Increasing Lung Allocation Scores Predict Worsened Survival Among Lung Transplant Recipients

Implemented in 2005, the lung allocation score (LAS) aims to distribute donor organs based on overall survival benefits for all potential recipients, rather than on waiting list time accrued. While prior work has shown that patients with scores greater than 46 are at increased risk of death, it is not known whether that risk is equivalent among such patients when stratified by LAS score and diagnosis. We retrospectively evaluated 5331 adult lung transplant recipients from May 2005 to February 2009 to determine the association of LAS (groups based on scores of ≤46, 47–59, 60–79 and ≥80) and posttransplant survival. When compared with patients with LAS ≤ 46, only those with LAS ≥ 60 had an increased risk of death (LAS 60–79: hazard ratio [HR], 1.52; 95% confidence interval [CI], 1.21–1.90; LAS ≥ 80: HR, 2.03; CI, 1.61–2.55; p < 0.001) despite shorter median waiting list times. This risk persisted after adjusting for age, diagnosis, transplant center volume and donor characteristics. By specific diagnosis, an increased hazard was observed in patients with COPD with LAS ≥ 80, as well as those with IPF with LAS ≥ 60.     

Geographic Disparities in Access to Lung Transplantation Before and After Implementation of the Lung Allocation Score

The 62 lung transplant centers in the United States are unevenly distributed. We examined whether remote dwelling (distance from one's primary residence to the nearest lung transplant center) or rural dwelling (as opposed to urban) influences patients’ access to lung transplantation, and whether such relationships changed following introduction of the lung allocation score (LAS) in May 2005. Between July 2001 and February 2009, 14 015 patients were listed for lung transplantation and 7923 (56.5%) were transplanted. Americans lived a median of 90.3 miles (IQR: 45.3–159.4) from the closest transplant center. Distance from a lung transplant center was inversely associated with the hazard of being listed before LAS implementation (adjusted HR for 100 miles = 0.87 [0.83–0.90]) and afterward (0.81 [0.78–0.85]); LAS implementation did not modify this relationship (p = 0.38). Once waitlisted, distance from the closest center was not associated with time to transplantation, and among those transplanted, distance was not associated with survival. Similar results were identified for rural, as opposed to urban, residence. We conclude that geographic disparaties exist in access to lung transplantation in the United States. These are mediated by listing practices rather than by transplantation rates, and were not mitigated by LAS implementation.     

Predictors of Lung Transplant Survival in Eurotransplant

This study was undertaken to assess the influence of patient/donor and center factors on lung transplantation outcome. Outcomes of all consecutive first cadaveric lung transplants performed at 21 Eurotransplant centers in 1997-99 were analyzed. The risk-adjusted center effect on mortality was estimated. A Cox model was built including donor and recipient age and gender, primary disease, HLA mismatches, patient's residence, cold ischemic time, donor's cause of death, serum creatinine, type of lung transplant, respiratory support status, clinical condition and percentage predicted FEV1. The center effect was calculated (expressed as the standardized difference between the observed and expected survival rates), and empirical and full Bayes methods were applied to evaluate between-center differences. A total of 590 adults underwent lung transplantation. The primary disease (p=0.01), HLA-mismatches (p = 0.02), clinical condition(p < 0.0001) and the patient's respiratory support status (p = 0.05) were significantly associated with survival. After adjusting for case-mix, no between-center differences could be found. An in-depth empirical Bayes analysis showed the between-center variation to be zero. Similar results were obtained from the full Bayes analysis. Based on these data, there is no scientific basis to support a hypothesis of possible association between center volume and lung survival rates.     

A Trial of Valganciclovir Prophylaxis for Cytomegalovirus Prevention in Lung Transplant Recipients

Cytomegalovirus (CMV) infection is common after lung transplantation. We performed a prospective trial of valganciclovir prophylaxis in lung recipients with outcomes compared to matched historical controls. The valganciclovir group (n = 40) (including D+/R- and R+ patients) was prospectively enrolled, and received oral valganciclovir 900 mg once daily for 12 weeks. Historical controls (n = 40) received 12 weeks of daily intravenous ganciclovir if D+/R- or 12 weeks of oral ganciclovir if R+. CMV viral load testing was done at two-week intervals until 6 months posttransplant. Baseline demographics and immunosuppression were comparable in the two groups. The incidence of CMV viremia was 16/40 (40.0%) in the valganciclovir arm versus 18/40 (45%) in the ganciclovir arm (p = NS). The incidence of symptomatic CMV disease was 8/40 (20%) versus 7/40 (17.5%), respectively (p = NS). In both groups viremia, while on prophylaxis, was uncommon (valganciclovir: 0/40 and ganciclovir: 2/40). Peak viral load and time to viremia were similar in the two arms. High rates of viremia and symptomatic disease occurred in the D+/R- patients after discontinuation of prophylaxis. Genotypic CMV sequence analysis demonstrated low rates of ganciclovir resistance in both groups. Valganciclovir prophylaxis had similar efficacy to either intravenous ganciclovir (D+/R- patients), or oral ganciclovir (R+ patients) in lung recipients.     

