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Metabolomics Evaluation of the Etiology of Pneumonia

肺炎病因的代谢组学评估

基本信息

批准号：
10097962
负责人：
Lilliam Ambroggio
金额：
$ 12.83万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-03-07 至 2024-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10097962
关键词：
11 year old Accident and Emergency department Active Learning Address Adult Advanced Development Age Antibiotic Resistance Antibiotic Therapy Antibiotics Appointment Award Bacteria Bacterial Infections Bacterial Pneumonia Biological Biometry Blood Blood specimen Child Childhood Clinical Clinical Data Clinical Management Clostridium difficile Colitis Collaborations Communicable Diseases Culture Techniques Data Data Set Databases Development Development Plans Diagnosis Diagnostic Diagnostic tests Disease Management Doctor of Pharmacy Doctor of Philosophy Education Educational workshop Emergency Medicine Enrollment Ensure Environment Epidemiologist Epidemiology Etiology Evaluation Faculty Fellowship Foundations Funding Future Goals Grant Hospitalization Hospitals Hour Infant Infection Infectious Disease Epidemiology Institution Joints K-Series Research Career Programs Knowledge Leadership Learning Lung Medical center Medicine Mentors Methodology Methods Michigan Molecular and Cellular Biology Morbidity - disease rate Multicenter Studies Mycoplasma pneumoniae Nasopharynx Nuclear Magnetic Resonance Pathogen detection Patients Pattern Pediatric Hospitals Pediatrics Pneumonia Population Postdoctoral Fellow Prospective cohort study Public Health Research Research Activity Research Design Research Infrastructure Research Personnel Resources Risk Sampling Science Source Specimen Sputum Statistical Data Interpretation Statistical Methods Streptococcus pneumoniae Structure Systems Biology Techniques Testing Thoracic Radiography Time Training Training Activity Translating Universities Urine Variant Viral Viral Pneumonia Virus Work accurate diagnosis adverse drug reaction aged antimicrobial bacterial community biobank career career development clinical database clinical decision-making clinical examination clinical phenotype clinical practice co-infection cohort community acquired pneumonia cost diagnostic accuracy improved improved outcome innovation inpatient service meetings member metabolic profile metabolome metabolomics metabolomics resource microbial mortality noninvasive diagnosis novel overtreatment pathogen pathogenic bacteria pathogenic virus patient population phenotypic data point-of-care diagnostics professor response sex skills small molecule smoking exposure success tool validation studies

项目摘要

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.

