pulmoПульмонологияPULMONOLOGIYA0869-01892541-9617Scientific and Practical Journal “PULMONOLOGIYA” LLC10.18093/0869-0189-2024-34-5-655-667pulmo-4442Research ArticleМАТЕРИАЛЫ КОНГРЕССА: ПРИМЕНЕНИЕ ВОДОРОДА В МЕДИЦИНЕCONGRESS: APPLICATION OF HYDROGEN IN MEDICINEЭффективность и безопасность ингаляционной терапии молекулярным водородом у пациентов с дыхательной недостаточностью на фоне обострения хронической обструктивной болезни легких в постковидном периодеEfficacy and safety of inhaled molecular hydrogen therapy in patients with respiratory failure due to chronic obstructive pulmonary disease exacerbation in post-COVID periodhttps://orcid.org/0000-0001-9285-9303ШогеноваЛ. В.ShogenovaL. V.

Шогенова Людмила Владимировна – к. м. н., доцент кафедры госпитальной терапии педиатрического факультета.

117997, Москва, ул. Островитянова, 1; тел.: (499) 780-08-50

Lyudmila V. Shogenova - Сandidate of Medicine, Associate Professor, Department of Hospital Therapy, Pediatric Faculty.

Ul. Ostrovityanova 1, Moscow, 117997; tel.: (499) 780-08-50

luda_shog@list.ruhttps://orcid.org/0000-0001-5618-5671ГуфрановХ. Ф.GufranovKh. F.

Гуфранов Хайдар Фаисович – аспирант кафедры фармакологии факультета фундаментальной медицины.

119992, Москва, Ленинские горы, 1; тел.: (495) 989-23-38

Khaidar F. Gufranov, Postgraduate Student, Department of Pharmacology, Faculty of Fundamental Medicine.

Leninskye gory 1, build. 40, Moscow, 119992; tel.: (495) 989-23-38

haidar@formed.ruФедеральное государственное автономное образовательное учреждение высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииРоссияFederal State Autonomous Educational Institution of Higher Education «N.I. Pirogov Russian National Research Medical University» of the Ministry of Health of the Russian FederationRussian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный университет имени М.В. Ломоносова» Правительства Российской ФедерацииРоссияFederal State Budget Educational Institution of Higher Education M.V.Lomonosov Moscow State UniversityRussian Federation202411102024345655667Copyright © Шогенова Л.В., Гуфранов Х.Ф., 20242024Шогенова Л.В., Гуфранов Х.Ф.Shogenova L.V., Gufranov K.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://journal.pulmonology.ru/pulm/article/view/4442

Молекулярный водород (H2) является мощным антиоксидантом и антиапоптотическим агентом. В последние годы H2 изучался по данным клинических исследований.

Целью данной работы явилось изучение эффективности и безопасности ингаляционной терапии Н2 у пациентов с гипоксемической и гиперкапнической дыхательной недостаточностью (ДН) на фоне обострения хронической обструктивной болезни легких (ХОБЛ) в постковидном периоде.

Материалы и методы

Материалы и методы. В рандомизированное проспективное в параллельных группах сравнительное исследование включены пациенты (n = 60: 40 мужчин в возрасте 71,2 ± 1,8 года, 20 женщин в возрасте 70,9 ± 2,8 года) с обострением ХОБЛ, развившимся после перенесенного COVID-19 (Corona Virus Disease 2019), осложненного гипоксемической / гиперкапнической ДН. Пациенты были распределены на 2 группы: 1-я (основная) (n = 30: 18 мужчин, 12 женщин), 2-я (контрольная) (n = 30: 18 мужчин, 12 женщин). Для поддержания сатурации артериальной крови не менее чем 90 % пациентам обеих групп оказывалась респираторная поддержка (неинвазивная вентиляция легких) при использовании аппарата Prisma 25ST (Lowenstein Medical, Германия) в режиме BiPAP S / T (BiLevel Positive Airway Pressure – создание двухуровневого положительного давления в дыхательных путях в спонтанно-принудительном режиме) 20–24 / 4–6 см вод. ст. и О2 соответственно; фракционная концентрация кислорода во вдыхаемой газовой смеси составляла ≥ 24 %. Помимо стандартного лечения, пациенты основной группы получали дополнительно терапию Н2 (аппарат Suisonia, Япония) через носовую канюлю по 90 мин ежедневно в течение 14 дней.

