Системное воспаление у больных хронической обструктивной болезнью легких и ожирением
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Ovsyannikov E.S., Avdeev S.N., Budnevsky A.V. Systemic inflammation in patients with chronic obstructive pulmonary disease and obesity. Therapeutic Archive. 2020; 92 (3): 13–18. DOI: 10.26442/00403660.2020.03.000265
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Цель. Оценить особенности про- и противовоспалительного цитокинового профиля, уровня биомаркеров легочной патологии и адипокинов у больных ХОБЛ и ожирением.
Материалы и методы. В исследование включены 88 больных ХОБЛ (GOLD 2–4, группа D). Пациенты распределены в 2 группы. Первая группа составила 44 больных ХОБЛ с нормальной массой тела: 35 мужчин и 9 женщин. Вторая группа –
44 больных ХОБЛ и ожирением: 34 мужчины и 10 женщин. Определяли уровни показателей про- и противовоспалительного цитокинового профиля – интерлейкина (ИЛ)-6, ИЛ-8, фактора некроза опухолей α (ФНО-α), ИЛ-4, ИЛ-10, а также концентрацию высокочувствительного С-реактивного белка, сурфактантного белка D, эластазы, лептина, адипонектина, α1-антитрипсина, рецепторов ФНО 1 и 2 (ФНО-R1, ФНО-R2).
Результаты. У больных ХОБЛ и ожирением по сравнению с больными ХОБЛ с нормальной массой тела достоверно выше были уровни С-реактивного белка, интерферона-γ, ФНО-α, ФНО-R1, ФНО-R2. При этом значения ИЛ-4, ИЛ-6, ИЛ-8, ИЛ-10 у больных в исследуемых группах достоверно не различались. Уровень лептина у больных ХОБЛ и ожирением по сравнению с больными ХОБЛ с нормальной массой тела был достоверно выше.
Заключение. У больных ХОБЛ и ожирением в отличие от больных ХОБЛ с нормальной массой тела выраженность системного воспаления достоверно выше. Однако требуются дальнейшие исследования в этой области.
Ключевые слова: хроническая обструктивная болезнь легких, ожирение, адипокины, интерлейкины, системное воспаление.
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Chronic obstructive pulmonary disease (COPD) is an important public health problem. According to various studies, the prevalence of obesity in patients with COPD is as high as 50%.
Aim. To evaluate pro- and anti-inflammatory cytokine profile, lung diseases biomarkers levels and adipokines levels in patients with COPD and obesity.
Materials and methods. The study included 88 patients with COPD (GOLD 2–4, group D). Patients were divided into two groups. The first group consisted of 44 patients with COPD and normal body weight: 35 men and 9 women. The second group – 44 patients with obesity and COPD: 34 men and 10 women. The levels of pro- and anti-inflammatory cytokines were determined – interleukin-6 (IL-6), interleukin-8
(IL-8), tumor necrosis factor α (TNF-α), interleukin-4 (IL-4), interleukin-10 (IL-10), as well as the concentration of highly sensitive C-reactive protein (CRP), surfactant protein D, elastase, leptin, adiponectin, α1-antitrypsin, receptors of tumor necrosis factor 1 and 2 (TNF-R1, TNF-R2).
Results. In patients with COPD and obesity, compared with patients with COPD and normal body weight, the levels of CRP, interferon-γ, TNF-α, TNF-R1, TNF-R2 were significantly higher. At the same time, the levels of IL-4, IL-6, IL-8, IL-10 did not differ significantly. The level of leptin in patients with COPD and obesity was significantly higher than in patients with COPD and normal body weight.
Conclusion. In patients with COPD and obesity, in contrast to patients with COPD with normal body weight, the severity of systemic inflammation is significantly higher. However, further research is needed in this area.
Key words: chronic obstructive pulmonary disease, obesity, adipokines, interleukins, systemic inflammation.
