Final Report: CECEHDPR - University of Michigan

EPA Grant Number: R826710
Center: Michigan Center for the Environment and Children’s Health
Center Director: Israel, Barbara A.
Title: CECEHDPR - University of Michigan
Investigators: Israel, Barbara A.
Institution: University of Michigan
EPA Project Officer: Louie, Nica
Project Period: September 1, 1998 through August 31, 2003 (Extended to August 31, 2005)
Project Amount: $2,830,746
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998) RFA Text |  Recipients Lists
Research Category: Human Health , Health , Children's Health , Health Effects

Objective:

The Michigan Center for the Environment & Children’s Health (MCECH) was comprised of three research projects (Community-Based Intervention Project; Indoor and Outdoor Exposure and Asthma Aggravation Project; and Chemokines in the Pathogensis of Asthma) and three supporting cores: Biostatistics, Exposure Assessment and Administrative. In addition, MCECH supported a New Center Scientist Program. Final reports of the three research projects are provided below.

The Intervention and Indoor/Outdoor Exposure Research Projects (Projects 1 and 2) of MCECH were so integrated and had the same participants and goals, their research teams and activities were combined into one “meta”-project called: Community Action Against Asthma, or CAAA. A Steering Committee, which met monthly and was comprised of the university and Detroit community partners involved in both projects, oversaw and was directly involved in decision making and other activities regarding the implementation of the research protocol. A separate Research Work Group, comprised of the university-based faculty and staff for CAAA, oversaw the technical aspects of research issues and worked closely and in coordination with the CAAA Steering Committee.

Summary/Accomplishments (Outputs/Outcomes):

Project 1: Community-Based Intervention Research Project

Specific Aim 1. To implement a comprehensive program to deliver interventions at the household and neighborhood level to reduce exposure to indoor and outdoor environmental health hazards associated with asthma in children.

Project Overview. A unique feature of the CAAA project was the use of a community-based participatory research (CBPR) approach. The CAAA partnership was guided by a Steering Committee (SC) comprised of representatives of community-based organizations, the local health department, an integrated managed care system and an interdisciplinary mix of academic researchers (environmental scientists, epidemiologists, pediatric pulmonologists, social scientists). The SC met monthly and was actively involved in all major phases of the research and intervention.

The primary household intervention component of CAAA consisted of a minimum of 9 visits to the homes of the families enrolled during a one -year period by a community outreach worker called a Community Environmental Specialist. The CESs were all Detroit residents, had a minimum of a high school education, and completed a 4 week training prior to beginning their duties. Activities during these home visits included the provision of education, materials and services that relate to the reduction of exposure to asthma triggers, and referrals for a range of issues, such as medical care and tenant rights. In order to tailor the activities to each family’s circumstance, information from the baseline questionnaire and the skin-test and dust samples were fed back to the families with a suggested plan for priority of action.

Specific Aim 2. To conduct a randomized, staggered design community-based intervention to test the following hypotheses (listed below in the context of specific findings) about this comprehensive intervention.

Recruitment. During the winter of 1999, an asthma screening questionnaire was mailed and/or hand-delivered to parents of 9,627 children, ages 6 to 10, who attended one of 44 schools in the two geographic intervention areas Among the 3,067 returned questionnaires, 1,570 (51.2% of returned surveys, 16.3% of eligible population) were consistent with asthma of any severity and 398 (12.9% of returned surveys, 4.1% of eligible population) with moderate to severe asthma (using NAEPP expert guidelines to categorize). Of the 1,570 children, 470 eligible children were invited to participate in the study on the basis of having persistent asthma on the screening questionnaire. Three-hundred and twenty-eight children were randomized to the initial intervention or control arm (with the control arm receiving the intervention after the first year intensive phase of the intervention was complete. 299 households actually began the intervention and were randomized into the intervention arm (n= 151 families) or the control arm (n=148).

Data Collection. For the CAAA intervention component, major data collection activities included: 1) annual surveys for the caregiver and child (which asked about the asthma-related health status and quality of life, neighborhood and social environmental stressors) and a household environmental walkthrough that measured both the conditions conducive to and the actual presence of environmental irritants and allergens; 2) annual dust samples at all households that were analyzed for cockroach, dust mite, cat, dog and mice/rat allergens; and 3) qualitative process interviews with Steering Committee members and caregivers who participated in the project. In addition, lung function data from the Exposure Assessment was used to evaluate the effects of the intervention. The major outcome variables of interest for evaluating the intervention included: pulmonary function, health care utilization, average symptom frequency, asthma severity and asthma-related quality of life. The intermediate outcome variables included cleaning behaviors, smoking behaviors, presence of allergens in the household dust, caregiver social support and caregiver depressive symptoms.

Household Intervention Results. The following describes the hypotheses of the community-based intervention and key findings for the intermediate and health outcome variables. All models are adjusted for differences between groups at baseline, change in the control group over time, age of child, gender of child, ethnicity of child, primary caregiver’s education, and level of family income. Logistic GEE regression models use empirical exchangeable covariance matrix.

Hypothesis A: A household level intervention involving visits by a CES to households of asthmatic children will: increase behaviors to reduce indoor exposures to environmental hazards (e.g., vacuuming); reduce indoor exposures to environmental hazards associated with asthma (e.g., cockroach antigens); increase positive and decrease negative psychosocial factors associated with asthma-related health status (e.g., social support, depressive symptoms); improve asthma-related health status (e.g., symptom severity); and reduce use of medications and asthma-related health services utilization.

