Evaluation of the Oral and Lung Microbiota and Inflammation in Chronic Obstructive Pulmonary Disease Frequent Exacerbators

慢性阻塞性肺疾病频繁加重者的口腔和肺部微生物群与炎症的评估

• 批准号: 9031299
• 负责人: ALEXA A PRAGMAN
• 金额: --
• 依托单位: MINNEAPOLIS VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-11-15 至 2020-11-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9031299
• 关键词: Academic Medical Centers; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Aspirate substance; Automobile Driving; Award; Azithromycin; Bacteria; Beryllium; Biological Markers; Biometry; Caring; Case-Control Studies; Cause of Death; Chronic Disease; Chronic Obstructive Airway Disease; Clinical; Clinical Investigator; Clinical Research; Clinical Trials Design; Communicable Diseases; Communities; Data; Data Set; Disease; Disease Progression; Doctor of Medicine; Doctor of Philosophy; Educational workshop; Elements; Evaluation; Excision; Foundations; Frequencies; Genomics; Goals; Grant; Growth; Health Care Costs; Healthcare Systems; Heterogeneity; Infection; Inflammation; Inflammatory; Inflammatory Response; K-Series Research Career Programs; Lead; Link; Lobectomy; Lung; Lung Inflammation; Lung diseases; Malignant neoplasm of lung; Medical center; Mentorship; Metagenomics; Methods; Minnesota; Molecular Epidemiology; Monitor; Morbidity - disease rate; Nose; Oral; Outcome; Pathogenesis; Pathology; Patients; Phenotype; Predisposition; Property; Prospective Studies; Publications; Publishing; Research; Research Personnel; Respiratory Signs and Symptoms; Respiratory physiology; Response Elements; Role; Sampling; Series; Source; Sputum; Structure of parenchyma of lung; Techniques; Testing; Therapeutic Intervention; Training Support; Translational Research; Universities; Validation; Veterans; Work; Writing; base; career development; cost; disease phenotype; experience; health care service utilization; improved; insight; microbiome; microbiota; mortality; new therapeutic target; novel; oral bacteria; patient oriented; prevent; professor; public health relevance; response; skills; symposium; tool; treatment strategy

 DESCRIPTION (provided by applicant) This is an application for a Career Development Award-2 (CDA-2) to Dr. Alexa A. Pragman, M.D., Ph.D., an Assistant Professor at the University of Minnesota with a record of research and publications on the lung microbiota. She is establishing herself as a young investigator in patient-oriented clinical research of the chronic obstructive pulmonary disease (COPD) lung microbiota. She intends to join the staff at the Minneapolis Veterans Affairs Medical Center (MVAMC) in the Infectious Diseases Section. This CDA-2 will provide Dr. Pragman with the support and training necessary to achieve the following goals: 1) become an expert in clinical and translational research involving the lung microbiota; 2) apply advanced biostatistical analysis tools in clinical microbiota studies; 3) design clinical trials involving COPD and the lun microbiota; and 4) become an independent clinical investigator. To achieve these goals, Dr. Pragman has assembled a mentorship team consisting of Dr. James R. Johnson, a MVAMC researcher and infectious disease clinician who studies molecular epidemiology; Dr. Christine Wendt, the Pulmonary Section chief at MVAMC, with expertise in COPD clinical studies; Dr. Richard E. Isaacson, a senior researcher with expertise in microbiome studies; and Dr. Cavan S. Reilly, a biostatistician with expertise in statistical approaches to metagenomic data sets. They will monitor Dr. Pragman's career development as she takes 4 biostatistics courses, attends two national genomics workshops, participates in seminar series at MVAMC and the University of Minnesota, develops her grant-writing skills, presents at national conferences, and submits foundation grants and a Merit Award application. COPD has multiple disease phenotypes and the mechanisms responsible for this heterogeneity are poorly understood. Inflammation in response to the COPD lung microbiota is one potential mechanism by which some patients suffer frequent exacerbations and others do not. In Aim 1, Dr. Pragman will identify patients undergoing clinically indicated lung lobectomy and sample their oral, nasal, sputum, and lung tissue microbiota in a manner that avoids upper airway contamination. This study will identify a method for accurate, non- invasive sampling of the lung microbiota. This work will define the microbiota of the COPD lung and the healthy lung without upper airway contamination and will establish a non-invasive technique for studying the lung microbiota. In Aim 2, Dr. Pragman will conduct a prospective study comparing the lung microbiota and lung inflammatory biomarkers of frequent exacerbators to infrequent exacerbators. She will identify specific co-varying microbiota and sputum inflammatory biomarkers that can identify exacerbation phenotype and also serve as targets for new COPD therapies. Both aims will utilize advanced biostatistical tools, which will allow Dr. Pragman to correlate specific features f the lung microbiota with lung inflammation. The overall objective in the proposed project is to determine key features that differentiate the upper airway and lung microbiota of COPD patients with a frequent exacerbator phenotype from those with the infrequent exacerbator phenotype. Dr. Pragman's long-term goal is to understand the role of the lung microbiota in the pathogenesis of inflammatory lung disorders. This work will form the basis for further clinical and translational research to establish the mechanisms by which the lung microbiota contributes to COPD pathogenesis. These studies will be proposed in a Merit Award application before the end of the CDA-2 period.

