2010-10-06 01:15:24 UTC
Air pollution alters immune function, worsens asthma symptoms
By Sarah Yang, Media Relations | 05 October 2010
BERKELEY — Exposure to dirty air is linked to decreased function of a
gene that appears to increase the severity of asthma in children,
according to a joint study by researchers at Stanford University and
the University of California, Berkeley.
While air pollution is known to be a source of immediate inflammation,
this new study provides one of the first pieces of direct evidence
that explains how some ambient air pollutants could have long-term
Researchers have linked exposure to dirty air to changes in a gene
that, in turn, is connected to more severe asthma symptoms. The
findings, published in the October 2010 issue of the Journal of
Allergy and Clinical Immunology, come from a study of 181 children
with and without asthma in the California cities of Fresno and Palo
The researchers found that air pollution exposure suppressed the
immune system's regulatory T cells (Treg), and that the decreased
level of Treg function was linked to greater severity of asthma
symptoms and lower lung capacity. Treg cells are responsible for
putting the brakes on the immune system so that it doesn't react to
non-pathogenic substances in the body that are associated with allergy
and asthma. When Treg function is low, the cells fail to block the
inflammatory responses that are the hallmark of asthma symptoms.
The findings have potential implications for altered birth outcomes
associated with polluted air, much the same as those noted for the
effects of cigarette smoke.
"When it came out that cigarettes can cause molecular changes, it
meant the possibility that mothers who smoked could affect the DNA of
their children during fetal development," said study lead author Dr.
Kari Nadeau, pediatrician at Stanford's Lucile Packard Children's
Hospital and an assistant professor of allergy and immunology at
Stanford's School of Medicine. "Similarly, these new findings suggest
the possibility of an inheritable effect from environmental
Forty-one participants came from the Fresno Asthmatic Children's
Environment Study (FACES), a longitudinal study led by principal
investigator Dr. Ira Tager, professor of epidemiology at UC Berkeley's
School of Public Health, and co-principal investigator S. Katharine
Hammond, UC Berkeley professor and chair of environmental health
sciences. The researchers also recruited 30 children from Fresno who
did not have asthma.
"I'm not aware of any other studies that have looked at how chemicals
can alter cells so early in the regulatory process, and then connected
that effect to clinical symptoms," said Tager. "There are people who
still question the direct link between air pollution and human health,
but these findings make the health impact of pollutants harder to
Fresno was chosen because it is located in California's Central
Valley, where trapped hot air mixes with high traffic and heavy
agriculture to create some of the highest levels of air pollution in
the country. It is also a region known for its high incidence of
asthma: Nearly one in three children there have the condition, earning
Fresno the nickname, "The Asthma Capitol of California."
The researchers compared the participants from Fresno with 80
children, half with asthma and half without, in the relatively low-
pollution city of Palo Alto, Calif. The children were matched by age,
gender and asthma status, among other variables. The children were
tested for breathing function, allergic sensitivity and Treg cells in
Daily air quality data came from California Air Resources Board
monitoring stations. The researchers calculated each child's annual
average exposure to polycyclic aromatic hydrocarbons (PAH), a
byproduct of fossil fuel and a major pollutant in vehicle exhaust.
The study found that the annual average exposure to PAH was 7 times
greater for the children in Fresno compared with the kids in Palo
Alto. Levels of ozone and particulate matter were also significantly
higher in Fresno.
Not surprisingly, the study found that the children in Fresno had
lower overall levels of Treg function and more severe symptoms of
asthma than the children in Palo Alto. For example, the non-asthmatic
children in Fresno had Treg function results that were similar to the
children with asthma in Palo Alto.
The study authors correlated increased exposure to PAH with
methylation of the gene, Forkhead box transcription factor (Foxp3),
which triggers Treg cell development. Methylation effectively disables
the gene's function, leading to reduced levels of Treg cells. The
connection between Treg function and the severity of asthma symptoms
was true for children in both groups.
While previous studies have found associations between pollution –
especially motor vehicle exhaust – and an increased risk of developing
asthma, few have traced its molecular pathway so completely, the study
"The link between diesel exhaust and asthma could simply have been
that the particulates were irritating the lungs," said Nadeau. "What
we found is that the problems are more systemic. This is one of the
few papers to have linked from A to Z the increased exposure to
ambient air pollution with suppressed Treg cell levels, changes in a
key gene and increased severity of asthma symptoms."
The researchers noted that Treg cells are important for other
autoimmune disorders, so the implications of this study could go
Other co-authors of the study are Dr. John Balmes, UC Berkeley
professor of environmental health sciences; Elizabeth Noth and Boriana
Pratt, UC Berkeley researchers at FACES; and Cameron McDonald-Hyman,
research assistant at Stanford University's School of Medicine.
The National Institutes of Health, U.S. Environmental Protection
Agency, the American Lung Association and the Mickey Leland National
Urban Air Toxics Research Center helped support this research.