Respiratory Viral Determinants of Chronic Lung Allograft Dysfunction

慢性同种异体肺移植功能障碍的呼吸道病毒决定因素

• 批准号: 10629762
• 负责人: Cynthia E Fisher
• 金额: $ 5.38万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10629762
• 关键词: Address; Allografting; Antiviral Agents; Area; Area Under Curve; Biological Assay; Biological Models; Biometry; Cessation of life; Characteristics; Chronic; Clinical; Clinical Investigator; Collection; Communities; Data; Data Set; Development; Diagnosis; Early Diagnosis; Early identification; Enrollment; Epidemiology; Event; Failure; Forced expiratory volume function; Fostering; Functional disorder; Future; Goals; Graft Survival; Home; Immunology; Impaired wound healing; Integration Host Factors; Intervention Studies; Intervention Trial; Kinetics; Knowledge; Laboratories; Life; Longitudinal Studies; Lung; Lung Transplantation; Mentored Patient-Oriented Research Career Development Award; Mentors; Methods; Modeling; Organ Transplantation; Outcome; Parents; Pathogenesis; Patient-Focused Outcomes; Patients; Process; Prospective cohort; Published Comment; Pulmonary Function Test/Forced Expiratory Volume 1; Pulmonary Inflammation; Pulmonology; Research; Research Personnel; Research Training; Resources; Risk; Risk Factors; Role; Sampling; Spirometry; Statistical Data Interpretation; Statistical Models; Therapeutic Studies; Time; Training Programs; Translational Research; Transplant Recipients; Transplantation; Viral; Viral Load result; Virus; Virus Diseases; base; complex data; design; graft failure; high risk population; improved; improved outcome; innovation; insight; lung allograft; lung injury; mortality; nasal swab; novel; pandemic influenza; primary endpoint; prospective; pulmonary function; rational design; respiratory; respiratory infection virus; response; skills; virology

PROJECT SUMMARY/ABSTRACT This K23 supplement proposal continues a five-year research training program that will foster Dr. Fisher’s transition into an independent clinically-oriented academic researcher, focusing on viral infections in transplant recipients. Her long-term objective is to improve outcomes following transplantation by performing translational research to define the role of viral infections in chronic lung allograft dysfunction (CLAD). The parent K23 award has provided her support to improve her knowledge in three major areas: 1) prospective cohort design and enrollment, 2) pulmonary transplant, and 3) statistical analysis and modeling of complex data sets. She has assembled an outstanding group of mentors who have expertise in virology, transplant, pulmonology, immunology, epidemiology, and biostatistics. This proposal will provide additional support to complete her K23 research and to overall allow her to continue her transition into an independent academic researcher. Dr. Fisher’s goal in this proposal mirrors her parent K23: to define how specific viral and host characteristics, and early pulmonary functional changes, associate with CLAD development in LTR with respiratory virus infection (RVI). In the first aim, Dr. Fisher has been prospectively enrolling LTR with symptomatic RVI and collecting frequent longitudinal nasal swabs, using a patient self-collection method, and home spirometry. She will: 1) characterize the detailed virologic course of symptomatic RVI in LTR, including virus type, peak viral load, duration of shedding, rate of viral load change, and area under the curve, 2) define the course of early lung function changes after RVI, as evidenced by the forced expiratory volume in one second (FEV1), and 3) analyze the association between virologic characteristics and early decline in FEV1. In her second aim, she will use the detailed virologic information from her first aim to identify specific viral and host determinants of CLAD in LTR with symptomatic RVI. In her third aim, she will analyze the detailed spirometry data to assess how the degree and magnitude of early decline in FEV1 after RVI is related to subsequent development of CLAD. Through accomplishing the aims in this proposal, Dr. Fisher will identify virologic, host, and early FEV1 characteristics associated with RVI that can predict subsequent development of CLAD. She will also refine a self-collection method that can be used for future longitudinal RVI studies and provide critical background data on the virologic course of RVI that can be used for the rational design of future interventional trials of novel antiviral agents. Ultimately, this proposal will allow Dr. Fisher to hone her skills as a clinical investigator and transition into an independent researcher who will advance our understanding of viral infections in transplant recipients to improve patient outcomes.

项目摘要/摘要 这项K23补充提案继续进行了一项为期五年的研究培训计划，该计划将促进费舍尔博士 过渡到独立的临床学术研究人员，重点关注移植的病毒感染 收件人。她的长期目标是通过进行翻译来改善移植后的结果 研究病毒感染在慢性肺同种异体功能障碍（CLAD）中的作用。父母K23 奖项提供了她在三个主要领域的知识的支持：1）潜在的队列设计 2）肺移植和3）复杂数据集的统计分析和建模。她 已经组建了一群杰出的导师，他们在病毒学，移植，肺病学， 免疫学，流行病学和生物统计学。该建议将提供额外的支持以完成她的K23 研究，总体上使她能够继续过渡到独立的学术研究员。 费舍尔博士在此提案中的目标反映了她的父母K23：定义特定的病毒和宿主特征， 和早期的肺功能变化，与LTR中的外壳发育与呼吸道病毒相关 感染（RVI）。在第一个目的中，费舍尔博士一直在症状RVI和 使用患者自我收集方法和家用肺活量测定法，经常收集纵向鼻拭子。她 意志：1）表征LTR中有症状的RVI的详细病毒学课程，包括病毒类型，峰值病毒 负载，脱落持续时间，病毒载荷变化率以及曲线下的面积，2）定义早期的过程 RVI后肺功能发生变化，这是一秒钟内强制呼气量（FEV1）和3）的变化。 分析病毒学特征与FEV1早期下降之间的关联。在她的第二个目标中，她将 使用她的第一个目的中的详细病毒学信息来识别特定的病毒和宿主决定者 在有症状的RVI中。在她的第三个目标中，她将分析详细的肺活量测定数据，以评估 RVI后FEV1早期下降的程度和幅度与随后的外壳发展有关。 通过在该提案中实现目标，费舍尔博士将确定病毒学，宿主和早期FEV1 与RVI相关的特征，可以预测随后的外壳发展。她还将完善 可用于未来纵向RVI研究并提供关键背景数据的自我收集方法 在RVI的病毒过程中，可用于新型介入试验的合理设计 抗病毒药。最终，该建议将使费舍尔博士成为临床研究者的技能，并 过渡到独立的研究人员，他将提高我们对移植中病毒感染的理解 提高患者预后的接受者。

项目成果

American Society of Transplantation and Cellular Therapy Series, 2: Management and Prevention of Aspergillosis in Hematopoietic Cell Transplantation Recipients.

• DOI: 10.1016/j.jtct.2020.10.003
• 发表时间: 2021-03
• 期刊: TRANSPLANTATION AND CELLULAR THERAPY
• 影响因子: 3.2
• 作者: Dadwal, Sanjeet S.;Hohl, Tobias M.;Fisher, Cynthia E.;Boeckh, Michael;Papanicolaou, Genofeva;Carpenter, Paul A.;Fisher, Brian T.;Slavin, Monica A.;Kontoyiannis, D. P.
• 通讯作者: Kontoyiannis, D. P.