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: 6732632
• 负责人: Adrienne G Randolph
• 金额: $ 12.58万
• 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 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6732632
• 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.

该提案旨在为首席研究员（PI）提供一个机会，在由高素质发起人和共同研究者组成的咨询委员会的监督下，获得设计和开展遗传流行病学研究的知识和技能。该K23奖结合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，为成功的独立研究事业的发展提供了极好的潜力，专注于复杂炎症性肺病遗传流行病学中以患者为导向的研究。本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毛细支气管炎与儿童哮喘后期发展之间的遗传关联。采用前瞻性队列设计，我们建议对1990年至2000年期间在波士顿儿童医院因确诊的RSV毛细支气管炎住院的大量婴儿患者进行随访，当他们达到3至13岁时，以确定是否有持续性或新发喘息。使用访谈者管理的问卷，我们将评估哮喘和特应性诊断、症状和环境暴露在亲生父母和指数儿童。父母将在2至5年的时间里每三个月接受一次调查，以评估孩子的喘息持续情况。问卷调查结果将被纳入多元logistic回归模型，以预测婴儿期RSV细支气管炎后儿童哮喘的发展。将从父母和索引孩子身上抽血进行DNA分析，以检测一氧化氮合酶基因等位基因分布的传播不平衡。我们假设遗传机制赋予婴儿期RSV细支气管炎后持续喘息的易感性，并且这种易感性存在于调节一氧化氮合酶的基因中。这项建议对美国600多万儿童哮喘患者的护理至关重要。确定与儿童哮喘发病相关的基因可能导致有针对性的干预措施，旨在预防和治疗这种疾病，这种疾病正以每年5%的速度增长。

项目成果

Vitamin D-binding protein haplotype is associated with hospitalization for RSV bronchiolitis.

维生素 D 结合蛋白单倍型与 RSV 细支气管炎住院相关。

• DOI: 10.1111/cea.12247
• 发表时间: 2014
• 期刊: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
• 作者: Randolph,AG;Yip,W-K;Falkenstein-Hagander,K;Weiss,ST;Janssen,R;Keisling,S;Bont,L
• 通讯作者: Bont,L

Mining for the genetic determinants of septic shock: when is it really gold?

挖掘感染性休克的遗传决定因素：什么时候才是真正的黄金？

• DOI: 10.1097/00003246-200205000-00037
• 发表时间: 2002
• 期刊: Critical care medicine
• 影响因子: 8.8
• 作者: Randolph,AdrienneG

Efficacy of interventions for bronchiolitis in critically ill infants: a systematic review and meta-analysis.

• DOI: 10.1097/01.pcc.0000128891.54799.67
• 发表时间: 2004-09-01
• 期刊: Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies
• 作者: Davison, Caroline;Ventre, Kathleen M;Randolph, Adrienne G
• 通讯作者: Randolph, Adrienne G