Pulmonary Function Measures. Pulmonary function was measured using data from the seasonal intensive measurements of the Exposure Assessment project. To evaluate the intervention effect, data from both the spring and summer intensives of 2000 (before intervention began) were combined and compared to the spring and summer intensives of 2001. There was an intervention effect for daily nadir peak flow and FEV1.


Figure 1: Mean Nadir Peak Flow and FEV1 Comparing Spring/Summer 2000 to Spring/Summer 2001

Child’s Average Asthma Symptom Frequency. Child’s asthma symptom frequency was measured by 8 items on the caregiver questionnaire that asked how often over the last 12 months had the child experienced that specific symptom (persistent cough, wheezing with cold, wheezing without cold, wheeze causing shortness of breath, wheezing with exercise, coughing with exercise, chest tightness, sleep disturbed) with 1=never and 6=everyday. The CAAA intervention was effective at improving persistent cough (3.81 down to 3.36 in intervention group compared to 3.48 to 3.44 in control group, p=.03) and cough with exercise (4.27 to3.69 in intervention group compared to 3.8 to 3.66 in control group, p=.017).

Unscheduled Health Care Visits. Health care utilization was measured using items from the caregiver questionnaire (unscheduled visits to the doctor, ER or hospitalization for asthma in the past 3 and 12 months) The CAAA intervention was effective at reducing unscheduled visits to the doctor, ER, or hospitalization for asthma .


Figure 2: Percent of Caregivers Reporting Urgent Visits to the Doctor, ER, or Hospitalization for Asthma in Past 3 and 12 Months.

Under-Medication of Children. The CAAA intervention was effective at reducing the percentage of children who, according to caregiver’s report of asthma symptoms and child’s medication use, were under-medicated. Children under medicated and needing a corticosteroid medication decreased from .59 to .38 in the intervention and increased from .49 to .51 in the control group (p=.018). Children under-medicated and needing a controller medication decreased from .51 to .27 percent in the intervention group compared to .37 to .40 in the control group (p=.001)

Intermediate Outcome Variables.

Psychosocial. The intervention had a statistically significant effect with a reduced report of caregiver depression from a mean 1.62 to 1.54 in the intervention group while the control group rose from 1.58 to 1.64 (p=0.0218) (as measured by the Center for Epidemiological Studies of Depression (CES-D) scale). While there were no statistically significant results for the social support variable (results not shown) there was a trend towards improvement in the intervention group in both general social support and instrumental support (p=.08, p=.09 respectively). Both control and intervention groups showed improvement in caregiver and child QOL (no statistical difference between groups).
Cleaning Behaviors.. The CAAA intervention was effective at increasing the proportion of families reporting behaviors and household factors related to reduced exposure to house dust mite (vacuuming, dusting, use of allergen covers), but not effective at changing the proportion of families reporting behaviors related to reducing mold or pet exposure or environmental tobacco smoke.

Allergens in Household Dust. The CAAA intervention was effective at reducing concentration of cat, and dog allergen per gram of bedroom dust, but did not change cockroach or dust mite allergen concentration.

Neighborhood Level Intervention Results.

Hypothesis B: A neighborhood level intervention, when combined with a household level intervention, will provide an enhanced effect on the outcomes at the household level and will also result in: increased knowledge of environmental hazards associated with asthma, and in neighborhood social support and capacity to address environmental hazards and reduced physical environmental hazards.

Hypothesis C: 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 as measured by items under hypothesis A and hypothesis B.

Due to the 10% reduction in the original grant funding, the neighborhood-level intervention component was not undertaken as part of the original activities of this program project. However, in September, 2000, funding was received from NIEHS under their CBPIR mechanism to implement an expanded neighborhood and community organizing project- the Community Organizing Network for Environmental Health (CONEH). CONEH builds upon the already existing CAAA intervention research project. The aims of CONEH include: to identify, prioritize and translate the relevant findings of the CAAA research project; to conduct and evaluate a CBPR intervention to reduce exposure to physical and psychosocial environmental stressors associated with asthma severity and exacerbations and to increase community awareness and knowledge of factors associated with the environment and asthma through the dissemination of findings to community residents in ways that are understandable and beneficial to the community. Project staff were hired and began their work by August 2001. Due to these reduced funds, and this delay in implementing this component of the intervention, these two hypotheses stated above were not able to be tested as part of this Center grant.

Specific Aim 3. To conduct a process and context evaluation using qualitative methods to identify factors which facilitate or hinder the implementation and success of the household and neighborhood components of the intervention.

Qualitative process evaluation of the partnership. A qualitative evaluation was undertaken to assess how well the CAAA project partnership process was going and to identify the challenges and successes of the partnership (Parker et al., 2003). Face-to-face in-depth interviews were conducted with Steering Committee members. The accomplishments identified included: the successful implementation of the project, identification of children with previously undiagnosed asthma, creation of a SC with participation of diverse institutions and individuals, and community influence and control in project decisions. Challenges included: ensuring ongoing influence in decision-making for all partners, the “different way of doing things” in CBPR, costs of doing CBPR to all partners, and communication and maintaining trust.

