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Introduction. In patients with uncontrolled asthma, the stress-induced production of glucocorticosteroids in response to a cold bronchoprovocation test is increased, which is associated with an increase in the level of thyroidstimulating hormone (TSH), characteristic of the syndrome of subclinical hypothyroidism (SH). The peculiarities of thyroid hormone metabolism and changes in pituitary-adrenal homeostasis that develop in asthma in a goiter-endemic region under the influence of cold stress factors on the respiratory system are poorly studied.Aim. To assess the activity of the pituitary-thyroid and pituitary-adrenal systems in response to bronchoprovocation with cold air in asthma patients with cold airway hyperresponsiveness (CAHR) and SH living in conditions of goiter endemic in the Amur Region.Materials and methods. In 34 asthma patients with CAHR, without symptoms of thyroid diseases, the level of disease control was assessed using the Asthma Control Test (ACT) questionnaire. Lung function and airway reaction to a cold stimulus (ΔFEV1IHCA) during 3-minute isocapnic hyperventilation with cold (-20ºC) air (IHCA) were measured. Methods of immunological diagnostics in the blood of patients before and after the IHCA test were used to measure the concentrations of thyroid-stimulating (TSH) and adrenocorticotropic (ACTH) hormones, common and active forms of thyroxine (T4) and triiodothyronine (T3), thyroglobulin (TG), autoantibodies to thyroperoxidase (AB-TPO), cortisol. The content of cyclic adenosine monophosphate (cAMP) was determined in leukocytes.Results. The patients were divided into two groups: group 1 included 25 patients with an initially low (4, 0) TSH level (4.80±0.46 mU/L, p0.05), base FEV1 was 95.8±3.3 and 81.0±5.4% (p=0.026), ΔFEV1IHCA -11.9±0.96 and -13.5±2.7 (p>0.05), respectively. In group 1, in response to IHCA, the level of free T4 increased from 14.2±0.70 to 15.2±0.71 pmol/L (p1 and the T4 level before (r=0.54; p50 and the initial level of cortisol in the blood serum (r=0.50; p=0.002).Conclusion. In asthma patients with CAHR living in the region of cold climate and goiter endemic, the presence of SH can be considered as a prognostic sign of the development of dysadaptation of the respiratory system to cold exposure.

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.

The results of recent studies indicate the potential role of gamma-aminobutyric acid (GABA), as an inhibitory mediator of the central nervous system, in the pathogenesis of obstructive sleep apnea syndrome (OSAS) ‒ a common disorder that often accompanies asthma. The aim of the study was to investigate the possible role of some GABAergic system genetic polymorphisms in the formation of OSAS in asthma patients. Overnight cardiorespiratory monitoring was performed to diagnose OSAS and spirometry was conducted to evaluate the airway reactivity to the bronchodilator fenoterol in 184 asthma patients. Polymorphisms of GAD1, GAD2, GABBR1 and GABBR2 genes (15 polymorphisms in total) were genotyped by LATE-PCR method. Significant results were obtained for rs3749034 polymorphism of GAD1 gene and rs35400353 of GABBR2 in association analysis with the presence of OSAS. rs3749034 significantly influenced the presence of OSAS in males, which was accompanied by the predominance of the CC genotype among patients with OSAS, while CT+TT genotypes were more common in patients without OSAS (OR 3.9 95%CI [1.36–11.67], p=0.01). In total sample GAD1 rs3749034 polymorphism was an independent factor increasing the likelihood of having OSAS after adjustment for significant confounders (OR 1.9 95%CI [1.23–3.15], p=0.005). rs35400353 polymorphism was also associated with OSAS after adjustment for confounders, although its relationship was less significant (OR 1.5 95%CI [1.1–2.3], p=0.04). There was a tendency for interrelation with airway hyperresponsiveness to bronchodilator for both polymorphisms: rs3749034 ‒ in case of CT+TT genotypes, rs35400353 ‒ in case of DD genotype. rs3749034 polymorphism also significantly influenced lung function parameters. After additional verification of the results, the identified genetic polymorphisms may be used to individually predict the risk of OSAS as well as for the development of personalized approaches in asthma treatment using GABA.

