Chronic alcohol abuse causes a profound deficiency of the antioxidant glutathione in the lungs, generating a marked susceptibility to serious lung diseases, according to research at the School of Medicine and the VA Medical Center.

Lowered glutathione levels can be as deadly to the lungs of alcohol abusers as alcohol itself can be to their livers and other organs, according to David Guidot, associate professor of medicine. Guidot explained how glutathione depletion affects the lungs at the Experimental Biology ’02 meeting in New Orleans on April 24.

Until six years ago, when Emory scientist Marc Moss first identified the connection between alcohol abuse and lung damage, scientists had not associated the two, even though alcohol’s ill effects on the liver, brain and other organs were well recognized.

“We now know that as many deaths occur every year from alcohol abuse related to lung injury as occur from alcohol abuse and liver disease or alcohol abuse and traffic accidents,” Guidot said.

Scientists previously had not focused on the connection between alcohol and lung disease because the causal relationship is indirect, unlike the direct effect of alcohol on the liver, Guidot explained. He began studying the effects of glutathione depletion on the lungs while reviewing the mechanisms of alcohol toxicity in other organs.

The body manufactures glutathione—a strong antioxidant molecule—from amino acids, which are the building blocks of proteins. Individuals with reasonably good diets maintain an adequate supply of glutathione, which constantly is being used up and replenished.

Although glutathione is manufactured in a variety of organs and tissues, including the liver, the lungs are particularly dependent on glutathione for protection from oxidative damage, especially in the small airways where breathing takes place. The lack of glutathione in the lungs leads to a variety of abnormalities, said Guidot, including: damage to the epithelial cells and fluid that line the lungs; changes in the barrier function of lung cells; and increased susceptibility to apoptosis, or cell death in the lungs.

These abnormal cell changes caused by chronic alcohol abuse leave the lung vulnerable to injury when a serious illness such as sepsis or pneumonia occurs. “Heavy drinking and its relationship to lung disease is like driving on the highway without a seat belt,” Guidot said. “It’s risky behavior, but it doesn’t cause injury unless you get in an accident. Alcohol doesn’t cause lung disease unless you get sick; then the lungs are less able to respond to the challenges of infection.”

The cure for alcohol-induced lung damage is not as simple as just taking extra doses of glutathione, Guidot added, because an acute lung infection often is the first sign of damage.

“If your house is on fire, it’s too late to install a smoke detector,” he said. Glutathione depletion cannot be quickly reversed. Only after the immediate illness is addressed can physicians consider treating a patient for alcoholism and consider long-term glutathione therapy.

By studying the mechanisms of glutathione damage, Guidot and his colleagues hope to design more effective therapies for preventing and treating the effects of chronic alcohol abuse.