Process evaluation interviews with caregivers. To assess caregivers’ satisfaction with the CAAA project, both quantitative and qualitative data were collected. Questions to assess the CESs’ performance and influence on the caregiver behaviors, questions were added to the annual questionnaire of Wave 1 caregivers administered after the intensive phase of the household intervention. Of the 108 Wave 1 caregivers responding, 94% were very or quite satisfied with their CES; 91% reported they had received very much or quite a bit of information from their CES and 90% responded that the CES had helped with things around the house to improve their child’s asthma (e.g., showing them special ways to clean). When asked if “they or anyone in their family did any of these things because of visits from their outreach worker”, 12% of the caregivers reported that they or someone in their family had stopped smoking; 48% reported that they or someone in their family had reduced smoking indoors; 79% reported that they or someone in their family cleaned more often; and 80% reported that they or someone in their family cleaned differently.

Project 2: Indoor and Outdoor Air Contaminant Exposures and Asthma Aggravation Among Children

Overview. 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.

Text Box: Fig. 1. Study area showing school locations and locations of households participating in CAAA. Approximately 15 x 20 km region shown.

Recruitment. The study took place in two communities within Detroit (eastside and southwest) that demographically had a high proportion of low-income residents from minority ethnic groups. (See Fig. 1 for a map of the study area and location of participants). During the winter of 1999, an asthma screening questionnaire was mailed and/or hand-delivered to parents of 9,627 children, ages 6 to 10, who attended one of 44 schools in the two geographic intervention areas Among the 3,067 returned questionnaires, 1,570 (51.2% of returned surveys, 16.3% of eligible population) were consistent with asthma of any severity and 398 (12.9% of returned surveys, 4.1% of eligible population) with moderate to severe asthma (using NAEPP expert guidelines to categorize). Of the 1,570 children, 470 eligible children were invited to participate in the study on the basis of having persistent asthma on the screening questionnaire. Children from 299 households provided health outcome data.

Data Collection. Major data collection activities included:

  1. Allergen sensitivity was determined by skin prick testing at the beginning of the study;
  2. Annually for all households: a) surveys for the caregiver and child (which asked about the asthma-related health status and quality of life, neighborhood and social environmental stressors), b) indoor home environment of each child was assessed annually, using a detailed observational checklist, completed by a trained inspector, and allergen levels were measured in settled bedroom dust; and
  3. Table 1. Baseline asthma characteristics (N=299)

    Child’s asthma severity

    Moderate-Severe Persistent
    Mild Persistent
    Mild Intermittent

    48%

    28%
    24%

    Asthma medication
    Persistent (mild to severe)

    Intermittent


    Any Controller
    SAB
    None

    Any Controller
    SAB
    None


    37%
    34%
    29%

    6%
    20%
    74%

    Skintest Sensitivity

    Cockroach
    Dust Mite
    Cat
    Dog
    Rat
    Mouse
    Grass
    Ragweed
    Alternaria

    25%
    39%
    24%
    9%
    16%
    13%
    40%
    29%
    28%

  4. Health data during intensive measurement periods: Daily symptom and medication usage diaries were kept during intensive measurement periods (“intensives”), conducted for 2 weeks each season over nearly 3 years (11 seasons). Twice daily (morning and evening) lung function measurements were made during the intensives using a hand-held spirometer (Airwatch®, iMetrikus, Inc., Carlsbad, CA; www.medicompass.com).
  5. Exposure data:
    1. ambient exposure air pollutants, PM10, PM2.5 and O3, and meteorological parameters were monitored on rooftops of a representative school in each of the two communities over the entire study period (PM was collected on quartz and Teflon filters for determination of daily PM mass and chemical composition); and
    2. indoor and personal measures of exposure: in a subset of homes, during the two-week intensive periods, in- home and personal PM exposure was collected on filters for determination of PM mass and chemical composition.

Demographics and baseline asthma and allergy health status of study participants. Of the 299 asthmatic children enrolled at the start of the intervention in the Spring of 2000, 57% were male and the mean age was 9.2 years. Most children were from minority ethnic groups, with 81% self-identifying as African-American and 10% as Hispanic. Seventy-five percent lived on the Eastside of Detroit; the remainder lived in Southwest. The cohort included many socio-economically disadvantaged children: 38% percent of caregivers had not completed high school and 77% had annual household incomes below $20,000. There was a high incidence of tobacco smoke exposure at home, with 55% of caregivers reporting at least one smoker in the household.

Text Box: Fig. 2. Seasonal variation of PM2.5 at two sites in Detroit

At baseline, 48% of our cohort had moderate-to-severe persistent asthma (Table 1). Among those with persistent asthma, only 37% were taking a controller medication, another 34% were using a short-acting bronchodilator only, and 29% were using no medication. The highest prevalence of sensitization on skin testing was for grass (40%) and dust mite (39%). Sensitization to rat, mouse, or dog was low. Despite more modest levels of sensitization to cockroach (24%), this allergen appeared to be the most important when considering the combination with high levels of allergen in house dust (14 percent with both high levels and sensitization versus 4 percent or less with this combination for any of the other allergens, results not shown).

Symptom diaries. Among lower respiratory symptoms, cough was the most frequent, reported (averaged frequency of daily report over 11 two-week seasonal intensives) as present on 31% of days, followed by shortness of breath or wheezing at 19% each, and chest tightness or heaviness, 12%. On 13% of days waking up during the night because of breathing problems was reported, and on 13% of days the child's usual activities were interrupted by problems with asthma. On 5% of days unscheduled medical attention (doctor office visit, emergency room visit, or hospitalization) was required.

