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Cigarette Smoke Exposure In Utero: Neonatal Immunity

Institution: University of California, San Diego
Investigator(s): Patricia Finn, M.D.
Award Cycle: 2009 (Cycle 18) Grant #: 18XT-0135H Award: $265,000
Subject Area: Pulmonary Disease
Award Type: Exploratory/Developmental Award

Initial Award Abstract
Cigarette smoke (CS) exposure may have long term physiological consequences, including an association with decreased lung function and increased airway hyperresponsiveness. In utero CS exposure and its influence on later outcomes, including immune responses, has not been well described. Our objective is to analyze the effect of CS exposure on neonatal allergic responses. Asthma is the most common chronic disease of childhood, with increasing incidence and severity. Due to the current nascent understanding of asthma pathogenesis, we propose that systems biology approaches are ideally suited to investigate immune responses that may be initiated in utero, modified by CS exposure, and potentially predisposed to clinical asthma. Thus, by using systems biology approaches, we will identify and characterize modulated genes and activated signal transduction pathways differentially regulated in children following in utero cigarette smoke exposure, a form of secondhand smoke.

Our preliminary data and published work shows that in utero CS exposure is associated with significantly increased human cord blood mononuclear cell (CBMC) allergic responses. We have previously reported an association of increased CBMC allergic responses with subsequent childhood wheezing. We plan to identify the pathways crucial in modifying allergic immune responses. To attain this goal, we build upon our analyses of immune and physiological outcomes and perform systems biology investigations. Our hypothesis is that in utero CS exposure exacerbates perinatal allergic immune responses which may predispose to childhood asthma. Aim 1 will determine the fetal cord blood neonatal immune responses and genes influenced by in utero CS exposure. Based on differential gene expression profiles, Aim 2 will identify candidate genes in activated signal transduction pathways induced in fetal cord blood by in utero smoke exposure. Aim 3 will determine whether candidate genes in activated immune pathways modulated by CS exposure are associated with enhanced childhood allergic responses.