Impact of Cumulative Exposure to Respiratory Viruses after Allogeneic Hematopoietic Cell Transplantation

同种异体造血细胞移植后累积暴露于呼吸道病毒的影响

• 批准号: 10092093
• 负责人: Chikara Ogimi
• 金额: $ 18.51万
• 依托单位: SEATTLE CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-15 至 2021-07-26
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10092093
• 关键词: Address; Adult; Air Movements; Allogenic; Antibiotics; Antiviral Agents; Bacterial Infections; Biostatistical Methods; Caring; Childhood; Clinic Visits; Clinical; Clinical Research; Cohort Studies; Communicable Diseases; Data; Diagnostic; Disease; Disease Progression; Dose; Ensure; Epidemiologic Methods; Exposure to; Frequencies; Goals; Healthcare; Home; Immunocompromised Host; Incidence; Infectious Disease Epidemiology; Inpatients; Knowledge; Laboratories; Link; Longterm Follow-up; Lower Respiratory Tract Infection; Lung; Lung infections; Medical; Medicine; Mentors; Molecular; Molecular Diagnosis; Molecular Virology; Monitor; Mycoses; Nose; Observational Study; Obstruction; Outcome; Outpatients; Patient-Focused Outcomes; Patients; Pattern; Prevention strategy; Prospective Studies; Research; Research Personnel; Research Training; Resources; Respiratory Signs and Symptoms; Retrospective cohort; Risk; Role; Sampling; Severity of illness; Surveys; Techniques; Testing; Therapeutic; Time; Training; Training Programs; Transplant Recipients; Transplantation; Upper Respiratory Infections; Vaccines; Viral; Viral Respiratory Tract Infection; Virus; Virus Diseases; Vulnerable Populations; airway inflammation; airway obstruction; antimicrobial; base; burden of illness; career development; clinical practice; cohort; health care service; hematopoietic cell transplantation; improved; improved outcome; innovation; insight; molecular diagnostics; mortality; nasal swab; novel; post-transplant; primary endpoint; programs; prospective; respiratory; respiratory virus; self testing; statistics; success; treatment strategy

PROJECT SUMMARY This proposal describes a five-year research training program that will allow the candidate to achieve his long-term goal of becoming an independent clinically-oriented academic researcher, focusing on respiratory viral infections (RVIs) in immunocompromised (IC) hosts. His objective is to improve hematopoietic cell transplantation (HCT) outcomes by improving the understanding of RVI disease burden and the association with antibiotic use. He will apply the knowledge gained through this proposal to develop therapeutic and preventive strategies that mitigate the disease burden and complications of RVI in IC hosts. This proposal builds upon his clinical training in infectious diseases as well as epidemiologic and biostatistical methods for clinical research in this field. He provides a detailed plan to enhance his knowledge of healthcare services, molecular virology and conducting prospective studies. This proposal incorporates the expertise of an outstanding group of mentors, including experts in transplant infectious diseases, epidemiology, statistics, antimicrobial stewardship, healthcare services, and laboratory medicine, who are dedicated to ensuring the success of this project and the development of his career as an independent clinical researcher. The first aim of this proposal involves a large retrospective cohort of allogeneic HCT recipients to determine the burden of multiple (concurrent or sequential) RVIs on airflow obstruction, fungal and bacterial pulmonary infections, mortality and healthcare resource utilization after HCT. Using a multiplex quantitative PCR, he will test a hypothesis that multiple RVIs have a dose-dependent association with increased risk of these outcomes. His second aim will examine whether specific or cumulative antibiotic exposure is associated with increased risk of respiratory viral disease progression. As is the case in first aim, a large cohort of patients will allow him to analyze these relationships while adjusting for multiple clinical covariates. The third aim will characterize the incidence and disease spectrum of RVI as well as antibiotic use following new respiratory symptoms late after allogeneic HCT. Capturing data regarding RVI and antibiotic use will be optimized by utilizing home-based self-collected nasal swabs and prospective monitoring. By accomplishing the aims in this proposal, he will address critical gaps in our knowledge of the contribution of multiple RVIs to disease burden in HCT recipients and the utility of multiplex molecular testing. Given that new antiviral therapeutics and vaccines are on the horizon, understanding the relative significance of multiple RVIs will provide the rationale to develop “multi”-target antiviral agents as well as therapeutic and preventive strategies. In addition, the clarification of the link between RVI and antibiotic use will inform optimized antibiotic strategies using viral diagnostics. Ultimately, this proposal will allow him to build a larger research program for better understanding of RVI disease burden in IC hosts and improve patient outcomes, which can then be applied to other vulnerable populations.

项目摘要 该提案描述了一个为期五年的研究培训计划，该计划将使候选人能够实现其 长期目标是成为一名独立的临床导向的学术研究人员，专注于呼吸 免疫受损（IC）宿主中的病毒感染（RVIs）。他的目标是改善造血细胞 通过提高对RVI疾病负担及其与肝移植（HCT）结局的相关性的认识， 使用抗生素。他将应用通过这项建议获得的知识来开发治疗和 预防策略，减轻疾病负担和并发症的RVI在IC主机。这项建议 基于他在传染病以及流行病学和生物统计学方法方面的临床培训， 在这个领域的临床研究。他提供了一个详细的计划，以提高他的医疗保健服务的知识， 分子病毒学和进行前瞻性研究。该提案包含了一个专家的专门知识， 杰出的导师小组，包括移植传染病，流行病学，统计学， 抗菌药物管理，医疗保健服务和实验室医学，他们致力于确保 该项目的成功以及他作为独立临床研究人员的职业发展。 该提案的第一个目的是对同种异体HCT接受者进行大型回顾性队列研究，以确定 多次（同时或顺序）RVI对气流阻塞、真菌和细菌性肺部疾病的负担 HCT后的感染、死亡率和医疗资源利用。使用多重定量PCR，他将 检验多种RVI与这些风险增加具有剂量依赖性相关性的假设 结果。他的第二个目标是研究特定的或累积的抗生素暴露是否与 呼吸道病毒性疾病进展的风险增加。与第一个目标的情况一样，一个大型患者队列 将允许他分析这些关系，同时调整多个临床协变量。第三个目标将 描述RVI的发病率和疾病谱以及新呼吸道感染后的抗生素使用情况 同种异体HCT后晚期症状。将通过以下方式优化获取有关RVI和抗生素使用的数据： 利用家庭自我采集的鼻拭子和前瞻性监测。 通过实现本提案中的目标，他将填补我们对贡献的认识方面的关键空白。 多种RVI对HCT受者疾病负担的影响以及多重分子检测的实用性。鉴于 新的抗病毒疗法和疫苗即将问世，了解 多个RVI将为开发“多”靶点抗病毒剂以及治疗和 预防战略。此外，澄清RVI和抗生素使用之间的联系将有助于 使用病毒诊断优化抗生素策略。最终，这一提议将使他能够建立一个更大的 研究计划，以更好地了解IC宿主中的RVI疾病负担并改善患者结局， 然后可以应用于其他弱势群体。