Viral and Host Biomarkers of Human Rhinovirus Disease Severity in Transplantation

移植中人类鼻病毒疾病严重程度的病毒和宿主生物标志物

• 批准号: 8985653
• 负责人: Alpana Amalkant Waghmare
• 金额: $ 17.24万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-12-11 至 2019-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8985653
• 关键词: Affect; Allogenic; Autologous; Biological Markers; Biostatistical Methods; Blood; Blood specimen; Cell Transplants; Clinical; Cohort Studies; Communicable Diseases; Cytokine Gene; Data; Development; Diagnostic; Disease; Disease Outcome; Disease Progression; Elderly; Ensure; Epidemiologic Methods; Gene Expression; Gene Expression Profile; Genes; Genetic; Goals; Health; Heart; Hematopoietic; Human; Immunocompromised Host; Immunology; Individual; Infant; Infection; Infectious Disease Epidemiology; Influenza; Integration Host Factors; Intervention; Knowledge; Laboratories; Lower Respiratory Tract Infection; Lung; Mentors; Microspheres; Modeling; Molecular; Molecular Profiling; Morbidity - disease rate; Nasal Lavage Fluid; Outcome; Pathway interactions; Patient risk; Patients; Pneumonia; Population; Prevention strategy; Protocols documentation; RNA; Research; Research Personnel; Research Training; Respiratory syncytial virus; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Risk; Risk Factors; Role; Sampling; Science; Serum; Severity of illness; Specimen; Statistical Data Interpretation; Stratification; Surveys; Symptoms; Techniques; Technology; Testing; Training; Training Programs; Transplant Recipients; Transplantation; Untranslated RNA; Upper Respiratory Infections; Viral; Viral Load result; Viral Respiratory Tract Infection; Virus; Virus Shedding; Vulnerable Populations; Whole Blood; base; biomarker identification; career; cohort; cytokine; data modeling; differential expression; improved; influenzavirus; innovation; insight; mortality; parainfluenza virus; pathogen; patient stratification; peripheral blood; primary outcome; programs; prospective; respiratory; respiratory virus; response; sample collection; secondary outcome; statistics; success; surveillance study; tool; treatment strategy; virology

 DESCRIPTION (provided by applicant): This proposal describes a five-year research training program that will allow me to achieve my goal of becoming an independent clinically-oriented academic researcher, focusing on respiratory viral infections in immunocompromised hosts. My goal is to improve patient transplant-related infectious disease outcomes through better defining risks for poor outcomes in human rhinovirus (HRV) and other respiratory viral infections, and applying this knowledge to develop biomarkers for disease severity. This proposal builds upon my training in clinical infectious diseases, epidemiologic and biostatistical methods and laboratory-based science, and provides a detailed plan to improve my knowledge of virology, immunology and genetics, conducting prospective cohort studies, and gene expression statistical analysis. This proposal incorporates the expertise of an outstanding group of mentors, including experts in infectious diseases, epidemiology, statistics, and data modeling, who are dedicated to ensuring the success of this project and the development of my career as an independent clinical researcher. The first aim of this proposal involves the analysis of viral factors that determine disease severity in HRV infection. Specifically, I will determine the role o viral load in serum and respiratory samples, viral species type, and viral shedding on disease outcomes including progression to lower tract disease and mortality. The success of this proposal is bolstered by the unique opportunity to perform uniform molecular testing on both retrospectively and prospectively collected specimens from a large cohort of patients, allowing the opportunity to develop multivariable models and adjust for multiple clinical covariates. For my second aim, I will identify host factors through the analysis of cytokine profiles and gene expression profiles that determine disease severity. Again utilizing access to a large cohort of HCT recipients and established prospective sample collection protocols, I will be able to develop robust biomarkers that will provide important insight into biologic pathways during HRV infection in immunocompromised hosts. Through accomplishing the aims in this proposal, I will contribute significantly to our knowledge of the impact of HRV infection in transplantation, and our ability to use viral and host biomarkers to predict disease severity. Despite improvements in transplant practices, HRV remains a significant cause of infectious mortality in HCT recipients. Identification of biomarkers has the potential to guide early and specific diagnostic tools and wil provide a basis to develop prevention and treatment strategies. Ultimately, the proposal will allow me to develop a larger research program to improve our understanding and affect outcomes of respiratory viral infections in immunocompromised hosts, which can then be applied to other vulnerable populations including infants, the elderly, and individuals with preexisting heart or pulmonary conditions.

 描述（由申请人提供）：该提案描述了一个为期五年的研究培训计划，该计划将使我能够实现成为一名独立的临床导向的学术研究人员的目标，重点研究免疫功能低下宿主的呼吸道病毒感染。我的目标是通过更好地确定人类鼻病毒 (HRV) 和其他呼吸道病毒感染不良结果的风险，并应用这些知识来开发疾病严重程度的生物标志物，从而改善患者与移植相关的传染病的结果。该提案建立在我在临床传染病、流行病学和生物统计方法以及基于实验室的科学方面的培训的基础上，并提供了详细的计划来提高我对病毒学、免疫学和遗传学的了解，进行前瞻性队列研究和基因表达统计分析。该提案融合了一批杰出导师的专业知识，包括传染病、流行病学、统计学和数据建模方面的专家，他们致力于确保该项目的成功以及我作为独立临床研究员的职业发展。 该提案的首要目标是分析决定 HRV 感染疾病严重程度的病毒因素。具体来说，我将确定血清和呼吸道样本中的病毒载量、病毒种类类型和病毒脱落对疾病结果（包括发展为下呼吸道疾病和死亡率）的作用。该提案的成功得益于对从大量患者中回顾性和前瞻性收集的标本进行统一分子测试的独特机会，从而有机会开发多变量模型并针对多个临床协变量进行调整。对于我的第二个目标，我将通过分析决定疾病严重程度的细胞因子谱和基因表达谱来确定宿主因素。再次利用大量 HCT 接受者并建立前瞻性样本收集方案，我将能够开发强大的生物标志物，为免疫功能低下宿主 HRV 感染期间的生物途径提供重要见解。 通过实现本提案中的目标，我将为我们了解 HRV 感染对移植的影响以及我们使用病毒和宿主生物标志物预测疾病严重程度的能力做出重大贡献。尽管移植实践有所改进，HRV 仍然是 HCT 受者感染性死亡的一个重要原因。生物标志物的鉴定有可能指导早期和特定的诊断工具，并将为制定预防和治疗策略提供基础。最终，该提案将使我能够开发一个更大的研究项目，以提高我们对免疫功能低下宿主呼吸道病毒感染的了解并影响结果，然后将其应用于其他弱势群体，包括婴儿、老年人和患有心脏病或肺部疾病的个人。