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Objective To evaluate the inflammatory pattern and the interferon (IFN)-γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1. The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r = −0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.

The scientific literature does not provide enough information on whether bronchial hyperresponsiveness to hypoosmotic stimulus in patients with asthma can lead to more pronounced disturbances of regional lung ventilation.Aim. to characterize lung inflation in asthma patients with osmotic airway hyperresponsiveness.Methods. The lung inflation was studied by body plethysmography, as well as by three-dimensional volumetry, planimetry, and multispiral CT densitometry in 24 patients (group 1) with persistent mild asthma and osmotic airway hyperresponsiveness, identified by the bronchoprovocation test with inhalation of distilled water (IDW) (the average ДРБУ1 was —21.1 ± 3.2%). The comparison group (group 2) consisted of 49 patients with no response to IDW (the average ДББУ1 was —3.7 ± 0.5%; p = 0.00001).Results. Group 1 had lower lung function (FEVj was 83.6 ± 4.5%; FEF50 was 58.1 ± 5.8%) at baseline in comparison with the group 2 (96.7 ± 2.2%, p = 0.0042 and 75.5 ± 2.2%, p = 0.016, respectively) and higher indices of lung inflation at body plethysmography (RV was 153.2 ± 12.5 and 127.5 ± 4.0%, respectively; p = 0,027; RV/TLC was 128.8 ± 5.5 and 109.9 ± 2.8%, respectively; p = 0.015). According to three-dimensional volumetry, the indicators of expiratory lung inflation (526.0 ± 117.8 vox) and average residual inflation of both lungs (13.1 ± 2.6 vox) in group 1 were significantly higher than in group 2 (301.5 ± 55.8 vox, р < 0.05 and 9.1 ± 1.6 vox,р < 0,05, respectively). The patients with osmotic airway hyperresponsiveness also showed higher values of the expiratory area in the middle zone (235.3 ± 29.4 and 149.2 ± 14.9 pix, respectively; p = 0.00 47) and the lower zone (292.3 ± 37.9 and 178.6 ± 18.6 pix, respectively; p = 0.0034) of the lungs.Conclusion. Asthma patients with osmotic airway hyperresponsiveness have lung hyperinflation with impaired lung ventilation predominantly in the middle and lower zones.

Introduction. Currently, COVID-19, which is rapidly spreading around the world in the form of a pandemic, is a serious public health problem that poses a significant epidemiological and medico-social threat to the population and its quality of life, and affects all spheres of public life and economy. Aim. To assess the degree of influence of the pandemic of the new respiratory viral infection COVID-19 on the level of registered primary morbidity by classes of diseases, including the class "Diseases of the respiratory system" in the territory of the Far Eastern Federal District.Materials and methods. To implement the tasks of the study, a complex of analytical, epidemiological and statistical studies was carried out. Methods used: epidemiological analysis and monitoring, statistical, comparative and correlation analysis and methods for analyzing time series. Epidemiological and statistical assessment of the incidence of the population was carried out on the basis of ICD-10 according to the data of the state statistical monitoring of the incidence of the population of the Russian Federation for 2019-2020 using the database of the Ministry of Health of the Russian Federation, the Central Research Institute of Organization and Informatization of Healthcare of the Ministry of Health of the Russian Federation.Results. The pandemic of the new respiratory viral infection COVID-19 significantly changed the dynamics of the registered morbidity in the adult population, which dropped sharply in all ICD-10 classes, most intensively in the classes "Diseases of the endocrine system" (by 27.8%), "Diseases of the blood and hematopoietic organs" (by 22.6%), "Neoplasms" (by 21.1%), "Diseases of the circulatory system" (by 18.5%), with the exception of the class "Diseases of the respiratory system", the level of primary morbidity for which in the territory of the Far Eastern Federal District in 2020 increased by 23.9%. The most common and severe clinical manifestation of COVID-19 is bilateral pneumonia, the incidence of which among the adult population in the Far Eastern Federal District increased 2.7 times, and in the territory of the Russian Federation – 3.8 times. At the same time, the incidence of pneumonia in the child population decreased by 36.4%. Along with the growth of acute forms of respiratory pathology during the COVID-19 pandemic in the Far Eastern Federal District, the level of registered primary morbidity of chronic respiratory diseases decreased: chronic bronchitis (by 22.3%), bronchialasthma (by 20.8%), COPD (by 3, 6%).Conclusion. The negative dynamics of the growth of the registered morbidity of the population can have negative consequences due to the late detection and untimely diagnosis of chronic forms of pathology, including respiratory diseases, their progression and the development of life-threatening complications of the disease and, as a consequence, an increase in mortality from these causes of the population, who did not receive timely and adequate medical assistance.

