VOLATILE MARKERS OF PULMONARY TUBERCULOSIS IN THE BREATH

DESCRIPTION (provided by applicant): Background: Pulmonary tuberculosis (TB) is a growing public health problem, but confirming the diagnosis in patients with suspected disease is often costly and time-consuming. Clinicians urgently need a screening test for active pulmonary tuberculosis that is faster, better and cheaper. An ideal screening test for pulmonary TB would be highly sensitive and specific as well as rapid, inexpensive and non-invasive. No test in current use fulfills these criteria: sputum staining for acid fast bacilli has high specificity but poor sensitivity, and culturing sputum for Mycobacteria has higher sensitivity, but it is expensive and time consuming. However, a Phase 1 pilot study provided evidence that a breath test for volatile organic compounds (VOCs) in the breath could provide a clinically useful new marker. Pattern recognition analysis of oxidative stress markers in breath identified patients with active pulmonary TB infection with 94.1% sensitivity and 95.1% specificity. Fuzzy logic analysis of breath VOCs predicted active pulmonary tuberculosis infection with sensitivity = 100% and specificity = 83.3%. Hypothesis: A test for breath VOCs combined with pattern recognition analysis or fuzzy logic analysis could provide a new screening test for pulmonary TB that is highly sensitive and specific as well as rapid, inexpensive and non-invasive. Plans to test the hypothesis: We will evaluate the breath test in a subset of patients enrolled in a large multicenter trial designed to evaluate antibody-detection assays in the detection of pulmonary TB. Results of the breath test will be compared to the "gold standard" of sputum culture for M. tuberculosis. Pattern recognition analysis and fuzzy logic analysis of breath VOCs will be employed to develop predictive models in a training set of patients. These models will be evaluated and compared in a test set of patients to determine the sensitivity, specificity and predictive value of the breath test as a marker of active pulmonary TB. Long term aims: a. Scientific: To validate the clinical findings of the Phase 1 study in a larger group of subjects. b. Technical: to develop a comparatively inexpensive miniaturized and rapid breath test suitable for point of care screening. c. Commercial: To obtain Food and Drug Administration (FDA) approval of the device and to market it. Importance of the research: A breath test for pulmonary TB could make an important clinical impact by detecting new infections rapidly at low cost, and also by monitoring the impact of therapy. Also, it could potentially reduce the mortality and morbidity caused by pulmonary TB.