Prospects for Clinical Application of Electronic-Nose Technology to Early Detection ofMycobacterium tuberculosisin Culture and Sputum

Abstract

Ziehl-Neelsen (ZN) staining for the diagnosis of tuberculosis (TB) is time-consuming and operator dependent and lacks sensitivity. A new method is urgently needed. We investigated the potential of an electronic nose (EN) (gas sensor array) comprising 14 conducting polymers to detect different Mycobacterium spp. and Pseudomonas aeruginosa in the headspaces of cultures, spiked sputa, and sputum samples from 330 cultureproven and human immunodeficiency virus-tested TB and non-TB patients. The data were analyzed using principal-component analysis, discriminant function analysis, and artificial neural networks. The EN differentiated between different Mycobacterium spp. and between mycobacteria and other lung pathogens both in culture and in spiked sputum samples. The detection limit in culture and spiked sputa was found to be 1 ؋ 10 4 mycobacteria ml ؊1 . After training of the neural network with 196 sputum samples, 134 samples (55 M. tuberculosis culture-positive samples and 79 culture-negative samples) were used to challenge the model. The EN correctly predicted 89% of culture-positive patients; the six false negatives were the four ZN-negative and two ZN-positive patients. The specificity and sensitivity of the described method were 91% and 89%, respectively, compared to culture. At present, the reasons for the false negatives and false positives are unknown, but they could well be due to the nonoptimized system used here. This study has shown the ability of an electronic nose to detect M. tuberculosis in clinical specimens and opens the way to making this method a rapid and automated system for the early diagnosis of respiratory infections.

Detection of Airway Colonization by Aspergillus fumigatus by Use of Electronic Nose Technology in Patients with Cystic Fibrosis

“…First of all, our in vivo findings extend the in vitro data of a number of research groups (43)(44)(45). These studies showed that A. fumigatus can be discriminated in vitro from multiple other microorganisms by an analysis of the metabolites they produce.…”

Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

“…In more recent years, an increasing number of studies have focused on the application of sensor array-based devices (e-noses) to obtain volatile smell prints in order to discriminate between TB patients and noninfected controls (66)(67)(68)). An earlier study used electroconductive sensor-based e-nose technology for demonstrating the discrimination of M. tuberculosis from other bacterial species in sputum samples (66).…”

Biomarkers in asthma and allergic rhinitis

“…Interestingly, asthmatics can also be discriminated from healthy controls and COPD patients (cross-validated accuracy 80-100%) [163,164,174]. In addition, eNoses are an attractive screening method for infectious diseases [175,176]. It is important to notice that all these data are based on cross-validation procedures in so-called 'training sets'.…”