Purpose Mucus secretion is excessively increased in airway epithelial cells in pathological states. This process is related to the cytoskeleton and the increase in exocytosis sites, but the movement of secreted molecules and how secretion increases remain unclear. In this study, we examined the potential role of myristoylated alanine rich C kinase substrate (MARCKS) and the cortical actin-binding protein cortactin in airway mucin secretion. Also we investigated the effect of activated Cdc42-associated kinase 1 (ACK1) in this process. Methods Human airway epithelial cells were treated with neutrophil elastase (NE) after treatment with siRNA to specifically knock down MARCKS, ACK1 and cortactin expression. The expression and localization of cortactin and MARCKS were observed by western blotting and immunofluorescence, and the phosphorylated forms of MARCKS, cortactin and ACK1 were detected. The interaction of cortactin and ACK1 was analyzed by coimmunoprecipitation. MUC5AC protein expression was measured by ELISAs. Results Phosphorylated cortactin was highly expressed, mainly at the cell membrane, after NE stimulation, and phosphorylated MARCKS was mainly expressed in the cytoplasm. Coimmunoprecipitation revealed that ACK1 and cortactin interacted with each other. Knockdown of MARCKS suppressed phosphorylation of cortactin, while cortactin siRNA had no significant effect on MARCKS activation. Knockdown of MARCKS, cortactin and ACK1 by siRNA attenuated the phosphorylation of cortactin and reduced MUC5AC secretion. Conclusion These results suggest that both cortactin and MARCKS are involved in MUC5AC secretion by increasing F-actin polymerization and translocation and that MARCKs and ACK1 play an important role in the activation of cortactin.

Introduction. Hypoalimentation with the formation of protein-energy malnutrition can reduce the body’s resistance to acute respiratory infections (ARI). Soy and pumpkin can be a promising source of normalization of the diet.Aim. To study the effectiveness of the use of soybean-pumpkin products in the diet of healthy people to increase the resistance of the human body to ARI.Materials and methods. An open, randomized, parallel group study was conducted. Group 1 included 18 people who took a soy-pumpkin drink and dessert for 10 weeks in addition to their usual diet. Group 2 included 17 people on a regular diet. The concentration of vitamin E, cholesterol, α- and β-lipoproteins was determined in blood serum. Diene conjugates and unoxidized lipids were determined in the expired air condensate (EAC) by means of spectrophotometry. Lung function was assessed using spirometry.Results. According to the questionnaire survey, 50% of the participants in group 1 registered a positive dynamics from the regular use of soybean-pumpkin products. Only one participant underwent ARI. In the 2nd group, 7 people (41%) applied for medical help (χ2=4.43; p˂0.05), of which 6 (35%) had ARIs. At the end of the observation, an increase in vitamin E (from 34.1±0.68 to 36.4±0.55 μg/mL, p=0.0036), a decrease in total cholesterol (from 4.85±0.23 to 4.32±0.14 mmol/L, p=0.0013) and β-lipoproteins (from 2.92±0.24 to 2.31±0.18 mmol/L, p=0.0003). At the beginning of the study, in individuals of group 1, there was a relationship between age and the concentration of total cholesterol (r=0.50; p=0.036) and β-lipoproteins (r=0.47; p=0.048), as well as the weight and level of α-lipoproteins (r=-0.49; p=0.041), the concentration of unoxidized lipids (r=0.55; p=0.02), diene conjugates (r=0.48; p=0.043) in EAC. After regular use of soybean-pumpkin products, this correlation dependence was lost.Conclusion. Regular use of soy-pumpkin products for 10 weeks has a beneficial effect on the lipid profile of the blood, increases antioxidant defence, and reduces the susceptibility of a healthy person to ARI.

