Breath Analysis Method Research Articles

Portable method of measuring gaseous acetone concentrations

Measurement of acetone in human breath samples has been previously shown to provide significant non-invasive diagnostic insight into the control of a patient's diabetic condition. In patients with diabetes mellitus, the body produces excess amounts of ketones such as acetone, which are then exhaled during respiration. Using various breath analysis methods has allowed for the accurate determination of acetone concentrations in exhaled breath. However, many of these methods require instrumentation and pre-concentration steps not suitable for point-of-care use. We have found that by immobilizing resorcinol reagent into a perfluorosulfonic acid polymer membrane, a controlled organic synthesis reaction occurs with acetone in a dry carrier gas. The immobilized, highly selective product of this reaction (a flavan) is found to produce a visible spectrum color change which could measure acetone concentrations to less than ppm. We here demonstrate how this approach can be used to produce a portable optical sensing device for real-time, non-invasive acetone analysis.

In situ detection of lung cancer volatile fingerprints using bronchoscopic air-sampling

Lung cancer diagnosis via breath analysis has to overcome some issues that can be summarized by two crucial points: (1) further developments for more performant breath sampling technologies; (2) discovering more differentiated volatile fingerprints to be ascribed to specific altered biological mechanisms. The present work merges these two aspects in a pilot study, where a breath volume, sampled via endoscopic probe, is analyzed by an array of non-selective gas sensors. Even if the original non-invasive methods of breath analysis has been laid in favour of the endoscopic means, the innovative technique here proposed allows the analysis of the volatile mixtures directly sampled near the tumor mass. This strategy could open the way for a better understanding of the already obtained discrimination among positive and negative cancer cases. The results obtained so far confirm the established discrimination capacity. This allows to discriminate the different subtypes of lung cancer with 75% of correct classification between adenocarcinoma and squamous cell carcinoma. This result suggests that a ‘zoom-in’ on the cancer settled inside the human body can increase the resolution power of key-volatiles detection, allowing the discrimination among different cancer fingerprints. We report this novel technique as a robust support for a better comprehension of the promising results obtained so far and present in literature; it is not to be intended as a replacement for non-invasive breath sampling procedure with the endoscope.

Can volatile compounds in exhaled breath be used to monitor control in diabetes mellitus?

Although it has been known for centuries that there are compounds in exhaled breath that are altered in disease, it is only in the last few decades that it has been possible to measure them with sufficient accuracy and precision to make them clinically useful. The clinical utility of breath analysis has also been limited by the practical difficulties of collecting representative breath samples, free from contaminants. More recent methods of breath analysis have allowed real-time analysis of breath, eliminating the need for sample collection, and therefore potentially allowing the rapid feedback of results to patient and clinician. One possible future application of breath analysis may be the monitoring of metabolic control in patients with diabetes mellitus. This perspective article provides an overview of the studies of breath analysis in diabetes, focusing on the breath metabolites; acetone, isoprene and also methyl nitrate that have previously been reported to be altered in diabetes, highlighting the factors that may potentially confound their interpretation. Specific attention is given to selected ion flow tube mass spectrometry (SIFT-MS) and proton transfer reaction mass spectrometry (PTR-MS), because they are techniques that have been developed specifically for the absolute quantification of breath metabolites in real time, although reference is made to some of the alternative techniques, including sensors and optical devices. Whilst breath analysis, using SIFT-MS, PTR-MS and other sensitive techniques, can potentially be used for the non-invasive monitoring of metabolic conditions that may include diabetes mellitus, further work is required in terms of the clinical and analytical validation. Furthermore, it is unclear at present what breath metabolites should be monitored and what factors may confound their interpretation. Although a non-invasive method of monitoring glycaemic control is clearly desirable, it will be important to demonstrate its analytical comparability with the well-established and validated methods for blood glucose measurement.

Determination of volatile organic compounds in human breath for Helicobacter pylori detection by SPME‐GC/MS

Helicobacter pylori living in the human stomach release volatile organic compounds (VOCs) that can be detected in expired air. The aim of the study was the application of breath analysis for bacteria detection. It was accomplished by determination of VOCs characteristic for patients with H. pylori and the analysis of gases released by bacteria in suspension. Solid-phase microextraction was applied as a selective technique for preconcentration and isolation of analytes. Gas chromatography coupled with mass spectrometry was used for the separation and identification of volatile analytes in breath samples and bacterial headspace. For data calculation and processing, discriminant and factor analyses were used. Endogenous substances such as isobutane, 2-butanone and ethyl acetate were detected in the breath of persons with H. pylori in the stomach and in the gaseous mixture released by the bacteria strain but they were not identified in the breath of healthy volunteers. The canonical analysis of discrimination functions showed a strong difference between the three examined groups. Knowledge of substances emitted by H. pylori with the application of an optimized breath analysis method might become a very useful tool for noninvasive detection of this bacterium.