Assessment of lung function. Across seasons mean lowest daily (i.e., whichever was lower between the morning and evening value in the same day) FEV1 percent of predicted was 71.8 % with a standard deviation of 18.3%. Mean FEV1 intraday variability was 15.3%, with a standard deviation of 12.1%.

Ambient Exposure Assessment and Source Apportionment

Text Box: Fig. 3. Estimated daily apportionments of 5 sources of PM10 mass estimated using absolute principal components analysis.

Over a 3-year period, PM2.5 levels, which were consistently higher at the Southwest Detroit site in each season (p<0.05, Fig. 2), averaging 17.6 and 16.1 µg m-3 at the SW and Eastside sites, respectively, exceeding the annual National Ambient Air Quality Standard (15 µg m-3). PM10 levels averaged 28.7 and 23.8 µg m-3 at the SW and Eastside sites, respectively, and again the SW site consistently experienced higher levels (p<0.05). The higher levels at the SW site likely result from nearby heavy industrial sources (e.g., coal-fired power plants, refineries, and iron/steel mills), and higher traffic density (diesel emissions). In addition to seasonal differences, day-to-day variability in the concentration and composition of PM2.5 and PM10 was significant. Sulfate and carbon species were major constituents of PM2.5.

Text Box: Table 2. PM2.5 and PM10 concentrations in Detroit, by smoking status and averaging period.

Source apportionment. Multivariate receptor modeling using absolute principal components analysis, PM10 mass, elemental and EC/OC concentrations was used to estimate the mass contributions of five sources in 82 24-hr samples of ambient air. Fig. 3 shows how contributions from these sources varies over time, and the fit to measured PM10 levels (R2 = 0.77). All five sources were statistically significant (p<0.05), and included soil/iron and steel and motor vehicles (high loadings of Al, Mn, Fe, and Ce, moderate loadings of OC, EC, Ba, La, Pb, Fe and Mn), coal combustion (As, Mn, Pb, and Ba), incinerator (Cd, Zn, and Pb), oil combustion (V and La), and regional sulfate (S). The largest contributors were coal combustion (25%) and sulfate (24%), the latter being especially large in summer. Oil was the smallest contributor (4%). Twenty-two percent of the PM10 mass could not be explained by this model.

Microenvironmental and personal measures. Significant differences in PM levels between smokers’ (at least one person in the home reported to smoke tobacco) and non-smokers’ homes with children in Detroit were found (Table 2).

Text Box: Table 3. Dust allergen concentration per gram of dust in children’s bedrooms (n=287) and relationship to allergic sensitization (*1U = 20 ng).

Allergen levels in household dust in CAAA study. We measured levels of common allergens in dust from each child’s bedroom. As compared to reference values, cockroach antigen concentrations (BlaG1 or BlaG2) were relatively high; dust mite (DerP1 or DerF1), cat (FelD1) and dog (Can F1) were substantially lower (Table 3). The percent of children with both high allergen dust levels and skin test sensitization were considerably higher for cockroach than for the other antigens evaluated.

Text Box: Fig. 4. Summary of personal and microenvironmental PM10 concentrations, 2000-2001 for children (Yip 2004).

Personal exposures. The children’s personal exposures to PM10, as determined using a backpack monitor, was dominated by indoor concentrations. Fig. 4 shows concentrations measured over 2 years for personal, home, classroom and ambient environments. While personal exposures are significantly correlated to ambient PM10 concentrations among children in non-smoking homes, the correlation coefficient is small (r=0.20) and a negative correlation is observed among children in homes with smokers.

Children’s exposures are typically dominated by PM levels at homes, which explain 36% and 50% of the variance for smoking and nonsmoking households, respectively, based on a multivariate regression model. Children’s personal PM10 exposures typically exceeded levels measured in any of the microenvironments, showing the ‘personal cloud’ likely due to specific and localized activities that the children participated in during the day as well as from particle re-entrainment from clothing and surfaces.

Associations between Exposures and Health Outcomes

Linear regression models of pulmonary function using generalized estimating equations (GEE), to account for lack of independence of repeated observations on the same individual, were stratified on: a) concurrent use of corticosteroids as a marker of greater severity of asthma, and b) reported presence of upper respiratory infection (URI) symptoms, which was expected to be associated with increased susceptibility to adverse effects of ambient air pollutants. Representative results are shown in Tables 4 and 5, which include results for children using corticosteroids and also, separately, for children reporting URI symptoms.

Table4. Associations of ambient pollutant concentrations with lung function of children with asthma: single pollutant models.1

A. Among children reporting use of maintenance corticosteroids2

B. Among children reporting presence of upper respiratory infection on day of lung function assessment

1 Each coefficient is an estimate of percent change in lung function shown, and is derived from a separate linear regression model using generalized estimating equations (GEE). Covariates in each model: gender, home location, annual family income, school grade, presence of one or more smokers in house, race, season, randomization assignment for the intervention, interaction between time and this randomization assignment.
2 Regressions limited to those children reporting use of inhaled and/or oral corticosteroids at least 50% of days in a given season on diary.
3 Assessment of a child’s lung function based on error-free expiratory maneuvers.
4 Lag is the no. days between pollutant measurement and lung function. Lag 3-5 is based on the mean of pollutant concentrations on those days.
5 The regression coefficient is the estimated change in lung function associated with an one interquartile range increase in the pollutant concentration.

