Blagoveschensk, Blagoveshchensk, Russian Federation
Blagoveschensk, Blagoveshchensk, Russian Federation
Blagoveschensk, Blagoveshchensk, Russian Federation
Russian Federation
The character of changes of inflammatory-cellular pattern of bronchial secretion in patients with asthma in association with cold airway hyperresponsiveness (CAHR) under the influence of standard therapy has been studied little. The aim of the present work is to study dynamics of cellular profile, neutrophilic component of bronchial inflammation under the combination therapy of asthmatics with CAHR. 12 asthma patients with CAHR were studied upon the number of cells of the induced sputum (IS), peroxidase, cytolytic and destructive activity of eosinophils and neutrophils in the sputum, lung function and asthma control with the help of questionnaire Asthma Control Test (АСТ) before and after the therapy with the combination of budesonide/formoterol. Before the therapy the patients had a low level of asthma control (14.4±1.2 points of ACT), FEV1 was 87.4±3.3% from predicted values; in IS neutrophils prevailed (26.4±1.7%) over eosinophils (18.5±2.6%); the level of myeloperoxidase (mean cytochemical coefficient) was 65.9±5.4 pixels. After 48 weeks of the observation only in 58% of patients the criteria of good control of asthma and the improvement of lung function were achieved. In IS there was a decrease of eosinophils (11.4±3.2%; p=0.045); the intensiveness of eosinophils and neutrophils cytolysis dropped; intracellular concentration of myeloperoxidase grew (98.2±14.1 pixels; p=0.0637); destructive changes in granulocytes were registered but the number of neutrophils remained high (34.0±8.2%, р=0.34), which was considered as the factor of stable initiation of inflammation and oxidative stress. Thus, the use of anti-inflammatory treatment regime lasting 48 weeks with combination of budesonide/formoterol oriented to achieve clinical criteria of asthma control in patients with CAHR does not allow to achieve correction of the level of neutrophilic inflammatory component. Quantitative index of neutrophils in IS in these patients has prognostic value for the possible loss of achieved asthma control.
inflammation, asthma, cold airway hyperresponsiveness, treatment, control, neutrophilic component of bronchial inflammation, budesonide/formoterol.
1. Ivanchuk I.I., Sazonov A.E., Petrovskiy F.I., Leshcheva I.S., Kop´eva A.P., Petrova I.V. The role of IL-5 in the mechanisms of apoptosis of peripheral blood eosinophils of patients with bronchial asthma. Byulleten´ Sibirskoy meditsiny 2003; 2:38-43(in Russian).
2. Ivanchuk L.I., Ogorodova L.M., Sazonov A.E., Lesheva I.S., Koljeva A.P., Petrova I.V., Malyshev I.Yu. The influence of recombinant interleukin-5 on eosinophil apoptosis in patients with bronchial asthma. Meditsinskaya immunologiya 2004; 6 (1-2):117-120 (in Russian).
3. Korotina O.L., Generalov I.I. Neutrophil extracellular traps: mechanisms of formation, functions. Immunopatologiya, allergologiya, infektologiya 2012; 4:23-32 (in Russian).
4. Mal´tseva T.A., Pirogov A.B. Markers of inflammation of the respiratory tract in patients with bronchial asthma with cold bronchial hyperresponsiveness. In: Scientific-practical conference “The questions of the maintenance and development of the health of the population of the North and Siberia”. Krasnoyarsk; 2013:50-51 (in Russian).
5. Matveeva L.А. Local protection of the respiratory tract in children. Tomsk; 1993 (in Russian).
6. Mayansky A.N. NADPH-oxidase of neutrophils: activation and regulation. Tsitokiny i vospalenie 2007; 6(3):3-13 (in Russian).
7. Nevzorova V.А., Pazych S.А., Barkhatova D.А., Kudryavtseva V.А. The role of process cell death in course of inflammation under bronchial asthma. Pacific Medical Journal 2006; (2):54−58 (in Russian).
8. Panasenko O.M., Sergienko V.I. Halogenizing stress and its biomarkers. Annals of the Russian Academy of Medical Science 2010; (1):27-39 (in Russian).
9. Panasenko O.M., Gorudko I.V., Sokolov A.V. Hypochlorous acid as a precursor of free radicals in living systems. Uspekhi biologicheskoy khimii 2013; 53:195-244 (in Russian).
10. Pirogov А.B., Zinov’ev S.V., Perelman J.М., Semirech Yu.O., Semenova G.V., Kolosov A.V. Myeloperoxidase activity of neutrophils and eosinophils in induced sputum of patients with bronchial asthma with cold bronchial hyperresponsiveness. Bûlleten´ fiziologii i patologii dyhaniâ 2014; (53):50-56 (in Russian).
