<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<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">rmt</journal-id><journal-title-group><journal-title xml:lang="ru">Общая реаниматология</journal-title><trans-title-group xml:lang="en"><trans-title>General Reanimatology</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1813-9779</issn><issn pub-type="epub">2411-7110</issn><publisher><publisher-name>FSBI "SRIGR" RAMS</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.15360/1813-9779-2014-6-6-14</article-id><article-id custom-type="elpub" pub-id-type="custom">rmt-1427</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>РЕДАКЦИОННАЯ СТАТЬЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>EDITORIAL</subject></subj-group></article-categories><title-group><article-title>БЕЛОК КЛЕТОК КЛАРА (CLUB CELL PROTEIN) — НОВЫЙ ДИАГНОСТИЧЕСКИЙ КАНДИДАТНЫЙ МОЛЕКУЛЯРНЫЙ БИОМАРКЕР ПРИ НОЗОКОМИАЛЬНОЙ ПНЕВМОНИИ</article-title><trans-title-group xml:lang="en"><trans-title>Clara Cell Protein (Club Cell Protein) is a New Diagnostic Molecular Candidate Biomarker in Nosocomial Pneumonia</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>Мороз</surname><given-names>В. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Moroz</surname><given-names>V. V.</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Голубев</surname><given-names>А. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Golubev</surname><given-names>A. M.</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузовлев</surname><given-names>А. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuzovlev</surname><given-names>A. N.</given-names></name></name-alternatives><email xlink:type="simple">artem_kuzovlev@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шабанов</surname><given-names>А. К.</given-names></name><name name-style="western" xml:lang="en"><surname>Shabanov</surname><given-names>A. K.</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Писарев</surname><given-names>В. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Pisarev</surname><given-names>V. M.</given-names></name></name-alternatives><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff xml:lang="ru" id="aff-1"><institution>НИИ общей реаниматологии им. В. А. Неговского, Москва, Россия 107031, Москва, ул. Петровка, д. 25, стр. 2</institution><country>Russian Federation</country></aff><aff xml:lang="ru" id="aff-2"><institution>НИИ скорой помощи им. Н. В. Склифосовского, Москва, Россия 129010, Москва, Б. Сухаревская пл., д. 3</institution><country>Russian Federation</country></aff><pub-date pub-type="collection"><year>2014</year></pub-date><pub-date pub-type="epub"><day>21</day><month>12</month><year>2014</year></pub-date><volume>10</volume><issue>6</issue><fpage>6</fpage><lpage>14</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Мороз В.В., Голубев А.М., Кузовлев А.Н., Шабанов А.К., Писарев В.М., 2014</copyright-statement><copyright-year>2014</copyright-year><copyright-holder xml:lang="ru">Мороз В.В., Голубев А.М., Кузовлев А.Н., Шабанов А.К., Писарев В.М.</copyright-holder><copyright-holder xml:lang="en">Moroz V.V., Golubev A.M., Kuzovlev A.N., Shabanov A.K., Pisarev V.M.