The specific aims of this study are to: 1) identify and quantify breath sulfur-and nitrogen-containing biomarkers of liver dysfunction; 2) generate a library of these breath biomarkers for various liver diseases; 3) investigate whether increased free radical generation, as measured by levels of breath ethane, occurs as a result of a 4-hour exposure to occupational levels of tetrachlorethylene; 4) investigate whether CNS toxicity, as measured by airway occlusion pressure, occurs as a result of a 4 hour exposure to occupational levels of tetrachloroethylene; and 5) demonstrate that breath biomarkers can be used to identify people who have liver dysfunction as a result of occupational exposure to tetrachloroethylene. During the period December 1, 1995 to November 30, 1996, breath and blood samples were collected from an additional 75 normal human subjects. On the basis of the complete patient population we have identified that three sulphur containing compounds (carbonyl sulfide, dimethyl sulfide, and carbon disulfide), and two hydrocarbons (isoprene and ethane) in human breath that can be used as indicators of liver disease. Various statistical methods (ANOVA, multiple regression analysis, logistic regression analysis, t Test, Scheffe test, Bonferroni multiple comparison test, nonparametric tests) have been used to examine the use of these breath biomarkers to distinguish between normal human subjects and patients with liver disease. We have also stratified patients liver diseases into two groups: hepatocellular diseases, and diseases of the bile duct. Briefly, the results of our studies to date are as follows: isoprene can be used to distinguish between normal human subjects and patients with diseases of the bile duct; carbonyl sulfide can be used to distinguish between normal human subjects and patients with diseases of the bile duct and between normal human subjects and patients with hepatocellular diseases; dimethyl sulfide can be used to distinguish between normal human subjects and patients with liver disease; and carbon disulfide can be used to distinguish between normal human subjects, patients with diseases of the bile duct, and patients with hepatocellular diseases. Carbonyl sulfide, carbon disulfide and isoprene can be used to stage liver disease.
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