Upper Airway Microbial Development During the First Year of Life

生命第一年的上呼吸道微生物发育

基本信息

批准号：
10311491
负责人：
Kirsten M Kloepfer
金额：
$ 18.3万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
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：
2017-12-08 至 2022-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10311491
关键词：
16S ribosomal RNA sequencing Address Adult Affect Age Age-Months Ambulatory Care Facilities American Asthma Atopic Dermatitis Award Bacteria Bioinformatics Biology Birth Chest Child Child Health Chronic Clinical Research Clinical Sciences Collaborations Communities Data Detection Development Diagnosis Discipline of obstetrics Epidemiology Epithelial Etiology Event Faculty Fellowship Forced expiratory volume function Future Genomics Goals Haemophilus influenzae Hospitals Immune Indiana Infant Inflammatory Inflammatory Response Informatics Institutes Institutional Review Boards Interleukin-13 Interleukin-4 Interleukin-5 K-Series Research Career Programs Laboratory Technicians Lead Life Link Liquid substance Longitudinal Studies Lung Measurement Mentorship Metagenomics Methods Moraxella catarrhalis National Institute of Child Health and Human Development Natural History Newborn Infant Pediatrics Physiological Population Prevalence Prevention Prospective Studies Public Health Pulmonary Function Test/Forced Expiratory Volume 1 Recurrence Research SECTM1 gene Sampling Scientist Signaling Protein Societies Structure of mucous membrane of nose TSLP gene Techniques Testing Time Translating Translational Research Universities Virus Visit Wheezing Work airway inflammation airway obstruction children with cystic fibrosis clinically relevant cytokine design dysbiosis fungus high risk infant improved infancy interest medical schools meetings member metagenomic sequencing microbial microbial community nasopharyngeal swab oropharyngeal swab pathogen personalized medicine prevent preventive intervention professor prospective pulmonary function recruit respiratory microbiome respiratory microbiota skin microbiome tenure track

项目摘要

PROJECT SUMMARY Dr. Kloepfer joined Indiana University School of Medicine (IUSM) as an assistant professor of Pediatrics as a tenure-track research scientist. Shortly after joining the IUSM faculty, she was awarded the departmental K12 Child Health Research Career Development Award from the Eunice Kennedy Shriver National Institute of Child Health and Human Development. During her time on the K12, she has: 1) compiled a four member panel to provide mentorship as she works towards independence; 2) established a relationship with IUSM Obstetrics department to recruit from two campus hospitals and multiple outpatient clinics; 3) obtained IRB approval for the proposed study; 4) developed her lab in the Translational Research and Integrated Biology Lab (TRIB) facility housed within the Children’s Clinical Research Center (CCRC); 5) hired a clinical study coordinator and laboratory technician ; 6) established a collaboration with Dr. Douglas Rusch, an informatics expert in the Center for Genomics and Bioinformatics (CGB), an Indiana Clinical and Translational Sciences Institute (ICTSI) core; 7) successfully recruited 63 newborns for the proposed study; and 8) presented abstracts detailing preliminary data included in the attached proposal at the May 2015 and 2016 American Thoracic Society (ATS) meeting. During fellowship, Dr. Kloepfer became interested in the influence of airway bacteria on airway development. Dr. Kloepfer’s preliminary data demonstrates that decreased bacterial diversity in the airway at three months of age is associated with increased expression of IL-33 and IL-5, and wheeze by six months of age, suggesting that decreased bacterial diversity, cytokine changes and lung function changes occur prior to 3 months of age. 16S rRNA sequencing has not been utilized to prospectively follow newborns with sampling starting at birth. Because the prevalence of asthma continues to increase every year (currently 10% of the population), the etiology of asthma development needs further delineation, particularly in the developing airway prior to an asthma diagnosis. Therefore, to address the above questions, the attached proposal is designed to investigate if airway dysbiosis precedes, coincides with, or follows changes in airway cytokines and lung function in children who develop wheeze. This project was developed to align with Dr. Kloepfer’s long-term research goals. They include: determining how bacterial metabolites produced from the bacteria identified in the attached study cause airway inflammation; and translating this research into clinically relevant prevention and intervention strategies for children who develop recurrent wheeze and asthma. As we enter the era of personalized medicine, the influence of bacteria on immune development and airway function must be elucidated before methods of prevention and treatment can be prescribed and/or designed.