11. Pirogov А.B., Prikhodko A.G., Perelman J.M., Zinov’ev S.V., Afanas´eva E.Yu., Kolosov V.P. Inflammatory pattern of bronchial mucosa in patients with bronchial asthma and airway hyperresponsiveness to hyposmotic stimulus. Byulleten´ eksperimental´noy biologii i meditsiny 2016; 161(4):542-546 (in Russian).
12. Prikhodko A.G., Perelman J.M., Kolosov V.P. Airway hyperresponsiveness. Vladivostok: Dal´nauka; 2011 (in Russian).
13. Prikhodko A.G., Perelman J.M., Pirogov A.B., Borodin E.A., Ushakova E.V., Ul´yanychev N.V., Kolosov A.V. Phenotypic differences and peculiarities of inflammation in asthmatics with isolated and combined airway hyperresponsiveness to cold air and distilled water. Bûlleten´ fiziologii i patologii dyhaniâ 2014; (54):8-16 (in Russian).
14. Prikhodko A.G., Perelman J.M., Kolosov V.P., Ul´yanychev N.V., Naryshkina S.V., Afanas´eva E.Yu. Features of bronchial asthma clinical course in patients with isolated and combined airway hyperresponsiveness to cold and hyposmotic stimuli. Bûlleten´ fiziologii i patologii dyhaniâ 2014; (53):36-41 (in Russian).
15. Hayhoe F.G.H., Quaglino D. Hematological cytochemistry. Moscow: Meditsina; 1983 (in Russian).
16. Bakakos P., Schleich F., Alchanatis M., Louis R. Induced sputum in asthma: from bench to bedside. Curr. Med. Chem. 2011; 18(10):1415-1422.
17. Bedenice D., Mazan M.R., Hoffman A.M. Association between cough and cytology of bronchoalveolar lavage fluid and pulmonary function in horses diagnosed with inflammatory airway disease. J. Vet. Intern. Med. 2008; 22(4):1022-1028.
18. Brinkmann V., Zychlinsky A. Beneficial suicide: why neutrophils die to make NETs. Nat. Rev. Microbiol. 2007; 5(8): 577-582.
19. Davis M.S., Williams C.C., Meinkoth J.H., Malayer J.R., Royer C.M., Williamson K.K., McKenzie E.C. Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air. Am. J. Vet. Res. 2007; 68(2):185-189.
20. Dewas C., Dang P.M., Gougerot-Pocidalo M.A., El-Benna J. TNF-α induces phosphorylation of p47(phox) in human neutrophils: partial phosphorylation of p47phox is a common event of priming of human neutrophils by TNF-α and granulocyte-macrophage colony-stimulating factor. J. Immunol. 2003; 171(8):4392-4398.
21. Elbim C., Guichard C., Dang P.M., Fay M., Pedruzzi E., Demur H., Pouzet C., El Benna J., Gougerot-Pocidalo M.A. Interleukin-18 primes the oxidative burst of neutrophils in response to formyl-peptides: role of cytochrome b558 translocation and N-formyl peptide receptor endocytosis. Clin. Diagn. Lab. Immunol. 2005; 12(3):436-446.
22. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (Updated 2016). Available at: www.ginasthma.com.
23. Klebanoff S.J. Myeloperoxidase: friend and foe. J. Leukoс. Biol. 2005; 77(5):598-625.
24. Kolosov V.P., Pirogov A.B., Perelman J.M., Naryshkina S.V., Maltseva T.A. Achievement of asthma control in patients with cold airway hyperresponsiveness at different variants of basic therapy. Eur. Respir. J. 2013; 42(57):400s.
25. Maltseva T.A., Pirogov A.B., Kolosov V.P., Naryshkina S.V., Ushakova E.V. Cell composition of induced sputum in patients with uncontrolled asthma and its participation in the formation of cold hyperresponsiveness. Eur. Respir. J. 2013; 42(57):401s.
26. Neeli I., Khan S.N., Radic M. Histone deimination as a response to inflammatory stimuli in neutrophils. J. Immunol. 2008; 180(3):1895-1902.
27. Puthothu B., Krueger M., Heinze J., Forster J., Heinzmann A. Impact of IL8 and IL8-receptor alpha polymorphisms on the genetics of bronchial asthma and severe RSV infections. Clin. Mol. Allergy 2006; 4:2s.
28. Sheppard F.R., Kelher M.R., Moore E.E., McLaughlin N.J., Banerjee A., Silliman C.C. Structural organization of the neutrophil NADPH oxidase: phosphorylation and translocation during priming and activation. J. Leukoc. Biol. 2005; 78:1025-1042.
29. Steinberg B.E., Grinstein S. Unconventional roles of the NADPH oxidase: signaling, ion hоmeostasis and cell death. Sci. STKE 2007; 379:pe11.
30. Wood L.G., Baines K.I., Fu J., Scott H.A., Gibson P.G. The neutrophilic inflammatory phenotype is associated with systemic inflammation in asthma. Chest 2012; 142(1):86-93.