Characterizing clinical and biologic features of persistent hypoxemic respiratory failure

持续性低氧性呼吸衰竭的临床和生物学特征

基本信息

批准号：
10462490
负责人：
Neha Alhad Sathe
金额：
$ 8.3万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2021-05-16 至 2023-05-15
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10462490
关键词：
Academic Medical Centers Acute Acute Respiratory Distress Syndrome Acute respiratory failure Address Admission activity Advanced Development Age Alveolar Angiopoietin-2 Apoptosis Award Biologic Characteristic Biological Biological Factors Biological Markers Biological Process Caring Classification Clinical Clinical Data Critical Care Critical Illness Data Disease Doctor of Philosophy Endothelium Enrollment Environment Epithelial Event Funding Future Heterogeneity Hypoxemia Hypoxemic Respiratory Failure Inflammation Injury Interleukin-6 Investigational Therapies Knowledge Learning Longitudinal cohort Lung Measurement Measures Mechanical ventilation Mentored Patient-Oriented Research Career Development Award Molecular Molecular Probes Morbidity - disease rate National Heart, Lung, and Blood Institute Outcome Pathologic Pathway interactions Patients Pharmacology Phenotype Plasma Pneumonia Population Prognosis Prospective cohort Research Research Priority Resource Allocation Respiratory Failure Risk Risk Factors Scientist Severity of illness Syndrome Testing Therapeutic Time Training Universities Washington Work acute hypoxemic respiratory failure biological heterogeneity career circulating biomarkers cohort cost endothelial dysfunction high risk improved inflammatory marker longitudinal analysis lung injury machine learning method male mortality mortality risk new therapeutic target novel participant enrollment patient subsets predictive modeling prevent prognostication prospective respiratory response sex skills targeted treatment translational physician treatment response

项目摘要

PROJECT SUMMARY/ABSTRACT Research: Acute hypoxemic respiratory failure (AHRF) requiring mechanical ventilation is a common, costly condition with high mortality, yet treatment remains supportive. Identifying effective targeted therapeutics in heterogeneous conditions like AHRF depends on characterizing subsets, or sub-phenotypes, of patients with high likelihood of disease related events or response to therapy. This project will characterize a novel sub- phenotype called persistent hypoxemic respiratory failure (PHRF) among mechanically ventilated AHRF patients, with PHRF defined by ongoing mechanical ventilation and hypoxemia on ICU day 3. Using clinical trajectory to define sub-phenotypes in other heterogeneous syndromes has helped delineate patients with distinct prognosis and highlight biologic mechanisms contributing to trajectories. With large, independent prospective ICU cohorts from the University of Washington and Vanderbilt University, Dr. Sathe will address the following aims: (1) identify clinical factors on ICU day 1 associated with PHRF (2) determine biologic features of PHRF by analyzing ICU day 1 and day 3 circulating biomarkers of lung injury and (3) develop and validate a multivariable model that predicts PHRF on ICU day 3. Understanding risk factors for PHRF will help hone in on the early mechanisms important for pathologic responses to lung injury. Advantages to sub- phenotyping within AHRF rather than ARDS (where prior efforts were focused) include expanding the scope of patients we target for therapy and improving reliability of study definitions. In addition, discriminating between patients who will and will not develop PHRF will aid clinical prognostication, resource allocation, and targeted trial enrollment of patients unlikely to improve with existing treatment. The results will fill key knowledge gaps prioritized by the NHLBI regarding which factors determine risk for persistent hypoxemia, and the degree to which these factors overlap across ARDS and other conditions in AHRF. Candidate/Environment: With the support of the University of Washington, Dr. Mark Wurfel, Dr. Catherine “Terri” Hough, and biostatistician Leila Zelnick, PhD, this award will help establish Dr. Sathe’s career as a translational physician-scientist practicing Pulmonary and Critical Care. Through the proposed research, she will develop fundamental skills for analysis of longitudinal cohort data, contemporary machine learning methods for prediction, and high-quality measurement and analysis of lung injury biomarkers. This work will identify biologic pathways for more in-depth study in prospective AHRF cohorts, which she will pursue in a future K23. She plans to establish a career examining the heterogeneity of acute respiratory failure and other ICU syndromes, to advance the development of targeted therapeutics for critically ill patients.

项目概要/摘要研究：需要机械通气的急性低氧性呼吸衰竭（AHRF）是一种常见且昂贵的疾病死亡率很高，但治疗仍然是支持性的。像 AHRF 这样的异质性疾病取决于患者的亚群或亚表型特征疾病相关事件或治疗反应的可能性很高，该项目将描述一个新的亚组。机械通气 AHRF 中称为持续性低氧血症性呼吸衰竭 (PHRF) 的表型患有 PHRF 的患者，定义为 ICU 第 3 天持续机械通气和低氧血症。使用临床定义其他异质综合征的亚表型的轨迹有助于描述患有以下疾病的患者不同的预后和突出的生物机制有助于大的、独立的轨迹。 Sathe 博士将在来自华盛顿大学和范德比尔特大学的未来 ICU 队列中发表演讲目标如下：(1) 确定 ICU 第 1 天与 PHRF 相关的临床因素 (2) 确定生物学通过分析 ICU 第 1 天和第 3 天的肺损伤循环生物标志物来确定 PHRF 的特征，并且 (3) 开发和验证预测 ICU 第 3 天 PHRF 的多变量模型。了解 PHRF 的风险因素将有所帮助深入了解对肺损伤病理反应重要的早期机制。 AHRF 而不是 ARDS（之前的努力重点）内的表型分析包括扩大我们针对治疗和提高研究定义的可靠性的患者进行区分。将会或不会发生 PHRF 的患者将有助于临床预后、资源分配和有针对性的治疗现有治疗不太可能改善患者的试验入组结果将填补关键的知识空白。 NHLBI 优先考虑哪些因素决定持续性低氧血症的风险，以及其程度这些因素在 ARDS 和 AHRF 的其他病症中重叠。候选人/环境：在华盛顿大学Mark Wurfel博士、Catherine博士的支持下 “Terri” Hough 和生物统计学家 Leila Zelnick 博士表示，该奖项将有助于奠定 Sathe 博士的职业生涯通过拟议的研究，她成为从事肺科和重症监护的转化医师科学家。将培养纵向队列数据分析、当代机器学习的基本技能这项工作将用于肺损伤生物标志物的预测、高质量测量和分析。确定在前瞻性 AHRF 队列中进行更深入研究的生物学途径，她将在未来的 K23，她计划建立一个研究急性呼吸衰竭和其他疾病异质性的职业。 ICU 综合征，推动危重患者靶向治疗的开发。