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2002 Progress Report: Growth and Development/Evaluation of Carcinogenic Risks
EPA Grant Number: R827027C002Subproject: this is subproject number 002 , established and managed by the Center Director under grant R827027
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - Columbia University School of Public Health
Center Director: Perera, Frederica P.
Title: Growth and Development/Evaluation of Carcinogenic Risks
Investigators: Perera, Frederica P.
Institution: Columbia University
EPA Project Officer: Fields, Nigel
Project Period: August 1, 1998 through July 31, 2001 (Extended to October 31, 2004)
Project Period Covered by this Report: August 1, 2001 through July 31, 2002
Project Amount: Refer to main center abstract for funding details.
RFA: Centers for Children's Environmental Health and Disease Prevention Research (1998)
Research Category: Children's Health , Health Effects
Description:
Objective:The objective of the Research Project on Asthma remains unchanged. It is designed to test the hypotheses a) that prenatal and/or postnatal exposure to home allergens (cockroach, house dust mite, and rodent) and ETS, as well as postnatal exposure to PM2.5 and diesel exhaust particulate (DEP), are significant contributors to risk of asthma, as indicated by related biomarkers and persistent wheezing, b) that the risk from home allergens is increased by co-exposure to the air pollutants (ETS, PM2.5 and DEP); and c) that impaired nutritional status (inadequate levels of antioxidants) heightens susceptibility to the pollutants.
Project investigators will conduct an etioloic study of environmental and susceptibility factors in the same cohort of 400 infants and will also contribute to the intervention study. The Project will make use of all of the questionnaire data as well as the biomarker data on cotinine and antioxidants collected by the G&D Project. Additional exposures of interest (home allergens, PM2.5 and DEP, and N02 as a potential confounder) will be monitored and modeled. In addition, the Project will obtain measurements of infants' IgE (total and allergen specific) at birth and at 24 months, as well as measurements of lymphocyte proliferation and cytokines at birth. Mothers will be interviewed at serial time points to obtain information on their children's respiratory symptoms.
Progress Summary:Studies and Results
Recruitment of Study Participants: To date, 462 non-smoking, African American and Dominican women have met the criteria for complete enrollment into the Mothers & Newborns 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 462 prior to delivery, 365 at 3 months, 356 at 6 months, 302 at 12 months, 185 at 24 months, and 67 at 36 months. There were no significant differences in loss to follow-up by ethnic identity. 363 samples of cord blood and 297 samples of postpartum maternal blood have been analyzed by investigators in the asthma core.
Infant Health: Investigators analyzed data on infants who had reached age 12 months (Meyer et al., J. of Asthma, 2002, in press) and 24 months. Overall the results from both year I and year 2 have been consistent in showing high risk for asthma-related symptoms in our sample. To assess risk for asthma we used an index classifying as high-risk infants with recurrent wheezing (2 or more episodes) and a history of physician-diagnosed eczema, and/or parental history of asthma (Castro-Rodriguez et al., Am J Respir Crit Care Med 2000; 162:1403-1406). At the end of year 1, 9% of the infants were thus classified as having a high risk for asthma. By the end of year 2, the prevalence of high risk for asthma has more than doubled to 19% of the children (23% of boys and 16% of the girls, not a significant difference by sex). At year 1, there were no significant differences between low and high risk infants in sex, ethnicity, maternal education level, or income; but risk for asthma was highly related to having had a lower respiratory tract illness (pneumonia, bronchiolitis, bronchitis or croup). The estimated high prevalence of high risk asthma among children is supported by other measures of risk for asthma that we examined. By age 2, 63 (35%) of the children were diagnosed by a physician as having or maybe having asthma and 56 (31%) were diagnosed as having eczema; 55 (31%) of the children had a history of 2 or more wheezing episodes. These estimates are also consistent with reported use of medications, especially Proventil, which was prescribed to 31 (17%) of the children during the 3 months prior to age 2 interview. During that time Prednisone was prescribed to 7 children (4%). The wide use of home remedies (such as "soups, teas, oils and salves") to treat "breathing problems", reported for 43 (24%) of the children, is also consistent with these findings. We also noted that during the first year of life, wheezing required significant care: 30 (33%) of the infants in the cohort visited a doctor's office, 20 (22%) were seen in an emergency department, and 6 (6%) were hospitalized overnight for a wheezing episode at least once. By age 2 years, 14 (19%) have had an emergency visit due to breathing problems, 2 (3%) had a hospitalization lasting at least one night due to breathing problems, and 17 (23%) had taken asthma medications (7 or 9% were taking medications on a daily basis) during the 3 month prior to the follow-up interview at age 2.
Immunoassays performed: The following immunoassays have been performed: Total IgE levels at birth by radioimmunoassay (RIA) (n=292); antigen-induced mononuclear cell proliferation assays at birth (n=265 newborns; n=228 mothers); cytokine analysis by enzyme-linked immunosorbent assay (ELISA) at birth (n= 1 12); total IgE levels at 24 months by radioimmunoassay (RIA) (n=175); allergen-specific IgE levels by fluorescence allergosorbent test (FAST) (n=97 mothers, n=75 at 24 months); total IgE levels at 36 months (by RIA) (n=63).