For children not on corticosteroids, as well as for children not reporting URI symptoms, no statistically significant relationships between ambient pollutant levels and pulmonary function were identified at the p=0.05 level (data not shown). Of note, across both Table 4, showing single pollutant models, and Table 5, showing two-pollutant models for children using corticosteroids, all statistically significant associations with increases in air pollutant levels showed changes in lung function in the expected direction (increased intraday variability and decreased lowest daily FEV1), indicating reasonable consistency across the models examined. Linear logistic regression results using GEE for lower respiratory symptoms (cough, wheeze, chest tightness, and shortness of breath) demonstrated results quite similar to those for pulmonary function, i.e., statistically significant lagged associations were seen frequently among children using corticosteroids and among those reporting URIs and were all in the expected direction of increased symptoms with higher pollution levels (results not shown).

Table 5. Among children with asthma reporting use of maintenance corticosteroids, associations of ambient pollutant concentrations with lung function: two pollutant models. 1, 2

A. Effect of concurrent exposure to both PM2.5 and ozone


Lung Function3

Time lag4

PM2.5 Daily Mean

Ozone Daily Mean

Coefficient 5

95% CI

p-val

Coefficient

95% CI

p-val

Intraday Variability
FEV1

Lag 1

0.99

-5.64, 7.62

0.77

1.27

-3.58, 6.11

0.61

Lag 2

4.62

-4.31, 13.54

0.31

3.51

-3.79, 10.81

0.35

Lag 3-5

2.70

1.0, 4.40

0.002

3.76

0.27, 7.26

0.04

Lowest Daily Value
FEV1

Lag 1

3.36

-3.92, 10.63

0.37

-2.53

-9.78, 4.71

0.49

Lag 2

0.88

-8.69, 10.46

0.86

-0.13

-8.09, 7.83

0.98

Lag 3-5

-2.78

-4.87, -0.70

0.009

-2.81

-9.02, 3.41

0.38

B. Effect of concurrent exposure to PM10 and ozone


Lung Function

Time lag

PM10 Daily Mean

Ozone Daily Mean

Coefficient

95% CI

p-val

Coefficient

95% CI

p-val

Intraday Variability
FEV1

Lag 1

2.94

-1.07, 6.96

0.15

5.32

1.82, 8.82

0.003

Lag 2

13.73

8.23, 19.23

<0.001

5.55

1.93, 9.17

0.003

Lag 3-5

3.30

0.58, 6.02

0.02

-1.63

-6.97, 3.72

0.55

Lowest Daily Value
FEV1

Lag 1

-6.25

-11.15, -1.36

0.01

-2.33

-4.85, 0.02

0.07

Lag 2

-5.97

-11.06, -0.87

0.02

-9.92

-13.28, -6.56

<0.001

Lag 3-5

1.98

-0.38, 4.33

0.10

-4.56

-7.92, -1.20

0.008

1 Each row represents a separate linear regression model using generalized estimating equations (GEE) in which both exposures to particulate matter and ozone were included. Covariates in each model: gender, home location, annual family income, grade in school, presence of one or more smokers in house, race, season, randomization assignment for the intervention, interaction between time and this randomization assignment.
2 Regressions limited to those children reporting use of inhaled and/or oral corticosteroids at least 50% of days in a given season on diary.
3 Assessment of a child’s lung function, based on error-free expiratory maneuvers. With airways obstruction, intraday variability is expected to increase and lowest daily value is expected to decrease.
4 Lag is the number of days between measurement of ambient pollutant concentration and lung function. Lag 3-5 is based on the mean of pollutant concentrations on those days.
5 The regression coefficient is the estimated change in lung function associated with an increase of one interquartile range in the ambient pollutant concentration.

Project 3: Chemokines in the Pathogenesis of Asthma

This project investigated the novel model of asthma like pulmonary inflammation induced by house dust containing high levels of cockroach allergens. Previous data had been generated from one lot of house dust. Project investigators sought to determine whether the findings could be generalized to house dust collected from other homes. For these investigations, house dust was collected from five different homes and prepared an aqueous extract of the house dust. Within this aqueous extract, allergen levels were measured including the cockroach allergens, dust mite allergens, and dog and cat allergens, and outdoor allergens. Additionally, endotoxin within this extract was determined. Each of the five house dust extracts contained high levels of cockroach allergens as well as endotoxin. These results were not surprising since the dust was collected from the kitchen where there is a higher likelihood of cockroach infestation compared to the bedrooms. Groups of mice were immunized with this aqueous extract and challenged twice. Measurements included airways hyperreactivity, pulmonary inflammatory cell recruitment, pulmonary and plasma chemokine production, and plasma levels of IgE. Each one of the house dust extracts was able to induce significant pulmonary inflammation in the sensitized mice. This pulmonary inflammation consisted of both neutrophilic and eosinophilic infiltration into the airways, increased airways reactivity to inhaled methacholine was also present, and there were elevated plasma levels of both CC chemokines as well as plasma IgE. These results indicate that this model of airways hyperreactivity may be induced by any house dust extract containing high levels of cockroach allergens. These data were used by the graduate student in the laboratory, Laura McKinley, as a portion of her Ph.D. thesis defense and have been published (McKinley, et al. 2004). Additionally, the investigators intend to submit these data for peer reviewed publication.

