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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.

项目总结/摘要原发性移植物功能障碍（PGD）是肺移植后发病和死亡的最常见原因。移植最近的数据表明，在急性肺损伤模型中，移植后PGD更好地了解这些特定的途径将提供机制线索PGD 发病机制和潜在的刺激研究的新的治疗途径。此外，识别 PGD的具体、个体化的风险因素可能允许未来的个性化治疗。我们的初步数据表明先天免疫激活在基于来自供体肺转录物的PGD发病机制中是重要的组织和在来自离体肺灌注失败（无移植）的灌注液中鉴定的细胞外囊泡中。鉴于这些发现，尽管正常的生理性肺损伤，需要进一步表征的测量。我们研究的长期目标是了解人肺PGD的机制移植，以确定战略，以确定捐助者的风险，防止受体死亡，并扩大通过更好的供体选择和使用离体肺灌注（EVLP）策略，我们的做法是使用供体肺支气管肺泡灌洗中的基因表达来预测PGD，并检查先天性参与移植供体和置于EVLP上的不可移植供体的PGD的免疫途径。的中心假设是，可以通过以下方法评估在获取供体肺之前供体肺中发生的肺损伤基因表达方法，以确定PGD风险和了解EVLP失败的常见机制。