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      Blood and breath profiles of volatile organic compounds in patients with end-stage renal disease

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          Abstract

          Background

          Monitoring of volatile organic compounds (VOCs) in exhaled breath shows great potential as a non-invasive method for assessing hemodialysis efficiency. In this work we aim at identifying and quantifying of a wide range of VOCs characterizing uremic breath and blood, with a particular focus on species responding to the dialysis treatment.

          Methods

          Gas chromatography with mass spectrometric detection coupled with solid-phase microextraction as pre-concentration method.

          Results

          A total of 60 VOCs were reliably identified and quantified in blood and breath of CKD patients. Excluding contaminants, six compounds (isoprene, dimethyl sulfide, methyl propyl sulfide, allyl methyl sulfide, thiophene and benzene) changed their blood and breath levels during the hemodialysis treatment.

          Conclusions

          Uremic breath and blood patterns were found to be notably affected by the contaminants from the extracorporeal circuits and hospital room air. Consequently, patient exposure to a wide spectrum of volatile species (hydrocarbons, aldehydes, ketones, aromatics, heterocyclic compounds) is expected during hemodialysis. Whereas highly volatile pollutants were relatively quickly removed from blood by exhalation, more soluble ones were retained and contributed to the uremic syndrome. At least two of the species observed (cyclohexanone and 2-propenal) are uremic toxins. Perhaps other volatile substances reported within this study may be toxic and have negative impact on human body functions. Further studies are required to investigate if VOCs responding to HD treatment could be used as markers for monitoring hemodialysis efficiency.

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          Most cited references41

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          Diagnostic potential of breath analysis--focus on volatile organic compounds.

          Breath analysis has attracted a considerable amount of scientific and clinical interest during the last decade. In contrast to NO, which is predominantly generated in the bronchial system, volatile organic compounds (VOCs) are mainly blood borne and therefore enable monitoring of different processes in the body. Exhaled ethane and pentane concentrations were elevated in inflammatory diseases. Acetone was linked to dextrose metabolism and lipolysis. Exhaled isoprene concentrations showed correlations with cholesterol biosynthesis. Exhaled levels of sulphur-containing compounds were elevated in liver failure and allograft rejection. Looking at a set of volatile markers may enable recognition and diagnosis of complex diseases such as lung or breast cancer. Due to technical problems of sampling and analysis and a lack of normalization and standardization, huge variations exist between results of different studies. This is among the main reasons why breath analysis could not yet been introduced into clinical practice. This review addresses the basic principles of breath analysis and the diagnostic potential of different volatile breath markers. Analytical procedures, issues concerning biochemistry and exhalation mechanisms of volatile substances, and future developments will be discussed.
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            Noninvasive detection of lung cancer by analysis of exhaled breath

