How Ozone Harms Lungs

Researchers have discovered why ozone, a common urban air pollutant, causes airway irritation and wheezing. The finding suggests new targets for medications to treat people suffering from wheezing, coughing and shortness of breath.

Ozone is formed in the presence of sunlight from pollutants emitted by vehicles and other sources. An analysis by the U.S. Environmental Protection Agency found that ozone costs the nation $5 billion a year in premature deaths, hospitalizations and school absences. Inhaling ozone can irritate the airways and cause wheezing, particularly in children and adults who have asthma and chronic obstructive lung disease. However, the biological mechanisms responsible for ozone’s effects have been poorly understood.

A sugar called hyaluronan was recently shown to play a central role in the response to lung injury. A team of scientists led by Dr. Stavros Garantziotis of NIH’s National Institute of Environmental Health Sciences (NIEHS) and Dr. John Hollingsworth at Duke University Medical Center set out to investigate whether hyaluronan plays a role in the lung’s response to ozone.

The researchers reported in the Journal of Biological Chemistry on February 13, 2009, that mice exposed to ozone produced high amounts of hyaluronan in their lungs. The scientists next used genetically engineered mice that were deficient in either CD44—the major cell-surface receptor for hyaluronan—or a molecule known to help hyaluronan bind to CD44. Both kinds of mice had elevated hyaluronan when they were exposed to ozone, but were protected from its damaging effects.

The researchers also showed that they could protect mice from the effects of ozone by pretreating the mice with a protein that binds hyaluronan.

“We found hyaluronan to be directly responsible for causing the airways to narrow and become irritated,” Hollingsworth said. “We believe this may contribute to asthma symptoms in humans as well.”

Although more research is needed before these findings can be translated to humans, the researchers are optimistic that this discovery could lead to successful treatments for people with asthma.