Grantee Research Project Results
2007 Progress Report: Research Project on Asthma: Prenatal and Postnatal Urban Pollutants and Childhood Asthma
EPA Grant Number: R832141C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R832141
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management
Center Director: Olabode, Lola
Title: Research Project on Asthma: Prenatal and Postnatal Urban Pollutants and Childhood Asthma
Investigators: Rothman, Paul B. , Lederman, Sally Ann , Barr, R. Graham , Miller, Rachel L. , Sheares, Beverly , Goldstein, Inge
Institution: Columbia University in the City of New York
EPA Project Officer: Callan, Richard
Project Period: November 1, 2003 through October 31, 2008 (Extended to October 31, 2010)
Project Period Covered by this Report: November 1, 2006 through October 31, 2007
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003) RFA Text | Recipients Lists
Research Category: Children's Health , Human Health
Objective:
The specific aims of the project are to: 1) Determine the relationship between environmental exposures experienced prenatally through early childhood and atopy, adverse respiratory outcomes and asthma at age 5-7 years; 2) Determine interaction between susceptibility factors and environmental exposures on respiratory outcomes and asthma through ages 5-7; 3) Determine if (a) antigen-induced cord blood mononuclear cell proliferation (CBMC) or cytokine production increases the risk for decreased lung function or atopy at age 5 among children with probable asthma at age 2, (b) allergen-specific IgE levels at ages 2, 3 years are associated with decreased lung function, atopy at age 5; and 4) Collaborate with COTAC to ensure that asthma risk factors of concern to the community are being addressed, translate research findings back to community, and assist in developing interventions and policies to prevent exposures that contribute to asthma and adverse respiratory health.
Progress Summary:
As previously reported, over half the babies in the study have been born with an immune response to cockroach proteins that may increase the risk of asthma in certain children (Miller et al., 2001). Combined prenatal exposure to airborne PAHs and postnatal secondhand smoke results in the increased likelihood of respiratory symptoms at age 1,2 years, that may be associated with increased children’s asthma risk (Miller et al., 2004).
Recruitment of Study Participants
Recruitment of cohort is complete.
Data collected
Questionnaire completion rates: 845 prior to delivery, 606 at 12 months, 515 at 24 months, and 442 at 36 months, 348 at 60 months, and 227 at 72 months. N=289 lung function tests on n=254 children have been completed at age 4-6 years and testing is ongoing. Personal prenatal airborne PAH data (n=702) collected by the Exposure Core for comparison with asthma outcomes are complete.
Findings
Allergen-specific IgE. The frequency of sensitization to cockroach and dust mite is increasing substantially between ages 2-7 years (Table 1). Allergic immune response to cockroach and mouse, allergens implicated in inner city asthma, can occur by age 2 years.
Respiratory symptoms/pulmonary function. Respiratory symptoms and probable asthma are common (Figure 1). Airway obstruction was measured among 26% of 4 year olds, 17% of 5 year olds, and 36% of 6 year olds. There was no difference in the patterns of lung function according to ethnicity.
Respiratory effects of PAH, ETS exposure. Combined prenatal exposure to PAHs and postnatal exposure to environmental tobacco smoke was associated with respiratory symptoms and possible asthma ages 1,2 (Miller et. al. 2004).
Effects of winter birth season and prenatal indoor allergen exposure on indoor allergen- specific cord blood proliferation, cytokine production (Lendor et al., in prep). Children born in the winter did not have increased levels of indoor allergen-induced cord blood mononuclear cell (CBMC) proliferation or Th cytokines. Although, an association between winter birth and greater cockroach IL-5 production was seen (p=0.019). Higher prenatal levels of cockroach and mouse allergen were not associated with greater CBMC proliferation, or Th cytokine production. A modest correlation was observed between mouse allergen and cord blood IgE levels (r=0.149; p=0.021).
