GENETIC EPIDEMIOLOGY OF RSV BRONCHIOLITIS AND ASTHMA

RSV 细支气管炎和哮喘的遗传流行病学

• 批准号: 6086055
• 负责人: Adrienne G Randolph
• 金额: $ 12.57万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-04-01 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6086055
• 关键词: adolescence (12-20); asthma; atopy; bronchioles; child (0-11); clinical research; disease /disorder etiology; family genetics; gene environment interaction; human subject; linkage disequilibriums; nitric oxide synthase; parents; respiratory disorder epidemiology; respiratory infections; respiratory syncytial virus

This proposal is designed to provide an opportunity for the Principal Investigator (PI) to gain knowledge and skills in designing and conducting genetic epidemiology research under the supervision of an advisory committee comprised of highly qualified sponsors and co-investigators. This K23 award in combination with the PI's background in pediatrics, critical care, outcomes research, clinical epidemiology and medical informatics, provides excellent potential for development of a successful independent research career focused on patient-oriented research in the genetic epidemiology of complex inflammatory lung diseases. The overall scientific goal of this proposal is to determine the genetic association between severe bronchiolitis in previously healthy infants caused by respiratory syncytial virus (RSV) and the later development of childhood asthma. Using a prospective cohort design, we propose to follow the large population of patients who were hospitalized for confirmed RSV bronchiolitis during infancy at Children's Hospital, Boston from 1990 to 2000 when they reach 3 to 13 years of age to identify those with persistent or new onset wheezing. Using an interviewer-administered questionnaire, we will assess asthma and atopy diagnoses and symptoms and environmental exposures in both biological parents and the index child. Parents will be surveyed every three months over a 2 to 5 year period to assess the persistence of wheezing in their child. Questionnaire findings will be incorporated into a multiple logistic regression model to predict the development of childhood asthma after RSV bronchiolitis in infancy. Blood will be drawn from both parents and the index child for DNA analysis to test for transmission disequilibrium in the distribution of alleles of nitric oxide synthase genes. We hypothesize that genetic mechanisms confer susceptibility to persistent wheezing after RSV bronchiolitis in infancy and that this susceptibility is found in genes regulating nitric oxide synthase. This proposal is vital to the care of the greater than 6 million childhood asthmatics in the United States. Identifying the genes associated with the onset of childhood asthma could lead to targeted interventions aimed at prevention and treatment of this disorder that is increasing at a rate of 5 percent per year.

该建议旨在为首席研究员（PI）提供机会，以在由高素质的赞助商和共同投资者组成的咨询委员会的监督下，在设计和进行遗传流行病学研究方面获得知识和技能。 这项K23奖与PI在儿科，重症监护，结果研究，临床流行病学和医学信息学方面的背景相结合，为开发成功的独立研究职业提供了极大的潜力，这些研究专注于以患者为导向的复杂炎症性肺部疾病的遗传流行病学研究。 该提案的总体科学目标是确定由呼吸道合胞病毒（RSV）引起的先前健康婴儿的严重细支气管炎与儿童哮喘的后期发展之间的遗传关联。 我们建议使用前瞻性队列设计，跟随1990年至2000年在波士顿儿童医院的婴儿期确认住院的大量患者，当时他们达到3至13岁，以识别患有持续或新发作的人。使用面试官管理的问卷，我们将评估亲生父母和指数儿童的哮喘和特征性诊断，症状以及环境暴露。在2至5年期间，将每三个月对父母进行一次调查，以评估孩子喘息的持久性。问卷调查结果将被纳入多个逻辑回归模型，以预测婴儿期RSV支气管炎后儿童哮喘的发展。 血液将从父母双方和指数子中进行DNA分析，以测试一氧化氮合酶基因等位基因分布中的传播不平衡。 我们假设遗传机制在婴儿期RSV支气管炎后具有持续喘息的敏感性，并且在调节一氧化氮合酶的基因中发现了这种敏感性。该提议对于美国超过600万童年哮喘患者至关重要。 识别与儿童哮喘发作相关的基因可能导致旨在预防和治疗这种疾病的靶向干预措施，该疾病以每年5％的速度增加。