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24. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941-6. doi: 10.1038/90984
25. Mohamed-Ali V, Flower L, Sethi J, et al. Beta-adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab. 2001;86(12):5864-9. doi: 10.1210/jc.86.12.5864
26. Bruun JM, Pedersen SB, Kristensen K, Richelsen B. Opposite regulation of interleukin-8 and tumor necrosis factor-alpha by weight loss. Obes Res. 2002;10(6):499-506. doi: 10.1038/oby.2002.68
27. Vernooy JH, Drummen NE, van Suylen RJ, et al. Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers. Thorax. 2009;64(1):26-32. doi: 10.1136/thx.2007.085423
28. Hansel NN, Gao L, Rafaels NM, et al. Leptin receptor polymorphisms and lung function decline in COPD. Eur Respir J. 2009;34(1):103-10. doi: 10.1183/09031936.00120408
29. Sorensen GL, Hjelmborg JV, Leth-Larsen R, et al. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice. Scand J Immunol. 2006;64(6):633-8. doi: 10.1111/j.1365-3083.2006.01853.x
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1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for the diagnosis, management, and prevention of COPD. https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018-WMS.pdf
2. Lange P, Celli B, Agustí A, et al. Lung-Function Trajectories Leading to Chronic Obstructive Pulmonary Disease. N Engl J Med. 2015;373(2):111-22. doi: 10.1056/NEJMoa1411532
3. Adeloye D, Chua S, Lee C, et al; Global Health Epidemiology Reference Group (GHERG). 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
4. Steuten LM, Creutzberg EC, Vrijhoef HJ, Wouters EF. COPD as a multicomponent disease: inventory of dyspnoea, underweight, obesity and fat free mass depletion in primary care. Prim Care Respir J. 2006;15(2):84-91. doi: 10.1016/j.pcrj.2005.09.001
5. Divo MJ, Cabrera C, Casanova C, et al. Comorbidity Distribution, Clinical Expression and Survival in COPD Patients with Different Body Mass Index. Chronic Obstr Pulm Dis. 2014;1(2):229-38. doi: 10.15326/jcopdf.1.2.2014.0117
6. Budnevsky AV, Malysh EY. Clinico-pathogenetic relationship of cardiovascular diseases and chronic obstructive pulmonary disease. Kardiologiya. 2017;57(4):89-93 (In Russ.) doi: 10.18565/cardio.2017.4.89-93
7. Budnevsky AV, Ovsyannikov ES, Labzhania NB. Chronic obstructive pulmonary disease concurrent with metabolic syndrome: pathophysiological and clinical features. Therapeutic Archive. 2017;89(1):123-7 (In Russ.) doi: 10.17116/
terarkh2017891123-127
8. Kozhevnikova SA, Budnevsky AV, Ovsyannikov ES, Belov VN. Particularity of the clinical course and quality of life of patients with chronic obstructive pulmonary disease on the background of the metabolic syndrome. Meditsinskiy vestnik Severnogo Kavkaza. 2017;12(1):20-3 (In Russ.) doi: 10.14300/mnnc.2017.12006
9. Chuchalin AG, Avdeev SN, Aysanov ZR, et al. Russian respiratory society. Federal clinical guidelines on diagnosis and management of chronic obstructive pulmonary disease. Pul’monologiya. 2014;3:15-36 (In Russ.) doi: 10.18093/0869-0189-2014-0-3-15-54
10. Wouters EF. Local and systemic inflammation in chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2005;2(1):26-33. doi: 10.1513/pats.200408-039ms
11. Fabbri LM, Rabe KF. From COPD to chronic systemic inflammatory syndrome? Lancet. 2007;370(9589):797-9. doi: 10.1016/s0140-6736(07)61383-x
12. Mannino DM, Ford ES, Redd SC. Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Am J Med. 2003;114(9):758-62. doi: 10.1016/s0002-9343(03)00185-2
