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

• 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
• 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

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.

项目摘要/摘要 研究：需要机械通气的急性低氧呼吸衰竭（AHRF）是一种常见，昂贵的 死亡率很高，但仍得到支持。确定有效的目标疗法 诸如AHRF之类的异质疾病取决于表征患者的子集或亚表征 疾病相关事件的可能性很高或对治疗的反应。这个项目将描述一个新颖的子 - 机械通风的AHRF中称为持续性低氧呼吸衰竭（PHRF）的表型 患者，由ICU第3天的持续机械通气和低氧血症定义的PHRF。使用临床 在其他异质综合症中定义亚表征的轨迹有助于描述患者 独特的预后和突出有助于轨迹的生物学机制。大，独立 华盛顿大学和范德比尔特大学的潜在ICU队列，Sathe博士将讲话 以下目的：（1）确定与PHRF相关的ICU第1天的临床因素（2）确定生物学 PHRF的特征是分析的ICU第1天和第3天循环的肺损伤生物标志物以及（3）发育和 验证一个可预测ICU第3天PHRF的多变量模型。了解PHRF的风险因素将有助于 对早期机制对肺损伤的病理反应很重要。子 - 在AHRF中而不是ARDS内的表型（以前的努力集中）包括扩大范围 我们针对治疗的患者并提高了研究定义的可靠性。另外，区分 将会也不会发展PHRF的患者将有助于临床编程，资源分配和目标 患者的试验入学率不太可能通过现有治疗来改善。结果将填补关键知识空白 NHLBI优先考虑哪些因素决定了持续性低氧血症的风险，以及程度 这些因素在AHRF中跨ARD和其他条件重叠。 候选人/环境：在华盛顿大学的支持下，Mark Wurfel博士，凯瑟琳博士 “ Terri” Hough和生物统计学家Leila Zelnick博士，该奖项将有助于建立Sathe博士的职业 转化的物理科学家实践肺和重症监护。通过拟议的研究，她 将开发基本技能，用于分析纵向队列数据，现代机器学习 预测方法，高质量的测量和肺损伤生物标志物的分析。这项工作将 确定生物学途径在潜在的AHRF队列中进行更深入的研究，她将在 Future K23。她计划建立一个职业，检查急性呼吸衰竭和其他其他 ICU综合征，以促进针对重症患者的靶向治疗的发展。