Microbiome-based diagnosis of pneumonia in the acute respiratory distress syndrome

基于微生物组的急性呼吸窘迫综合征肺炎诊断

基本信息

批准号：
10321637
负责人：
Georgios Kitsios
金额：
$ 16.19万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
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：
2018-01-22 至 2022-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10321637
关键词：
16S ribosomal RNA sequencing Accounting Acute Lung Injury Acute Respiratory Distress Syndrome Address Admission activity Advisory Committees Antibiotic Resistance Antibiotics Antimicrobial susceptibility Bioinformatics Caring Categories Clinical Clinical Research Clinical Trials Clinical Trials Design Communities Computational Biology Critical Care Critical Illness Culture Techniques DNA DNA analysis DNA sequencing Data Development Diagnosis Diagnostic Ecology Etiology Future Genes Goals Hour Hypersensitivity Immune response Individual Infection Inflammation Inflammatory Inflammatory Response Infrastructure Injury Intensive Care Units Interleukin-6 K-Series Research Career Programs Laboratories Lead Lower respiratory tract structure Lung Mechanical ventilation Medicine Mentored Patient-Oriented Research Career Development Award Mentors Mentorship Methods Microbiology Modernization Organism Pathogen detection Patients Pattern Physicians Pneumonia Positioning Attribute Prospective cohort study Public Health Regimen Research Research Design Sampling Scientist Sensitivity and Specificity Techniques Time Training Universities Validation Work accurate diagnosis advanced analytics antimicrobial bacterial community base biobank career development clinical sequencing cohort cost effectiveness design diagnostic tool effective therapy effectiveness outcome emerging antimicrobial resistance experience genome sequencing human microbiota improved indexing individual patient infection management inflammatory marker innovation lung injury lung microbiome microbial microbial community microbiome microbiome research microbiota microbiota profiles mortality mortality risk nanopore next generation sequencing novel pathogen personalized management point of care procalcitonin prospective receptor for advanced glycation endproducts standard of care technique development training opportunity translational physician translational scientist translational study whole genome

项目摘要

PROJECT ABSTRACT This application is for a Mentored Patient-Oriented Research Career Development Award entitled “Microbiome-based diagnosis of pneumonia in the acute respiratory distress syndrome”. I am a Pulmonary and Critical Care Medicine Fellow at the University of Pittsburgh and I require additional training to develop expertise as a translational researcher in the microbiome of critical illness. The central objective of my research is to utilize emerging microbial DNA sequencing techniques for faster and more accurate diagnosis of pneumonia in critically-ill patients. The focus of my research is the acute respiratory distress syndrome (ARDS), a serious form of inflammatory lung injury often caused by pneumonia and accounting for 10% of intensive care unit admissions in the US with 40% mortality. With diagnostic limitations of the current standard- of-care of microbial cultures, patients often receive empiric, broad-spectrum antibiotics that can be inappropriate or inadequate for their individual needs, and also promote antibiotic resistance – a major public health threat. My preliminary data demonstrate feasibility and proof-of-concept that sequencing of microbial DNA directly from patient samples can lead to faster and more accurate diagnosis of pneumonia compared to cultures. The aims of the study are to develop sequencing-based definitions for pneumonia in (1) culture- positive and (2) culture-negative patients by integrating microbiome and host response data, and then 3) to assess the anticipated impact of sequencing on antibiotic selection. I will execute a prospective cohort study in patients with ARDS and use modern culture-independent sequencing techniques and computational biology methods to study the lung microbiome in relation to host-responses and microbiologic cultures. The proposed sequencing-based approach has the potential to improve accuracy of pneumonia diagnosis (capturing both cultivable and non-cultivable organisms) and to provide information to clinicians much faster than cultures. Thus, my proposal addresses a high priority issue for development of innovative diagnostics of infections to improve antibiotic usage and provides a unique translational training opportunity. I propose a research- intensive period of career development with hands-on and didactic training in advanced sequencing techniques, bioinformatics, computational biology and clinical trial design and implementation. The work will be conducted within the Division of Pulmonary, Allergy, and Critical Care Medicine at the University of Pittsburgh, which has an outstanding record of training physician-scientists and a highly-developed infrastructure for the conduct of translational studies. I am supported by a committed mentoring partnership with convergent expertise in microbiome and critical care research, and a diverse Mentoring Advisory Committee. With support from the K23 Mentored Career Development Award, I will develop an independent project examining sequencing-based pneumonia diagnostics for an R01 proposal over the next five years.

