Preview

PULMONOLOGIYA

Advanced search

The protective effect of beclomethasone dipropionate in the modeling of chronic obstructive pulmonary disease

https://doi.org/10.18093/0869-0189-2020-30-1-61-68

Abstract

The purpose of the study was to evaluate the protective effect of the inhaled glucocorticosteroids of beclomethasone dipropionate (BDP) using the experimental model of chronic obstructive pulmonary disease (COPD). Materials and Methods. The COPD model was reproduced in rats (n = 30) during a discrete 60-day exposure to nitrogen dioxide, 9 individuals formed an intact group. Inhalation of BDP (50 micrograms per day) and control (n = 15) placebo inhalation were performed for 60 days in the rats in the experimental group (n = 15). The cell composition and cytokine enzymatic profile of bronchoalveolar lavage fluid (BALF), its content of secretory immunoglobulin A (sIgA) and surfactant protein D (SP-D) were determined by ELISA. Histological and morphometric lungs examination was performed. Results. Typical for COPD pathomorphological changes in the lungs were determined in the placebo group, the content of inflammatory cells and pro-inflammatory mediators in BALF increased, the functional activity of bronchoalveolar epithelium (SP-D, sIgA) deteriorated. There was a clear trend in the activity of neutrophilic-lymphocytic inflammation decrease with normalization of the profile of pro-inflammatory cytokines and enzymes in BALF In the group of animals receiving BDP; there was also a restoration of the morphological structure of the bronchoalveolar epithelium and improvement of its functional activity. Conclusion. The using of BDP in rats with the experimental COPD model had an expressed anti-inflammatory effect associated with the activation of physiological repair processes in the lungs, manifested by the restoration of structural, immune barrier integrity and functional activity of the bronchoalveolar epithelium.

About the Authors

O. N. Titova
Academician I.P.Pavlov First Federal Saint-Petersburg State Medical University, Healthcare Ministry of Russia
Russian Federation

Ol'ga N. Titova, Doctor of Medicine, Professor, Director of Pulmonology Research Institute

ul. L'va Tolstogo 6–8, Saint-Petersburg, 197089
tel.: (812) 338-78-40 


Competing Interests:

 

 



N. A. Kuzubova
Academician I.P.Pavlov First Federal Saint-Petersburg State Medical University, Healthcare Ministry of Russia
Russian Federation

Nataliya A. Kuzubova, Doctor of Medicine, Deputy Director, Pulmonology Research Institute

ul. L'va Tolstogo 6–8, Saint-Petersburg, 197089
tel.: (812) 338-66-16 



E. S. Lebedeva
Academician I.P.Pavlov First Federal Saint-Petersburg State Medical University, Healthcare Ministry of Russia
Russian Federation

Elena S. Lebedeva, Candidate of Biology, Leading Researcher, Pulmonology Research Institute

ul. L'va Tolstogo 6–8, Saint-Petersburg, 197089
tel.: (812) 338-78-20 



References

1. Global Initiative for Chronic Obstructive Lung Disease. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2019 Report. Available at: https://goldcopd.org/wp-content/uploads/2018/11/GOLD-2019-v1.7-FINAL-14Nov2018WMS.pdf [Accessed: September 6, 2019].

2. Rutgers S.R., Postma D.S., ten Hacken N.H. et al. Ongoing airway inflammation in patients with COPD who do not currently smoke. Thorax. 2000; 55 (1): 12–18. DOI: 10.1136/thorax.55.1.12.

3. Barnes P.J. Inhaled corticosteroids in COPD: a controversy. Respiration. 2010; 80 (2): 89–95. DOI: 10.1159/000315416.

4. 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; 13: 183–187. DOI: 10.2147/COPD.S153770.

5. Agusti A., Fabbri L.M., Singh D. et al. Inhaled corticosteroids in COPD: friend or foe? Eur. Respir. J. 2018; 52 (6). pii: 1801219. DOI: 10.1183/13993003.01219-2018.