</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.reanimatology.com/rmt/article/view/1427">https://www.reanimatology.com/rmt/article/view/1427</self-uri><abstract><p>Нозокомиальная пневмония (НП) остается актуальной проблемой реаниматологии. Значительными перспективами в отношении диагностики НП обладают молекулярные биомаркеры. Цель исследования. Оценить информативность содержания белка клеток Клара (Club Cell Protein, CCP) в плазме крови в качестве диагностического кандидатного молекулярного биомаркера при НП. Материалы и методы. Исследование было проведено в НИИ ОР РАМН в 2010—2013 гг. В исследование было включено 85 больных в соответствии с критериями включения и исключения, а также 30 доноров. Диагностика ОРДС и его стадий проводилась по критериям НИИ ОР РАМН. Измерение содержания белка клеток Клара (CCP) в плазме выполняли с помощью иммуноферментного метода Human Clara Cell Protein ELISA, RD191022200, BioVendor, США. Статистический анализ полученных данных производили при помощи пакета Statistica 7,0. Для определения чувствительности и специфичности CCP был проведен ROCанализ. Достоверным считали различие при p&lt;0,05. Результаты. Содержание CCP в плазме больных НП было в течение 1, 3,5 и 7 суток исследования ниже, чем у больных без НП. Содержание CCP в плазме больных НП и больных без НП было в течение всех суток исследования выше, чем у здоровых доноров. Нами показано, что у больных, у которых НП была вызвана Pseudomonas aeruginosa (в ассоциации с другими возбудителями), содержание CCP в плазме крови в 1е и 3и сут. было значительно ниже, чем у больных без Pseudomonas aeruginosa. Содержание CCP в первые сутки исследования 17,5 нг/мл обладает чувствительностью 86,5% и специфичностью 66,7% в отношении диагностики НП, вызванной Pseudomonas aeruginosa (площадь под кривой 0,74; 95% доверительный интервал 0,630—0,829;p=0,0001). Прогностическая ценность положительного результата данного теста составила 81,8%, отрицательного результата — 74,1%. Заключение. Изучена динамика содержания в плазме крови больных нозокомиальной пневмонией белка клеток Клара. Показано, что белок клеток Клара информативен для диагностики нозокомиальной пневмонии, вызванной Pseudomonas aeruginosa — содержание в плазме крови CCP в день диагностики нозокомиальной пневмонии 17,5 нг/мл обладает чувствительностью 86,5% и специфичностью 66,7% в отношении диагностики НП, вызванной Pseudomonas aeruginosa.</p></abstract><trans-abstract xml:lang="en"><p>Nosocomial pneumonia (NP) remains a relevant problem of resuscitation. Molecular biomarkers are significant promises for diagnosing NP. Objective: to estimate the informative value of the plasma levels of Clara cell protein (Club Cell Protein, CCP) as a diagnostic molecular candidate biomarker in NP. Subjects and methods. The investigation was conducted at the Research Institute of General Reanimatology (RIGR), Russian Academy of Medical Sciences (RAMS), in 2010—2013. It included 85 patients in accordance with the criteria of inclusion and exclusion and 30 donors. Acute respiratory distress syndrome and its stages were diagnosed using the criteria of RIGR, RAMS. Plasma Clara cell protein (CCP) levels were measured by the enzyme immunoassay Human Clara Cell Protein ELISA, RD191022200, BioVendor, USA. The findings were statistically analyzed using the package Statistica 7.0. ROC curve analysis was made to determine the sensitivity andspecificity of CCP. The difference at p&lt;0.05 was considered significant. Results. On days 1, 3, 5, and 7 of the investigation, the plasma CCP levels in patients with NP were lower than in those without this disease. Within all these days, the plasma CCP concentrations in patients with and without NP were higher than in healthy donors. On days 1 and 3, the plasma content of CCP was much lower in patients in whom NP had been caused by Pseudomonas aeruginosa (in association with other pathogens) than in those with NP uncaused by Pseudomonas aeruginosa. Within the first 24 hours, the CCP level of 17.5 ng/ml had 86.5% sensitivity and 66.7% specificity in diagnosing Pseudomonas aeruginosainduced NP (area undercurve, 0.74; 95% confidence interval, 