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Objective. To evaluate the ability of a combination of budesonide and azithromycin to influence the migration of blood monocytes and lymphocytes in patients with chronic obstructive pulmonary disease (COPD).Materials and methods. Peripheral blood mononuclear cells from patients with COPD (n=8) were incubated with glucocorticoid budesonide (10 nM), macrolide antibiotic azithromycin (10 µg/mL), or their combination, and then transferred to chemotaxis chambers containing chemokines RANTES (CCL5, 10 nM) or IP-10 (CXCL10, 10 nM). Cells migrated to the lower compartment of the chamber were collected, stained with monoclonal antibodies to CD3, CD14, CD19, CD45 and counted on a flow cytometer.Results. Azithromycin alone and in combination with budesonide inhibited the migration of blood T-lymphocytes and B-cells and enhanced the migration of blood monocytes to RANTES and IP-10. The combination of azithromycin and budesonide had a more suppressive effect on the chemotaxis of blood T- and B-lymphocytes to RANTES and IP-10 than budesonide alone. The combination of azithromycin and budesonide had an effect similar to azithromycin alone on the migration of blood T- and B-lymphocytes, as well as monocytes in patients with COPD.Conclusion. The results of the study demonstrate the ability of azithromycin alone to modulate the chemotaxis of peripheral blood monocytes and lymphocytes in patients with COPD and the lack of advantages of its combination with budesonide.

Currently, no drugs have been identified that could slow progression of chronic obstructive pulmonary disease (COPD), or have a significant impact on patient mortality. Therefore, research continues aimed at studying the mechanisms of COPD development and searching for drugs that affect its molecular pathogenesis. The aim of our work was to determine the ability of azithromycin combined with corticosteroids to affect the migration of peripheral blood NK cells from the COPD patients. In the present study, we have measured expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, CXCR6 on the surface of peripheral blood NK cells (CD3- CD56+) by means of flow cytometry in 54 smoking patients with COPD, 21 healthy smokers, and 20 healthy non-smokers. Moreover, the effect of azithromycin (10 µg/mL) and budesonide (10 nM) on the migration of NK cells from COPD patients (n = 8) towards CCL5 (10 nM) and CXCL10 (10 nM) was determined. We found that the percentage of NK cells expressing CXCR3 and CCR5 chemokine receptors was increased in smoking patients with COPD compared with healthy smokers and healthy non-smokers. However, the proportion of these NK cell subsets did not differ between healthy smokers and healthy non-smokers. There were no significant differences in the percentage of NK cells expressing CXCR4, CXCR6, CCR6, CCR7 chemokine receptors between the three groups of subjects. Addition of budesonide to the cell suspensions decreased the migration of blood NK cells towards CCL5 and CXCL10. Azithromycin was also shown to suppress the migration of blood NK cells towards these chemokines. The combination of azithromycin and budesonide was more potent at inhibiting NK cell chemotaxis towards CCL5 and CXCL10 than any of these drugs added alone. Our results demonstrate a change in the chemokine receptor profile of NK cells in COPD patients and indicate the advantages of the combined use of corticosteroids and azithromycin for COPD treatment.

The frequency of the occurrence of polymorphic variants rs2234693 (PvuII, T→C) of the ESR1 gene and rs731236 (TaqI, T→C) of the VDR gene was investigated in 95 patients with chronic obstructive pulmonary disease (COPD) and in 95 healthy people. A statistically significant increase (p = 0.006) in the frequency of the occurrence of the heterozygous TC genotype rs2234693 in the intron 1 of the ESR1 gene was found in the group of patients with COPD compared to the group of conditionally healthy people. The heterozygous TC genotype rs2234693 is associated with chronic obstructive pulmonary disease (OR = 5.21 CI = 1.43–19.0) was established. As for the rs731236 polymorphism of the VDR gene, there were no significant differences in the frequency of occurrence of one of the genotypes in patients with COPD and healthy people.

