A decrease of nonspecific body resistance, an imbalance of local and systemic immunity and a free-radical oxidation abnormality substantially contribute to the pathogenesis of community-acquired pneumonia (CAP).Purpose: To study the efficiency of including immunomodulators into the comprehensive treatment of nonsevere community-acquired pneumonia and assess the long-term effects of the treatment conducted.Patients (n = 55) with non-severe CAP (41 (31-48) years old, with CRB-65 score of 0.15 (0-1)) are included in the study. Group 1 (control) received only standard CAP therapy; the other two groups received immunomodulators concurrently with the standard therapy: bacterial lysate (BL) for group 2 and azoximer bromide (AzB) for group 3. TNFα and IL-6 concentration was determined on the day of visit, on day 13 and day 60 of follow-up. During 2 years, the incidence of low respiratory tract infections (LRTI) was studied in the same patients with CAP in past (n = 55). All patients (n = 55) had clinical signs of non-severe community-acquired pneumonia. The overall duration of all symptoms was lower in immunomodulators groups as compared to the control group: 12 (11-13) days in BL group (p < 0.001) and 12 (11-12) days in AzB group (p < 0.001) with no statistically significant difference between intervention groups (p = 0.36). During treatment, TNFα and IL-6 concentration decreased on day 13 and day 60 in all patients; in patients who received immunomodulators, TNFα and IL-6 were reliably lower as compared to the control. Changes of TNFα and IL-6 concentration in the groups on day 60 of the study as compared to the baseline showed a decrease in BL group by 85 (-89 – -82) % and 86 (-90 – -85) % (p < 0.001; p = 0.001 and control); in AzB group by 82 (-86 – -80) % and 86 (-88 – -84) % (p = 0.002; p = 0.007 and control). Intensity of IL-6 concentration decrease on day 60 in BL and AzB groups did not differ (p = 0.72). Gender- and age-adjusted odds ratio for the development of low respiratory tract diseases (during 2 years after CAP) in AzB group was 0.15 (0.02-0.93) (p = 0.04) suggesting its protective effect. Inclusion of immunomodulators in basic treatment of non-severe community-acquired pneumonia reduces duration of symptoms and is associated with improvement of the proinflammatory cytokine profile. In 2 years of follow-up, long-term effects of the immunomodulatory therapy showed statistically significant lower incidence of low respiratory tract infections in AzB group only.

Community-acquired pneumonia is one of the most common acute infectious diseases, especially in organized groups. Community-acquired pneumonia in military personnel is a serious problem of the medical service and is diagnosed 2–3 times more often than among civilians. The purpose of the study. To study the clinical features of the action of “Immunovac-VP-4 ®” in the complex treatment of community-acquired pneumonia in new recruits. Materials and methods. The study group included 88 conscripted military personnel from among the new recruits who were hospitalized with a diagnosis of mild community-acquired pneumonia. The main group of the study included 35 patients receiving basic antibacterial therapy in combination with the therapeutic vaccine “Immunovak-VP-4 ®”. The control group included 53 patients who received only standard basic antibacterial therapy. Results. In the main study group, the frequency of repeated respiratory infections in all nosologies was lower than in the control group, statistically significant differences were noted in relation to pneumonia and acute rhinosinusitis. A decrease in the level of IL-1β in blood serum was revealed after 15 days (p = 0.05) and 6 months after discharge from the hospital (p = 0.002) in the main group compared with the control group. After 15 days, in the group of patients receiving “Immunovak-VP-4 ®”, there was a decrease in IL-6 levels relative to the baseline (p = 0.04) and it became lower than the control group (p = 0.04). Conclusion. The use of the “Immunovak-VP-4 ®” vaccine can be considered as a way to improve the treatment of community-acquired pneumonia: it can be a drug for treatment, prevention of complications, and an instrument in immunorehabilitation. The use of “Immunovak-VP-4 ®” in the complex treatment of community-acquired pneumonia of mild course is accompanied by a decrease in the activity of systemic inflammation: a decrease in serum levels of IL-1β, IL-6.

Создание руководства поддержано Советом по терапевтическим наукам отделения клинической медицины Российской академии наук.