Результаты

Результаты. У пациентов основной группы выявлено снижение индекса ригидности сосудов с 14,6 ± 1,2 до 6,2 ± 0,6 м / c, уровня лактата артериальной крови – с 2,84 ± 0,1 до 0,02 ± 0,1 ммоль / л (р < 0,001), расчетного показателя фракции шунта Qs / Qt (венозное примешивание) – с 27,21 ± 3,4 до 7,14 ± 1,23 (р < 0,01) и увеличение следующих параметров: индекса отражения – с 42,2 ± 2,0 до 66,2 ± 4,9 % (p < 0,05), вирус-специфического иммуноглобулина G – с 134 ± 125 до 669 ± 164 (р < 0,05), скорости кровотока в артериолах – с 473 ± 108 до 868 ± 64 мкм / с (р < 0,05), скорости кровотока в венулах – с 299 ± 56 до 862 ± 69 мкм / с (р < 0,05), расстояния, пройденного при выполнении 6-минутного шагового теста, – с 57,1 ± 4,4 до 328,9 ± 33,7 м (р < 0,05).

Заключение

Заключение. При включении ингаляций Н2 в стандартную терапию пациентов с гипоксемической и гиперкапнической ДН на фоне обострения ХОБЛ в постковидном периоде отмечены безопасность и существенный дополнительный лечебный эффект.

Molecular hydrogen (H2) is a powerful antioxidant and anti-apoptotic agent. H2 has been studied in a number of clinical studies in the recent years.

The aim of this research was to investigate the efficacy and safety of H2 inhalation therapy in patients with hypoxemic and hypercapnic respiratory failure (RF) against exacerbation of chronic obstructive pulmonary disease (COPD) in the post-COVID (Corona Virus Disease 2019) period.

Methods

Methods. The randomized prospective parallel comparative study included patients (n = 60: 40 men aged 71.2 ± 1.8 years, 20 women aged 70.9 ± 2.8 years) with a post-COVID-19 exacerbation of COPD complicated by hypoxemic/hypercapnic RF. The patients were divided into 2 groups: group 1 (main) (n = 30: 18 men, 12 women), group 2 (control) (n = 30: 18 men, 12 women). To maintain arterial blood saturation ≥ 90 %, patients in both groups received respiratory support (non-invasive ventilation) using the Prisma 25ST device (Lowenstein Medical, Germany) in the BiPAP S/T mode (BiLevel Positive Airway Pressure Spontaneous/Time spontaneous/forced mode 20–24/4–6 cm H2O and O2, respectively; the fractional oxygen concentration in the inhaled gas mixture was ≥ 24%). In addition to standard treatment, patients in the main group received additional H2 therapy (Suisonia device, Japan) through a nasal cannula for 90 minutes daily for 14 days.

Results

Results. In patients of the main group, a decrease in the stiffness index was detected from 14.6 ± 1.2 to 6.2 ± 0.6 m/s, and the arterial blood lactate level – from 2.84 ± 0.1 to 0.02 ± 0.1 mmol/l (p < 0.001), the calculated shunt fraction Qs/Qt (venous admixture) – from 27.21 ± 3.4 to 7.14 ± 1.23 (p < 0.01) and an increase in the following parameters: reflection index – from 42.2 ± 2.0 to 66.2 ± 4.9% (p < 0.05), virus-specific IgG level – from 134 ± 125 to 669 ± 164 (p < 0. 05), blood flow velocity in arterioles – from 473 ± 108 to 868 ± 64 μm/s (p < 0.05), blood flow velocity in venules – from 299 ± 56 to 862 ± 69 μm/s (p < 0.05), the 6-minute walk distance – from 57.1 ± 4.4 to 328.9 ± 33.7 m (p < 0.05).

