Viral Pathogenesis of Early Cystic Fibrosis Lung Disease

早期囊性纤维化肺病的病毒发病机制

基本信息

批准号：
8688346
负责人：
Stephanie Duggins Davis
金额：
$ 53.01万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
起止时间：
2012-09-26 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8688346
关键词：
Adoption Age-Months Air Australia Bacterial Infections Biological Assay Bronchiectasis Bronchoalveolar Lavage Bronchoalveolar Lavage Fluid Cell Death Cells Child Chloride Channels Clinical Trials Cystic Fibrosis Defect Detection Development Diagnosis Disease Environment Environmental air flow Epithelial Etiology Event Evolution Frequencies Image Immune Incidence Indiana Infant Infection Inflammation Inflammatory Inflammatory Response Irrigation Kinetics Lead Life Liquid substance Lower Respiratory Tract Infection Lung Lung diseases Measurement Measures Mediator of activation protein Methods Missouri Modeling Morbidity - disease rate Mucociliary Clearance Neonatal Screening Normalcy Nose Nucleic Acids Organism Pathogenesis Physiological Pulmonary Cystic Fibrosis Reporting Research Resources Respiratory physiology Role Structure of respiratory epithelium Surveillance Program Symptoms Techniques Testing Therapeutic Time Universities Viral Pathogenesis Virus Virus Diseases Washington abstracting airway epithelium airway inflammation airway obstruction base computerized cystic fibrosis airway design early cystic fibrosis infancy inflammatory marker injured airway innovation insight lung volume mortality prevent pulmonary function respiratory respiratory infection virus respiratory virus treatment strategy

项目摘要

DESCRIPTION (provided by applicant): The development and evolution of CF lung disease can be variable, but it is clear from our previous research that physiological and structural defects begin in infancy and are frequently present prior to the detection of bacterial infection, implicating other etiologies or infectious insults. Little is known about the impact of viruses on bacterial colonization, airway inflammation, physiological measures, and structural changes in the CF lung. In this proposal, we will define the role(s) of viral infections in the origins of eary CF pulmonary disease. Combining the expertise and resources available at the University of Indiana (Indianapolis, Indiana), Washington University (St. Louis, Missouri), and the Australian Early Surveillance Team for Cystic Fibrosis (AREST CF) (Melbourne and Perth, Australia), we will define the incidence and type of viral infections in CF infants. Bronchoalveolar lavage fluid and pharyngeal secretions will be collected at predetermined times during infancy, and highly sensitive nucleic acid-based detection and powerful microbiomic assays will be used to characterize lower respiratory tract infections. Also, we will systematically define the earliest physiological changes in the CF lung, combining analyses for inflammatory markers in lavage fluid, pulmonary function measurements, and computerized x-ray tomographic imaging, in a surveillance program for infants diagnosed shortly after newborn screening. Innovative airway modeling techniques will be applied to better detect and measure airway disease that precedes bronchiectasis. We will examine the relationship between viral infections and initial pathophysiological changes in the CF lung, and test the hypothesis that early respiratory viral infections alter the bacterial flora and inflammatory profile in the airway and accelerate progression of pulmonary disease in CF infants. The proposal has three Specific Aims, which will (i) define the frequency of respiratory virus infections and their impact on the evolution of endobronchial bacterial infection and inflammation in CF infants; (ii) examine the impact of early virus infections on the development of respiratory symptoms and physiological changes in the lungs of CF infants; and (iii) evaluate the relationship between virus infections and airway disease as de- fined by structural and airway modeling techniques. If successful, these studies will provide new insights into the pathogenesis of CF lung disease, aid the design of therapeutic strategies to reduce virus-induced pulmonary morbidity, and potentially prevent the development of irreversible airway disease. (End of Abstract)

描述（由申请人提供）：CF肺部疾病的发育和演变可能是可变的，但是从我们先前的研究中可以明显看出，生理和结构缺陷始于婴儿期，并且在发现细菌感染之前经常出现，这意味着其他病因或感染性侮辱。关于病毒对细菌定植，气道炎症，生理测量和CF肺结构变化的影响知之甚少。在此提案中，我们将定义病毒感染在Eary CF肺部疾病起源中的作用。将印第安纳大学（印第安纳州印第安纳波利斯），华盛顿大学（密苏里州圣路易斯）和澳大利亚囊性纤维化早期监视小组（AREST CF）（墨尔本和澳大利亚珀斯）结合使用的专业知识和资源。在婴儿期预定的时间将收集支气管肺泡灌洗液和咽部分泌物，并且高度敏感的基于核酸的检测和强大的微生物分析将用于表征下呼吸道感染。此外，我们将系统地定义CF肺中最早的生理变化，结合了灌洗液中的炎症标记，肺功能测量和计算机化的X射线断层造影成像的分析，该分析是针对新生儿筛查后不久诊断的婴儿的监视计划中的。创新的气道建模技术将用于更好地检测和测量支气管扩张之前的气道疾病。我们将研究CF肺病毒感染与初始病理生理变化之间的关系，并检验以下假设：早期呼吸道病毒感染改变了气道中的细菌菌群和炎症性菌群和CF婴儿肺部疾病的加速进展。该提案具有三个特定的目的，这将（i）定义呼吸道病毒感染的频率及其对CF婴儿的支撑菌细菌感染和炎症的影响；（ii）检查早期病毒感染对CF婴儿肺部呼吸症状和生理变化的发展的影响；（iii）评估病毒感染与气道疾病之间的关系，以结构和气道建模技术限制。如果成功，这些研究将为CF肺部疾病的发病机理提供新的见解，帮助设计治疗策略，以减少病毒诱导的肺部发病率，并有可能阻止不可逆气道疾病的发展。（抽象的结尾）