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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">tiblj</journal-id><journal-title-group><journal-title xml:lang="ru">Туберкулез и болезни легких</journal-title><trans-title-group xml:lang="en"><trans-title>Tuberculosis and Lung Diseases</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2075-1230</issn><issn pub-type="epub">2542-1506</issn><publisher><publisher-name>Медицинские знания и технологии</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.21292/2075-1230-2015-0-2-4-11</article-id><article-id custom-type="elpub" pub-id-type="custom">tiblj-334</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОБЗОРЫ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>REVIEWS</subject></subj-group></article-categories><title-group><article-title>Метаболомические исследования в пульмонологии</article-title><trans-title-group xml:lang="en"><trans-title>Metabolomic studies in pulmonology</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фурина</surname><given-names>Р. Р.</given-names></name><name name-style="western" xml:lang="en"><surname>Furina</surname><given-names>R. R.</given-names></name></name-alternatives><bio xml:lang="ru"><p>врач-эндоскопист эндоскопического отделения,</p><p>424030, г. Йошкар-Ола, ул. Осипенко, д. 33</p></bio><email xlink:type="simple">furina_raisa@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff xml:lang="ru" id="aff-1"><institution>ГБУ РМЭ «Республиканская клиническая больница»</institution><country>Russian Federation</country></aff><pub-date pub-type="collection"><year>2015</year></pub-date><pub-date pub-type="epub"><day>01</day><month>02</month><year>2015</year></pub-date><volume>0</volume><issue>2</issue><fpage>4</fpage><lpage>11</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Фурина Р.Р., 2015</copyright-statement><copyright-year>2015</copyright-year><copyright-holder xml:lang="ru">Фурина Р.Р.</copyright-holder><copyright-holder xml:lang="en">Furina R.R.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://www.tibl-journal.com/jour/article/view/334">https://www.tibl-journal.com/jour/article/view/334</self-uri><abstract><p>В обзоре отражены результаты применения метаболомических исследований в пульмонологии. Ключевая идея метаболомики заключается в обнаружении специфических биомаркеров в биологическом образце для диагностики заболеваний бронхов и легких. Приведены основные методы разделения и идентификации летучих органических веществ как биомаркеров (газовая хроматография, масс-спектрометрия, спектроскопия ядерного магнитного резонанса), применяемые в метаболомике. Также освещен метод твердофазной микроэкстракции, применяемой в качестве предварительной подготовки образца. Представлены результаты лабораторных исследований по поиску биомаркеров рака легких, острого респираторного дистресс-синдрома, хронической обструктивной болезни легких, муковисцедоза, хронических инфекций, туберкулеза легких. Кроме того, уделено внимание применению возможностей метаболомики в экспериментальной медицине, в том числе изучению бронхиальной астмы. Информация интересна как для теоретиков, так и для практикующих врачей.</p></abstract><trans-abstract xml:lang="en"><p>The review shows the results of metabolomic studies in pulmonology. The key idea of metabolomics is to detect specific biomarkers in a biological sample for the diagnosis of diseases of the bronchi and lung. Main methods for the separation and identification of volatile organic substances as biomarkers (gas chromatography, mass spectrometry, and nuclear magnetic resonance spectrometry) used in metabolomics are given. A solid-phase microextraction method used to pre-prepare a sample is also covered. The results of laboratory tests for biomarkers for lung cancer, acute respiratory distress syndrome, chronic obstructive pulmonary disease, cystic fibrosis, chronic infections, and pulmonary tuberculosis are presented. In addition, emphasis is placed on the possibilities of metabolomics used in experimental medicine, including to the study of asthma. The information is of interest to both theorists and practitioners.