posted on 2022-08-31, 14:59authored byDahlia Salman, Wadah Ibrahim, Amisha Kanabar, Abigail Joyce, Bo Zhao, Amisha Singapuri, Michael Wilde, Rebecca Cordell, Teresa McNally, Dorota M. Ruszkiewicz, Andria Hadjithekli, Robert Free, Neil Greening, Erol Gaillard, Caroline Beardsmore, Paul S. Monks, Christopher E. Brightling, Salman Siddiqui, C.L. Paul Thomas
The development of clinical breath-analysis is confounded by the variability of background volatile organic compounds (VOC). Reliable interpretation of clinical breath-analysis at individual, and cohort levels requires characterisation of clinical-VOC levels and exposures. Active-sampling with thermal-desorption/gas chromatography-mass spectrometry recorded and evaluated VOC concentrations in 245 samples of indoor air from three sites in a large NHS provider trust in the UK over 27 months. Data deconvolution, alignment and clustering isolated 7344 features attributable to VOC and described the variability (composition and concentration) of respirable clinical VOC. 328 VOC were observed in more than 5% of the samples and 68 VOC appeared in more than 30% of samples. Common VOC were associated with exogenous and endogenous sources and 17 VOC were identified as seasonal differentiators. The presence of metabolites from the anaesthetic sevoflurane, and putative-disease biomarkers in room air, indicated that exhaled VOC were a source of background-pollution in clinical breath-testing activity. With the exception of solvents, and PPE waxes, exhaled VOC concentrations above 3 µg m-3 are unlikely to arise from room air contamination, and in the absence of extensive survey-data, this level could be applied as a threshold for inclusion in studies, removing a potential environmental confounding-factor in developing breath-based diagnostics.
Funding
This research was funded by the Medical Research Council (MRC), Engineering and Physical Sciences Research Council (EPSRC) Stratified Medicine Grant for Molecular Pathology Nodes (Grant No. MR/N005880/1), Midlands Asthma and Allergy Research Association (MAARA) And British Lung Foundation (GrantNo.BLFPHD17-1).The work was carried out at the University Hospitals of Leicester NHS Trust, University of Leicester and Loughborough University, supported by the NIHR Leicester Biomedical Research Centre and the NIHR Leicester Clinical Research Facility.