter wait from transplant eligibility to waitlist than PF patients (329 vs 2,369 days, respectively [25th percentile], p < 0.05). Patients with PF and CF both faced delays from eligibility to referral and waitlist. Quality improvement efforts are needed to better identify and refer appropriate patients for lung transplant evaluation. Targeted interventions may facilitate more efficient evaluation completion and waitlist appearance.

(70) - Improved Waitlist and Transplant Outcomes for Pediatric Lung Transplantation After Implementation of the Lung Allocation Score

Implementation of the lung allocation score (LAS) has reduced waiting time and increased transplant rates in the adolescent and adult lung transplant populations, however it has not been considered valid for lung allocation to children. We examined the indirect impact of the LAS on waitlist and transplant outcomes in children. The UNOS database was reviewed for all waitlist entries for pediatric lung transplantation from 1986 to July, 2014 (age at listing <18 yr). Patients receiving heart-lung transplant or living related transplant were excluded. The lung allocation score was implemented in May 2005 for patients ≥12 years of age. Waitlist and transplant outcomes were analyzed based on patient age at listing (child = 0-11 yr, adolescent = 12-17 yr) and date of listing (pre-LAS <5/2005, post-LAS ≥5/2005). Of 2551 waitlist entries identified, 45% (1136) were for children age 0-11 yr at listing. In patients listed after 5/2005, median LAS at listing was higher in adolescents than children (35.2 vs 32.9 respectively, p<0.001), although LAS was not used for allocation in children. Median waiting time decreased after LAS for both children and adolescents (173 to 109 days, p<0.001, and 377 to 104 days, p<0.001; Figure). Death on the waitlist also decreased after LAS in both groups (31.1 to 21.6% of listings for children, p<0.001, and 31.9 to 15.5% for adolescents, p=<0.001), despite a higher prevalence of ventilator support at listing (19 to 27.4% for children, p=0.002, and 2.9 to 9.2% for adolescents, p<0.001). Recipient survival at 5 years post-transplant increased after LAS in children (53.1 to 61.9%, p=0.0162) but not adolescents (40.8 to 46.4%, p=0.1340). Indirect improvements in waitlist time, mortality, and post-transplant survival have occurred in children after LAS implementation. The balance of medical necessity and post-transplant survival remains a challenge in lung allocation for all age groups, particularly adolescents.

Canada's Longest Experience With Extracorporeal Membrane Oxygenation as a Bridge to Lung Transplantation: A Case Report

IntroductionExtracorporeal membrane oxygenation (ECMO) is a method of enabling gas exchange through an external membrane used to treat respiratory failure in critically ill patients. ECMO as a bridge to lung transplantation has been investigated as a potential method of reducing lung transplantation waitlist mortality. Herein we describe a case of ECMO as a bridge-to-lung transplantation for the duration of 35 days, which is the longest documented length of ECMO support before successful transplantation in Canada. Case DescriptionThe prospective recipient was a 28-year-old female suffering from stage 4 pulmonary sarcoidosis. Given an acute exacerbation of her chronic respiratory failure, ECMO had to be initiated. She remained on ECMO for 35 days until a suitable set of donor lungs became available. The recipient had a prolonged course in hospital but was successfully discharged home where she continues to have good lung function. She remains alive and well at home 5 months post-transplantation and continues to improve and gain strength. ConclusionOur case provides hope that in the future we may be able to expand the population of recipients who may be candidates for lung transplantation. This case adds to the growing literature on the role of ECMO as a bridge-to-lung transplantation with the potential to reduce patient deaths while wait-listed for lung transplantation as well as increase the number of transplantations being performed.