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>метаболомика</kwd><kwd>летучие органические вещества</kwd><kwd>метаболомический профиль</kwd><kwd>биомаркеры</kwd><kwd>газовая хроматография</kwd><kwd>масс-спектрометрия</kwd></kwd-group><kwd-group xml:lang="en"><kwd>metabolomics</kwd><kwd>volatile organic substances</kwd><kwd>metabolomic profile</kwd><kwd>biomarkers</kwd><kwd>gas chromatography</kwd><kwd>mass spectrometry</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Царев Н. И., Царев В. И., Катраков И. Б. Практическая газовая хроматография. - Барнаул: Изд-во Алт. ун-та, 2000. - 156 с.</mixed-citation><mixed-citation xml:lang="en">Царев Н. И., Царев В. И., Катраков И. Б. Практическая газовая хроматография. - Барнаул: Изд-во Алт. ун-та, 2000. - 156 с.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Arora A. , Willhite C. A., Liebler D. C. Interactions of β-carotene and cigarette smoke in human bronchial epithelial cells // Carcinogenesis. - 2001. - Vol. 22, № 8. - P. 1173-1178.</mixed-citation><mixed-citation xml:lang="en">Arora A. , Willhite C. A., Liebler D. C. Interactions of β-carotene and cigarette smoke in human bronchial epithelial cells // Carcinogenesis. - 2001. - Vol. 22, № 8. - P. 1173-1178.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Bos L., Weda H., Wang Y. et al. Exhaled breath metabolomics as a noninvasive diagnostic tool for acute respiratory distress syndrome // ERJ Express. - 2014. - P. 1-10.</mixed-citation><mixed-citation xml:lang="en">Bos L., Weda H., Wang Y. et al. Exhaled breath metabolomics as a noninvasive diagnostic tool for acute respiratory distress syndrome // ERJ Express. - 2014. - P. 1-10.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Brown M. V., McDunn J. E., Gunst P. R. et al. Cancer detection and biopsy classification using concurrent histopathological and metabolomic analysis of core biopsies // Genom Med. - 2012. - Vol. 4. - P. 33.</mixed-citation><mixed-citation xml:lang="en">Brown M. V., McDunn J. E., Gunst P. R. et al. Cancer detection and biopsy classification using concurrent histopathological and metabolomic analysis of core biopsies // Genom Med. - 2012. - Vol. 4. - P. 33.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Chambers S. T., Bhandari S., Scott-Thomas A. et al. Novel diagnostics: progress toward a breath test for invasive Aspergillus fumigatus // Med. Mycol. - 2011. - Vol. 49. - P. 54-61.</mixed-citation><mixed-citation xml:lang="en">Chambers S. T., Bhandari S., Scott-Thomas A. et al. Novel diagnostics: progress toward a breath test for invasive Aspergillus fumigatus // Med. Mycol. - 2011. - Vol. 49. - P. 54-61.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Catchpole G., Platzer A., Weikert C. et al. Metabolic profiling reveals key metabolic features of renal cell carcinoma // J. Cell. Mol. Med. - 2011 - Vol. 15 - P. 109-118.</mixed-citation><mixed-citation xml:lang="en">Catchpole G., Platzer A., Weikert C. et al. Metabolic profiling reveals key metabolic features of renal cell carcinoma // J. Cell. Mol. Med. - 2011 - Vol. 15 - P. 109-118.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Dally H., Gassner K., Jager B., Schmezer P. Myeloperoxidase (mpo) genotype and lung cancer histologic types: the mpo-463 a allele is associated with reduced risk for small cell lung cancer in smokers // Int. J. Cancer. - 2002 - Vol. 102, № 5 - P. 530-535.</mixed-citation><mixed-citation xml:lang="en">Dally H., Gassner K., Jager B., Schmezer P. Myeloperoxidase (mpo) genotype and lung cancer histologic types: the mpo-463 a allele is associated with reduced risk for small cell lung cancer in smokers // Int. J. Cancer. - 2002 - Vol. 102, № 5 - P. 530-535.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Daviss. Growing pains for metabolomics // Scientist. - 2005 - Vol. 19, № 8 - P. 25-28.</mixed-citation><mixed-citation xml:lang="en">Daviss. Growing pains for metabolomics // Scientist. - 2005 - Vol. 19, № 8 - P. 25-28.