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

• 批准号: 10396528
• 负责人: Janet Sojung Lee
• 金额: $ 11.47万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396528
• 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; 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; 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; day length; extracellular; improved; insight; lung injury; microbial; mortality; novel; pathogen; pathogenic bacteria; patient oriented research; priority pathogen; programs; prospective; research facility; respiratory; skills

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：该新申请的总体目标是以患者为导向的中级研究员奖 研究是为了使李博士能够在急性研究中建立研究和指导计划 肺部受伤和宿主防御。 ICU中的急性下呼吸牵引感染（LRTI）仍然是巨大的 美国和全球的医疗保健负担。 LRTI仍然是脓毒症和急性肺风险因素的主要原因 受伤。细菌LRTI也是急性肺损伤的常见并发症，可增加患者的发病率，长度 住宿和医疗保健费用。李博士是一位专注于扩大分子理解的医师科学家 通过探测宿主 - 病原体相互作用来阐明生物学 宿主因子使个体易于病原体诱导的损伤。该奖项将为受保护的时间 包括初级教师，研究员，居民和医学在内的学员的专门教学，培训和指导 转化研究的学生重点是重病患者​​出现的问题。具体来说，指导意志 支持对急性下呼吸道感染的新型研究 ICU中的病原体。主要假设是宿主 - 病原体相互作用的不同分子决定因素 在替补席上确定的对与与宿主防御机制的损害相关的损害提供了独特的见解 ICU中的不良临床结果。提出了两个目标，以利用 转化研究的研究者。 AIM 1将评估使患者易于组织的微生物因子 革兰氏阴性病原体铜绿假单胞菌（PA）呼吸引起的炎症和损伤 ICU中的分离物。我们将测试在板凳上确定的分子途径，以探索 病原体蛋白酶功能对患者结局的功能，例如下呼吸道中的微生物持久性， 无呼吸机的日子，住院时间和死亡率。 AIM 2将评估宿主体液免疫的损害 在重症疾病期间，检查与患者结局的关系，包括多个器官功能障碍， 死亡率，抗多药ICU感染以及封装的革兰氏阴性症的血清杀死 病原体肺炎。该K24奖将使Lee博士实现两个主要目标：（1）Forge链接 通过探测ICU环境中的宿主 - 病原体相互作用并改进，在基本生物学和医学之间 了解诸如ARDS之类的重症疾病综合征； （2）进一步发展她的指导技能 从事分子重症监护研究的学员，同时扩大了专门用于指导的时间。 该奖项的成功执行将提高K24调查员的生产率和提高 训练有素的临床医生调查员库，他们有能力将基本生物学转化为床边 然后回来。