New Research Suggests Pollution-Related Asthma May Start in the Womb

EMBARGOED 2-13-09 8pm

NEW YORK CITY/CINCINNATI—Children born in areas with increased traffic-related pollution may be at greater risk of developing asthma due to genetic changes acquired in the womb, according to new research from Columbia University Mailman School of Public Health and the University of Cincinnati (UC). The team reports its findings in the Feb. 16, 2009, issue of PLoS ONE.

In a study of umbilical cord blood from New York City children, researchers have discovered evidence of a possible new biomarker—an epigenetic alteration in the gene ACSL3—associated with prenatal exposure to polycyclic aromatic hydrocarbons (PAHs). These chemical compounds are created as byproducts of incomplete combustion from carbon-containing fuels, resulting in high levels in heavy-traffic areas. Exposure to PAHs has been linked to diseases such as cancer and childhood asthma.

Researchers say this finding provides a potential clue for predicting environmentally related asthma in children—particularly those born to mothers who live in high-traffic areas like Northern Manhattan and the South Bronx when pregnant.

This is the first study to examine the effects of prenatal ambient air pollutant exposure on epigenetic changes linked to asthma. Epigenetic changes may disrupt the normal functioning of genes by affecting their expression but do not cause structural changes or mutations in the genes.

For this study, UC researchers teamed with Columbia’s Mailman School of Public Health to study the relationship between prenatal PAH exposure and childhood asthma, hypothesizing that transplacental exposure to PAHs could “reprogram” fetal genes and lead to airway inflammation or asthma during childhood. Epigenetic reprogramming is the result of an organism’s genes interacting with the environment.

“Our data support the concept that environmental exposures can interact with genes during key developmental periods to trigger disease onset later in life, and that tissues are being reprogrammed to become abnormal later,” says Shuk-mei Ho, PhD, senior author of the paper and chair of UC’s Department of Environmental Health and the director of the Center for Environmental Genetics.

“This research is aimed at detecting early signs of asthma risk so that we can better prevent this chronic disease that affects as many as 25 percent of children in Northern Manhattan and elsewhere,” adds Frederica Perera, DrPH, professor of environmental health sciences and director of the Columbia Center for Children’s Environmental Health (CCCEH) at the Mailman School of Public Health and co-first author on the paper.

Using biological specimens from the CCCEH birth cohort of mothers and children living in Northern Manhattan and the South Bronx, UC scientists analyzed umbilical cord white blood cell samples from 56 children for epigenetic alterations related to prenatal PAH exposure. (The mothers’ exposure to PAHs was monitored during pregnancy using backpack air monitors).

The researchers found a significant association between changes in ACSL3 methylation—a gene expressed in the lung—and maternal PAH exposure. ACSL3 also was associated with a parental report of asthma symptoms in the children prior to age 5.

With confirmation in further studies, researchers say, changes in the ACSL3 gene could serve as a novel biomarker for early diagnosis of pollution-related asthma.

“This study provides a blueprint for the discovery of epigenetic biomarkers relevant to other investigations of exposure-disease relationships in birth cohorts,” says Wan-yee Tang, PhD, a UC research scientist and a co-first author on the paper.

“Understanding early predictors of asthma is an important area of investigation,” adds Rachel Miller, MD, director of the CCCEH asthma project and study co-author, “because they represent potential clinical targets for intervention.”

The CCCEH birth cohort was launched in 1998 to study the effects of prenatal exposure to common urban pollutants on the health of mothers and their children. Children in the cohort were born to non-smoking Dominican and African-American women in Northern Manhattan or the South Bronx and follow-up is ongoing.

Funding for the multi-institutional study comes from the National Institute of Environmental Health Sciences (NIEHS), the U.S. Environmental Protection Agency (EPA) and private foundations. UC’s Linda Levin, PhD and Columbia University Mailman School’s Julie Herbstman, PhD, and Deliang Tang, MD, DrPH, were also co-authors of the study.

This research is part of the Columbia Center for Children’s Environmental Health, one of 11 National Centers funded by the NIEHS and EPA and one of three Disease Investigation through Specialized Clinically-Oriented Ventures In Environmental Research (DISCOVER) Centers funded by the NIEHS. The CCCEH is a leading research organization dedicated to understanding and preventing environmentally related disease in children.

This research is also part of UC’s Center for Environmental Genetics, one of 16 environmental centers funded by the NIEHS. It supports state-of-the-art core facilities and technologies needed to conduct innovative research that focuses on how environmental agents interact with genetic and epigenetic factors to influence disease risk and outcome.

NOTE TO EDITORS: High-resolution images of Frederica Perera, DrPH, and Rachel Miller, MD, are available by emailing [email protected]. High-resolution images of Wan-yee Tang, PhD, and Shuk-mei Ho, PhD, are available for download at www.healthnews.uc.edu.

The Columbia Center for Children’s Environmental Health – part of the Mailman School of Public Health at Columbia University – is a leading research organization dedicated to understanding and preventing environmentally related disease in children. Founded in 1998, the Center conducts research in New York City, including the study of mothers and children in Northern Manhattan and South Bronx, a World Trade Center Study, as well as Krakow, Poland, and Chongqing, China. Its mission is to improve the respiratory health and cognitive development of children and to reduce their cancer risk by identifying environmental toxicants and conditions related to poverty that increase their risk of disease. In NYC, the Center collaborates with residents and partner organizations in Washington Heights, Harlem and the South Bronx to share research findings with the local communities in ways that are meaningful and usable in daily life. (www.ccceh.org)

About the Mailman School of Public Health
The only accredited school of public health in New York City and among the first in the nation, Columbia University Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting millions of people locally and globally. The Mailman School is the recipient of some of the largest government and private grants in Columbia University’s history. Its more than 1000 graduate students pursue master’s and doctoral degrees, and the School’s 300 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as infectious and chronic diseases, health promotion and disease prevention, environmental health, maternal and child health, health over the life course, health policy, and public health preparedness. www.mailman.columbia.edu