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

• 批准号: 10335238
• 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
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-02-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10335238
• 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 Injury; 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 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; Pulmonary Inflammation; 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; chronic respiratory disease; 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

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.

项目总结/摘要 这个指导以患者为导向的研究职业发展奖（K23）的目的是提供埃里克 A.詹森，医学博士，医学硕士，宾夕法尼亚大学和宾夕法尼亚州儿童医院儿科讲师。 费城的导师，培训和研究经验，需要成为一个独立的 临床科学家和新生儿肺部疾病研究的领导者。他的长期职业目标是减少 通过新的转化研究和大规模、多中心研究， 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项目。为了实现这些目标， 独立性，詹森博士和他的导师制定了一个全面的职业发展计划的基础上： (1)与他有着良好合作记录的团队进行深入的指导;（2）深入 微生物组研究方法的实践和教学培训;以及（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。它影响了一半的生存极其 早产儿，与健康和认知方面的持久缺陷有关，并携带着巨大的社会风险。 负担和成本。不幸的是，BPD率没有改善，几乎没有安全的预防性治疗方法。小说 需要BPD的研究范式，以发现新的、基于证据的BPD方法 预防新生儿气道微生物组作为潜在的治疗靶点具有重要的前景。 现代分子检测表明，在微生物群落的病理改变（生态失调）， 在年龄较大儿童和成人中，气道与慢性炎症和肺损伤有关。胃- 食管反流（格尔）相关的微抽吸是慢性阻塞性肺疾病患者气道生态失调的一个潜在因素， 呼吸道疾病此外，最近的证据表明，改善格尔相关的微抽吸可能 通过恢复正常气道植物群来改善肺功能。气道微生物生态失调是否有助于 BPD的发展是一个紧迫的，没有答案的问题。詹森博士的研究计划将解决这一问题 通过（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， 极早产儿肺部炎症增加和BPD的发展，以及（2）表征 早产儿肺部微生物生态失调与格尔相关微抽吸之间的潜在关联。 詹森博士的K23研究将产生新的见解BPD的病理生理学，将直接 告知他未来旨在预防新生儿肺损伤的R 01提案。他的职业发展计划概述了 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。

项目成果

Adverse effects of small for gestational age differ by gestational week among very preterm infants.

• DOI: 10.1136/archdischild-2017-314171
• 发表时间: 2019-03
• 期刊: Archives of disease in childhood. Fetal and neonatal edition
• 作者: Jensen EA;Foglia EE;Dysart KC;Simmons RA;Aghai ZH;Cook A;Greenspan JS;DeMauro SB
• 通讯作者: DeMauro SB

Is it time to study routine car seat tolerance screening in a randomized controlled trial? An international survey of current practice and clinician equipoise.

• DOI: 10.1038/s41372-021-01167-7
• 发表时间: 2022-04
• 期刊: Journal of perinatology : official journal of the California Perinatal Association
• 作者: Jensen EA;Greenspan JS;Aghai ZH;Carola DL;Eichenwald EC;DeMauro SB;Dysart K
• 通讯作者: Dysart K

Loop Diuretics in Severe Bronchopulmonary Dysplasia: Cumulative Use and Associations with Mortality and Age at Discharge.

• DOI: 10.1016/j.jpeds.2020.10.073
• 发表时间: 2021-04
• 期刊: The Journal of pediatrics
• 作者: Bamat NA;Nelin TD;Eichenwald EC;Kirpalani H;Laughon MM;Jackson WM;Jensen EA;Gibbs KA;Lorch SA
• 通讯作者: Lorch SA

Associations of neighborhood social vulnerability with emergency department visits and readmissions among infants with bronchopulmonary dysplasia.

邻里社会脆弱性与支气管肺发育不良婴儿的急诊就诊和再入院之间的关系。

• DOI: 10.1038/s41372-023-01735-z
• 发表时间: 2023
• 期刊: Journal of perinatology : official journal of the California Perinatal Association
• 作者: Nelin,TimothyD;Yang,Nancy;Radack,Joshua;Lorch,ScottA;DeMauro,SaraB;Bamat,NicolasA;Jensen,ErikA;Gibbs,Kathleen;Just,AllanC;Burris,HeatherH
• 通讯作者: Burris,HeatherH

Prevention of Bronchopulmonary Dysplasia: A Summary of Evidence-Based Strategies.

• DOI: 10.1542/neo.20-4-e189
• 发表时间: 2019-04-01
• 期刊: NeoReviews
• 作者: Jensen, Erik A