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2005 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: Columbia Center for Children’s Environmental Health
Center Director: Perera, Frederica P.
Title: Research Project on Asthma: Prenatal and Postnatal Urban Pollutants and Childhood Asthma
Investigators: Perera, Frederica P.
Current Investigators: Rothman, Paul B.
Institution: Columbia University
EPA Project Officer: Fields, Nigel
Project Period: November 1, 2003 through October 31, 2008
Project Period Covered by this Report: November 1, 2004 through October 31, 2005
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2003)
Research Category: Children's Health , Health Effects
Description:
Objective:The specific objectives of this research project are to: (1) determine the relationship between environmental exposures experienced prenatally through early childhood and atopy and 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 years; (3) determine if antigen-induced cord blood mononuclear cell proliferation or cytokine production increases the risk for decreased lung function or atopy at age 5 years among children receiving physician diagnosis of probable asthma at age 2 years and allergen-specific IgE levels at ages 2 and 3 years are associated with decreased lung function or atopy at age 5 years; and (4) collaborate with the Community Outreach, Translation and Application Core to ensure that asthma risk factors of concern to the community are being addressed, translate research findings back to the community, and assist in developing interventions and policies to prevent exposures that contribute to asthma and adverse respiratory health in New York City and elsewhere.
Progress Summary:Recruitment of Study Participants
To date, 673 nonsmoking, African American and Dominican women have met the criteria for complete enrollment into the Mothers and Children Study cohort (i.e., underwent prenatal monitoring, provided a prenatal questionnaire, and had a blood sample collected at delivery from either the mother and/or her newborn).
Data Collected
Questionnaire completion rates are 775 prior to delivery, 530 at 3 months, 519 at 6 months, 477 at 12 months, 383 at 24 months, and 342 at 36 months, and 204 at 60 months. More than 40 allergy skin tests and 180 lung function tests have been completed at age 5 years. Numbers are expected to increase as children more recently enrolled into the study reach older ages.
Immunoassays Performed
A selected summary of the performed immunoassays is as follows: total IgE levels at birth by radioimmunoassay (Immunocap): 330; at age 2 years: 312; at age 3 years: 157; at age 5 years: 112; among the mothers following pregnancy: 382. Anti-cockroach, mouse, and dust mite-specific IgE (by fluorescence allergosorbent test or Immunocap) at age 2 years: 239 each; anti-cockroach, mouse, and dust mite IgE levels at age 3 years: 174 each; anti-cockroach, mouse, and dust mite IgE levels at age 5 years: 139. Assays are ongoing; therefore, these numbers will increase.
Findings
In utero Sensitization. There continues to be a high rate of sensitization to multiple inhalant indoor antigens, especially cockroach, in newborns. Rates have not altered significantly from those previously reported.
Allergen-Specific IgE. There continues to be evidence of cockroach, mouse, and more rarely, dust mite allergy as early as ages 2 and 3 years (Table 1).
Table 1. Allergen-Specific IgE (% > 0.35 IU/mL)
|
Cockroach IgE |
Mouse IgE |
Dust Mite IgE |
Age 2 (n=217) |
8.7 |
9.4 |
3.6 |
Age 3 (n=75) |
10.7 |
8.0 |
4.0 |
Sixteen percent of children in the cohort had a positive allergen-specific IgE to at least one of the antigens at age 2 years. These frequencies were not affected by gender of the child, mother’s reported asthma, ethnicity, or mother’s IgE. We also did not find a relationship between allergen exposure measured prenatally and allergen-specific IgE at age 2 years. Our results demonstrate that the allergic immune response to cockroach and mouse, allergens implicated in inner-city asthma, can occur by age 2 years.
Association Between Prenatal Airborne Pyrene Exposure and Outcomes at Birth and at Age 2. Numerous studies suggest that prenatal environmental exposures may affect cord blood reactivity in response to allergens and IgE isotype class switching. Hence, we asked whether increased prenatal polycyclic aromatic hydrocarbon (PAH) exposure may be associated with increased antigen-specific cytokine production or IgE at birth. Sixty-six percent of our cord blood samples analyzed to date (n = 115) had total IgE levels below the detection limit of the enzyme-linked immunosorbent assay of 0.5 IU/mL. Allergen-specific IgE levels were not detected in cord blood samples tested. We did not detect any correlation between PAH exposure and total IgE levels in cord blood. We also did not find any significant correlations between PAH exposure, antigen-specific proliferation, and the level of allergen-specific IFNg, and/or IL-5 cytokine production. These results suggest that prenatal exposure to total PAH does not affect antigen-specific cytokine production, proliferation, or IgE production at birth. As demonstrated in Table 2, however, increased prenatal exposure to the PAH pyrene was associated with increased mouse, and dust mite IgE at age 2 years.