0.630—0.829; p=0.0001). The prognostic value of the positive and negative results of this test was 81.8 and 74.1%, respectively. Conclusion. The time course of changes in the plasma levels of Clara cell protein was studied in the patients with nosocomial pneumonia. Clara cell protein was shown to be of informative value in the diag nosis of Pseudomonas aeruginosainduced NP; on the day when nosocomial pneumonia was diagnosed, the plasma CCP level of 17.5 ng/ml had 86.5% sensitivity and 66.7% specificity in diagnosing Pseudomonas aeruginosainduced NP.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>Нозокомиальная пневмония</kwd><kwd>биомаркер</kwd><kwd>белок клеток Клара</kwd><kwd>диагностика</kwd><kwd>сепсис.</kwd></kwd-group><kwd-group xml:lang="en"><kwd>nosocomial pneumonia</kwd><kwd>biomarker</kwd><kwd>Clara cell protein</kwd><kwd>diagnosis</kwd><kwd>sepsis.</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">Karpun N.A., Moroz V.V., Klimova G.M., Akimkin V.G., Zhuravlev A.G., Kolesnik A.V. Profilaktika nozokomialnykh infektsii dykhatelnykh putei. Obshchaya Reanimatologiya. [Prevention of nosocomial espira tory infections. General Reanimatology]. 2007; 3 (3): 100–104. http://dx.doi.org/10.15360/1813977920073100. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Karpun N.A., Moroz V.V., Klimova G.M., Akimkin V.G., Zhuravlev A.G., Kolesnik A.V. Profilaktika nozokomialnykh infektsii dykhatelnykh putei. Obshchaya Reanimatologiya. [Prevention of nosocomial espira tory infections. General Reanimatology]. 2007; 3 (3): 100–104. http://dx.doi.org/10.15360/1813977920073100. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Golubev A.M., Moroz V.V., Sundukov D.V. Patogenez ostrogo respira tornogo distresssindroma. Obshchaya Reanimatologiya. [Pathogenesis of acute respiratory distress syndrome. General Reanimatology]. 2012; 8 (4): 13–21. http://dx.doi.org/10.15360/181397792012413. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Golubev A.M., Moroz V.V., Sundukov D.V. Patogenez ostrogo respira tornogo distresssindroma. Obshchaya Reanimatologiya. [Pathogenesis of acute respiratory distress syndrome. General Reanimatology]. 2012; 8 (4): 13–21. http://dx.doi.org/10.15360/181397792012413. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Kuzovlev A.N., Moroz V.V., Golubev A.M., Polovnikov S.G., Smelaya T.V. Diagnostika ostrogo respiratornogo distresssindroma pri nozokomial noi pnevmonii. Obshchaya Reanimatologiya. [Diagnosis of acute respi ratory distress syndrome in nosocomial pneumonia. General Reanimatology]. 2009; 5 (6): 5–12. http://dx.doi.org/10.15360/1813 9779200965. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Kuzovlev A.N., Moroz V.V., Golubev A.M., Polovnikov S.G., Smelaya T.V. Diagnostika ostrogo respiratornogo distresssindroma pri nozokomial noi pnevmonii. Obshchaya Reanimatologiya. [Diagnosis of acute respi ratory distress syndrome in nosocomial pneumonia. General Reanimatology]. 2009; 5 (6): 5–12. http://dx.doi.org/10.15360/1813 9779200965. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Chuchalin A.G. (red.). Nozokomialnaya pnevmoniya u vzroslykh. Natsionalnye rekomendatsii. [Adultonset pneumonia. National guide lines]. Moscow; 2009. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Chuchalin A.G. (red.). Nozokomialnaya pnevmoniya u vzroslykh. Natsionalnye rekomendatsii. [Adultonset pneumonia. National guide lines]. Moscow; 2009. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Fagon J.Y. Diagnosis and treatment of ventilatorassociated pneumo nia: fiberoptic bronchoscopy with bronchoalveolar lavage is essential. Semin. Respir. Crit. Care Med. 2006; 27 (1): 34–44. http://dx.doi.org/10.1055/s2006933672. PMID: 16508880</mixed-citation><mixed-citation xml:lang="en">Fagon J.Y. Diagnosis and treatment of ventilatorassociated pneumo nia: fiberoptic bronchoscopy with bronchoalveolar lavage is essential. Semin. Respir. Crit. Care Med. 2006; 27 (1): 34–44. http://dx.doi.org/10.1055/s2006933672. PMID: 16508880</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Torres A., Rello J. Update in communityacquired and nosocomial pneumonia. Am. J. Respir. Crit. Care Med. 2010; 181 (8): 782–787. http://dx.doi.org/10.1164/rccm.2010010030UP. PMID: 20382801</mixed-citation><mixed-citation xml:lang="en">Torres A., Rello J. Update in communityacquired and nosocomial pneumonia. Am. J. Respir. Crit. Care Med. 2010; 181 (8): 782–787. http://dx.doi.org/10.1164/rccm.2010010030UP. PMID: 20382801</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Croce M.A. Diagnosis of acute respiratory distress syndrome and differentiation from ventilatorassociated pneumonia. Am. J. Surg. 2000; 179 (2 Suppl 1): 26–29. http://dx.doi.org/10.1016/S00029610(00)003196. PMID: 10874108</mixed-citation><mixed-citation xml:lang="en">Croce M.A. Diagnosis of acute respiratory distress syndrome and differentiation from ventilatorassociated pneumonia. Am. J. Surg. 2000; 179 (2 Suppl 1): 26–29. http://dx.doi.org/10.1016/S00029610(00)003196. PMID: 10874108</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Fagon J.Y. Biologcal markers and diagnosis of ventilatorassociated pneumonia. Crit. Care. 2011; 15 (2): 130. http://dx.doi.org/10.1186/cc10050. PMID: 21418551</mixed-citation><mixed-citation xml:lang="en">Fagon J.Y. Biologcal markers and diagnosis of ventilatorassociated pneumonia. Crit. Care. 2011; 15 (2): 130. http://dx.doi.org/10.1186/cc10050. PMID: 21418551</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Vanspauwen M.J., Linssen C.F., Bruggeman C.A., Jacobs J.A., Drent M., Bergmans D.C., van Mook W.N. Clara cell protein in bronchoalveolar lavage fluid: a predictor of ventilatorassociated pneumonia? Crit. are. 2011; 15 (1): R14. http://dx.doi.org/10.1186/cc9418. PMID: 21223571</mixed-citation><mixed-citation xml:lang="en">Vanspauwen M.J., Linssen C.F., Bruggeman C.A., Jacobs J.A., Drent M., Bergmans D.C., van Mook W.N. Clara cell protein in bronchoalveolar lavage fluid: a predictor of ventilatorassociated pneumonia? Crit. are. 2011; 15 (1): R14. http://dx.doi.org/10.1186/cc9418. PMID: 21223571</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Johnston P., McAuley D.F., O’Kane C.M. Novel pulmonary biomarkers in the diagnosis of VAP. Thorax. 2010; 65 (3): 190–192. http://dx.doi.org/10. 1136/thx.2009.127308. PMID: 20335284</mixed-citation><mixed-citation xml:lang="en">Johnston P., McAuley D.F., O’Kane C.M. Novel pulmonary biomarkers in the diagnosis of VAP. Thorax. 2010; 65 (3): 190–192. http://dx.doi.org/10. 1136/thx.2009.127308. PMID: 20335284</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Luyt C.E., Combes A., Reynaud C., Hekimian G., Nieszkowska A., Tonnellier M., Aubry A., Trouillet J.L., Bernard M., Chastre J. Usefulness of procalcitonin for the diagnosis of ventilatorassociated pneumonia. Intensive Care Med. 2008; 34 (8): 1434–1440. http://dx.doi.org/ 10.1007/s001340081112x. PMID: 18421435</mixed-citation><mixed-citation xml:lang="en">Luyt C.E., Combes A., Reynaud C., Hekimian G., Nieszkowska A., Tonnellier M., Aubry A., Trouillet J.L., Bernard M., Chastre J. Usefulness of procalcitonin for the diagnosis of ventilatorassociated pneumonia. Intensive Care Med. 2008; 34 (8): 1434–1440. http://dx.doi.org/ 10.1007/s001340081112x. PMID: 18421435</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Tang H., Huang T., Jing J., Shen H., Cui W. Effect of procalcitoninguid ed treatment in patients with infections: a systematic review and meta analysis. Infection. 