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

• 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
• 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

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.

项目摘要 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获得了Eunice Kennedy Shrier国家研究所 儿童健康和人类发展。在K12上的期间，她有：1）编译了一个四个会员面板 在努力独立时提供精神训练； 2）与IUSM产科建立关系 部门从两家校园医院和多家门诊诊所招募； 3）获得了IRB的批准 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）雇用了临床研究协调员和 实验室技术员； 6）与该中心的信息专家Douglas Rusch博士建立了合作 用于基因组学和生物信息学（CGB），印第安纳州的临床和转化科学研究所（ICTSI）核心； 7）成功招募了63名新生儿进行拟议的研究； 8）提出摘要详细介绍了初步 在2015年5月和2016年5月的美国胸部学会（ATS）会议上包含的数据。 在团契期间，Kloepfer博士在气道细菌对气道的影响方面变得有趣 发展。 Kloepfer博士的初步数据表明，在AIR道路中的细菌多样性降低了 三个月大于IL-33和IL-5的表达增加，而Wheeleze则六个月 年龄，表明细菌多样性降低，细胞因子的变化和肺功能变化发生在3 几个月。 16S rRNA测序尚未用于前瞻性跟随新生儿进行采样 从出生开始。因为哮喘的患病率每年继续增加（目前有10％ 人口）哮喘发育的病因需要进一步描述，尤其是在发展中的气道中 在进行哮喘诊断之前。因此，为了解决上述问题，所附的建议旨在 调查气道营养不良之前，与气道细胞因子和肺功能的变化相吻合或关注 在发展方向的孩子中。 该项目的开发是为了与Kloepfer博士的长期研究目标保持一致。它们包括： 确定从附着的研究中发现的细菌产生的细菌代谢产物如何导致气道 炎;并将这项研究转化为临床相关的预防和干预策略 患有复发性的轮子和哮喘的孩子。当我们进入个性化医学时代时，影响 在预防方法之前必须阐明细菌对免疫发育和气道功能的 可以开处方和/或设计治疗。

项目成果

Role of the Microbiome in Allergic Disease Development.

• DOI: 10.1007/s11882-020-00944-2
• 发表时间: 2020-06-16
• 期刊: Current allergy and asthma reports
• 影响因子: 5.5
• 作者: Aguilera AC;Dagher IA;Kloepfer KM
• 通讯作者: Kloepfer KM

Nonsteroidal anti-inflammatory drug hypersensitivity in a pediatric severe asthmatic population.

儿童严重哮喘人群中的非甾体抗炎药过敏。

• DOI: 10.1002/ppul.26618
• 发表时间: 2023
• 期刊: Pediatric pulmonology
• 影响因子: 3.1
• 作者: Hadley,Abigail;Slaven,JamesE;Krupp,NadiaL;Kloepfer,KirstenM
• 通讯作者: Kloepfer,KirstenM

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

• DOI: 10.3389/falgy.2023.1135412
• 发表时间: 2023
• 期刊: FRONTIERS IN ALLERGY
• 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-Mills, Joan M.
• 通讯作者: Cook-Mills, Joan M.

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: 10.1016/j.anai.2022.05.016
• 发表时间: 2022
• 期刊: Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology
• 作者: Huddleston,ChristinaM;Slaven,JamesE;Weist,AndreaD;Krupp,NadiaL;Kloepfer,KirstenM
• 通讯作者: Kloepfer,KirstenM