To date, there are no drugs that can prevent progressive destruction of lung tissue and small airway fibrosis in patients with chronic obstructive pulmonary disease (COPD). Therefore, molecular mechanisms of this disease are being studied. The aim of this study was to determine the chemokine receptor expression pattern of B-lymphocytes from peripheral blood and airways of patients with COPD. Peripheral blood was collected from 51 smokers with COPD, 21 healthy smokers, and 20 healthy non-smokers. Seven smokers with COPD and 7 healthy smokers were recruited to undergo bronchoscopy with bronchoalveolar lavage (BAL). The expression of chemokine receptors CCR5, CCR6, CCR7, CXCR3, CXCR4, and CXCR5 on the surface of blood and BAL B-lymphocytes was determined by flow cytometry. It was found that the percentage of blood B-lymphocytes expressing chemokine receptors CCR5 and CXCR3 was higher in smokers with COPD compared with healthy smokers and healthy non-smokers. The percentage of CD27⁺ B-cells expressing CCR5 and CXCR3 receptors exceeded the proportion of CD27⁻ B-lymphocytes expressing these receptors in peripheral blood of patients with COPD and healthy controls. In smoking patients with COPD, the percentage of BAL B-cells expressing receptors CCR5 and CXCR3 was also increased compared with healthy smokers. There were no differences in the percentage of B-lymphocytes expressing receptors CXCR4, CXCR5, CCR6, and CCR7 in both peripheral blood and BAL between smokers with COPD and healthy smokers. A greater percentage of CD27⁻ B-lymphocytes than CD27⁺ B-cells expressed receptors CXCR4, CXCR5, CCR6, and CCR7 in the peripheral blood of smokers with COPD and healthy controls. The results of this study indicate a modification in the chemokine receptor profile of B-lymphocytes in COPD.K nastoiashchemu vremeni ne sushchestvuet lekarstvennykh sredstv, sposobnykh predotvratit' progressiruiushchuiu destruktsiiu legochnoĭ tkani i fibroz nizhnikh dykhatel'nykh puteĭ u patsientov s khronicheskoĭ obstruktivnoĭ bolezn'iu legkikh (KhOBL). Poétomu prodolzhaiutsia issledovaniia mekhanizmov razvitiia étogo zabolevaniia. Tsel'iu nastoiashcheĭ raboty bylo opredelenie zakonomernosteĭ kolichestvennogo izmeneniia subpopuliatsiĭ B-limfotsitov, soderzhashchikh khemokinovye retseptory, v krovi i dykhatel'nykh putiakh patsientov s KhOBL. Perifericheskuiu krov' zabirali u 51 kuriashchego patsienta s KhOBL, 21 zdorovogo kuril'shchika i 20 zdorovykh nekuriashchikh lits. Bronkhoskopiiu s polucheniem bronkhoal'veoliarnoĭ lavazhnoĭ zhidkosti (BALZh) provodili 7 kuriashchim patsientam s KhOBL i 7 kuriashchim zdorovym litsam. Ékspressiiu khemokinovykh retseptorov CCR5, CCR6, CCR7, CXCR3, CXCR4 i CXCR5 na poverkhnosti V-limfotsitov krovi i BALZh opredeliali metodom protochnoĭ tsitometrii. Ustanovleno, chto protsentnoe soderzhanie V-limfotsitov krovi, ékspressiruiushchikh khemokinovye retseptory CCR5 i CXCR3, vyshe u kuriashchikh patsientov s KhOBL po sravneniiu so zdorovymi kuriashchimi i nekuriashchimi liud'mi. V perifericheskoĭ krovi patsientov s KhOBL i zdorovykh liudeĭ otnositel'noe kolichestvo CD27⁺ B-kletok, soderzhashchikh retseptory CCR5 i CXCR3, prevyshaet doliu CD27⁻ B-limfotsitov, ékspressiruiushchikh éti retseptory. U kuriashchikh patsientov s KhOBL protsentnoe soderzhanie B-kletok, imeiushchikh retseptory CCR5 i CXCR3, takzhe povysheno v BALZh po sravneniiu so zdorovymi kuril'shchikami. Ne vyiavleny razlichiia v protsentnom soderzhanii B-limfotsitov, ékspressiruiushchikh retseptory CXCR4, CXCR5, CCR6 i CCR7, kak v perifericheskoĭ krovi, tak i v BALZh, mezhdu kuriashchimi patsientami s KhOBL i kuriashchimi zdorovymi liud'mi. Protsentnoe soderzhanie CD27⁻ B-limfotsitov, nesushchikh na svoeĭ poverkhnosti retseptory CXCR4, CXCR5, CCR6 i CCR7, v perifericheskoĭ krovi patsientov s KhOBL i zdorovykh liudeĭ bylo vyshe, chem CD27⁺ B-kletok. Rezul'taty nastoiashchego issledovaniia svidetel'stvuiut ob izmenenii profilia khemokinovykh retseptorov B-limfotsitov pri KhOBL.

