Genetics and ambient air pollutants are contributors to childhood respiratory diseases; however, gaps in the? scientific knowledge base concerning the roles of specific sources, components and characteristics of air? pollution and the role of inter-individual variation in susceptibility to air pollution's adverse effects impede? effective intervention. The overall objective of the proposed program of research is to address these key? gaps by investigating the contribution of genetics and exposure to air pollutants during childhood to the? occurrence of asthma and deficits in lung function growth. Accordingly, the overall theme of the program? project remains """"""""Genetics, air pollution and children's respiratory health."""""""" The program of research proposed? in this application builds on the rich health, exposure and genetic data resources of the Children's Health? Study (CHS), an ongoing cohort study investigating both genetic and environmental factors related to? children's respiratory disease in over 11,000 southern California children. The research hypotheses are? based on mounting evidence that oxidant gases, traffic-related exposures and specific combustion-exhaust? particle-bound constituents activate oxidative/nitrosative stress and inflammatory pathways and contribute to? respiratory morbidity. Our research questions target the following health issues: (1) Are chronic respiratory? health effects associated with exposure to near source combustion particles from vehicular exhaust? (2) Do? PM mass in specific size fractions (PM[0.25], PM[0.25-2.5], and PM[2.5.-10]) or specific size-fractionated constituents? (e.g., water-soluble or total organic carbon, elemental carbon, or selected transition metals) affect health? (3)? Do genetic variants involved in innate or adaptive immune responses or nitrosative/oxidative stress? pathways contribute to respiratory disease, deficits in lung development, or differences in susceptibility to the? adverse effects of near source combustion products or regional gaseous or particulate pollutants? These? questions will be investigated in three inter-related projects with support from three cores (Exposure? Assessment, Integrative Health Sciences, and Biostatistics and Data Management). The projects will? evaluate the relationship between respiratory health (asthma, lung function growth, exhaled NO) and? combustion particulate and gaseous pollutants; examine genetic variation in key pathways that modulate? response to air pollution and disease occurrence; and develop new biostatistical methods for GxE studies? and integrated analysis across multiple outcomes and exposures. Building upon our large and wellcharacterized? children's cohorts, rich exposure data, and substantial genetic resources, our collaborative? multidisciplinary team will apply an integrative approach to efficiently address key gaps in the knowledge? base needed for timely and effective disease prevention and treatment.?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
5P01ES011627-07
Application #
7477355
Study Section
Special Emphasis Panel (ZES1-TN-E (FG))
Program Officer
Gray, Kimberly A
Project Start
2002-09-13
Project End
2012-05-31
Budget Start
2008-06-01
Budget End
2009-05-31
Support Year
7
Fiscal Year
2008
Total Cost
$2,474,168
Indirect Cost
Name
University of Southern California
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
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Zhou, Hui; Li, Xia Iona; Kim, Jeong Hee et al. (2018) Effect of inhaled allergens and air pollutants on childhood rhinitis development. Ann Allergy Asthma Immunol 120:212-214
Urman, Robert; Eckel, Sandrah; Deng, Huiyu et al. (2018) RISK EFFECTS OF NEAR-ROADWAY POLLUTANTS AND ASTHMA STATUS ON BRONCHITIC SYMPTOMS IN CHILDREN. Environ Epidemiol 2:
Kothari, Parul H; Qiu, Weiliang; Croteau-Chonka, Damien C et al. (2018) Role of local CpG DNA methylation in mediating the 17q21 asthma susceptibility gasdermin B (GSDMB)/ORMDL sphingolipid biosynthesis regulator 3 (ORMDL3) expression quantitative trait locus. J Allergy Clin Immunol 141:2282-2286.e6
Kerin, Tara; Volk, Heather; Li, Weiyan et al. (2018) Association Between Air Pollution Exposure, Cognitive and Adaptive Function, and ASD Severity Among Children with Autism Spectrum Disorder. J Autism Dev Disord 48:137-150
Zhang, Yue; Salam, Muhammad T; Berhane, Kiros et al. (2017) Genetic and epigenetic susceptibility of airway inflammation to PM2.5 in school children: new insights from quantile regression. Environ Health 16:88
Chen, Zhanghua; Salam, Muhammad T; Alderete, Tanya L et al. (2017) Effects of Childhood Asthma on the Development of Obesity among School-aged Children. Am J Respir Crit Care Med 195:1181-1188
McConnell, Rob; Barrington-Trimis, Jessica L; Wang, Kejia et al. (2017) Electronic Cigarette Use and Respiratory Symptoms in Adolescents. Am J Respir Crit Care Med 195:1043-1049
Breton, Carrie V; Yao, Jin; Millstein, Josh et al. (2016) Prenatal Air Pollution Exposures, DNA Methyl Transferase Genotypes, and Associations with Newborn LINE1 and Alu Methylation and Childhood Blood Pressure and Carotid Intima-Media Thickness in the Children's Health Study. Environ Health Perspect 124:1905-1912
Berhane, Kiros; Chang, Chih-Chieh; McConnell, Rob et al. (2016) Association of Changes in Air Quality With Bronchitic Symptoms in Children in California, 1993-2012. JAMA 315:1491-501

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