Point-of-care breath test for biomarkers of active pulmonary tuberculosis

Rationale: Volatile organic compounds (VOCs) in breath provide biomarkers of tuberculosis (TB) because Mycobacterium tuberculosis manufactures VOC metabolites that are detectable in the breath of infected patients. Objectives: We evaluated breath VOC biomarkers in subjects with active pulmonary TB, using an internet-linked rapid point-of-care breath test. Methods: 279 subjects were studied at four centers in three countries, Philippines, UK, and India, and data was analyzed from 251 (130 active pulmonary TB, 121 controls). A point-of-care system collected and concentrated breath and air VOCs, and analyzed them with automated thermal desorption, gas chromatography, and surface acoustic wave detection. A breath test was completed in 6 min. Chromatograms were converted to a series of Kovats Index (KI) windows, and biomarkers of active pulmonary TB were identified by Monte Carlo analysis of KI window alveolar gradients (abundance in breath minus abundance in room air). Measurements and main results: Multiple Monte Carlo simulations identified eight KI windows as biomarkers with better than random performance. Four KI windows corresponded with KI values of VOCs previously identified as biomarkers of pulmonary TB and metabolic products of M. tuberculosis, principally derivatives of naphthalene, benzene and alkanes. A multivariate predictive algorithm identified active pulmonary TB with 80% accuracy (area under curve of receiver operating characteristic curve), sensitivity = 71.2%, and specificity = 72%. Accuracy increased to 84% in age-matched subgroups. In a population with 5% prevalence, the breath test would identify active pulmonary TB with 98% negative predictive value and 13% positive predictive value. Conclusions: A six-minute point-of-care breath test for volatile biomarkers accurately identified subjects with active pulmonary TB. © 2011 Elsevier Ltd. All rights reserved

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 8 s 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. © 2010 Elsevier Ltd. All rights reserved