The combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype wit1 dysregulation of pro- and anti-inflammatory cytokines as one of t1e leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1^st was healthy control (Normal); the 2^nd had allergic BA associated with CRSwNP; the 3^rd had nonallergic BA associated with CRSwNP; the 4^th had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORgt transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dys-regulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.

The need for safe and effective treatment is becoming increasingly urgent due to the high COVID-19 mortality rates observed worldwide. The choice of drug products for COVID-19 treatment regimens is based on the efficacy and safety data, the mechanism of action, and potential interactions. N-acetylcysteine's (NAC) pharmacological activity and its potential to suppress the progression of COVID-19 make it a promising therapeutic agent for COVID-19. Aim of the study was to evaluate the efficacy of NAC in the complex treatment of moderate COVID-associated pneumonia. Methods. The study included adult patients (n = 46) with moderate COVID-associated (the 2^nd degree on CT) pneumonia (age 57 (51; 71) years, body mass index - 30 (27.1; 32.3) kg/m², duration of the disease before hospitalization - 7 (6; 8) days, body temperature at the admission - 37.5 (37.1; 37.8)°С). The patients were randomized into two study groups. The 1^st group (n= 22) received standard COVID-19 treatment [1]. The 2^nd group (n= 24) additionally received NAC 1,200 - 1,500 mg/day intravenously. Treatment with NAC was started together with the standard therapy. Results. Our study showed that the inclusion of NAC in the complex treatment of moderate COVID-associated pneumonia led to a statistically significant increase in blood oxygen saturation, oxygenation index, the difference in delta increase in oxygenation index, a quicker reduction in the volume of lung damage and the difference between the groups in delta reduction of this index. Also, the rate of reduction of C-reactive protein and reduction of the duration of hospitalization in the group of patients who received NAC was statistically significantly more profound than in the standard treatment group. Conclusion. The study confirmed the effectiveness of NAC as a part of the complex treatment of moderate COVID-associated pneumonia.

The aim was to evaluate the ventilation inhomogeneity (VIH) by the multiple-breath nitrogen washout test (MBNW) after COVID-19 and to identify the relationship of the lung clearance index (LCI) with other functional parameters of the respiratory system. Methods. The cross-sectional study included 35 patients (97% men); the median age was 44 years. Spirometry, body plethysmography, diffusing capacity of the lung for carbon monoxide (DL_co), MBNW test, and impulse oscillometry were performed. Dyspnea was evaluated by mMRC scale. MBNW test was performed using the Easy-one Pro, MBW Module (ndd Medizintechnik AG, Switzerland). Results. The patients were divided into 2 groups. Group 1 included 21 (60%) patients who were not diagnosed with VIH. Group 2 included 14 (40%) patients with VIH. The median testing period was 72 (47 - 109) days from the onset of COVID-19. The median of the maximum volume of lung damage determined by high-resolution computed tomography (CT_max) was 50% in the acute period of the disease and 12% during the study. The medians of all analyzed parameters remained normal in the study cohort as well as in groups 1 and 2, except the resonance frequency (f_res) in group 2. Statistically significant differences were found between groups 1 and 2 in the absolute frequency dependence of resistance (R5 - R20), reactance area (A_X), f_res. Significant differences were also found in pathological changes of vital capacity, forced expiratory volume in the first second (FEV₁), (R5 - R20). The abnormalities were more common in group 2. A significant correlation was shown between LCI with the ratio of residual lung volume to total lung capacity, (R5 - R20), AX, fres, relative frequency dependence of resistance, CTmax, FEV1 and trasfer-factor (DL_co). Conclusion. Seventy-two days after the onset of CoVID-19, the ventilation inhomogeneity was detected in 40% of the patients, decreased DL_co - in 23%, airway obstruction - in 11.4%, and restrictive ventilatory defect - in 8.6%. Correlations were found between LCI and DL_co, spirometry parameters, body plethysmography, impulse oscillometry, and CT_max.

