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

基本信息

批准号：
10609043
负责人：
EDWARD CANTU
金额：
$ 59.89万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/10609043
关键词：
Acute Acute Lung Injury Address Affect American Assessment tool Blood Body Temperature Cause of Death Cessation of life Chronic lung disease Clinical Cohort Studies Collaborations Complex Decision Making Disease Donor Selection Donor person Early identification Fright Funding Future Gene Expression Hour Hypoxia Infiltration 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 Toll-Like Receptor Pathway Toll-like receptors Transcript Transplant Recipients Transplantation Uncertainty United States National Institutes of Health Update Waiting Lists Work biomarker identification candidate selection clinical predictors 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 ventilation

项目摘要

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。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Primary graft dysfunction after lung transplantation.

肺移植后原发性移植物功能障碍。

DOI：
10.1097/mot.0000000000001065
发表时间：
2023
期刊：
Current opinion in organ transplantation
影响因子：
2.2
作者：
Hunt,MalloryL;Cantu,Edward
通讯作者：
Cantu,Edward

Airway epithelial cell identity and plasticity are constrained by Sox2 during lung homeostasis, tissue regeneration, and in human disease.

DOI：
10.1038/s41536-023-00344-w
发表时间：
2024-01-05
期刊：
NPJ REGENERATIVE MEDICINE
影响因子：
7.2
作者：
Shiraishi, Kazushige;Morley, Michael P.;Jones, Dakota L.;Zhao, Gan;Weiner, Aaron I.;Basil, Maria C.;Cantu, Edward;Ferguson, Laura T.;Oyster, Michele;Babu, Apoorva;Ying, Yun;Zhou, Su;Li, Shanru;Vaughan, Andrew E.;Morrisey, Edward E.
通讯作者：
Morrisey, Edward E.

Epidemiology, risk factors, and outcomes of lung retransplantation: An analysis of the International Society for Heart and Lung Transplantation Thoracic Transplant Registry.

DOI：
10.1016/j.healun.2022.06.022
发表时间：
2022-10
期刊：
JOURNAL OF HEART AND LUNG TRANSPLANTATION
影响因子：
8.9
作者：
Harhay, Michael O.;Cherikh, Wida S.;Toll, Alice E.;Christie, Jason D.;Stehlik, Josef;Chambers, Daniel;Hayes Jr, Don;Cantu, Edward
通讯作者：
Cantu, Edward

Continuing progress toward improved lung assessment.

DOI：
10.1016/j.healun.2021.04.019
发表时间：
2021-07
期刊：
JOURNAL OF HEART AND LUNG TRANSPLANTATION
影响因子：
8.9
作者：
Cantu, Edward
通讯作者：
Cantu, Edward

Cell-Free DNA Maps Tissue Injury and Correlates with Disease Severity in Lung Transplant Candidates.

无细胞 DNA 绘制了肺移植候选者的组织损伤图并与疾病严重程度相关。

DOI：
10.1164/rccm.202306-1064oc
发表时间：
2024
期刊：
American journal of respiratory and critical care medicine
影响因子：
24.7
作者：
Balasubramanian,Shanti;Richert,MaryE;Kong,Hyesik;Fu,Sheng;Jang,MoonKyoo;Andargie,TemesgenE;Keller,MichaelB;Alnababteh,Muhtadi;Park,Woojin;Apalara,Zainab;Sun,Jian;Redekar,Neelam;Orens,Jonathan;Aryal,Shambhu;Bush,ErrolL;Ca
通讯作者：
Ca