Cytokines play an important role in the organization of chronic inflammation in the airways of patients with asthma. The purpose of this study was to conduct a comparative analysis of IL-1b, IL-5, IL-8, IL-10, IL-13, IL-18 and TNFa cytokines levels in induced sputum of patients with asthma and chronic bronchitis (CB), to clarify their relationship with airway hyperresponsiveness and to determine their dynamics in response to cold exposure. The study enrolled 46 patients with mild to moderate asthma and 18 patients with CB. Cold airway hyperresponsiveness (CAH) was detected spiro-metrically by 10% or more decrease in FEV₁ after the test with 3-minute isocapnic cold air hyperventilation (ICAH). Induced sputum was collected and processed by the standard method twice - before and after the test with ICAH. Cytokines concentrations were determined by multiplex analysis on BD FACSCanto II flow cytometer. We found no significant differences in the cytokines levels between patients with asthma and CB. Among patients with asthma, the presence of CAH was associated with a higher initial concentration of IL-10 (7.1 (4.7; 8.7) pg/ml vs. 5.1 (2.9; 7.9) pg/ml, p=0.06). In addition, IL-10 adversely affected the spirometric indices of the airway patency (FEV₁ R=-0.44, p=0.002) and the airway response to bronchodilator (ΔFEV₁ R=0.52, p<0.001). There was an increase in the levels of all cytokines in response to ICAH in patients with asthma, while in CB their concentrations rather decreased. Significant differences were found in the dynamics of IL-5 concentrations in response to ICAH between asthma and CB patients (31.2 (-21.7; 83.5)% vs. -29.9 (-50.5; 16.8)%, p=0.02). Thus, the cold exposure indeed provokes an inflammatory response in the airways of the majority of asthma patients, however its pattern is heterogeneous. The mechanism of the observed effect of IL-10 on the airway reactivity requires further investigation.

There is no information on relief of clinical symptoms, achievement of criteria for disease control and regulation of inflammatory patterns of the bronchi in the application of the strategy of long-term anti-inflammatory therapy with various fixed combinations of inhaled glucocorticosteroids with long-acting β₂-agonists (ICS/LABA) in patients with asthma with combinedcold and osmotic airway hyperresponsiveness. The aim of the study was to compare the effectiveness of anti-inflammatory therapy with combinations of beclometh-asone dipropionate/formoterol fumarate and budesonide/formoterol in asthma patients with combined airway hyperresponsiveness to cold and osmotic triggers. The clinical study involved 37 patients with asthma of a mixed form, and of a persistent course with documented combined cold and osmotic airway hyperresponsiveness. After randomization into groups, two fixed combination drugs ICS/LABA were used for treatment for 12 weeks: the 1^st group (n=22) took the therapy with a combination of beclomethasone dipro-pionate/formoterol fumarate; the 2nd group (n=15) had the therapy with a combination of budesonide/formote-rol. The control of asthma using Asthma Control Test questionnaire (ACT), a lung function and a reaction of airways to the inhalation of β₂-agonist were assessed initially (1st visit), after 6 weeks (2nd visit) and 12 weeks (3^rd visit). At the 1^st and 3^rd visits, the collection and cyto-logical examination of induced sputum (IS) were carried out. At the time of randomization in groups, patients in groups 1 and 2 had no differences in ACT (17.1±1.1 and 16.5±1.6 points, p>0.05) and FEV₁ (94.0±3.7 and 98.0±5.0%, p>0.05). By the end of treatment the patients of the 1st group had the achievement of a good level of asthma control (an average of 21.7±0.6 points, p=0.0001), improvement of airway conductivity at the level of large (FEV₁ 101.9±3.3; p=0.009) and small (FEF_25-75 75.0±4.5%; p=0.011) bronchi, and a decrease in airway response to the inhalation of broncho-dilator (the growth of FEV1 decreased from 16.1±3.5 till 8.0±1.74%, p=0.01). In patients of the 2^nd group at the time of the 3rd visit, the level of asthma control was 19.0±1.2 points (p=0.08), FEV₁ was 96.9±4.78% (p=0.67), MEF_25-75 was 76.5±9.53% (p=0.84), the growth of FEV₁ under bronchodilator did not significantly change (7.2±1.4% at the 1^st visit and 6.1±2.6% at the 3rd visit; p=0.84). In the study of cytological smears of IS in patients of 1^st group, there was a significant decrease in the number of eosinophils (from 12.7±2.5 to 3.3±0.64%; p=0.0015) and an increase in the number of neutrophils (from 42.3±3.0 to 60.4±1.3%; p=0.00004). The number of neutrophils in IS in the patients the 2^nd group by the end of the observation decreased (from 55.8±5.0 to 42.8±3.5%; p=0.021), the number of eosinophils remained at the same level (9.2±2.95 and 6.5±2.53%; p=0.37). Thus, a 12-week therapy with a combination of beclomethasone dipro-pionate/formoterol fumarate leads to an improvement in clinical and functional parameters and a decrease in the number of eosinophils in induced sputum.