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">de Laurentiis G., Paris D., Melck D. et al. Metabonomic analysis of exhaled breath condensate in adults by nuclear magnetic resonance spectroscopy // Eur. Respir. J. - 2008 - Vol. 32, № 5 - P. 1175-1183.</mixed-citation><mixed-citation xml:lang="en">de Laurentiis G., Paris D., Melck D. et al. Metabonomic analysis of exhaled breath condensate in adults by nuclear magnetic resonance spectroscopy // Eur. Respir. J. - 2008 - Vol. 32, № 5 - P. 1175-1183.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Denkert C., Budczies J., Fiehn O. et al. Metabolite profiling of human colon carcinoma-deregulation of TCA cycle and amino acid turnover // Mol. Cancer. - 2008 - Vol. 7 - P. 72.</mixed-citation><mixed-citation xml:lang="en">Denkert C., Budczies J., Fiehn O. et al. Metabolite profiling of human colon carcinoma-deregulation of TCA cycle and amino acid turnover // Mol. Cancer. - 2008 - Vol. 7 - P. 72.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Goeminne P. C., Vandendriessche T., Eldere J. V. et al. Detection of Pseudomonas aeruginosa in sputum headspace through volatile organic compound analysis // BioMed Central. - 2012. - Vol. 13 - P. 83.</mixed-citation><mixed-citation xml:lang="en">Goeminne P. C., Vandendriessche T., Eldere J. V. et al. Detection of Pseudomonas aeruginosa in sputum headspace through volatile organic compound analysis // BioMed Central. - 2012. - Vol. 13 - P. 83.</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Hakim M., Broza Y. Y., Barash O., Peled N. et al. Volatile Organic Compounds of Lung Cancer and Possible Biochemical Pathways // Chemical Reviews. - 2012 - Vol. 112, № 11. - P. 5949-5966.</mixed-citation><mixed-citation xml:lang="en">Hakim M., Broza Y. Y., Barash O., Peled N. et al. Volatile Organic Compounds of Lung Cancer and Possible Biochemical Pathways // Chemical Reviews. - 2012 - Vol. 112, № 11. - P. 5949-5966.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Hawkins C. L., Davies M. J. Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals // Chem. Res. Toxicol. - 2002 - Vol. 15, № 1 - P. 83-92.</mixed-citation><mixed-citation xml:lang="en">Hawkins C. L., Davies M. J. Hypochlorite-induced damage to DNA, RNA, and polynucleotides: formation of chloramines and nitrogen-centered radicals // Chem. Res. Toxicol. - 2002 - Vol. 15, № 1 - P. 83-92.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Jin L., Lloyd R. V. In situ hybridization: methods and applications // J. Clin. Lab. Anal. - 1997. - Vol. 11 - P. 2-9.</mixed-citation><mixed-citation xml:lang="en">Jin L., Lloyd R. V. In situ hybridization: methods and applications // J. Clin. Lab. Anal. - 1997. - Vol. 11 - P. 2-9.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Jordan K. W., Nordenstam J., Lauwers G. Y. et al. Metabolomic characterization of human rectal adenocarcinoma with intact tissue magnetic resonance spectroscop // Diseases of the Colon &amp; Rectum. - 2009 - Vol. 52, № 3 - P. 520-525.</mixed-citation><mixed-citation xml:lang="en">Jordan K. W., Nordenstam J., Lauwers G. Y. et al. Metabolomic characterization of human rectal adenocarcinoma with intact tissue magnetic resonance spectroscop // Diseases of the Colon &amp; Rectum. - 2009 - Vol. 52, № 3 - P. 520-525.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Kouremenos К. А., Pitt J., Marriott P. J. Metabolic profiling of infant urine using comprehensive two-dimensional gas chromatography: Application to the diagnosis of organic acidurias and biomarker discovery // J. Chromatography A. - 2010 - Vol. 1217. - P. 104-111.</mixed-citation><mixed-citation xml:lang="en">Kouremenos К. А., Pitt J., Marriott P. J. Metabolic profiling of infant urine using comprehensive two-dimensional gas chromatography: Application to the diagnosis of organic acidurias and biomarker discovery // J. Chromatography A. - 2010 - Vol. 1217. - P. 104-111.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Lau D., Mollnau H., Eiserich J. P., Freeman B. A. et al. Myeloperoxidase mediates neutrophil activation by association with cd11b/cd18 integrins // Proc Natl Acad Sci USA. - 2005. - Vol. 102, № 2. - P. 431-436.