Pathogenesis of virus-induced acute otitis media

病毒引起的急性中耳炎的发病机制

• 批准号: 8490333
• 负责人: Tasnee Chonmaitree
• 金额: $ 71.71万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-20 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8490333
• 关键词: 1 year old; Acute; Age; Age-Months; Archives; Bacteria; Bacterial Infections; Birth; Breast Feeding; Case-Control Studies; Child; Childhood; Clinical Research; Complex; Complication; Cytokine Gene; DNA; Data; Disease; Enrollment; Environment; Environmental Risk Factor; Ethnic Origin; Etiology; Feeding Patterns; Frequencies; Funding; Gender; Genes; Genetic; Genetic Polymorphism; Genetic Predisposition to Disease; Genetic Risk; Genotype; Health; IL8 gene; Incidence; Individual; Infant; Inflammation; Inflammatory; Interferons; Interleukin-10; Interleukin-12; Interleukin-13; Interleukin-2; Interleukin-4; Interleukin-5; Interleukin-6; Knowledge; Lead; Life; Methods; Microbe; Monitor; Otitis; Otitis Media; Pathogenesis; Predisposition; Prevention; Prevention strategy; Public Health; RANTES; Race; Recovery; Research; Research Personnel; Risk; Risk Factors; Role; Sample Size; Sampling; Statistical Models; TNF gene; Techniques; Testing; Time; Update; Urine; Viral; Virus Diseases; Work; base; chemokine; cigarette smoking; cytokine; data mining; design; feeding; follow-up; genetic risk factor; high risk; innovation; microbial; pathogen; pathogenic bacteria; prevent; prospective; virus development; virus pathogenesis

DESCRIPTION (provided by investigator): Otitis media (OM) is the most common disease seen in pediatric practice and is recognized as a multifactorial disease with complex and interrelated genetic, environmental and infectious etiologies. The long- term objectives of our research group are to elucidate the contribution of infectious pathogens, and their complex interactions with other OM risk factors in the pathogenesis of and recovery from acute otitis media (AOM), and to identify possible strategies for more effective prevention and/or treatment. We have recently found an important association between proinflammatory cytokine gene polymorphisms (TNF1-308 and IL- 6-174) and increased OM susceptibility, and possible modifying effects of environmental factors such as breastfeeding (BF) and cigarette smoke exposure (CSE) on OM susceptibility in polymorphic individuals. During the next funding period, we propose to study further the pathogenesis of virus-induced AOM, specifically on the mechanisms by which genetic risk factors (as represented by TNF1-308 and IL- 6-174 polymorphisms) render the host OM susceptible and whether environmental factors could modify OM risks in children with genetic predisposition. Aim 1: Perform a prospective, case-control study of 300 infants with and without TNF1-308 polymorphism followed to the first AOM episode up to 1 year of age. Subjects will be screened for the gene polymorphism; equal number of polymorphic and normal infants (matched for gender and race) will be enrolled into the study within the first month of life. The dynamics of nasopharyngeal bacterial colonization in the first 6 mos. of life will be studied; symptomatic URI episodes will be monitored for AOM complication. Information on BF, CSE, and DC attendance will be collected prospectively and updated continuously. Incidence of AOM in the first year of life (per cent of cases with at least one episode in the first year) will be compared between polymorphic and normal children groups; modifying effects of environmental risk factors on bacterial colonization, incidence of viral URI and AOM will be assessed. Sample size will also be adequate for parallel comparison between IL- 6-174 polymorphic and normal children. Aim 2: Investigate further the association between several other cytokine/ chemokine gene polymorphisms and OM susceptibility. Archived and new DNA samples from the proposed Study 1 (from OM-susceptible and non-OM susceptible children, n=800) will be tested for 11 cytokine/ chemokine gene polymorphisms using the state-of-the-art microarray technique. Gene polymorphisms will be associated with OM susceptibility; data mining will be used to analyze complex data. Information generated from our studies will be important to public health as it will lay the ground work for the design of innovative approaches to prevent OM, especially in children born with genetic predisposition and those exposed to OM environmental risks.

描述（由研究者提供）：中耳炎 (OM) 是儿科实践中最常见的疾病，被认为是一种多因素疾病，具有复杂且相互关联的遗传、环境和感染病因。我们研究小组的长期目标是阐明传染性病原体的作用，以及它们与其他 OM 危险因素在急性中耳炎 (AOM) 发病机制和恢复中的复杂相互作用，并确定更有效预防的可能策略和/或治疗。我们最近发现促炎细胞因子基因多态性（TNF1-308 和 IL-6-174）与 OM 易感性增加之间存在重要关联，并且母乳喂养 (BF) 和香烟烟雾暴露 (CSE) 等环境因素可能对 OM 产生改变作用多态个体的易感性。在下一个资助期内，我们建议进一步研究病毒诱导的AOM的发病机制，特别是遗传风险因素（以TNF1-308和IL-6-174多态性为代表）使宿主OM易感的机制以及是否环境因素可能会改变具有遗传倾向的儿童的 OM 风险。目标 1：对 300 名有或没有 TNF1-308 多态性的婴儿进行一项前瞻性病例对照研究，研究对象为第一次 AOM 发作后直至 1 岁。对受试者进行基因多态性筛查；同等数量的多态性婴儿和正常婴儿（性别和种族相匹配）将在出生后第一个月内被纳入研究。前 6 个月内鼻咽部细菌定植动态。将研究生活的内容；将监测有症状的 URI 发作是否有 AOM 并发症。 BF、CSE 和 DC 出勤信息将前瞻性收集并持续更新。将在多态性儿童组和正常儿童组之间比较出生后第一年 AOM 的发病率（第一年至少发作一次的病例百分比）；将评估环境风险因素对细菌定植、病毒 URI 和 AOM 发生率的影响。样本量也足以用于IL-6-174多态性和正常儿童之间的平行比较。目标 2：进一步研究其他几种细胞因子/趋化因子基因多态性与 OM 易感性之间的关联。来自拟议研究 1 的存档和新 DNA 样本（来自 OM 易感性和非 OM 易感性儿童，n=800）将使用最先进的微阵列技术测试 11 种细胞因子/趋化因子基因多态性。基因多态性与 OM 易感性相关；数据挖掘将用于分析复杂的数据。我们的研究产生的信息对公共卫生很重要，因为它将为设计预防 OM 的创新方法奠定基础，特别是对于出生时有遗传倾向的儿童和暴露于 OM 环境风险的儿童。