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

Abstract

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.

Physiological variability in volatile organic compounds (VOCs) in exhaled breath and released from faeces due to nutrition and somatic growth in a standardized caprine animal model

“…Environmental volatile compounds can significantly contribute to the body's pool of VOCs through inhalation, ingestion, and percutaneous or mucosal absorption (Miekisch et al 2004, Pleil et al 2013. In agreement with our study, Mochalski et al (2013) found higher concentrations of 2-butanone in room air when compared with exhaled breath, and suggested a contribution of inhaled exogenous 2-butanone to blood levels.…”

“…Additionally, volatile compounds originating from exogenous sources can be absorbed into the body and thus contribute to the body's pool of VOCs that have been endogenously generated (Miekisch et al 2004, Pleil et al 2013. Thus, clinical studies are often hampered by non-avoidable, host-related, confounding factors that could lead to erroneous conclusions when searching for biomarkers indicating diseases (Filipiak et al 2012).…”

Real-time monitoring of respiratory absorption factors of volatile organic compounds in ambient air by proton transfer reaction time-of-flight mass spectrometry

“…The mean respiratory AFs of benzene, toluene, and C8-aromatics from all test subjects were 55.0%, 55.9%, and 66.9%, respectively. The mean respiratory AFs of BTEX in the present study appeared in an order of benzene < toluene < C8-aromatics, the same order as their partition coefficients between blood and air (K B ) [56,100]. No excellent correlation (0.5 < R 2 < 0.6) was observed between body fat rate and the AFs of BTEX.…”

Volatile Organic Compounds Off-gassing from Firefighters’ Personal Protective Equipment Ensembles after Use

“…At steady state, the exhaled/inhaled fractional value (f-value) for benzene has been estimated at 0.17-0.50 and the central compartment (blood) half-life has been estimated at 1.3-3 min. (21,22) Using mean estimates for the f -value and half-life, a 12 ppb exposure to benzene over 3 min would result in an exhaled breath concentration of 0.5 ppb when collected 6 min later (mean collection time). This is < 15% of the mean post-burn breath concentration of benzene (4.2 ppb) we measured.…”