2009; 37 (6): 497–507. http://dx.doi.org/10.1007/s1501000990342. PMID: 19826761</mixed-citation><mixed-citation xml:lang="en">Tang H., Huang T., Jing J., Shen H., Cui W. Effect of procalcitoninguid ed treatment in patients with infections: a systematic review and meta analysis. Infection. 2009; 37 (6): 497–507. http://dx.doi.org/10.1007/s1501000990342. PMID: 19826761</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Póvoa P., Coelho L., Almeida E., Fernandes A., Mealha R., Moreira P., Sabino H. Creactive protein as a marker of ventilatorassociated pneumonia resolution: a pilot study. Eur. Respir. J. 2005; 25 (5): 804–812. http://dx.doi.org/10.1183/09031936.05.00071704. PMID: 15863636</mixed-citation><mixed-citation xml:lang="en">Póvoa P., Coelho L., Almeida E., Fernandes A., Mealha R., Moreira P., Sabino H. Creactive protein as a marker of ventilatorassociated pneumonia resolution: a pilot study. Eur. Respir. J. 2005; 25 (5): 804–812. http://dx.doi.org/10.1183/09031936.05.00071704. PMID: 15863636</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Duflo F., Debon R., Monneret G., Bienvenu J., Chassard D., Allaouchiche B. Alveolar and serum procalcitonin: diagnostic and prognostic value in venti latorassociated pneumonia. Anesthesiology. 2002; 96 (1): 74–79. http://dx.doi.org/10.1097/0000054220020100000018. PMID: 11753005</mixed-citation><mixed-citation xml:lang="en">Duflo F., Debon R., Monneret G., Bienvenu J., Chassard D., Allaouchiche B. Alveolar and serum procalcitonin: diagnostic and prognostic value in venti latorassociated pneumonia. Anesthesiology. 2002; 96 (1): 74–79. http://dx.doi.org/10.1097/0000054220020100000018. PMID: 11753005</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Gibot S., Cravoisy A. Soluble form of the triggering receptor expressed on myeloid cells1 as a marker of microbial infection. Clin. Med. Res. 2004; 2 (3): 181–187. http://dx.doi.org/10.3121/cmr.2.3.181. PMID: 15931355</mixed-citation><mixed-citation xml:lang="en">Gibot S., Cravoisy A. Soluble form of the triggering receptor expressed on myeloid cells1 as a marker of microbial infection. Clin. Med. Res. 2004; 2 (3): 181–187. http://dx.doi.org/10.3121/cmr.2.3.181. PMID: 15931355</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Determann R.M., Millo J.L., Gibot S., Korevaar J.C., Vroom M.B., van der Poll T., Garrard C.S., Schultz M.J. Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during evelopment of ventilator associated pneumonia. Intensive Care Med. 2005; 31 (11): 1495–1500. http://dx.doi.org/10.1007/s0013400528187. PMID: 16195904</mixed-citation><mixed-citation xml:lang="en">Determann R.M., Millo J.L., Gibot S., Korevaar J.C., Vroom M.B., van der Poll T., Garrard C.S., Schultz M.J. Serial changes in soluble triggering receptor expressed on myeloid cells in the lung during evelopment of ventilator associated pneumonia. Intensive Care Med. 2005; 31 (11): 1495–1500. http://dx.doi.org/10.1007/s0013400528187. PMID: 16195904</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Oppert M., Reinicke A., Müller C., Barckow D., Frei U., Eckardt K. Elevations in procalcitonin but not Creactive protein are associated with pneumonia after cardiopulmonary resuscitation. Resuscitation. 2002; 53 (2): 167–170. http://dx.doi.org/10.1016/S0300 9572(02)000084. PMID: 12009220</mixed-citation><mixed-citation xml:lang="en">Oppert M., Reinicke A., Müller C., Barckow D., Frei U., Eckardt K. Elevations in procalcitonin but not Creactive protein are associated with pneumonia after cardiopulmonary resuscitation. Resuscitation. 