项目概要 Kloepfer 博士加入印第安纳大学医学院 (IUSM)，担任儿科助理教授作为一名终身教授的研究科学家，在加入 IUSM 教师后不久，她就被授予了院系荣誉称号。尤尼斯·肯尼迪·施赖弗国家研究所颁发的 K12 儿童健康研究职业发展奖儿童健康和人类发展在 K12 期间，她：1) 组建了一个四人小组。在她走向独立的过程中提供指导；2) 与 IUSM 产科建立关系；部门从两家校园医院和多个门诊诊所招聘； 3) 获得IRB批准拟议的研究；4) 在转化研究和综合生物学实验室 (TRIB) 设施中开发了她的实验室位于儿童临床研究中心 (CCRC) 内；5) 聘请了一名临床研究协调员，并且 6）与中心信息学专家Douglas Rusch博士建立了合作关系基因组学和生物信息学 (CGB)，印第安纳临床和转化科学研究所 (ICTSI) 核心； 7) 成功招募了 63 名新生儿参与拟议的研究，并且 8) 提交了详细说明初步研究的摘要；数据包含在 2015 年 5 月和 2016 年美国胸科学会 (ATS) 会议上所附提案中。在进修期间，Kloepfer 博士对气道细菌对气道的影响产生了兴趣 Kloepfer 博士的初步数据表明，气道中的细菌多样性下降。三个月大时与 IL-33 和 IL-5 表达增加有关，六个月大时出现喘息年龄，表明细菌多样性下降、细胞因子变化和肺功能变化发生在 3 岁之前 16S rRNA 测序尚未用于前瞻性跟踪新生儿采样。因为哮喘的患病率每年都在持续增加（目前占总人口的 10%）。人群），哮喘发展的病因学需要进一步描述，特别是在气道发育中因此，为了解决上述问题，所附建议旨在调查气道生态失调是否先于、同时或随后气道细胞因子和肺功能的变化发生喘息的儿童。该项目的开发是为了与 Kloepfer 博士的长期研究目标保持一致，其中包括：确定所附研究中鉴定的细菌产生的细菌代谢物如何导致气道炎症；并将这项研究转化为临床相关的预防和干预策略随着我们进入个性化医疗时代，出现反复喘息和哮喘的儿童。在采取预防和预防措施之前，必须先阐明细菌对免疫发育和气道功能的影响。可以规定和/或设计治疗。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Increased health care use in patients with moderate-to-severe asthma due to frequent preferred medication changes.

由于频繁更换首选药物，中度至重度哮喘患者的医疗保健使用量增加。

DOI：
发表时间：
2022-08
期刊：
影响因子：
0
作者：
Huddleston, Christina M;Slaven, James E;Weist, Andrea D;Krupp, Nadia L;Kloepfer, Kirsten M
通讯作者：
Kloepfer, Kirsten M

Dysbiotic lung microbial communities of neonates from allergic mothers confer neonate responsiveness to suboptimal allergen.

过敏母亲的新生儿肺部微生物群落失调，导致新生儿对次优过敏原的反应性。

DOI：
发表时间：
2023
期刊：
影响因子：
0
作者：
Bloodworth, Jeffery C;Hoji, Aki;Wolff, Garen;Mandal, Rabindra K;Schmidt, Nathan W;Deshane, Jessy S;Morrow, Casey D;Kloepfer, Kirsten M;Cook
通讯作者：
Cook

Exposure: Staphylococcus aureus skin colonization predisposes to food allergy in the Learning Early about Allergy to Peanut (LEAP) and LEAP-On studies.

暴露：在早期了解花生过敏 (LEAP) 和 LEAP-On 研究中，金黄色葡萄球菌皮肤定植易导致食物过敏。

DOI：
发表时间：
2019
期刊：
影响因子：
0
作者：
Cook;Kaplan, Mark H;Turner, Matthew J;Kloepfer, Kirsten M;Kumar, Rajesh
通讯作者：
Kumar, Rajesh

Role of the Microbiome in Allergic Disease Development.

微生物组在过敏性疾病发展中的作用。

DOI：
发表时间：
2020
期刊：
影响因子：
5.5
作者：
Aguilera, Andrea C;Dagher, Isabelle A;Kloepfer, Kirsten M
通讯作者：
Kloepfer, Kirsten M

Increased microbiota diversity associated with higher FEV0.5 in infants.

婴儿的微生物群多样性增加与较高的 FEV0.5 相关。

DOI：
发表时间：
2020
期刊：
影响因子：
3.1
作者：
Kloepfer, Kirsten M;Ross, Sydney E;Hemmerich, Christopher M;Slaven, James E;Rusch, Douglas B;Davis, Stephanie D
通讯作者：
Davis, Stephanie D