Measurement of volatile organic compounds in exhaled breath of children of the ALL Age Asthma Cohort

Rationale: Currently, for the asthma syndrome no predictors of distinct phenotypes and future disease course exist. We aim to decode underlying mechanisms and to discover biomarkers for distinct wheeze and asthma phenotypes by measurements of volatile organic compounds (VOCs) in exhaled breath (EB) by gas chromatography-mass spectrometry (GC-MS). Methods: As part of the multi-centre All Age Asthma Cohort (ALLIANCE) of wheezing or asthmatic children and asthmatic adults, deep phenotyping is performed by comprehensive clinical assessment and 'omics' analyses. This includes measurements of the 'breathome' by analysis of VOCs in EB. Episodic viral wheeze (EVW), multiple-trigger wheeze (MTW) and asthma were defined per guidelines. During quiet tidal breathing, children inhaled pre-cleaned room air (RA) and exhaled into an aluminum reservoir tube. Together, RA and EB were loaded on adsorption tubes and shipped for analysis by GC-MS. Results: So far, 157 VOCs were assessed in EB and RA samples for 82 children (13 controls, 47 asthmatics, 10 with EVW, and 12 with MTW). Preliminary analyses show typical VOC compositions for EB (isoprene, acetone) and RA (propanols, ethanol). In univariate analyses, we found 20 VOCs to differ between asthmatics and controls, and 13 VOCs to differ between EVW and MTW after correction for multiple testing. Conclusions: Sampling of VOCs is feasible even in young children. The number of VOCs that differ between asthmatics and controls as well between wheeze phenotypes suggests that this non-invasive method will be an excellent complementary measure for in-depth characterization and identification of possible wheeze or asthma biomarkers and predictors in ALLIANCE.