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: 8465053
• 负责人: Tasnee Chonmaitree
• 金额: $ 4万
• 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 2014-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8465053
• 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. PUBLIC HEALTH RELEVANCE Otitis media is a highly prevalent disease in infants and children. This study is relevant to public health because information to be generated will be the basis for the design of innovative approaches to prevent otitis media, especially in children born with genetic predisposition and those exposed to OM environmental risks.

描述（由研究者提供）：耳炎培养基（OM）是小儿实践中最常见的疾病，被认为是一种具有复杂且相互关联的遗传，环境和感染性病因的多因素疾病。我们研究小组的长期目标是阐明感染性病原体的贡献，以及它们与其他OM风险因素的复杂相互作用在急性中耳炎（AOM）的发病机理和恢复中的复杂相互作用，并确定了更有效的预防和/或治疗的可能策略。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易感性的提高与环境因素（如母乳喂养（BF）（BF）（BF）和香烟烟雾暴露（CSE）对多态性个体OM敏感性等环境因素的影响。在下一个资金期间，我们建议进一步研究病毒诱导的AOM的发病机理，特别是基于遗传危险因素（由TNF1-308和IL-6-174多态性代表的机制）使宿主OM易感性以及环境环境因素是否可以改变遗传性抗胃抗presticportive的儿童的OM风险。 AIM 1：对300名患有有或没有TNF1-308多态性的婴儿进行前瞻性，病例对照研究，直到第一次AOM发作，直至1岁。将筛选受试者的基因多态性；在生命的第一个月内，将招募相等数量的多态性和正常婴儿（与性别和种族相匹配）。前6个MO中鼻咽细菌定殖的动力学。将研究生活；有症状的URI发作将受到AOM并发症的监测。有关BF，CSE和DC出勤的信息将被预期收集并连续更新。在生命的第一年中，AOM的发病率（第一年至少发作的病例中的百分比）将在多态和正常儿童群体之间进行比较；将评估环境危险因素对细菌定殖，病毒URI和AOM的发生率的改变。样本量也足以与IL-6-174多态和正常儿童之间的并行比较。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。拟议的研究1中的存档和新的DNA样品（来自OM敏感和非易感儿童，n = 800）将使用最先进的微阵列技术测试11个细胞因子/趋化因子基因多态性。基因多态性将与OM易感性有关。数据挖掘将用于分析复杂数据。从我们的研究中产生的信息对公共卫生至关重要，因为它将为预防OM的创新方法设计奠定基础工作，尤其是在患有遗传易感性的儿童中以及暴露于OM环境风险的孩子中。公共卫生相关性中耳炎是婴儿和儿童中高度普遍的疾病。这项研究与公共卫生有关，因为要产生的信息将是设计创新方法以预防中耳炎的基础，尤其是在患有遗传易感性的儿童中以及暴露于OM环境风险的孩子中。