Breath Test Offers Hope For Early Detection Of Lung-bacteria Growth In Cystic Fibrosis

By using a chemical analysis method developed for air-pollution testing, UCI chemists and pediatricians have found that people with cystic fibrosis exhale higher concentrations of sulfur compounds from their lungs than do people who don't have the disease.

These sulfur compounds, called sulfides, are known to be produced by bacteria, and lung disease in cystic fibrosis is accompanied by bacterial infections that cause chronic damage. The researchers found that the worse the pulmonary function in the cystic fibrosis patient, the higher the sulfide concentration in the breath sample, suggesting an increased amount of bacterial growth in the lungs.

"Early detection and antibiotic therapy has been promoted as a means to delay chronic bacterial lung growth and prolong life, and breath analysis may be an effective first step toward treatment," said Dr. Dan Cooper, a pediatric pulmonologist at UCI Medical Center, who led the study with F. Sherwood Rowland, the Donald Bren Research Professor of Chemistry, and fellow chemistry professor Donald Blake. "In the long term, these findings on sulfide levels also might help uncover some of the underlying mechanisms of the disease."

Study results appear this week in the early online version of the Proceedings of the National Academy of Sciences.

Cystic fibrosis is a genetic disease marked by an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. Although many lung bacteria are prevalent with the disease, in teens and adults, the Pseudomonas aeruginosa bacteria appears as the most prevalent cystic fibrosis pathogen and is strongly associated with respiratory deterioration and mortality. Over time, the bacteria transforms into treatment-resistant variants, and early detection is seen as key for aggressive antibiotic treatments to delay its growth.

In the study, graduate student Michael Kambourse, working with Blake and Rowland, examined exhaled breath from people with and without cystic fibrosis using laboratory methods developed for their atmospheric chemistry work. In that work, they measure the levels of trace gases in excess of the parts-per-billion range that contribute to local and regional air pollution. Their research group is one of the few in the world recognized for its ability to measure accurately at such small amounts.

In analyzing the breath samples, the researchers monitored levels of three sulfides in the cystic fibrosis patients -- carbonyl sulfide, dimethylsulfide and carbon disulfide. Significantly, they found that cystic fibrosis patients exhaled carbonyl sulfide (OCS) at rates up to 2½ times higher than people who don't have the disease, making it an attractive target for future breath analysis.

The study determined that the regular air the test subjects breathed in had about 600 parts-per-trillion volume (pptv) of OCS. The non-cystic fibrosis subjects exhaled a mean average of 350 pptv of OCS, meaning that about 250 pptv of OCS was removed from the inhaled air. The cystic fibrosis subjects exhaled a mean average 490 pptv of OCS, and the three individuals with the weakest pulmonary function exhaled as much as 800 pptv, producing an excess of OCS. This suggests a substantial OCS source, probably bacterial, exists in their lungs, in addition to poorer processing of inhaled gas.

The researchers are continuing their breath-analysis work in areas of autism, diabetes and oral glucose tolerance testing. Most relevant are ongoing studies in which they are testing the profile of gases produced by bacteria, like P. aeruginosa.

"The ultra-trace gas breath analysis techniques used in this study not only show potential for cystic fibrosis treatment but possess wide-ranging clinical possibilities," Blake said.

The National Institutes of Health, the Cystic Fibrosis Foundation and the Joan Irvine Smith and Athalie R. Clarke Foundation supported the study.

About Cystic Fibrosis: Cystic fibrosis is a genetic disease affecting approximately 30,000 children and adults in the United States. A defective gene causes the body to produce an abnormally thick, sticky mucus that clogs the lungs and leads to life-threatening lung infections. These thick secretions also obstruct the pancreas, preventing digestive enzymes from reaching the intestines to help break down and absorb food. The mucus also can block the bile duct in the liver, eventually causing permanent liver damage in approximately six percent of people with the disease. Because of improvements in antibiotics, exercise and diet, people with cystic fibrosis on average live into their 30s. (Source: Cystic Fibrosis Foundation)