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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">pulmo</journal-id><journal-title-group><journal-title xml:lang="ru">Пульмонология</journal-title><trans-title-group xml:lang="en"><trans-title>PULMONOLOGIYA</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">0869-0189</issn><issn pub-type="epub">2541-9617</issn><publisher><publisher-name>Scientific and Practical Journal “PULMONOLOGIYA” LLC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18093/0869-0189-2023-33-6-739-749</article-id><article-id custom-type="elpub" pub-id-type="custom">pulmo-4372</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>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>ORIGINAL STUDIES</subject></subj-group></article-categories><title-group><article-title>Эффективность терапии хронической обструктивной болезни легких после вирус-ассоциированного обострения</article-title><trans-title-group xml:lang="en"><trans-title>Efficacy of treatment of chronic obstructive pulmonary disease after virus-induced exacerbations</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0871-7551</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шпагина</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Shpagina</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шпагина Любовь Анатольевна – доктор медицинских наук, профессор, заведующая кафедрой госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.: (383) 279-99-45</p></bio><bio xml:lang="en"><p>Lyubov A. Shpagina - Doctor of Medicine, Professor, Head of the Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p></bio><email xlink:type="simple">lashpagina@gmail.com</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-0724-1539</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Котова</surname><given-names>О. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Kotova</surname><given-names>O. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Котова Ольга Сергеевна – доктор медицинских наук, доцент кафедры госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.: (383) 279-99-45</p></bio><bio xml:lang="en"><p>Olga S. Kotova - Doctor of Medicine, Assistant Professor, Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p><p> </p></bio><email xlink:type="simple">ok526@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3109-9811</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Шпагин</surname><given-names>И. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Shpagin</surname><given-names>I. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Шпагин Илья Семенович – доктор медицинских наук, доцент, профессор кафедры госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.: (383) 279-99-45</p></bio><bio xml:lang="en"><p>Ilya S. Shpagin - Doctor of Medicine, Assistant Professor, Professor, Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-7428-9159</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кузнецова</surname><given-names>Г. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Kuznetsova</surname><given-names>G. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кузнецова Галина Владимировна – кандидат медицинских наук, доцент кафедры госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.: (383) 279-99-45</p></bio><bio xml:lang="en"><p>Galina V. Kuznetsova - Candidate of Medicine, Associate Professor, Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3446-8018</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Кармановская</surname><given-names>С. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Karmanovskaya</surname><given-names>S. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Кармановская Светлана Александровна – доктор медицинских наук, доцент кафедры госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.: (383) 279-99-45</p></bio><bio xml:lang="en"><p>Svetlana A. Karmanovskaya, Doctor of Medicine, Assistant Professor, Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-8230-8142</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Паначева</surname><given-names>Л. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Panacheva</surname><given-names>L. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Паначева Людмила Алексеевна – доктор медицинских наук, доцент, профессор кафедры госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.:(383) 279-99-45</p></bio><bio xml:lang="en"><p>Lyudmila A. Panacheva - Doctor of Medicine, Associate Professor, Professor, Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-6047-1707</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Аникина</surname><given-names>Е. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Anikina</surname><given-names>E. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Аникина Екатерина Валентиновна – ассистент кафедры госпитальной терапии и медицинской реабилитации.</p><p>630091, Новосибирск, Красный проспект, 52; тел.: (383) 279-99-45</p></bio><bio xml:lang="en"><p>Ekaterina V. Anikina - Assistant, Internal Medicine and Rehabilitation Department.</p><p>Krasnyy prospect 52, Novosibirsk, 630091; tel.: (383) 279-99-45</p></bio><email xlink:type="simple">mkb-2@yandex.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Новосибирский государственный медицинский университет» Министерства здравоохранения Российской Федерации</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Federal State Budgetary Educational Institution of Higher Education “Novosibirsk State Medical University”, Healthcare Ministry of Russian Federation</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2023</year></pub-date><pub-date pub-type="epub"><day>12</day><month>12</month><year>2023</year></pub-date><volume>33</volume><issue>6</issue><fpage>739</fpage><lpage>749</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Шпагина Л.А., Котова О.С., Шпагин И.С., Кузнецова Г.В., Кармановская С.А., Паначева Л.А., Аникина Е.В., 2023</copyright-statement><copyright-year>2023</copyright-year><copyright-holder xml:lang="ru">Шпагина Л.А., Котова О.С., Шпагин И.С., Кузнецова Г.В., Кармановская С.А., Паначева Л.А., Аникина Е.В.</copyright-holder><copyright-holder xml:lang="en">Shpagina L.A., Kotova O.S., Shpagin I.S., Kuznetsova G.V., Karmanovskaya S.A., Panacheva L.A., Anikina E.V.</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://journal.pulmonology.ru/pulm/article/view/4372">https://journal.pulmonology.ru/pulm/article/view/4372</self-uri><abstract><p>Респираторная вирусная инфекция (РВИ) – одна из наиболее частых причин обострения хронической обструктивной болезни легких (ХОБЛ). Особенности течения заболевания после обострения, ассоциированного с вирусной инфекцией, включая ответ на терапию, изучены недостаточно.</p><p>Целью исследования явилось определение влияния фиксированной тройной комбинации длительно действующих антихолинергических препаратов (ДДАХП) / длительно действующих β2-агонистов (ДДБА) адренорецепторов / ингаляционных глюкокортикостероидов (иГКС) на симптомы ХОБЛ, функцию легких, переносимость физической нагрузки по данным 6-минутного шагового теста (6-МШТ), активность воспаления в сравнении со свободными комбинациями у больных, перенесших вирус-ассоциированное обострение ХОБЛ.</p><sec><title>Материалы и методы</title><p>Материалы и методы. Выполнено наблюдательное проспективное когортное исследование с участием больных ХОБЛ (спирографический критерий), госпитализированных с обострением ХОБЛ с вирусной (n = 60) или вирусно-бактериальной (n = 60) инфекцией, группа сравнения (n = 60) – больные ХОБЛ с бактериальным обострением. Вирусная инфекция определялась при исследовании мокроты или лаважной жидкости методом полимеразной цепной реакции в режиме реального времени на РНК риновируса, респираторно-синцитиального вируса, вирусов гриппа А и В, SARS-CoV-2; бактериальная – при наличии гнойной мокроты и / или по результатам теста на прокальцитонин и / или исследования мокроты культуральным методом. В период обострения исследовались цитокины крови методом твердофазного иммуноферментного анализа. В реальной клинической практике больным назначалась тройная комбинация ДДАХП / ДДБА / иГКС – фиксированная (исследуемая терапия) или свободная (терапия сравнения). Наблюдение для оценки эффективности начиналось через 4 нед. после завершения обострения и выписки из стационара.</p></sec><sec><title>Результаты</title><p>Результаты. Через 52 нед. лечения у больных группы исследуемой терапии наблюдалось меньшее снижение объема форсированного выдоха за 1-ю секунду (ОФВ1). Отмечены более существенные различия в показателях пациентов подгруппы свободной комбинации, перенесших обострения при вирусной инфекции (–69 (–75; –10) мл vs –75 (–78; –72) мл) и вирусно-бактериальной инфекции (–67,5 (–69; –37,25) мл vs –75,5 (–84; –70,25) мл), и терапии сравнения соответственно. Увеличение диффузионной способности легких по монооксиду углерода (DLCO) с поправкой на альвеолярный объем (Va) (DLCO / Va), снижение коэффициента бронходилатации, результатов 6-МШТ, числа эозинофилов и концентрации фибриногена крови отмечено только у больных после вирус-ассоциированных или вирусно-бактериальных обострений на фоне терапии фиксированной тройной комбинацией. В модели линейной регрессии выявлена прямая связь концентрации интерлейкина-5 с динамикой ОФВ1 (В = 0,848) на фоне исследуемой терапии, а также DLCO / Va (B = 0,117), и отрицательная – концентрации N-терминального пептида проколлагена-III с DLCO / Va (В = –0,021).