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.