Investigation into the Utility of Gas Signature Detection as a Diagnostic Tool for Infectious Diseases
Abstract
This thesis will explore the diagnostic and monitoring potential of exhaled breath for various infectious diseases. The specific infections studied include Borrelia hermsii, salmonella enterica, and two forms of endotoxin. Samples of breath were collected from mice both individually and in groups as well as from rats. The animals were awake and restrained in a breath sample tower for a majority of the studies. One study was also conducted using awake unrestrained rats in a glass bulb that was designed for breath sample collection by the Rowland Blake lab. In addition to the breath samples, feces samples were obtained from mice infected with salmonella enterica and incubated in bioreactors from which the headspace was collected for analysis. Samples were collected in evacuated stainless steel canisters. Blank samples were also collected to determine concentrations in the air used during sampling.
All samples, excluding the feces samples, were analyzed for carbon monoxide and carbon dioxide concentrations using gas chromatography. Several samples were also analyzed for various volatile organic compounds using the Rowland Blake non-methane hydrocarbon gas chromatography system. The results of the gas chromatography measurements were analyzed to determine if differences existed between infected and uninfected samples throughout each study. This was accomplished statistically, as well as visually using plots.
The results of the Borrelia and endotoxin studies revealed a significant increase in the ratio of CO/CO2 in the breath of the infected mice and rats, with a dose response being observed for the endotoxin study. Upon treatment, the ratio of CO/CO2 returned to normal within several hours of antibiotic administration. For the salmonella study, carbonyl sulfide, dimethyl disulfide, carbon disulfide, heptanal, i-propylbenzene, and isoprene were identified in the feces; and acetone, isopropanol, and a gas of unknown identity in the breath. The endotoxin study identified i-pentane in the breath of mice. The study with rats identified two gases, acetone and an unknown gas. The results of these studies suggest that exhaled breath has potential for monitoring of the infections studied, however further studies are needed to explore the diagnostic potential.