The initial efforts to describe the inflammatory mechanisms associated with SARS-CoV-2 have revealed upregulation of circulating proinflammatory cytokines as well as activation of innate immune cells.The aim of the study was to investigate the phagocytic activity of leukocytes in hospitalized patients with COVID-19 (COronaVIrus Disease 2019).Methods. The phagocytic activity of leukocytes was studied in admitted patients with COVID-associated lung disease (n = 105). The mean age of the studied patients was 43.5 (37; 51) years; 69 for men, and 36 for women; the mean duration of the disease before hospitalization was 6 (4; 8) days. Using cluster analysis, two groups of patients (clusters) were formed according to the severity of COVID-19: Group 1 with the moderate course (n = 34) and Group 2 with the mild course (n = 71). Flow cytofluorimetry with determination of neutrophil (NI) and monocyte index (MI) was used to determine the phagocytic activity of neutrophils and monocytes in the peripheral blood.Results. The median NI in the studied patients was 97.9% (96.3; 99); the mean median MI was 91.2% (84.6; 95). The correlation analysis revealed statistically significant direct correlation of MI with SpO2 level (r = 0.21; 95% CI: 0.005 – 0.39; p = 0.04); inverse correlation of MI with CRP level (r = –0.31; 95% CI: –0.11 to –0.48; p = 0.003) and degree of lung damage by CT (r = –0.2; 95% CI: –0.11 to –0.48); p = 0.05). MI in the group with moderate course was statistically significantly lower than in the group with mild course of COVID-19 (86.7 (81.4; 91.7) and 92.6 (86.5; 95.4), p = 0.01). The blood MI of the initially more severe patients statistically significantly increased.Conclusion. Complicated forms of SARS-CoV-2 infection lead to a decrease in phagocytic activity of the monocytic-macrophage link of innate immunity. The degree of decrease in monocyte phagocytic activity is directly related to the severity of COVID-19, and the MI is comparable in the patients with severe and mild course after 30 days of treatment.

The mucosal immunity performs an important function in prevention of respiratory infections including COVID-19. The search for approaches to activate the synthesis of post-infectious antibodies by correcting the factors of innate and adaptive immunity at mucous membranes of respiratory tract in patients with infection caused by the new coronavirus may be relevant for the treatment of patients with COVID-19. The aim of our study was to assess the concentrations of sIgA in the upper respiratory tract in patients with a confirmed diagnosis of Coronavirus infection caused by the COVID-19, and to evaluate the effect of an immunostimulating drug of bacterial origin upon the sIgA secretion. The patients were divided into two groups: group 1 (n = 45), received basic therapy; group 2 (n = 33), in addition to basic therapy, received the bacterial vaccine Immunovac-VP-4 according to a combined scheme. The biomaterial sampling was carried out by scraping of epithelial cells from the nasal mucosa, pharyngeal scraping and salivary gland secretion on days 1, 14 and 30 of the study. sIgA levels in all biological fluids were studied using ELISA technique (JSC Vector-Best, Russia). 14 days after the start of observation, the dynamics of sIgA levels in nasal scrapings in group 1showed a significant decrease relative to the baseline values (p = 0.02), whereas the level of sIgA remained unchanged during the specified period (p = 0.07) in the group of patients receiving, along with basic therapy, additional Immunovac-VP-4 treatment. The dynamics of sIgA level in pharyngeal scrapings in the group of patients receiving only basic therapy did not change throughout the study period. Menwhile, the group of patients receiving basic therapy supplemented with Immunovac-VP-4 showed a significant increase in sIgA levels by the 30th day of follow-up over the baseline values (p = 0.02). The level of sIgA in salivary gland secretions did not differ significantly between the study groups during the entire follow-up period. The results of our study showed that, in order to assess the state of mucosal immunity in patients with COVID-19, one may recommend determination of sIgA in nasal secretions. The Immunovac-VP-4 prescribed in complex therapy is accompanied by an increase in the sIgA levels at the mucous surfaces of the respiratory tract.

