Exhaled breath volatile organic compounds: window into preterm lung disease?

<bold>Background:</bold> Respiratory complications of preterm birth remain common, but current definitions do not include direct pathophysiological markers in the lung. We investigated the potential of exhaled breath volatile organic compounds (VOCs) in a preclinical and clinical setting, as they reflect lipid per oxidation originating from inflammation and oxidative stress. <bold>Methods:</bold> Exhaled breath was sampled in preterm neonates (with and without BPD) and preterm lambs via proton transfer reaction - high resolution - mass spectrometry (PTR-HRMS). In the ovine experiments, exhaled breath VOCs were quantified before and after exposure to both nasal CPAP and endotracheal ventilation. At euthanasia, lung tissue was collected to assess inflammation, oxidative stress and histological changes. <bold>Results:</bold> Exhaled breath collection was feasible and safe in the human and ovine setting. sPLS-DA showed good distinction between BPD patients and controls based on exhaled VOCs. Furthermore, it was possible to distinguish pre- versus post-nasal CPAP, pre- versus post- endotracheal ventilation and post-nasal CPAP versus post-endotracheal ventilation ovine breathprints. We identified significant correlations between exhaled VOCs and inflammation, oxidative stress and lung structure (e.g. m/z149.024 correlated positively with catalase, r=0.67, p<0.05). m/z47.09, m/z74.06 and m/z118.90 were identified as relevant exhaled VOCs in both the human and ovine experiments. <bold>Conclusion:</bold> Exhaled VOCs analysis can distinguish BPD patients from preterm controls and seems to truly reflect local inflammatory and oxidative stress as shown in our ovine model. This stresses the potential of VOCs as non-invasive markers for prematurity-related lung disease.