Real-time mass spectrometric identification of metabolites characteristic of chronic obstructive pulmonary disease in exhaled breath

New mass spectrometry (MS) techniques analysing exhaled breath have the potential to better define airway diseases. Here, we present our work to profile the volatile organic compounds (VOCs) in exhaled breath from patients with chronic obstructive pulmonary disease (COPD), using real-time MS, and relate this disease-specific breath profile to functional disease markers. In a matched cohort study, patients with COPD, according to GOLD criteria, were recruited. Exhaled breath analysis by untargeted MS was performed using secondary electrospray ionization - high-resolution MS (SESI-HRMS). Exhaled breath from 22 patients with COPD (mean age 58.6 ± 6.9 years, FEV 58.5 ± 19.9% predicted, 32.4 ± 19.2 pack years smoking) and 14 controls (mean age 58.1 ± 8.1 years, FEV 102.5 ± 11.3% predicted, 23.6 ± 12.5 pack years smoking) was analysed using SESI-HRMS. From 1441 different features, 43 markers were identified that allowed discrimination between the two groups with an accuracy of 89% (CI 74-97%), a sensitivity of 93%, and a specificity of 86%. The markers were determined to be metabolites of oxidative stress processes, such as fatty acids, aldehydes and amino acids, resulting from lung muscle degradation. Real-time breath analysis by SESI-MS allows molecular profiling of exhaled breath, can distinguish patients with COPD from matched healthy controls and provides insights into the disease pathogenesis.