cfpdБюллетень физиологии и патологии дыханияBulletin Physiology and Pathology of Respiration1998-5029Дальневосточный научный центр физиологии и патологии дыхания10.36604/1998-5029-2022-85-32-36cfpd-1037Research ArticleОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯORIGINAL RESEARCHВыделение биомаркеров хронической обструктивной болезни легких с применением ROC-анализаDetection of chronic obstructive pulmonary disease biomarkers using ROC-analysishttps://orcid.org/0000-0002-1009-9011ВиткинаТ. И.VitkinaT. I.

Татьяна Исааковна Виткина, д-р биол. наук, профессор РАН, зав. лабораторией медицинской экологии и рекреационных ресурсов

690105, г. Владивосток, ул. Русская, 73г

Tatiana I. Vitkina, PhD, DSc (Biol.), Professor of RAS, Head of Laboratory of Medical Ecology and Recreational Resources

73g Russkaya Str., Vladivostok, 690105

tash30@mail.ruКондратьеваЕ. В.KondratyevaE. V.

Елена Викторовна Кондратьева, канд. биол. наук, научный сотрудник, лаборатория медицинской экологии и рекреационных ресурсов

690105, г. Владивосток, ул. Русская, 73г

Elena V. Kondratyeva, PhD (Biol.), Staff Scientist, Laboratory of Medical Ecology and Recreational Resources

73g Russkaya Str., Vladivostok, 690105

elena.v.kondratyeva@yandex.ruВладивостокский филиал Федерального государственного бюджетного научного учреждения «Дальневосточный научный центр физиологии и патологии дыхания» – Научно-исследовательский институт медицинской климатологии и восстановительного леченияРоссияVladivostok Branch of Far Eastern Scientific Center of Physiology and Pathology of Respiration – Research Institute of Medical Climatology and Rehabilitative TreatmentRussian Federation2022220920220853236Copyright © Виткина Т.И., Кондратьева Е.В., 20222022Виткина Т.И., Кондратьева Е.В.Vitkina T.I., Kondratyeva E.V.This work is licensed under a Creative Commons Attribution 4.0 License.https://cfpd.elpub.ru/jour/article/view/1037

Цель. Выявление ключевых диагностических критериев хронической обструктивной болезни легких (ХОБЛ).Материалы и методы. Обследовано 112 больных ХОБЛ лёгкой, средней и тяжёлой степени тяжести, и 32 относительно здоровых добровольца с отсутствием нарушений функций внешнего лёгочного дыхания. Методом проточной цитофлуориметрии определяли уровень IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ, TGF-β1 и CD4+CD126+ клеток. Прооксидантные и антиоксидантные маркёры окислительного стресса 8-OH-дезоксигуанозин, протеин карбонил, глутатион, глутатион редуктаза, глутатион пероксидаза, тиоредоксин-1 и тиоредоксин редуктаза-1 оценивали иммуноферментным анализом.Результаты. Выявлено наличие высокоранговых корреляций провоспалительного звена иммунитета и компонентов прооксидантной системы, что свидетельствует о наличии системных альтеративных процессов у пациентов с ХОБЛ. На базе ROC-анализа выделены ключевые биомаркёры у пациентов с ХОБЛ стабильного течения: 8-OH-дезоксигуанозин, CD4+CD126+ клетки, IL-17 и тиоредоксин, установлены их пороговые уровни.Заключение. Рекомендуемые диагностические критерии позволят оптимизировать терапевтические стратегии при ХОБЛ.

Aim. To identify key diagnostic criteria for chronic obstructive pulmonary disease (COPD).Materials and methods. We examined 112 patients with mild, moderate and severe COPD and 32 relatively healthy volunteers with no disturbances in the lung function. The level of IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ, TGF-β1 and CD4+CD126+ cells was determined by means of flow cytometry method. Prooxidant and antioxidant markers of oxidative stress 8-OHdeoxyguanosine, protein carbonyl, glutathione, glutathione reductase, glutathione peroxidase, thioredoxin-1, and thioredoxin reductase-1 were assessed by enzyme immunoassay.Results. The presence of high-ranking correlations of the proinflammatory link of immunity and components of the prooxidant system was revealed, which indicates the presence of systemic alterative processes in patients with COPD. Based on ROC-analysis, key biomarkers were identified in patients with stable COPD: 8-OH-deoxyguanosine, CD4+CD126+ cells, IL-17, and thioredoxin, and their threshold levels were established.Conclusion. The recommended diagnostic criteria will optimize the therapeutic strategies for COPD.