Conclusion

Conclusion. H2 inhalations were safe and increased the therapeutic effect when added to standard therapy for patients with hypoxemic and hypercapnic RF during exacerbation of COPD in the post-COVID period.

хроническая обструктивная болезнь легкихдыхательная недостаточностьгипоксемиягиперкапниямолекулярный водородCOVID-19chronic obstructive pulmonary diseaserespiratory failurehypoxemiahypercapniamolecular hydrogenCOVID-19Исследование проводилось за счет бюджетных средств Федерального государственного автономноо образовательного учреждения высшего образования «Российский национальный исследовательский медицинский университет имени Н.И. Пирогова» Министерства здравоохранения Российской ФедерацииThe study was carried out at the expense of the budget funds of the Federal State Autonomous Educational Institution of Higher Education “N.I. Pirogov Russian National Research Medical University” of the Ministry of Health of the Russian FederationReferencesHirano S.I., Ichikawa Y., Kurokawa R. et al. A “philosophical molecule,” hydrogen may overcome senescence and intractable diseases. Med. Gas Res. 2020; 10 (1): 47–49. DOI: 10.4103/2045-9912.279983.Hirano S.I., Ichikawa Y., Kurokawa R. et al. A “philosophical molecule,” hydrogen may overcome senescence and intractable diseases. Med. Gas Res. 2020; 10 (1): 47–49. DOI: 10.4103/2045-9912.279983.Ichihara M., Sobue S., Ito M. et al. Beneficial biological effects and the underlying mechanisms of molecular hydrogen–comprehensive review of 321 original articles. Med. Gas Res. 2015; 5: 12. DOI: 10.1186/s13618-015-0035-1.Ichihara M., Sobue S., Ito M. et al. Beneficial biological effects and the underlying mechanisms of molecular hydrogen–comprehensive review of 321 original articles. Med. Gas Res. 2015; 5: 12. DOI: 10.1186/s13618-015-0035-1.Artamonov M.Yu., Martusevich A.K., Pyatakovich F.A. et al. Molecular hydrogen: from molecular effects to stem cells management and tissue regeneration. Antioxidants (Basel). 2023; 12 (3): 636. DOI: 10.3390/antiox12030636.Artamonov M.Yu., Martusevich A.K., Pyatakovich F.A. et al. Molecular hydrogen: from molecular effects to stem cells management and tissue regeneration. Antioxidants (Basel). 2023; 12 (3): 636. DOI: 10.3390/antiox12030636.Ohsawa I., Ishikawa M., Takahashi K. et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 2007; 13 (6): 688–694. DOI: 10.1038/nm1577.Ohsawa I., Ishikawa M., Takahashi K. et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 2007; 13 (6): 688–694. DOI: 10.1038/nm1577.Cui J., Chen X., Zhai X. et al. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats – a possible new hydrogen resource for clinical use. Neuroscience. 2016; 335: 232–241. DOI: 10.1016/j.neuroscience.2016.08.021.Cui J., Chen X., Zhai X. et al. Inhalation of water electrolysis-derived hydrogen ameliorates cerebral ischemia-reperfusion injury in rats – a possible new hydrogen resource for clinical use. Neuroscience. 2016; 335: 232–241. DOI: 10.1016/j.neuroscience.2016.08.021.Zhang Y., Xu J., Yang H. Hydrogen: an endogenous regulator of liver homeostasis. Front. Pharmacol. 2020; 11: 877. DOI: 10.3389/fphar.2020.00877.Zhang Y., Xu J., Yang H. Hydrogen: an endogenous regulator of liver homeostasis. Front. Pharmacol. 