asthma gene

Researchers at Stanford University and the University of California, Berkeley, have researched asthma causes and come up with direct evidence that the asthma gene in children is affected by air pollution. The researchers studied a group of 181 children with and without asthma in the California cities of Fresno and Palo Alto. Exposure to air pollution was found to suppress the immune system's regulatory T cells (known as Treg for short). Treg cells have the job of putting the brakes on the immune system so it doesn't react to harmless substances (remember, asthma triggers are harmless to those without asthma). This decreased level of Treg function was linked to greater severity of asthma symptoms and lower lung capacity in the children.

"When it came out that cigarette smoke 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, paediatrician 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 pollution." Forty-one children came from the Fresno Asthmatic Children's Environment Study (FACES), which is led by Dr. Ira Tager, professor of epidemiology at UC Berkeley's School of Public Health, and 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 deny."

Fresno was chosen because it is located in California's Central Valley, where trapped hot air mixes with air pollution from traffic and agriculture to create high levels of air pollution. 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 Capital of California." The researchers compared the participants from Fresno with 80 children, half with asthma and the half without, in the relatively low-pollution city of Palo Alto. 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 the blood. 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 by-product 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 asthma symptoms 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 researchers found a link between increased exposure to PAH with specific changes in a gene called Foxp3, which triggers Treg cell development. The change effectively disables the gene's function, leading to reduced levels of Treg cells. The connection between Treg function and the severity of asthma symptoms held for children in both groups. While previous studies have found associations between pollution, particularly car exhausts, and an increased risk of developing asthma, few have gone into such detail on the cells, molecules, and genes involved.

"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."

Source: Nadeau K et al Ambient air pollution impairs regulatory T-cell function in asthma Journal of Allergy and Clinical Immunology October 2010.