2002; 53 (2): 167–170. http://dx.doi.org/10.1016/S0300 9572(02)000084. PMID: 12009220</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Moroz V.V. (red.). Ostryi respiratornyi distresssindrom: klassifikat siya, diagnostika, differentsirovannoe lechenie. Uchebnometodich eskoe posobie. [Acute respiratory distress syndrome: lassification, diagnosis, differentiated treatment. Guidance manual]. Moscow: NIIOR RAMN; 2013: 99. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Moroz V.V. (red.). Ostryi respiratornyi distresssindrom: klassifikat siya, diagnostika, differentsirovannoe lechenie. Uchebnometodich eskoe posobie. [Acute respiratory distress syndrome: lassification, diagnosis, differentiated treatment. Guidance manual]. Moscow: NIIOR RAMN; 2013: 99. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Kuzovlev A.N., Moroz V.V., Golubev A.M., Polovnikov S.G. Ingalyatsionnye antibiotiki v lechenii nozokomialnoi pnevmonii. Obshchaya Reanimatologiya. [Inhaled antibiotics in the treatment of nosocomial pneumonia. General Reanimatology]. 2013; 9 (6): 61–70. http://dx.doi.org/10.15360/181397792013661. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Kuzovlev A.N., Moroz V.V., Golubev A.M., Polovnikov S.G. Ingalyatsionnye antibiotiki v lechenii nozokomialnoi pnevmonii. Obshchaya Reanimatologiya. [Inhaled antibiotics in the treatment of nosocomial pneumonia. General Reanimatology]. 2013; 9 (6): 61–70. http://dx.doi.org/10.15360/181397792013661. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Bernard A., Marchandise F.X., Depelchin S., Lauwerys R., Sibille Y. Clara cell protein in serum and bronchoalveolar lavage. Eur. Respir. J. 1992; 5 (10): 1231–1238. PMID: 1486970</mixed-citation><mixed-citation xml:lang="en">Bernard A., Marchandise F.X., Depelchin S., Lauwerys R., Sibille Y. Clara cell protein in serum and bronchoalveolar lavage. Eur. Respir. J. 1992; 5 (10): 1231–1238. PMID: 1486970</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Kropski J.A., Fremont R.D., Calfee C.S.,Ware L.B. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest. 2009; 135 (6): 1440–1447. http://dx.doi.org/10.1378/chest.082465. PMID: 19188556</mixed-citation><mixed-citation xml:lang="en">Kropski J.A., Fremont R.D., Calfee C.S.,Ware L.B. Clara cell protein (CC16), a marker of lung epithelial injury, is decreased in plasma and pulmonary edema fluid from patients with acute lung injury. Chest. 2009; 135 (6): 1440–1447. http://dx.doi.org/10.1378/chest.082465. PMID: 19188556</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Moroz V.V., Golubev A.M., Kuzovlev A.N., Pisarev V.M., Shabanov A.K., Golubev M.A. Surfaktantnyi protein D – biomarker ostrogo respira tornogo distresssindroma. Obshchaya Reanimatologiya. [Surfactant protein D is a biomarker of acute respiratory distress syndrome. General Reanimatology]. 2013; 9 (4): 11–17. http://dx.doi.org/10.15360/181397792013411. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Moroz V.V., Golubev A.M., Kuzovlev A.N., Pisarev V.M., Shabanov A.K., Golubev M.A. Surfaktantnyi protein D – biomarker ostrogo respira tornogo distresssindroma. Obshchaya Reanimatologiya. [Surfactant protein D is a biomarker of acute respiratory distress syndrome. General Reanimatology]. 2013; 9 (4): 11–17. http://dx.doi.org/10.15360/181397792013411. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit23"><label>23</label><citation-alternatives><mixed-citation xml:lang="ru">Moroz V.V., Golubev A.M., Kuzovlev A.N., Pisarev V.M., Polovnikov S.G., Shabanov A.K., Golubev M.A. Surfaktantnyi protein A (SPA) prognostichesky molekulyarnyi biomarker pri ostrom respiratornom dis tresssindrome. Obshchaya Reanimatologiya. [Surfactant protein А (SPA) is a prognostic molecular biomarker in acute respiratory dis tress syndrome. General Reanimatology]. 