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


OBJECTIVE
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).


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.
Menssana Research Inc., Breath Research Laboratory, EDC III, 211 Warren Street, Newark, NJ 07103, USA. mphillips@menssanaresearch.com
Michael
M
Phillips
Victoria
V
Basa-Dalay
Jaime
J
Blais
Graham
G
Bothamley
Anirudh
A
Chaturvedi
Kinjal D
KD
Modi
Mauli
M
Pandya
Maria Piedad R
MP
Natividad
Urvish
U
Patel
Nagsen N
NN
Ramraje
Peter
P
Schmitt
Zarir F
ZF
Udwadia
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000465:Algorithms; D015415:Biomarkers / Q000378:metabolism; D001944:Breath Tests / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019095:Point-of-Care Systems; D011237:Predictive Value of Tests; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis*; D055549:Volatile Organic Compounds / Q000378:metabolism; D055815:Young Adult
D015415:Biomarkers; D055549:Volatile Organic Compounds