Identification of volatile biomarkers of pulmonary tuberculosis collected in a non invasive method and their role in Mycobacterium tuberculosis infection progression

Abstract

Study of human volatome has become possible with the advancement of technologies which may provide for a novel disease diagnosis modality. Human volatome exhibits changes in its composition upon onset of any disease and as such reflect the pathophysiological condition of a subject. Tuberculosis (TB: Tubercle bacillus), a highly infectious disease is curable, but delayed diagnosis leads to unexpected early deaths and disease mismanagement. Development of a non-invasive, highly sensitive method for TB diagnosis, with the potential to be administered in point of care facility remains as an overwhelming challenge. Exhaled breath and urine contain a wide range of volatile organic compounds (VOCs) which may exhibit some alteration with the inception of an infection or disease. newlineIn this cross-sectional study, breath samples from 368 subjects and urine samples from 205 subjects including active TB patients, patients undergoing anti-TB therapy, relapse TB, lung cancer (LC), chronic obstructive pulmonary diseases (COPD), latent TB and unexposed healthy controls were collected. Samples were analyzed using thermal desorption unit (TDS) for breath and headspace sampler (HSS) for urine, coupled to a gas chromatography mass spectrometry (GC-MS) unit. Individual breath and urine samples consistently identify about 500 VOCs and 50 VOCs, respectively. Chemometric analysis of breath samples revealed unique molecular signature comprising of seven TB specific metabolites (test accuracy : 97%) and from individual urine samples, five VOCs were identified as biomarkers (test accuracy : 95%). Identified VOC biomarker profile was found to classify newly infected TB subjects successfully from patients undergoing anti-TB therapy as well as healthy and other control pulmonary diseases (Lung cancer and COPD).The current study highlights TB specific VOCs biomarker fingerprint from human exhaled breath and urine samples that may provide a basis for the development of a novel modality for effective TB management as well as other similar disorders. newline