The influence of basic treatment with tiotropium bromide of patients with chronic obstructive pulmonary disease stage II on the morpho-functional state of bronchial mucosa and the level of type IV collagen in bronchoalveolar lavage fluid.
PDF

Keywords

chronic obstructive pulmonary disease
morphological rearrangement of the bronchial mucosa
tiotropium bromide

Abstract

The objective of the research was to evaluate the influence of basic treatment of patients with chronic obstructive pulmonary disease with tiotropium bromide on the processes of morphological rearrangement and local barrier defence mechanisms in the bronchial mucosa.          Stage II chronic obstructive pulmonary disease is associated with the damage to the bronchi with proliferation of the connective tissue in its proper plate, clear identification of the basal membrane alteration, the presence of fibroblasts, the activation of fibroblasts/myofibroblasts and mucous glands, which is accompanied by the significant increase of type ІV collagen levels by 6.19 times (p<0.05) in bronchoalveolar lavage fluid as compared to the control group indices.          The elimination of stage II chronic obstructive pulmonary disease exacerbation and the use of tiotropium bromide within a month was accompanied only by partial improvement of morpho-functional state in relation to both cells of bronchial epithelial lining and adjacent connective tissue of mucosal plate. The prolongation of tiotropium bromide administration from 2 to 6 months, provided positive dynamics of structural morphological changes of the bronchial mucosa (the restoration of the ciliary apparatus of epithelial cells, the normalization of the secretory function of goblet cells, the inactivation of fibroblasts, the initial degeneration of myofibroblasts), thus leading to complete absence of morphological signs of edema or epithelial cell dystrophy.          Conclusions. In patients with stage II chronic obstructive pulmonary disease, complete absence of morphological signs of edema or dystrophy of epithelial cells, against the background of collagenolysis in the connective tissue of the proper mucous plate of the bronchi and the highest possible decrease in the number of myofibroblasts, with near-complete levels of type IV collagen normalization in the bronchoalveolar lavage fluid, were identified only within a 6-month treatment with tiotropium bromide.
https://doi.org/10.21802/gmj.2018.4.1
PDF

References

On Approval and Implementation of Medical-Technological Documents on the Standardization of Medical Care in Chronic Obstructive Pulmonary Disease. The Order of the Ministry of Health of Ukraine of 27.07.2013, No 555

Ovcharenko SI, Galetskaite YaK. Evolyutsiya globalnoy informatsiyi o khronicheskoy obstruktivnoy bolezni legkikh i novyy podkhod k protivovospalitelnoy terapiyi. Lechashshiy vrach. 2014;1: Available from: http: //www.lvrach.ru/2014/01/15435880/.

Pertseva TO, Gorovenko NG, Ostrovskyy MM. Sovremennyye vozmozhnosti lecheniya khronicheskikh obstruktivnykh zabolevaniy legkikh: v fokuse fiksirovannaya kombinatsiya bronkholitikov dlitelnogo deystviya. Zdorovia Ukraiiny. 2017;4(41):21-22.

Serov VV, Shekhter AB. Soyedinitelnaya tkan (funktsionalnaya morfologiya i obshchaya patologiya). Moscow: Medicine; c1981. 312 p.

Feshchenko YuI, Yashyna LO, Dziublyk OYa et al. Khronichne obstruktyvne zakhvoriuvannia lehen: etiolohiia, patohenez, klasyfikatsiia, diahnostyka, terapiia (proekt natsionalnoii uhody). Ukraiinskyi pulmonolohichnyi zhurnal. 2013;3:7-12.