Lung transplant waitlist mortality: Height as a predictor of poor outcomes

The LAS was designed to minimize pretransplant mortality while maximizing post-transplant outcome. Recipients <12 are not allocated lungs based on LAS. Waitlist mortality has decreased for those >12, but not <12, suggesting this population may be disadvantaged. To identify predictors of waitlist mortality, a retrospective analysis of the UNOS database was performed since implementation of the LAS. There were 16,973 patients listed for lung transplant in the United States; 12,070 (71.1%) were transplanted, and 2498 (14.7%) patients died or were removed from the wait list. Significantly more pediatric patients died or were removed compared with adults (22.0% vs. 14.4%, p < 0.01). In multivariate analysis, in addition to higher LAS at time of listing (adj. HR1.058, 1.055-1.060), shorter height (1.008, 1.006-1.010), male gender (1.210, 1.110-1.319), and requiring ECMO (1.613, 1.202-2.163) were associated with pretransplant mortality. Post-transplant survival was not affected by height. The current age cutoff may impose limitations within the current lung allocation system in the United States. Height is an independent predictor of waitlist mortality and may be a valuable factor for the development of a comprehensive lung allocation system.

Quality of Life Assessment in Two Consecutive Years of Patients in a Waiting List for Lung Transplantation

BackgroundPatients on a waiting list for lung transplantation (LT) have physical and emotional setbacks due to limiting symptoms such as dyspnea and cough. Time on a waiting list may worsen the conditions of these patients and affect their quality of life (QoL). ObjectiveOur objective was to evaluate QoL components in patients in 2 consecutive years who were waiting for transplantation. Material and MethodsWe studied patients who remained on a waiting list for transplantation in the first 2 years after inclusion on the list. Evaluation was performed using the Short-Form-36 (SF-36) Questionnaire and the Saint George's Respiratory Questionnaire (SGRQ). ResultsFifty-six patients were included (38.5 ± 15 years), 33 women (59%) and 23 men (41%). Of these, 18 had bronchiectasis, 14 had cystic fibrosis, 9 had lung fibrosis, 8 had lung emphysema, and 7 had other diseases. The domains with greater involvement in the first and second year were Functional Capacity and Physical Aspects. In the second year there was a significant worsening in Physical Aspects (2.5-0 points; P = .032). The domains related to the emotional component did not have significant changes. ConclusionThe progression of the disease and progressive worsening of symptoms of patients on a transplantation waiting list led to less physical exercise, worsening the effects of inactivity. After 1 year on a waiting list for LT, patients had a significant loss of functionality, which had an impact on QoL.

Too High for Transplantation? Single-Center Analysis of the Lung Allocation Score

Recent studies using United Network for Organ Sharing data suggest that lung transplantation in patients with high lung allocation scores (LAS) may lead to organ and resource wastage. Therefore, to determine whether a LAS cutoff value should be considered, we evaluated the relation of LAS to waitlist and posttransplant mortality in our center to determine if it could identify patients for whom listing for transplantation may be futile. From May 1, 2005 to July 1, 2010, 537 adults were listed and 426 underwent primary lung transplantation at our institution. Endpoints were mortality before and after lung transplantation. The relationships of LAS at listing to waitlist mortality and of pretransplant LAS to posttransplant mortality were both analyzed by multiphase hazard function methodology. Higher LAS was strongly associated with waitlist mortality (p<0.0001), with the highest quartile (LAS ranging from 47 to 95) experiencing 75% mortality within a year of listing. Although early (p=0.05), but not late (p=0.4), posttransplant survival was associated with higher LAS at transplantation, once other clinical characteristics predictive of early mortality were accounted for, neither waitlist nor pretransplant LAS was independently related to posttransplant mortality (p=0.12). Higher LAS strongly predicts higher mortality on the lung transplantation waitlist, underscoring the value of LAS in prioritizing patients with the highest scores for transplantation. Early posttransplant mortality is modestly higher with higher pretransplant LAS, but the data of our center do not suggest a value above which transplantation should be denied as futile. This suggests that donor organs and resources are not being wasted.

