Microbiome of the Airway and the Risk for Bronchopulmonary Dysplasia in the Lungs of Extreme Preterms: The MARBLE Study

气道微生物组和极度早产儿肺部支气管肺发育不良的风险：MARBLE 研究

基本信息

批准号：
10094070
负责人：
ERIK ALLEN JENSEN
金额：
$ 16.33万
依托单位：
CHILDREN'S HOSP OF PHILADELPHIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-01 至 2023-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10094070
关键词：
Address Adult Affect Age Antibiotics Award Bile Acids Biological Assay Biological Markers Bronchopulmonary Dysplasia Cardiopulmonary Categories Cause of Death Cessation of life Child Childhood Chronic Chronic lung disease Clinical Research Cognition Collaborations Development Development Plans Disease Equilibrium Exhibits Functional disorder Future Gastroesophageal reflux disease Goals Growth Health Health Care Costs Heterogeneity Individual Infant Inflammation Inflammation Mediators Interferon Type II Interleukin-1 beta K-Series Research Career Programs Knowledge Life Liquid substance Lower respiratory tract structure Lung Lung Inflammation Lung diseases Measures Mechanical ventilation Mediating Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Microbe Modernization Molecular Multi-Institutional Clinical Trial Neonatal Neurodevelopmental Disability Neurodevelopmental Impairment Organism Pathologic Pattern Pediatric Hospitals Pediatrics Pennsylvania Pepsinogen A Philadelphia Pregnancy Premature Birth Premature Infant Prevention Preventive therapy Probiotics Prospective cohort Research Research Methodology Research Proposals Risk Risk Factors Role Sampling Scientist Severities Site TNF gene Training Universities Upper respiratory tract airway inflammation antimicrobial base career career development cost cytokine disability dysbiosis endotracheal evidence base experience functional restoration improved indexing innovation insight instructor lung development lung injury microbial microbial community microbiome microbiome research microbiota neonatal care neonatal lung injury neutrophil novel novel therapeutics oropharyngeal swab prevent primary outcome programs pulmonary function respiratory respiratory colonization respiratory microbiome respiratory microbiota skills therapeutic target translational study

项目摘要

PROJECT SUMMARY/ABSTRACT The purpose of this Mentored Patient-Oriented Research Career Development Award (K23) is to provide Erik A. Jensen, MD, MSCE, Instructor of Pediatrics at the University of Pennsylvania and the Children's Hospital of Philadelphia with the mentorship, training, and research experience needed to become an independent clinician scientist and leader in neonatal lung disease research. His long-term career goal is to reduce the burden of bronchopulmonary dysplasia (BPD) through novel translational studies and large scale, multi-center clinical trials of promising new therapies. His immediate goal is to acquire the skills needed to direct a research program studying the airway microbiome in extremely preterm infants. To achieve these goals and transition to independence, Dr. Jensen and his mentors developed a comprehensive career development plan based on: (1) intensive mentorship from a team with whom he has a proven track record of collaboration; (2) in-depth hands on and didactic training in microbiome research methods; and (3) an innovative research plan to describe the role of the airway microbiome in the development of BPD. BPD is among the most devastating complications of preterm birth. It affects half of surviving extremely preterm infants, is associated with enduring deficits in health and cognition, and carries an enormous societal burden and cost. Unfortunately, BPD rates are not improving and few safe, preventative therapies exist. Novel research paradigms in BPD are needed to enable discovery of new, evidence based approaches to BPD prevention. The neonatal airway microbiome holds significant promise as a potential therapeutic target. Modern molecular assays demonstrate that pathologic alterations (dysbiosis) in the microbial communities in the airway are associated with chronic inflammation and lung injury in older children and adults. Gastro- esophageal reflux (GER) related microaspiration is one potential contributor to airway dysbiosis in chronic respiratory disease. Moreover, recent evidence suggests that amelioration of GER related microaspiration may improve lung function by restoring normal airway flora. Whether airway microbial dysbiosis contributes to the development of BPD is a pressing, unanswered question. Dr. Jensen's research proposal will address this knowledge gap by (1) identifying patterns in the upper and lower respiratory tract microbiota associated with increased lung inflammation and the development of BPD in extremely preterm infants and (2) characterizing the potential association between microbial dysbiosis in the preterm lung and GER related microaspiration. Dr. Jensen's K23 studies will produce novel insights into the pathophysiology of BPD that will directly inform his future R01 proposals aimed at preventing neonatal lung injury. His career development plan outlines a clear path to gain the knowledge, skills, and experience needed to become an independent clinician scientist, leader, and innovator in neonatal lung disease research.

项目概要/摘要这个以患者为导向的研究职业发展奖（K23）的目的是为埃里克提供 A. Jensen，医学博士，理学硕士，宾夕法尼亚大学和儿童医院儿科讲师费城拥有成为独立机构所需的指导、培训和研究经验临床科学家和新生儿肺病研究的领导者。他的长期职业目标是减少通过新颖的转化研究和大规模、多中心的研究来减轻支气管肺发育不良（BPD）的负担有前途的新疗法的临床试验。他的近期目标是获得指导研究所需的技能研究极早产儿气道微生物组的计划。为了实现这些目标并过渡到独立后，Jensen 博士和他的导师根据以下内容制定了全面的职业发展计划： (1) 来自与他有良好合作记录的团队的深入指导； (二)深入微生物组研究方法的实践和教学培训； (3) 创新研究计划描述气道微生物组在 BPD 发展中的作用。 BPD 是早产最具破坏性的并发症之一。它极大地影响了一半的生存早产儿与健康和认知方面的持久缺陷有关，并带来巨大的社会影响负担和成本。不幸的是，边缘性人格障碍的发病率并没有改善，而且几乎没有安全的预防性治疗方法。小说需要 BPD 的研究范式来发现新的、基于证据的 BPD 方法预防。新生儿气道微生物群作为潜在的治疗靶点具有重要的前景。现代分子检测表明，微生物群落的病理改变（生态失调）气道与年龄较大的儿童和成人的慢性炎症和肺损伤有关。肠胃- 食管反流（GER）相关的微误吸是慢性气道菌群失调的潜在因素之一。呼吸道疾病。此外，最近的证据表明，改善 GER 相关的微抽吸可能通过恢复正常气道菌群来改善肺功能。气道微生物失调是否会导致 BPD的发展是一个紧迫的、悬而未决的问题。詹森博士的研究计划将解决这个问题知识差距：(1) 识别与以下疾病相关的上呼吸道和下呼吸道微生物群模式极度早产儿肺部炎症增加和 BPD 的发展；(2) 表征早产儿肺部微生物失调与 GER 相关微抽吸之间的潜在关联。 Jensen 博士的 K23 研究将对 BPD 的病理生理学产生新的见解，这将直接告知他未来旨在预防新生儿肺损伤的 R01 提案。他的职业发展计划概述获得成为独立临床科学家所需的知识、技能和经验的明确途径，新生儿肺病研究的领导者和创新者。