Aaron SD, Tan WC, Bourbeau J et al. Diagnostic instability and reversals of chronic obstructive pulmonary disease diagnosis in individuals with mild to moderate airflow obstruction. Am J Respir Crit Care Med. 2017;196(3):306-314. DOI: https://doi.org/10.1164/rccm.201612-2531OC

Alagha K, Palot A, Sofalvi T et al. Long-acting muscarinic receptor antagonists for the treatment of chronic airway diseases. Ther Adv Chronic Dis. 2014;5(2):85-98. doi: [10.1177/2040622313518227] DOI: https://doi.org/10.1177/2040622313518227 [PMid:24587893 PMCid:PMC3926345]

Barnes PJ. Immunology of asthma and chronic obstructive pulmonary disease. Nat Rev Immunol. 2008;8(3):183-192. DOI: https://doi.org/10.1038/nri2254

Barnes PJ. Kinases as novel therapeutic targets in asthma and chronic obstructive pulmonary disease. Pharmacol Rev. 2016;68(3):788-815. DOI: https://doi.org/10.1124/pr.116.012518

Decramer MD. Clinical Trial Design Considerations in Assessing Long-Term Functional Impacts of Tiotropium in COPD: the UPLIFT Trial. Eur Respir J. 2008;31:742-750. [PMid:18256071]

Gizycki MJ, Adelroth E, Rogers AV et al. Myofibroblast involvement in the allergen-induced late response in mild atopic asthma. Am J Respir Cell Mol Biol. 1997;16:664-673. DOI: https://doi.org/10.1165/ajrcmb.16.6.9191468 [PMid:9191468]

Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD, 2017. Available from: http://goldcopd.org/

Haag S, Matthiesen S, Juergens UR et al. Muscarinic receptors mediate stimulation of collagen synthesis in human lung fibroblasts. Eur Respir J. 2008;32:555-562. DOI: https://doi.org/10.1183/09031936.00129307

Hirota N, Martin JG. Mechanisms of airway remodeling. Chest. 2013;144(3):1026-1032. DOI: https://doi.org/10.1378/chest.12-3073

Hollins F, Sutcliffe A, Gomez E et al. Airway smooth muscle NOX4 is upregulated and modulates ROS generation in COPD. Respir Res. 2016;17(1):84. DOI: https://doi.org/10.1186/s12931-016-0403-y

Hong W, Peng G, Hao B et al. Nicotine-induced airway smooth muscle cell proliferation involves TRPC6-dependent calcium influx via alpha7 nAChR. Cell Physiol Biochem. 2017;43(3):986-1002. DOI: https://doi.org/10.1159/000481651

Klingberg F, Hinz B, White ES. The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol. 2013;229(2):298-309. DOI: https://doi.org/10.1002/path.4104

Matera MG, Cazzola M. Muscarinic Receptor Antagonists. Handb Exp Pharmacol. 2017;237:41-62. DOI: https://doi.org/10.1007/164_2016_68

Matthiesen S, Bahulayan A, Kempkens S et al. Muscarinic receptors mediate stimulation of human lung fibroblast proliferation. Am J Respir Cell Mol Biol. 2006;35(6):621-627. DOI: https://doi.org/10.1165/rcmb.2005-0343RC

Miravitlles M, Urrutia G, Mathioudakis AG et al. Efficacy and safety of tiotropium and olodaterol in COPD: a systematic review and meta-analysis. Respir Res. 2017;18(1):196. DOI: https://doi.org/10.1186/s12931-017-0683-x

Moulton BC, Fryer AD. Muscarinic receptor antagonists, from folklore to pharmacology; Finding drugs that actually work in asthma and COPD. Br J Pharmacol. 2011;163(1):44-52. DOI: https://doi.org/10.1111/j.1476-5381.2010.01190.x

Pera T, Zuidhof A, Valadas J et al. Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. Eur Respir J. 2011;38(4):789-96. DOI: https://doi.org/10.1183/09031936.00146610

Wiegman CH, Michaeloudes C, Haji G et al. Oxidative stress-induced mitochondrial dysfunction drives inflammation and airway smooth muscle remodeling in patients with chronic obstructive pulmonary disease. J Allergy Clin Immunol. 2015;136(3):769-780. DOI: https://doi.org/10.1016/j.jaci.2015.01.046

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

Downloads

Download data is not yet available.