            Background Lung cancer is one of the leading causes of death in Europe and the western world. At present, diagnosis of lung cancer very often happens late in the course of the disease since inexpensive, non-invasive and sufficiently sensitive and specific screening methods are not available. Even though the CT diagnostic methods are good, it must be assured that "screening benefit outweighs risk, across all individuals screened, not only those with lung cancer". An early non-invasive diagnosis of lung cancer would improve prognosis and enlarge treatment options. Analysis of exhaled breath would be an ideal diagnostic method, since it is non-invasive and totally painless. Methods Exhaled breath and inhaled room air samples were analyzed using proton transfer reaction mass spectrometry (PTR-MS) and solid phase microextraction with subsequent gas chromatography mass spectrometry (SPME-GCMS). For the PTR-MS measurements, 220 lung cancer patients and 441 healthy volunteers were recruited. For the GCMS measurements, we collected samples from 65 lung cancer patients and 31 healthy volunteers. Lung cancer patients were in different disease stages and under treatment with different regimes. Mixed expiratory and indoor air samples were collected in Tedlar bags, and either analyzed directly by PTR-MS or transferred to glass vials and analyzed by gas chromatography mass spectrometry (GCMS). Only those measurements of compounds were considered, which showed at least a 15% higher concentration in exhaled breath than in indoor air. Compounds related to smoking behavior such as acetonitrile and benzene were not used to differentiate between lung cancer patients and healthy volunteers. Results Isoprene, acetone and methanol are compounds appearing in everybody's exhaled breath. These three main compounds of exhaled breath show slightly lower concentrations in lung cancer patients as compared to healthy volunteers (p < 0.01 for isoprene and acetone, p = 0.011 for methanol; PTR-MS measurements). A comparison of the GCMS-results of 65 lung cancer patients with those of 31 healthy volunteers revealed differences in concentration for more than 50 compounds. Sensitivity for detection of lung cancer patients based on presence of (one of) 4 different compounds not arising in exhaled breath of healthy volunteers was 52% with a specificity of 100%. Using 15 (or 21) different compounds for distinction, sensitivity was 71% (80%) with a specificity of 100%. Potential marker compounds are alcohols, aldehydes, ketones and hydrocarbons. Conclusion GCMS-SPME is a relatively insensitive method. Hence compounds not appearing in exhaled breath of healthy volunteers may be below the limit of detection (LOD). PTR-MS, on the other hand, does not need preconcentration and gives much more reliable quantitative results then GCMS-SPME. The shortcoming of PTR-MS is that it cannot identify compounds with certainty. Hence SPME-GCMS and PTR-MS complement each other, each method having its particular advantages and disadvantages. Exhaled breath analysis is promising to become a future non-invasive lung cancer screening method. In order to proceed towards this goal, precise identification of compounds observed in exhaled breath of lung cancer patients is necessary. Comparison with compounds released from lung cancer cell cultures, and additional information on exhaled breath composition in other cancer forms will be important.
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              Exhaled volatile organic compounds in patients with non-small cell lung cancer: cross sectional and nested short-term follow-up study

              Background Non-invasive diagnostic strategies aimed at identifying biomarkers of lung cancer are of great interest for early cancer detection. The aim of this study was to set up a new method for identifying and quantifying volatile organic compounds (VOCs) in exhaled air of patients with non-small cells lung cancer (NSCLC), by comparing the levels with those obtained from healthy smokers and non-smokers, and patients with chronic obstructive pulmonary disease. The VOC collection and analyses were repeated three weeks after the NSCLC patients underwent lung surgery. Methods The subjects' breath was collected in a Teflon® bulb that traps the last portion of single slow vital capacity. The 13 VOCs selected for this study were concentrated using a solid phase microextraction technique and subsequently analysed by means of gas cromatography/mass spectrometry. Results The levels of the selected VOCs ranged from 10-12 M for styrene to 10-9 M for isoprene. None of VOCs alone discriminated the study groups, and so it was not possible to identify one single chemical compound as a specific lung cancer biomarker. However, multinomial logistic regression analysis showed that VOC profile can correctly classify about 80 % of cases. Only isoprene and decane levels significantly decreased after surgery. Conclusion As the combination of the 13 VOCs allowed the correct classification of the cases into groups, together with conventional diagnostic approaches, VOC analysis could be used as a complementary test for the early diagnosis of lung cancer. Its possible use in the follow-up of operated patients cannot be recommended on the basis of the results of our short-term nested study.
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                Author and article information

                Contributors
                Journal
                BMC Nephrol
                BMC Nephrol
                BMC Nephrology
                BioMed Central
                1471-2369
                2014
                8 March 2014
                : 15
                : 43
                Affiliations
                [1 ]Breath Research Institute, University of Innsbruck, Rathausplatz 4, A-6850 Dornbirn, Austria
                [2 ]Institute of Nuclear Physics PAN, Radzikowskiego 152, PL-31342 Kraków, Poland
                [3 ]Univ.-Clinic for Anesthesia, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
                [4 ]Department of Internal Medicine IV-Nephrology and Hypertension, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
                Article
                1471-2369-15-43
                10.1186/1471-2369-15-43
                3984739
                24607025
                86cf6214-c30b-4872-a44b-8d9cb5043879
                Copyright © 2014 Mochalski et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.

                History
                : 9 April 2013
                : 28 February 2014
                Categories
                Research Article

                Nephrology
                blood analysis,end-stage renal disease,breath analysis,hemodialysis,uremic syndrome,volatile organic compounds

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