Clinical and host microbiome features in the development of acute otitis media

急性中耳炎发生过程中的临床和宿主微生物组特征

基本信息

批准号：
10735848
负责人：
Jillian Heyward Hurst
金额：
$ 12.74万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-07-10 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10735848
关键词：
Acute Adolescent Age Age Months Antibiotics Asthma Award Biochemistry Biological Birth COVID-19 Characteristics Child Child health care Childhood Clinical Clinical Data Clinical Research Cohort Studies Communicable Diseases Corynebacterium Data Data Mart Data Set Development Disease Electronic Health Record Enrollment Epidemiologist Evaluation Exposure to Functional disorder Funding Goals Growth Health Health Care Visit Home Human Microbiome Immune response Infant Infection Infectious Agent Inflammatory Response Integration Host Factors Interdisciplinary Study K-Series Research Career Programs Lead Life Link Mediating Mentors Mentorship Methodology Methods Molecular Biology Mothers Nose Otitis Media Otolaryngology Pathogenesis Pattern Pediatric Research Physicians Population Positioning Attribute Predisposition Prevention Prospective cohort Public Health Informatics Recording of previous events Recurrence Research Research Activity Research Design Research Personnel Respiratory Tract Infections Risk Role Sampling Scientist Serotyping Specimen Statistical Data Interpretation Statistical Models Streptococcus pneumoniae Testing Time Training Training Activity United States National Institutes of Health Upper Respiratory Infections Upper respiratory tract Vaccination Wheezing Work antimicrobial atopy bacteriome career career development chronic respiratory disease cohort data resource dysbiosis ear infection ear microbiome educational atmosphere experience gut microbiome health care service utilization host microbiome improved intrapartum large datasets metagenomic sequencing microbial microbial community microbiome microbiome alteration middle ear middle ear fluid multidisciplinary nasal swab observational cohort study pathogen pathogenic bacteria population health prevent programs recurrent infection research study respiratory respiratory health respiratory microbiome sex therapeutic target virome

项目摘要

ABSTRACT This Mentored Career Development (K01) Award proposal will provide an outstanding educational environment, mentoring, and training for Dr. Jillian Hurst, a pediatric infectious diseases researcher whose overarching career goal is to integrate clinical and biological data to further our understanding of the role of the microbiome and related host factors in modifying susceptibility to common childhood infections Dr. Hurst originally trained in biochemistry and molecular biology and has worked in translational pediatric research for the past five years. This career development award will allow her to receive training in omics and advanced statistical analyses using large datasets, permitting her to lead multidisciplinary teams that use large clinical and omics datasets to evaluate factors underlying common pediatric infections. The proposed research studies center on the role of the upper respiratory microbiome in the development and recurrence of acute otitis media (AOM; middle ear infection), the most common infectious disease of childhood. Dr. Hurst will test the hypothesis that early life antibiotic exposures disrupt the development of the URT microbiome, predisposing children to AOM and other common respiratory infections. She will use over eight years of electronic health records data, banked longitudinal upper respiratory specimens collected from children from birth to age 2, and samples and data from a prospective cohort of children with recurrent AOM to accomplish the following specific aims: 1) Assess the impact of early life antibiotic exposures on recurrent AOM development.; 2) Delineate the effects of early life antibiotic exposures on URT microbiome development; and 3) Evaluate associations between antibiotic exposures and the URT microbiome in children with recurrent AOM. Findings from these studies will guide the development of new strategies to prevent and treat AOM and associated infections, including guidance for antibiotic use and identification of therapeutic targets within the URT microbiome that could be leveraged to restore URT microbiome function and improve respiratory health among young children. Mentorship will be provided by a group of three established investigators with complementary expertise: Dr. Christopher Woods, an infectious diseases physician and clinical epidemiologist with expertise in the evaluation of host responses to infectious agents; Dr. Matthew Kelly, a pediatric infectious diseases physician with expertise in the human microbiome and clinical omics analyses; and Dr. Benjamin Goldstein, a biostatistician with expertise in the use of electronic health records data for population health analyses. Additionally, Dr. Hurst will be advised by internal and external advisors with expertise in antimicrobial stewardship, pediatric otolaryngology, health informatics and omics analyses, and the treatment and pathophysiology of AOM. Completion of the proposed training and research activities will establish Dr. Hurst as an independent investigator who will lead an NIH-funded research program investigating host factors and exposures underlying common infections in children.

抽象的该指导性职业发展（K01）奖提案将提供出色的教育环境，为儿科传染病研究员 Jillian Hurst 博士提供指导和培训，她的总体职业生涯目标是整合临床和生物学数据，以进一步了解微生物组的作用和改变对常见儿童感染的易感性的相关宿主因素赫斯特博士最初接受过培训生物化学和分子生物学，过去五年一直从事转化儿科研究。该职业发展奖将使她能够接受组学和高级统计分析方面的培训大型数据集，使她能够领导使用大型临床和组学数据集的多学科团队评估常见儿科感染的潜在因素。拟议的研究中心是作用上呼吸道微生物组在急性中耳炎（AOM；中耳炎）发生和复发中的作用感染），儿童期最常见的传染病。赫斯特博士将检验早期生活的假设抗生素暴露会破坏 URT 微生物群的发育，使儿童容易患 AOM 和其他疾病常见的呼吸道感染。她将使用八年多的电子健康记录数据，这些数据已存入银行采集自出生至 2 岁儿童的纵向上呼吸道标本，以及来自一组患有复发性 AOM 的儿童的前瞻性队列，以实现以下具体目标： 1) 评估生命早期接触抗生素对 AOM 复发的影响。 2）描述早年生活的影响抗生素暴露对 URT 微生物组发育的影响； 3) 评估抗生素之间的关联复发性 AOM 儿童的暴露和 URT 微生物组。这些研究的结果将指导制定预防和治疗 AOM 及相关感染的新策略，包括指导抗生素的使用和 URT 微生物组内治疗靶点的识别可用于恢复 URT 微生物组功能并改善幼儿的呼吸道健康。辅导将是由三名具有互补专业知识的资深研究人员组成的小组提供：Christopher Woods 博士，传染病医生和临床流行病学家，具有评估宿主反应的专业知识传染源；马修·凯利 (Matthew Kelly) 博士是一位儿科传染病医生，具有人类方面的专业知识微生物组和临床组学分析； Benjamin Goldstein 博士是一位生物统计学家，在使用方面具有专业知识用于人口健康分析的电子健康记录数据。此外，赫斯特博士将得到内部人士的建议以及在抗菌药物管理、儿科耳鼻喉科、健康信息学方面具有专业知识的外部顾问组学分析，以及 AOM 的治疗和病理生理学。完成拟议的培训并研究活动将使赫斯特博士成为一名独立调查员，领导 NIH 资助的研究调查儿童常见感染的宿主因素和暴露的计划。