Acute Respiratory Distress Syndrome after Isolated Traumatic Brain Injury: Platelet Biology, Endothelial Activation, and Mechanical Ventilation

孤立性脑外伤后的急性呼吸窘迫综合征：血小板生物学、内皮激活和机械通气

• 批准号: 9983146
• 负责人: Carolyn Marie Hendrickson
• 金额: $ 19.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9983146
• 关键词: Acute; Address; Adult; Adult Respiratory Distress Syndrome; Angiopoietin-2; Animals; Automobile Driving; Biological; Biological Factors; Biological Markers; Biology; Blood Coagulation Disorders; Blood Flow Cytometry; Blood Platelets; Body Weight; California; Cell Adhesion Molecules; Clinical; Coagulation Process; Cohort Studies; Complex; Critical Care; Data; Development; Disabled Persons; Disease; Endothelium; Enrollment; Exposure to; Functional disorder; General Hospitals; Goals; Health; Healthcare; Hospitalization; Hospitals; Hour; Incidence; Inflammation; Injury; Interleukin-8; Intervention; Intervention Studies; Intervention Trial; Investigation; Knowledge; Lead; Leukocytes; Lung; Lung diseases; Machine Learning; Measures; Mechanical ventilation; Mediating; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Neurological outcome; Neurosurgeon; Organ; Outcome; Pathogenesis; Pathway interactions; Patient Care; Patient-Focused Outcomes; Patients; Physicians; Plasma; Platelet Activation; Play; Prevention; Prospective cohort; Protocols documentation; Public Health; Research; Research Personnel; Research Training; Risk; Risk Assessment; Risk Factors; Role; San Francisco; Supportive care; TBI Patients; TIMP3 gene; Testing; Thrombelastography; Thromboxane B2; Tidal Volume; Translational Research; Trauma; Trauma patient; Traumatic Brain Injury; Traumatic injury; Ultrasonography; United States; Universities; Urine; Vascular Endothelium; Vascular Permeabilities; Ventilator-induced lung injury; Vulnerable Populations; Whole Blood; Work; adjudicate; adjudication; blood-brain barrier disruption; career; career development; cohort; design; electric impedance; experience; high risk; high risk population; improved; improved outcome; in vivo; innovation; lung injury; multidisciplinary; novel; patient oriented research; patient population; platelet function; pressure; prevent; prospective; response; stem; training opportunity; translational scientist

PROJECT SUMMARY/ ABSTRACT This is an application for a K23 award for Dr. Carolyn Hendrickson, a pulmonary and critical care physician at the University of California, San Francisco. Dr. Hendrickson is establishing herself as a young investigator in patient-oriented research of acute respiratory distress syndrome (ARDS), with a focus on the biologic mechanisms of ARDS after traumatic brain injury (TBI). This K23 award will provide Dr. Hendrickson with the support necessary to accomplish the following goals: (1) to become an expert clinical and translational researcher in ARDS after traumatic injury; (2) to study the biologic mechanisms of ARDS after TBI involving platelet biology, endothelial activation, and lung injury induced by mechanical ventilation; (3) to implement advanced analyses of complex observational data, including machine learning; (4) to develop an independent translational research career. Dr. Hendrickson's plan to achieve these goals is supported by a multidisciplinary mentoring team of experts. Her primary mentor, Dr. Michael Matthay, has extensive experience in translational ARDS research and in the career development of early stage investigators. Dr. Hendrickson will work with four co-mentors: Dr. Mitchell Cohen, a translational researcher studying coagulation after trauma, Dr. Alan Hubbard, a biostatistician specializing in causal inference, Dr. Geoffrey Manley, a neurosurgeon and leading investigator in TBI research, and Dr. Mark Looney, an expert platelet biology and lung injury. The development of ARDS after TBI is common and is associated with worse neurological outcomes. The biologic mechanisms driving ARDS after TBI are poorly understood. The central hypothesis of this proposal is that the risk of ARDS after TBI is mediated through activated vascular endothelium and platelets as well as non-protective mechanical ventilation strategies that use large tidal volumes. Dr. Hendrickson will investigate these causal pathways utilizing previously collected data and plasma from an ongoing observational cohort study. In this same cohort she will prospectively collect biospecimens, detailed mechanical ventilation data, and lung ultrasound images. This proposal represents an innovative approach to studying ARDS after TBI using carefully adjudicated exposures and outcomes. Dr. Hendrickson will test whether plasma biomarkers of endothelial activation, vascular permeability, and inflammation (Aim 1) and platelet function, activation, and aggregation (Aim 2) are associated with ARDS after TBI. She will collect lung ultrasound images and frequent mechanical ventilation data including tidal volumes and plateau pressures. She will test whether early exposure to non-protective mechanical ventilation is associated with ARDS after TBI (Aim 3). Addressing this gap in knowledge may lead to interventions that prevent ARDS and improve outcomes in this patient population. The research and training outlined in this proposal will form the basis for an R01-level proposal designed to study interventions to prevent and treat ARDS after traumatic injury.

项目摘要/摘要

项目成果

Potential Value of Biomarker Signatures in Sepsis and Acute Respiratory Distress Syndrome in Children and Adults.

生物标志物特征在儿童和成人脓毒症和急性呼吸窘迫综合征中的潜在价值。

• DOI: 10.1097/ccm.0000000000004169
• 发表时间: 2020
• 期刊: Critical care medicine
• 影响因子: 8.8
• 作者: Hendrickson,CarolynM;Matthay,MichaelA
• 通讯作者: Matthay,MichaelA

Elevated plasma levels of TIMP-3 are associated with a higher risk of acute respiratory distress syndrome and death following severe isolated traumatic brain injury.

• DOI: 10.1136/tsaco-2018-000171
• 发表时间: 2018
• 期刊: Trauma surgery & acute care open
• 影响因子: 2
• 作者: Hendrickson CM;Gibb SL;Miyazawa BY;Keating SM;Ross E;Conroy AS;Calfee CS;Pati S;Cohen MJ
• 通讯作者: Cohen MJ

Endothelial biomarkers in human sepsis: pathogenesis and prognosis for ARDS.

• DOI: 10.1177/2045894018769876
• 发表时间: 2018-04
• 期刊: Pulmonary circulation
• 影响因子: 2.6
• 作者: Hendrickson CM;Matthay MA
• 通讯作者: Matthay MA