Stress, Environment, and Genetics in Urban Asthma

城市哮喘的压力、环境和遗传学

• 批准号: 7125450
• 负责人: Rosalind J Wright
• 金额: $ 83.03万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-26 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7125450
• 关键词: air pollution; allergens; asthma; behavioral /social science research tag; clinical research; corticosteroids; cytokine; early experience; family structure /dynamics; gene environment interaction; genetic susceptibility; helper T lymphocyte; human pregnant subject; human subject; immunoglobulin E; infant human (0-1 year); inflammation; longitudinal human study; preschool child (1-5); psychological stressor; questionnaires; respiratory disorder epidemiology; smoking; socioenvironment; tobacco abuse; urban area

DESCRIPTION (provided by applicant): The overall goal is to examine the role of psychosocial stressors in a systems biology framework considering multiple biologic pathways by which stress can contribute to asthma causation. We will not only study the independent effect of stress on asthma/wheeze phenotypes in early childhood but also will consider stress as a modifier of physical environmental factors (allergens, cigarette smoking and diesel-related air pollutants) and genetic predisposition on asthma risk. We will determine the independent effect of maternal stress (both prenatal and postnatal) on early childhood asthma phenotypes. We further hypothesize that multi-life stressors prevalent in disadvantaged populations can cumulatively influence immune system development and airway inflammation in early life, thus making the populations more susceptible to other environmental factors and genetic risk factors explaining, in part, observed asthma disparities associated with SES and race/ethnicity. We will take a multi-level approach, measuring both individual-level stress (negative life events, perceived stress, pregnancy anxiety) and community-level stress [neighborhood disadvantage (e.g., percent of subjects living in poverty, percent unemployed), diminished social capital, and high crime/violence rates]. We will also assess the influence of stress on the infant hormonal stress response and on T-helper cell differentiation as reflected in cytokine profiles and IgE expression (a topic or pro inflammatory phenotype). Additional physical environmental (indoor allergens, diesel-related air pollutants, tobacco smoke) and genetic factors will be assessed given their influence on the immune response and expression of early childhood asthma/wheeze. This interdisciplinary approach is unique because we are considering the context in which physical exposures and host susceptibility occurs, analyzing their multiplicative joint effects and considering multiple biologic pathways, as such it is consistent with the NIH roadmap objectives.

描述（由申请人提供）：总体目标是研究心理压力源在系统生物学框架中的作用，考虑到多种生物学途径，压力可以促进哮喘因果关系。我们不仅将在幼儿研究压力对哮喘/喘息表型的独立影响，而且还将压力视为身体环境因素（过敏原，吸烟和与柴油相关的空气污染物）的修饰者，以及对哮喘风险的遗传倾向。我们将确定孕产妇应力（产前和产后）对幼儿哮喘表型的独立影响。我们进一步假设，在处境不利的人群中普遍存在的多生命压力子可以累积影响免疫系统的发育和早期的气道炎症，从而使人口更容易受到其他环境因素和遗传风险因素的影响，部分地观察到与SES和种族/种族/种族/种族/族裔相关的哮喘差异。我们将采用多层次的方法，衡量个人级别的压力（负面的生活事件，感知到的压力，怀孕焦虑）和社区级别的压力[社区劣势（例如，生活在贫困中的受试者百分比，失业百分比，失业），社会资本减少和高犯罪/暴力率降低）。我们还将评估胁迫对婴儿激素应激反应的影响和对T型康复细胞分化的影响，如细胞因子谱和IgE表达（主题或促炎性表型）所反映。鉴于它们对儿童早期哮喘/喘息的影响，将评估其他物理环境（室内过敏原，与柴油相关的空气污染物，烟草烟雾）和遗传因素。这种跨学科的方法是独一无二的，因为我们正在考虑发生身体暴露和宿主易感性，分析其乘法关节效应并考虑多种生物学途径的环境，因此它与NIH路线图目标是一致的。