Free Radicals Implicated In Impaired Lung Function

BUFFALO, N.Y. -- High levels of toxic free radicals in the blood can literally take one's breath away.

Epidemiologists at the University at Buffalo have found that a miniscule increase above an acceptable threshold of a substance in the blood that indicates cell damage caused by bombardment from free oxygen molecules (a condition defined as oxidative stress) reflects damage to the lungs equivalent to the effect of 3-5 years of aging, or of approximately 15-20 pack years of smoking.

"It is well known that oxidative stress plays a role in atherosclerosis, cancer and other chronic conditions," said Holger Schunemann, M.D., UB research assistant professor and lead author on the study. "But information on the relation of blood levels of oxidants and antioxidants with lung function is sparce. Our results suggest that free-radical damage also is associated with narrowing of the pulmonary airways."

The study is one of the first investigations of the relationship between lung function, oxidative stress caused by free oxygen molecules, also known as free radicals, and blood levels of antioxidants, substances that can help prevent free-radical damage.

The study is published in the Dec. 2 issue of the American Journal of Epidemiology, which is dedicated to research by faculty members and graduates of the UB Department of Social and Preventive Medicine.

The study involved 132 non-smoking subjects between the ages of 37 and 73 years, selected randomly from two counties in Western New York. Researchers assessed lung function by measuring the volume of air participants could force from their lungs during a one-second exhale.

They also collected blood samples from all participants, and measured levels of thiobarbituric acid-reactive substances, or TBARS, a marker of oxidative stress, and levels of several compounds thought to protect against oxidative stress: red-cell glutathione, glutathione peroxidase, trolox equivalent antioxidant capacity and total serum bilirubin, the main pigment found in bile. Schunemann said both laboratory and clinical studies have found that bilirubin may function as an antioxidant.

Results showed that oxidative stress was associated with obstruction of the pulmonary airways. Higher levels of TBARS and of red-cell glutathione were associated with lowered lung volume, even though the effects observed were relatively small. Schunemann said there has been conflicting evidence on the antioxidant activity of red-cell glutathione. In this study, it was associated with lowered pulmonary functioning.

Bilirubin was the only potential antioxidant measured that showed a positive relationship to lung function. Researchers are continuing their analysis of the relationship between lung function, oxidative stress and antioxidant vitamins.

"We know that obstruction of the pulmonary airways, as revealed by test of lung capacity, is a strong predictor of cardiovascular disease and all-cause mortality," said Schunemann.

"These findings suggest a possible role of oxidants and antioxidants in determining lung function, and that these substances could represent, in part, the physiological link between impaired expiratory lung function and increased risk of death from chronic diseases, such as heart disease and lung cancer."

Additional researchers on the study were Paula Muti, M.D.; Jo L. Freudenheim, Ph.D.; and Maurizio Trevisan, M.D., of the UB Department of Social and Preventive Medicine; Donald Armstrong, Ph.D., and Richard Browne, of the UB Department of Clinical Laboratory Science, and Robert A. Klocke, M.D., of the UB Department of Medicine.