2020; 11: 877. DOI: 10.3389/fphar.2020.00877.Данилова Д.А., Бричкин Ю.Д., Медведев А.П. и др. Использование молекулярного водорода при кардиохирургических операциях в условиях искусственного кровообращения. Современные технологии в медицине. 2021; 13 (1): 71–77. DOI: 10.17691/stm2021.13.1.09.Danilova D.A., Brichkin Y.D., Medvedev A.P. et al. [The use of molecular hydrogen in cardiac surgery under conditions of artificial circulation]. Sovremennye tekhnologii v meditsine. 2021; 13 (1): 71–77. DOI: 10.17691/stm2021.13.1.09 (in Russian).Kawamura T., Huang C.S., Tochigi N. et al. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Ransplantation. 2010; 90 (12): 1344–1351. DOI: 10.1097/TP.0b013e3181fe1357.Kawamura T., Huang C.S., Tochigi N. et al. Inhaled hydrogen gas therapy for prevention of lung transplant-induced ischemia/reperfusion injury in rats. Ransplantation. 2010; 90 (12): 1344–1351. DOI: 10.1097/TP.0b013e3181fe1357.Russell G., Rehman M., LeBaron T.W. et al. An overview of SARS-CoV-2 (COVID-19) infection and the importance of molecular hydrogen as an adjunctive therapy. Reactive Oxygen Species. 2020; 10 (28): 150–165. Available at: https://www.rosj.org/index.php/ros/article/view/271Russell G., Rehman M., LeBaron T.W. et al. An overview of SARS-CoV-2 (COVID-19) infection and the importance of molecular hydrogen as an adjunctive therapy. Reactive Oxygen Species. 2020; 10 (28): 150–165. Available at: https://www.rosj.org/index.php/ros/article/view/271Liu Z., Geng W., Jiang C. et al. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats. Exp. Biol. Med. (Maywood). 2017; 242 (15): 1534–1541. DOI: 10.1177/1535370217725249.Liu Z., Geng W., Jiang C. et al. Hydrogen-rich saline inhibits tobacco smoke-induced chronic obstructive pulmonary disease by alleviating airway inflammation and mucus hypersecretion in rats. Exp. Biol. Med. (Maywood). 2017; 242 (15): 1534–1541. DOI: 10.1177/1535370217725249.Wang T., Zhao L., Liu M. et al. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats. Toxicol. Appl. Pharmacol. 2014; 280 (1): 169–176. DOI: 10.1016/j.taap.2014.06.011.Wang T., Zhao L., Liu M. et al. Oral intake of hydrogen-rich water ameliorated chlorpyrifos-induced neurotoxicity in rats. Toxicol. Appl. Pharmacol. 2014; 280 (1): 169–176. DOI: 10.1016/j.taap.2014.06.011.Chen X., Liu Q., Wang D. et al. Protective effects of hydrogen-rich saline on rats with smoke inhalation injury. Oxid. Med. Cell. Longevity. 2015; 2015: 106836. DOI: 10.1155/2015/106836.Chen X., Liu Q., Wang D. et al. Protective effects of hydrogen-rich saline on rats with smoke inhalation injury. Oxid. Med. Cell. Longevity. 2015; 2015: 106836. DOI: 10.1155/2015/106836.Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2023 Report. Available at: https://goldcopd.org/wp-content/uploads/2023/03/GOLD-2023-ver-1.3-17Feb2023_WMV.pdf [Accessed: January 25, 2024].Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2023 Report. Available at: https://goldcopd.org/wp-content/uploads/2023/03/GOLD-2023-ver-1.3-17Feb2023_WMV.pdf [Accessed: January 25, 2024].GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 385 (9963): 117–171. DOI: 10.1016/S0140-6736(14)61682-2.GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015; 385 (9963): 117–171. DOI: 10.1016/S0140-6736(14)61682-2.Lopez A.D., Shibuya K., Rao C. et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur. Respir. J. 2006; 27 (2): 397–412. DOI: 10.1183/09031936.06.00025805.Lopez A.D., Shibuya K., Rao C. et al. Chronic obstructive pulmonary disease: current burden and future projections. Eur. Respir. J. 2006; 27 (2): 397–412. DOI: 10.1183/09031936.06.00025805.Mathers C.D., Loncar D. Projections of mortality and causes of death, 2016 and 2060, online information available here. PLoS Med. 2006; 3 (11): e442. DOI: 10.1371/journal.pmed.0030442.Mathers C.D., Loncar D. Projections of mortality and causes of death, 2016 and 2060, online information available here. PLoS Med. 2006; 3 (11): e442. DOI: 10.1371/journal.pmed.0030442.Adeloye D., Chua S., Lee C. et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J. Glob. Health. 2015; 5 (2): 020415. DOI: 10.7189/jogh.05.020415.Adeloye D., Chua S., Lee C. et al. Global and regional estimates of COPD prevalence: systematic review and meta-analysis. J. Glob. Health. 2015; 5 (2): 020415. DOI: 10.7189/jogh.05.020415.Lamprecht B., McBurnie M.A., Vollmer W.M. et al. COPD collaborative research group: COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest. 2011; 139 (4): 752–763. DOI: 10.1378/chest.10-1253.Lamprecht B., McBurnie M.A., Vollmer W.M. et al. COPD collaborative research group: COPD in never smokers: results from the population-based burden of obstructive lung disease study. Chest. 2011; 139 (4): 752–763. DOI: 10.1378/chest.10-1253.Berganza C.J., Zhang J.H. The role of helium gas in medicine. Med. Gas Res. 2013; 3 (1): 18. DOI: 10.1186/2045-9912-3-18.Berganza C.J., Zhang J.H. The role of helium gas in medicine. Med. Gas Res. 2013; 3 (1): 18. DOI: 10.1186/2045-9912-3-18.Liu S., Liu K., Sun Q. et al. Hydrogen therapy may be a novel and effective treatment for COPD. Front. Pharmacol. 2011; 2: 19. DOI: 10.3389/fphar.2011.00019.Liu S., Liu K., Sun Q. et al. Hydrogen therapy may be a novel and effective treatment for COPD. Front. Pharmacol. 2011; 2: 19. DOI: 10.3389/fphar.2011.00019.Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol. Ther. 2014; 144 (1): 1–11. DOI: 10.1016/j.pharmthera.2014.04.006.Ohta S. Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine. Pharmacol. Ther. 2014; 144 (1): 1–11. DOI: 10.1016/j.pharmthera.2014.04.006.Steinhubl S.R. Why have antioxidants failed in clinical trials? Am. J. Cardiol. 2008; 101 (10A): 14–19D. DOI: 10.1016/j.amjcard.2008.02.003.Steinhubl S.R. Why have antioxidants failed in clinical trials? Am. J. Cardiol. 2008; 101 (10A): 14–19D. DOI: 10.1016/j.amjcard.2008.02.003.Fischer B.M., Voynow J.A., Ghio A.J. COPD: balancing oxidants and antioxidants. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 261–276. DOI: 10.2147/COPD.S42414.Fischer B.M., Voynow J.A., Ghio A.J. COPD: balancing oxidants and antioxidants. Int. J. Chron. Obstruct. Pulmon. Dis. 2015; 10: 261–276. DOI: 10.2147/COPD.S42414.Schaberg T., Klein U., Rau M. et al. Subpopulations of alveolar macrophages in smokers and nonsmokers: relation to the expression of CD11/CD18 molecules and superoxide anion production. Am. J. Respir. Crit. Care Med. 1995; 151 (5): 1551–1558. DOI: 10.1164/ajrccm.151.5.7735614.Schaberg T., Klein U., Rau M. et al. Subpopulations of alveolar macrophages in smokers and nonsmokers: relation to the expression of CD11/CD18 molecules and superoxide anion production. Am. J. Respir. Crit. Care Med. 1995; 151 (5): 1551–1558. DOI: 10.1164/ajrccm.151.5.7735614.Dekhuijzen P.N., Aben K.K., Dekker I. et al. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1996; 154 (3, Pt 1): 813–816. DOI: 10.1164/ajrccm.154.3.8810624.Dekhuijzen P.N., Aben K.K., Dekker I. et al. Increased exhalation of hydrogen peroxide in patients with stable and unstable chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1996; 154 (3, Pt 1): 813–816. DOI: 10.1164/ajrccm.154.3.8810624.Maziak W., Loukides S., Culpitt S. et al. Exhaled nitric oxide in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1998; 157 (3, Pt 1): 998–1002. DOI: 10.1164/ajrccm.157.3.97-05009.Maziak W., Loukides S., Culpitt S. et al. Exhaled nitric oxide in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 1998; 157 (3, Pt 1): 998–1002. DOI: 10.1164/ajrccm.157.3.97-05009.Praticò D., Basili S., Vieri M. et al. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2a-III, an index of oxidant stress. Am. J. Respir. Crit. Care Med. 1998; 158 (6): 1709–1714. DOI: 10.1164/ajrccm.158.6.9709066.Praticò D., Basili S., Vieri M. et al. Chronic obstructive pulmonary disease is associated with an increase in urinary levels of isoprostane F2a-III, an index of oxidant stress. Am. J. Respir. Crit. Care Med. 1998; 158 (6): 1709–1714. DOI: 10.1164/ajrccm.158.6.9709066.Montuschi P., Collins J.V., Ciabattoni G. et al. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am. J. Respir. Crit. Care Med. 1998; 158 (6): 1709–1714. DOI: 10.1164/ajrccm.158.6.9709066.Montuschi P., Collins J.V., Ciabattoni G. et al. Exhaled 8-isoprostane as an in vivo biomarker of lung oxidative stress in patients with COPD and healthy smokers. Am. J. Respir. Crit. Care Med. 1998; 158 (6): 1709–1714. DOI: 10.1164/ajrccm.158.6.9709066.Kanazawa H., Shoji S., Yoshikawa T. et al. Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease. Clin. Exp. Allergy. 1998; 28 (10): 1244–1250. DOI: 10.1046/j.1365-2222.1998.00342.x.Kanazawa H., Shoji S., Yoshikawa T. et al. Increased production of endogenous nitric oxide in patients with bronchial asthma and chronic obstructive pulmonary disease. Clin. Exp. Allergy. 1998; 28 (10): 1244–1250. DOI: 10.1046/j.1365-2222.1998.00342.x.Kishimoto Y., Kato T., Ito M. et al. Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects. J. Thorac. Cardiovasc. Surg. 2015; 150 (3): 645–654. DOI: 10.1016/j.jtcvs.2015.05.052.Kishimoto Y., Kato T., Ito M. et al. Hydrogen ameliorates pulmonary hypertension in rats by anti-inflammatory and antioxidant effects. J. Thorac. Cardiovasc. Surg. 2015; 150 (3): 645–654. DOI: 10.1016/j.jtcvs.2015.05.052.Lu W., Li D., Hu J. et al. Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. J. Thorac. Dis. 2018; 10 (6): 3232–3243. DOI: 10.21037/jtd.2018.05.93.Lu W., Li D., Hu J. et al. Hydrogen gas inhalation protects against cigarette smoke-induced COPD development in mice. J. Thorac. Dis. 2018; 10 (6): 3232–3243. DOI: 10.21037/jtd.2018.05.93.Barnes P.J. New anti-inflammatory targets for chronic obstructive pulmonary disease. Nat. Rev. Drug Discovery. 