Title: | Breath biomarkers of active pulmonary tuberculosis |
Author(s): | Phillips M; Basa-Dalay V; Bothamley G; Cataneo RN; Lam PK; Natividad MP; Schmitt P; Wai J; |
Address: | "Menssana Research Inc., 1 Horizon Road, Suite 1415, Fort Lee, NJ 07024-6510, USA. mphillips@menssanaresearch.com" |
DOI: | 10.1016/j.tube.2010.01.003 |
ISSN/ISBN: | 1873-281X (Electronic) 1472-9792 (Linking) |
Abstract: | "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" |
Keywords: | "Adolescent Adult Aged Biomarkers/metabolism *Breath Tests Female *Gas Chromatography-Mass Spectrometry Humans Male Middle Aged Mycobacterium tuberculosis/*metabolism *Oxidative Stress Philippines/epidemiology Tuberculosis, Pulmonary/diagnosis/epidemiology;" |
Notes: | "MedlinePhillips, Michael Basa-Dalay, Victoria Bothamley, Graham Cataneo, Renee N Lam, Phung Kim Natividad, Maria Piedad R Schmitt, Peter Wai, James eng R43 DE015923/DE/NIDCR NIH HHS/ R44 HL070411/HL/NHLBI NIH HHS/ R44 AI52504-03/AI/NIAID NIH HHS/ R41 CA081842/CA/NCI NIH HHS/ R43 AI052504/AI/NIAID NIH HHS/ R44 HL059715/HL/NHLBI NIH HHS/ R44 AI052504/AI/NIAID NIH HHS/ Multicenter Study Research Support, N.I.H., Extramural Scotland 2010/03/02 Tuberculosis (Edinb). 2010 Mar; 90(2):145-51. doi: 10.1016/j.tube.2010.01.003. Epub 2010 Feb 26" |