Metabolomics Evaluation of the Etiology of Pneumonia

肺炎病因的代谢组学评估

• 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
• 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

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，MPH是一种传染病流行病学家，其总体职业目标是 通过开发改善诊断的方法来改善患有常见，严重感染的儿童的结局 准确性并将这些方法实施到临床实践中。她提出的研究标题为 肺炎病因（MEEP）的代谢组学评估结合了先进的统计技术与 1H核磁共振（NMR）代谢组学方法可以识别代谢物，这将有助于促进 儿童社区获得性肺炎（CAP）的病因学诊断。这种病原体鉴定会导致 在及时，准确的诊断中，将允许对该疾病的有针对性和有效治疗。 候选人：Ambroggio博士是儿科助理教授，在 辛辛那提儿童医院医疗中心的医院医学与生物统计学和流行病学 （CCHMC）。她完成了公共卫生硕士学位和博士学位。德雷克塞尔大学流行病学博士学位之前 在CCHMC开始博士后奖学金。她以前在CAP聚焦临床管理方面的工作 关于抗生素的处方和诊断工具，可检测肺炎 分子和细胞生物学使她准备进行拟议的研究。拟议的职业 发展计划将以她以前的培训为基础，并以四个培训目标来增强她的轨迹 成为独立研究者：1）在研究设计和执行中的体验和教学学习 定量1H-NMR代谢组学； 2）获取和应用高级统计分析； 3）解释 代谢组学数据及其生物环境以及4）发展领导和专业技能以执行 多中心研究。 Ambroggio博士提出的培训活动包括教学和体验式学习 使她能够获得代谢组研究的必要技能。 导师/环境：Ambroggio博士和她的主要导师Samir S. Shah，医学博士，MSCE，已经组装了 强大的联合会和顾问团队通过拟议的培训和研究指导Ambroggio博士 活动。拟议的职业发展计划利用可用的知识和代谢组学资源 通过辛辛那提大学和CCHMC大学以及密歇根大学提供的资源 通过Ambroggio博士的外部导师，Pharmd的Kathleen Stringer。此外，Ambroggio博士将参加 最佳培训在本地无法获得的国家研讨会和讲习班。作为一个机构CCHMC是 致力于通过内部赠款，行政支持和结构化支持初级教师 教师网络和教育的机会。 Ambroggio博士将为此获得生物标本 来自全面运营的外部资助的前瞻性队列研究的提案，Carpe Diem。 ED和 CCHMC的住院服务提供了既定的研究基础设施和大型的门诊和 住院的患者人群进行拟议的研究。此外，所有导师都同意 参加Ambroggio博士的学术监督委员会，该委员会自2013年以来一直在季刊。 研究：目前尚无准确的方法来识别儿童CAP的病因。这导致 过度治疗抗生素或在有帽帽有关的儿童中适当治疗 发病率。该建议是为病原体开发特定，快速和无创方法的第一步 被诊断为CAP的儿童的识别。 AIM 1表征变异的来源（例如年龄和性别） 这在健康的孩子的代谢组中存在于三分以上。 AIM 2比较儿童的代谢物概况 从鼻咽或血液进行阳性PCR测试的病毒，细菌感染，例如 肺炎支原体或肺炎链球菌患有尚无已知感染的儿童。这 此目的的目的是使用定量的1H-NMR鉴定独特的代谢物剖面 确定。 AIM 3将使用CAP患者的尿液样品，并将其与健康的样品进行比较 在三个时间点上的contorls确定抗生素处理对代谢产物谱的影响。这 这些目标的完成将生成与与 儿童时期的帽子并驱动系统生物学方法限制帽子诊断和治疗。 摘要：拟议研究的创新是从一个稳健的临床表型数据整合 具有定量NMR代谢组学使用新型统计方法来解决该问题的卧床种群 小儿帽诊断的临床具有挑战性的问题。分界之间的强大合作 CCHMC的医院医学，生物统计学和流行病学以及急诊医学以及 密歇根大学的代谢组学核心确保了拟议的研究的成功。这个奖项将 向Ambroggio博士提供培训和研究，需要在未来的多中心研究中取得成功 验证病原体的代谢物谱，导致儿童的帽子。此外，这种职业发展 奖项将使Ambroggio博士的发展成为全国认可的独立调查员和 领导者进行研究，以改善感染性疾病儿童的诊断工具，特别是 帽。

项目成果

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
• 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

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
• 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
• 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