Table 1. Allergen-specific IgE (%>0.35 IU/ml)
|
Anti-Cockroach IgE |
Anti-Mouse |
Anti- D. Farinae |
Age 2 (n=410) |
7.3 |
7.4 |
2.7 |
Age 3 (n=342) |
9.6 |
7.6 |
4.4 |
Age 5 (n=275) |
20.4 |
10.2 |
8.1 |
Age 7 (n=140) |
35.7 |
18.6 |
20.1 |
Figure 1. Asthma-associated symptoms
Cockroach, mouse-specific IgE is associated with early wheeze (Donohue et. al., in prep). Among those children who were sensitized to cockroach, a strong correlation between measured cockroach allergen levels in home dust and anti-cockroach IgE levels by age 2-3 years was present (bed dust: Spearman’s Rho 0.762, p < 0.001). Children with wheeze had a higher average anti-cockroach and anti-mouse IgE than children without wheeze on Mann Whitney U analysis. Children with higher IgE to mouse were more likely to develop eczema and rhinitis than children with lower IgE class (test for trend p =0.002 for eczema, 0.03 for rhinitis). Children with higher IgE class to cockroach were more likely to develop eczema, but not rhinitis, when compared to children with lower cockroach IgE class (test for trend p <0.001 for eczema, NS for rhinitis).
Cat ownership is a risk factor for developing IgE to cat but not wheeze at age 5 (Perzanowski et. al., submitted). Cat ownership was a significant risk factor for developing anti-cat IgE antibodies by age 2 (RR 6.4 [1.9-22]), but not for incidence of anti-cat IgE between ages 2 and 5 (RR 0.88 [0.24-2.3]). Wheeze was significantly more common among those children with anti-cat IgE at ages 3 (RR 3.5 [2.1-6.0]) and 5 (RR 3.4 [2.3-4.9]). Cat ownership was inversely associated with wheeze at age 5 among children without anti-cat IgE (RR 0.26 [0.083-0.81], p=0.007). Among children with anti-cat IgE a similar trend was observed, (RR 0.57 [0.32-1.03], p=0.044), but the association was of borderline statistical significance.
GST polymorphisms and asthma outcomes. A significant association was found between a polymorphism in Glutathione-S-Transferase Theta 2-02 (GSTT2-02) and the development of wheeze or asthma by age 3 years among the Dominican children in the cohort from the first n=318 children analyzed.
Allergen levels and increased asthma among public housing residents (Chew et al. 2006). Details are discussed in the Community-Based Intervention and Exposure Core Progress Reports.
Significance
Winter birth season and prenatal cockroach and mouse allergen exposure are not associated with allergen-specific T cell immune responses at birth. Sensitization to cockroach and mouse by age 3 years is associated with wheeze and eczema. Cat ownership in this inner-city cohort was inversely associated with wheeze and allergic rhinitis, regardless of sensitization, suggesting an IgE-independent protective mechanism. Our results support an important early role of the environment in asthma pathogenesis and identify areas for potential intervention.
Future Activities:
We plan to continue expanding data collection and analysis as the cohort ages. Evaluation of the relationship between birth biomarkers and findings at age two through seven years is ongoing. Evaluation of the modifying effects of obesity is underway. Collaboration with COTAC continues.
Journal Articles:
No journal articles submitted with this report: View all 2 publications for this subprojectSupplemental Keywords:
Health, RFA, Scientific Discipline, ENVIRONMENTAL MANAGEMENT, HUMAN HEALTH, Health Risk Assessment, Epidemiology, Children's Health, Biochemistry, Health Effects, Genetics, Risk Assessment, genetic mechanisms, Human Health Risk Assessment, diesel exhaust, asthma, maternal exposure, environmental risks, prenatal exposure, genetic risk factors, genetic susceptibility, nutritional risk factors, assessment of exposure, children's environmental healthProgress and Final Reports:
Original AbstractMain Center Abstract and Reports:
R832141 Water Environment and Reuse Foundation's National Center for Resource Recovery and Nutrient Management Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R832141C001 Growth and Development Research Project: Prenatal and Postnatal Urban Pollutants and Neurobehavioral Developmental Outcomes
R832141C002 Research Project on Asthma: Prenatal and Postnatal Urban Pollutants and Childhood Asthma
R832141C003 Mechanistic Research Project
R832141C004 Community-Based Intervention Project: Reduction of Exposure and Risk from Pesticides and Allergens
R832141C005 Community Translation and Application Core (COTAC)
R832141C006 Exposure Assessment Facility Core
R832141C007 Data Management, Statistics and Community Impact Modeling Core
R832141C008 Administrative Core
The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.