Rationale: 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. Objectives: To determine whether volatile organic compound measurement could distinguish viral from bacterial infection in COPD. Methods: We used serial sampling within in vitro and in vivo 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. Measurements and Main Results: 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. Conclusions: 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.
Rationale: 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. Objectives: To determine whether volatile organic compound measurement could distinguish viral from bacterial infection in COPD. Methods: We used serial sampling within in vitro and in vivo 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. Measurements and Main Results: 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. Conclusions: 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.
Authors: Alex Pizzini; Wojciech Filipiak; Johannes Wille; Clemens Ager; Helmut Wiesenhofer; Róbert Kubinec; Jaroslav Blaško; Christoph Tschurtschenthaler; Chris A Mayhew; Günter Weiss; Rosa Bellmann-Weiler Journal: J Breath Res Date: 2018-03-06 Impact factor: 3.262
Authors: Alex J Mackay; Gavin C Donaldson; Anant R C Patel; Paul W Jones; John R Hurst; Jadwiga A Wedzicha Journal: Am J Respir Crit Care Med Date: 2012-01-26 Impact factor: 21.405
Authors: Aran Singanayagam; Nicholas Glanville; Leah Cuthbertson; Nathan W Bartlett; Lydia J Finney; Elena Turek; Eteri Bakhsoliani; Maria Adelaide Calderazzo; Maria-Belen Trujillo-Torralbo; Joseph Footitt; Phillip L James; Peter Fenwick; Samuel V Kemp; Thomas B Clarke; Jadwiga A Wedzicha; Michael R Edwards; Miriam Moffatt; William O Cookson; Patrick Mallia; Sebastian L Johnston Journal: Sci Transl Med Date: 2019-08-28 Impact factor: 17.956
Authors: Aran Singanayagam; Nicholas Glanville; Jason L Girkin; Yee Man Ching; Andrea Marcellini; James D Porter; Marie Toussaint; Ross P Walton; Lydia J Finney; Julia Aniscenko; Jie Zhu; Maria-Belen Trujillo-Torralbo; Maria Adelaide Calderazzo; Chris Grainge; Su-Ling Loo; Punnam Chander Veerati; Prabuddha S Pathinayake; Kristy S Nichol; Andrew T Reid; Phillip L James; Roberto Solari; Peter A B Wark; Darryl A Knight; Miriam F Moffatt; William O Cookson; Michael R Edwards; Patrick Mallia; Nathan W Bartlett; Sebastian L Johnston Journal: Nat Commun Date: 2018-06-08 Impact factor: 14.919
Authors: Sheraz R Markar; Tom Wiggins; Stefan Antonowicz; Sung-Tong Chin; Andrea Romano; Konstantin Nikolic; Benjamin Evans; David Cunningham; Muntzer Mughal; Jesper Lagergren; George B Hanna Journal: JAMA Oncol Date: 2018-07-01 Impact factor: 31.777
Authors: Patrick Mallia; Jessica Webber; Simren K Gill; Maria-Belen Trujillo-Torralbo; Maria Adelaide Calderazzo; Lydia Finney; Eteri Bakhsoliani; Hugo Farne; Aran Singanayagam; Joseph Footitt; Richard Hewitt; Tatiana Kebadze; Julia Aniscenko; Vijay Padmanaban; Philip L Molyneaux; Ian M Adcock; Peter J Barnes; Kazihuro Ito; Sarah L Elkin; Onn Min Kon; William O Cookson; Miriam F Moffat; Sebastian L Johnston; John S Tregoning Journal: J Allergy Clin Immunol Date: 2018-01-05 Impact factor: 10.793
Authors: Sîobhán N George; Davinder S Garcha; Alexander J Mackay; Anant R C Patel; Richa Singh; Raymond J Sapsford; Gavin C Donaldson; Jadwiga A Wedzicha Journal: Eur Respir J Date: 2014-03-13 Impact factor: 16.671