Volatile organic compounds in exhaled breath are independent of systemic inflammatory syndrome caused by intravenous lipopolysaccharide infusion in humans: results from an experiment in healthy volunteers

Abstract

Systemic inflammatory response syndrome (SIRS) is observed during critical illness in most patients. It is defined by a clinical definition. The composition of volatile organic compounds (VOCs) in exhaled breath may change during SIRS and may thus serve as a diagnostic tool. We investigated whether exhaled breath VOCs can serve as biomarker for SIRS in a human model of endotoxemia. Eighteen healthy volunteers received 2 ng Eschericia coli lipopolysaccharide (LPS) kg^-1 body weight intravenously. Venous blood and exhaled breath were collected before infusion of LPS and every 2 h thereafter, up to 8 h after infusion. The interleukin (IL)-6 concentration was measured in plasma. VOCs in the exhaled breath were measured by gas chromatography and mass spectrometry. A mixed effects model was fitted to examine the relation between the measured compounds in exhaled breath and time after LPS infusion or IL-6 levels in plasma. Partially-least squares discriminant analysis (PLS-DA) was used to investigate whether we could discriminate between samples collected before and after LPS infusion. The exhaled concentrations of 3-methyl-pentane, 4-methyl-pentanol, 1-hexanol, 2,4-dimethyl-heptane, decane and one unknown compound changed after LPS infusion. However, the false-discovery rate was 43% for the total set of 52 compounds that were present in all samples. Of these VOCs only the unknown compound was associated with systemic levels of IL-6. The PLS-DA algorithm resulted in a moderate discriminatory accuracy. SIRS induced by endotoxemia in human volunteers resulted in minor changes in exhaled VOCs. We therefore conclude that LPS infusion in healthy volunteers does not induce metabolic effects that can be detected through VOC analysis of the exhaled breath. This trial is registered at the Dutch Trial Register: NTR4455.