University of Michigan Center for the Environment and Children's Health (1998-2005)
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Center Director: Barbara Israel
Project 2: Chemokines in the Pathogenesis of Asthma
The Michigan Center for the Environment and Childrens Health (MCECH) was established in 1998. MCECH was structured as a community-based participatory research initiative seeking to investigate childhood asthma, how and why children have and how it operates, as well as evaluate comprehensive community and household level interventions aimed at reducing asthma-related environmental threats to children, families and neighborhoods.
The Centers aims included: 1) to assess characteristics of the household, school and neighborhood environment of asthmatic children; 2) to identify environmental factors and co-factors involved in the exacerbation and progression of childhood asthma; 3) to identify cellular and molecular targets which modulate immune system responses to environmental contaminants; 4) to use a community-based participatory research approach to implement a household and neighborhood-level intervention to reduce exposure to environmental hazards and improve childrens asthma-related health status; and 5) to develop effective mechanisms for communication and dissemination of laboratory and community-based participatory research results.
There were three projects of MCECH. The exposure assessment and intervention studies were integrated into an interdisciplinary, community-based participatory research project, Community Action Against Asthma (CAAA) in the southwest and east sides of Detroit. The third project, based at the University of Michigan School of Medicine, studied Chemokines in the Pathogenesis of Asthma .
The three projects engaged in coordinated interdisciplinary research aimed at:
- Increasing knowledge and behavior to reduce environmental hazards in households and neighborhoods, thereby improving asthma-related health status, through a community-based household and neighborhood level intervention;
- Examining the effects of daily and seasonal fluctuations in indoor and outdoor ambient air quality on pulmonary function and severity of asthma symptoms; and
Determining the effects of allergen-induced local, excessive production of chemokines on redox status and innervation of the bronchial tree.
Primary Exposures: Air pollutants (including PM10, PM2.5, ozone), insect allergens, household dust
Primary Outcomes: Asthma
Project 1: Indoor and Outdoor Air Contaminant Exposures and Asthma Aggravation Among Children
This component of the CAAA study was conducted from Fall 1999 to Summer 2003, using a community-based participatory research (CBPR) approach in which community representatives served as co-investigators for all aspects of the research process. This project combined a longitudinal exposure assessment of air pollutant exposures and an epidemiologic study of the health effects of these exposures among almost 300 children with asthma described here, with a randomized trial of a household intervention to reduce indoor exposure to asthma triggers described above.
Project 2: Chemokines in the Pathogenesis of Asthma
Hypothesis: The pathophysiologic pulmonary responses of asthma are due to excessive local production and release of chemokines
Objective: To determine if the mechanism of chronic pulmonary inflammation due to repeated exposure to allergens is mediated by the excessive local production of chemokines.
Specific Aim I: To determine if repeated intratracheal injections of chemokines into mice will induce asthma-like chronic pulmonary inflammation.
Researchers evaluated pulmonary inflammation and bronchial smooth muscle innervation observed after repeated, long term exposure to purified recombinant chemokines. This was a kinetics study evaluating parameters over several weeks. Mice were exposed to recombinant chemokines by intratracheal injections of the purified material and measurements of pulmonary inflammation determined. These measurements included analysis of infiltrating cells and bronchial innervation. Mice were also exposed by aerosol to recombinant chemokines.
Specific Aim II: To determine if immunization with household dust containing cockroach allergens followed by repeated aerosol exposure to the dust will result in asthma-like chronic pulmonary inflammation.
Mice were immunized by intraperitoneal injection with dust from households where children have allergic asthma using standard methods and adjuvants. The mice were then exposed by aerosol to the same household allergens and measurements of chronic inflammation determined. Pulmonary secretions of chemokines were determined and the location of the chemokines determined by in situ hybridization and immunohistochemistry.
Specific Aim III: To determine if reactive oxygen intermediates (ROI) or reactive nitrogen intermediates (RNI) are responsible for enhanced chemokine gene expression following exposure to cockroach allergens.
Mice were immunized with household dust as defined in specific aim II. After appropriate immunization cells were harvested from the lung and peritoneum and re-stimulated in vitro by exposure to the allergen again. Following the in vitro stimulation chemokine production in the supernatant was determined. These experiments were repeated but now the chemokine production will be inhibited by the addition of scavengers of ROI or inhibitors of nitric oxide synthase.
