Collaborative Network Study of Airway Microbiome and Host Responses in Pediatric Respiratory Failure

儿科呼吸衰竭气道微生物组和宿主反应的协作网络研究

基本信息

批准号：
8991004
负责人：
PETER M MOURANI
金额：
$ 25.18万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-24 至 2019-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8991004
关键词：
Acute Lung Injury Adult Animals Area Awareness Back Bacteria Basic Science Beds Biological Biology Cardiovascular system Caring Catchment Area Child Childhood Clinical Clinical Research Clinical Sciences Clinical Trials Clinical Trials Network Colorado Complication Critical Care Critical Illness Critically ill children Data Development Discipline Disease Enrollment Environment Equilibrium Evaluation Faculty Family Fellowship Functional disorder Funding Hand Health Services Accessibility Housing Human Immune response Immunosuppression Institutes Institution Integration Host Factors Knowledge Laboratories Laboratory Research Laboratory Scientists Leadership Link Lung Lung diseases Mechanical ventilation Methodology Molecular National Institute of Child Health and Human Development Organ Outcome Assessment Outpatients Pathogenesis Patients Pediatric Hospitals Pediatric Intensive Care Units Population Population Growth Prevention strategy Process Public Health Recording of previous events Rehabilitation therapy Research Research Infrastructure Research Personnel Research Training Resources Respiratory Failure Services Specimen Stimulus Technology Training Training Programs Translational Research Translations United States National Institutes of Health Universities Virulence Virus Diseases Work arm base behavioral response clinical investigation clinical phenotype design effective therapy evaluation/testing experience follow-up human subject immune activation improved injured innovation insight medical specialties microbial host microbiome multidisciplinary neurodevelopment next generation novel novel therapeutics outreach program pathogen programs public health relevance research study response success translational approach translational clinical trial translational study treatment strategy ventilator-associated pneumonia

项目摘要

DESCRIPTION (provided by applicant): Recent discoveries across a broad range of basic science, technology and translational research have enhanced our understanding of disease processes and resulted in a multitude of potentially effective treatments for critically ill and injured children that require evaluation in the clinical environment. There is a tremendous need for a collaborative research network in pediatric critical care to facilitate the swift and effectie translation of scientific and technologic discoveries into clinical advances as well as to facilitae the flow of ideas from the bedside back to the laboratory. Access to appropriate patients and expertise in the execution of clinical trials must be linked to scientists and laboratories working within and across disciplines at the cutting edge of scientific advancement. At the University of Colorado Denver (UCD) and Children's Hospital Colorado (CHCO), we have a long history of successful collaborative basic and translational science programs, focused on integrated studies of cardiovascular-pulmonary responses to injurious stimuli at the molecular, cellular, organ, whole animal, and human subject levels. We will provide several unique areas of strength to the CPCCRN, including: 1) a distinctive translational approach to cardiovascular-pulmonary diseases, 2) experience with pediatric clinical trials execution, including innovative programs to enhance research awareness and participation among patients and families, 3) an eight state catchment area with high volumes of critically ill and injured children, 4) an in-house rehabilitation program and extensive outpatient outreach program in all pediatric specialties capable of providing follow-up care to nearly all our critically ill patients, and 5) a dynamic partnership with the Colorado Clinical Translational Science Institute to provide extensive research resources. Utilizing these assets, we will augment the contributions of CPCCRN to the care of critically ill children through innovative translational and clinical trial proposals, participation in Network leadership committees, and training the next generation of pediatric critical care researchers. Our concept proposal demonstrates our capacity to design innovative and relevant studies utilizing cutting edge methodologies. Ventilator associated pneumonia (VAP) is a serious complication of mechanical ventilation in critically ill children, yet there is limited understanding of the microbial and host factors associated with VAP. Endogenous bacteria are likely critical regulators of both pathogen behavior and host responses in the airways, modulating the virulence of potential pathogens. Limited understanding of the microbial and host factors associated with VAP has precluded development of truly effective prevention and treatment strategies. This study will assess how viral infection, bacterial populations, and the balance between host immune activation and immune suppression interact to determine whether a given patient develops VAP. Understanding how these critical interactions are involved in the pathogenesis of VAP will improve public health by identifying targets for more effective prevention and treatment strategies that will decrease the burden of VAP. 1

描述（由适用提供）：广泛的基础科学，技术和转化研究的最新发现增强了我们对疾病过程的理解，并导致了对临床环境中需要评估的重症患病和受伤儿童的多种潜在有效治疗。小儿重症监护的协作研究网络非常需要，以促进科学和技术发现迅速有效地转化为临床进步，以及改善从床边回到实验室的思想流动。获得适当的患者和执行临床试验的专业知识必须与科学家和实验室有关在科学进步的最前沿的学科内部和跨学科。在科罗拉多大学丹佛大学（UCD）和科罗拉多州儿童医院（CHCO），我们拥有成功的协作基础和翻译科学计划的悠久历史，重点是对分子，细胞，细胞，器官，整个动物和人类受害性刺激的心血管肺部对伤害性刺激的综合研究。我们将为CPCCRN提供几个独特的优势领域，包括：1）一种独特的转化方法对心血管 - 肺疾病疾病，2）具有儿科临床试验执行的经验，包括提高患者和家庭的研究意识和参与的创新计划，3）八个州关注领域，具有巨大的疾病和受伤的儿童，一个人受伤的儿童，4）所有儿科专业的康复计划和广泛的门诊外展计划，能够为几乎所有重病患者提供后续护理，以及5）与科罗拉多州临床转化科学学院的动态伙伴关系，以提供广泛的研究资源。利用这些资产，我们将通过创新的转化和临床试验建议，参与网络领导力承诺以及培训下一代儿科关注护理研究人员，通过创新的转化和临床试验建议来增强CPCCRN对重症儿童的照顾。我们的概念提案展示了我们使用尖端方法设计创新和相关研究的能力。呼吸机相关的肺炎（VAP）是重症儿童机械通气的严重并发症，但对与VAP相关的微生物和宿主因子的了解有限。内源性细菌可能是病原体行为和气道中宿主反应的关键调节剂，可调节潜在病原体的病毒。对与VAP相关的微生物和宿主因素的了解有限，无法发展真正有效的预防和治疗策略。这项研究将评估病毒感染，细菌群体以及宿主免疫激活与免疫抑制之间的平衡如何相互作用，以确定给定患者的发育是否是否为VAP。了解这些关键相互作用如何参与VAP的发病机理将通过确定可以减少VAP燃烧的更有效预防和治疗策略的目标来改善公共卫生。 1