In the scientific literature, there is no information on the effectiveness of the use of beclomethasone dipropionate/formoterol fumarate in the form of extrafine aerosol for inhalations in asthma patients with osmotic airway hyperresponsiveness. We aimed to study additional possibilities of targeted use of beclomethasone dipropionate/formoterol fumarate in patients with asthma, aimed at reducing the sensitivity of the bronchi to osmotic stimulus and achieving better control. There were examined 16 patients with mild persistent asthma and proven osmotic airway hyperresponsiveness; the analysis of clinical symptoms of asthma was done in them; the control of asthma by Asthma Control Test (ACT), the lung function, the airway reaction to the inhalation of aerosol of distilled water (IDW) at the beginning and after a 12-week course of therapy with beclomethasone dipropionate/formoterol fumarate at a dose equivalent to the severity of asthma were assessed. By the end of the treatment period, 81% of patients had well control (≥20-24 points according to the results of ACT), 19% achieved complete control (25 points), the ACT value in the group averaged 22.5±3.0 points (p=0.00001). The frequency of episodes of shortness of breath during the day (χ²=18.66; p<0.001) and at night (χ²=12.96; p<0.001) decreased. Along with the positive dynamics of the clinical picture, there was a significant increase in the lung function: FEV₁ from 92.1±3.9 to 102.1±3.4% (p=0.0296); MEF_25-75 from 56.8±7.0 to 76.8±4.3% (p=0.0058). Against the background of the 12-week treatment 75% of patients had regression of response to IDW: ΔFEV₁ from -18.1±2.3 to -5.3±1.9% (p=0.0001); ΔMEF_25-75 from -27.5±3.8 to -7.8±3.3% (p=0.0003). Thus, the results of the clinical study showed that in asthma patients with osmotic airway hyperresponsiveness the use of extrafine aerosol for inhalation of beclomethasone dipropionate/formoterol fumarate for 12 weeks leads to a decrease in clinical symptoms, improvement of asthma control, and a decrease in airway hyperresponsiveness to hypoosmotic stimulus.

TRPM8 cold receptors are widely expressed in the human respiratory tract and are able to mediate inflammatory and secretory response upon cooling. The aim of the study was to investigate the expression of TRPM8 at mRNA level in nasal epithelium of asthma patients with cold-induced airway hyperresponsiveness (CAH). The study involved 54 people, including 36 patients with asthma and 18 patients with chronic bronchitis. All the patients underwent 3-minute isocapnic cold air hyperventilation (ICAH) through the mouth and through the nose. Expression was studied by quantitative PCR with reverse transcription in the brush-biopsy specimens obtained before and after the nasal ICAH. It was established that the basal expression of TRPM8 is increased in smokers, however, it is not associated with lung function in asthma patients. CAH is accompanied by 3.3-fold increase in TRPM8 expression of (p=0.03). In addition, the basal level of expression is inversely correlated with the degree of lung function decrease in response to the oral ICAH both among asthma patients (ΔFEV₁ p =-0.37, p=0.02) and in the general group (ΔFEV₁ p=-0.33, p=0.01). Apparently, the effect of cold in vivo causes an adaptive response decreasing the transcription of TRPM8, which is especially well observed in patients with moderate persistent asthma (3.2-fold decrease, p=0.02). Further assessment of the diagnostic and prognostic potential of TRPM8 expression level in the evaluation of CAH development is necessary in patients with chronic obstructive lung pathology.

