N.G. SHAMSUTDINOVA¹, G.I. NURULLINA¹, N.A. BOLSHAKOV¹, A.K. KHUSAINOVA¹, E.V. DYAKOVA²

¹Kazan State Medical University, 49 Butlerov Str., Kazan, Russian Federation, 420012

²Republican Clinical Hospital of the Ministry of Healthcare of the Republic of Tatarstan, 138 Orenburgskiy Trakt, Kazan, Russian Federation, 420064

 Shamsutdinova N.G. ― PhD (medicine), Assistant of the Department of Hospital Therapy, e-mail: nailya@e-diva.ru

Nurullina G.I. ― PhD (medicine), Assistant of the Department of Hospital Therapy, tel. (843) 290-18-20, e-mail: nurguzel@yandex.ru, ORCID ID: 0000-0002-7697-187X

Bolshakov N.A. ― student of Therapy Faculty, e-mail: decker344@gmail.com, ORCID ID: 0000-0003-0349-6040

Khusainova A.K. ― student of Therapy Faculty, e-mail: aida.husainowa@yandex.ru, ORCID ID: 0000-0002-7209-0549

Dyakova E.V. ― pulmonologist, tel. (843) 237-36-26, e-mail: vrkaty.dyakowa@yandex.ru

Chronic obstructive pulmonary disease (COPD) is known to be one of the most common causes of death in the world – the fourth place in the structure of death. Over the last years, it has been recognized that inflammation in COPD is not limited to pulmonary tissue and is systemic in nature. Pro-inflammatory cytokines such as interleukin-1-beta (IL-1β), gamma-interferon (IFN-γ), tumor necrosis factor-alpha (TNF-α), as well as C-reactive protein (CRP), fibrinogen, matrix metalloproteinases, etc. play an important role in the pathogenesis of systemic manifestations of COPD. These mechanisms serve as the basis for comorbid states under COPD. The most frequent  states include cardio-vascular diseases, muscle atrophy, osteoporosis, cachexia, thrombosis, and depression. Therapy of these conditions in COPD is not properly studied, as comorbid patients are, as a rule, excluded from clinical studies. The study of pathogenesis of these diseases will allow developing effective methods of their therapy and prevention.

Key words: comorbidity, COPD, pathogenesis, systemic inflammation.

(For citation: Shamsutdinova N.G., Nurullina G.I., Bolshakov N.A., Khusainova A.K., Dyakova E.V. Mechanisms of COPD systemic manifestations. Practical Medicine. 2018)