项目摘要 Lilliam Ambroggio博士是一位传染病流行病学家，其首要职业目标是通过开发改善诊断方法，改善患有常见严重感染的儿童的结局并将这些方法应用于临床实践。她提出的研究题目是代谢组学评价肺炎病因学（MEEP）结合了先进的统计技术， 1H-核磁共振（NMR）代谢组学方法，以确定代谢物，这将有助于儿童社区获得性肺炎（CAP）的病原学诊断。这种病原体鉴定将导致及时和准确的诊断，将允许有针对性的和有效的管理这种疾病。候选人：Ambroggio博士是儿科助理教授，在以下部门联合任命：辛辛那提儿童医院医学中心医院医学、生物统计学和流行病学（CCHMC）。她完成了公共卫生硕士和博士学位。在德雷克塞尔大学的流行病学，在CCHMC开始博士后研究。她以前在CAP聚焦的临床管理方面的工作抗生素处方和诊断工具，以检测肺炎结合她以前的培训，分子和细胞生物学为她进行这项研究做好了准备。提议的职业发展计划将建立在她以前的培训基础上，有四个培训目标，以提高她的发展轨迹，成为一名独立的研究者：1）在研究设计和执行中的经验和教学学习定量1H-NMR代谢组学; 2）获取并应用先进的统计分析; 3）解释代谢组学数据及其生物背景; 4）培养领导力和专业技能，多中心研究。Ambroggio博士提出了包括教学和体验式学习在内的培训活动，使她能够获得代谢组学研究的必要技能。导师/环境：Ambroggio博士和她的主要导师Samir S. Shah，MD，MSCE，已经组装了一个强大的共同导师和顾问团队，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，以及密歇根大学提供的资源通过安布罗吉奥医生的外部导师凯瑟琳·斯特林格药学博士此外，Ambroggio博士将出席在当地无法提供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是致力于通过内部补助金，行政支持和结构化支持初级教师教师网络和教育的机会。安布罗吉奥博士将为此采集生物样本这是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。艾德和 CCHMC的住院服务提供了一个成熟的研究基础设施和一个大型的门诊和住院患者人群进行拟议的研究。此外，所有导师都同意 Ambroggio博士的学术监督委员会自2013年以来每季度举行一次会议。研究：目前还没有准确的方法来确定儿童CAP的病因。这导致有CAP相关风险的儿童过度使用抗生素治疗或延迟适当治疗发病率这一建议是发展一种特异、快速和非侵入性的病原体检测方法的第一步。确诊为CAP的儿童中的识别。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组中超过三个点。目的2比较了儿童的代谢产物谱鼻咽部或血液中的病毒、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。的本研究的目的是使用定量1H-NMR确定每种病原体的独特代谢物谱鉴定目的3将使用CAP患者的尿液样本并与健康人的样本进行比较控制三个时间点以确定抗生素治疗对代谢物谱的影响。的这些目标的完成将产生一个与以下疾病有关的常见病原体的代谢物谱数据库：儿童CAP，并推动系统生物学方法来诊断和治疗CAP。摘要：拟议研究的创新之处在于整合了来自一个研究小组的可靠临床表型数据，使用新的统计方法对非卧床人群进行定量NMR代谢组学研究，儿科CAP诊断的临床挑战性问题。各司之间的密切合作，医院医学，生物统计学和流行病学，急诊医学在CCHMC和与密歇根大学的代谢组学核心确保了拟议研究的成功。这个奖项将为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的病原体的代谢谱。此外，这种职业发展该奖项将促进Ambroggio博士发展成为国家认可的独立调查员，领导人进行研究，改善诊断工具，为儿童传染病，特别是章

项目成果

期刊论文数量（15）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Urinary Proadrenomedullin and Disease Severity in Children With Suspected Community-acquired Pneumonia.

DOI：
10.1097/inf.0000000000003336
发表时间：
2021-12-01
期刊：
The Pediatric infectious disease journal
影响因子：
0
作者：
Florin TA;Ambroggio L;Shah SS;Ruddy RM;Nylen ES;Balmert L
通讯作者：
Balmert L

Impact of Adjunct Corticosteroid Therapy on Quality of Life for Children With Suspected Pneumonia.

DOI：
10.1097/pec.0000000000002984
发表时间：
2023-07-01
期刊：
Pediatric emergency care
影响因子：
1.4
作者：
通讯作者：

Mycoplasma Pneumoniae Testing and Treatment Among Children With Community-Acquired Pneumonia.

社区获得性肺炎儿童的肺炎支原体检测和治疗。

DOI：
10.1542/hpeds.2020-005215
发表时间：
2021
期刊：
Hospital pediatrics
影响因子：
0
作者：
Desai,Sanyukta;Hall,Matthew;Lipsett,SusanC;Shah,SamirS;Brogan,ThomasV;Hersh,AdamL;Williams,DerekJ;Grijalva,CarlosG;Gerber,JeffreyS;Blaschke,AnneJ;Neuman,MarkI;Ambroggio,Lilliam
通讯作者：
Ambroggio,Lilliam

Method/ology of Phases of Biomarker Discovery.

生物标志物发现阶段的方法/学。

DOI：
10.1542/hpeds.2022-007012
发表时间：
2023
期刊：
Hospital pediatrics
影响因子：
0
作者：
Navanandan,Nidhya;Searns,Justin;Ambroggio,Lilliam
通讯作者：
Ambroggio,Lilliam

Time to Clinical Stability in Children With Community-Acquired Pneumonia.

社区获得性肺炎儿童临床稳定的时间。

DOI：
10.1542/peds.2023-063480
发表时间：
2024
期刊：
Pediatrics
影响因子：
8
作者：
Field,MadelineR;Ambroggio,Lilliam;Lorenz,Douglas;Shah,SamirS;Ruddy,RichardM;Florin,ToddA
通讯作者：
Florin,ToddA