Impulse oscillometry (IOS) is an innovative method of diagnosing ventilation disorders, although relatively little is known about its clinical application. The aim of this study was to evaluate the possibilities of IOS in the diagnosis of the severe airway obstruction (AO). A total of 114 patients (mean age 53±19 years old, 98 (86%) male and 16 (14%) female) with various bronchopulmonary pathologies were examined. The degree of obstructive impairment was defined by FEV₁. The patients were divided into three groups: group 1 included 40 patients with severe AO; group 2 had 30 patients with moderate AO; group 3 (comparison) consisted of 44 patients who had no functional disorders of the lung function according to the spirometry, bodyplethysmography and diffusion test. The parameters of the IOS were compared with the data of spirometry, bodyplethysmography and diffusion test. The analysis of IOS data showed the presence of statistically significant differences between the groups concerning all the studied indices, the degree of deviation from the norm of which increased with the increase of obstruction. The frequency of detection of deviations from the norm of basic indicators of IOS (Rrs5 and Xrs5) in patients with moderate obstruction was 57%; in patients with severe obstruction it was 95 %. Correlation analysis showed that most of the IOS indices significantly correlated with bronchial resistance and peak expiratory flow. Thus, IOS can be used as an alternative method for assessing the ventilation function of the lungs in patients with severe obstructive disorders.

The aim of the research was to study the influence for each seasons of the year on the results of the sanatorium medical rehabilitation (SMR) of patients with asthma on the Southern Coast of the Crimea (SCC). The research included 518 patients with asthma who completed course of the SMR on SCC. 129 patients completed the course in the winter, 139 patients completed it in the spring, 116 patients completed it in the summer and 133 patients in the autumn. All patients were screened and received complex SMR. Methods of rehabilitation were identical, except of climatotherapy which corresponded to seasons of year. The results of the SMR were estimated by efficiency and criteria of the ICF. The aeropalynological research was conducted. The static processing was evaluated by SPSS 25. The results of the study suggest that the patients were admitted on rehabilitation with the activity of the allergic process, an obstructive syndrome and lack of current asthma control. The groups of patients were comparable among themselves. Aeropalynological researches revealed that the main producers of pollen were Cu-pressus sp. and Cedrus sp. in the winter, in the spring they were Cupressus sp., Pinus sp. and Fraxinus sp., in the summer they were Poaceae and Ambrosia sp., and in the winter it was Cedrus sp. Pollen loading considerably prevailed during the spring period. By all analyzed criteria of SMR efficiency the reliable positive dynamics is reached in every season. Differences of SMR efficiency between seasons are not revealed, despite sharply different pollen loading. Thus, the expediency of year-round use of SCC potential for carrying out the rehabilitation of patients with asthma has been proved.

Serological, immunoenzyme and molecular genetic markers of viral infections in 100 women in the second trimester of pregnancy, uncomplicated and complicated by chronic simple bronchitis in remission, and in their full-term newborns were studied. The first group included 30 women with physiological pregnancy; the second group consisted of 38 patients suffering from chronic simple bronchitis out of exacerbation; the third group had 32 women with chronic simple bronchitis in remission and the threat of miscarriage in the second trimester of gestation. It was found out that in the second group there was one case of diagnosed signs of influenza A(H3N2), one case of influenza B, in 2 patients there was parainfluenza type 3 and in 1 case there was an acute phase of cytomegalovirus infection, in the absence of those in women of the first group. In the third group, asymptomatic influenza A(N3N2) (n=6), parainfluenza type 3 (n=8) and acute phase of cytomegalovirus infection (n=9) were more often observed and were found in patients of the second group, respectively, in 1 case (p<0.05), in 2 patients (p<0.05) and in 1 woman (p<0.01). At the same time, 2 patients of the third group had an exacerbation of herpes-virus infection (herpes simplex virus type 1). Thus, in women suffering from chronic simple bronchitis outside of exacerbation, the threat of interruption in the second trimester of pregnancy was associated mainly with the asymptomatic course of respiratory viral infection (influenza A(H3N2) and parainfluenza type 3), as well as exacerbation of persistent DNA viral infections.

