Metabolomics Evaluation of the Etiology of Pneumonia

项目摘要 Lilliam Ambroggio博士，公共卫生硕士，传染病流行病学家，其首要职业目标是 通过开发改进诊断的方法来改善患有常见严重感染的儿童的预后 并将这些方法应用到临床实践中。她提出的这项研究题为 肺炎病因学代谢组学评价(MEEP)结合先进的统计技术和 核磁共振(核磁共振)代谢组学方法识别代谢物，这将有助于 儿童社区获得性肺炎的病原学诊断。这样病原体鉴定将导致 及时和准确的诊断，这将使有针对性和有效的管理这种疾病。 候选人：Ambroggio博士是儿科学助理教授，在 辛辛那提儿童医院医学中心的医院医学、生物统计学和流行病学 (CCHMC)。她在德雷克塞尔大学获得公共卫生硕士学位和流行病学博士学位 开始在CCHMC获得博士后奖学金。她之前在CAP焦点临床管理方面的工作 关于抗生素处方和诊断工具以检测肺炎，并结合她以前的培训 分子和细胞生物学已经为她进行这项拟议的研究做好了准备。计划中的职业 发展计划将以她之前的培训为基础，制定四个培训目标，以增强她的发展轨迹 成为一名独立的调查者：1)在研究设计和实施中的体验式和指导性学习 定量1H-核磁共振代谢组学；2)获得并应用先进的统计分析；3)解释 代谢组学数据及其生物学背景和4)发展领导力和专业技能以执行 多中心研究。Ambroggio博士建议培训活动包括指导性和体验式学习 使她能够获得新陈代谢研究所需的技能。 导师/环境：Ambroggio博士和她的主要导师Samir S.Shah，医学博士，MSCE，已经组建了一个 强大的联合导师和顾问团队，指导Ambroggio博士完成拟议的培训和研究 活动。拟议的职业发展计划利用现有的智力和代谢组学资源。 通过辛辛那提大学和CCHMC，以及密歇根大学可用的资源 通过Ambroggio博士的外部导师，制药D凯瑟琳·斯特林格。此外，安布罗吉奥博士将出席 在当地没有最佳培训的情况下，举办国家研讨会和讲习班。作为一个机构，CCHMC是 致力于通过内部拨款、行政支持和结构化支持来支持初级教职员工 教职员工网络和教育的机会。安布罗吉奥博士将为此获取生物标本 来自一项完全可操作的、外部资助的前瞻性队列研究Carpe Diem的建议。教育署和教育署 CCHMC的住院服务提供了成熟的研究基础设施和大型门诊和 住院患者人群进行拟议研究。此外，所有导师都同意 参加安布罗吉奥博士的学术监督委员会，该委员会自2013年以来每季度召开一次会议。 研究：目前还没有准确的方法来确定儿童CAP的病因。这将导致 有CAP相关风险的儿童过度使用抗生素或延误适当治疗 发病率。这项提议是开发一种特异、快速和非侵入性病原体检测方法的第一步。 诊断为慢性阻塞性肺病的儿童的身份识别。目标1描述变异的来源(如年龄和性别) 存在于健康儿童的代谢物中的物质超过三点。目标2比较儿童的代谢物特征 从鼻咽或血液中检测出病毒阳性的人，细菌感染，如 肺炎支原体，或肺炎链球菌与儿童谁没有已知的感染。这个 此目的是使用定量~1H-核磁共振为每个病原体识别独特的代谢物图谱。 已确认身份。Aim 3将使用CAP患者的尿样，并将它们与健康人的尿样进行比较 在三个时间点上进行扭曲，以确定抗生素治疗对代谢物图谱的影响。这个 这些目标的完成将产生一个与以下方面相关的常见病原体的代谢物概况数据库 儿童慢性阻塞性肺病并推动系统生物学方法诊断和治疗慢性阻塞性肺病。 摘要：拟议研究的创新之处在于整合了来自 使用新的统计方法用定量核磁共振代谢组学研究流动人口 儿科CAP诊断学的临床挑战性问题。各部门之间的紧密合作 CCHMC的医院医学、生物统计学和流行病学以及急诊医学 密歇根大学的代谢组学核心确保了拟议研究的成功。这一奖项将 为Ambroggio博士提供在未来的多中心研究中取得成功所需的培训和研究 验证引起儿童CAP的病原体的代谢物特征。此外，这一职业发展 该奖项将促进Ambroggio博士发展成为全国公认的独立调查员，并 领导开展研究，改进儿童传染病的诊断工具，特别是 帽子。

Project Summary Lilliam Ambroggio, PhD, MPH is an infectious diseases epidemiologist whose overarching career goal is to improve outcomes for children with common, serious infections by developing methods to improve diagnostic accuracy and implementing these methods into clinical practice. The research she proposes entitled Metabolomic Evaluation in the Etiology of Pneumonia (MEEP) combines advanced statistical techniques with 1H-Nuclear Magnetic Resonance (NMR) metabolomics methodology to identify metabolites, which will facilitate etiologic diagnosis of community-acquired pneumonia (CAP) in children. Such pathogen identification will result in timely and accurate diagnosis that will permit targeted and effective management of this disease. Candidate: Dr. Ambroggio is an Assistant Professor of Pediatrics with a joint appointment in the Divisions of Hospital Medicine and Biostatistics and Epidemiology at Cincinnati Children's Hospital Medical Center (CCHMC). She completed a Master's in Public Health and a Ph.D. in Epidemiology at Drexel University prior to beginning a post-doctoral fellowship at CCHMC. Her previous work in the clinical management of CAP focusing on antibiotic prescribing and diagnostic tools to detect pneumonia in combination with her previous training in molecular and cellular biology have prepared her to conduct the proposed research. The proposed career development plan will build upon her previous training with four training goals to enhance her trajectory toward becoming an independent investigator: 1) Experiential and didactic learning in study design and execution of quantitative 1H-NMR metabolomics; 2) Acquire and apply advanced statistical analyses; 3) Interpret metabolomics data and its biological context and 4) Develop leadership and professional skills to execute multicenter studies. Dr. Ambroggio proposes training activities that include