 描述（由申请人提供） 这是一个职业发展奖-2（CDA-2）的应用程序博士。Pragman，医学博士，哲学博士、明尼苏达大学助理教授，在肺部微生物群方面有研究和出版记录。她正在建立自己作为一个年轻的研究者在以患者为导向的临床研究慢性阻塞性肺疾病（COPD）肺微生物群。她打算加入明尼阿波利斯退伍军人事务医疗中心（MVAMC）传染病科的工作人员。该CDA-2将为Pragman博士提供必要的支持和培训，以实现以下目标：1）成为涉及肺部微生物群的临床和转化研究专家; 2）在临床微生物群研究中应用先进的生物统计分析工具; 3）设计涉及COPD和肺部微生物群的临床试验; 4）成为独立的临床研究者。为了实现这些目标，Pragman博士组建了一个由James R.约翰逊，MVAMC研究员和传染病临床医生谁研究分子流行病学;克莉丝汀温特博士，在MVAMC肺科主任，在COPD临床研究的专业知识;理查德E。Isaacson博士是微生物组研究方面的资深研究员;他是一位生物统计学家，擅长宏基因组数据集的统计方法。他们将监测Pragman博士的职业发展，因为她参加了4门生物统计学课程，参加了两个国家基因组学研讨会，参加了MVAMC和明尼苏达大学的系列研讨会，发展了她的赠款写作技能，出席了全国会议，并提交了基金会赠款和优异奖申请。COPD具有多种疾病表型，导致这种异质性的机制知之甚少。响应于COPD肺微生物群的炎症是一种潜在的机制，通过该机制，一些患者遭受频繁的急性加重，而另一些患者则没有。在目标1中，Pragman博士将识别接受有临床指征的肺叶切除术的患者，并以避免上呼吸道污染的方式对他们的口腔、鼻、痰和肺组织微生物群进行采样。这项研究将确定一种方法，用于准确，非侵入性的肺部微生物群采样。这项工作将定义COPD肺和没有上呼吸道污染的健康肺的微生物群，并将建立一种用于研究肺微生物群的非侵入性技术。在目标2中，Pragman博士将进行一项前瞻性研究，比较频繁加重者与罕见加重者的肺部微生物群和肺部炎症生物标志物。她将确定特定的共变微生物群和痰炎性生物标志物，这些生物标志物可以识别急性加重表型，也可以作为新的COPD治疗的靶点。这两个目标都将利用先进的生物统计工具，这将使Pragman博士能够将肺部微生物群的特定特征与肺部炎症相关联。该项目的总体目标是确定区分具有频繁加重表型的COPD患者的上呼吸道和肺微生物群与具有罕见加重表型的COPD患者的关键特征。Pragman博士的长期目标是了解肺部微生物群在炎症性肺部疾病发病机制中的作用。这项工作将为进一步的临床和 转化研究，以建立肺微生物群促进COPD发病机制的机制。这些研究将在CDA-2期结束前在优异奖申请中提出。