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: 9178636
• 负责人: Alpana Amalkant Waghmare
• 金额: $ 18.3万
• 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/9178636
• 关键词: Affect; Allogenic; Autologous; Biological Markers; Biostatistical Methods; Blood; Blood specimen; Cell Transplants; Clinical; Communicable Diseases; Cytokine Gene; Data; Development; Diagnostic; Disease; Disease Outcome; Disease Progression; Elderly; Ensure; Epidemiologic Methods; Gene Expression; Gene Expression Profile; Genes; Genetic; Goals; Heart; Hematopoietic; Human; Hybrids; 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; Nose; Outcome; Pathway interactions; Patient risk; Patients; Pneumonia; Population; Prevention strategy; Prospective cohort; Prospective cohort study; Protocols documentation; RNA; Research; Research Personnel; Research Training; Respiratory syncytial virus; Reverse Transcriptase Polymerase Chain Reaction; Rhinovirus; Risk; Risk Factors; Risk Management; Risk stratification; Role; Sampling; Science; Serum; Severity of illness; Specimen; Statistical Data Interpretation; 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; public health relevance; 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.