Since the beginning of the 50s of the last century, numerous classifications of sarcoidosis have been proposed, which to one degree or another satisfied specialists at certain stages of the development of medical technologies. Currently, sarcoidosis of the respiratory system is divided into five stages (from 0 to IV) based on the results of chest Xray examination. Active introduction into clinical practice of computed tomography and its more advanced version – lowdose multislice computed tomography (MSCT) – allows to carry out an effective diagnosis of sarcoidosis, including in outpatient practice, as well as when performing active screening and dynamic monitoring of the course of the disease. On the basis of the studies which were carried out, the dissonance between the progress in technology (from X-ray pattern to MSCT) and the stagnation of the conceptual issues of the classification of sarcoidosis is discussed, which urgently requires its reforming. Firstly, the category of patients with concomitant lesions of the intrathoracic lymph nodes (ITLN) and parenchyma (stage II) has sharply increased, which reflects the increased technological level of radiological diagnostics. As a result, the percentage of stages with isolated lymph node involvement (stage I) and isolated dissemination of the parenchyma (stage III) decreased. The classification based on MSCT data allows to more accurately determine the severity of the disease. This is of therapeutic and prognostic importance, since most patients of stage I generally do not need treatment, while symptomatic stage II requires hormone therapy. One should also take into account the possibility of spontaneous remission, which is observed more often in stage I. The main conclusion is that at present day the principle of staging in the classification of sarcoidosis can no longer satisfy the realities of modern clinics. It is more correct to single out the clinical and radiological forms of sarcoidosis: sarcoidosis of the ITLN, sarcoidosis of the ITLN and lungs, sarcoidosis of the lungs, as well as sarcoidosis of the respiratory system, combined with a single lesion of other organs.

Free radical damage to the respiratory tract in patients with asthma leads to the destruction of the bronchial parenchyma and the generation of signaling molecules of inflammation by parenchymal cells. Objective: to study the role of the structural and functional status of granulocytes in the development of epithelial destruction and oxidative lipid modification in the bronchi of asthma patients with airway hyperresponsiveness to cold and hyperosmolar stimuli. Material and methods. In 48 asthma patients, the level of asthma control was assessed according to the Asthma Control Test (ACT) questionnaire; lung function; bronchial response to 3-minute isocapnic hyperventilation with cold (- 20 °C) air (IHCA) and with ultrasonic inhalation of hypertonic (4.5 %) NaCl solution (IHS). The cellular composition and the degree of cellular destruction in induced sputum (IS) were measured. Reaction products for enzymes from the group of heme-containing peroxidases (myeloperoxidase in neutrophils, peroxidase in eosinophils) with the calculation of the average cytochemical coefficient were studied. The content of lipid peroxidation products in according to ultraviolet absorption spectra of lipid extracts in exhaled breath condensate (EBC) was assessed. Results. Patients of group 1 (n=15) with airway hyperresponsiveness to IHCA and IHS in relation to group 2 (n=33) with a negative reaction had lower ACT (14.7±1.4 vs. 18.4±0.8 points, p=0.017). In sputum, the number of neutrophils in groups 1 and 2 was 41.8±6.4 vs. 33.6±3.4 %, eosinophils – 23.5±3.5 vs. 14.9±2.6 %; average cytochemical coefficient of peroxidase 117.5±12.5 vs. 88.8±8.9 pixels (p=0.07), cell destruction index (CDI) of bronchial epithelium 0.56±0.04 vs. 0.39±0.02 r.u. (p =0.0002). The content of diene conjugates (E233) in EBC in group 1 was higher than in group 2 (0.07±0.008 vs. 0.05±0.005 optical units, p˂0.05). A correlation was found between peroxidase level and CDI, the number of totally destroyed cells (IV class of cell destruction), between the number of neutrophils in IS and E233, as well as the ratio of E233 to E206 (non-oxidized lipids) in EBC. Conclusion. In asthma patients with airway hyperresponsiveness to cold and hyperosmolar stimuli, changes in the structure of the epithelium and the structural and functional profile of granulocytes are associated with the activation of the peroxidase function of granulocytes and are interrelated with lipid peroxidation.

