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PublicationsResearch on Children's Health
Asthma, Lead, and Indoor Air
ORD/NCER STAR GRANTS Research on Children's Health Asthma, Lead, and Indoor Air April 2001 Introduction The research projects described below are funded by NCER grants. For ease of understanding, all grants have been placed under topic areas that describe the overall, general objectives of the projects. Specific information is given for each grant that includes: title, web address, EPA grant number, principal investigator(s), institution (university), NCER project officer, dates during which the grant is funded, and a brief description of the research. Science Questions and Issues that NCER Is Addressing Related to Asthma, Lead, and Indoor Air Quality as they Affect Children's Health
Other Information on Asthma, Lead, and Indoor Air Quality Related to Children's Health HOW CAN THE ANALYTICAL METHODS FOR DETECTING LEAD IN PAINT BE IMPROVED? Improved Technology for Measuring Lead Detection in Lead-Based
Paint Phase II Lead paint is a primary source of lead poisoning, particularly in children. A central problem to a more vigorous attack on finding lead-paint surfaces is the lack of an inexpensive, portable method for measuring levels of lead in concentrations as least as low as 1 mg per cm2. In Phase I, Niton Corporation proposed to show the L x-ray lines of lead rather then K x-rays could be used to measure lead concentrations buried beneath many layers of non-lead paint. It is the primary purpose of Phase II to develop the technique further with the specific aims of dramatically reducing the costs of the instrument. The commercial potential for such an instrument is extremely high. WHAT TYPES OF COMMUNITY INTERVENTIONS ARE BEING IMPLEMENTED TO REDUCE ASTHMA IN CHILDREN? Asthma in Children: A Community-based Intervention Project In this study, inner-city, primarily minority, children with asthma are being identified through a school-based mobile asthma clinic, the Breathmobile, which delivers high-quality asthma care to these children. Working with school nurses and community organizations and 3 Breathmobile units, we propose a community-based intervention aimed at reducing asthma triggers in the home. The major goal of this study is to determine whether a comprehensive environmental health education program, enhanced by least-toxic integrated pest management for cockroach control, will result in reduction of dust mites or cockroaches in children's homes and clinical improvement in asthma. Multi-component Intervention Study of Asthma in Children from
Rural Communities The goal of this study is to develop, implement, and test a community-based, multi-component model for the prevention of asthma among rural children. The overall hypothesis of this study is that environmental intervention is an essential component of an asthma intervention program that must be coordinated with other improvements in health care to reduce the prevalence and severity of asthma among rural children. A Community-Based Intervention to Reduce Environmental Triggers
for Asthma Among Children The first aim of this household and neighborhood level community-based intervention research project is to reduce exposure of children to environmental contaminants within their homes and neighborhoods that trigger asthma. The second goal is to conduct a community-based intervention to test the following hypotheses: 1) household-level intervention will improve asthma-related health problems and increase behaviors to reduce home environmental hazards; 2) neighborhood-level intervention, combined with household-level intervention, will provide an enhanced effect on the outcomes at the household level; 3) a less intensive household intervention, following an initial intensive intervention, will maintain similar level effects; 4) a long-term neighborhood intervention, when combined with a household-level intervention, will result in greater intervention effects than a household level intervention with a short-term neighborhood component. A Randomized, Controlled Trial of Home Exposure Control in Asthma This community-based prevention research project will conduct a randomized, controlled trial of the effectiveness of current intervention methods to reduce hazardous exposures and their adverse health effects. It will test a global intervention that is composed of several components that have already proven to be effective in middle-class homes. The goal of this research is to examine the feasibility of modifying inner city home environments with currently recommended procedures. Community-Based Intervention: Reducing Risks of Asthma The Community-Based Intervention Project is structured to test the hypotheses that: a) community education can be effective in raising awareness of environmental health risks and preventive behaviors, thus in reducing the risk of asthma; and b) individual maternal education to reduce exposure to environmental tobacco smoke, a household intervention to reduce allergen exposures, and antioxidant supplementation will reduce the risk of asthma- related biomarkers and persistent wheeze among infants in the cohort identified as "high risk" based on elevated immunoglobulin at 24 months. HOW DOES ENVIRONMENTAL TOBACCO SMOKE AFFECT CHILDREN'S HEALTH? Children's Susceptibility to Air Pollution This research focuses on the effects of air pollution on children residing in Southern California. In conjunction with the University of Southern California School of Medicine's Children's Health Study, researchers will find out how long-term exposure to air pollution in 12 southern California communities affects respiratory health among children and adolescents. This project will also investigate whether certain foods children eat - fruits, vegetables, and antioxidant nutrients - along with genetic factors involved in lung defenses, might affect susceptibility to air pollution. Children's Exposure to Environmental Tobacco Smoke: Changes