Obstructive sleep apnea syndrome (OSAS) is a pathogenetically heterogeneous condition that aggravates the course of asthma. For this reason, timely diagnosis and treatment of OSAS may improve asthma control, reduce the number of exacerbations and the frequency of short-acting bronchodilators use. The aim of the study was to describe the clinical and functional features of patients with asthma and OSAS, and to identify risk factors that allow suspecting the comorbidity. A total of 194 patients with asthma were examined. The research methods included assessment of symptoms using the ACT questionnaire, spirometry with bronchoprovocational tests, body plethysmography and determination of lung diffusion capacity, analysis of the cellular composition of induced sputum, echocardiography, overnight cardiorespiratory monitoring. According to the results of cardio-respiratory monitoring OSAS of varying severity was detected in 33% of patients (n=65). Epworth sleepiness scale did not allow specific discrimination of OSAS among the examined patients. In general, patients with the comorbid pathologies were more often men of older age groups, they had a long history of disease and smoking. In patients with OSAS diabetes and cardiovascular diseases were more common in the structure of concomitant pathology. The presence of OSAS did not significantly affect spirometry but was associated with a pronounced airway hyperresponsiveness regardless of the provocative stimulus. In addition, a higher airway resistance and an increase in lung diffusion capacity were noted in OSAS patients. Neutrophilic phenotype of inflammation was three times more common in case of concomitant OSAS, and signs of cardiac remodeling and an increase in pulmonary artery pressure were also observed in these patients. Thus, knowledge of the above features of asthma-OSAS phenotype will facilitate timely diagnosis and optimal therapeutic care for patients with a combination of pathologies.

The state of health of 100 full-term newborns from mothers with uncomplicated course of pregnancy and with chronic simple bronchitis in remission was studied. The first group consisted of 30 newborns from mothers with physiological pregnancy. The second group consisted of 38 children of a similar age from mothers who were diagnosed with simple chronic bronchitis without exacerbation in the period of gestation. The third group was represented by 32 newborns with antenatal history, burdened with chronic simple bronchitis in remission and the threat of miscarriage in their mothers in the second trimester of pregnancy. It was shown that in children of the third group, in comparison with the second group, there was a lower score on the Apgar scale at 5th minute (7.7±0.14 and 8.1±0.12 points, respectively, p

An approach to the study of cellular inflammation using methods of cytochemical analysis of sputum in patients with bronchial asthma with different types of airway reactions to bronchoprovocation with cold air is presented. Endotyping of patients contributes to a better understanding of the pathophysiological mechanisms and the choice of treatment tactics for the disease.

The aim of the study was to analyze the peculiarities of TRPM8 receptor expression at protein level in induced sputum and nasal epithelium of asthma patients, and to evaluate their relationship to maintenance therapy and cold airway hyperresponsiveness. The study enrolled 43 patients, including those with persistent mild-to-moderate asthma and those with chronic non-obstructive bronchitis (control group). Analysis of TRPM8 expression was performed by indirect flow cytometry. In addition, patients underwent spirometry and a bronchoprovocation test with 3-minute cold air hyperventilation. As a result, we found that TRPM8 was expressed on macrophages of induced spleen and nasal epithelium. Its expression in patients with asthma who did not receive maintenance therapy was more pronounced as compared to the treated patients or the control group. Moreover, the relationship between increased expression of TRPM8 on macrophages and cold airway hyperresponsiveness was established. Further studies should reveal the possibility of TRPM8 usage as a prognostic biomarker of asthma at various stages of the disease development.

