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

• 批准号: 8875578
• 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
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8875578
• 关键词: Agriculture; Algorithms; Analytical Chemistry; Antifungal Agents; Antifungal Therapy; Area; Aspergillosis; Aspergillus; Bioinformatics; 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; diagnostic assay; improved; medical schools; microbial; mortality; novel; novel diagnostics; patient oriented; patient population; point of care; pressure; professor; programs; prospective; volatile organic compound

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）：该重新提议的提案概述了为索菲亚·库（Sophia Koo）作为一个以患者为导向的临床医生而独立的五年发展计划，该计划在开发和评估新型诊断型侵入性霉菌感染（IMI）方面具有特殊专业知识。该提案中概述的策略将使Koo博士能够以其临床背景为基础，以照顾有IMI风险的患者和她的诊所研究，从而定义了当前可用的诊断方式的局限性 通过利用Brigham和妇女医院的独特临床和研究优势以及Dana-Farber癌症研究所，Charles Stark Draper实验室的生物医学工程和生物信息学能力，以及在哈佛大学，Northeral Health University，Massachusets sthernsters and Massachusets sthermits of Charles Stark Draper实验室以及流行病学，生物统计学和分析化学培训机会。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博士共同登记。 Baden博士是真菌诊断专家，Cook博士是研究设计和统计学习/数据挖掘的专家，包括对高度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，他们将就执行拟议的研究计划的执行以及她的合作者Drs提供职业指导和科学建议。保罗·沃罗斯（Paul Vouros），特伦斯·里斯比（Terence Risby）和詹姆斯·科洛利（James Comolli）将为她的研究计划贡献他们的分析化学和呼吸分析专业知识。该研究计划将采用分析化学和统计监督学习方法来定义新兴的入侵性霉菌物种在体外和患者呼吸中的挥发性挥发性有机化合物（VOC）代谢物模式，为有新兴IMI的患者进行无创，病态的呼气测试奠定了基础。具体来说，该程序提出了（1） 最常见引起人类IMI的粘膜，镰刀菌和Scedosporium物种的VOC代谢组的详细定义，以及（2）（2）在具有临床和放射线图的患者的呼吸中，在临床和放射线摄影的患者的呼吸中收集了VOC代谢物，这些患者伴有呼吸道和呼吸道菌落的效果，并在呼吸道上进行了验证，并具有呼吸道的效果，并具有呼吸道的效果，并具有呼吸道的验证。算法与其他真菌感染或非真菌肺部过程的患者区分出现IMI的患者。这些感染的当前诊断方式是不足的，通常是不可接受的病态，而这种新颖的无创诊断方法的发展应允许对这些感染的早期诊断，而不是目前可能的诊断，对不断增长的患者人群的前瞻性监视，对新出现的IMI风险，对抗真菌治疗的合理靶向更合理地靶向抗真菌治疗的临床和改进的临床。