Upper Airway Microbial Development During the First Year of Life

项目摘要 Kloepfer博士加入印第安纳州大学医学院（IUSM），担任儿科助理教授 作为一名终身研究科学家加入IUSM教师后不久，她被授予部门 K12儿童健康研究职业发展奖由尤尼斯肯尼迪施莱佛国家研究所 儿童健康和人类发展。在K12期间，她：1）编制了一个四人小组 在她走向独立的过程中提供指导; 2）与IUSM产科建立了关系 部门从两个校园医院和多个门诊诊所招募; 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 儿童临床研究中心（CCRC）; 5）聘请了一名临床研究协调员， 实验室技术员; 6）与该中心的信息学专家道格拉斯鲁施博士建立了合作关系 基因组学和生物信息学（CGB），印第安纳州临床和转化科学研究所（ICTSI）的核心; 7)成功招募了63名新生儿进行拟议的研究;和8）提交了详细说明初步 数据包含在2015年5月和2016年美国胸科学会（ATS）会议的随附提案中。 在研究期间，Kloepfer博士对气道细菌对气道的影响产生了兴趣。 发展Kloepfer博士的初步数据表明，气道中细菌多样性的减少， 三个月大的婴儿与IL-33和IL-5的表达增加有关， 年龄，表明细菌多样性降低，细胞因子变化和肺功能变化发生在3岁之前 月龄。16 S rRNA测序尚未用于前瞻性随访新生儿采样 从出生开始由于哮喘的患病率每年持续增加（目前占全国的10%）， 人群），哮喘发展的病因需要进一步阐明，特别是在气道发育中 在哮喘诊断之前。因此，为解决上述问题，所附提案旨在 研究气道微生态失调是否在气道细胞因子和肺功能变化之前、同时或之后发生 发生喘息的儿童。 该项目的开发与Kloepfer博士的长期研究目标保持一致。它们包括： 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， 患有反复喘息和哮喘的儿童。随着我们进入个性化医疗时代， 细菌对免疫发育和气道功能的影响必须在预防方法和 可以规定和/或设计治疗。

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.