</mixed-citation><mixed-citation xml:lang="en">Lau D., Mollnau H., Eiserich J. P., Freeman B. A. et al. Myeloperoxidase mediates neutrophil activation by association with cd11b/cd18 integrins // Proc Natl Acad Sci USA. - 2005. - Vol. 102, № 2. - P. 431-436.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Liu C., Wang X.-D., Bronson R. T. et al. Effects of physiological versus pharmacological β-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets // Carcinogenesis. - 2000. - Vol. 21, № 12. - P. 2245-2253.</mixed-citation><mixed-citation xml:lang="en">Liu C., Wang X.-D., Bronson R. T. et al. Effects of physiological versus pharmacological β-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets // Carcinogenesis. - 2000. - Vol. 21, № 12. - P. 2245-2253.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Martano G., Vogl C., Bojaxhi E. et al. Solid-phase extraction and GC-MS analysis of potentially genotoxic cleavage products of β-carotene in primary cell cultures // An. Bioanal Chem. - 2011. - Vol. 400 - P. 2415-242.</mixed-citation><mixed-citation xml:lang="en">Martano G., Vogl C., Bojaxhi E. et al. Solid-phase extraction and GC-MS analysis of potentially genotoxic cleavage products of β-carotene in primary cell cultures // An. Bioanal Chem. - 2011. - Vol. 400 - P. 2415-242.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Mehta A. K., Arora N., Gaur S. N. et al. Choline supplementation reduces oxidative stress in mouse model of allergic airway disease // Eur. J. Clin. Invest. - 2009. - Vol. 39. - P. 934-941.</mixed-citation><mixed-citation xml:lang="en">Mehta A. K., Arora N., Gaur S. N. et al. Choline supplementation reduces oxidative stress in mouse model of allergic airway disease // Eur. J. Clin. Invest. - 2009. - Vol. 39. - P. 934-941.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Mehta A. K., Singh B. P., Arora N. et al. Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma // Immunobiology. - 2010. - Vol. 215. - P. 527-534.</mixed-citation><mixed-citation xml:lang="en">Mehta A. K., Singh B. P., Arora N. et al. Choline attenuates immune inflammation and suppresses oxidative stress in patients with asthma // Immunobiology. - 2010. - Vol. 215. - P. 527-534.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Palozza P., Serini S., Di Nicuolo F. et al. β-Carotene exacerbates DNA oxidative damage and modifies p53-related pathways of cell proliferation and apoptosis in cultured cells exposed to tobacco smoke condensate // Carcinogenesis. - 2004 - Vol. 25, № 8. - P. 1315-1325.</mixed-citation><mixed-citation xml:lang="en">Palozza P., Serini S., Di Nicuolo F. et al. β-Carotene exacerbates DNA oxidative damage and modifies p53-related pathways of cell proliferation and apoptosis in cultured cells exposed to tobacco smoke condensate // Carcinogenesis. - 2004 - Vol. 25, № 8. - P. 1315-1325.</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Palozza P. Can β-carotene regulate cell growth by a redox mechanism? An answer from cultured cells // Biochim. Biophys. Acta Mol. Basis Dis. - 2005 - Vol. 1740, № 2. - P. 215-221.</mixed-citation><mixed-citation xml:lang="en">Palozza P. Can β-carotene regulate cell growth by a redox mechanism? An answer from cultured cells // Biochim. Biophys. Acta Mol. Basis Dis. - 2005 - Vol. 1740, № 2. - P. 215-221.</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Paolini M., Antelli A., Pozzetti L. et al. Induction of cytochrome p450 enzymes and over-generation of oxygen radicals in beta-carotene supplemented rats // Carcinogenesis - 2001. - Vol. 22, № 9. - P. 1483-1495.</mixed-citation><mixed-citation xml:lang="en">Paolini M., Antelli A., Pozzetti L. et al. Induction of cytochrome p450 enzymes and over-generation of oxygen radicals in beta-carotene supplemented rats // Carcinogenesis - 2001. - Vol. 22, № 9. - P. 1483-1495.</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Paolini M., Abdel-Rahman S. Z., Sapone A. et al. β-Carotene: a cancer chemopreventive agent or a co-carcinogen? // Mutat. Res. Rev. Mutat. Res. - 2003. - Vol. 543, № 3. - P. 195-200.