Breath biomarkers of active pulmonary tuberculosis.
BACKGROUND
Volatile organic compounds (VOCs) in breath may contain biomarkers of active pulmonary tuberculosis derived from the infectious organism (metabolites of Mycobacterium tuberculosis) and from the infected host (products of oxidative stress).


METHODS
We analyzed breath VOCs in 226 symptomatic high-risk patients in USA, Philippines, and UK, using gas chromatography/mass spectroscopy. Diagnosis of disease was based on sputum culture, smear microscopy, chest radiography and clinical suspicion of tuberculosis (CSTB). Chromatograms were converted to a series of 8s overlapping time slices. Biomarkers of active pulmonary tuberculosis were identified with a Monte Carlo analysis of time-slice alveolar gradients (abundance in breath minus abundance in room air).


RESULTS
Breath VOCs contained apparent biomarkers of active pulmonary tuberculosis comprising oxidative stress products (alkanes and alkane derivatives) and volatile metabolites of M. tuberculosis (cyclohexane and benzene derivatives). Breath biomarkers identified active pulmonary tuberculosis with C-statistic (area under curve of receiver operating characteristic)=0.85 (i.e. 85% overall accuracy, sensitivity=84.0%, specificity=64.7%) when sputum culture, microscopy, and chest radiography were either all positive or all negative. Employing a single criterion of disease, C-statistic=0.76 (smear microscopy), 0.68 (sputum culture), 0.66 (chest radiography) and 0.65 (CSTB).


CONCLUSIONS
A breath test identified apparent biomarkers of active pulmonary tuberculosis with 85% accuracy in symptomatic high-risk subjects.
Phillips
Michael
M
Menssana Research Inc., 1 Horizon Road, Suite 1415, Fort Lee, NJ 07024-6510, USA. mphillips@menssanaresearch.com
Basa-Dalay
Victoria
V
Bothamley
Graham
G
Cataneo
Renee N
RN
Lam
Phung Kim
PK
Natividad
Maria Piedad R
MP
Schmitt
Peter
P
Wai
James
J
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D018384:Oxidative Stress; D010679:Philippines / Q000453:epidemiology; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism*; D006113:United Kingdom / Q000453:epidemiology; D014481:United States / Q000453:epidemiology; D055549:Volatile Organic Compounds / Q000378:metabolism*; D055815:Young Adult
D015415:Biomarkers; D055549:Volatile Organic Compounds