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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.

摘要这个指导职业发展（K 01）奖提案将提供一个优秀的教育环境，指导和培训Jillian Hurst博士，一位儿科传染病研究员，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，相关的宿主因素改变了对常见儿童感染的易感性赫斯特博士最初在生物化学和分子生物学，并在过去五年中一直从事转化儿科研究。这个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。拟议的研究中心的作用，上呼吸道微生物组在急性中耳炎（AOM;中耳）的发展和复发中的作用感染），儿童最常见的传染病。赫斯特博士将检验早期生命抗生素暴露会破坏URT微生物组的发育，使儿童易患AOM和其他疾病。常见的呼吸道感染她将使用超过八年的电子健康记录数据，从出生到2岁的儿童中收集的纵向上呼吸道标本，以及来自对复发性AOM的儿童进行前瞻性队列研究，以实现以下特定目标：1）评估生命早期抗生素暴露对AOM复发的影响。2)描述早期生活的影响抗生素暴露对URT微生物组发育的影响;以及3）评价抗生素暴露和URT微生物组在患有复发性AOM的儿童中。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，包括抗生素的使用和确定URT微生物组中的治疗靶点，恢复URT微生物组功能，改善幼儿的呼吸系统健康。导师制将是由三位具有互补专业知识的知名研究人员组成的小组提供：克里斯托弗·伍兹博士，一位传染病医生和临床流行病学家，在评估宿主对感染因子;马修·凯利博士，一位儿科传染病医生，在人类微生物组学和临床组学分析;以及本杰明·戈尔茨坦博士，一位生物统计学家，电子健康记录数据用于人口健康分析。此外，赫斯特博士将由内部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以及AOM的治疗和病理生理学。完成拟议的培训，研究活动将使赫斯特博士成为一名独立的研究者，他将领导一项由NIH资助的研究该项目调查儿童常见感染的宿主因素和暴露情况。