Introduction: An antidepressant nortriptyline potentiates glucocorticoid (GC) action with synergistic suppression of inflammatory mediator release, but the precise molecular mechanism is unknown. Materials and methods: Peripheral blood cells from patients with chronic obstructive pulmonary disease (COPD) (n = 21) were incubated with nortriptyline (1 μM or 10 μM), budesonide (10 nM), or their combinations, followed by stimulation with phorbol myristate acetate (PMA) and ionomycin. Cytokine production, glucocorticoid receptor β (GRβ), histone deacetylase 2 (HDAC2) and histone H4 acetylation of K8 (HAT) expression, p65 NF-kB and p38 mi­togen-activated protein kinase (p38 MAPK) phosphorylation in NK (CD3-CD56+) and NKT-like (CD3+CD56+) cells were analyzed by flow cytometry. Results: We observed that nortriptyline (10 μM) significantly attenuated the effects of PMA/ionomycin on the synthe­sis of interferon γ (IFNγ), interleukin 4 (IL-4), and IL-8, expression of GRβ and HAT, as well as p65 NF-kB and p38 MAPK phosphorylation in NK and NKT-like cells, whereas nortriptyline (1 μM) only inhibited IL-4 production by NK and NKT-like cells. Discussion: The combination of nortriptyline (10 μM) and budesonide decreased IFNγ, tumor necrosis factor α, IL-4, IL-8, and GRβ expression, as well as phosphorylated p38 MAPK and p65 NF-κB levels by NK and NKT-like cells above that of budesonide alone. Furthermore, the same association of drugs enhanced HDAC2 expression in NK and NKT-like cells. Conclusion: Collectively, our results show that nortriptyline might enhance GC function through modulation of HAT, HDAC2, GRβ, phospho-p38 MAPK expression. These data provide a strong rationale for combining nortriptyline with budesonide to treat COPD.

To estimate the significance of measuring the concentrations of cytokines and immunoglobulins and the relative counts of lymphocyte subpopulations in peripheral blood, as well as clinical parameters in patients with chronic obstructive pulmonary disease (COPD) in order to assess the risk of exacerbations.Thirty-seven patients with COPD were examined. A study group consisted of 31 patients. Patients with rare exacerbations were assigned to those who had no or one case; patients with frequent exacerbations were those who had two or more cases a year after examination. A prognostic model was created using the binary logistic regression analysis.A significant statistical model was developed as a regression equation involving 4 indicators (vascular endothelial growth factor, C-reactive protein, CAT scores, and number of exacerbations in the previous year). This mathematical model can predict frequent exacerbations in next year with a sensitivity of 94.1% and a specificity of 80%.The mathematical model created to estimate the risk of frequent exacerbations may be used to elaborate adequate individual treatment regimens for both smoking and non-smoking patients with COPD.Цель исследования. Определить значение измерения концентрации цитокинов, иммуноглобулинов и относительного количества субпопуляций лимфоцитов в периферической крови, а также клинических показателей у пациентов с хронической обструктивной болезнью легких (ХОБЛ) для оценки риска развития обострений. Материалы и методы. Обследовали 37 больных ХОБЛ. Основную группу составил 31 больной. К пациентам с редкими обострениями относили лиц с 0-1 обострением, частыми считали 2 обострения и более через 1 год после обследования. Построение прогностической модели осуществляли с помощью метода бинарной логистической регрессии. Результаты. Разработана достоверная статистическая модель в виде регрессионного уравнения, включающая 4 показателя (фактор роста эндотелия сосудов, С-реактивный белок, результат CAT-теста, число обострений в предыдущем году). Данная математическая модель позволяет прогнозировать с чувствительностью 94,1% и специфичностью 80% наличие у пациентов частых обострений в следующем году. Заключение. Созданная математическая модель для расчета вероятности частых обострений может использоваться при выработке адекватных индивидуальных схем лечения как для курящих, так и некурящих пациентов с ХОБЛ.