Patient-Oriented Research in Acute Lung Injury and Host Defense in the ICU

ICU 中以患者为中心的急性肺损伤和宿主防御研究

基本信息

批准号：
10814680
负责人：
Janet Sojung Lee
金额：
$ 11.34万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10814680
关键词：
Acute Acute Lung Injury Acute Respiratory Distress Syndrome Award Back Bacterial Antibiotic Resistance Basic Science Biology Characteristics Clinical Clinical Medicine Communities Complement Complication Country Critical Care Critical Illness Dedications Defect Educational process of instructing Elements Encapsulated Faculty Foundations Functional disorder Goals Gram-Negative Bacteria Growth Health Health Care Costs Healthcare Hospital Mortality Host Defense Host Defense Mechanism Humoral Immunities Impairment In Vitro Individual Infection Inflammation Inflammatory Response Injury Integration Host Factors Intensive Care Intensive Care Units International Invaded Investigation Klebsiella pneumoniae Length of Stay Link Lower Respiratory Tract Infection Lower respiratory tract structure Lung Mechanical ventilation Medical Students Medicine Mentors Mid-Career Clinical Scientist Award (K24)Midcareer Investigator Award in Patient-Oriented Research Molecular Morbidity - disease rate Multi-Drug Resistance Nosocomial Infections Organ Outcome Pathway interactions Patient-Focused Outcomes Patients Peptide Hydrolases Physicians Predisposing Factor Prevalence Prevalence Study Productivity Proteolysis Pseudomonas aeruginosa Pulmonary Inflammation Research Research Personnel Research Support Research Training Resources Risk Factors Scientist Sepsis Serum Site Syndrome Testing Time Tissues Traction Training Translating Translational Research Universities Ventilator World Health Organization carbapenem resistance care burden extracellular forging improved insight lung injury microbial mortality novel pathogen pathogenic bacteria patient oriented research priority pathogen programs prospective respiratory skills

项目摘要

Abstract: The overall goal of this new application for a Midcareer Investigator Award in Patient-Oriented Research is to enable Dr. Lee to build a research and mentoring program in patient-oriented research in acute lung injury and host defense. Acute lower respiratory traction infections (LRTI) in the ICU remains an enormous healthcare burden in the US and worldwide. LRTI remains a major cause of sepsis and risk factor for acute lung injury. Bacterial LRTI is also a frequent complication of acute lung injury that increases patient morbidity, length of stay and health-care costs. Dr. Lee is a physician scientist focused on broadening molecular understanding of critical illness syndromes such as acute lung injury by probing host-pathogen interplay to elucidate the biology of host factors that predispose individuals to pathogen-induced injury. This award will allow protected time for dedicated teaching, training, and mentoring of trainees that include junior faculty, fellows, residents, and medical students in translational research focusing on problems arising in critically ill patients. Specifically, mentoring will support novel investigations into acute lower respiratory tract infections from common Gram-negative bacterial pathogens in the ICU. The major hypothesis is that distinct molecular determinants of host-pathogen interplay identified at the bench provide unique insights into impairments of host defense mechanisms that associate with adverse clinical outcomes in the ICU. Two aims are proposed that leverage the unique capabilities of the investigator in translational research. Aim 1 will evaluate microbial factors that predispose patients to tissue inflammation and injury instigated by the Gram-negative pathogen Pseudomonas aeruginosa (PA) respiratory isolates in the ICU. We will test molecular pathways identified at the bench to explore the relationship between pathogen protease function to patient outcomes such as microbial persistence in the lower respiratory tract, ventilator-free days, length of stay and mortality. Aim 2 will evaluate impairments in host humoral immunity during critical illness and examine the relationship to patient outcomes including multiple organ dysfunction, mortality, acquisition of multi-drug resistant ICU infections, and serum killing of encapsulated Gram-negative pathogen Klebsiella pneumoniae. This K24 award will allow Dr. Lee to achieve two principal goals: (1) forge links between basic biology and medicine by probing host-pathogen interplay in the ICU setting and improve understanding of critical illness syndromes such as ARDS; and (2) to further develop her skills in mentoring trainees in patient-oriented research in molecular critical care while expanding her time devoted to mentoring. The successful execution of this award will enhance the productivity of both the K24 investigator and increase the pool of well-trained clinician investigators who are equipped to translate fundamental biology to the bedside and back.

摘要：这项以患者为导向的职业生涯中期调查员奖新申请的总体目标研究目的是让李博士能够建立一个以患者为导向的急症研究的研究和指导计划。肺损伤和宿主防御。 ICU 中的急性下呼吸道牵引感染 (LRTI) 仍然是一个巨大的问题美国和全世界的医疗保健负担。 LRTI 仍然是败血症的主要原因和急性肺的危险因素受伤。细菌性 LRTI 也是急性肺损伤的常见并发症，会增加患者的发病率、寿命住宿和医疗保健费用。李博士是一位专注于拓宽分子理解的医师科学家通过探究宿主与病原体的相互作用来阐明急性肺损伤等危重疾病综合征的生物学使个体容易受到病原体引起的损伤的宿主因素。该奖项将为以下人员提供受保护的时间对学员（包括初级教师、研究员、住院医师和医疗人员）进行专门的教学、培训和指导从事转化研究的学生，重点关注危重患者出现的问题。具体来说，辅导将支持对常见革兰氏阴性细菌引起的急性下呼吸道感染的新研究 ICU 内的病原体。主要假设是宿主-病原体相互作用的不同分子决定因素工作台上确定的对与宿主防御机制相关的损伤提供了独特的见解 ICU 中的不良临床结果。提出了两个目标，以利用独特的能力转化研究研究员。目标 1 将评估使患者倾向于组织的微生物因素由革兰氏阴性病原体铜绿假单胞菌 (PA) 呼吸道引起的炎症和损伤隔离在 ICU 中。我们将测试在实验室确定的分子途径，以探索之间的关系病原体蛋白酶对患者结果的作用，例如下呼吸道中的微生物持续存在，无呼吸机天数、住院时间和死亡率。目标 2 将评估宿主体液免疫的损伤在危重疾病期间并检查与患者结果的关系，包括多器官功能障碍，死亡率、多重耐药 ICU 感染的获得以及封装革兰氏阴性菌的血清杀灭病原体为肺炎克雷伯菌。这个 K24 奖项将使李博士能够实现两个主要目标：(1) 建立联系通过探索 ICU 环境中宿主与病原体的相互作用，建立基础生物学和医学之间的联系，并改进了解ARDS等危重疾病综合征； (2) 进一步发展她的指导技能学员们从事以患者为导向的分子重症监护研究，同时扩大了她用于指导的时间。该奖项的成功执行将提高 K24 研究者的生产力并增加一群训练有素的临床研究人员，他们有能力将基础生物学转化为临床应用然后回来。