Alcohol abuse is rampant in the U.S., estimates run as high as 1 in 20 adults, and cost tens of billions of dollars in treatment and economic loss. One especially intransigent problem has been alcohol-induced organ disease such as alcoholic hepatitis and cirrhosis. These diseases can currently be diagnosed, but this requires invasive procedures such as liver biopsy, which are typically not applied until the disease process is in a late stage. Late detection of organ disease leads to substantially worse outcomes. Organs affected by alcohol, such as the liver, are highly metabolically active, and the compounds produced by the organs are often volatile and therefore appear in the breath. Breath odor profiles are altered by disease processes, for example the clinical odor syndrome called fetor hepaticus in liver disease, and are composed of many compounds which are altered by many metabolic processes, not just the disease process. To determine the exact disease process responsible for changes in breath odor, many compounds must be measured simultaneously. Odor analysis instruments are capable of profiling complex mixtures of volatile organic compounds (VOCs) at parts-per-billion concentrations. Odor of breath and urine have long been recognized as clinically valuable but have proven to be impractical due to the complexity of chemical analyzers and difficulties in interpreting the complex mixtures of compounds. This project will investigate the feasibility of early detection of alcohol induced organ damage using a new, compact and simplified gas analyzer technology based on gas chromatography and differential ion mobility spectrometry. This technology operates at ambient pressures, does not require a carrier gas supply, and can be configured with a non-radioactive ionizer unlike typical laboratory analyzers. This instrument creates profiles of the complex mixtures of compounds present in a gas sample which can be used to assess patterns of compounds. Recent work has identified several breath marker compound candidates and these will be mapped with the gas analyzer in the breath of patients with alcoholic liver disease. Patterns of the compounds detected in patient breath will be tested against the patterns found in breath of healthy subjects to build an algorithm for detecting alcoholic liver disease. The project will proceed in two stages The first will confirm that the analyzer can detect the candidate biomarkers of alcoholic liver disease and match those candidates to compounds observed in the breath of patients. The second stage will use the sets of confirmed compounds to test the ability of the technology to distinguish another set of patients from healthy controls. Breath analysis is almost completely noninvasive and shows great promise for health surveillance. This project will apply it to a pernicious clinical and social problem, alcohol induced organ damage. Success will lead to a sensitive, specific and timely clinical tool in the fight against the consequences of alcohol abuse.
Alcohol abuse causes organ damage that is difficult to detect until late stages of the disease, at which point effective treatment is difficult or impossible. Ths project will develop the use of a novel electronic nose technology to analyze trace compounds in breath as a means to detect the onset of organ damage from alcohol as early as possible and allow for the most prompt intervention treatment.