6. Cataldo D., Derom E., Liistro G. et al. Overuse of inhaled corticosteroids in COPD: five questions for withdrawal in daily practice. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 2089–2099. DOI: 10.2147/COPD.S164259.

7. Crim C., Calverley P.M.A., Anderson J.A. et al. Pneumonia risk in COPD patients receiving inhaled corticosteroids alone or in combination: TORCH study results. Eur. Respir. J. 2009; 34 (3): 641–647. DOI: 10.1183/09031936.00193908.

8. Vanfleteren L., Fabbri L.M., Papi A. et al. Triple therapy (ICS/LABA/LAMA) in COPD: time for a reappraisal. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 3971–3981. DOI: 10.2147/COPD.S185975.

9. Thomas B.J., Porritt R.A., Hertzog P.J. et al. Glucocorticosteroids enhance replication of respiratory viruses: effect of adjuvant interferon. Sci. Rep. 2014; 4: 7176. DOI: 10.1038/srep07176.

10. Contoli M., Pauletti A., Rossi M.R. et al. Long-term effects of inhaled corticosteroids on sputum bacterial and viral loads in COPD. Eur. Respir. J. 2017; 50 (4): 1700451. DOI: 10.1183/13993003.00451-2017.

11. Pavord I.D., Lettis S., Locantore N. et al. Blood eosinophils and inhaled corticosteroid/long-acting β-2 agonist efficacy in COPD. Thorax. 2016; 71 (2): 118–125. DOI: 10.1136/thoraxjnl-2015-207021.

12. Bafadhel M., Pavord I.D., Russell R.E.K. Eosinophils in COPD: just another biomarker? Lancet Respir. Med. 2017; 5 (9): 747–759. DOI: 10.1016/S2213-2600(17)30217-5.

13. Barnes P.J. Role of HDAC2 in the pathophysiology of COPD. Annu. Rev. Physiol. 2009; 71: 451–464. DOI: 10.1146/annurev.physiol.010908.163257.

14. Hoonhorst S.J.M., ten Hacken N.H.T., Vonk J.M. et al. Steroid resistance in COPD? Overlap and differential antiinflammatory effects in smokers and ex-smokers. PLoS One. 2014; 9 (2): e87443. DOI: 10.1371/journal.pone.0087443.

15. Sims M.W., Tal-Singer R.M., Kierstein S. et al. Chronic obstructive pulmonary disease and inhaled steroids alter surfactant protein D (SP-D) levels: a cross-sectional study. Respir. Res. 2008; 9: 13. DOI: 10.1186/1465-9921-9-13.

16. Lebedeva E.S., Kuzubova N.A., Danilov L.N. et al. Experimental modelling of chronic obstructive pulmonary disease. Bull. Exp. Biol. Med. 2012; 152 (5): 659–663. DOI: 10.1007/s10517-012-1601-3.

17. Fedin A.N., Kuzubova N.A., Danilov L.N., Lebedeva E.S. [Dysfunction of airway nervous structures in rats inhaled with nitrogen dioxide]. Rossiyskiy fiziologicheskiy zhurnal im. I.M.Sechenova. 2007; 93 (9): 1071–1077 (in Russian).

18. Fedin A.N., Kuzubova N.A., Danilov L.N. et al. [Broncholytic effect of prednisolone in the rats inhaled with nitrogen dioxide]. Rossiyskiy fiziologicheskiy zhurnal im. I.M.Sechenova. 2010; 96 (3): 293–300 (in Russian).

19. Kuzubova N.A., Fedin A.N., Lebedeva E.S., Platonova I.S. [Effect of different therapy options on bronchial contraction in rats with modeled obstructive pulmonary disease]. Rossiyskiy fiziologicheskiy zhurnal im. I.M.Sechenova. 2014; 100 (9): 1049–1058 (in Russian).

20. Ueki S., Melo R.C.N., Ghiran I. et al. Eosinophil extracellular DNA trap cell death mediates lytic release of free secretion-competent eosinophil granules in humans. Blood. 2013; 121 (11): 2074–2083. DOI: 10.1182/blood-2012-05-432088.