хроническая обструктивная болезнь легкихвоспалениепероксидативный балансбиомаркерыROC-анализchronic obstructive pulmonary diseaseinflammationperoxidative balancebiomarkersROC-analysisReferencesАнаев Э.Х. Биологические маркёры при хронической обструктивной болезни лёгких // Практическая пульмонология. 2018. №1. С.26‒32. EDN: OVTGDL.Anaev E.Kh. [Biological markers of chronic obstructive pulmonary disease]. Prakticheskaya pul'monologiya 2018; (1):26‒32 (in Russian).Barnes P.J. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease // J. Allergy Clin. Immunol. 2016. Vol.138, Iss.1. P.16‒27. https://doi.org/10.1016/j.jaci.2016.05.011Barnes P.J. Inflammatory mechanisms in patients with chronic obstructive pulmonary disease. J. Allergy Clin. Immunol. 2016; 138(1):16‒27. https://doi.org/10.1016/j.jaci.2016.05.011Ni L., Dong Ch. Roles of myeloid and lymphoid cells in the pathogenesis of chronic obstructive pulmonary disease // Front. Immunol. 2018. Vol.9. Article number: 1431. https://doi.org/10.3389/fimmu.2018.01431Ni L., Dong Ch. Roles of myeloid and lymphoid cells in the pathogenesis of chronic obstructive pulmonary disease. Front. Immunol. 2018; 9: 1431. https://doi.org/10.3389/fimmu.2018.01431Boukhenouna S., Wilson A., Bahmed K., Kosmider B. Reactive oxygen species in chronic obstructive pulmonary disease // Oxid. Med. Cell. Longev. 2018. Article number: 5730395. https://doi.org/10.1155/2018/5730395Boukhenouna S., Wilson A., Bahmed K., Kosmider B. Reactive oxygen species in chronic obstructive pulmonary disease. Oxid. Med. Cell. Longev. 2018: 5730395. https://doi.org/10.1155/2018/5730395Nurwidya F., Damayanti T., Yunus F. The role of innate and adaptive immune cells in the immunopathogenesis of chronic obstructive pulmonary disease // Tuberc. Respir. Dis. (Seoul). 2016. Vol.79, Iss.1. Р.5–13. https://doi.org/10.4046/trd.2016.79.1.5Nurwidya F., Damayanti T., Yunus F. The role of innate and adaptive immune cells in the immunopathogenesis of chronic obstructive pulmonary disease. Tuberc. Respir. Dis. (Seoul) 2016; 79(1):5–13. https://doi.org/10.4046/trd.2016.79.1.5Otasevic V., Vucetic M., Grigorov I., Martinovic V., Stancic A. Ferroptosis in different pathological contexts seen through the eyes of mitochondria // Oxid. Med. Cell. Longev. 2021. Article number: 5537330. https://doi.org/10.1155/2021/5537330Otasevic V., Vucetic M., Grigorov I., Martinovic V., Stancic A. Ferroptosis in different pathological contexts seen through the eyes of mitochondria. Oxid. Med. Cell. Longev. 2021: 5537330. https://doi.org/10.1155/2021/5537330Rahman I., Adcock I. M. Oxidative stress and redox regulation of lung inflammation in COPD // Eur. Respir. J. 2006. Vol.28. P.219‒242. https://doi.org/10.1183/09031936.06.00053805Rahman I., Adcock I. M. Oxidative stress and redox regulation of lung inflammation in COPD. Eur. Respir. J. 2006; 28:219‒242. https://doi.org/10.1183/09031936.06.00053805Antus B., Kardos Z. Oxidative stress in COPD: molecular background and clinical monitoring // Curr. Med. Chem. 2015. Vol.22, Iss.5. P.627‒650. https://doi.org/10.2174/092986732205150112104411Antus B., Kardos Z. Oxidative stress in COPD: molecular background and clinical monitoring. Curr. Med. Chem. 2015; 22(5):627‒650. https://doi.org/10.2174/092986732205150112104411Mahmood D.F.D., Abderrazak A., El Hadri K., Simmet T., Rouis M. The thioredoxin system as a therapeutic target in human health and disease // Antioxid. Redox Signal. 