Abstract

Introduction: Infections commonly trigger COPD exacerbations but aetiology is difficult to distinguish clinically. We hypothesised that VOCs in exhaled breath could distinguish between viral and bacterial infections. Methods: Pathogen-related VOC production using in vitro and in vivo disease models were measured by Gas Chromatography-Mass Spectrometry (GC-MS) analysis of agar plate headspace cultured with bacteria and/or human airway epithelial cells infected with virus or bacteria. VOC profiles were prospectively studied from 22 healthy subjects infected with rhinovirus and 130 COPD patients at stable state and during exacerbations (n= 537). Results: 23 and 13 VOCs respectively were produced by Streptococcus pneumoniae (SP) and Haemophilus influenzae (HI) culture on agar plates. 8/23 VOCs showed dose dependent increase with bacterial concentration plated. Similarly, VOCs specific to viral and bacterial infection were identified from bronchial epithelial cells stimulated with rhinovirus(RV) 16, RSV, SP and HI. We found similarly induced VOCs in breath of healthy subjects following RV-16 infection. Preliminary findings from COPD patients identified 14 increased VOCs in patients with positive bacterial sputum cultures. Conclusion: Specific VOCs are associated with viral and bacterial infection. VOCs could accurately determine aetiology, guiding judicious antimicrobial use in exacerbations and pneumonia.

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