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).
CONCLUSION: A breath test identified apparent biomarkers of active pulmonary 
tuberculosis with 85% accuracy in symptomatic high-risk subjects.