Oxidative Stress and Exhaled Breath Analysis: A Promising Tool for Detection of Lung Cancer

Lung cancer is one of the few neoplasia in which the principal aetiology is known, with cigarette smoke donating a considerable oxidative burden to the lungs. This may be part of the aetiology of lung cancer, but the neoplastic process is also associated with increased oxidative stress. Nonetheless, it is difficult to study the mechanisms behind the induction of lung cancer in smokers, but newer techniques of breath analysis targeting markers of oxidative stress and anti-oxidant capacity show promise in unravelling some of the pathways. This review highlights recent developments in the assessment of oxidative stress by non-invasive methods of breath analysis which are becoming powerful research techniques with possible clinical applications.

Evidence for Cancer Biomarkers in Exhaled Breath

A Review: Cancer cell growth releases molecular biomarkers into blood that can be useful in diagnostic tests, e.g., serum biomarkers. The use of serum biomarkers involves an invasive sample collection procedure. Human exhaled breath is potentially a noninvasive source of cancer biomarker compounds. A few breath analysis studies have reported sensitivities > 90% and specificities > 80% using a suite of exhaled breath biomarkers to differentiate cancer subjects from controls. A significant challenge for establishing breath analysis as a feasible cancer diagnostic procedure is the lack of validated diagnostic procedure. We found over 2000 breath-related studies published since circa 1900 reporting on a wide variety of breath chemical analysis methods and diagnostic findings; only a small fraction of these studies were directly related to cancer molecular biomarkers in breath. Compared to other detectors and separation techniques, mass spectrometry and gas chromatography are most suitable techniques for breath analysis. Compounds detectable in exhaled breath, with potential diagnostic utility in cancer detection, include small gaseous molecules, volatile organic compounds, proteins, and DNA. The types of cancers previously investigated using chemical analysis of exhaled breath was breast, colon, liver, lung, ovarian, and stomach cancers. Lack of multiple studies using the same breath analysis method(s) precluded meta-analysis. Our review covers the reported methods on breath analysis and assumed exhaled biomarkers. This review makes available to other researchers a catalog of published data on breath analysis for cancer detection. We make recommendations to standardize methods for more accurate breath tests in cancer detection.

Analysis of human breath with micro extraction techniques and continuous monitoring of carbon dioxide concentration

The detection of volatile organic compounds (VOCs) in human breath can be useful for the clinical routine diagnosis of several diseases in a non-invasive manner. Traditional methods of breath analysis have some major technical problems and limitations. Membrane extraction with a sorbent interface (MESI), however, has many advantages over current methods, including good selectivity and sensitivity, and is well suited for breath analysis. The aim of this project was to develop a simple and reproducible sampling device and method based on the MESI system for breath analysis. The feasibility and validity of the MESI system was tested with real human breath samples. Internal standard calibration methods were used for the quantitative analysis of various breath samples. Calibration curves for some main components (target analytes such as acetone and pentane) were determined in the research. The optimized stripping-side and feeding-side gas velocities were determined. The use of breath CO2 as an internal standard for the analysis of breath VOCs is an effective method to solve the difficulties associated with variations in the target analyte concentrations in a sample, which are attributed to mass losses and different breathing patterns of different subjects. In this study, the concentration of breath acetone was successfully expressed normalized to CO2 as in the alveolar air. Breath acetone of healthy males and females profiled at different times of the day was plotted using the MESI system, and results were consistent with the literature. This technique can be used for monitoring breath acetone concentrations of diabetic patients and for applications with other biomarker monitoring.

過酸化脂質実験法 ２ 生体内過酸化脂質の測定 （１） ２） ケミルミネッセンス法，呼気分析法，ヨウ素比色法

過酸化脂質実験法 ２ 生体内過酸化脂質の測定 （１） ２） ケミルミネッセンス法，呼気分析法，ヨウ素比色法

BREATHALYZER AND KITAGAWA-WRIGHT METHODS OF MEASURING BREATH ALCOHOL.

Breath-alcohol levels reflect blood-alcohol levels, since an equilibrium exists between pulmonary blood and alveolar air. Three methods of estimating breath alcohol have been studied: the breathalyzer using samples collected directly, the breathalyzer using samples stored in plastic bags, and the Kitagawa-Wright method. Various doses of distilled spirits were given to 18 healthy young men and the alcohol content of their alveolar air was measured each half-hour for several hours, using the three methods; venous blood was also analysed chemically for alcohol on three occasions in each subject, by the Nickolls method, at times when the arteriovenous difference would be negligible. All three methods of breath analysis were suitable for practical use, the readings were reproducible, and they correlated well with blood analysis. Experiments showed that the error in breath-alcohol readings due to alcohol in the mouth was negligible 15 minutes after the drink. The merits of breath-alcohol analysis and of the breathalyzer, breathalyzer bags, and Kitagawa-Wright instrument are discussed.