Development of the New Lung Allocation System in the United States

This article reviews the development of the new U.S. lung allocation system that took effect in spring 2005. In 1998, the Health Resources and Services Administration of the U.S. Department of Health and Human Services published the Organ Procurement and Transplantation Network (OPTN) Final Rule. Under the rule, which became effective in 2000, the OPTN had to demonstrate that existing allocation policies met certain conditions or change the policies to meet a range of criteria, including broader geographic sharing of organs, reducing the use of waiting time as an allocation criterion and creating equitable organ allocation systems using objective medical criteria and medical urgency to allocate donor organs for transplant. This mandate resulted in reviews of all organ allocation policies, and led to the creation of the Lung Allocation Subcommittee of the OPTN Thoracic Organ Transplantation Committee. This paper reviews the deliberations of the Subcommittee in identifying priorities for a new lung allocation system, the analyses undertaken by the OPTN and the Scientific Registry for Transplant Recipients and the evolution of a new lung allocation system that ranks candidates for lungs based on a Lung Allocation Score, incorporating waiting list and posttransplant survival probabilities.     

Rational Rationing or Discrimination: Balancing Equity and Efficiency Considerations in Kidney Allocation

After 6 years of deliberation, the Organ Procurement and Transplantation Network recently released a concept document proposing changes to the kidney allocation algorithm, sparking a heated debate about priority‐setting of scarce health resources and discrimination. Proponents of the proposal argue that it will result in an additional 15 223 life years following transplant annually for recipients, yet the benefit will not be equally distributed and will likely benefit younger patients. Critics argue that the new model will promote age discrimination and may lead to a further decrease in live kidney donation. If true, these concerns could undermine fairness and damage public trust in the organ allocation system. We address these objections and consider their merit, highlighting both benefits and shortcomings of the proposal. We argue that, despite weaknesses of the proposal and the importance of maintaining consistency in patient and provider expectations over time, the proposal represents a needed first step in balancing equity and efficiency.     

Development of Low Potassium Solution (EP4 Solution) for Long-Term Preservation of a Lung Transplant: Evaluation in Primate and Murine Lung Transplant Model

Abstract: The results of recent studies on long-term preservation using low potassium flush solution, which was originally produced in our department, are presented and discussed. In the primate model, a lung preserved for 24 h with EP4 solution retained sufficient function in single lung allotransplantation. In the murine experiments, we have evaluated the ion transport properties across alveolar epithelial cells in the transplanted lung using the tools of alveolar fluid clearance tests. The alveolar fluid clearance rate, which can be inhibited by 10^-3 M ouabain, is also well preserved for the first 24 h, indicating that the alveolar epithelial Na-K-ATPase is still functioning and that the 72 h preservation decreases those function of Na-K-ATPase in a time-dependent manner. In conclusion, because 24 h hypothermic preservation with EP4 solution did not show any obvious disadvantage on primate lung allografts and the cellular and molecular viability of the preserved lung flushed with EP4 solution could be retained for 24 h, this kind of solution with extracellular electrolyte composition can be applicable in the clinical settings.     

Hepatocellular Carcinoma Patients Are Advantaged in the Current Liver Transplant Allocation System

Patients with hepatocellular carcinoma (HCC) within Milan criteria receive priority on the liver transplant waiting list (WL) and compete with non‐HCC patients. Dropout from the WL is an indirect measure of transplant access. Competing risks (CR) evaluation of dropout for HCC and non‐HCC patients has not previously been reported. Patients listed between 16 March 2005 and 30 June 2008 were included. Probability of dropout was estimated using a CR technique as well as a Cox model for time to dropout. Overall, non‐HCC patients had a higher dropout rate from the WL than HCC patients (p < 0.0001). This was reproducible throughout all regions. In Cox regression, tumor size, model for end‐stage liver disease (MELD) score and alpha fetoprotein (AFP) were associated with increased dropout risk. Multivariable analysis with CR showed that MELD score and AFP, were most influential in predicting dropout for HCC patients. The index of concordance for predicting dropout with the CR was 0.70. HCC patients appear to be advantaged in the current allocation scheme based on lower dropout rates without regard to geography. A continuous score incorporating MELD, AFP and tumor size may help to prioritize HCC patients to better equate dropout rates with non‐HCC patients and equalize access.     

Lung and Heart Allocation in the United States

Lung and heart allocation in the United States has evolved over the past 20–30 years to better serve transplant candidates and improve organ utilization. The current lung allocation policy, based on the Lung Allocation Score, attempts to take into account risk of death on the waiting list and chance of survival posttransplant. This policy is flexible and can be adjusted to improve the predictive ability of the score. Similarly, in response to the changing clinical phenotype of heart transplant candidates, heart allocation policies have evolved to a multitiered algorithm that attempts to prioritize organs to the most infirm, a designation that fluctuates with trends in therapy. The Organ Procurement and Transplantation Network and its committees have been responsive, as demonstrated by recent modifications to pediatric heart allocation and mechanical circulatory support policies and by ongoing efforts to ensure that heart allocation policies are equitable and current. Here we examine the development of US lung and heart allocation policy, evaluate the application of the current policy on clinical practice and explore future directions for lung and heart allocation.     