Background. After the first wave of the new SARS-CoV-2 coronavirus infection, the researchers focused on identifying potential short-and long-term complications of COVID-19, especially in high-risk patients, after prolonged hospitalization and intensive care. Objective. To study the outcomes, adverse effects of severe COVID-19 and their predictors 90 days after hospital discharge in elderly patients with asthma. Material and methods. The study included elderly patients (101 subjects, 42 males and 59 females;median age 74 (67;79) years) with asthma, discharged from the hospital after treatment of severe COVID-19. They were followed up for 90 days after discharge. In the hospital, COVID-19 was confirmed by laboratory tests (polymerase chain reaction method) and/or clinically and radiologically. All patients had a documented history of asthma according to GINA 2020 criteria. Results and discussion. During the 90-day post-hospital follow-up, 86 (85%) patients survived, and 15 (15%) died after discharge. Deaths were reported within 1 to 4 weeks after discharge: 6 subjects died during re-hospitalization, 6 at home, and 3 in a rehabilitation center. The multivariate regression analysis model, adjusted for all statistically significant indicators, and the ROC analysis showed the most significant predictors of 90-day post-hospital mortality and their threshold values. They include the Charlson comorbidity index >=4 points, lung damage according to computed tomography >=30%, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The analysis showed that 90-day post-hospital mortality depends on combinations of identified risk factors;a combination of two, three, and especially four risk factors statistically significantly is associated with patients' lower average survival time. Conclusion. The key risk factors for 90-day post-hospital mortality in elderly patients with asthma after severe COVID-19 include the Charlson comorbidity index, lung damage >=30% according to computed tomography, the absolute number of eosinophils <=100 cells/muL, and concomitant diabetes mellitus. The 90-day post-hospital survival rate is correlated with the number of risk factors identified in patients. The effect of asthma severity on 90-day post-hospital mortality in elderly patients was not observed.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

The objective : to study the effect of immunomodulators on markers of the acute inflammation phase in patients with mild community-acquired pneumonia (CAP). Subjects and methods . Patients (n = 64) with mild CAP (39.62 ± 9.82 years, CRB – 650.15 ± 0.04 scores) were enrolled in the study. The patients were divided into 2 groups: Group 1 (control) received only standard CAP therapy; in the other two groups, immunomodulators were prescribed simultaneously with standard therapy: in Group 2 – bacterial lysate (BL), in Group 3 – azoximer bromide (AB). In the patients, the blood levels of IL-6, TNF-α, C-reactive protein (CRP), lactoferrin were tested before treatment (day 1), and on days 13 and 60 of observation. Results . The initial levels of TNF-α, IL-6, CRP and lactoferrin in the patients were statistically significantly higher above normal ones. A significant decrease in the levels of TNF-α, IL-6, CRP was found in all patients on the 13th and 60th days of observation compared to the 1st day, the maximum reduction was observed in the patients receiving immunomodulators. The biggest decrease in the level of lactoferrin on the 60th day of observation was noted in the group of patients taking BL. The changes in the rate of TNF-α and IL-6 levels decrease on the 13th and 60th days were also statistically significantly more pronounced (compared to the control group). The changes in the rate of decreasing from the baseline on the 13th and 60th days in TNF-α in the BL Group made 44 [-64; -32]% and 85 [-89; -82]%; in the AB Group – 28 [-40; -20]% and 82 [-86; -80]%; in IL-6 in the BL group – 32 [-40; -18]% and 86 [-90; -85]%, in the AB group – 45 [-53; -38]% and 86 [-88; -84]%. In the control group, this parameter for TNF-α was 18 [-32; -8]% and 64 [-78; -56]%, for IL-6 – 11 [-20; -1]% and 75 [-81; -74]%. Conclusion . The addition of immunomodulators (BL, AB) to the therapy of patients with mild CAP results in statistically significant decrease in the blood levels of biomarkers of the acute inflammation phase on the 13th and 60th days.

AIM:To evaluate the efficacy of mechanical bacterial lysate on the prevention of infectious exacerbations of chronic obstructive pulmonary disease in patients with frequent exacerbations.MATERIALS AND METHODS:The study included patients (n=60) with frequent exacerbations of COPD (groups C and D according to the GOLD classification). All COPD patients were divided into two groups by blind method. The first group (n=30) received conventional therapy for COPD plus MBL (the course included 3 cycles of 10 days therapy with 20-day intervals between them). The second group of patients (control, n=30) received conventional therapy for COPD without MBL.We evaluated the severity of symptoms, frequency of recurrence of COPD exacerbations, readmissions, need for emergency care and changes in basic therapy of COPD. Evaluations were done on 10 days, 1, 3 and 6 months from the start of the study.RESULTS:Adding of MBL to the therapy list of COPD resulted in a significant decrease of biomarkers of systemic inflammation and sputum purulence during compared to the control group. After 6 months of observation MBL group demonstrated statistically significant improvement of respiratory function, decrease in frequency of COPD exacerbations, needs for emergency medical service, reduced changes in basic therapy and hospitalization for exacerbation of COPD. Therapy with MBL showed a high degree of safety and low incidence of adverse events.CONCLUSION:The results of the study indicate that MBL may be used for the prevention of severe infectious exacerbations of COPD.

