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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL080674-04
Application #
7485597
Study Section
Special Emphasis Panel (ZRG1-RPHB-J (04))
Program Officer
Taggart, Virginia
Project Start
2005-09-26
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2009-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$880,086
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Bose, Sonali; Rosa, Maria José; Mathilda Chiu, Yueh-Hsiu et al. (2018) Prenatal nitrate air pollution exposure and reduced child lung function: Timing and fetal sex effects. Environ Res 167:591-597
Lee, Alison G; Le Grand, Blake; Hsu, Hsiao-Hsien Leon et al. (2018) Prenatal fine particulate exposure associated with reduced childhood lung function and nasal epithelia GSTP1 hypermethylation: Sex-specific effects. Respir Res 19:76
Sheffield, Perry E; Speranza, Rosa; Chiu, Yueh-Hsiu Mathilda et al. (2018) Association between particulate air pollution exposure during pregnancy and postpartum maternal psychological functioning. PLoS One 13:e0195267
Lee, Alison; Leon Hsu, Hsiao-Hsien; Mathilda Chiu, Yueh-Hsiu et al. (2018) Prenatal fine particulate exposure and early childhood asthma: Effect of maternal stress and fetal sex. J Allergy Clin Immunol 141:1880-1886
Chiu, Yueh-Hsiu Mathilda; Sheffield, Perry E; Hsu, Hsiao-Hsien Leon et al. (2017) Subconstructs of the Edinburgh Postnatal Depression Scale in a multi-ethnic inner-city population in the U.S. Arch Womens Ment Health 20:803-810
Lee, Alison G; Chiu, Yueh-Hsiu M; Rosa, Maria J et al. (2017) Association of prenatal and early childhood stress with reduced lung function in 7-year-olds. Ann Allergy Asthma Immunol 119:153-159
Rosa, Maria José; Pajak, Ashley; Just, Allan C et al. (2017) Prenatal exposure to PM2.5 and birth weight: A pooled analysis from three North American longitudinal pregnancy cohort studies. Environ Int 107:173-180
Brunst, Kelly J; Rosa, Maria José; Jara, Calvin et al. (2017) Impact of Maternal Lifetime Interpersonal Trauma on Children's Asthma: Mediation Through Maternal Active Asthma During Pregnancy. Psychosom Med 79:91-100
Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon; Wilson, Ander et al. (2017) Prenatal particulate air pollution exposure and body composition in urban preschool children: Examining sensitive windows and sex-specific associations. Environ Res 158:798-805
Bose, Sonali; Chiu, Yueh-Hsiu Mathilda; Hsu, Hsiao-Hsien Leon et al. (2017) Prenatal Nitrate Exposure and Childhood Asthma. Influence of Maternal Prenatal Stress and Fetal Sex. Am J Respir Crit Care Med 196:1396-1403

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