Abstract
Background Breath analyses in a burgeoning field, with interest in volatile organic compounds (VOCs) as a non-invasive diagnostic tool or an outcome measure, but no randomised clinical trials (RCT) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCs via multiple techniques, assessing relationships between VOCs and Haemophilus colonisation, and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with chronic obstructive pulmonary disease (COPD).
Method 43 participants had VOCs and sputum biomarkers evaluated. VOCs and induced sputum were collected after 6 h of fasting at screening, Days 1, 7 and 14. VOCs were analysed via gas chromatography mass spectrometry (GCMS), field asymmetric ion mobility spectrometry and eNose. The primary outcome for these analyses was the relationship between VOCs and Haemophilus abundance determined by 16S rRNA sequencing.
Results A joint effects model demonstrated a modest relationship between 4 exhaled VOCs and Haemophilus relative abundance (R2=0.55) measured only by GCMS, but not as measured GC FAIMs or eNose. There was considerable variability in absolute quantities of individual VOCs longitudinally.
Conclusions VOC measurement in clinical trials to identify subsets of COPD is feasible but assessment of new VOC technologies must include concurrent GCMS validation. Further work to standardise collection of VOCs and measuring a background or “housekeeper” VOC is required to understand and normalise individual VOC quantities.
Footnotes
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Conflict of interest: Dr. Mohan reports other from GSK, during the conduct of the study; and Current employee and shareholder of Genentech/Roche.
Conflict of interest: Dr. Keir has nothing to disclose.
Conflict of interest: Dr. Richardson has nothing to disclose.
Conflict of interest: Dr. Mayhew reports other from GSK, during the conduct of the study.
Conflict of interest: Dr. Boyer reports other from GSK, during the conduct of the study.
Conflict of interest: Dr. van der Schee reports other from Owlstone Medical Ltd, during the conduct of the study; .
Conflict of interest: Dr. Allsworth reports other from Owlstone Medical Ltd, during the conduct of the study; .
Conflict of interest: Dr. Miller reports other from GSK, during the conduct of the study.
Conflict of interest: Dr. Tal-Singer reports other from GSK, during the conduct of the study; and Received personal fees from Immunomet, Vocalis Health, and Ena Respiratory.
Conflict of interest: Dr. Chalmers reports grants and personal fees from GSK, during the conduct of the study; and Research grants from Boehringer-Ingelheim, Astrazeneca, Gilead Sciences, Grifols and Insmed and has received personal fees from BI, AZ, Chiesi, Grifols, Napp, Novartis, Insmed and Zambon.
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- Received April 11, 2021.
- Accepted July 19, 2021.
- Copyright ©The authors 2021
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