</mixed-citation><mixed-citation xml:lang="en">Paolini M., Abdel-Rahman S. Z., Sapone A. et al. β-Carotene: a cancer chemopreventive agent or a co-carcinogen? // Mutat. Res. Rev. Mutat. Res. - 2003. - Vol. 543, № 3. - P. 195-200.</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Patti G. J., Yanes O., Siuzdak G. Innovation: Metabolomics: the apogee of the omics trilogy // Nat. Rev. Mol. Cell. Biol. - 2012. - Vol. 13. - P. 263-269.</mixed-citation><mixed-citation xml:lang="en">Patti G. J., Yanes O., Siuzdak G. Innovation: Metabolomics: the apogee of the omics trilogy // Nat. Rev. Mol. Cell. Biol. - 2012. - Vol. 13. - P. 263-269.</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Pauling L., Robinson A. B., Teranishi R. et al. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography // Proc. Natl Acad. Sci. USA. - 1971. - Vol. 68. - P. 2374-2376.</mixed-citation><mixed-citation xml:lang="en">Pauling L., Robinson A. B., Teranishi R. et al. Quantitative analysis of urine vapor and breath by gas-liquid partition chromatography // Proc. Natl Acad. Sci. USA. - 1971. - Vol. 68. - P. 2374-2376.</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Phillips M., Cataneo R. N., Cummin A. R. C. et al. Detection of lung cancer with volatile markers in the breath // Chest. - 2003. - Vol. 123, № 6. - P. 2115-2123.</mixed-citation><mixed-citation xml:lang="en">Phillips M., Cataneo R. N., Cummin A. R. C. et al. Detection of lung cancer with volatile markers in the breath // Chest. - 2003. - Vol. 123, № 6. - P. 2115-2123.</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Phillips M., Cataneo R. N., Condos R. et al. Volatile biomarkers of pulmonary tuberculosis in the breath // Tuberculosis. - 2007. - Vol. 87. - P. 44-52.</mixed-citation><mixed-citation xml:lang="en">Phillips M., Cataneo R. N., Condos R. et al. Volatile biomarkers of pulmonary tuberculosis in the breath // Tuberculosis. - 2007. - Vol. 87. - P. 44-52.</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Phillips M., Altorki N., Austin J. H. M. et al. Detection of lung cancer using weighted digital analysis of breath biomarkers // Clin. Chim. Acta. - 2008. - Vol. 393, № 2. - P. 76-84.</mixed-citation><mixed-citation xml:lang="en">Phillips M., Altorki N., Austin J. H. M. et al. Detection of lung cancer using weighted digital analysis of breath biomarkers // Clin. Chim. Acta. - 2008. - Vol. 393, № 2. - P. 76-84.</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Phillips M., Basa-Dalay V., Bothamley G. et al. Breath biomarkers of active pulmonary tuberculosis // Tuberculosis (Edinb.). - 2010. - Vol. 90. - P. 145-151.</mixed-citation><mixed-citation xml:lang="en">Phillips M., Basa-Dalay V., Bothamley G. et al. Breath biomarkers of active pulmonary tuberculosis // Tuberculosis (Edinb.). - 2010. - Vol. 90. - P. 145-151.</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Reid D. W., Misso N., Aggarwal S. et al. Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis // Respirology. - 2007. - Vol. 12. - P. 63-69.</mixed-citation><mixed-citation xml:lang="en">Reid D. W., Misso N., Aggarwal S. et al. Oxidative stress and lipid-derived inflammatory mediators during acute exacerbations of cystic fibrosis // Respirology. - 2007. - Vol. 12. - P. 63-69.</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Sands C. J., Coen M., Ebbels T. M. et al. Data-driven approach for metabolite relationship recovery in biological 1H NMR data sets using iterative statistical total correlation spectroscopy // An. Chem. - 2011. - Vol. 83. - P. 2075-2082.</mixed-citation><mixed-citation xml:lang="en">Sands C. J., Coen M., Ebbels T. M. et al. Data-driven approach for metabolite relationship recovery in biological 1H NMR data sets using iterative statistical total correlation spectroscopy // An. Chem. - 2011. - Vol. 83. - P. 2075-2082.