An important axis exists between the innate and the adaptive immune response in several inflammatory conditions. Neutrophil chemoattractants such as the CXC chemokines are classically considered part of the innate immune response. However, emerging data indicates that neutralization of the CXC chemokines has significant impact upon the adaptive immune response. There are multiple CXC chemokines within the murine inflammatory system, but two of the best characterized are KC and MIP-2. Neutralizing antibodies to both of these chemokines were raised and used to treat mice prior to the onset of the pulmonary inflammation. Results indicated that neutralization of a classically considered portion of the innate response would significantly decrease the adaptive immune response. These results have been accepted for publication in the journal Cytokine (McKinley, et al. forthcoming).

Clinically, glucocorticoids are only used for the treatment of asthma. These potent immunosuppressants are also used to “break" an acute asthmatic attack. That is, after the onset of inflammation, these compounds may still be effective. Investigators sought to determine whether the novel model of asthma like pulmonary inflammation may be decreased once the inflammatory process is well established by treatment. This will extend the range of the utility of the model, if the mice can be treated in the same manner as human patients, and observed the same improvement. For these experiments, the mice are immunized at the house dust extract and then subjected to 2 pulmonary challenges. Twenty-four hours after the second pulmonary challenge, airways hyperreactivity was measured. A group of mice was treated with dexamethasone, while the control group was treated with the vehicle alone. The dexamethasone was able to significantly reverse the airways hyperreactivity. Additionally, if the mice were pretreated with dexamethasone prior to the pulmonary challenge, there was a significant reduction in the total plasma IgE, airways hyperreactivity, and inflammatory cell recruitment into the lung. These data demonstrate the clinical utility of this novel model. These data have been published (Kim, et al. 2004).

Finally, this application was used as a starting point for submitting a RO1 grant to the NIH. We are fortunate that this application receive a priority score 131 and a percentile of 7.3.

MCECH Supporting Cores

The Administrative Core, through its Executive Committee (comprised of investigators and community partners from all three research projects), was responsible for monitoring progress of the three research projects and ensuring coordination and integration among the Center’s research and facilities cores. In addition, the Administrative Core coordinated annual meetings and periodic conference calls with the External Advisory Committee (EAC), which provided feedback and suggestions on research related issues, e.g., study design, questionnaire development, and intervention design. These meetings were held over a two day period in Detroit with the CAAA Steering Committee during the EAC meeting, and in Ann Arbor with the university-based partners.

The Biostatistics Core provided statistical support, data analysis, and data management and coordinated with the Intervention, Exposure, and Chemokine Research Projects of MCECH to integrate data collected by each respective project into a central database. The Biostatistics Core was responsible for the accuracy of all data codes and data entry and worked closely with data entry staff to guarantee such accuracy. The Biostatistics Core ran a final, validity check on all study data to ensure that data was within plausible parameters and logically consistent with similar sources of data. Discrepancies were investigated and corrected; corrections are properly documented.

The Exposure Assessment Core provided instrumentation for PM exposure measurements and facilities for calibration and maintenance of air sampling equipment. In addition, this Core provided state-of-the-art analytical facilities and expertise for collection, processing and analysis of environmental and laboratory samples.

Through the New Center Scientist Program, MCECH hired two new scientists to work on two of the three research projects. Timothy Dvonch, an Exposure Assessment Scientist, who currently has an appointment as an Assistant Research Professor at the University of Michigan School of Public Health, worked under the direction of the Principal Investigator for the Exposure Assessment Facility Core (Gerald Keeler). In addition, Dr. Dvonch participated as a member of the CAAA Steering Committee and Research Work Group and was directly involved in the indoor and outdoor air monitoring and dust collection and assessment activities. Toby Lewis, a Pediatric Pulmonologist, was hired as the new Pediatric Center Scientist, and currently has an Assistant Professor appointment in the University of Michigan School of Medicine. Dr. Lewis worked under the direction of Thomas Robins, the PI for the Indoor/Outdoor Exposure Research Project. Dr. Lewis participated on the CAAA Steering Committee and Research Work Group, and was involved in the analysis of data collected through the peak flow meters used by the study participants. Both Dr. Dvonch and Dr.Lewis continue to be involved in data analysis and manuscript preparation.