The article presents the results of a study of potential drug interactions in the treatment of moderate and severe community-acquired pneumonia (CAP) in hospital settings. The study was conducted by analysis of treatment standards and data from real clinical practice regarding antimicrobial therapy. Methods. The study used the lists of drug products for medical use for the treatment of CAP (according to the standards of specialized medical care for moderate and severe CAP with complications). Also, the medical records of patients (n = 165) with CAP, hospitalized in hospitals of medical organizations (Nizhny Novgorod) were used. The study period was 2 years (2015 - 2016). The study included all patients admitted to the hospital during the analyzed period. CAP was treated in accordance with treatment standards. Results. The analysis of potential interactions of drugs used for moderate and severe CAP according to the treatment standards, showed that 27 and 72 drugs can be used, respectively. 325 potential interactions are possible in hospital settings for moderate CAP and 2,485 for severe CAP. According to the treatment standard, the number of minimally clinically significant potential interactions during the pharmacotherapy of moderate CAP in hospital settings is 8, the number moderately clinically significant interactions - 19; undesirable interactions - 7. In case of severe CAP, the number of potential interactions increases and amounts to 27 minimally clinically significant, 105 moderately clinically significant, and 41 undesirable. The analysis of the results of antimicrobial therapy in real clinical practice showed 4 therapeutic duplications (prescribing 2 β-lactam antibacterial drugs simultaneously) and 2 moderately clinically significant interactions during antimicrobial therapy in hospital 1. Only 1 therapeutic duplication was noted during antimicrobial therapy in hospital 2. Therapeutic overlap has been found between β-lactam antibacterial drugs (ceftaroline fosamil and meropenem). It is advisable to prescribe no more than one в-lactam antibacterial drug and it is inappropriate to include > 3 antimicrobial drugs in an antimicrobial regimen. Conclusion. Electronic databases simplify the selection of medicines and thus ensure the safe and effective use of registered drug interactions.

The modern concept of development of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) implies the leading role of immune reactions with the true inflammatory autoimmune pathogenetic components. Aim of the study was to evaluate the autoreactivity in patients with chronic immune-mediated respiratory diseases: BA, COPD, and their combination — ACO. Methods. The study enrolled 155 patients with the average age of 49 ± 17 years old. We modified quantitative ELISA for detection of IgE and IgG4-autoantibodies using commercial tissue antigens of epithelial keratin, type III and VI collagen, myosin and elastin (Sigma, USA), conjugates of monoclonal anti-IgE or anti-IgG4 antibodies and IgE and IgG4 reference reagents (Dr. Fooke, Germany). Results. Concomitant COPD and BA symptoms were accompanied by significantly higher levels of IgE autoAbs to epithelial keratin, type III and VI collagen and myosin and were associated with a higher detection rate of these Abs, especially in severe forms of the disease (50 — 80%). The IgE-autoAbs to myosin increased in individuals with ACO as compared to BA and reached the maximum values in patients with COPD. There was an opposite trend: the frequency of detection and concentration of IgG4-autoAbs decreased with the disease severity. The levels of IgG4-autoAbs to type III and IV collagens and to elastin decreased as the obstruction worsened and were undetectable in patients with COPD and ACO. IgE and IgG4 autoAbs were inversely correlated to type VI collagen, type III collagen, elastin and myosin (r = -0.38; -0.61). The spirometry showed the inverse correlations between the increased IgE-autoAbs to type III collagen and high-speed ventilation parameters (R = -0.79; p = 0.01). So, IgE-autoAbs may be considered a factor of the progressive course of BA in combination with COPD associated with a significant bronchial obstruction. Conclusion. Thus, the detection of IgE and IgG4-AT to tissue antigens of collagen, elastin and myosin can be further used for clinical and immunological monitoring of BA and COPD, especially with their combined phenotype (ACO). The increased levels of IgE-autoAbs can be considered one of the immunological prognostic markers of intense remodeling processes in the bronchial wall. These processes are also confirmed by an increased IgE-mediated immune response to miosine and elastine EG in patients with the severe disease. The developed assay of the level of autoAbs to tissue antigens can be used in the early diagnostics of adverse course of asthma, especially ACO, and can be used as a laboratory criterion of the control over the disease when making decisions on personalized pharmacotherapy and patient management.