</mixed-citation></citation-alternatives></ref><ref id="cit34"><label>34</label><citation-alternatives><mixed-citation xml:lang="ru">Siems W., Capuozzo E., Crifo C. et al. Carotenoid cleavage products modify respiratory burst and induce apoptosis of human neutrophils // Biochim. Biophys. Acta Mol. Basis Dis. - 2003 - Vol. 1639, № 1. - P. 27-33.</mixed-citation><mixed-citation xml:lang="en">Siems W., Capuozzo E., Crifo C. et al. Carotenoid cleavage products modify respiratory burst and induce apoptosis of human neutrophils // Biochim. Biophys. Acta Mol. Basis Dis. - 2003 - Vol. 1639, № 1. - P. 27-33.</mixed-citation></citation-alternatives></ref><ref id="cit35"><label>35</label><citation-alternatives><mixed-citation xml:lang="ru">Siems W., Wiswedel I., Salerno C., Crifo C. et al. β-Carotene breakdown products may impair mitochondrial functions - potential side effects of high-dose β-carotene supplementation // J. Nutr. Biochem. - 2005. - Vol. 16, № 7. - P. 385-397.</mixed-citation><mixed-citation xml:lang="en">Siems W., Wiswedel I., Salerno C., Crifo C. et al. β-Carotene breakdown products may impair mitochondrial functions - potential side effects of high-dose β-carotene supplementation // J. Nutr. Biochem. - 2005. - Vol. 16, № 7. - P. 385-397.</mixed-citation></citation-alternatives></ref><ref id="cit36"><label>36</label><citation-alternatives><mixed-citation xml:lang="ru">Silva C. L., Passos M., Camara J. S. Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry // Brit. J. Cancer. - 2011. - Vol. 105. - P. 1894-1904.</mixed-citation><mixed-citation xml:lang="en">Silva C. L., Passos M., Camara J. S. Investigation of urinary volatile organic metabolites as potential cancer biomarkers by solid-phase microextraction in combination with gas chromatography-mass spectrometry // Brit. J. Cancer. - 2011. - Vol. 105. - P. 1894-1904.</mixed-citation></citation-alternatives></ref><ref id="cit37"><label>37</label><citation-alternatives><mixed-citation xml:lang="ru">Smith D., Španel P., Sule-Suso J. Advantages of breath testing for the early diagnosis of lung cancer // Expert Rev. Mol. Diagn. - 2010. - Vol. 10. - P. 255-257.</mixed-citation><mixed-citation xml:lang="en">Smith D., Španel P., Sule-Suso J. Advantages of breath testing for the early diagnosis of lung cancer // Expert Rev. Mol. Diagn. - 2010. - Vol. 10. - P. 255-257.</mixed-citation></citation-alternatives></ref><ref id="cit38"><label>38</label><citation-alternatives><mixed-citation xml:lang="ru">Sreekumar A., Poisson L. M., Rajendiran T. M. et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression // Nature. - 2009. - Vol. 457. - P. 910-914.</mixed-citation><mixed-citation xml:lang="en">Sreekumar A., Poisson L. M., Rajendiran T. M. et al. Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression // Nature. - 2009. - Vol. 457. - P. 910-914.</mixed-citation></citation-alternatives></ref><ref id="cit39"><label>39</label><citation-alternatives><mixed-citation xml:lang="ru">Syhre M., Chambers S. T. The scent of Mycobacterium tuberculosis // Tuberculosis (Edinb.). - 2008 - Vol. 88 - P. 317-323.</mixed-citation><mixed-citation xml:lang="en">Syhre M., Chambers S. T. The scent of Mycobacterium tuberculosis // Tuberculosis (Edinb.). - 2008 - Vol. 88 - P. 317-323.</mixed-citation></citation-alternatives></ref><ref id="cit40"><label>40</label><citation-alternatives><mixed-citation xml:lang="ru">Syhre M., Manning L., Phuanukoonnon S. et al. The scent of Mycobacterium tuberculosis - part II breath // Tuberculosis (Edinb.). - 2009. - Vol. 89 - P. 263-266.</mixed-citation><mixed-citation xml:lang="en">Syhre M., Manning L., Phuanukoonnon S. et al. The scent of Mycobacterium tuberculosis - part II breath // Tuberculosis (Edinb.). - 2009. - Vol. 89 - P. 263-266.</mixed-citation></citation-alternatives></ref><ref id="cit41"><label>41</label><citation-alternatives><mixed-citation xml:lang="ru">Taylor C. R., Barr N. J. Techniques of Immunohistochemistry: Principles, Pitfalls, and Standardization // In Diagnostic Immunohistochemistry. Edited by: Dabbs D. Philadelphia: Saunders Elsevier. - 2010. - P. 1-41.