Virus-induced Volatile Organic Compounds Are Detectable in Exhaled Breath during Pulmonary Infection

• Published in: American journal of respiratory and critical care medicine Vol. 204; no. 9; pp. 1075 - 1085
• Main Authors: Kamal, Faisal, Kumar, Sacheen, Edwards, Michael R., Veselkov, Kirill, Belluomo, Ilaria, Kebadze, Tatiana, Romano, Andrea, Trujillo-Torralbo, Maria-Belen, Shahridan Faiez, Tasnim, Walton, Ross, Ritchie, Andrew I., Wiseman, Dexter J., Laponogov, Ivan, Donaldson, Gavin, Wedzicha, Jadwiga A., Johnston, Sebastian L., Singanayagam, Aran, Hanna, George B.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 01.11.2021
• Subjects: Adult; Aged; Aged, 80 and over; Antibiotics; Antiviral drugs; Biomarkers; Biomarkers - analysis; Breath Tests - methods; Chronic obstructive pulmonary disease; Early Diagnosis; Female; Humans; Infections; Male; Middle Aged; Original; Picornaviridae Infections - diagnosis; Picornaviridae Infections - physiopathology; Pulmonary Disease, Chronic Obstructive - physiopathology; Respiratory diseases; Studies; VOCs; Volatile organic compounds; Volatile Organic Compounds - analysis; viral infection; volatile organic compound; rhinovirus; chronic obstructive pulmonary disease
• DOI: 10.1164/rccm.202103-0660OC
• ISSN: 1073-449X; 1535-4970

Chronic obstructive pulmonary disease (COPD) is a condition punctuated by acute exacerbations commonly triggered by viral and/or bacterial infection. Early identification of exacerbation triggers is important to guide appropriate therapy, but currently available tests are slow and imprecise. Volatile organic compounds (VOCs) can be detected in exhaled breath and have the potential to be rapid tissue-specific biomarkers of infection etiology. To determine whether volatile organic compound measurement could distinguish viral from bacterial infection in COPD. We used serial sampling within and studies to elucidate the dynamic changes that occur in VOC production during acute respiratory viral infection. Highly sensitive gas chromatography-mass spectrometry techniques were used to measure VOC production from infected airway epithelial-cell cultures and in exhaled breath samples from healthy subjects experimentally challenged with rhinovirus (RV)-A16 and from subjects with COPD with naturally occurring exacerbations. We identified a novel VOC signature comprising decane and other long-chain alkane compounds that is induced during RV infection of cultured airway epithelial cells and is also increased in the exhaled breath from healthy subjects experimentally challenged with RV and from patients with COPD during naturally occurring viral exacerbations. These compounds correlated with the magnitude of antiviral immune responses, viral burden, and exacerbation severity but were not induced by bacterial infection, suggesting that they represent a specific virus-inducible signature. Our study highlights the potential for measurement of exhaled breath VOCs as rapid, noninvasive biomarkers of viral infection. Further studies are needed to determine whether measurement of these signatures could be used to guide more targeted therapy with antibiotic/antiviral agents for COPD exacerbations.