in Allergic Response The purpose of this research study is to investigate the ability of environmental tobacco smoke to alter the amount and types of IgE and other mediators (cytokines). The study will determine if exposure to tobacco smoke plus pollen produces greater amounts of IgE and mediators in the nose than exposure to pollen alone. The research will also determine whether children are more susceptible to tobacco smoke than adults. This research will be important in determining the potential role of secondhand smoke in causing or exacerbating allergic disease. STAR fellowship - Tobacco smoke as a serious environmental hazard The overall goal of this research is to investigate the mechanisms underlying nicotine-induced injury to the developing brain. WHAT TYPES OF DEVELOPMENTAL EFFECTS RESULT FROM LEAD EXPOSURE IN CHILDREN? STAR fellowship - Behavioral and Neurochemical Effects of Developmental
and Chronic Lead Exposure and Amelioration of Effects Using DMSA The aims of this research project are threefold: (1) to elucidate the nature of the cognitive changes produced by early low-level lead exposure using a rodent model of childhood lead exposure, (2) to gain insight into the underlying neural bases of these effects, and (3) to determine whether the effects can be ameliorated by chelation with dimercaptosuccinic acid (DMSA), a promising new chelating agent. HOW DO AIR CONTAMINANT EXPOSURES INITIATE OR AGGRAVATE ASTHMA? Research on Asthma The Research Project on Asthma is designed to test the hypotheses that: a) prenatal and/or postnatal exposure to home allergens (cockroach, housedust mite, and rodent) and environmental tobacco smoke, as well as postnatal exposure to PM2.5 and diesel exhaust particulate, are significant contributors to risk of asthma, as indicated by related biomarkers and persistent wheezing, b) the risk from home allergens is increased by co-exposure to air pollutants; and c) impaired nutritional status (inadequate levels of antioxidants) heightens susceptibility to the pollutants. Indoor and Outdoor Air Contaminant Exposures and Asthma Aggravation
Among Children (Asthma Exposure) The first specific aim of this research project is to determine the prevalence of asthma among the elementary age school children in African-American and Latino populations in Detroit. The second specific aim is to identify which components of outdoor air and indoor air contaminants, and family and neighborhood characteristics, are associated with increased risk for asthma in this population. The third specific aim is to examine whether seasonal and daily changes in outdoor air pollution and indoor air contaminants explain fluctuations in the severity of asthma. Ultrafine Particles in Urban and Respiratory Health Among Children
with Respiratory Symptoms The investigators will conduct diary studies of asthmatic school children to examine the association between different measures of particulate air pollution and peak flow and symptom reporting in those children. The major focus of the study will be to investigate hypotheses about which subfraction of particulate air pollution is responsible for the association. The researchers will examine ultrafine particles and soluble transition metals, as well as fine fraction. The researchers will also attempt to separate local fine particles from long range transport particles to see whether the associations differ between these fractions. The Relationship of Airborne Pollutants and Allergens to Asthma
Morbidity This community-based epidemiologic research will compare ambient and indoor exposures to a variety of antigens in the home and ambient environment to children's morbidity from asthma. This study will provide the first interaction of the Center with families in East Baltimore, and will have recruited a group of collaborating families from which to recruit an intervention trial and other projects such as genetic linkage studies. Particulate Air Pollution and Initiation of Asthma This project will study the effects of particulate air pollution on the initiation of the asthmatic phenotype using a novel mouse model. The central postulate is that air particulate-mediated oxidant stress/injury within developing lungs promotes initiation of hypersensitivity (asthmatic-type) responses to otherwise innocuous inhaled antigens. The first aim of the project is to characterize the development of hypersensitivity to aerosolized antigen in young mice exposed to concentrated air particulates. The second aim of the research is to test the hypothesis that oxidant-compounds of air pollution are critical for initiation of hypersensitivity to inhaled antigens. Mechanisms of Age-dependent Ozone Induced Airway Dysfunction
The purpose of this proposal is to examine age-related changes in ozone-induced airway hyper-responsiveness (AHR) in mice and to determine the mechanistic basis for observed changes. The hypothesis is that ozone-induced TNFa formation is required for AHR, and that ozone causes more pronounced AHR in young than adult mice. WHY ARE CHILDREN ESPECIALLY VULNERABLE TO LEAD EXPOSURES? Vulnerability of Young Children to Organophosphate Pesticides
and Selected Metals Through Intermittent Exposures in Yuma County,
Arizona The goal of this research is the accurate determination of the routes and amounts of exposure to various contaminants experienced by young children. The researchers will test the null hypotheses that: (1) frequent intermittent contact with contaminated surfaces is not associated with elevated urinary metabolite yield, (2) contaminant levels found in the handled food of children will not differ from that of unhandled food (as determined by NHEXAS, Border and Children's Pesticide Surveys); (3) exposure through intermittent contact will not significantly increase the total exposure for children; and (4) no differences in hand-to-mouth activity will be evident in a subset of children evaluated longitudinally within one year. WHAT IS THE PATHOGENESIS OF ASTHMA? Chemokines in the Pathogenesis of Asthma (Asthma Chemokines) This research project will test the hypothesis that asthma-like pulmonary injury is mediated by the local production of