Specific Aim IV: To determine if specific inhibition of chemokine biological activity will prevent asthma-like chronic pulmonary inflammation following exposure to allergens.
For the final specific aim researchers attempted to block the pulmonary inflammation by inhibition of the chemokines. This was done with specific anti-chemokine antibodies. This was expected to provide the final verification of the hypothesis that chemokines are important mediators of pathologic sequalea of asthma.
Project 3: A Community-Based Intervention to Reduce Environmental Triggers for Asthma Among Children
The exposure assessment and intervention studies were integrated into an interdisciplinary, community-based participatory research project, Community Action Against Asthma (CAAA) in the southwest and east sides of Detroit.
CAAA combined an investigation of environmental triggers of asthma with an intervention designed to reduce exposure to these triggers and improve the health status of children with asthma. The central research hypotheses were:
- Exposure to outdoor air contaminants will potentiate the adverse effects of common indoor air contaminants on the health status of asthmatic children;
- An intensive household level intervention will increase behaviors and psychosocial factors associated with improved asthma-related health status, reduce indoor exposures to environmental triggers, and improve asthma-related health status; and
- The addition of an neighborhood intervention will enhance the positive effects of the household intervention.
The household intervention consisted of a one-year intensive phase followed by another one-year less intensive phase. Each of the approximately 300 households participating in the project was visited eleven times by a Community Environmental Specialist in the first year and three times in the second year. Activities during visits include:
- Formulation of a household-specific environmental plan,
- Education on reduction of exposure to asthma triggers,
- Provision of materials needed for modification of the home environment, and
- Referrals for medical care, tenant issues, and smoking cessation.
A staggered design was used in which one half of the participants received the household intervention beginning immediately after the collection of baseline data and the other half received the intervention beginning one year later. At the same time that the intervention was initiated for the second group, the neighborhood intervention, based on the community organizing model, began for both groups.
Data Collection and Evaluation Methods
The CAAA intervention was evaluated through a comprehensive baseline assessment, which was repeated on an annual basis. This assessment included:
- Questionnaires for parents and children covering demographics, asthma severity, medication use, asthma health services utilization, quality of life measures, psychosocial factors and potential confounding factors;
- Observational checklists measuring household and neighborhood environmental hazards;
- Standardized household dust sampling for concentrations of cockroach, dust mite, cat, dog, mouse, and rat antigens; and,
- Skin prick testing (performed only at baseline) of participating children for these same antigens plus ragweed, mixed grasses, and Alternaria.
In addition, seasonal data collected to investigate associations between outdoor and indoor exposures and the children's health status were also used to assess intervention success.
The seasonal data were collected during intensive two-week periods in each of eleven consecutive seasons over 2+ years. Exposure quantification was based on the following measures collected in each of these time periods (note: PM = particulate matter):
- Information routinely collected on, for example, PM10, PM2.5, and ozone at several stationary sites in Detroit by governmental agencies;
- Outdoor and indoor sampling at 2 school sites for PM2.5 and PM10, continuous PM2.5 using tapered element oscillating microbalance (TEOM) instruments; with analysis for mass, XRF (trace elements), elemental and organic carbon;
- Similar outdoor/indoor sampling at 20 of the participating households including indoor measures of vapor phase nicotine (e.g., tobacco smoke);
- Personal samples on children in the same 20 households for PM10.
Health outcomes were assessed on a daily basis during the same two-week periods in each of the eleven consecutive seasons. The assessment included:
- A diary of symptoms, medications, and activity level; and
- Morning and evening measurement of forced expiratory volume at one second (FEV1) and peak expiratory flow (PEF) using a portable, hand-held, computerized device (Air Watch brand lung function monitor).
MCECH involved partners working in the southwest and east sides of Detroit, including:
- Butzel Family Center
- Community Health and Social Services Center (CHASS)
- Detroit Department of Health and Wellness Promotion
- Detroit Hispanic Development Corporation
- Detroiters Working for Environmental Justice
- Friends of Parkside
- Henry Ford Health System
- Kettering/Butzel Health Initiative
- Latino Family Services
- Michigan Department of Agriculture - Pesticide and Plant Pest Management Division
- United Community Housing Coalition
- Warren/Conner Development Coalition