(247) - Lung Transplant Waitlist Mortality: Height as a Predictor of Poor Outcomes

PurposeThe lung allocation score (LAS) was designed to minimize pre-transplant mortality while maximizing post-transplant outcomes. Recipients under 12 years are not allocated lungs based on LAS. Since adoption of the LAS, waitlist mortality has decreased for those >12, but not for <12, suggesting this population may be disadvantaged. While age is used as the cut-off for lung allocation based on LAS, we sought to determine a more appropriate predictor of waitlist mortality.MethodsWe performed a retrospective analysis of the United Network of Organ Sharing (UNOS) database focusing on stature for those listed for transplant since LAS implementation in May 2005. Competing risk regression, Kaplan-Meir survival analysis and Cox proportional hazard modeling were used to assess pre- and post-transplant outcomes.ResultsThere were 16,973 patients listed for lung transplant since LAS implementation. 12,070 (71.1%) were transplanted and 2,498 (14.7%) patients died or were removed from the waitlist. Significantly more pediatric patients died or were removed compared to adults (22.0% vs. 14.4%, p<0.01). Patients whose height at listing was ≤1.25m and 1.25-1.5m had significantly increased waitlist mortality compared to those >1.5m (p=0.015 and p<0.001 respectively) (Figure 1a). While in univariate analysis younger age was associated with increased risk of pre-transplant mortality (HR 1.004, 95% CI 1.001-1.007), in multivariate analysis, only shorter height (adj. HR 1.008, 95% CI 1.006-1.010), male gender (1.210, 1.110-1.319), higher LAS (1.058, 1.055-1.060), and requiring extracorporeal membrane oxygenation (ECMO) (1.613, 1.202-2.163) were associated with pre-transplant mortality. Post-transplant survival was not affected by height (Figure 1b).Conclusion PurposeThe lung allocation score (LAS) was designed to minimize pre-transplant mortality while maximizing post-transplant outcomes. Recipients under 12 years are not allocated lungs based on LAS. Since adoption of the LAS, waitlist mortality has decreased for those >12, but not for <12, suggesting this population may be disadvantaged. While age is used as the cut-off for lung allocation based on LAS, we sought to determine a more appropriate predictor of waitlist mortality. The lung allocation score (LAS) was designed to minimize pre-transplant mortality while maximizing post-transplant outcomes. Recipients under 12 years are not allocated lungs based on LAS. Since adoption of the LAS, waitlist mortality has decreased for those >12, but not for <12, suggesting this population may be disadvantaged. While age is used as the cut-off for lung allocation based on LAS, we sought to determine a more appropriate predictor of waitlist mortality. MethodsWe performed a retrospective analysis of the United Network of Organ Sharing (UNOS) database focusing on stature for those listed for transplant since LAS implementation in May 2005. Competing risk regression, Kaplan-Meir survival analysis and Cox proportional hazard modeling were used to assess pre- and post-transplant outcomes. We performed a retrospective analysis of the United Network of Organ Sharing (UNOS) database focusing on stature for those listed for transplant since LAS implementation in May 2005. Competing risk regression, Kaplan-Meir survival analysis and Cox proportional hazard modeling were used to assess pre- and post-transplant outcomes. ResultsThere were 16,973 patients listed for lung transplant since LAS implementation. 12,070 (71.1%) were transplanted and 2,498 (14.7%) patients died or were removed from the waitlist. Significantly more pediatric patients died or were removed compared to adults (22.0% vs. 14.4%, p<0.01). Patients whose height at listing was ≤1.25m and 1.25-1.5m had significantly increased waitlist mortality compared to those >1.5m (p=0.015 and p<0.001 respectively) (Figure 1a). While in univariate analysis younger age was associated with increased risk of pre-transplant mortality (HR 1.004, 95% CI 1.001-1.007), in multivariate analysis, only shorter height (adj. HR 1.008, 95% CI 1.006-1.010), male gender (1.210, 1.110-1.319), higher LAS (1.058, 1.055-1.060), and requiring extracorporeal membrane oxygenation (ECMO) (1.613, 1.202-2.163) were associated with pre-transplant mortality. Post-transplant survival was not affected by height (Figure 1b). There were 16,973 patients listed for lung transplant since LAS implementation. 12,070 (71.1%) were transplanted and 2,498 (14.7%) patients died or were removed from the waitlist. Significantly more pediatric patients died or were removed compared to adults (22.0% vs. 14.4%, p<0.01). Patients whose height at listing was ≤1.25m and 1.25-1.5m had significantly increased waitlist mortality compared to those >1.5m (p=0.015 and p<0.001 respectively) (Figure 1a). While in univariate analysis younger age was associated with increased risk of pre-transplant mortality (HR 1.004, 95% CI 1.001-1.007), in multivariate analysis, only shorter height (adj. HR 1.008, 95% CI 1.006-1.010), male gender (1.210, 1.110-1.319), higher LAS (1.058, 1.055-1.060), and requiring extracorporeal membrane oxygenation (ECMO) (1.613, 1.202-2.163) were associated with pre-transplant mortality. Post-transplant survival was not affected by height (Figure 1b). Conclusion

