Tuberculosis biomarkers research case study

Publication information: Amandip S. Sahota et al. (2016) A simple breath test for tuberculosis using ion mobility: A pilot study Tuberculosis 99, 143-146. DOI: 10.1016/j.tube.2016.05.005

Disease Area: Tuberculosis

Application: Diagnostics

Sample medium: Breath

Products: Lonestar^® VOC Analyzer

Analysis approach: FAIMS

Summary:

Treatment of TB in low-income countries is particularly hampered by the lack of cheap, simple and accurate diagnostic tests.
This pilot study found that Lonestar could distinguish between patients with pulmonary or extra-pulmonary tuberculosis and healthy controls.
FAIMS may therefore provide a solution for targeting TB treatment in a global context.

There are around 8.6 million new cases, and 1.3 million deaths from tuberculosis (TB) every year. Diagnosis is still mostly performed by trained technicians examining sputum samples under a microscope (WHO tuberculosis factsheet).

Treatment and prevention of TB in low-income countries is particularly hampered by the lack of cheap, simple and accurate diagnostic tests. In particular, patients who are suspected of having TB but who test negative using the sputum ZN-smear pose a diagnostic problem. Breath analysis using technologies like FAIMS have great potential to provide a simple, point of care diagnostic service that could revolutionise TB detection.

A pilot study by Sahota et al. found that Owlstone Medical's Lonestar^® instrument was able to distinguish between patients with either pulmonary or extra-pulmonary tuberculosis and healthy controls. They analysed the FAIMS data using a wavelet feature extraction process followed by a random forest classifier, to identify features in FAIMS spectra. This allowed discrimination of cases from controls with a sensitivity of 81% and a specificity of 79%.

Tuberculosis pilot study box plot — Classification probabilities for the control and TB groups in pilot study using Lonestar by Sahota et al. Applying a Wilcoxon rank-sum test to the sets of classification probabilities from the two groups, we get a p-value of 2.89E6, showing that there is a highly statistically significant difference between the control and TB groups.

The results of this pioneering study indicate that FAIMS, in particular, has potential as a technology that can be applied to breath testing for clinical diseases including TB.

Receiver Operator Curve for breath analysis of patients with TB. — Receiver Operator Curve from Sahota et al. (AUC = 0.92; 95% CI: 084, 1) for breath analysis of patients with TB.

The advantages of FAIMS in terms of sensitivity, ease of setup with minimal training and minimal instrumental drift and variability, may provide a solution for targeting TB treatment in a global context.

DOWNLOAD PAPER

Detection of TB in patients with negative ZN-smear tests

A team from the Pulmonology Department at the Academic Medical Centre, University of Amsterdam, have also used Owlstone Medical's Lonestar as part of an eNose array to conduct a proof-of-concept study. They were particularly interested to test whether TB could be detected in patients suspected to have TB, but who got negative results from ZN-smear tests. They showed that tuberculosis could be diagnosed using this system via chemical markers in exhaled breath. Importantly, they also found that TB could be detected in the patients with negative ZN-smear results.