</mixed-citation><mixed-citation xml:lang="en">Taylor C. R., Barr N. J. Techniques of Immunohistochemistry: Principles, Pitfalls, and Standardization // In Diagnostic Immunohistochemistry. Edited by: Dabbs D. Philadelphia: Saunders Elsevier. - 2010. - P. 1-41.</mixed-citation></citation-alternatives></ref><ref id="cit42"><label>42</label><citation-alternatives><mixed-citation xml:lang="ru">Thorn R. M., Greenman J. Microbial volatile compounds in health and disease conditions // J. Breath Research. - 2012. - Vol. 6 - P. 1-25.</mixed-citation><mixed-citation xml:lang="en">Thorn R. M., Greenman J. Microbial volatile compounds in health and disease conditions // J. Breath Research. - 2012. - Vol. 6 - P. 1-25.</mixed-citation></citation-alternatives></ref><ref id="cit43"><label>43</label><citation-alternatives><mixed-citation xml:lang="ru">Thorn R. M., Reynolds D. M., Greenman J. Multivariate analysis of bacterial volatile compound profiles for discrimination between selected species and strains in vitro // J. Microbiol. Methods. - 2011 - Vol. 84. - P. 258-264.</mixed-citation><mixed-citation xml:lang="en">Thorn R. M., Reynolds D. M., Greenman J. Multivariate analysis of bacterial volatile compound profiles for discrimination between selected species and strains in vitro // J. Microbiol. Methods. - 2011 - Vol. 84. - P. 258-264.</mixed-citation></citation-alternatives></ref><ref id="cit44"><label>44</label><citation-alternatives><mixed-citation xml:lang="ru">Torday J. S., Torday D. P., Gutnick J. et al. Biologic role of fetal lung fibroblast triglycerides as antioxidants // Pediatr. Res. - 2001 - Vol. 49. - P. 843-849.</mixed-citation><mixed-citation xml:lang="en">Torday J. S., Torday D. P., Gutnick J. et al. Biologic role of fetal lung fibroblast triglycerides as antioxidants // Pediatr. Res. - 2001 - Vol. 49. - P. 843-849.</mixed-citation></citation-alternatives></ref><ref id="cit45"><label>45</label><citation-alternatives><mixed-citation xml:lang="ru">Veenstra T. D. Metabolomics: the final frontier // Genome Med. - 2012. - Vol. 4. - P. 40.</mixed-citation><mixed-citation xml:lang="en">Veenstra T. D. Metabolomics: the final frontier // Genome Med. - 2012. - Vol. 4. - P. 40.</mixed-citation></citation-alternatives></ref><ref id="cit46"><label>46</label><citation-alternatives><mixed-citation xml:lang="ru">Vincent J. L., Rello J., Marshall J. et al. International study of the prevalence and outcomes of infection in intensive care units // JAMA. - 2009. - Vol. 302. - P. 2323-2329.</mixed-citation><mixed-citation xml:lang="en">Vincent J. L., Rello J., Marshall J. et al. International study of the prevalence and outcomes of infection in intensive care units // JAMA. - 2009. - Vol. 302. - P. 2323-2329.</mixed-citation></citation-alternatives></ref><ref id="cit47"><label>47</label><citation-alternatives><mixed-citation xml:lang="ru">We H., Xu Y. J., Xu F. et al. Metabolomics reveals altered metabolic pathways in experimental asthma // Am. J. Respir. Cell. Mol. Biol. - 2013 - Vol. 48, № 2. - P. 204-211.</mixed-citation><mixed-citation xml:lang="en">We H., Xu Y. J., Xu F. et al. Metabolomics reveals altered metabolic pathways in experimental asthma // Am. J. Respir. Cell. Mol. Biol. - 2013 - Vol. 48, № 2. - P. 204-211.</mixed-citation></citation-alternatives></ref><ref id="cit48"><label>48</label><citation-alternatives><mixed-citation xml:lang="ru">Weetjens B. J. et al. African pouched rats for the detection of pulmonary tuberculosis in sputum samples // Int. J. Tuberc. Lung Dis. - 2009. - Vol. 13 - P. 737-743.</mixed-citation><mixed-citation xml:lang="en">Weetjens B. J. et al. African pouched rats for the detection of pulmonary tuberculosis in sputum samples // Int. J. Tuberc. Lung Dis. - 2009. - Vol. 13 - P. 737-743.</mixed-citation></citation-alternatives></ref><ref id="cit49"><label>49</label><citation-alternatives><mixed-citation xml:lang="ru">Wehinger A., Schmid A., Mechtcheriakov S. et al. Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas // Int. J. Mass Spectrom. - 2007. - Vol. 265, № 1. - P. 49-59.