Breath Volatile Metabolites for the Diagnosis of Emerging Invasive Mold Infection

呼吸挥发性代谢物用于诊断新发侵袭性霉菌感染

基本信息

批准号：
8528464
负责人：
Sophia Koo
金额：
$ 13.72万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-08-15 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8528464
关键词：
Agriculture Algorithms Analytical Chemistry Antifungal Agents Antifungal Therapy Area Aspergillosis Aspergillus Bioinformatics Biological Assay Biological Markers Biomedical Engineering Biometry Biopsy Breath Tests Cereals Classification Clinical Clinical Research Collection Comorbidity Complex Mixtures Dana-Farber Cancer Institute Data Derivation procedure Detection Development Development Plans Diagnosis Diagnostic Diagnostic Procedure Disease Dolin Early Diagnosis Environmental Health Epidemiology European Organization for Research and Treatment of Cancer Exhalation Fingerprint Fusarium Gas Chromatography Gases Goals Growth Hematopoietic stem cells Hospitals Human Immune system Immunocompromised Host Immunosuppressive Agents In Vitro Incidence Industry Infection Institutes Institution Investigation Kinetics Laboratories Learning Lung Lung nodule Machine Learning Mass Spectrum Analysis Massachusetts Medicine Mentors Metabolic Metabolism Modality Molds Mucorales Mucormycosis Mycoses Nutritional Operative Surgical Procedures Organ Transplantation Outcome Patient Care Patients Pattern Phase Pneumonia Population Process Public Health Schools Regimen Research Research Design Research Personnel Resistance Respiratory System Respiratory tract structure Risk Risk Factors Scedosporium Scientist Signal Transduction Sodium Glutamate Solid Specimen Spectrometry Syndrome Technology Testing The science of Mycology Training Transplant Recipients Universities Validation Vial device Woman Work air sampling base career clinically relevant cooking data mining improved medical schools microbial mortality novel novel diagnostics patient oriented patient population point of care pressure professor programs prospective volatile organic compound

项目摘要

DESCRIPTION (provided by applicant): This resubmission K23 proposal outlines a five-year development plan for Sophia Koo to achieve independence as a patient-oriented clinician-scientist with particular expertise in the development and assessment of novel diagnostic modalities for invasive mold infections (IMI). The strategy outlined in this proposal will enable Dr. Koo to build upon her clinical background in caring for patients at risk for IMI and her clinicl research defining the limitations of currently available diagnostic modalities for these infections by taking advantage of the unique clinical and research strengths of Brigham and Women's Hospital and the Dana-Farber Cancer Institute, biomedical engineering and bioinformatics capabilities of the Charles Stark Draper Laboratory, and epidemiology, biostatistics, and analytical chemistry training opportunities at the Harvard School of Public Health, Northeastern University, and Massachusetts Institute of Technology. She will be co-mentored by Dr. Lindsey Baden, Associate Professor of Medicine at Harvard Medical School, and Dr. Earl Francis Cook, Professor of Epidemiology at the Harvard School of Public Health. Dr. Baden is an expert in fungal diagnostics, and Dr. Cook is an expert in study design and statistical learning/data mining, including analysis of highly dimensional biomarker data. Dr. Koo will also work closely with Drs. Daniel Kuritzkes, Raphael Dolin, Francisco Marty, John Perfect, and John Wingard, who will provide career guidance and scientific advice on the execution of the proposed research plan, and her collaborators Drs. Paul Vouros, Terence Risby, and James Comolli, who will contribute their expertise in analytical chemistry and breath analysis to her research plan. The research program will employ analytical chemistry and statistical supervised learning approaches to define volatile organic compound (VOC) metabolite patterns of emerging invasive mold species in vitro and in patient breath to lay the groundwork for a noninvasive, point-of-care breath test for patients with emerging IMI. Specifically, this program proposes (1) a detailed definition of the VOC metabolome of the Mucorales, Fusarium, and Scedosporium species that most commonly cause human IMI, and (2) the prospective collection of VOC metabolites in the breath of patients with emerging IMI, patients with clinical and radiographic findings suggestive of an emerging IMI, and patients with respiratory tract colonization by these molds, with derivation and validation of VOC feature support vector machine classification algorithms to discriminate patients with emerging IMI from patients with other fungal infections or non-fungal pulmonary processes. Current diagnostic modalities for these infections are inadequate and often unacceptably morbid, and development of this novel, noninvasive diagnostic approach should allow earlier diagnosis of these infections than currently possible, prospective surveillance in the growing population of patients at risk for emerging IMI, more rational targeting of antifungal therapy, and improved clinical outcomes.

描述（由申请人提供）：这份重新提交的 K23 提案概述了 Sophia Koo 的五年发展计划，以实现独立，成为一名以患者为导向的临床医生科学家，在开发和评估侵袭性霉菌感染的新型诊断方式（IMI）方面具有特殊的专业知识）。该提案中概述的策略将使 Koo 博士能够利用她在护理有 IMI 风险的患者方面的临床背景，以及她的临床研究来确定目前可用的这些感染诊断方式的局限性通过利用布莱根妇女医院和丹娜法伯癌症研究所独特的临床和研究优势、查尔斯·斯塔克·德雷珀实验室的生物医学工程和生物信息学能力，以及哈佛大学的流行病学、生物统计学和分析化学培训机会公共卫生、东北大学和麻省理工学院。她将由哈佛医学院医学副教授 Lindsey Baden 博士和哈佛公共卫生学院流行病学教授 Earl Francis Cook 博士共同指导。巴登博士是真菌诊断方面的专家，库克博士是研究设计和统计学习/数据挖掘方面的专家，包括高维生物标志物数据的分析。 Koo 博士还将与 Drs. 密切合作。 Daniel Kuritzkes、Raphael Dolin、Francisco Marty、John Perfect 和 John Wingard 将为拟议研究计划的执行提供职业指导和科学建议，她的合作者 Drs. Paul Vouros、Terence Risby 和 James Comolli 将为她的研究计划贡献他们在分析化学和呼吸分析方面的专业知识。该研究计划将采用分析化学和统计监督学习方法来定义体外和患者呼吸中新兴侵入性霉菌物种的挥发性有机化合物（VOC）代谢模式，为患者的非侵入性护理点呼气测试奠定基础随着新兴的IMI。具体来说，该计划提出（1）最常引起人类 IMI 的毛霉目、镰刀菌属和 Scedosporium 物种的 VOC 代谢组的详细定义，以及 (2) 新兴 IMI 患者呼吸中 VOC 代谢物的前瞻性收集，以及临床和放射学结果提示存在 IMI 的患者的呼吸中 VOC 代谢物的前瞻性收集新兴 IMI 以及这些霉菌在呼吸道定植的患者，通过 VOC 特征支持向量机分类算法的推导和验证，将新兴 IMI 患者与其他真菌感染患者区分开来或非真菌性肺部过程。目前对这些感染的诊断方式不足，而且往往病态程度不可接受，而这种新型非侵入性诊断方法的开发应该能够比目前更早地诊断这些感染，对不断增长的有新出现 IMI 风险的患者群体进行前瞻性监测，更合理的靶向治疗抗真菌治疗，并改善临床结果。