Grantee Research Project Results

2005 Progress Report: Biomarkers of PAH Exposure and Asthma in an Inner City Birth Cohort

EPA Grant Number: R832096
Title: Biomarkers of PAH Exposure and Asthma in an Inner City Birth Cohort
Investigators: Miller, Rachel L. , Whyatt, Robin M. , Perera, Frederica P. , Lendor, Cynthia
Current Investigators: Miller, Rachel L. , Whyatt, Robin M. , Perera, Frederica P.
Institution: Columbia University in the City of New York
EPA Project Officer: Aja, Hayley
Project Period: December 1, 2004 through December 31, 2007
Project Period Covered by this Report: December 1, 2004 through December 31, 2005
Project Amount: $749,872
RFA: Application of Biomarkers to Environmental Health and Risk Assessment (2004) RFA Text |  Recipients Lists
Research Category: Biomarkers to Environmental Health and Risk Assessment

Objective:

Living in areas with high volumes of traffic has been associated with asthma in children. Research suggests that polycyclic aromatic hydrocarbons (PAHs) may be the biologically active components that increase the risk of airway allergic inflammation that characterizes most asthma. Our recent data suggest that the PAH pyrene may promote symptoms by upregulating the production of the antibody that typifies asthma, namely immunoglobulin E (IgE). But despite such progress, direct associations between exposure to PAHs, biomarkers for PAH exposure, biomarkers for biological effects of such exposures, and the onset of immunological or clinical signs of asthma have not been demonstrated yet.

We hypothesized that biomarkers for PAH exposure at age 5 years will help predict increased risk for asthma. The objectives of this research project are to: (1) determine whether increased PAH levels in the air or increased PAH DNA adducts in the blood of 5-year-old children are associated with increased urinary PAH metabolites in an inner city birth cohort; (2) determine whether increased urinary PAH metabolites are associated with early indicators of asthma or allergy; and (3) determine whether the presence of increased urinary PAH metabolites increases the association between environmental levels of allergens in home dust and indicators of asthma or allergy.

Our strategy is to take advantage of an established Northern Manhattan birth cohort as part of the Columbia Center for Children’s Environmental Health in which multiple environmental exposures, biomarkers, and health outcomes already are being measured prospectively.

Progress Summary:

Recruitment of Subjects

We have recruited 113 subjects and our goal is 200 subjects.

Analyses for Urinary PAH Metabolites

The Centers for Disease Control and Prevention laboratories have analyzed 48 urine samples as of January 1, 2006. Each subject’s sample was tested for a set of 24 PAH metabolites (Table 1). The urinary metabolites are measured by using liquid-liquid extraction into pentene using the Gilson 215 Liquid Handler (Gilson Inc., Middleton, WI). The sample extracts will be evaporated under a chemical fume hood to remove the pentene solvent. Finally, the extracts are reconstituted in toluene and derivatized to yield the trimethysiloxane derivatives. Analytical determination of the target analytes are performed by gas chromatography isotope-dilution high-resolution mass spectrometry employing a MAT95XP (ThermoFinnigan MAT, Bremen, Germany) instrument.

We found that 11 out of 24 PAH metabolites (Table 1) yielded results above the limits of detec­tion. The following metabolites had values below the limits of detection: 1-hydroxy­benzo(c)phenanthrene, 2-hydroxybenzo(c)phenanthrene, 3-hydroxybenzo(c)phenanthrene, 1-hy­droxybenz(a)anthracene, 3-hydroxybenz(a)anthracene, 9-hydroxybenz(a)anthracene, 1-hydroxy­chrysene, 2-hydroxychrysene, 3-hydroxychrysene, 4-hydroxychrysene, 6-hydroxychrysene, 3-hydroxybenzo(a)pyrene, 7-hydroxybenzo(a)pyrene, and 3-hydroxyfluoranthene. The concentra­tions of the analytes are given as creatinine adjusted concentrations (ng/g creatinine), determined by enzymatic in vitro assay using clinical chemistry analyzers, Creatinine Plus (Roche Diagnos­tic, Indianapolis, IN). Creatinine is a biomarker for kidney function. Table 1 shows a summary of the mean concentrations of each metabolite for the 48 subjects tested.

Table 1. PAH Metabolite Levels (Creatinine Adjusted)

PAHs (metabolite)	Mean (range) ng/g
1-hydroxypyrene	183.5 (28.9-504.5)
1-hydroxynaphthalene	8679.5 (535.9-88748.2)
2-hydroxynaphthalene	6419.9 (1938.1-28849.4)
2-hydroxyfluorene	294.8 (100.1-546.1)
3-hydroxyfluorene	131.2 (31.9-318.5)
9-hydroxyfluorene	359.7 (93.6-1455.9)
1-hydroxyphenanthrene	217.7 (38.5-463.4)
2-hydroxyphenanthrene	71.6 (18.1-234.9)
3-hydroxyphenanthrene	216.2 (25.2- 545.6)
4-hydroxyphenanthrene	54.2 (9.3-234.7)
9-hydroxyphenanthrene	32.4 (9.3-230.9)

As shown in Table 1, a wide distribution of multiple PAH urinary metabolites were detected. Future analyses will involve comparison of these levels with outcomes of interest.

Future Activities:

We will continue sample collection, and more samples will be analyzed in the near future. We have reached our goal of sample collection for 100 samples in the first year to remain on schedule within the award period.

Journal Articles:

No journal articles submitted with this report: View all 10 publications for this project

Supplemental Keywords:

polycylic aromatic hydrocarbons, PAHs, urinary metabolites, airborne particulate matter, asthma indices, asthma triggers, atmospheric aerosol particles, atmospheric particulate matter,, RFA, Health, Air, Scientific Discipline, Susceptibility/Sensitive Population/Genetic Susceptibility, Health Risk Assessment, Risk Assessments, particulate matter, genetic susceptability, Environmental Chemistry, Allergens/Asthma, Environmental Monitoring, sensitive populations, health risks, inner city, chemical characteristics, airway inflammation, asthma indices, asthma triggers, asthma, Manhattan, aerosol composition, airborne particulate matter, human exposure, ambient air monitoring, environmental risks, second hand smoke, atmospheric particles, atmospheric aerosol particles, particulates, exposure, atmospheric particulate matter, airborne pollutants, allergic response, ambient air quality, air pollution, human health risk, human susceptibility, PAH, air toxics, inhalation, airway disease

Progress and Final Reports:

Original Abstract

2006 Progress Report

2007 Progress Report

Final Report