Breath Analysis: Analytical Methodologies and Clinical Applications

General metabolic conditions and developing diseases in human beings can very often be traced by evaluating chemical markers in exhaled air. This is principally due to an almost instantaneous equilibrium between the pulmonary blood and the air in the alveoli of the lung. Since Hippocrates' time, physicians have known that human breath might provide sound information on health conditions and in a fewcases even a diagnosis. In fact, a skilled clinician can easily recognize, for example, the typical fruity smell in diabetes, the musty and fishy smell of advanced liver disease, the urinelike smell of kidney failure, and the putrid smell of a lung abscess. Nevertheless, breath analysis has taken a long time to become a useful diagnostic tool after the pioneering work that demonstrated that large amount of acetone was excreted through the lung in patients suffering from diabetes mellitus. The composition of human breath was also found to be far more complex than formerly believed: by concentrating hundreds of compounds in a cryogenic trapping system and analyzing the sample by gas chromatography (GC) coupled with mass spectrometry (MS), has allowed the number of compounds to be increased to more than 1000. Further progress was achieved by coupling the diagnosis of metabolic disorders and of respiratory diseases to studies by which many chemicals of either clinical or toxicological significance were determined in breath. At present, typical routine applications of breath tests include the evaluation of the ethanol blood level, for example, for breathalyser tests, and the detection of 13C-urea for the diagnosis of the Helicobacter pylori infection. Breath analysis is thus an attractive procedure for biochemical monitoring in order to follow the evolution of other diseases and malfunctions of the human body. It can even help predicting such diseases, particularly so since it is not an invasive procedure and can be applied to a wide range of compounds. Furthermore, the analysis is rather simple since the matrix is less complex than blood or urine. One of the major drawbacks of diagnostic breath analysis is related to the difficulties in demonstrating the correlation between identified marker compounds with a pathology, since in most cases the specific metabolic pathways are unknown. Moreover, substance concentrations in the exhaled air change under various conditions and often they are at the trace level that makes sampling a very critical step. An overview is presented of the analytical techniques applied to the chemical characterization of breath samples as well as of the most promising clinical applications with emphasis on the state-of-the-art and possible future developments.