В режиме силовой спектроскопии выполнена количественная оценка жесткости клеточной мембраны нейтрофилов у больных хронической обструктивной болезнью легких (ХОБЛ). Исследования поверхности клеток проводили в жидкостной ячейке на АСМ Agilent 5500. Жесткость мембраны оценивалась по модулю Юнга, который рассчитывали согласно теории Герца. В серии экспериментов сравнивали показатели жесткости мембраны нейтрофилов, полученных из крови здоровых доноров и больных ХОБЛ. Анализ результатов атомно-силовой спектроскопии упругих деформаций нейтрофилов позволил выявить, что клеточная мембрана нейтрофилов больных ХОБЛ по сравнению с контрольной группой характеризуется более высокими значениями модуля упругости. Roc-анализ показал, что чувствительность определения модуля Юнга для прогнозирования увеличения жесткости мембраны нейтрофилов составила 85 %, а специфичность 75 %.

Results of study elastic properties of blood neutrophils of patients with a chronic obstructive pulmonary disease (COPD) by method of atomic microscopy are given in article. The assessment of elastic properties of membrane of neutrophils was carried out in the mode of power spectroscopy. Researches of a surface of cages were conducted in a liquid cell on ASM Agilent 5500 with use of silicon probes of PPP-CONTPt (Nanosensors) and colloidal V-shaped probes of CP-PNPL-SiO-C with a round tip (diameter of 6.62 microns). Rigidity of membranes was estimated on Young’s modulus counted according to the theory of Hertz. The cellular membrane of neutrophils of patients with COPD in comparison with control group is characterized by higher values of the module of elasticity. It is established that the Young's modulus of a membrane of native cages of control group is 15.29 ± 0.05 КPa in average whereas this indicator is about 2.5 times higher for patients with COPD and it is equal 38.79 ± 0.32 КPa (p < 0.05). This fact testifies to decrease in elasticity and viscosity of a cellular membrane and increase of rigidity of neutrophils of patients with COPD. The revealed features of neutrophils can contribute to the existing ideas of a system inflammation at COPD and can be used as the indicator of degree of expressiveness of an inflammation for this category of patients.

Results of study by atomic microscopy of structurally functional properties of peripheral blood neutrophils of patients with a chronic obstructive pulmonary disease are presented in article. For an assessment of morphometric parameters of neutrophils and structural not uniformity of cellular surface, neutrophils were extracted from blood. Having received surface scans of neutrophils, three-dimensional images of neutrophils were created in the 3D mode. Curves of a profile of side section, on which the cage height concerning a substrate (nanometer) and the maximum height of granules of cytoplasm (nanometer) were counted, were built. Using the software of Pico Image Basic 5.1, the nucleus and cells area (nm 2) were calculated as well. Results of the conducted research showed that neutrophils are characterized by reduction of the nucleus and cells area and increase in their phase height; there are many granules in cytoplasm. The use of an informative diagnostic method of atomic-force microscopy allowed the authors to make precise estimation of complex structural and functional changes of neutrophils, to reveal their role in a system inflammation at chronic obstructive pulmonary disease.

Pulmonary hypertension (PH) and its direct result chronic pulmonary heart are the most frequent and prognostically unfavorable complications of chronic obstructive pulmonary disease (COPD). According to the classification (Dana Point, 2008), in patients with COPD, refers to the group of PH associated with lung diseases and / or hypoxemia. For maintenance therapy (guidelines ESC/ ERS, 2009) diuretics, long low-flow oxygen therapy, oral anticoagulants, glycosides are recommended. PAH specific therapy may be used depending on the functional class and involves vasodilators, prostacyclin and its derivatives, inhibitors of phosphodiesterase type V and endothelin receptor antagonists -1. Other methods of treatment are nitric oxide (NO), phlebotomy, lung volume reduction surgery, (LVRS).