Asthma, Heredity, and Air Pollution
Asthma is a common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchial spasms. Symptoms include wheezing, coughing, chest tightness, and shortness of breath. Dirty polluted air is known to cause respiratory inflammation. Now exposure to dirty air has been 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.
Many environmental risk factors have been associated with asthma development in children.
Environmental tobacco smoke, especially maternal cigarette smoking, is associated with high risk of asthma prevalence and respiratory infections. Poor air quality, from traffic pollution or high ozone levels, has been repeatedly associated with increased asthma morbidity and has a suggested association with asthma development that needs further research.
The new 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 Fresno and Palo Alto.
Regulatory T cells (Treg, sometimes known as suppressor T cells) are a specialized subpopulation of T cells that act to suppress activation of the immune system and thereby maintain immune system homeostasis and tolerance to self-antigens. When these cells are absent or not functioning correctly, the body auto immune system will respond incorrectly.
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.
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 stated: "Similarly, these new findings suggest the possibility of an inheritable effect from environmental pollution."
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.
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 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 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 held for children in both groups.
"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.
For further information: http://www.universityofcalifornia.edu/news/article/24239