Certain transient receptor potential (TRP) channels including TRPM8 and TRPA1 are widely expressed in the respiratory tract and have been shown to be the receptors of cigarette smoke and particulate matter—the main causative factors of chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effect of TRPM8 and TRPA1 polymorphisms on COPD predisposition and lung function in COPD patients. The study enrolled 143 COPD patients and 104 smokers with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 70%. Lung function was measured by spirometry. TRPM8 and TRPA1 polymorphisms were genotyped by LATE-PCR. None of the polymorphisms significantly influenced COPD predisposition after correction for covariates and multiple testing. Among COPD patients, the TT genotype of TRPA1 rs7819749 was significantly associated with higher degree of bronchial obstruction. In addition, we established that carriers of the C allele of TRPM8 rs11562975 more commonly had post-bronchodilator FEV1 < 60% (OR 3.2, 95%CI (1.14–8.94), p = 0.03) and revealed the effect of TRPA1 rs959976 and TRPM8 rs17865682 on bronchodilator response in COPD. Thus, the obtained results suggest possible involvement of TRPM8 and TRPA1 in COPD pathogenesis, indicating the necessity to further investigate their functional role in this pathology.

Background: Airway hyperresponsiveness is related to the intensification of the lipid peroxidation (LP) in asthma. We aimed to study the effect of smoking on the LP status of asthma patients with EIB. Methods: 62 subjects (36.2±1.3 years) with EIB (drop of FEV1 -21.9±2.0%) were divided into 2 groups: the 1st included 30 non-smokers, the 2nd - 32 smokers (8.2±1.5 pack/year). The contents of conjugated dienes and non-oxidized lipids in the exhaled breath condensate were analyzed before and after 6-minute submaximal exercise on treadmill, using ultraviolet spectra of lipid extracts absorption and evaluated in terms of optical density at 233 nm (E233) and 206 nm (E206), respectively. Results: In group 2, FEV1 was lower (84.6±2.7 vs. 92.0±2.5%; p 0.05) in the2nd group led to a change in E233/E206 after exercise: 0.39±0.09 (p>0.05) vs. 0.38±0.05 (p Conclusion: Smoking in asthmatics with EIB leads to changes in the LP, which is accompanied by a deterioration of airway patency and a decrease of the response to dosed exercise.

Background: Features of bronchial inflammation that contribute to the development of cold airway hyperresponsiveness in patients with asthma have been poorly studied. We aimed to investigate the correlation between the neutrophils and airway response to cold stimulus. Methods: In 116 patients with uncontrolled asthma (mean age 43.2±0.8 years), the lung function (FEV1,%), airway response to 3-minute isocapnic hyperventilation with cold air (IHCA), the cell composition of induced sputum (IS, %), the activity of myeloperoxidase (MPO, in pixels), and the degree of structural integrity of cells using the destruction index (DI, relative units) were studied. Asthma control was assessed by ACT questionnaire. Results: The patients were divided into 2 groups based on the number of neutrophils in IS: group 1 (n=52) less than 40%, and group 2 (n=64) more than 40%. The number of eosinophils in IS was 21.2±1.4 vs. 14.3±1.4%, respectively (p=0.001). The baseline FEV1 was 87.3±1.7 and 84.3±2.6% (p>0.05); the FEV1 drop in response to IHCA was -10.9±1.3 and -10.9±1.6%. The level of ACT in group 1 was higher (13.7±0.33 vs. 12.4±0.44 points, p=0.026), the MPO content of granulocytes was lower (81.7±3.6 vs. 135.9±12.1 pixels, p=0.00001), as well as neutrophil DI (0.47±0.02 vs. 0.56±0.04, p=0.047) and DI of the bronchial epithelium (0.52±0.02 vs. 0.63±0.06, p=0.05). The correlation was found between the content of neutrophils in IS and the airway response to IHCA (r=-0.18, p=0.047). Conclusion: An increase in the number of neutrophils with an escalation of their functional activity in patients with uncontrolled asthma is related to the severity of the airway response to the IHCA.