Modification of the Arterial Anastomotic Technique Improves Survival in a Porcine Single Lung Transplant Model

Background: Lung transplantation is a valuable therapeutic option for selected patients with end-stage pulmonary disease. However, this treatment is complicated by ischaemia-reperfusion injury (IRI) of the lung in 10–20% of the recipients.

We developed an unilateral porcine lung transplant model to study IRI and describe our experience with two different arterial anastomotic techniques.

Material & methods: Twenty four domestic pigs [n = 6 χ (donor + recipient)/group] were used in this study. Donor lungs were harvested using an antegrade flush with cold Perfadex® and stored in the same solution for ± 8 hours. Recipient animals underwent a left thoracotomy. After native pneumonectomy, the left donor lung was transplanted in the following order: 1. left atrial cuff; 2. bronchus; 3 pulmonary artery. 2 The outcome in recipients from historical groups differing in anastomotic technique was compared. An end-to-end anastomosis on the left pulmonary artery was performed in group I versus a patch anastomosis on the main pulmonary artery in group II. One hour after reperfusion, the right pulmonary artery and main bronchus were ligated forcing the recipient to survive on the transplanted lung only. The animals were further observed for 6 hours.

Results: Survival 6 hours after exclusion of the right lung was 33% (2/6) in group I versus 83% (5/6) in group II. Animals in group I died of right heart failure manifested by acute dilation of the right ventricle following ligation of the hilum of the right lung.

Conclusion: Single lung transplantation with exclusion of the contralateral native lung is a critical model. Arterial end-to-end anastomosis resulted in an increased right ventricular afterload. The use of a patch technique improved the compliance of the arterial anastomosis and decreased early mortality. This transplant model is currently used in our laboratory to assess new methods for pulmonary preservation.     

The Impact of Pretransplant Mechanical Ventilation on Short‐ and Long‐Term Survival After Lung Transplantation

Lung transplantation in mechanically ventilated (MV) patients has been associated with decreased posttransplant survival. Under the Lung Allocation Score (LAS) system, patients at greatest risk of death on the waiting list, particularly those requiring MV, are prioritized for lung allocation. We evaluated whether pretransplant MV is associated with poorer posttransplant survival in the LAS era. Using a national registry, we analyzed all adults undergoing lung transplantation in the United States from 2005 to 2010. Propensity scoring identified nonventilated matched referents for 419 subjects requiring MV at the time of transplantation. Survival was evaluated using Kaplan–Meier methods. Risk of death was estimated by hazard ratios employing time‐dependent covariates. We found that pretransplant MV was associated with decreased overall survival after lung transplantation. In the first 6 months posttransplant, ventilated subjects had a twofold higher risk of death compared to nonventilated subjects. However, after 6 months posttransplant, survival did not differ by MV status. We also found that pretransplant MV was not associated with decreased survival in noncystic fibrosis obstructive lung diseases. These results suggest that under the LAS, pretransplant MV is associated with poorer short‐term survival posttransplant. Notably, the increased risk of death appears to be strongest the early posttransplant period and limited to certain pretransplant diagnoses.     

Lung Transplant Recipients Holding Companion Animals: Impact on Physical Health and Quality of Life

Since lung transplant recipients are susceptible to infections and inhaled pollution, many centers warn against pets. However, data supporting this recommendation are lacking. Our program is less restrictive regarding pets. This study, for the first time, investigates the association of pets with physiological and psychological parameters in these patients. A questionnaire concerning pets was sent to 104 lung transplant recipients. Lung function tests, levels of exhaled nitric oxide (FE(NO)), need for antibiotic treatments and hospitalizations, creatinine clearance, body mass index (BMI) and demographic data were assessed. Additionally, the questionnaire of life satisfaction (FLZ), a question on summarized life satisfaction (LS), the life orientation test (LOT), the hospital anxiety depression scale (HADS) and the social support questionnaire (F-SozU) were assessed. Response rate was 86%. Fifty-two percent defined themselves as pet owners, whereas 48% did not. The two groups did not differ in demographic or physiological data. Significant differences in FLZ (79/65, p = 0.04), in LS (4.3/3.9, p = 0.01), LOT (32/29, p = 0.006) and F-SozU (4.5/4.2, p = 0.04) were found in favor of pet owners. In lung transplant recipients keeping pets the frequency of somatic complications is not higher compared to lung transplant recipients without pets. After lung transplantation, pets are associated with a better quality of life.     

Lung Retransplantation Due to Chronic Lung Allograph Dysfunction: Results From a Spanish Transplant Unit

Introduction

Long-term survival of lung transplantation (LT) patients is mainly limited by the development of chronic lung allograft dysfunction (CLAD). Lung retransplantation (LR) is an alternative for a selected population. The aim of this study was to review the LR experience in our center.