The Equitable Allocation of Deceased Donor Lungs for Transplant in Children in the United States

On June 5, 2013, a US Federal Court ordered a temporary restraining order to allow two children within the court's jurisdiction to be registered on the adolescent lung transplant waiting list. On June 10, 2013, the Organ Procurement and Transplantation Network's Executive Committee altered lung allocation policy to offer candidates aged younger than 12 years greater access to adult lungs at the discretion of the national Lung Review Board. The Scientific Registry of Transplant Recipients reviewed trends over time in deceased donor lung transplant waitlist mortality and transplant rates, comparing children and adults. Mortality rates of candidates active on the waiting list have been higher for children aged 0-5 years, but have not differed for children aged 6-11 years compared with adolescents aged 12-17 years or adults aged 18 years or older. Transplant rates among active waitlist candidates have been comparable across all age groups. Thus, there is little evidence that the allocation system led to differences in waitlist mortality or transplant rates for children compared with adults. However, these comparisons are difficult to interpret given that current policies likely led to unaccounted differences in the severity of illness at the time of listing.

Impact of the Lung Allocation Score

The number of donors falls short of the number of patients on the wait list for lung transplantation making it necessary to ration the available donor organs. The ideal allocation system is guided by ethical principles and scientifically accurate at identifying patients who will gain the greatest degree of benefit from receiving the organ, in terms of both pre- and posttransplantation survival. The lung allocation score (LAS) was developed in 2005 to reduce mortality on the wait list, prioritize candidates based on urgency, minimize the role of geography, and maximize transplant benefit. The LAS has not made much of an impact on the geographic disparity of listing patients for lung transplantation, but it did achieve the goal of reducing wait-list mortality and prioritizing patients based on urgency. In prioritizing patients with the most urgent status, a new controversy has come into the forefront: whether or not the increased number of critically ill recipients maximizes transplant benefit. Despite the controversy, the LAS system is an improvement compared with the traditional first-come, first-served system, and it has even been adopted by Eurotransplant. In the future, as modifications are made to improve the LAS, the issue of critically ill patients and maximizing posttransplant benefit will be the focus.

Survival Benefit of Lung Transplant for Cystic Fibrosis since Lung Allocation Score Implementation

The survival benefit of lung transplantation (LT) in adult patients with cystic fibrosis (CF) is debated. We sought to assess the survival benefit of LT in adult patients with CF. We used data from the United Network for Organ Sharing Registry to identify adult patients with CF on a wait list for LT in the United States between 2005 and 2009. Survival times while on the wait list and after LT were modeled by use of a Cox model that incorporated transplantation status as a time-dependent covariate. Evolution in lung allocation score (LAS) while on the wait list was used as a surrogate for disease severity. We fitted a model for the joint distribution of survival and longitudinal disease process (LAS over time). A total of 704 adult patients with CF were registered on a wait list during the study period. The cumulative incidence of LT was 39.3% (95% confidence interval, 35.6-42.9%) at 3 months and 64.7% (61.0-68.4%) at 12 months, whereas the incidence of death while on the wait list at the same times was 8.5% (6.4-10.6%) and 12.9% (10.3-15.5%), respectively. Survival after LT was 96.5% (94.7-98.2%) at 3 months; 88.4% (85.1-91.8%) at 12 months; and 67.8% (59.9-76.8%) at 3 years. LT conferred a 69% reduction in the instantaneous risk of death (51-80%). The interaction between LAS and LT was significant: the higher the LAS, the greater the survival benefit of LT (P < 0.001). LT confers a survival benefit for adult patients with CF.