2013; 9 (3): 5–13. http://dx.doi.org/10.15360/18139779201335. [In Russ.]</mixed-citation><mixed-citation xml:lang="en">Moroz V.V., Golubev A.M., Kuzovlev A.N., Pisarev V.M., Polovnikov S.G., Shabanov A.K., Golubev M.A. Surfaktantnyi protein A (SPA) prognostichesky molekulyarnyi biomarker pri ostrom respiratornom dis tresssindrome. Obshchaya Reanimatologiya. [Surfactant protein А (SPA) is a prognostic molecular biomarker in acute respiratory dis tress syndrome. General Reanimatology]. 2013; 9 (3): 5–13. http://dx.doi.org/10.15360/18139779201335. [In Russ.]</mixed-citation></citation-alternatives></ref><ref id="cit24"><label>24</label><citation-alternatives><mixed-citation xml:lang="ru">Harrod K.S., Mounday A.D., Stripp B.R., Whitsett J.A. Clara cell secre tory protein decreases lung inflammation after acute virus infection. Am. J. Physiol. Lung Cell Mol. Physiol. 1998; 275 (5 Pt 1): L924–L930. PMID: 9815110</mixed-citation><mixed-citation xml:lang="en">Harrod K.S., Mounday A.D., Stripp B.R., Whitsett J.A. Clara cell secre tory protein decreases lung inflammation after acute virus infection. Am. J. Physiol. Lung Cell Mol. Physiol. 1998; 275 (5 Pt 1): L924–L930. PMID: 9815110</mixed-citation></citation-alternatives></ref><ref id="cit25"><label>25</label><citation-alternatives><mixed-citation xml:lang="ru">Yao X.L., Levine S.J., Cowan M.J., Logun C., Shelhamer J.H. Tumor necrosis factoralpha stimulates human Clara cell secretory protein production by human airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 1998; 19 (4): 629–635. PMID: 9761760</mixed-citation><mixed-citation xml:lang="en">Yao X.L., Levine S.J., Cowan M.J., Logun C., Shelhamer J.H. Tumor necrosis factoralpha stimulates human Clara cell secretory protein production by human airway epithelial cells. Am. J. Respir. Cell Mol. Biol. 1998; 19 (4): 629–635. PMID: 9761760</mixed-citation></citation-alternatives></ref><ref id="cit26"><label>26</label><citation-alternatives><mixed-citation xml:lang="ru">Johnston C.J., Mango G.W., Finkelstein J.N., Stripp B.R. Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. Am. J. Respir. Cell Mol. Biol. 1997; 17 (2): 147–155. http://dx.doi.org/10. 1165/ajrcmb.17.2.2676. PMID: 9271302</mixed-citation><mixed-citation xml:lang="en">Johnston C.J., Mango G.W., Finkelstein J.N., Stripp B.R. Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. Am. J. Respir. Cell Mol. Biol. 1997; 17 (2): 147–155. http://dx.doi.org/10. 1165/ajrcmb.17.2.2676. PMID: 9271302</mixed-citation></citation-alternatives></ref><ref id="cit27"><label>27</label><citation-alternatives><mixed-citation xml:lang="ru">Lakind J.S., Holgate S.T., Ownby D.R., Mansur A.H., Helms P.J., Pyatt D., Hays S.M. A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects. Biomarkers. 2007; 12 (5): 445–467. http://dx.doi.org/10.1080/13547500701359327. PMID: 17701745</mixed-citation><mixed-citation xml:lang="en">Lakind J.S., Holgate S.T., Ownby D.R., Mansur A.H., Helms P.J., Pyatt D., Hays S.M. A critical review of the use of Clara cell secretory protein (CC16) as a biomarker of acute or chronic pulmonary effects. Biomarkers. 