Advanced diagnostics for donor lung assessment and ex vivo lung perfusion candidate selection

用于供体肺评估和离体肺灌注候选选择的高级诊断

基本信息

批准号：
9223995
负责人：
EDWARD CANTU
金额：
$ 8.05万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-16 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9223995
关键词：
Acute Lung Injury Address Adoption Affect Allografting American Biopsy Bronchoalveolar Lavage Bronchoalveolar Lavage Fluid Cause of Death Cessation of life Chronic lung disease Classification Clinical Trials Data Development Diagnostic Donor Selection Donor person Drug Targeting Evolution Failure Functional disorder Future Gene Expression Gene Expression Profile Gene Expression Profiling Health Care Costs Human Immune Individual Injury Investigation Irrigation Ischemia Lead Lung Lung Transplantation Lung diseases Measurement Measures Methods Modeling Molecular Morbidity - disease rate Natural Immunity Organ Organ Donor Outcome Pathogenesis Pathway interactions Patients Pattern Perfusion Perioperative Physiological Population Predisposition Public Health Reperfusion Therapy Research Risk Risk Factors Rosa Sampling Selection Criteria Specimen Staging Structure of parenchyma of lung Technology Testing Therapeutic Tissues Transcript Transplant Recipients Transplant Surgeon Transplantation Up-Regulation Validation Variant Waiting Lists Work abstracting base biomarker panel candidate selection clinical decision-making cohort cost efficacy testing extracellular vesicles genome-wide high risk immune activation improved lung injury mortality new technology novel novel therapeutics personalized medicine predict clinical outcome prevent research clinical testing targeted treatment tool transcriptome wasting

项目摘要

Project Summary/Abstract Primary graft dysfunction (PGD) is the most common cause of morbidity and mortality after lung transplantation. Recent data indicate participation of a few specific pathways in acute lung injury models and post-transplant PGD. A better understanding of these specific pathways would offer mechanistic clues to PGD pathogenesis and potentially stimulate investigation of novel therapeutic avenues. In addition, identification of specific, individualized risk factors for PGD might allow future personalized therapy. Our preliminary data indicate that innate immune activation is important in PGD pathogenesis based on transcripts from donor lung tissue and in extracellular vesicles identified in perfusate from ex vivo lung perfusion failures (no transplant). Given these findings, there appears to be unmeasured injury to the lung despite normal physiologic measurements which needs to be further characterized. The long-term objective of our line of research is to understand the mechanism of PGD in human lung transplantation in order to identify strategies to identify donors at risk, prevent recipient death and expand the donor pool through better donor selection and use of ex vivo lung perfusion (EVLP) strategies. Our approach is to use gene expression in donor lung bronchoalveolar lavage to predict PGD and to examine the innate immunity pathways involved in PGD of transplanted donors and untransplantable donors placed on EVLP. The central hypotheses are that lung injury occurring in the donor lung prior to procurement can be evaluated by gene expression methods to determine PGD risk and understand common mechanisms of EVLP failure.

项目摘要/摘要原发性移植功能障碍（PGD）是肺后发病和死亡率的最常见原因移植。最近的数据表明，一些特定途径参与急性肺损伤模型和移植后PGD。更好地了解这些特定途径将为PGD提供机械线索发病机理并可能刺激新型治疗途径的研究。另外，识别 PGD的特定个性化危险因素可能允许将来的个性化治疗。我们的初步数据表明先天免疫激活在供体肺的转录本中在PGD发病机理中很重要组织和细胞外囊泡在灌注液中从体内肺灌注衰竭（无移植）中鉴定出来。鉴于这些发现，尽管生理正常，但似乎对肺部造成了无法测量的损伤需要进一步表征的测量。我们研究线的长期目标是了解人类肺中PGD的机制移植以确定识别有风险捐助者的策略，防止接受者死亡并扩大通过更好的供体选择和使用离体肺灌注（EVLP）策略的供体池。我们的方法是在供体肺支气管肺泡灌洗中使用基因表达来预测PGD并检查先天涉及移植供体PGD的免疫途径和置于EVLP上的不可转移供体的供应途径。这中心假设是，在采购之前，供体肺中发生的肺损伤可以通过确定PGD风险并了解EVLP失败的常见机制的基因表达方法。