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

Background: Role of interferon-gamma (IFNγ) in asthma remains controversial. While certain studies found association of this cytokine with severe asthma and bronchial hyperresponsiveness, the other ones established its rather beneficial effect on mucin secretion and asthma development. Objectives: The aim of the study was to investigate IFNγ levels in exhaled breath condensate (EBC) of asthma patients. Methods: The study included 46 patients with asthma (mostly newly diagnosed - 52% and moderate - 30%) and 23 patients with chronic bronchitis. Mean age of patients was 38.1±1.60 years. Among asthma patients, 78% had uncontrolled disease according to ACQ5. Lung function was tested by spirometry. IFNγ was measured in EBC by BD cytometric bead array method with enhanced sensitivity. Results: Asthma patients had higher level of IFNγ than patients of control group (2654 (1328.9; 3123.9) fg/ml vs. 1872 (1707.8; 2506.3) fg/ml) but the difference was not significant. IFNγ was increased in moderate asthma (2199 (1764.8; 2519) fg/ml) compared to newly diagnosed asthma (1666 (928.8; 2048.5), p=0.01). Moreover, IFNγ was positively correlated with ACQ5 score (R=0.39, p=0.01). In uncontrolled asthma concentration of the cytokine was more than two times higher compared to patients with partially or fully controlled disease (2807 (1512.9; 3123.9) fg/ml vs. 1158 (995.5; 1589.6) fg/ml, p=0.02). 10-days treatment with oral glucocorticoids decreased IFNγ from the initial (2654 (1328.9; 3123.9) fg/ml) to “normal” values (1790 (1124.4; 3070.1) fg/ml, p=0.08). Conclusions: Our observations suggest detrimental effect of IFNγ in asthma pathogenesis. The study was supported by RFBR (#18-54-53019).

Background: Airway hyperresponsiveness (AHR) to osmotic stimuli is common and clinically relevant in asthma. AQP5 is a membrane water channel that may be functionally implicated in airway inflammation and hypersecretion. Objectives: The aim was to assess the effect of AQP5 SNPs on osmotic AHR in asthma patients. Methods: The study enrolled 274 patients with mild-to-moderate asthma, mean age 36.2±0.67 years. The patients underwent bronchoprovocation with 3-min inhalation of distilled water (hypoosmotic stimulus) and hypertonic saline aerosol (hyperosmotic stimulus). Lung function was measured by spirometry before and after each challenge. AQP5 SNPs (rs3759129, rs3736309, rs296756, rs1964676) were genotyped by LATE-PCR. Results: Association with hypoosmotic AHR was found for rs3759129 and rs296756. C allele of rs3759129 was protective against hypoosmotic AHR as AC heterozygotes had less profound response to the challenge compared to AA carriers (ΔFEV1 -1.4 (-6.3; 2.33)% vs. -5.4 (-12.0; -1.0)%, p=0.001; ΔFEF25-75 -1.0 (-18.0; 14.0)% vs. -9.1 (-21.1; 1.2)%, p=0.009). G allele of rs296756 in homozygous state also had protective effect. AA and AG (but not GG) carriers showed marked reduction in airway patency (ΔFEV1 -5,5 (-12,0; -0,8)% vs. -0,2 (-4,5; 3,4)%, p=0.004; ΔFEF25-75 -9,6 (-22,0; 2,3)% vs. 2,0 (-8,9; 9,0)%, p=0.008, for AA and GG genotypes, respectively). rs3759129 also influenced hyperosmotic AHR: all patients with the AHR had AA genotype while 27% of patients without the AHR had AC genotype (p=0.006). Conclusions:AC genotype of rs3759129 and GG genotype of rs296756 exert a protective effect on hypoosmotic AHR. AC genotype of rs3759129 also protects asthma patients from hyperosmotic AHR.

The aim of the research was to study the state of the bronchial mucosa epi-thelium in relation to the severity of clinical manifestations in severe uncon-trolled asthma depending on the pattern of inflammation and the presence of cold airway hyperresponsiveness. Materials and methods. In 48 patients with severe uncontrolled asthma, there were assessed asthma symptoms, clinical signs of cold airway hyperre-sponsiveness, and lung function; the samples of slides were analyzed in the cytological examination of the sputum; the degree of damage to epithelial cells and granulocytes was estimated using the total cell destruction index (CDI). Results. According to the analysis of sputum cytograms, the patients were divided into two groups: group I (22 patients) included persons with eosin-ophilic inflammation pattern (31.0±3.1% of eosinophils and 22.0±2.2% of neutrophils), group II (26 patients) was with mixed inflammation pattern (7.2±1.4 and 71.8±4.2%, respectively). The patients of group II had lower disease control according to Asthma Control Test (ACT; 12.1±0.7 and 17.8±0.2 points, respectively; р