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      The Use of Selected Ion Flow Tube-Mass Spectrometry Technology to Identify Breath Volatile Organic Compounds for the Detection of Head and Neck Squamous Cell Carcinoma: A Pilot Study

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          Abstract

          Background: Head and neck squamous cell carcinoma (HNSCC) is the sixth most common form of cancer worldwide, with approximately 630,000 new cases diagnosed each year. The development of low-cost and non-invasive tools for the detection of HNSCC using volatile organic compounds (VOCs) in the breath could potentially improve patient care. The aim of this study was to investigate the feasibility of selected ion flow tube mass spectrometry (SIFT-MS) technology to identify breath VOCs for the detection of HNSCC. Materials and Methods: Breath samples were obtained from HNSCC patients (N = 23) and healthy volunteers (N = 21). Exhaled alveolar breath samples were collected into FlexFoil ® PLUS (SKC Limited, Dorset, UK) sampling bags from newly diagnosed, histologically confirmed, untreated patients with HNSCC and from non-cancer participants. Breath samples were analyzed by Selected Ion Flow Tube-Mass Spectrometry (SIFT-MS) (Syft Technologies, Christchurch, New Zealand) using Selective Ion Mode (SIM) scans that probed for 91 specific VOCs that had been previously reported as breath biomarkers of HNSCC and other malignancies. Results: Of the 91 compounds analyzed, the median concentration of hydrogen cyanide (HCN) was significantly higher in the HNSCC group (2.5 ppb, 1.6–4.4) compared to the non-cancer group (1.1 ppb, 0.9–1.3; Benjamini–Hochberg adjusted p < 0.05). A receiver operating curve (ROC) analysis showed an area under the curve (AUC) of 0.801 (95% CI, 0.65952–0.94296), suggesting moderate accuracy of HCN in distinguishing HNSCC from non-cancer individuals. There were no statistically significant differences in the concentrations of the other compounds of interest that were analyzed. Conclusions: This pilot study demonstrated the feasibility of SIFT-MS technology to identify VOCs for the detection of HNSCC.

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          Most cited references27

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          Human exhaled air analytics: biomarkers of diseases.

          Over the last few years, breath analysis for the routine monitoring of metabolic disorders has attracted a considerable amount of scientific interest, especially since breath sampling is a non-invasive technique, totally painless and agreeable to patients. The investigation of human breath samples with various analytical methods has shown a correlation between the concentration patterns of volatile organic compounds (VOCs) and the occurrence of certain diseases. It has been demonstrated that modern analytical instruments allow the determination of many compounds found in human breath both in normal and anomalous concentrations. The composition of exhaled breath in patients with, for example, lung cancer, inflammatory lung disease, hepatic or renal dysfunction and diabetes contains valuable information. Furthermore, the detection and quantification of oxidative stress, and its monitoring during surgery based on composition of exhaled breath, have made considerable progress. This paper gives an overview of the analytical techniques used for sample collection, preconcentration and analysis of human breath composition. The diagnostic potential of different disease-marking substances in human breath for a selection of diseases and the clinical applications of breath analysis are discussed. Copyright 2007 John Wiley & Sons, Ltd.
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            Selected ion flow tube mass spectrometry (SIFT-MS) for on-line trace gas analysis.

            Selected ion flow tube mass spectrometry (SIFT-MS) is a new analytical technique for the real-time quantification of several trace gases simultaneously in air and breath. It relies on chemical ionization of the trace gas molecules in air/breath samples introduced into helium carrier gas using H(3)O(+), NO(+), and O(2) (+.) precursor ions. Reactions between the precursor ions and trace gas molecules proceed for an accurately defined time, the precursor and product ions being detected and counted by a downstream mass spectrometer, thus effecting quantification. Absolute concentrations of trace gases in single breath exhalation can be determined by SIFT-MS down to ppb levels, obviating sample collection and calibration. Illustrative examples of SIFT-MS studies include (i) analysis of gases from combustion engines, animals and their waste, and food; (ii) breath and urinary headspace studies of metabolites, ethanol metabolism, elevated acetone during ovulation, and exogenous compounds; and (iii) urinary infection and the presence of tumors, the influence of dialysis on breath ammonia, acetone, and isoprene, and acetaldehyde released by cancer cells in vitro. Flowing afterglow mass spectrometry (FA-MS) is briefly described, which allows on-line quantification of deuterium in breath water vapor.
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              Detection of lung cancer by sensor array analyses of exhaled breath.

              Electronic noses are successfully used in commercial applications, including detection and analysis of volatile organic compounds in the food industry. We hypothesized that the electronic nose could identify and discriminate between lung diseases, especially bronchogenic carcinoma. In a discovery and training phase, exhaled breath of 14 individuals with bronchogenic carcinoma and 45 healthy control subjects or control subjects without cancer was analyzed. Principal components and canonic discriminant analysis of the sensor data was used to determine whether exhaled gases could discriminate between cancer and noncancer. Discrimination between classes was performed using Mahalanobis distance. Support vector machine analysis was used to create and apply a cancer prediction model prospectively in a separate group of 76 individuals, 14 with and 62 without cancer. Principal components and canonic discriminant analysis demonstrated discrimination between samples from patients with lung cancer and those from other groups. In the validation study, the electronic nose had 71.4% sensitivity and 91.9% specificity for detecting lung cancer; positive and negative predictive values were 66.6 and 93.4%, respectively. In this population with a lung cancer prevalence of 18%, positive and negative predictive values were 66.6 and 94.5%, respectively. The exhaled breath of patients with lung cancer has distinct characteristics that can be identified with an electronic nose. The results provide feasibility to the concept of using the electronic nose for managing and detecting lung cancer.
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                Author and article information

                Journal
                Medicina (Kaunas)
                medicina
                Medicina
                MDPI
                1010-660X
                1648-9144
                25 June 2019
                June 2019
                : 55
                : 6
                : 306
                Affiliations
                [1 ]Discipline of Surgery, College of Medicine and Public Health, Flinders University, Adelaide 5042, Australia; eooi.entsurgery@ 123456gmail.com (E.H.O.); david.watson@ 123456flinders.edu.au (D.I.W.); simone.jaenisch@ 123456flinders.edu.au (S.J.); roger.yazbek@ 123456flinders.edu.au (R.Y.)
                [2 ]Flinders Centre for Innovation in Cancer, Flinders University, Adelaide 5042, South Australia
                [3 ]Flinders Center for Epidemiology and Biostatistics, Flinders University, Adelaide 5042, South Australia; feruza.kholmurodova@ 123456flinders.edu.au
                Author notes
                [* ]Correspondence: dhinac20@ 123456gmail.com ; Tel.: +61-424-436-579
                Author information
                https://orcid.org/0000-0002-7201-815X
                https://orcid.org/0000-0002-7683-2693
                https://orcid.org/0000-0002-5953-5881
                https://orcid.org/0000-0002-1038-4998
                Article
                medicina-55-00306
                10.3390/medicina55060306
                6631766
                31242578
                5d308363-1a62-4c8c-bc68-134e8c146afe
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 April 2019
                : 20 June 2019
                Categories
                Article

                breath test,head and neck cancer,neoplasms head and neck,cancer screening,cancer screening tests,volatile organic compounds

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