2013; 12 (7): 543–559. DOI: 10.1038/nrd4025.Barnes P.J. New anti-inflammatory targets for chronic obstructive pulmonary disease. Nat. Rev. Drug Discovery. 2013; 12 (7): 543–559. DOI: 10.1038/nrd4025.Cazzola M., Page C.P., Calzetta L., Matera M.G. Emerging anti-inflammatory strategies for COPD. Eur. Respir J. 2012; 40 (3): 724–741. DOI: 10.1183/09031936.00213711.Cazzola M., Page C.P., Calzetta L., Matera M.G. Emerging anti-inflammatory strategies for COPD. Eur. Respir J. 2012; 40 (3): 724–741. DOI: 10.1183/09031936.00213711.Paredi P., Kharitonov S.A., Leak D. et al. Exhaled ethane, a marker of lipid peroxidation, is elevated in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2000; 162 (2, Pt 1): 369–373. DOI: 10.1164/ajrccm.162.2.9909025.Paredi P., Kharitonov S.A., Leak D. et al. Exhaled ethane, a marker of lipid peroxidation, is elevated in chronic obstructive pulmonary disease. Am. J. Respir. Crit. Care Med. 2000; 162 (2, Pt 1): 369–373. DOI: 10.1164/ajrccm.162.2.9909025.Li Y., Wang Z., Lian N. et al. Molecular hydrogen: a promising adjunctive strategy for the treatment of the COVID-19. Front. Med. (Lausanne). 2021; 8: 671215. DOI: 10.3389/fmed.2021.671215.Li Y., Wang Z., Lian N. et al. Molecular hydrogen: a promising adjunctive strategy for the treatment of the COVID-19. Front. Med. (Lausanne). 2021; 8: 671215. DOI: 10.3389/fmed.2021.671215.Zheng Z.G., Sun W.Z., Hu J.Y. et al. Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Respir. Res. 2021; 22 (1): 149. DOI: 10.1186/s12931-021-01740-w.Zheng Z.G., Sun W.Z., Hu J.Y. et al. Hydrogen/oxygen therapy for the treatment of an acute exacerbation of chronic obstructive pulmonary disease: results of a multicenter, randomized, double-blind, parallel-group controlled trial. Respir. Res. 2021; 22 (1): 149. DOI: 10.1186/s12931-021-01740-w.Шогенова Л.В., Туе Т.Ч., Крюкова Н.О. и др. Ингаляционный водород в реабилитационной программе медицинских работников, перенесших COVID-19. Кардиоваскулярная терапия и профилактика. 2021; 20 (6): 2986. DOI: 10.15829/1728-8800-2021-2986.Shogenova L.V., Truong T.T., Kryukova N.O. et al. [Inhalation hydrogen in the rehabilitation program of medical workers who underwent COVID-19]. Kardiovaskulyarnaya terapiya i profilaktika. 2021; 20 (6): 24–32. DOI: 10.15829/1728-8800-2021-2986 (in Russian).Koyama Y., Taura K., Hatano E. et al. Effects of oral intake of hydrogen water on liver fibrogenesis in mice. Hepatol. Res. 2014; 44 (6): 663–677. DOI: 10.1111/гепр.12165.Koyama Y., Taura K., Hatano E. et al. Effects of oral intake of hydrogen water on liver fibrogenesis in mice. Hepatol. Res. 2014; 44 (6): 663–677. DOI: 10.1111/гепр.12165.Zhang Y., Sun Q., He B. et al. Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion. Int. J. Cardiol. 2011; 48 (1): 91–95. DOI: 10.1016/j.ijcard.2010.08.058.Zhang Y., Sun Q., He B. et al. Anti-inflammatory effect of hydrogen-rich saline in a rat model of regional myocardial ischemia and reperfusion. Int. J. Cardiol. 2011; 48 (1): 91–95. DOI: 10.1016/j.ijcard.2010.08.058.

The authors declare that there are no conflicts of interest present.