Diagnosis of pulmonary tuberculosis and assessment of treatment response through analyses of volatile compound patterns in exhaled breath samples

Abstract

Objectives We determined the performance of a sensor array (an electronic nose) made of 8 metalloporphyrins coated quartz microbalances sensors for the diagnosis and prognosis of pulmonary tuberculosis (TB) using exhaled breath samples. Methods TB cases and healthy controls were prospectively enrolled. Signals from volatile organic compounds (VOCs) in breath samples were measured at days 0, 2, 7, 14, and 30 of TB therapy and correlated with clinical and microbiological measurements. Results 51 pulmonary TB cases and 20 healthy HIV-uninfected controls were enrolled in the study. 31 (61%) of the 51 pulmonary TB cases were coinfected with HIV. At day 0 (before TB treatment initiation) the sensitivity of our device was estimated at 94.1% (95% confidence interval [CI], 83.8-98.8%) and specificity was 90.0% (95% CI, 68.3-98.8%) for distinguishing TB cases from controls. Time-dependent changes in the breath signals were identified as time on TB treatment progressed. Time-dependent signal changes were more pronounced among HIV-uninfected patients. Conclusion The identification of VOCs signals in breath samples using a sensor array achieved high sensitivity and specificity for the diagnosis of TB and allowed following signal changes during TB treatment.

Update on tuberculosis biomarkers: From correlates of risk, to correlates of active disease and of cure from disease

“…products of oxidative stress). A breath test based on the detection and quantification of VOC identified pulmonary TB with high accuracy in symptomatic high‐risk subjects and in active TB patients, and the signals significantly decreased after TB therapy . However, detection of VOC is still technically difficult because most VOC in breath are excreted in picomolar concentrations and most current analytical instruments cannot detect VOC at such low levels.…”

Bulk and Surface Acoustic Wave Sensor Arrays for Multi-Analyte Detection: A Review

“…In the following, similar arrays were used for early diagnosis of lung cancer and for tuberculosis diagnosis. The exhaled breath of lung cancer patients and from patients with pulmonary tuberculosis could be distinguished from the corresponding samples of healthy controls with sufficient selectivity [40,118].…”

Sensors for detecting pulmonary diseases from exhaled breath

“…Diagnosis of TB remains a major global public health challenge, with its social burden increasing because many patients may also be infected with HIV. The rates of multidrug-resistant TB are increasing [58,91]. In 2010, there was an estimated incident case count of 8.8 million active TB infections, resulting in 1.5 million deaths [57].…”

“…Current diagnostic methods rely on either insensitive smear microscopy or sensitive, but lengthy, microbiologic culture, unlikely to be used in poorly resourced centres [56,59]. More recently, the Xpert MTB/RIF assay, a fully automated sample-to-answer nucleic acid amplification test, has significantly improved sensitivity compared with smear microscopy [58]. However, this assay requires a sputum sample or an invasive sample from patients that cannot expectorate.…”

“…Breath samples of 51 patients with TB and 20 controls were analysed before and 2, 7, 14 and 30 days after therapy. The sensors response was validated and correlated with clinical and microbiological measurements on sputum samples [58]. The sensors scored 93% accuracy in distinguishing TB cases from controls; additionally, serial measurements of VOCs also showed signal changes during TB treatment among patients.…”