MECHANISTIC INDICATORS OF CHILDHOOD ASTHMA (MICA)
Impact/Purpose:
Phase 1 of MICA includes an assessment gene expression data collected from rodent blood and respiratory tissues RNA produced by short-term controlled exposures to concentrated particulate matter. Mobile units housed with rodent exposure chambers (State University) were employed in Grand Rapids, Michigan and in the Detroit Metropolitan Area. Phase 1 will provide 1) information on the reliability of surrogate blood RNA samples to predict target tissues effects and 2) context for the human gene expression data, collected in phase 2 planned for the summer of 2006. Phase 2 is a children exposure assessment/biomarker study focusing on three broad classes of particulate associated chemicals: volatile organic compounds (VOCs), metals, and polycyclic aromatic hydrocarbons (PAHs). MICA will study 150 asthmatic and 50 non-asthmatic children. Blood and urinary measures of these chemicals will be compared to benchmark levels of these chemicals and metabolites from the Center for Disease Control and Prevention’s (CDC) National Exposure Report. MICA consists of clinical measurements including (a) a skin prick test for allergen sensitivity; (b) analysis of blood, urine, nail clippings, and DNA; (c) immunological markers, odor testing, lung function and breath analysis; (d) gene expression and protein tests, viewed in the context of environmental assessments and respiratory health history.
Description:
The US Environmental Protection Agency (EPA) is interested in the interplay of environmental and genetic factors on the development and exacerbation of asthma. The Mechanistic Indicators of Childhood Asthma (MICA) study will use exposure measurements and markers of environmental exposure and health effects. Based on epidemiological studies of air pollution and asthma, there is sufficient evidence to justify investigations that incorporate state-of-the art technologies including genomics and proteomics, to study how and which genes and environmental factors interact in a way that increases the risk of worsening asthmatic responses. EPA scientists will use collected markers of exposure and effects to analyze, characterize, and possibly quantify combined risk factors that relate to asthma severity from multiple agents/stressors. Our study will also provide information on some key molecular events associated with chemical exposures, giving risk assessors more reliable data to assist in defining exposure-response relationships and in making estimates on the range of risks expected in the population compared to data based on biological monitoring and/or screening level hazard data.
Record Details:
Record Type:PROJECT
Projected Completion Date:09/30/2008
OMB Category:Other
Record ID:
149111
Project Information:
Progress
:New start Jan 2005. Rodent exposures completed. Blood RNA isolated from two species and two sites in Michigan. Isolation of RNA from matching rodent lung samples ongoing. Collaborations and/or contracts for over 30 exposure and health effects markers have been identified.
Approach
:Phase 1 of MICA includes an assessment gene expression data collected from rodent blood and respiratory tissues RNA produced by short-term controlled exposures to concentrated particulate matter. Mobile units housed with rodent exposure chambers (State University) were employed in Grand Rapids, Michigan and in the Detroit Metropolitan Area. Phase 1 will provide 1) information on the reliability of surrogate blood RNA samples to predict target tissues effects and 2) context for the human gene expression data, collected in phase 2 planned for the summer of 2006. Phase 2 is a children exposure assessment/biomarker study focusing on three broad classes of particulate associated chemicals: volatile organic compounds (VOCs), metals, and polycyclic aromatic hydrocarbons (PAHs). MICA will study 150 asthmatic and 50 non-asthmatic children. Blood and urinary measures of these chemicals will be compared to benchmark levels of these chemicals and metabolites from the Center for Disease Control and Prevention’s (CDC) National Exposure Report. MICA consists of clinical measurements including (a) a skin prick test for allergen sensitivity; (b) analysis of blood, urine, nail clippings, and DNA; (c) immunological markers, odor testing, lung function and breath analysis; (d) gene expression and protein tests, viewed in the context of environmental assessments and respiratory health history.
Relevance
:1). MICA provides linkages in the source-to-outcome paradigm
2). Enhancement of quantitative risk assessment, produce better methods and predictive models for quantitative risk assessment and to provide a useful tool for large-scale biomonitoring in humans.
3). Better determination of the shape of the exposure-response curve, especially in the low-exposure region, through the incorporation of gene expression data into experimental systems.
4). The development of more accurate, biologically-based mathematical exposure-response models that predict responses outside the range of experimental values.
5)The identification of regulatory metabolic or physiologic pathways, that may act in concert and lead to adverse health outcomes, through the evaluation of multiple health end points with linkages to gene expression changes. •Identification of molecular indicators of exposure and toxicity that can be applied to other epidemiological studies or risk assessment.
More specifically the Office of Air and Radiation (Office of Indoor Air, Office of Air Quality Standards and Planning and the Office of Transportation and Air Quality) and the Office of
Environmental Information. Our study will provide information on some key molecular events associated with chemical exposures, giving risk assessors more reliable data to assist in defining exposure-response relationships and in making estimates on the range of risks expected in the population compared to data based on biological monitoring and/or screening level hazard data. Research will support the Government Performance and Results Act (GPRA) goal "Risk Assessment for Susceptible Subpopulations", Long-Term Goal 4 of the Human Health Multi-Year Plan (MYP), Objective 4.4 Science/Research, Sub-Objective 4.4.2 Research. More specifically, the proposed research would be associated with Annual Performance Goal (APG) #6: "By 2012, provide risk assessors and managers with methods and tools for measuring exposure and predicting effects in children, including adolescents, characterizing cancer and non-cancer hazards and risk to children, and reducing risks to children in schools from harmful environmental agents to support EPA risk assessment and risk management"
Project IDs:
ID Code
:IA-7
Project type
:Partner Specific