REFERENCES

1. Khronicheskaya obstruktivnaya boleznʹ legkikh (KHOBL) [Chronic obstructive pulmonary disease]. Khronicheskaya obstruktivnaya boleznʹ legkikh (KHOBL), available at: http://www.who.int/ru/news-room/fact-sheets/detail/chronic-obstructive-pulmonary-disease-(copd)
2. Chuchalin A.G., Avdeev S.N., Aysanov Z.R. et al. Klinicheskie rekomendatsii: Khronicheskaya obstruktivnaya boleznʹ legkikh [Clinical recommendations: Chronic obstructive pulmonary disease]. Moscow: Rossiyskoe respiratornoe obshchestvo, 2016. 68 p.
3. Vertkin A.L., Skotnikov A.S. Tikhonovskaya E.Yu. et al. Comorbidity in COPD: the role of chronic systemic inflammation. RMZH “Meditsinskoe obozrenie”, 2014, no. 11, pp. 811-817 (in Russ.).
4. Avdeev S.N., Baymakanova G.E. Cardiovascular diseases in patients with COPD: problems of drug choice. Pulʹmonologiya i allergologiya, 2008, no. 2, pp. 3-8 (in Russ.).
5. Clarenbach C.F., Senn O., Kohler M. COPD – eine Systemerkrankung. Swiss Medical Forum, 2013, vol. 13 (4), pp. 60-63. DOI: 10.5167/uzh-90990.
6. Marcu C. Veränderungen der Körperzusammensetzung von COPD-Patienten: Dissertation zur Erlangung des Grades eines Doktors der Medizin; Medizinischen Fakultät der Universität des Saarlandes. Kronstadt, Rumänien, 2009. 98 p.
7. Global Inititative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD. Gold Reports 2018 ― Global Inititative for Chronic Obstructive Lung Disease ― GOLD, available at: http://goldcopd.org/wp-content/uploads/2017/11/GOLD-2018-v6.0-FINAL-revised-20-Nov_WMS.pdf
8. Gan W.Q., Man S.F.P, Senthilselvan A., Sin D.D. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a metaanalysis. Thorax, 2004, vol. 59 (7), pp. 574-580. DOI: 10.1136/thx.2003.019588
9. Rybasʹ E.G., Naryshkina S.V. Modern ideas about anti-inflammatory therapy of chronic obstructive pulmonary disease. Byulletenʹ fiziologii i patologii dykhaniya, 2013, no. 48, pp. 90-96 (in Russ.).
10. Hurst J.R., Perera W.R., Wilkinson T.M.A. et al. Systemic and Upper and Lower Airway Inflammation at Exacerbation of Chronic Obstructive Pulmonary Disease. AJRCCM, 2006, vol. 173, pp. 71-78. DOI:10.1164/rccm.200505-704OC.
11. Sevenoaks M.J., Stockley R.A. Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity ― a common inflammatory phenotype? Respiratory Research, 2006, vol. 7, pp. 70-78. DOI: 10.1186/1465-9921-7-70.
12. Kirillova N.A., Chernogoryuk G.Eh., Fedosenko S.V. et al. Apoptosis of neutrophils in the region of aseptic inflammation as a manifestation of a systemic reaction in chronic obstructive pulmonary disease (COPD). Sbornik nauchnykh tezisov i statey «Zdorovʹe i obrazovanie v XXI Veke», 2009, vol. 11, no. 2, pp. 174-175 (in Russ.).
13. Bosse S. Einfluss von Beclometason HFA-134 auf die Lungenfunktion, die Lebens qualität und die Freisetzung pro-und antiin flammatorischer Zytokinebei Patienten mit chronischobstruktiver Lungenerkrankung: Zur Erlangung des akademischen Grades Doctor medicinae; Medizinischen Fakultät der Charité ― Universitätsmedizin Berlin. Brandenburg, 2006. 75 p.
14. Budnevskiy A.V., Ovsyannikov E.S., Chernov A.V., Drobysheva E.S. Diagnostic value of biomarkers of systemic inflammation in chronic obstructive pulmonary disease. Klinicheskaya meditsina, 2014, vol. 92 (9), pp. 16-21 (in Russ.).
15. Murali Mohan B.V., Sen T., Ranganatha R. Systemic Manifestations of COPD. The Journal of the Association of Physicians of India, 2012, vol. 60, pp. 44-47.
16. Avdeev S.N., Baymakanova G.E. What information does C-reactive protein provide in patients with COPD? Pulʹmonologiya i allergologiya, 2007, no. 3, pp. 11-14 (in Russ.).
17. Agapova Yu.R., Gulin A.V., Malysheva E.V. Autoimmune syndrome as a marker of long-term and prognostically unfavorable course of chronic obstructive pulmonary disease and bronchial asthma. Lechebnoe delo, 2014, no. 1, pp. 84-90 (in Russ.).
18. Meshcheryakova N.N. Principles of pulmonary rehabilitation of patients with chronic obstructive pulmonary disease. Prakticheskaya pulʹmonologiya, 2013, no. 2, pp. 27-31 (in Russ.).
19. Abeer M.R., Fathalla D. Left ventricular diastolic dysfunction in patients with chronic obstructive pulmonary disease (COPD), prevalence and association with disease severity: Using tissue Doppler study. Egyptian Journal of Chest Diseases and Tuberculosis, 2015, vol. 64, issue 4, pp. 785-792. DOI: 10.1016/j.ejcdt.2015.06.010.
20. Demochko E.A., Minushkina L.O. The value of biomarkers in the diagnosis and evaluation of the prognosis of patients with cardiovascular and pulmonary pathology. Rossiyskiy meditsinskiy zhurnal, 2014, no. 6, pp. 43-47 (in Russ.).
