Objective lung assessment tools for improved organ use in lung transplantation

用于改善肺移植中器官使用的客观肺部评估工具

• 批准号: 10447648
• 负责人: EDWARD CANTU
• 金额: $ 60.88万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10447648
• 关键词: Acute; Acute Lung Injury; Address; Affect; American; Assessment tool; Biological Markers; Blood; Body Temperature; Cause of Death; Cessation of life; Chronic lung disease; Clinical; Cohort Studies; Collaborations; Complex; Decision Making; Disease; Donor Selection; Donor person; Fright; Funding; Future; Gene Expression; Hour; Hypoxia; Infrastructure; Knowledge; Life; Lung; Lung Transplantation; Measures; Methods; Morbidity - disease rate; Multicenter Studies; Organ; Organ Donor; Organ Procurements; Organ Transplantation; Organ failure; Outcome; Pathogenesis; Pathway interactions; Patients; Perfusion; Perioperative; Population; Positioning Attribute; Postoperative Period; Predisposition; Preparation; Preventive; Probability; Prospective cohort; Public Health; Quality of life; Reproducibility; Research; Risk; Risk Assessment; Selection Criteria; Signal Pathway; Specialized Center; Structure of parenchyma of lung; Syndrome; Technology; Therapeutic; Time; Toll-Like Receptor Pathway; Toll-like receptors; Transcript; Transplant Recipients; Transplantation; Uncertainty; United States National Institutes of Health; Update; Waiting Lists; Work; base; clinical trial enrollment; cost; graft dysfunction; high risk; immune activation; implantation; improved; innate immune pathways; lung injury; mortality; new technology; novel; oncology trial; predictive tools; prevent; prospective; radiological imaging; risk stratification; tool; transplant centers

Project Summary/Abstract Primary graft dysfunction (PGD) is the most common cause of morbidity and mortality after lung transplantation resulting in significant negative effects on quality of life and cost. PGD has a complex relationship with donor organ use because uncertainty in organ quality and concern that poor donor quality causes susceptibility to PGD results in high discard rates for potentially transplantable organs. With almost 1 in 5 candidates dying awaiting lungs for transplant, calls for new methods to define donor quality and PGD risk have become a major public health challenge. The long-term objective of our line of research is to prevent recipient death and expand the donor pool through better donor selection. Recent evidence suggests innate immune activation is important in PGD pathogenesis based on transcripts from donor lung tissue, bronchial wash and blood. Using these transcripts, we have developed two objective gene expression based risk assessment tools to stratify PGD risk and identify organs which may be suitable for transplant from the pool of unused organs. Utilizing these tools, we will conduct a prospective multicenter cohort study to externally validate our prediction tools for donor pool expansion. Successful completion of our aims will lead to an objective marker of donor organ quality whose application will simplify subjective decision making in donor selection and identification of new organs for donor pool expansion.

项目概要/摘要 原发性移植物功能障碍（PGD）是仅次于肺移植术后发病和死亡的最常见原因。 移植对生活质量和费用产生显着的负面影响。 PGD​​ 有一个 由于器官质量和关注的不确定性，与供体器官使用的复杂关系 捐献者质量差会导致对 PGD 的敏感性，从而导致潜在的高废弃率 可移植器官。近五分之一的候选人在等待肺部移植时死亡，呼吁 定义捐献者质量和 PGD 风险的新方法已成为一项重大公共卫生问题 挑战。 我们研究的长期目标是防止受者死亡并扩大 通过更好的捐助者选择来捐助者库。最近的证据表明先天免疫激活 基于供体肺组织、支气管冲洗液的转录本，在 PGD 发病机制中很重要 和血。使用这些转录本，我们开发了两种基于目标基因表达的 风险评估工具可对 PGD 风险进行分层并识别可能适合的器官 从未使用的器官库中进行移植。利用这些工具，我们将进行前瞻性 多中心队列研究，从外部验证我们对捐助者库扩张的预测工具。 成功完成我们的目标将产生捐赠器官质量的客观标志，其 应用程序将简化捐赠者选择和新捐赠者识别中的主观决策 扩大捐献者库的器官。