Optimizing Donor Management in Lung Transplantation

优化肺移植供体管理

• 批准号: 10153871
• 负责人: Varun Puri
• 金额: $ 39.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153871
• 关键词: Accounting; Address; Affect; Age; Americas; Blinded; Brain Death; Caring; Characteristics; Chest; Chronic; Clinical; Data; Databases; Donor Selection; Functional disorder; Goals; Guidelines; Health care facility; Heart-Lung Transplantation; Heterogeneity; Hospitals; Image; International; Lead; Lung; Lung Transplantation; Lung diseases; Modeling; Morbidity - disease rate; Nomograms; Organ; Organ Donor; Organ Model; Organ Procurements; Organ Transplantation; Outcome; Patients; Performance; Perioperative; Protocols documentation; Quality of life; Recommendation; Resources; Risk; Sample Size; Scanning; Smoking; Smoking History; Societies; Solid; Standardization; System; Transplant Recipients; Transplantation; Uncertainty; Validation; Vasoconstrictor Agents; Waiting Lists; X-Ray Computed Tomography; cohort; curative treatments; data registry; economic impact; graft function; improved; instrument; mortality; novel; predictive modeling; primary endpoint; prospective; radiologist; tool; transplant database

Project Summary End-stage lung disease (ESLD) affects over 1 million patients in the U.S. and has an estimated annual economic impact exceeding $ 50 billion. Lung transplantation (LT), the only curative therapy for ESLD, improves survival as well as quality of life. Scarcity of donor organs remains the predominant barrier towards wider application of LT. Despite this discrepancy, only 20% of brain dead donors are considered for LT. Two predominant factors account for the low lung utilization rates in donors. Firstly, though the International Society for Heart and Lung Transplantation has proposed guidelines for lung donor assessment, these recommendations are fairly broad and are variably implemented, leading to significant heterogeneity in assessment of organs for potential transplantation. Unfortunately, there are no validated instruments available to inform donor lung utilization, thereby hampering optimization of a limited resource. Secondly, the impact of donor quality on early graft function after LT is unknown. Severe primary graft dysfunction (PGD) after LT leads to significant morbidity and mortality and lowers long-term survival. Donor factors associated with severe PGD remain inadequately understood and lead to further uncertainty in the decision to accept organs. In this proposal we will address both the principal reasons for low lung utilization rates nationally. Aim 1: To develop and validate a predictive model for lung utilization in brain dead donors. With the access to large, prospectively maintained database providing detailed donor level information for donors whose lungs were accepted or declined for LT, we will use multivariable analyses to create a predictive model for likelihood of lung utilization from a brain dead donor. A nomogram will be developed and validated in independent cohorts from other organ procurement organizations (OPOs) and presented as an electronic app. Aim 2: To understand the impact of donor factors on early outcomes in lung transplant recipients. We will evaluate lung donors at three collaborating OPOs with well-maintained databases. Detailed information on 90-day outcomes in recipients will be obtained from institutional and national registry data. We will develop multivariable models to understand the impact of donor clinical and CT scan imaging characteristics on the risk of early graft dysfunction and 90-day mortality after LT. The models will be externally validated and will be used to generate a donor score that can predict lung performance after transplant. By developing a tool to guide donor selection for LT and by delineating donor characteristics that impact early outcomes in LT recipients, we will address two critical questions for any clinician evaluating a donor offer: Can we accept these lungs? Will they function adequately? Our findings will be easily incorporated into routine donor care and will guide LT clinicians and policymakers in optimal management of a scarce resource. The models developed would also be readily adaptable for other solid organ transplants.

项目概要 终末期肺病 (ESLD) 影响着美国超过 100 万患者，预计每年会带来经济损失 影响超过500亿美元。肺移植 (LT) 是 ESLD 的唯一治疗方法，可提高生存率 以及生活质量。供体器官的稀缺仍然是更广泛应用的主要障碍 LT。尽管存在这种差异，但只有 20% 的脑死亡捐献者被考虑进行 LT。 捐献者肺利用率低有两个主要因素。首先，虽然国际 心肺移植协会提出了肺捐献者评估指南，这些指南 建议相当广泛，实施情况也各不相同，导致各方面存在显着的异质性 评估潜在移植的器官。不幸的是，没有可用的经过验证的仪器 告知供体肺的利用情况，从而阻碍有限资源的优化。其次，影响 供体质量对 LT 后早期移植物功能的影响尚不清楚。 LT 导联后严重原发性移植物功能障碍 (PGD) 导致显着的发病率和死亡率，并降低长期生存率。与严重 PGD 相关的供体因素 仍然没有得到充分的了解，并导致接受器官的决定进一步不确定。 在这项提案中，我们将解决全国肺利用率低的两个主要原因。 目标 1：开发并验证脑死亡供体肺利用的预测模型。随着 访问大型、前瞻性维护的数据库，为捐助者提供详细的捐助者级别信息 肺部接受或拒绝接受 LT，我们将使用多变量分析来创建预测模型 脑死亡供体的肺利用的可能性。将在独立的机构中开发和验证列线图 来自其他器官获取组织（OPO）的队列并以电子应用程序的形式呈现。 目标 2：了解供体因素对肺移植受者早期结果的影响。我们 将在三个拥有维护良好数据库的合作 OPO 中评估肺捐赠者。详细信息 接受者的 90 天结果将从机构和国家登记数据中获得。我们将开发 多变量模型以了解供体临床和 CT 扫描成像特征对风险的影响 LT 后早期移植物功能障碍和 90 天死亡率。这些模型将经过外部验证并使用 生成可以预测移植后肺功能的供体评分。 通过开发一种工具来指导 LT 捐献者的选择，并描述影响早期的捐献者特征 对于 LT 接受者的结果，我们将为任何评估捐赠者报价的临床医生解决两个关键问题： 我们接受这些肺吗？它们能充分发挥作用吗？我们的研究结果将很容易融入常规捐赠者中 护理并将指导 LT 临床医生和政策制定者对稀缺资源进行最佳管理。型号 所开发的技术也很容易适用于其他实体器官移植。