Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

Sethi, Shneh; Nanda, Ranjan Kumar; Chakraborty, Trinad

doi:10.1128/cmr.00020-13

Cited by 270 publications

(201 citation statements)

References 133 publications

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“…Bacteria and fungi [5,6] are known to produce a broad spectrum of secondary metabolites including a wealth of volatile molecules. However, most of the microbial VOCs are released in very low concentrations requiring and the exact composition of the emitted volatile compounds varies with different environmental conditions.…”

Section: Introductionmentioning

confidence: 99%

A rapid method for breath analysis in cystic fibrosis patients

Kramer

Sauer-Heilborn

Welte

et al. 2014

Eur J Clin Microbiol Infect Dis

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Purpose: For easy handling and speed of lung diseases diagnostic, approaches based on volatile organic compounds (VOCs), including those emitted by pathogenic microorganisms, are considered but currently require considerable sampling efforts. We tested whether easy to handle and fast detection of lung infections is possible using Solid-Phase-Micro-Extraction (SPME) of 100 ml of exhaled breath. Methods: An analytical procedure for the detection of VOCs from the headspace of epithelial lung cells infected with four human pathogens was developed. The feasibility of this method was tested in a cystic fibrosis (CF) outpatient clinic in vivo. Exhaled breath was extracted by SPME and analyzed by gas chromatography-mass spectrometry. Results: The compositions of VOCs released in the infection model were characteristic for all individual pathogens tested.Exhaled breath of CF patients allowed clear distinction of CF patients and controls by their VOC compositions using multivariate analyses. Interestingly, the major specific VOCs detected in exhaled breath of infected CF patients in vivo differed from those monitored during bacterial in vitro growth. Conclusions: SPME extraction of VOCs from 100 ml of human breath allowed the distinction between CF patients and healthy probands. Our results highlight the importance of assessing the entire pattern of VOCs instead of selected biomarkers for diagnostic purposes, as well as the need for using clinical samples to identify reliable biomarkers. This study provides the proof-of-concept for the approach using the composition of exhaled VOCs in human breath for rapid identification of infectious agents in patients with lower respiratory tract infections.

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Section: Introductionmentioning

confidence: 99%

A rapid method for breath analysis in cystic fibrosis patients

Kramer

Sauer-Heilborn

Welte

et al. 2014

Eur J Clin Microbiol Infect Dis

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“…Alkane is not a breath biomarker characteristics of pneumonia (41,42), whereas the concentration of exhaled ethane was found to be higher in the patients with IPF compared to the healthy subjects (43). On the other hand, although there is no independent association between lung cancer and smoking-related respiratory diseases, namely tuberculosis and asthma (39,44), alkanes are associated with oxidative stress resulting from infection by Mycobacterium tuberculosis as well as airway inflammation by asthma (45,46).…”

Section: Discussionmentioning

confidence: 99%

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer

Tan¹,

Yong

Liam³

2016

J. Thorac. Dis.

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Background: Breath alkanes are reported to be able to discriminate lung cancer patients from healthy people. A simple chemiresistor-based sensor was designed to respond to alkanes by a change in resistance measured by a digital multimeter connected to the sensor. In preclinical experiments, the sensor response was found to have a strong positive linear relationship with alkane compounds and not responsive to water.This study aimed to determine the ability of the alkane sensor to distinguish the exhaled breaths of lung cancer patients from that of chronic obstructive pulmonary disease (COPD) patients and control subjects without lung cancer. Methods: In this cross-sectional study, 12 treatment-naive patients with lung cancer, 12 ex-or current smokers with COPD and 13 never-smokers without lung disease were asked to exhale through a drinking straw into a prototype breath-in apparatus made from an empty 125 mL Vitagen ® bottle with the chemiresistor sensor attached at its inside bottom to measure the sensor peak output (percentage change of baseline resistance measured before exhalation to peak resistance) and the time taken for the baseline resistance to reach peak resistance. In recent years, there has been an increasing interest in finding a diagnostic method for lung cancer that is minimally invasive, free of radiation and accurate in detecting lung cancer at its early stage. This is because the National Lung Screening Trial (NLST) (3) conducted on 53,454 study subjects demonstrated that the chest tomography (CT) scan and chest X-ray imaging are associated with very high false-positive results in detecting lung cancer in early stages (96.4% for low-dose CT scan; 94.5% for chest X-ray). Furthermore, one person out of 2,500 people screened by chest imaging will die of radiationinduced cancer (4). To address this issue, previous studies show that using the pattern of endogenous volatile organic compounds (VOCs) in the exhaled breath for the detection of lung cancer is one of the promising solutions. Cellular metabolisms produce VOCs, such as alcohols, alkanes, etc., that will be carried in the bloodstream. Subsequently, the VOCs diffuse into the alveolar air in the blood-gas interface quickly in the lung because of their low solubility in the blood, and they are exhaled out of the lung (5). Therefore, analysing the composition of VOCs in exhaled breath can provide a window into the biochemical process of the body and detect altered metabolism, particularly in cancer cells. This method has a few advantages: it is non-invasive, potentially inexpensive and it is very easy to obtain exhaled breath (6,7). Compared to biomarkers in serum, the breath contains a less complicated mixture of VOCs. Moreover, breath testing provides direct and real-time monitoring, and has the potential of detecting lung cancer when it is still localised as VOCs markers are transmitted to the alveoli to be exhaled at the onset of the disease. Another important advantage is the presence of lung cancer tumour is not masked by other diseases sin...

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“…The current focus for "cell breath" research is to measure volatile emissions from bacterial mono-cultures to identify patterns of VOCs in vitro and develop a "fingerprint" library (Shestivska et al 2015;Zhu et al 2013;Sethi et al 2013). Subsequently, measurements of human exhaled breath could be explored for such patterns to diagnose infectious state and monitor treatment (Risby and Solga 2006;Barker et al 2006;Christ-Crain and Müller 2007).…”

Section: In Vitro To In Vivo Linkage; Cell Line Toxicity Prioritizatimentioning

confidence: 99%

Breath biomarkers in toxicology

Pleil

2016

Arch Toxicol

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Clinical Application of Volatile Organic Compound Analysis for Detecting Infectious Diseases

Cited by 270 publications

References 133 publications

A rapid method for breath analysis in cystic fibrosis patients

A rapid method for breath analysis in cystic fibrosis patients

Using a chemiresistor-based alkane sensor to distinguish exhaled breaths of lung cancer patients from subjects with no lung cancer

Breath biomarkers in toxicology

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