21. Kuznetsova O.Yu., Moiseeva I.E., Pokhaznikova M.A. Mechanisms of the formation of comorbid conditions in chronic obstructive pulmonary disease. Rossiyskiy semeynyy vrach, 2011, vol. 15 (4), pp. 7-11 (in Russ.).
22. Gaynitdinova V.V., Bakirov A.B., Akhmetzyanova Eh.Kh. et al. Arterial stiffness of peripheral vessels in patients with chronic obstructive pulmonary disease and when combined with arterial hypertension. Kazanskiy meditsinskiy zhurnal, 2013, vol. 94 (6), pp. 808-812 (in Russ.).
23. Gaynitdinova V.V., Bakirov A.B., Akhmetzyanova Eh.Kh. Structural and functional changes in large peripheral vessels in patients. Prakticheskaya meditsina, 2013, no. 5 (71), pp. 56-61 (in Russ.).
24. Funk G.C., Lang I., Schenk P. et al. Left Ventricular Diastolic Dysfunction in Patients With COPD in the Presence and Absence of Elevated Pulmonary Arterial Pressure. CHEST, 2008, vol. 133, issue 6, pp. 1354-1359. DOI: 10.1378/chest.07-2685.
25. Anderson W.J., Lipworth B.J., Rekhraj S. et al. Left Ventricular Hypertrophy in COPD Without Hypoxemia: the elephant in the room? CHEST, 2013, vol. 143, issue 1, pp. 91-97. DOI: 10.1378/chest.12-0775.
26. Li V.V., Zadionchenko V.S., Adasheva T.V. et al. Arterial hypertension in patients with chronic obstructive pulmonary disease — in search of phenotypes. Part I. Arkhivʺ vnutrenney meditsiny, 2013, no. 1 (9), pp. 19-24 (in Russ.).
27. Dolinina L.Yu., Delieva A.N., Galkina O.V., Trofimov V.I. Comparative analysis of markers of systemic inflammatory process in patients with chronic obstructive pulmonary disease in combination with coronary heart disease. Arkhivʺ vnutrenney meditsiny, 2015, no. 5 (13), pp. 21-24 (in Russ.).
28. Tseymakh I.Ya., Momot A.P., Kostyuchenko G.I. et al. The role of endothelial dysfunction, conjugation of hemostatic and systemic inflammatory reactions in the pathogenesis of exacerbation of chronic obstructive pulmonary disease, dependent on infectious inflammation. Terapevticheskiy arkhiv, 2013, no. 3, pp. 17-22 (in Russ.).
29. Barreiro E., Gea J. Molecular and biological pathways of skeletal muscle dysfunction in chronic obstructive pulmonary disease. Chronic Respiratory Disease, 2016, vol. 13 (3), pp. 297-311. DOI: 10.1177/1479972316642366.
30. Gaur S.N., Goel N. Systemic manifestations of COPD. The Association of Physicians of India, 2012, vol. 7 (5), pp. 386-389, available at: http://www.apiindia.org/pdf/medicine_update_2012/pulmonology_05.pdf
31. Gurko G.I. Sistemnye proyavleniya khronicheskoy obstruktivnoy bolezni legkikh v pozhilom vozraste (kliniko-ehpidemiologicheskoe, neyroimmunoehndokrinologicheskoe, mediko-organizatsionnoe issledovanie): avtoref. dis. … dok. med. nauk [Systemic manifestations of chronic obstructive pulmonary disease in the elderly (clinical and epidemiological, neuroimmune-endocrinological, medical and organizational research). Synopsis of dis. Dr med. sciences]. Saint Petersburg, 2012. 205 p.: il.
32. Lemeshevskaya S.S., Makarevich A.Eh., Pochtavtsev A.Yu. et al. Systemic manifestations of chronic obstructive pulmonary disease (COPD): the state of muscle tissue. Meditsinskiy zhurnal, 2014, no. 3 (49), pp. 127-131 (in Russ.).
33. Chen R., Li X., Guan L. Effectiveness of neuromuscular electrical stimulation for the rehabilitation of moderate-to-severe COPD: a meta-analysis. International Journal of COPD, 2016, vol. 11 (1), P. 2965-2975. DOI: 10.2147/COPD.S120555
34. Kunafina T.V., Belevskiy A.S., Kozhevnikova O.V. The role of electromyostimulation in increasing the physical activity of patients with chronic obstructive pulmonary disease. Prakticheskaya pulʹmonologiya, 2017, no. 3, pp. 22-26 (in Russ.).
35. Lapteva E.A., Lapteva I.M., Kharevich O.N. Systemic effects of chronic obstructive pulmonary disease at the stages of its progression. Kazanskiy meditsinskiy zhurnal, 2013, vol. 94 (5), pp. 605-609 (in Russ.).
36. Shoykhet Ya.N., Titova E.A., Konovalov V.K., Titova L.A. The course of chronic obstructive pulmonary disease in diabetes mellitus. Kazanskiy meditsinskiy zhurnal, 2008, vol. 89 (5), pp. 651-656 (in Russ.).
37. Kireev S.A., Ryazanov A.S., Eremenko N.N., Demenko E.G. COPD in combination with metabolic syndrome: features of clinical manifestations and laboratory indicators of systemic inflammation. Biomeditsina, 2010, no. 4, pp. 40-45 (in Russ.).
38. Mironova N.V., Naryshkina S.V. Anxiety-depressive disorders in patients with chronic obstructive pulmonary disease. Byulletenʹ fiziologii i patologii dykhaniya, 2015, no. 55, pp. 132-139 (in Russ.).
39. Tatarskiy A.R., Kirillov D.A. Edematous syndrome is a criterion for severe, life-threatening COPD. Pathogenetic mechanisms of development and treatment. Prakticheskaya pulʹmonologiya, 2013, no. 4, pp. 48-53 (in Russ.).