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，让其在由高素质申办者和共同研究者组成的咨询委员会的监督下获得设计和进行遗传流行病学研究的知识和技能。 该 K23 奖项与 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，为成功的独立研究生涯的发展提供了巨大的潜力，该职业专注于以患者为导向的复杂炎症性肺病遗传流行病学研究。 该提案的总体科学目标是确定先前健康婴儿中由呼吸道合胞病毒（RSV）引起的严重细支气管炎与后来发展为儿童哮喘之间的遗传关联。 使用前瞻性队列设计，我们建议对 1990 年至 2000 年波士顿儿童医院婴儿期因确诊 RSV 细支气管炎住院的大量患者进行跟踪，当他们年满 3 至 13 岁时，以识别那些持续或新发的患者喘息。使用采访者管理的问卷，我们将评估亲生父母和指标孩子的哮喘和特应性诊断、症状以及环境暴露。在 2 至 5 年内，每三个月对家长进行一次调查，以评估孩子喘息的持续情况。问卷调查结果将纳入多重逻辑回归模型，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取血液进行 DNA 分析，以测试一氧化氮合酶基因等位基因分布的传递不平衡。 我们假设遗传机制导致婴儿期 RSV 细支气管炎后对持续性喘息的易感性，并且这种易感性存在于调节一氧化氮合酶的基因中。该提案对于美国超过 600 万儿童哮喘患者的护理至关重要。 识别与儿童哮喘发病相关的基因可能会导致有针对性的干预措施，旨在预防和治疗这种以每年 5% 的速度增长的疾病。

项目成果

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？

• 发表时间: 2002-05
• 影响因子: 8.8
• 作者: Randolph; Adrienne G
• 通讯作者: Adrienne G

Risk of bacterial infection in previously healthy respiratory syncytial virus-infected young children admitted to the intensive care unit.

先前健康的呼吸道合胞病毒感染幼儿入住重症监护室时存在细菌感染的风险。

• 发表时间: 2004-11
• 作者: Randolph, Adrienne G;Reder, Lindsay;Englund, Janet A
• 通讯作者: Englund, Janet A

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。

• 发表时间: 2014-02
• 作者: Randolph, A G;Yip, W;Falkenstein;Weiss, S T;Janssen, R;Keisling, S;Bont, L
• 通讯作者: Bont, L

Growth of pediatric intensive care units in the United States from 1995 to 2001.

1995 年至 2001 年美国儿科重症监护病房的增长。

• 发表时间: 2004-06
• 作者: Randolph, Adrienne G;Gonzales, Calle A;Cortellini, Lynelle;Yeh, Timothy S
• 通讯作者: Yeh, Timothy S

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

危重婴儿细支气管炎干预措施的疗效：系统评价和荟萃分析。

• 发表时间: 2004-09
• 作者: Davison, Caroline;Ventre, Kathleen M;Luchetti, Marco;Randolph, Adrienne G
• 通讯作者: Randolph, Adrienne G