didactic and experiential learning to enable her to gain the necessary skills for metabolomic research. Mentors/Environment: Dr. Ambroggio and her primary mentor, Samir S. Shah, MD, MSCE, have assembled a strong team of co-mentors and advisors to guide Dr. Ambroggio through the proposed training and research activities. The proposed career development plan utilizes the intellectual and metabolomics resources available through the University of Cincinnati and CCHMC, as well as resources available at the University of Michigan through Dr. Ambroggio's external mentor, Kathleen Stringer, PharmD. In addition Dr. Ambroggio will attend national seminars and workshops when optimal training is not available locally. As an institution CCHMC is committed to supporting junior faculty members through internal grants, administrative support and structured opportunities for faculty networking and education. Dr. Ambroggio will be obtaining biological specimens for this proposal from a fully operational, externally-funded prospective cohort study, CARPE DIEM. Both the ED and inpatient services at CCHMC provide an established research infrastructure and a large ambulatory and hospitalized patient population to conduct the proposed research. In addition all mentors have agreed to participate on Dr. Ambroggio's scholarly oversight committee which has been meeting quarterly since 2013. Research: There is currently no accurate method to identify the etiology of CAP in children. This results in overtreatment with antibiotics or delays in appropriate treatment in children who are at risk for CAP-related morbidity. This proposal is the first step in developing a specific, fast and noninvasive approach for pathogen identification in children diagnosed with CAP. Aim 1 characterizes the sources (e.g. age and sex) of variation that exist in a healthy child's metabolome over three points. Aim 2 compares metabolite profiles from children who had a positive PCR test from either the nasopharynx or the blood for a virus, bacterial infection such as Mycoplasma pneumoniae, or Streptococcus pneumoniae with children who have no known infections. The purpose of this aim is to identify unique metabolite profiles using quantitative 1H-NMR for each pathogen identified. Aim 3 will use urine samples from patients with CAP and compare them with samples from healthy contorls over three time points to determine the impact of antibiotic treatment on metabolite profiles. The completion of these aims will generate a metabolite profile database of common pathogens associated with childhood CAP and drive a systems biology approach to CAP diagnosis and treatment. Summary: The innovation of the proposed research is the integration of robust clinical phenotype data from an ambulatory population with quantitative NMR metabolomics using novel statistical methods to address the clinically challenging problem of pediatric CAP diagnostics. The strong collaborations between the Divisions of Hospital Medicine, Biostatistics and Epidemiology, and Emergency Medicine at CCHMC and with the metabolomics core at the University of Michigan ensure the success of the proposed research. This award will provide Dr. Ambroggio with the training and research needed to be successful in a future, multi-center study to validate the metabolite profiles of pathogens causing CAP in children. Furthermore, this career development award will facilitate Dr. Ambroggio's development into a nationally-recognized independent investigator and leader conducting research that improves diagnostic tools for children with infectious diseases, specifically CAP.