</mixed-citation><mixed-citation xml:lang="en">Wehinger A., Schmid A., Mechtcheriakov S. et al. Lung cancer detection by proton transfer reaction mass-spectrometric analysis of human breath gas // Int. J. Mass Spectrom. - 2007. - Vol. 265, № 1. - P. 49-59.</mixed-citation></citation-alternatives></ref><ref id="cit50"><label>50</label><citation-alternatives><mixed-citation xml:lang="ru">Wishart D. S., Tzur D., Knox C. et al. HMDB: the Human Metabolome Database // Nucleic Acids Research. - 2007. - Vol. 35. - P. 521-526.</mixed-citation><mixed-citation xml:lang="en">Wishart D. S., Tzur D., Knox C. et al. HMDB: the Human Metabolome Database // Nucleic Acids Research. - 2007. - Vol. 35. - P. 521-526.</mixed-citation></citation-alternatives></ref><ref id="cit51"><label>51</label><citation-alternatives><mixed-citation xml:lang="ru">Wolak J. E., Esther C. R., O’Connell T. M. Metabolomic analysis of bronchoalveolar lavage fluid from cystic fibrosis patients // Biomarkers. - 2009. - Vol. 14. - P. 55-60.</mixed-citation><mixed-citation xml:lang="en">Wolak J. E., Esther C. R., O’Connell T. M. Metabolomic analysis of bronchoalveolar lavage fluid from cystic fibrosis patients // Biomarkers. - 2009. - Vol. 14. - P. 55-60.</mixed-citation></citation-alternatives></ref><ref id="cit52"><label>52</label><citation-alternatives><mixed-citation xml:lang="ru">Wright S. M., Hockey P. M., Enhorning G. et al. Altered airway surfactant phospholipid composition and reduced lung function in asthma // J. Appl. Physiol. - 2000. - Vol. 89. - P. 1283-1292.</mixed-citation><mixed-citation xml:lang="en">Wright S. M., Hockey P. M., Enhorning G. et al. Altered airway surfactant phospholipid composition and reduced lung function in asthma // J. Appl. Physiol. - 2000. - Vol. 89. - P. 1283-1292.</mixed-citation></citation-alternatives></ref><ref id="cit53"><label>53</label><citation-alternatives><mixed-citation xml:lang="ru">Wu H., Xue R., Tang Z. Metabolomic investigation of gastric cancer tissue using gas chromatography/mass spectrometry // An. Bioanal. Chem. - 2010. - Vol. 396. - P. 1385-1395.</mixed-citation><mixed-citation xml:lang="en">Wu H., Xue R., Tang Z. Metabolomic investigation of gastric cancer tissue using gas chromatography/mass spectrometry // An. Bioanal. Chem. - 2010. - Vol. 396. - P. 1385-1395.</mixed-citation></citation-alternatives></ref><ref id="cit54"><label>54</label><citation-alternatives><mixed-citation xml:lang="ru">Yang J., Eiserich J. P., Cross C. E. et al. Metabolomic Profiling of Regulatory Lipid Mediators in Sputum from Adult Cystic Fibrosis Patients // Free Radic. Biol. Med. - 2012. - Vol. 53, № 1 - P. 160-171.</mixed-citation><mixed-citation xml:lang="en">Yang J., Eiserich J. P., Cross C. E. et al. Metabolomic Profiling of Regulatory Lipid Mediators in Sputum from Adult Cystic Fibrosis Patients // Free Radic. Biol. Med. - 2012. - Vol. 53, № 1 - P. 160-171.</mixed-citation></citation-alternatives></ref><ref id="cit55"><label>55</label><citation-alternatives><mixed-citation xml:lang="ru">Zakrzewski J. T., Barnes N. C., Piper P. J. et al. Detection of sputum eicosanoids in cystic fibrosis and in normal saliva by bioassay and radioimmunoassay // Br. J. Clin. Pharmacol. - 1987. - Vol. 23 - P. 19-27.</mixed-citation><mixed-citation xml:lang="en">Zakrzewski J. T., Barnes N. C., Piper P. J. et al. Detection of sputum eicosanoids in cystic fibrosis and in normal saliva by bioassay and radioimmunoassay // Br. J. Clin. Pharmacol. - 1987. - Vol. 23 - P. 19-27.</mixed-citation></citation-alternatives></ref><ref id="cit56"><label>56</label><citation-alternatives><mixed-citation xml:lang="ru">Zakrzewski J. T., Barnes N. C., Costello J. F. et al. Lipid mediators in cystic fibrosis and chronic obstructive pulmonary disease // Am. Rev. Respir. Dis. - 1987. - Vol. 136. - P. 779-782.</mixed-citation><mixed-citation xml:lang="en">Zakrzewski J. T., Barnes N. C., Costello J. F. et al. Lipid mediators in cystic fibrosis and chronic obstructive pulmonary disease // Am. Rev. Respir. Dis. - 1987. - Vol. 136. - P. 779-782.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
