Validation of exhaled volatile organic compounds as biomarkers for COPD exacerbations

<bold>Rationale:</bold> Exhaled volatile organic compounds (VOCs) have been proposed as potential biomarkers for early detection and monitoring of COPD exacerbations. <bold>Aim:</bold> To list VOCs associated with COPD exacerbations and to validate those in an existing dataset. <bold>Methods:</bold> To identify potential relevant VOCs, we systematically searched in the Cochrane Library, Embase, and MEDLINE databases (01-2016 to 01-2024). Validation of the identified VOCs was done by targeted sparse Partial Least-Squares Discriminant Analysis (sPLSDA) combined with Wilcoxon testing using previously collected longitudinal data from patients included in the TEXACOLD trial (time points: baseline [A], exacerbation [B], follow-up [C]), which were analyzed by Gas Chromatography-Mass Spectrometry. <bold>Results:</bold> Our search, combined with findings from Christiansen et al. [J Breath Res. 2016], resulted in 12 candidate VOCs, which were tested in a dataset of 42 samples originating from 14 COPD patients [age 67 (8.4) years, 86% male, GOLD stage 1:1, 2:8, 3:5, FEV1/FVC 0.43 (0.12)]. The resulting sPLSDA model showed significant differences between the three time points in the second dimension (A vs B p<0.01; B vs C p=0.01; A vs C p=0.22), see Figure 1-a to c. <bold>Conclusion:</bold> While the obtained findings hold promise for early detection of exacerbations, further validation in larger datasets is required to evaluate the role of this composite VOC model in COPD disease monitoring.