Dataset Information

Detection of Tuberculosis by The Analysis of Exhaled Breath Particles with High-resolution Mass Spectrometry.

ABSTRACT: Tuberculosis remains a global health threat killing over 1 million people per year. Current sputum-based diagnostics are specific but lack sensitivity resulting in treatment of many sputum negative cases. In this proof-of-concept study, we used high-resolution mass spectrometry to identify specific lipids in peripheral lung fluid samples of TB patients and controls, captured using a novel non-invasive sampling system. Exhaled respiratory particles were collected in liquid and after concentration and lipid extraction directly infused into a high-resolution mass spectrometer. High-resolution mass spectrometric data collection was conducted in a dual ion mode and chemical compositions were constructed using accurate mass measurement. Over 400 features with high segregating capacity were extracted and optimized using feature selection algorithm and machine learning, from which the accuracy of detection of positive tuberculosis patients was estimated. This current strategy provides sensitivity offered by high-resolution mass spectrometry and can be readily susceptible for developing a novel clinical assay exploring peripheral lung fluid for the detection of active TB cases.

SUBMITTER: Chen D

PROVIDER: S-EPMC7203136 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Detection of Tuberculosis by The Analysis of Exhaled Breath Particles with High-resolution Mass Spectrometry.

Chen Dapeng D Bryden Wayne A WA Wood Robin R

Scientific reports 20200506 1

Tuberculosis remains a global health threat killing over 1 million people per year. Current sputum-based diagnostics are specific but lack sensitivity resulting in treatment of many sputum negative cases. In this proof-of-concept study, we used high-resolution mass spectrometry to identify specific lipids in peripheral lung fluid samples of TB patients and controls, captured using a novel non-invasive sampling system. Exhaled respiratory particles were collected in liquid and after concentration ...[more]

PMID: 32376992

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Project description:Despite the attractiveness of breath analysis as a non-invasive means to retrieve relevant metabolic information, its introduction into routine clinical practice remains a challenge. Among all the different analytical techniques available to interrogate exhaled breath, secondary electrospray ionization high-resolution mass spectrometry (SESI-HRMS) offers a number of advantages (e.g., real-time, yet wide, metabolome coverage) that makes it ideal for untargeted and targeted studies. However, so far, SESI-HRMS has relied mostly on lab-built prototypes, making it difficult to standardize breath sampling and subsequent analysis, hence preventing further developments such as multi-center clinical studies. To address this issue, we present here a number of new developments. In particular, we have characterized a new SESI interface featuring real-time readout of critical exhalation parameters such as CO2, exhalation flow rate, and exhaled volume. Four healthy subjects provided breath specimens over a period of 1 month to characterize the stability of the SESI-HRMS system. A first assessment of the repeatability of the system using a gas standard revealed a coefficient of variation (CV) of 2.9%. Three classes of aldehydes, namely 4-hydroxy-2-alkenals, 2-alkenals and 4-hydroxy-2,6-alkedienals-hypothesized to be markers of oxidative stress-were chosen as representative metabolites of interest to evaluate the repeatability and reproducibility of this breath analysis analytical platform. Median and interquartile ranges (IQRs) of CVs for CO2, exhalation flow rate, and exhaled volume were 3.2% (1.5%), 3.1% (1.9%), and 5.0% (4.6%), respectively. Despite the high repeatability observed for these parameters, we observed a systematic decay in the signal during repeated measurements for the shorter fatty aldehydes, which eventually reached a steady state after three/four repeated exhalations. In contrast, longer fatty aldehydes showed a steady behavior, independent of the number of repeated exhalation maneuvers. We hypothesize that this highly molecule-specific and individual-independent behavior may be explained by the fact that shorter aldehydes (with higher estimated blood-to-air partition coefficients; approaching 100) mainly get exchanged in the airways of the respiratory system, whereas the longer aldehydes (with smaller estimated blood-to-air partition coefficients; approaching 10) are thought to exchange mostly in the alveoli. Exclusion of the first three exhalations from the analysis led to a median CV (IQR) of 6.7 % (5.5 %) for the said classes of aldehydes. We found that such intra-subject variability is in general much lower than inter-subject variability (median relative differences between subjects 48.2%), suggesting that the system is suitable to capture such differences. No batch effect due to sampling date was observed, overall suggesting that the intra-subject variability measured for these series of aldehydes was biological rather than technical. High correlations found among the series of aldehydes support this notion. Finally, recommendations for breath sampling and analysis for SESI-HRMS users are provided with the aim of harmonizing procedures and improving future inter-laboratory comparisons. Graphical abstract.

Dataset Information

Detection of Tuberculosis by The Analysis of Exhaled Breath Particles with High-resolution Mass Spectrometry.

Publications

Detection of Tuberculosis by The Analysis of Exhaled Breath Particles with High-resolution Mass Spectrometry.

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