2007; 12 (5): 445–467. http://dx.doi.org/10.1080/13547500701359327. PMID: 17701745</mixed-citation></citation-alternatives></ref><ref id="cit28"><label>28</label><citation-alternatives><mixed-citation xml:lang="ru">Broeckaert F., Clippe A., Knoops B., Hermans C., Bernard A. Clara cell secre tory protein (CC16): features as a peripheral lung biomarker. Ann. N.Y.Acad. Sci. 2000; 923: 68–77. http://dx.doi.org/10.1111/j.17496632.2000.tb05520.x. PMID: 11193780</mixed-citation><mixed-citation xml:lang="en">Broeckaert F., Clippe A., Knoops B., Hermans C., Bernard A. Clara cell secre tory protein (CC16): features as a peripheral lung biomarker. Ann. N.Y.Acad. Sci. 2000; 923: 68–77. http://dx.doi.org/10.1111/j.17496632.2000.tb05520.x. PMID: 11193780</mixed-citation></citation-alternatives></ref><ref id="cit29"><label>29</label><citation-alternatives><mixed-citation xml:lang="ru">Determann R., Millo J., Waddy S., Lutter R., Garrard C., Schultz M. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilatorassociated pneumonia: a retrospective obser vational study. BMC Pulm. Med. 2009; 9: 49. http://dx.doi.org/ 10.1186/14712466949. PMID: 19958527</mixed-citation><mixed-citation xml:lang="en">Determann R., Millo J., Waddy S., Lutter R., Garrard C., Schultz M. Plasma CC16 levels are associated with development of ALI/ARDS in patients with ventilatorassociated pneumonia: a retrospective obser vational study. BMC Pulm. Med. 2009; 9: 49. http://dx.doi.org/ 10.1186/14712466949. PMID: 19958527</mixed-citation></citation-alternatives></ref><ref id="cit30"><label>30</label><citation-alternatives><mixed-citation xml:lang="ru">Cowan M., Huang X., Yao X.L., Shelhamer J.H. Tumor necrosis factor alpha stimulation of human Clara cell secretory protein production by human airway epithelial cells. Ann. N.Y. Acad. Sci. 2000; 923: 193–201. http://dx.doi.org/10.1111/j.17496632.2000.tb05530.x. PMID: 11193757</mixed-citation><mixed-citation xml:lang="en">Cowan M., Huang X., Yao X.L., Shelhamer J.H. Tumor necrosis factor alpha stimulation of human Clara cell secretory protein production by human airway epithelial cells. Ann. N.Y. Acad. Sci. 2000; 923: 193–201. http://dx.doi.org/10.1111/j.17496632.2000.tb05530.x. PMID: 11193757</mixed-citation></citation-alternatives></ref><ref id="cit31"><label>31</label><citation-alternatives><mixed-citation xml:lang="ru">Harrod K., Mounday A., Whitsett J. Adenoviral E3–14.7K protein in LPSinduced lung inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 2000; 278 (4): L631–L639. PMID: 10749739</mixed-citation><mixed-citation xml:lang="en">Harrod K., Mounday A., Whitsett J. Adenoviral E3–14.7K protein in LPSinduced lung inflammation. Am. J. Physiol. Lung Cell Mol. Physiol. 2000; 278 (4): L631–L639. PMID: 10749739</mixed-citation></citation-alternatives></ref><ref id="cit32"><label>32</label><citation-alternatives><mixed-citation xml:lang="ru">Hayashida S., Harrod K., Whitsett J. Regulation and function of CCSP during pulmonary Pseudomonas aeruginosa infection in vivo. Am. J. Physiol. Lung Cell Mol. Physiol. 2000; 279 (3): L452–L459. PMID: 10956619</mixed-citation><mixed-citation xml:lang="en">Hayashida S., Harrod K., Whitsett J. Regulation and function of CCSP during pulmonary Pseudomonas aeruginosa infection in vivo. Am. J. Physiol. Lung Cell Mol. Physiol. 2000; 279 (3): L452–L459. PMID: 10956619</mixed-citation></citation-alternatives></ref><ref id="cit33"><label>33</label><citation-alternatives><mixed-citation xml:lang="ru">Harrod K.S., Jaramillo R.J. Pseudomonas aeruginosa and tumor necrosis factoralpha attenuate Clara cell secretory protein promoter func tion. Am. J. Respir. Cell Mol. Biol. 2002; 26 (2): 216–223. PMID: 11804873</mixed-citation><mixed-citation xml:lang="en">Harrod K.S., Jaramillo R.J. Pseudomonas aeruginosa and tumor necrosis factoralpha attenuate Clara cell secretory protein promoter func tion. Am. J. Respir. Cell Mol. Biol. 2002; 26 (2): 216–223. PMID: 11804873</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>
