Relationship between Volatile Organic Compounds (VOCs) in exhaled breath determined by Proton Transfer Reaction Time of Flight Mass Spectrometry (PTR-TOF-MS), clinical characteristics and airway inflammation in COPD

Background: Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition. Breathomics presents an opportunity to phenotype this heterogeneity but how breath volatile organic compounds (VOCs) relate to clinical features, airway physiology and inflammation is uncertain. Methods: We undertook a single centre prospective study in subjects with moderate to severe COPD. We assessed 379 breath samples obtained at stable visits. The breath VOCs were examined using Proton Transfer Reaction-Time Flight-Mass Spectrometry (PTR-TOF-MS). Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) models were undertaken to determine whether there were distinct VOC profiles associated with spirometry, plethysmography lung volumes, gas transfer, symptoms (mMRC and CAT questionnaires), sputum eosinophils ( Results: 34 COPD subjects were studied of which 8 were women. The subjects had a mean age 70 (66-74) years and FEV1 52% predicted (32.2-72.3%). There were no distinct VOC breath profiles that were associated with airway physiology or symptoms. The sputum eosinophil and sputum neutrophil cut-offs did identify distinct profiles with a receiver operator characteristic (ROC) curve area-under-the-curve (95% confidence intervals) 0.84 (0.77-0.86) and 0.80 (0.69-0.81) respectively. Conclusion: VOC breath profiles are related to airway inflammation but not physiology or symptoms in COPD.