</p></sec><sec><title>Заключение</title><p>Заключение. У больных ХОБЛ, перенесших обострение с вирусной, вирусно-бактериальной инфекцией, при использовании фиксированной тройной терапии ДДАХП / ДДБА / иГКС эффективнее свободных комбинаций замедляется снижение ОФВ1, увеличиваются DLCO, результаты 6-МШТ, уменьшается активность воспаления дыхательных путей.</p></sec></abstract><trans-abstract xml:lang="en"><p>Viral respiratory infection is one of the main etiologic factors for acute exacerbations of COPD (AECOPD). The disease course after virus-associated AECOPD and the response to treatment have not been studied adequately.</p><p>The aim was to evaluate the efficacy of single-inhaler triple therapy (SITT) of long-acting anticholinergic drugs (LAMA)/long-acting β2-agonists (LABA) of adrenergic receptors/inhaled glucocorticosteroids (ICS) on COPD symptoms, lung function, exercise tolerance, and inflammatory activity compared with multiple-inhaler triple therapy (MITT) after a virus-associated COPD exacerbation.</p><sec><title>Methods</title><p>Methods. This was an observational prospective cohort study of COPD patients (spirographус criterion) hospitalized for AECOPD with viral (n = 60) or viral-bacterial (n = 60) infection. The comparison group included patients with bacterial AECOPD (n = 60). Viral infection was diagnosed by PCR-RT of sputum or bronchoalveolar lavage fluid for RNAs of rhinovirus, RS virus, influenza A and B viruses, or SARS-CoV-2 virus. Bacterial infection was demonstrated by sputum purulence and/or procalcitonin test results and/or standard culture data. During AECOPD, blood cytokines were measured by ELISA. The patients were treated with SITT (investigational treatment) or MITT (comparison treatment) of LAMA/LABA/ICS in real-world clinical practice. The follow-up started 4 weeks after AECOPD regression and discharge from hospital.</p></sec><sec><title>Results</title><p>Results. After 52 weeks of treatment, FEV1 decline was smaller than in the SITT group. Differences from the MITT group were greater in patients with viral AECOPD (–69 (–75; –10) ml vs –75 (–78; –72) ml) or viral-bacterial AECOPD (–67.5 (–69; –37.25) ml vs –75.5 (–84; –70.25) ml). An increase in DLCO/Va, 6-minut walk test (6MWT) results, a decrease in bronchodilation coefficient, blood eosinophils and fibrinogen was seen only in subjects who received SITT and had viralor viral-bacterial AECOPD. A multiple regression model revealed a direct association between blood interleukin-5 and improvement in FEV1 (В = 0.848) and DLCO/Va (B=0.117) and a negative correlation with blood levels of amino-terminal propeptide of type-III procollagen and improvement in DLCO/Va (В = –0.021).</p></sec><sec><title>Conclusion</title><p>Conclusion. SITT with LAMA/LABA/ICS was more effective in preventing FEV1 decline, increasing DLCO, 6MWT results, and decreasing airway inflammation in virus-associated or viral-bacterial AECOPD.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>хроническая обструктивная болезнь легких</kwd><kwd>обострение</kwd><kwd>респираторная вирусная инфекция</kwd><kwd>ингаляционные глюко-кортикостероиды</kwd><kwd>длительно действующие β2-агонисты</kwd><kwd>длительно действующие антихолинергические препараты</kwd></kwd-group><kwd-group xml:lang="en"><kwd>сhronic obstructive pulmonary disease</kwd><kwd>exacerbation</kwd><kwd>respiratory viral infection</kwd><kwd>inhaled corticosteroid</kwd><kwd>long-acting β2-agonist</kwd><kwd>longacting muscarinic antagonist</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">Исследование осуществлялось за счет средств федерального бюджета на исполнение государственного задания № 05600034-21-00</funding-statement><funding-statement xml:lang="en">Federal budget funds for the implementation of state task No.056-00034-21-00 were used</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">GBD 2019 Chronic Respiratory Diseases Collaborators. 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