The aim of the work was to study the state of the hepatobiliary system in newborns from mothers with chronic simple bronchitis in remission and the threat of miscarriage. Liver function was studied in 100 full-term newborns from mothers with uncomplicated pregnancy and mothers suffering from chronic simple bronchitis without exacerbation. The first group included 30 children whose mothers had a physiological course of pregnancy, the second one had 38 newborns from mothers with chronic simple bronchitis without exacerbation during gestation, the third group consisted of 32 children with antenatal ontogenesis, complicated with chronic simple bronchitis in remission and the threat of miscarriage in the second trimester of pregnancy. In the blood of newborns in the second group there was a decrease in total protein to 58.3±1.01 g/L (in the first group it was 64.2±1.07 g/L, р<0.001); at the same time there were no significant differences in the content of albumins, total, indirect and direct bilirubin, as well as total cholesterol, high and low density lipoproteins (LDLP) and triglycerides (p>0.05). The lower values of total protein (52.1±1.06 g/L; p<0.001) were recorded in the third group compared with the first group, at the same time there was registered the increase in total bilirubin (32.1±1.58 and 25.4±1.67 pmol/L, respectively; р1<0,01) and indirect bilirubin (30.1±1.54 and 23.3±1.66 pmol/L, respectively; p<0.01), the decrease in total cholesterol (1.84±0.05 and 2.02±0.07 mmol/L, respectively; p<0.05) and LDLP (0.26±0.03 and 0.52±0.03 mmol/L, respectively; p<0.001), as well as the growth in the concentration of triglycerides (0.53±0.03 and 0.43±0.03 mmol/L, respectively; p<0.05). Attention was drawn to the lower concentration of LDLP in the third group compared with the second (0.26±0.03 and 0.44±0.03 mmol/L, respectively; p<0.001). The results indicate an important role of chronic simple bronchitis without exacerbation, combined with the development of the threat of miscarriage in women in the second trimester of pregnancy, in disturbance of the functional state of the hepatobiliary system in their newborns.

The gas-liquid chromatography method was used to study the content of ω -3 polyunsaturated eicosapentaenoic acid in peripheral blood plasma of first trimester pregnant women with cytomegalovirus infection, depending on the specific titer of IgG antibodies to cytomegalovirus. The study included 135 pregnant women who were divided into groups. A comparison group was in the amount of 45 healthy pregnant women with the physiological course of the first trimester of gestation. The values of the indices studied in this group were used as the starting point of comparison as physiologically normal values. The study group included 90 pregnant women with exacerbation of chronic cytomegalovirus infection in the first trimester, divided into two subgroups, depending on the titer of IgG antibodies to cytomegalovirus: subgroup A (45 women with active cytomegalovirus infection, IgG antibody titer to cytomegalovirus 1:1600); subgroup B (45 women with latent form of cytomegalovirus infection, antibody IgG titer to cytomegalovirus 1:800). Based on the data obtained, it was found out that reactivation of cytomegalovirus infection in the first trimester of gestation leads to the decrease in the concentration of ω -3 polyunsaturated eicosapentaenoic acid in women with peripheral blood plasma by 30% (p<0.001) in subgroup A and by 18% (p<0.01) in subgroup B, in comparison with the similar index of the control group. This dynamics of changes in eicosapentaenoic acid in plasma of peripheral blood of pregnant women with cytomegalovirus infection depends on the specific titer of IgG antibodies to cytomegalovirus and is most pronounced with the active form of cytomegalovirus infection (IgG antibody titer to cytomegalovirus 1:1600). A further study of the level of free polyunsaturated fatty acids of the ω -3 family during pregnancy can allow the development of therapy for the timely correction of perinatal pathology, preventing cell death and improving health outcomes in subsequent life periods of newborns.

The use of collagen or gelatin-based scaffolds mimicking the in vivo conditions of the microenvironment is beginning to be used more widely. This is facilitated by the deepening of the understanding of cell-cell interactions in vivo, which allows to artificially form a his-toarchitecture suitable for cells and the microenvironment of the scaffold. Gelatin is a collagen derivative. This is one of the most promising and inexpensive materials for creating scaffolds. The purpose of the study was to investigate the morphological, biodegradable and antibacterial properties, as well as the rate of scaffold degradation in vivo and in vitro of glu-taraldehyde-crosslinked gelatin polymer modified by dihydroquercetin and arabinogalactan. The study of the morphological properties of the scaffold was performed using histological examination with hematoxy-lin-eosin staining and scanning electron microscopy. The study of the rate of degradation of the scaffold was performed at 37°C and the action of enzymes (trypsin, collagenase). In vivo degradation was studied morphologically after subcutaneous implantation of the studied scaffold to laboratory rats. When morphological study, the scaffold has a high porosity - up to 35-45%. Scaffold shows high thermal stability and does not degrade at 37°C. When exposed to trypsin and type I collagenase solutions, degradation is observed for 540±15 and 200±10 minutes, respectively. When the morphological study of in vivo degradation, scaffold completely degrades within 3 weeks, being replaced by the granulation tissue. The results obtained indicate the possibility of using glutaraldehyde-crosslinked gelatin scaffold modified by dihydroquercetin and arabinogalactan for research in tissue engineering of the lungs.