specific mediators which are called chemokines. The first specific aim is to determine the acute and chronic pulmonary inflammation that develops after direct injection of the chemokines into the lung. The second specific aim is to develop a mouse model of asthma-like pulmonary inflammation in response to cockroach allergens. The third specific aim is to investigate the signals responsible for inducing the cells to make the chemokines. The last specific aim is to rigorously test the central hypothesis that chemokines are important in causing asthma. Successful completion of this project will both delineate the underlying mechanisms of disease and identify potential novel targets for intervention. Mechanisms Of Particulate-Induced Allergic Asthma This project will examine the mechanisms by which particulate matter (PM) may exacerbate an allergen-driven inflammatory response in the airways. The project will first establish the exposure response relationship between PM and allergic airway responses in genetically susceptible A/J mice. Secondly, it will determine the biological effects of PM exposure in nonallergic strains of mice. Third, it will determine the role of IL-6 in mediating PM-induced inflammation and exacerbations or allergic asthmatic symptoms by neutralizing its activity in vivo and examining PM induced effects on allergic airway responses. Mechanisms that Initiate, Promote, and Resolve Grain Dust/LPS
Induced Inflammation The overall hypothesis in this study is that mechanisms that initiate, promote, and resolve grain dust-induced inflammation may be distinct from those mechanisms involved in lipopolysaccharide (LPS) induced airway inflammation. Researchers will examine the mechanisms responsible for the initiation, promotion, and resolution of LPS/grain dust-induced inflammation in order to understand better the pathogenesis of asthma in children from rural communities. Role of RSV Infection and Endotoxin in Airway Inflammation Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract infection in young children that is associated with both recruitment of neutrophils and an enhanced risk of developing asthma. This observation suggested that interleukin-8 (IL-8), a potent neutrophil chemotactic agent in the lung, may play a prominent role in RSV-induced airway inflammation. This project proposes that RSV infection upregulates the response of airway epithelium to endotoxin. The study will focus on regulation of IL-8 gene expression by mitogen-activated protein kinase (MAPK) pathways. Researchers further hypothesize that endotoxin triggers a marked increase in activation of multiple MAPK kinase pathways that regulate IL-8 gene expression. A Model to Study the Development of Persistent Environmental
Airway Disease This project will address a fundamental issue in childhood asthma: why only a minority of children who wheeze at an early age develop persistent airway disease that continues throughout their life. Inhalation of grain dust is a common problem in the rural setting that acutely induces airway inflammation and airflow obstruction, and chronically has been shown to cause asthma. The goal of this project is to determine which specific elements of the acute inflammatory response to inhaled grain dust are essential to the development of chronic grain dust induced airway disease - defined as persistent airway hyperreactivity and airway remodeling. HOW DOES INDOOR AIR QUALITY AFFECT THE HEALTH OF CHILDREN? School-Based Study of Complex Environmental Exposures and Related
Health Effects in Children Part A - Exposure The objectives of this study are to: (1) document complex exposure patterns involving multiple acute exposures and exposures to chemical mixtures for school children (K - 5) from two low-income, racially diverse neighborhoods in Minneapolis, (2) examine temporal variability by monitoring complex exposures three times over a twelve-month period, (3) apportion the relative contribution to measured personal exposure of outdoor community air, air inside the child's school, and air inside the child's residence, (4) evaluate the relationship between measured exposures and internal dose using biological markers of exposure in blood and urine, and (5) compare children's exposures between a new school designed to enhance indoor air quality and an older school with more traditional architecture, mechanical systems, and furnishings. Health Effects of HAPs Among Inner Urban School Children
This research project will examine the association between exposure to a variety of hazardous air pollutants (HAP) and adverse effects on children's health. The primary hypothesis to be tested by this study is that documented HAP exposures are not associated with measured health effects in inner urban children. HOW IS PESTICIDE EXPOSURE RELATED TO ASTHMA? The Epidemiological Investigation of the Effects of Pesticide
Exposure on Neurodevelopmental, Growth, and Respiratory Health of
Farmworker Children The objectives of the research project are to: (1) estimate sources, pathways and levels of in utero and postnatal pesticide exposures of children living in an agricultural community by measuring biological and environmental samples; (2) determine whether exposure to pesticides is associated with poorer neurodevelopmental functioning and behavioral problems, delayed growth, and increased respiratory symptoms and disease; (3) determine whether exposure to environmental allergens and respiratory irritants is associated with increased respiratory symptoms and disease; and (4) evaluate the impact of "Healthy Homes" interventions on the reduction of pesticide exposure to farmworker children. See Website for Publications/Presentations OTHER RESEARCH IN CHILDREN'S HEALTH RELATING TO ASTHMA, LEAD, AND INDOOR AIR QUALITY EPA's Office of Children's Health Protection
EPA Region 1
EPA Region 8
National Institutes of Health, National Institute of Allergy
and Infectious Diseases
Centers for Disease Control and Prevention
National Institutes of Environmental Health Sciences (NIEHS)
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