13. Prescott E, Almdal T, Mikkelsen KL, et al. Prognostic value of weight change in chronic obstructive pulmonary disease: results from the Copenhagen City Heart Study. Eur Respir J. 2002;20(3):539-44. doi: 10.1183/09031936.02.00532002
14. Petersen AM, Penkowa M, Iversen M, et al. Elevated levels of IL-18 in plasma and skeletal muscle in chronic obstructive pulmonary disease. Lung. 2007;185(3):161-71. doi: 10.1007/s00408-011-9330-3
15. Margretardottir OB, Thorleifsson SJ, Gudmundsson G, et al. Hypertension, systemic inflammation and body weight in relation to lung function impairment-an epidemiological study. COPD. 2009;6(4):250-5. doi: 10.1080/15412550903049157
16. Dentener MA, Creutzberg EC, Schols AM, et al. Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations. Thorax. 2001;56(9):721-6. doi: 10.1136/thorax.56.9.721
17. Aisanov Z, Avdeev S, Arkhipov V, et al. Russian guidelines for the management of COPD: algorithm of pharmacologic treatment. Int J Chron Obstruct Pulmon Dis. 2018;8(13):183-7. doi: 10.2147/COPD.S153770
18. Bolton CE, Evans M, Ionescu AA, et al. Insulin resistance and inflammation – A further systemic complication of COPD. COPD. 2007;4(2):121-6. doi: 10.1080/15412550701341053
19. Poulain M, Doucet M, Major GC, et al. The effect of obesity on chronic respiratory diseases: pathophysiology and therapeutic strategies. CMAJ. 2006;174(9):1293-9. doi: 10.1503/cmaj.051299
20. Trayhurn P, Wood IS. Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr. 2004;92(3):347-55. doi: 10.1079/bjn20041213
21. Loffreda S, Yang SQ, Lin HZ, et al. Leptin regulates proinflammatory immune responses. FASEB J. 1998;12(1):57-65. doi: 10.1096/
fasebj.12.1.57
22. Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation. 2003;107(11):1514-9. doi: 10.1161/01.cir.0000056767. 69054.b3
23. Bruun JM, Lihn AS, Verdich C, et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab. 2003;285(3):E527-33. doi: 10.1152/ajpendo.00110.2003
24. Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med. 2001;7(8):941-6. doi: 10.1038/90984
25. Mohamed-Ali V, Flower L, Sethi J, et al. Beta-adrenergic regulation of IL-6 release from adipose tissue: in vivo and in vitro studies. J Clin Endocrinol Metab. 2001;86(12):5864-9. doi: 10.1210/jc.86.12.5864
26. Bruun JM, Pedersen SB, Kristensen K, Richelsen B. Opposite regulation of interleukin-8 and tumor necrosis factor-alpha by weight loss. Obes Res. 2002;10(6):499-506. doi: 10.1038/oby.2002.68
27. Vernooy JH, Drummen NE, van Suylen RJ, et al. Enhanced pulmonary leptin expression in patients with severe COPD and asymptomatic smokers. Thorax. 2009;64(1):26-32. doi: 10.1136/thx.2007.085423
28. Hansel NN, Gao L, Rafaels NM, et al. Leptin receptor polymorphisms and lung function decline in COPD. Eur Respir J. 2009;34(1):103-10. doi: 10.1183/09031936.00120408
29. Sorensen GL, Hjelmborg JV, Leth-Larsen R, et al. Surfactant protein D of the innate immune defence is inversely associated with human obesity and SP-D deficiency infers increased body weight in mice. Scand J Immunol. 2006;64(6):633-8. doi: 10.1111/j.1365-3083.2006.01853.x
1 ФГБОУ ВО «Воронежский государственный медицинский университет им. Н.Н. Бурденко» Минздрава России, Воронеж, Россия;
2 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
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E.S. Ovsyannikov1, S.N. Avdeev2, A.V. Budnevsky1
1 Burdenko Voronezh State Medical University, Voronezh, Russia;
2 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia