Due to the great potentials in clinical diagnosis, disease state monitoring, and environmental exposure assessment, the breath test is becoming one of the most desirable noninvasive procedures for clinical diagnostics. This article reviews the technical aspects of breath analysis including sample collection, analyte preconcentration, vapor desorption, and various measurement techniques, as well as some recent developments in the field. Because the exhaled breath is affected by the composition of ambient air, the elimination of background influence on the analyte detection is also discussed. Both advantages and major obstacles of breath analysis techniques in clinical practice are presented and summarized. This article not subject to United States Copyright law.

Current Status of Methods and Techniques for Breath Analysis

Systems and methods for analyzing glucose present in exhaled breath condensate (EBC). In certain embodiments, electrochemical- or coulometnc-based sensing technologies are used to analyze EBC for the presence and/or concentration of glucose. Based on the detected glucose m EBC, the subject invention provides systems and methods for non-mvasive, accurate assessment of blood glucose levels.

Condensate glucose analyzer

The present invention includes a method and apparatus for monitoring drug compliance by detecting markers, such as odors, upon exhalation by a patient after medication is taken, wherein such markers result either directly from the medication itself or from an additive combined with the medication. In the case of olfactory markers, the invention preferably utilizes electronic sensor technology, such as the commercial devices referred to as 'artificial noses' or 'electronic noses', to non-invasively monitor compliance. The invention further includes a reporting system capable of tracking compliance (remote or proximate) and providing the necessary alerts.

Marker detection method and apparatus to monitor drug compliance

Volatile organic compounds (VOCs) in exhaled breath originate from current or previous environmental exposures (exogenous compounds) and internal metabolic (anabolic and catabolic) production (endogenous compounds). The origins of certain VOCs in breath presumed to be endogenous have been proposed to be useful as preclinical biomarkers of various undiagnosed diseases including lung cancer, breast cancer, and cardio-pulmonary disease. The usual approach is to develop difference algorithms comparing VOC profiles from nominally healthy controls to cohorts of patients presenting with a documented disease, and then to apply the resulting rules to breath profiles of subjects with unknown disease status. This approach to diagnosis has a progression of sophistication; at the most rudimentary level, all measurable VOCs are included in the model. The next level corrects exhaled VOC concentrations for current inspired air concentrations. At the highest level, VOCs exhibiting discriminatory value also require a plausible biochemical pathway for their production before inclusion. Although these approaches have all shown some level of success, there is concern that pattern recognition is prone to error from environmental contamination and between-subject variance. In this paper, we explore the underlying assumptions for the interpretation and assignment of endogenous compounds with probative value for assessing changes. Specifically, we investigate the influence of previous exposures, elimination mechanisms and partitioning of exogenous compounds as confounders of true endogenous compounds. We provide specific examples based on a simple classical pharmacokinetic approach to identify potential misinterpretations of breath data and propose some remedies.

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Clinical breath analysis: discriminating between human endogenous compounds and exogenous (environmental) chemical confounders.

Benzene exposure of chemical workers was studied, during the entire workshift, by continuous monitoring of workplace benzene concentration, and 16 hours after the end of the workshift by the measurement of alveolar and blood benzene concentrations and excretion of urinary phenol. Exposure of hospital staff was studied by measuring benzene concentrations in the alveolar and blood samples collected during the hospital workshift. Instantaneous environmental air samples were also collected, at the moment of the biological sampling, for all the subjects tested. A group of 34 chemical workers showed an eight hour exposure to benzene, as a geometric mean, of 1.12 micrograms/l which corresponded, 16 hours after the end of the workshift, to a geometric mean benzene concentration of 70 ng/l in the alveolar air and 597 ng/l in the blood. Another group of 27 chemical workers (group A) turned out to be exposed to an indeterminable eight hour exposure to benzene that corresponded, the morning after, to a geometric mean benzene concentration of 28 ng/l in the alveolar air and 256 ng/l in the blood. The group of hospital staff (group B) had a benzene concentration of 14 ng/l in the alveolar air and 269 ng/l in the blood. Instantaneous environmental samples showed that in the infirmaries the geometric mean benzene concentration was 58 ng/l during the examination of the 34 chemical workers, 36 ng/l during the examination of the 27 chemical workers (group A), and 5 ng/l during the examination of the 19 subjects of the hospital staff (group B). Statistical analysis showed that the alveolar and blood benzene concentrations in the 34 workers exposed to 1.12 microgram/l of benzene differed significantly from those in groups A and B. It was found, moreover, that the alveolar and blood benzene concentrations were higher in the smokers in groups A and B but not in the smokers in the group of 34 chemical workers. The slope of the linear correlation between the alveolar and the instantaneous environmental benzene concentrations suggested a benzene alveolar retention of about 55%. Blood and alveolar benzene concentrations showed a highly significant correlation and the blood/air partition coefficient, obtained from the slope of the regression line, was 7.4. In the group of the 34 chemical workers no correlation was found between the TWA benzene exposure and the urinary phenol excretion.

J. C. Gage

Papers

A method for the determination of low concentrations of organic vapours in air and exhaled breath.