Journal Articles: 22 Displayed | Download in RIS Format

Other center views: All 45 publications 24 publications in selected types All 22 journal articles
Type Citation Sub Project Document Sources
Journal Article Clark NM, Brown RW, Parker E, Robins TG, Remick Jr. DG, Philbert MA, Keeler GJ, Israel BA. Childhood asthma. Environmental Health Perspectives 1999;107(Suppl 3):421-429. R826710 (Final)
R826710C001 (1999)
R826710C002 (1999)
R826710C003 (1999)
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  • Journal Article Dvonch JT, Marsik FJ, Keeler GJ, Robins TG, Yip F, Morishita M. Field comparison of PM2.5 teom and PM2.5 manual filter-based measurement methods in urban atmospheres. Journal of Aerosol Science 2000;31(Suppl 1):190-191. R826710 (Final)
  • Full-text: ScienceDirect - Full Text PDF
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  • Abstract: ScienceDirect - Abstract & Full Text HTML
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  • Journal Article Edgren KK, Parker EA, Israel BA, Lewis TC, Salinas MA, Robins TG, Hill YR. Community involvement in the conduct of a health education intervention and research project: Community Action Against Asthma. Health Promotion Practice 2005;6(3):263-269. R826710 (Final)
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  • Abstract: Sage Publications-Abstract
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  • Journal Article Eggleston PA, Diette G, Lipsett M, Lewis T, Tager I, McConnell R, Chrischilles E, Lanphear B, Miller R, Krishnan J. Lessons learned for the study of childhood asthma from the Centers for Children’s Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1430-1436. R826710 (Final)
    R827027 (2002)
    R829389 (2003)
    R829389 (2004)
    R829389 (2005)
    R829389 (Final)
    R831710 (2004)
    R831710 (2005)
    R831710 (Final)
    R831861 (2005)
    R831861 (2006)
    R831861C001 (2006)
    R832139 (2004)
    R832139 (2005)
    R832139 (2006)
    R832139C002 (2005)
    R832139C003 (2005)
    R832141 (2006)
    R832141 (2007)
    R832141 (Final)
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  • Journal Article Farquhar SA, Parker EA, Schulz AJ, Israel BA. In their words: how Detroit residents perceive the effects of their physical environment. Local Environment:The International Journal of Justice and Sustainability 2005;10(3):259-274. R826710 (Final)
  • Abstract: Taylor & Francis Online-Abstract
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  • Journal Article Gilliland F, Avol E, Kinney P, Jerrett M, Dvonch T, Lurmann F, Buckley T, Breysse P, Keeler G, de Villiers T, McConnell R. Air pollution exposure assessment for epidemiologic studies of pregnant women and children: lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1447-1454. R826710 (Final)
    R826708 (2000)
    R826708 (2001)
    R826708 (2002)
    R826708 (Final)
    R827027 (2002)
    R831845 (2005)
    R831861 (2004)
    R831861 (2005)
    R831861 (2006)
    R831861 (Final)
    R831861C001 (2006)
    R831861C001 (Final)
    R831861C002 (Final)
    R831861C003 (2006)
    R831861C003 (Final)
    R832139 (2006)
    R832141 (2006)
    R832141 (2007)
    R832141 (Final)
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  • Journal Article Israel BA, Parker EA, Rowe Z, Salvatore A, Minkler M, Lopez J, Butz A, Mosley A, Coates L, Lambert G, Potito PA, Brenner B, Rivera M, Romero H, Thompson B, Coronado G, Halstead S. Community-based participatory research:lessons learned from the Centers for Children's Environmental Health and Disease Prevention Research. Environmental Health Perspectives 2005;113(10):1463-1471. R826710 (Final)
    R829391 (2004)
    R829391 (2005)
    R829391 (2006)
    R829391C005 (2006)
    R831709 (2005)
    R831709 (2007)
    R831709C003 (2005)
    R831709C003 (2006)
    R831710 (2004)
    R831710 (2005)
    R831710 (Final)
    R831710C001 (2006)
    R831710C002 (2006)
    R831710C004 (2006)
    R831711 (2005)
    R831711 (2006)
    R831711 (2007)
    R831711 (Final)
    R831711C001 (2006)
    R831711C002 (2006)
    R831711C003 (2006)
    R832139 (2006)
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  • Journal Article Keeler GJ, Dvonch T, Yip FY, Parker EA, Isreal BA, Marsik FJ, Morishita M, Barres JA, Robins TG, Brakefield-Caldwell W, Sam M. Assessment of personal and community-level exposures to particulate matter among children with asthma in Detroit, Michigan, as part of Community Action Against Asthma (CAAA). Environmental Health Perspectives 2002;110(Suppl 2):173-181. R826710 (2002)
    R826710 (Final)
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  • Journal Article Kim J, Merry AC, Nemzek JA, Bolgos GL, Siddiqui J, Remick DG. Eotaxin represents the principal eosinophil chemoattractant in a novel murine asthma model induced by house dust containing cockroach allergens. Journal of Immunology 2001;167(5):2808-2815. R826710 (2002)
    R826710 (Final)
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  • Full-text: Journal of Immunology-Full Text PDF
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  • Abstract: Journal of Immunology-Abstract & Full Text HTML
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  • Journal Article Kim J, McKinley L, Siddiqui J, Bolgos GL, Remick DG. Prevention and reversal of pulmonary inflammation and airway hyperresponsiveness by dexamethasone treatment in a murine model of asthma induced by house dust. American Journal of Physiology-Lung Cellular and Molecular Physiology 2004;287(3):L503-L509. R826710 (2002)
    R826710 (Final)
  • Abstract from PubMed
  • Full-text: American Physiological Society-Full Text HTML
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  • Abstract: American Physiological Society-Abstract
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  • Other: American Physiological Society-Full Text PDF
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  • Journal Article Kim J, McKinley L, Natarajan S, Bolgos GL, Siddiqui J, Copeland S, Remick DG. Anti-tumor necrosis factor-α antibody treatment reduces pulmonary inflammation and methacholine hyper-responsiveness in a murine asthma model induced by house dust. Clinical and Experimental Allergy 2006;36(1):122-132. R826710 (Final)
  • Abstract from PubMed
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  • Abstract: Wiley-Abstract
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  • Journal Article Lewis TC, Robins TG, Joseph CLM, Parker EA, Israel BA, Rowe Z, Edgren KK, Salinas MA, Martinez ME, Brown RW. Identification of gaps in the diagnosis and treatment of childhood asthma using a community-based participatory research approach. Journal of Urban Health 2004;81(3):472-488. R826710 (Final)
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  • Journal Article Lewis TC, Robins TG, Dvonch JT, Keeler GJ, Yip FY, Mentz GB, Lin X, Parker EA, Israel BA, Gonzalez L, Hill Y. Air pollution-associated changes in lung function among asthmatic children in Detroit. Environmental Health Perspectives 2005;113(8):1068-1075. R826710 (Final)
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  • Journal Article Lopez ED, Parker EA, Edgren KK, Brakefield-Caldwell W. Disseminating research findings back to partnering communities: lessons learned from a community-based participatory research approach. Metropolitan Universities Journal 2005;16(1):57-76. R826710 (Final)
  • Full-text: IUPUI-Full Text PDF
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  • Abstract: IUPUI-Abstract
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  • Journal Article McKinley L, Kim J, Bolgos GL, Siddiqui J, Remick DG. Reproducibility of a novel model of murine asthma-like pulmonary inflammation. Clinical & Experimental Immunology 2004;136(2):224-231. R826710 (Final)
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  • Full-text: Wiley-Full Text PDF
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  • Abstract: Wiley-Abstract
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  • Journal Article McKinley L, Kim J, Bolgos GL, Siddiqui J, Remick DG. CXC chemokines modulate IgE secretion and pulmonary inflammation in a model of allergic asthma. Cytokine 2005;32(3-4):178-185. R826710 (2002)
    R826710 (Final)
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  • Abstract: ScienceDirect-Abstract
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  • Journal Article McKinley L, Kim J, Bolgos GL, Siddiqui J, Remick DG. Allergens induce enhanced bronchoconstriction and leukotriene production in C5 deficient mice. Respiratory Research 2006;7(1):129. R826710 (Final)
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  • Full-text: Respiratory Research - Full Text HTML
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  • Other: Respiratory Research - Full Text PDF
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  • Journal Article Parker EA, Israel BA, Williams M, Brakefield-Caldwell W, Lewis TC, Robins T, Ramirez E, Rowe Z, Keeler G. Community action against asthma: examining the partnership process of a community-based participatory research project. Journal of General Internal Medicine 2003;18(7):558-567. R826710 (Final)
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  • Abstract: Springer-Abstract
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  • Journal Article Parker EA, Baldwin GT, Israel B, Salinas MA. Application of health promotion theories and models for environmental health. Health Education & Behavior 2004;31(4):491-509. R826710 (Final)
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  • Full-text: SemanticScholars-Full Text PDF
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  • Abstract: Sage Journals-Abstract
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  • Journal Article Parker EA, Israel BA, Robins TG, Mentz G, Lin X, Brakefield-Caldwell W, Ramirez E, Edgren KK, Salinas M, Lewis TC. Evaluation of community action against asthma: a community health worker intervention to improve children's asthma-related health by reducing household environmental triggers for asthma. Health Education & Behavior 2008;35(3):376-395. R826710 (Final)
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  • Abstract: Sage Journals-Abstract
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  • Journal Article Trout D, Weissman DN, Lewis D, Brundage RA, Franzblau A, Remick D. Evaluation of hypersensitivity pneumonitis among workers exposed to metal removal fluids. Applied Occupational and Environmental Hygiene 2003;18(11):953-960. R826710 (Final)
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  • Abstract: Taylor and Francis-Abstract
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  • Journal Article Yip FY, Keeler GJ, Dvonch JT, Robins TG, Parker EA, Israel BA, Brakefield-Caldwell W. Personal exposures to particulate matter among children with asthma in Detroit, Michigan. Atmospheric Environment 2004;38(31):5227-5236. R826710 (Final)
  • Full-text: ScienceDirect-Full Text HTML
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  • Abstract: ScienceDirect-Abstract
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  • Supplemental Keywords:

    RFA, Health, Scientific Discipline, Air, Geographic Area, HUMAN HEALTH, Environmental Chemistry, Health Risk Assessment, State, Indoor Air Pollution, Risk Assessments, Allergens/Asthma, Health Effects, Children's Health, indoor air, Molecular Biology/Genetics, asthma, asthma triggers, acute lung injury, respiratory disease, second hand smoke, airway disease, respiratory problems, exposure, asthma indices, children, indoor air chemistry, air pollution, Human Health Risk Assessment, airway inflammation, assessment of exposure, childhood respiratory disease, children's vulnerablity, susceptibility, asthmatic children, human exposure, airborne pollutants, inhalation, cigarette smoke, children's environmental health, allergic response, environmental tobacco smoke, air quality, cockroaches, airborne urban contaminants, allergen, exposure assessment, human health risk

    Progress and Final Reports:

    Original Abstract
  • 1999
  • 2000 Progress Report
  • 2001
  • 2002 Progress Report
  • 2003
  • 2004
  • Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R826710C001 Indoor and Outdoor Air Contaminant Exposures and Asthma Aggravation Among Children (Asthma Exposure)
    R826710C002 Chemokines in the Pathogenesis of Asthma (Asthma Chemokines)
    R826710C003 A Community-Based Intervention to Reduce Environmental Triggers for Asthma Among Children (Asthma Intervention)