There was done analysis of epidemiological monitoring of respiratory diseases (RD) on the territory of the Far Eastern Federal District (FEFD), which allows to assess the levels, structure and regional features of the spread of pathology among different populations and territorial formations, the dynamics of the disease and its relationship with the environmental factors of the region. To organize the study, the methods of cluster, structural and comparative analysis, predictive modeling, dynamic series analysis, statistical and information-analytical methods, databases of the Ministry of Health of the Russian Federation, the Federal State Statistics Service of the Russian Federation were used. The epidemiological analysis of the main indicators of RD level and dynamics in the FEFD territory indicates the presence of regional differences in the registered morbidity, the degree of which is due to the natural-climatic and socio-demographic characteristics of the habitat. 77.8% of the region's subjects are in the zone of low morbidity. At the same time, the values of maximum and minimum levels of general and primary RD morbidity in the region differ by 2.2 and 2.4 times, respectively, becoming the most pronounced among the adult population (by 3.6 times). In chronic bronchitis and COPD, the regional gradients of the registered morbidity are 10.9 and 9.8 times, respectively. It was found that the values of the primary RD morbidity in children's population in the FEFD are 14.4% higher than at the federal level, and among the adult population the gradient of values has the opposite indicators: 24.9% lower. At the same time, if the incidence of pneumonia in the region is 15.2% higher than the incidence of pneumonia in the Russian Federation as a whole, the incidence of chronic forms of RD in the region is 17.3-28.9% lower than at the federal level. The level of primary RD morbidity in 2005-2016 in the Far Eastern Federal District increased by 23.3%, including bronchial asthma (by 20.3%) and COPD (by 47.7%), and the incidence of pneumonia significantly decreased. At the same time, the average annual rate of increase in primary RD morbidity is higher than in the Russian Federation as a whole. This is shown by the predictive model of morbidity dynamics, the linear trends of which are more progressive in the FEFD compared to the dynamics at the federal level. The rate of positive dynamics of morbidity, significantly exceeding the same rate of morbidity growth at the federal level, indicates an increase in the level of availability and quality of medical care for patients with pulmonological profile, timely and early detection of chronic forms of respiratory diseases, positive motivation of the population for treatment in medical organizations. These trends in the dynamics of the registered morbidity are due to the active introduction of effective methods of diagnosis and treatment of chronic respiratory diseases, preventive and educational programs implemented both at the federal and regional level.

To date, the role of dysfunction of the bronchial ciliated epithelium (BCE) in the formation of mucociliary disorders during cold exposure has not been fully established. The aim of the study was to investigate the nature and severity of changes in the ciliary motility of the BCE under the influence of a cold stimulus in vitro. Ten volunteers with asthma underwent a bronchoscopy with biopsy of the lobar bronchus mucosa. The biopsy specimens were placed in a Hank’s balanced salt solution (HBSS) on a slide, located on the thermal stage, used to simulate the effect of various temperature on the BCE. Ciliary beat frequency (CBF, Hz) was recorded using a microscope, high-sensitivity digital camera and computer with specially developed software. The initial recording of CBF was performed at 24ºC, after which the temperature of HBSS was gradually increased to physiological level and repeated recording was made at the control points (28ºC and 36ºC). Then, the temperature of the solution was lowered and CBF was registered again at 28ºC, 21ºC and 17ºC. The initial CBF of the BCE varied from 6.74 to 3.77 Hz with average of 5.25±1.48 Hz (M±m). There was a statistically significant increase in CBF when the solution was heated: at 28ºC it was 6.33±1.36 Hz (p=0.004) and remained at this level up to 36ºC – 7.14±1.33 Hz (p=0.002). A gradual decrease in the solution temperature produced a reduction in CBF in comparison with the physiological conditions: 28ºC – 6.12±1.31 Hz (p=0.121), 21ºC – 5.27±1.32 Hz (p=0.001) and 17ºC – 3.95±1.18 Hz (p=0.0001). By the end of the experiment, CBF of the BCE decreased almost 2-fold in comparison with the physiological conditions. A mathematical model that characterizes the behavior of BCE cilia under cold stress was developed. Thus, the results of the study demonstrate a marked decrease in the motor activity of the BCE cilia under cold stress, which underlines a significant contribution of the functional disturbance of BCE to the pathophysiological mechanisms of hypersecretory disorders induced by inhalation of cold air.

The contents of anti-influenza antibodies, secretory immunoglobulin A (sIgA) and circulating immune complexes (CIC) were studied in 145 women in the second trimester of pregnancy. All women were divided into 5 groups. The first group included 30 women with the physiologic course of pregnancy. The second one consisted of 30 patients with chronic simple bronchitis (CB) in remission. The third group had 30 patients with the exacerbation of CB caused by influenza A(H3N2) (antibody titers were 1:16-1:64); the fourth group included 30 patients with CB, whose exacerbation was caused by influenza (antibody titers were 1:32-1:128). It was found out that in the second group there were higher concentrations of sIgA (7.34±0.37 mg/L) and CIC (0.191±0.006 units of optical density), than in the first group (5.86±0.43 mg/L, p

The aim of the study was to determine the role of rs11562975 polymorphism of TRPM8 gene and tobacco smoking in the formation of severe bronchial obstruction in asthma patients. According to this aim, 416 patients with varying severity of asthma were examined. The study design included standard spirometry, genotyping of rs11562975 TRPM8 gene polymorphism and evaluation of the status and duration of smoking. The study revealed the detrimental effect of smoking on the respiratory function in patients with a pack/year index ≥10. rs11562975 polymorphism had a modulating effect on the smoking in patients with asthma. The influence of smoking ≥10 packs-years on the formation of severe bronchial obstruction was more pronounced among carriers of GC genotype, compared to patients with GG genotype. In case of pack-year history ≥20, the GC genotype significantly increased the risk of severe bronchial obstruction in the examined patients

The contents of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the blood serum were studied in 89 women in the first trimester of pregnancy. The first group (control) was made out of 25 women with uncomplicated pregnancy; the second had 23 women with the exacerbation of chronic simple bronchitis caused by parainfluenza of the 3rd type with antibody titer 1:16-1:64; the third one consisted of 21 patients with the exacerbation of chronic simple bronchitis induced by parainfluenza infection with antibody titers 1:32-1:128; the fourth group had 20 women with exacerbation of chronic simple bronchitis of parainfluenza etiology with antibody titer 1:64-1:256 at early stages of gestation. In the second group in comparison with the first one there were higher contents of IL-4: 21.1±2.00 pg/ml and INF-γ: 29.5±2.31 pg/ml than in the control group: 12.9±1.16 pg/ml (р

The features of postnatal development in 160 women with physiologic course of pregnancy and with chronic placental insufficiency in the second trimester of pregnancy in the patients infected with the herpes simplex virus type 1 (HSV-1) were studied. The first group (the control group) included 30 women with physiologic course of pregnancy. The second group had 41 patients with chronic placental insufficiency of herpes etiology. The third group consisted of 89 women with chronic placental insufficiency and the threat of premature delivery caused by HSV-1. It was found out that in neonatal period of development and in the course of the first year of life the patients of the third group unlike the women of the second group oftener had bottle feeding (30.3 and 9.8%, respectively, р

The effectiveness of medical care in most cases depends on the quality of informational exchange between the doctor and the patient. Often, selected models of the therapeutic interaction, which are the basis for the doctor-patient relationship and form a common psychological background of this communication are very important. The article presents a brief review of the main models of the therapeutic interaction in the foreign and domestic literature. Also we determined the most preferable of them. We showed the important role of doctor’s communicative competence, as well as the fact that possession of communicative skills allow them to solve medical-diagnostic and organizational problems more effectively while treating the patient. Also we studied the main components of effective interaction, promoting the formation of trust between the patient and the doctor.

The analysis of the implementation of prevention programs, using materials and methods of epidemiological and statistical monitoring of the population incidence of pneumonia and generalized regional experience of complex of organizational, methodological and control activities to prevention of pneumococcal disease in the territory of the Amur region. Pneumococcal conjugate vaccine "Prevenar-13" and flu vaccine were used for immunization against acute respiratory viral infections and pneumococcal infection. We take into account information about the rate of pneumonia and respiratory viral infections for the period from 2010 to 2015. To assess the effectiveness of vaccination we used indicators and specific criteria. Comparative statistical analysis revealed a high degree of efficiency of the regional programs with the use of methods of pneumococcal immunization: the coefficient of efficiency of preventive vaccination reaches 75-100% using the incidence of pneumonia as indicator. The incidence of pneumonia in vaccinated contingent decreased by 2.3 times for 2 years in the region.

The contents of anti-inflammatory and pro-inflammatory cytokines in 95 women in the first trimester of gestation were studied. The first (control) group included 25 women with physiologic course of pregnancy; the second group consisted of 25 patients with exacerbation of chronic simple bronchitis caused by influenza virus B (antibody titers were 1:16-1:64); the third group consisted of 24 pregnant women with exacerbation of chronic simple bronchitis under influenza virus В (antibody titers were 1:32-1:128); the fourth group consisted of 21 women with exacerbation of chronic simple bronchitis induced by influenza virus B (antibody titers were 1:64-1:256) at early stages of gestation. In the patients of the second group in comparison with the patients of the first group there was an increase of IL-4 till 19.7±2.17 pg/ml, of TNF-α till 33.4±3.09 pg/ml and of INF-γ till 30.9±2.64 pg/ml (in the control it was 12.9±1.16 pg/ml, р