Findings:
In utero sensitization to multiple indoor antigens has been assessed in 257 newborns and 217 maternal blood samples. There was a high rate of sensitization to multiple inhalant indoor antigens, especially cockroach, in newborns. The presence of proliferation in response to antigens significantly differed between mothers and newborns (p <0.05 for cockroach, p<0.001 for D. Pteronyssinus, D. farinae and tetanus). In many cases, antigen-induced proliferation occurred in cord blood in the absence of antigen-induced proliferation in maternal blood, suggesting that prenatal priming may be occurring in the placenta (Miller et a]., Am J. Respir Crit Care Med, 200 1).
Association between prenatal airborne pyrene exposure and antigen-induced sensitization and IgE. Investigators have begun to analyze the relationship between prenatal pyrene exposure, increased antigen-induced cord blood, mononuclear cell proliferation, and elevated serum IgE at birth and age 2 years. Results on 265 newborns (those with history consistent with elevated cotinine levels excluded) yielded the following preliminary findings: Regression analysis demonstrated that antigen-induced cord blood proliferation and prenatal pyrene exposure were weakly associated with increased IgE level at birth (OR 1.52 (CI 1.22, 13.04) p=0.14, n=185) and increased total IgE at age 24 months (p=0.12, n=99). Mouse antigen-induced cord blood proliferation in the presence of high prenatal pyrene exposure was associated with increased mouse IgE level age 2 months (p=0.04). In addition, increased prenatal pyrene exposure was significantly correlated with increased mouse (r=0.47, p<0.0001, n=65) and dust mite (r=0.35, p=0.02, n=43) IgE levels at age 24 months. These results suggest that prenatal pyrene exposure may be an important coexposure in the development of indoor antigen-specific B and T cell immune responses.
Future Activities:Their full significance with respect to asthma causation is not known, but these results suggest that sensitization to indoor allergens occurs as early as in utero. Our cohort appears to be demonstrating increased respiratory complaints, elevated total and allergen-specific IgE levels, and possibly early signs of asthma. The prevalence of these in our cohort is much higher than the 3%-5% prevalence reported for United States children ages 0-5. On the other hand, our findings are consistent with the upper end of prevalences reported by other studies of high-risk infants. In sum, the urban population that investigators are studying is at high risk for asthma and respiratory diseases. In addition, investigators have preliminary evidence that prenatal pyrene exposure may be an important co-factor in the development of allergic immune responses.
Investigators plan to continue expanding data collection and analysis. Evaluation of the relationship between birth biomarkers and findings at age two and three is ongoing (i.e., associations between sensitization patterns at birth and development of total and allergen-specific IgE levels at age two years and frequency of respiratory symptoms/diagnosis of asthma are reevaluated). Relationships between outcomes and PAH/diesel and pyrene exposure prenatally and early postnatally are being assessed, again both at birth and early childhood. Evaluation of the contribution of nutritional status to onset of asthma is underway.
Publications and Presentations:
Please refer to the main center progress report.
Supplemental Keywords:Allergens/Asthma, Biochemistry, Children's Health, Disease and Cumulative Effects, Ecological Risk Assessment, Epidemiology, Human Health Risk Assessment, age-related differences, air pollutants, air toxics, airborne urban contaminants, airway disease, airway inflammation, ambient particulates, asthma, respiratory disease, nutrition. , Air, Scientific Discipline, Health, RFA, Susceptibility/Sensitive Population/Genetic Susceptibility, Biology, indoor air, Risk Assessments, genetic susceptability, Health Risk Assessment, Epidemiology, air toxics, Chemistry, Children's Health, particulate matter, Environmental Chemistry, Allergens/Asthma, Environmental Monitoring, tropospheric ozone, copollutants, exposure assessment, exposure and effects, environmental hazard exposures, diesel particulates, allergen, health effects, indoor air quality, inhalation, dust , nutrition, diesel exhaust particulates, diesel exhaust, dust mite, indoor environment, assessment of exposure, childhood respiratory disease, dust mites, human health risk, sensitive population, toxics, maternal exposure, epidemeology, cockroaches, home, infants, PM 2.5, respiratory, sensitive populations, biological response, airway disease, biological markers, children, stratospheric ozone, disease, exposure, human health, children's vulnerablity, asthma triggers, allergic response, asthma, human exposure, Human Health Risk Assessment, PM
Relevant Websites:
Columbia Center for Children's Environmental Health
http://epa.gov/ncer/centers/cecehdpr/98/columbia/
Progress and Final Reports:
2000 Progress Report
2001 Progress Report
Original Abstract
Main Center Abstract and Reports:
R827027 CECEHDPR - Columbia University School of Public Health
Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R827027C001 Community-Based Intervention: Reducing Risks of Asthma
R827027C002 Growth and Development/Evaluation of Carcinogenic Risks
R827027C003 Research Project on Asthma