项目摘要该应用程序是针对以患者为导向的研究职业发展奖的题为标题为标题的 “基于微生物组的急性呼吸窘迫综合征肺炎诊断”。我是一个匹兹堡大学的肺和重症监护医学研究员，我需要其他培训发展专业知识是重症疾病微生物组的翻译研究人员。我的核心目标研究是利用新兴的微生物DNA测序技术，以更快，更准确地诊断严重的患者肺炎。我研究的重点是急性呼吸窘迫综合征（ARDS），一种严重的炎症性肺损伤，通常是由肺炎引起的，占10％美国重症监护病房的死亡率为40％。具有当前标准的诊断限制 - 大量的微生物培养物，患者经常接受经验性的，广谱的抗生素，可以是不适当或不足以满足他们的个人需求，并促进抗生素耐药性 - 主要公众健康威胁。我的初步数据证明了微生物测序的可行性和概念证明与患者样本的DNA直接导致肺炎的更快，更准确的诊断文化。该研究的目的是在（1）培养中开发基于测序的肺炎定义正面和（2）通过将微生物组和宿主反应数据整合，然后3）的培养阴性患者评估测序对抗生素选择的预期影响。我将在 ARDS患者并使用现代文化独立的测序技术和计算生物学研究肺微生物组与宿主响应和微生物学培养物有关的方法。提议基于测序的方法有可能提高肺炎诊断的准确性（捕获两者可栽培和不可培养的生物），向临床医生提供信息比文化快得多。这，我的建议解决了开发感染创新诊断的高优先问题我提出了一项研究 - 高级测序中的动手和教学培训的职业发展密集时期技术，生物信息学，计算生物学以及临床试验设计和实施。工作将是在匹兹堡大学的肺部，过敏和重症监护医学师内进行它具有培训物理科学家的出色记录，以及高度发达的基础设施转化研究的进行。我得到了坚定的心理伙伴关系的支持微生物组和重症监护研究的专业知识，以及潜水员指导咨询委员会。支持从K23指导的职业发展奖中，我将开发一个独立的项目检查在未来五年内，基于测序的R01提案的肺炎诊断。

项目成果

期刊论文数量（27）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Protecting the lungs but hurting the kidneys: causal inference study for the risk of ventilation-induced kidney injury in ARDS.

保护肺部但伤害肾脏：ARDS 通气诱发肾损伤风险的因果推断研究。

DOI：
10.21037/atm-20-2050
发表时间：
2020
期刊：
Annals of translational medicine
影响因子：
0
作者：
Yang,Haopu;Benos,PanayiotisV;Kitsios,GeorgiosD
通讯作者：
Kitsios,GeorgiosD

A Pilot Double-Blind Placebo-Controlled Randomized Clinical Trial to Investigate the Effects of Early Enteral Nutrients in Sepsis.

DOI：
10.1097/cce.0000000000000550
发表时间：
2021-10
期刊：
Critical care explorations
影响因子：
0
作者：
Shah FA;Kitsios GD;Yende S;Dunlap DG;Scholl D;Chuan B;Al-Yousif N;Zhang Y;Nouraie SM;Morris A;Huang DT;O'Donnell CP;McVerry BJ
通讯作者：
McVerry BJ

Inter-rater reliability and prognostic value of baseline Radiographic Assessment of Lung Edema (RALE) scores in observational cohort studies of inpatients with COVID-19.