Table 2. Correlation Coefficients Between PAH and IgE Levels (Total and Antigen-Specific)
|
Cockroach |
Mouse |
Dust Mite |
Total IgE |
Total (8 PAH) |
-0.058 |
0.079 |
0.035 |
0.020 |
Pyrene |
0.057 |
0.164* |
0.199** |
0.051 |
*p < 0.05, **p < 0.01 |
||||
Cough, difficulty breathing, wheeze, and report of probable asthma were reported in 47, 16.3, 14.6, and 14.7 percent of the cohort at age 2. To determine if the presence of increased anti-cockroach, mouse, or dust mite IgE level was associated with adverse respiratory outcomes as early as age 2, IgE levels were compared to data obtained from respiratory questionnaires. Increased prevalence of coughing (p = 0.012), difficulty breathing (p = 0.006), and possibly wheezing (p = 0.097, NS), but not probable asthma, were observed among children with an increase in any of the three allergen-specific IgEs measured. In contrast, respiratory symptoms were not associated with increased total IgE at age 2. Children in homes with higher endotoxin concentration were less likely to have eczema at age 1 (O.R. 0.70 [0.53-0.93]) and more likely to wheeze at age 2 (O.R. 1.34 [1.01-78]). These associations were stronger among children with a maternal history of asthma.
Association Between Prenatal PAH, Postnatal ETS, and Respiratory Symptoms Age 12-24 Months. We analyzed data on personal PAH exposure measurements and histories of environmental tobacco smoke (ETS) exposure for the initial 303 women during pregnancy and followed their children prospectively for adverse respiratory effects. We found that by 12 months of age, more cough and wheeze were reported among children prenatally exposed to PAH in concert with ETS postnatally (PAH x ETS OR 3.26 p < 0.01, 3.38 p < 0.05, respectively). By 24 months, difficulty breathing and probable asthma were reported more frequently among children exposed parentally to PAH and ETS postnatally (PAH x ETS OR 5.37 p < 0.05, 7.52 p < 0.01, respectively). Our results suggest that early exposure to PAH and ETS can lead to frequent respiratory symptoms and probable asthma by age 12-24 months.
IgE, Allergy Symptoms, and Their Association With Birth Order (Goldstein, et al., 2005). An inverse association between birth order and allergic disease has been observed widely but has not been examined in the high asthma prevalence, inner-city populations of the United States. In our ongoing prospective birth cohort, the prevalence of early phenotypes of asthma and/or allergy was compared with those reported in other studies, and the association with birth order was evaluated. We found that the total sera IgE was detectable (> 0.5 IU/mL) in 35 percent of the children's cord blood and averaged 15 IU/mL, and 21 IU/mL at age 24 and 36 months, respectively. They were not significantly different at any age between children with and without older siblings. Additionally, at these ages there were no consistent associations between birth order and either wheeze, itchy eyes, or eczema. Hence, despite a substantially higher prevalence of asthma in the Northern Manhattan community compared to other areas, total IgE levels at age 24 and 36 months, but not cord blood, are similar to those reported in other areas of the world. Results at this age in this community do not support a protective effect of higher birth order.
Significance
The full significance of our results with respect to asthma causation is not known, given the young age of the cohort. Our results support an important early role of the environment in asthma causation. Specifically: (1) sensitization to indoor allergens occurs as early as in utero, (2) birth order does not affect IgE outcomes; (3) elevated total and allergen-specific IgE levels, and possibly early signs of asthma, in relation to environmental exposures, occurs at an early age; and (4) prenatal PAHs, and possibly pyrene exposure specifically, may be important co-factors in the development of allergic immune responses.
Future Activities:We plan to continue expanding data collection and analysis. Evaluation of the relationship between birth biomarkers and findings at age 2 through 7 years is ongoing. Evaluation of the contribution of maternal stress to onset of asthma is underway.
Journal Articles on this Report: 1 Displayed | Download in RIS Format
| Other subproject views: | All 2 publications | 2 publications in selected types | All 2 journal articles |
| Other center views: | All 100 publications | 89 publications in selected types | All 86 journal articles |
| Type | Citation | ||
|---|---|---|---|
|
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Goldstein IF, Perzanowski MS, Lendor C, Garfinkel RS, Hoepner LA, Chew GL, Perera FP, Miller RL. Prevalence of allergy symptoms and total IgE in a New York City cohort and their association with birth order. International Archives of Allergy and Immunology 2005;137:249-57. |
R832141 (2006) R832141C002 (2005) R827027 (2002) |
not available |
children’s health, health effects, health risk assessment, asthma, genetics, assessment of exposure, PAH, ETS, environmental risks, environmental exposure, exposure assessment, genetic risk factors, genetic susceptibility, maternal exposure, nutritional risk factors,
,
HUMAN HEALTH, ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, Health Effects, Risk Assessment, Health Risk Assessment, Epidemiology, Children's Health, Biochemistry, Genetics, exposure assessment, genetic risk factors, children's environmental health, diesel exhaust, assessment of exposure, prenatal exposure, genetic susceptibility, maternal exposure, nutritional risk factors, genetic mechanisms, environmental risks, asthma
Relevant Websites:
Progress and Final Reports:
2004 Progress Report
Original Abstract
2006 Progress Report
Main Center Abstract and Reports:
R832141 Columbia Center for Children’s Environmental Health
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