Lung Transplantation for Idiopathic Pulmonary Arterial Hypertension

In the past decade, there have been remarkable advances in the medical management of patients with idiopathic pulmonary arterial hypertension (IPAH). These therapies have improved the quality of life, saved many lives, and, in some cases, obviated the need for lung transplantation. However, the reality is that the majority of patients with IPAH, even with access to the best medical therapy, continue to progress and will require lifesaving lung transplantation. Article see p 2503 Lung transplantation for IPAH has traditionally been viewed as a higher up-front surgical-risk lung transplant to perform, but with excellent long-term survival and quality of life. The concern in the current management strategy for patients with IPAH is that, by virtue of the seriousness of the condition, they tend to have the highest mortality on the lung transplant waitlist, and, then, with the practice of listing them after they begin to fail first-, second-, and sometimes third-line medical therapies, they are in even poorer medical condition and, in general, are deteriorating very rapidly. With a limited supply of donor organs, onc can see that this might exacerbate the problem of waitlist mortality in this particular patient population that cannot afford to wait. One can also appreciate then, that when the United Network for Organ Sharing Lung Allocation Score (LAS) was initially introduced, this caused some concern regarding the potential for placing IPAH patients on the list at a disadvantage. The LAS score was designed with the intent to optimize the use of the scarce resource, donor lungs, by the allocation of lungs to patients who have the best potential for a good outcome after transplantation, balancing mortality on the waitlist with survival probability after transplant. To optimally treat patients with IPAH, the treating physicians in the IPAH and lung transplant community need to (1) optimize medical …

Predicting Lung Transplant Waitlist Survival with the Lung Allocation Score in British Columbia, Canada

Purpose The Lung Allocation Score (LAS), implemented in 2005 in the United States, allocates donor organs according to predicted pre and post-lung transplant mortality based on clinical parameters. In Canada, allocation is based on a dichotomous Status ranking of 1 (active and stable) or 2 (urgent, rapidly deteriorating). The purpose of this study was to assess if LAS scores predicted waitlist and post-transplant mortality in our population, and to compare its ability to do so in comparison to the traditional Status risk stratification. Methods and Materials LAS scores were retrospectively calculated for all patients listed for lung transplantation between January 2007 and July 2012 in British Columbia, Canada. Using measures of model goodness-of-fit (Akaike Information Criterion [AIC]), we compared proportional hazards regression for time to death on the waitlist and post-transplant with either LAS score or Status at time of activation as the predictor. Likelihood-ratio tests were used to test if models with LAS or status as predictors were significantly better than models without any predictor. Results 125 patients were listed for transplant. 96 were listed Status 1 (mean LAS 35.46, SD 5.32) and 9 listed Status 2 (Mean LAS 50.38, SD 15.22). Pulmonary diagnoses included IPF (31%), COPD (25%), CF (19%) and PAH (9%). Mortality on the waitlist was 23.2% (n=29), 48.8% (n=61) patients were transplanted and 28% (n=35) were still awaiting transplant or deactivated. In predicting death on the waitlist, LAS score outperformed Status (AIC of 149.66 versus 154.44; likelihood ratio p=0.008). In predicting post-transplant mortality, however, neither model with LAS (likelihood ratio p=0.19) or Status ranking (likelihood ratio p=0.051) were shown to be different than models without any predictor. Conclusions In this single center study, LAS score was a better predictor of waitlist mortality than the currently implemented Status ranking. Further analysis including other Canadian transplant centers is underway to validate these findings.

133 The Impact of Vaccination on Allosensitization in Candidates on the Lung Transplant Wait List

133 The Impact of Vaccination on Allosensitization in Candidates on the Lung Transplant Wait List

487: Waitlist Mortality among Children under 12 Years of Age Listed for Lung Transplantation in the United States

Risk factors for lung transplant waitlist mortality are not well described for children under 12 years of age where the indications for lung transplant differ substantially from older candidates and time-on-the-waitlist remains the primary determinant of lung allocation.The purpose of the study was to determine the incidence and risk factors associated with waitlist mortality in children awaiting lung transplantation under 12 years of age.