2013. Vol.19, Iss.11. P.1266–1303. https://doi.org/10.1089/ars.2012.4757Mahmood D.F.D., Abderrazak A., El Hadri K., Simmet T., Rouis M. The thioredoxin system as a therapeutic target in human health and disease. Antioxid. Redox Signal. 2013; 19(11):1266–1303. https://doi.org/10.1089/ars.2012.4757El Hadri K., Smith R., Duplus E., El Amri C. Inflammation, oxidative stress, senescence in atherosclerosis: Thioredoxine- 1 as an emerging therapeutic target // Int. J. Mol. Sci. 2022. Vol.23, Iss.1. Article number: 77. https://doi.org/10.3390/ijms23010077El Hadri K., Smith R., Duplus E., El Amri C. Inflammation, oxidative stress, senescence in atherosclerosis: Thioredoxine-1 as an emerging therapeutic target. Int. J. Mol. Sci. 2022; 23(1):77. https://doi.org/10.3390/ijms23010077Mohamed I.N., Li L., Ismael S., Ishrat T., El-Remessy A.B. Thioredoxin interacting protein, a key molecular switch between oxidative stress and sterile inflammation in cellular response // World J. Diabetes. 2021. Vol.12, Iss.12. P.1979‒1999. https://doi.org/10.4239/wjd.v12.i12.1979Mohamed I.N., Li L., Ismael S., Ishrat T., El-Remessy A.B. Thioredoxin interacting protein, a key molecular switch between oxidative stress and sterile inflammation in cellular response. World J. Diabetes 2021; 12(12):1979‒1999. https://doi.org/10.4239/wjd.v12.i12.1979Pichavant M., Rémy G., Bekaert S., Le Rouzic O., Kervoaze G., Vilain E., Just N., Tillie-Leblond I., Trottein F., Cataldo D., Gosset P. Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis // Mucosal Immunol. 2014. Vol.7, Iss.3. P.568–578. https://doi.org/10.1038/mi.2013.75Pichavant M., Rémy G., Bekaert S., Le Rouzic O., Kervoaze G., Vilain E., Just N., Tillie-Leblond I., Trottein F., Cataldo D., Gosset P. Oxidative stress-mediated iNKT-cell activation is involved in COPD pathogenesis. Mucosal Immunol. 2014; 7(3):568–578. https://doi.org/10.1038/mi.2013.75Rossman M.J., Groot H.J., Reese V., Zhao J., Amann M., Richardson R.S. Oxidative stress and COPD: The effect of oral antioxidants on skeletal muscle fatigue // Med. Sci. Sports Exerc. 2013. Vol.45, Iss.7. P.1235–1243. https://doi.org/10.1249/MSS.0b013e3182846d7eRossman M.J., Groot H.J., Reese V., Zhao J., Amann M., Richardson R.S. Oxidative stress and COPD: The effect of oral antioxidants on skeletal muscle fatigue. Med. Sci. Sports Exerc. 2013; 45(7):1235–1243. https://doi.org/10.1249/MSS.0b013e3182846d7eEeden S., Sin D.D. Oxidative stress in chronic obstructive pulmonary disease: A lung and systemic process // Can. Res pir. J. 2013. Vol.20, Iss.1. P.27–29. https://doi.org/10.1155/2013/509130Eeden S., Sin D.D. Oxidative stress in chronic obstructive pulmonary disease: A lung and systemic process. Can. Respir. J. 2013; 20(1):27–29. https://doi.org/10.1155/2013/509130

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