21. Ueki S., Tokunaga T., Fujieda S.et al. Eosinophil Etosis and DNA traps: a new look at eosinophilic inflammation. Curr. Allergy Asthma Rep. 2016; 16 (8): 54. DOI: 10.1007/s11882016-0634-5.

22. Uribe Echevarría L., Leimgruber C., Garcia González J. et al. Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease? Int. J. COPD. 2017; 12: 885–896. DOI: 10.2147/COPD.S115969.

23. Snoeck-Stroband J.B., Lapperre T.S., Sterk P.J. et al. Prediction of long-term benefits of inhaled steroids by phenotypic markers in moderate-to-severe COPD: a randomized controlled trial. PLoS One. 2015; 10 (12): e0143793. DOI: 10.1371/journal.pone.0143793.

24. Russo P., Tomino C., Santoro A. et al. FKBP5 rs4713916: a potential genetic predictor of interindividual different response to inhaled corticosteroids in patients with chronic obstructive pulmonary disease in a real-life setting. Int. J. Mol. Sci. 2019; 20 (8): pii: Е2024. DOI: 10.3390/ijms20082024.

25. Cosío B.G., Jahn A., Iglesias A. et al. Haemophilus influenzae induces steroid-resistant inflammatory responses in COPD. BMC Pulm. Med. 2015; 15: 157. DOI: 10.1186/s12890-015-0155-3.

26. Ito K., Lim S., Caramori G. et al. A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc. Natl. Acad. Sci. USA. 2002; 99 (13): 8921–8926. DOI: 10. 1073/pnas.132556899.

27. Kobayashi Y., Wada H., Rossios C. et al. A novel macrolide/fluoroketolide, solithromycin (CEM-101), reverses corticosteroid insensitivity via phosphoinositide 3-kinase pathway inhibition. Br. J. Pharmacol. 2013; 169 (5): 10241034. DOI: 10.1111/bph.12187.

28. Pirina P., Foschino Barbaro M.P., Paleari D., Spanevello A. Small airway inflammation and extrafine inhaled corticosteroids plus long-acting beta2-agonists formulations in chronic obstructive pulmonary disease. Respir. Med. 2018; 143: 74–81. DOI: 10.1016/j.rmed.2018.08.013.

29. Leshchenko I.V., Kudelya L.M., Ignatova G.L. et al. [Resolution of the Board of Experts «Place of anti-inflammatory therapy in COPD in real clinical practice» dated April 8th , 2017, Novosibirsk]. Russkiy meditsinskiy zhurnal. 2017; 25 (18): 1322–1324 (in Russian).

30. De Backer J., Vos W., Vinchurkar S. et al. The effects of extrafine beclometasone/formoterol (BDP/F) on lung function, dyspnea, hyperinflation, and airway geometry in COPD patients: novel insight using functional respiratory imaging. J. Aerosol. Med. Pulm. Drug Deliv. 2015; 28 (2): 88–99. DOI: 10.1089/jamp.2013.1064.

31. Postma D.S., Roche N. Colice G. et al. Comparing the effectiveness of small-particle versus large-particle inhaled corticosteroid in COPD. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9 (1): 1163–1186. DOI: 10.2147/COPD.S68289.

32. Papi A., Vestbo J., Fabbri L. et al. Extrafine inhaled triple therapy versus dual bronchodilator therapy in chronic obstructive pulmonary disease (TRIBUTE): a double-blind, parallel group, randomised controlled trial. Lancet. 2018; 391 (10125): 1076–1084. DOI: 10.1016/S0140-6736(18)30206-X.


Review

For citations:


Titova O.N., Kuzubova N.A., Lebedeva E.S. The protective effect of beclomethasone dipropionate in the modeling of chronic obstructive pulmonary disease. PULMONOLOGIYA. 2020;30(1):61-68. (In Russ.) https://doi.org/10.18093/0869-0189-2020-30-1-61-68

Views: 1090


ISSN 0869-0189 (Print)
ISSN 2541-9617 (Online)