The study was aimed to identify the impact of living conditions, primarily social conditions (education, employment, housing conditions, economic status and other relations) on pregnant women of the Amur region with genital tract dysbiosis in combination with urogenital mycoplasmas. 75 pregnant women were examined, 32 of them (the main group) were diagnosed with dysbiosis (Lactobacillus spp. <10⁶ GE/ml) with detected urogenital mycoplasmas (Ureaplasma spp. and Mycoplasma hominis) at clinically significant concentrations (≥10⁴ GE/ml). The control group consisted of 43 pregnant women with normocenosis (Lactobacillus spp. ≥10⁶ GE/ml). The analysis of medical and social factors revealed that women with genital tract dysbiosis in most cases live on the territory of the Amur region since birth, among them there were patients who had a second or third marriage who assessed their living conditions and material security as unsatisfactory, and the relationship with the husband as satisfactory (against the good ones in the control group); these women also smoked during pregnancy and often had physical activity at work both before and during pregnancy. Almost half of the women in the main group were unemployed. Women with genital dysbiosis were significantly more likely to undergo intrauterine intervention to terminate an unwanted pregnancy, and delivery by cesarean section was 4.1 times more likely than in the control group. The intensity of the influence of medical and social risk factors for infection of the genital tract with urogenital mycoplasmas was assessed.

The article contains modern views on the etiology and pathogenesis of Pickwickian syndrome, a rare fatal disease whose mandatory clinical manifestations are a high degree of obesity and alveolar hypoventilation of the lungs. The disease is more common in men. The author introduces two cases of Pickwickian syndrome in women that occurred almost simultaneously in different areas of the Amur Region, which is a medical casuistry.

Organizing pneumonia (OP), formerly known as obliterating bronchitis with organizing pneumonia, is a form of idiopathic interstitial pneumonia. There are two forms of OP: predominant (90%) cryptogenic (unknown in etiology) organizing pneumonia and secondary pneumonia affiliated to other mainly interstitial diseases. Cryptogenic OP is believed to be a consequence of alveolar damage and is characterized by the formation of organized buds of the granulation tissue that prevent alveolar lumen and bronchioles, which in its turn leads to respiratory failure. The organization of pneumonia is a pathological diagnosis and it can be secondary to the identified etiology. Cryptogenic OP should be diagnosed only after the exclusion of any other possible etiology.

This report, along with a review of the world literature in the historical aspect, presents modern achievements in the diagnosis and management of patients. The possibilities of multispiral computed tomography with extensive use of basic image postprocessing are emphasized. Personal experience of clinical and radiological diagnostics and differential diagnostics of idiopathic interstitial pneumonia and, in particular, OP is systematized. Diagnostic (clinical and radiological) patterns have been developed and demonstrated in practical work.

Chronic obstructive pulmonary disease (COPD) remains the focus of medical science and practice. The article presents a review of contemporary literature on the problem of COPD in women. The data are presented on the prevalence of the disease, on the characteristics of sensitivity to the effects of risk factors, age-related aspects of development, progression, outcomes and clinical manifestations of COPD, as well as on the difference in response to the pharmacotherapy in women and men. Thus, a number of studies have demonstrated a high susceptibility of women to exposure to tobacco smoke, a predisposition to the development of the bronchitis phenotype of COPD, severe course with frequent exacerbations and a low risk of death after exacerbations. Based on the results of the review, it can be concluded that gender differences can be explained by the anatomical features of the respiratory system development and the cyclic hormonal activity of the female body, which is manifested by a greater degree of airway hyperresponsiveness, and, as a consequence, a high frequency of severe COPD.

The science of researching the health-related quality of life has not only occupied a certain niche in modern medicine, but continues to evolve rapidly. The article presents a review of the literature data on the concepts of "quality of life” and "health-related quality of life”, the history of the issue and its methodological basics.

The article is a two-part review of the literature in which modern data on the receptors of the most important hormones during pregnancy, estrogens, are analyzed. The first part of the review describes the types of estrogen receptors and shows the features of their structure. Genomic and non-genomic mechanisms of hormone action are considered, which are realized through different types of receptors: nuclear and membrane-associated. There are also briefly characterized intracellular signaling pathways stimulated by estrogens. The paramount importance of accurate and dynamic regulation of the activity of hormones is emphasized. It was concluded that there is a necessity for further research of the estrogen receptors. The second part of the literature review focuses on the role of estrogen receptors during pregnancy.