Tobacco smoking is one of the most widespread and at the same time difficult to control risk factors for chronic noncommunicable diseases, which make the most significant contribution to the mortality. Smoking intensity, development of airflow restrictions, and damage to vascular endothelium are connected to the accelerated development of atherosclerosis. At the same time, there is no evidence of a possible relationship between the development of myocardial dysfunction and exposure to tobacco combustion products. It is of interest to study the incidence of airflow restrictions, arterial hypertension, and markers of early damage to target organs - the brachiocephalic arteries (BCA) and myocardium, in so-called relatively healthy smoking individuals. The aim of the study was to describe the incidence of airflow restrictions, hypertension, the state of the brachiocephalic arteries, and indicators of global and regional longitudinal strain of the left ventricle (GLSLV and RLSLV) in actively smoking conditionally healthy individuals. Methods. 100 active smokers were examined (smoking person index or ICH > 10 (17 ± 2 packs/year)) at the mean age of 48,80± 0,68years. 55% of the patients were male. The diagnosis of COPD was made based on spirometry values before and after the test with bronchodilators (400 mcg of salbutamol) (FEV1/FVC < 70% and FEV1 increase <12% of the initial values). Blood pressure measurement, duplex scanning of brachiocephalic arteries, transthoracic echocardiography with GLSLV and RLSLV with 17-segment division by Strain method were performed in all patients. Results. COPD was diagnosed in 35% of the patients, hypertension - in 45%. Evaluation of BCA showed increased thickness of intimamedia complex in the patients with hypertension (р= 0.002) and a significantly higher degree of stenosis and number of plaques in patients with concomitant COPD and hypertension. Type 1 diastolic dysfunction of LV was detected both in patients with hypertension and in the patients with COPD, but it was most common in the patients with concomitant COPD and hypertension. The GLSLV values did not change in all patients, but the RLSLV values depended on the segment (basal, medial, apical) and were significantly lower in the patients with concomitant COPD and hypertension. Conclusion. Tobacco combustion products not only are risk factors of airflow restriction and systemic vascular dysfunction, but also cause preclinical myocardial damage, a marker of which is a violation of the longitudinal strain of the left ventricle.

Achieving the control of bronchial asthma (BA) in real clinical practice remains an unresolved problem, despite the expansion of therapeutic options in this area. Guidelines about when and for whom should a particular treatment be used continue to develop. Increasing of inhaled corticosteroid dose (ICS) in combination with a long-acting β₂-agonist (LABA) does not always lead to the desired result, although a combined LABA-ICS inhaler could improve the course of asthma and increase adherence. The addition of tiotropium bromide to LABA-ICS requires the use of two inhalers. The targeted biological therapy is associated with the complexity of phenotyping and is possible only in specialized medical centers. Mometasone furoate, indacaterol acetate, and glycopyrronium bromide in fixed doses were combined in Breezhaler® inhaler for asthma maintenance therapy once per day. This way of treatment helps to realize full potential of maintenance inhalation therapy of bronchial asthma and to simplify the achievement of control over the disease in routine clinical practice.

Chronic obstructive pulmonary disease (COPD) is the leading cause of death in the structure of respiratory diseases. The problem of rational pharmacotherapy of COPD have attracted attention of the medical scientific society for many years. The understanding of the pathogenesis of the disease has deepened and approaches to the therapy have changed. Some COPD patients need regular fixed-combination therapy: long-acting bronchodilators (LABD) and inhaled corticosteroids (ICS) in order to prevent exacerbations and reduce the severity of symptoms of the disease. Blood eosinophils count is one of criteria for choosing regular therapy. The appearance of fixed triple combinations of ICS/LABD increased the effectiveness of COPD therapy, and a new delivery device for fixed combination of budesonide/formoterol makes it possible to use ICS successfully in the most severe patients.

Hypersensitivity pneumonitis (HP) is an inflammatory disease of the lungs and airways that develops in response to repeated inhalation of a wide range of aerosol antigens. The clinical picture and course of HP are highly variable and depend on such factors as the nature of the antigen, the intensity and duration of exposure to the antigen, as well as on the characteristics of the patient's immune response. The annual incidence of HAP is 1.28 -1.94 cases per 100 000. Currently, the diagnosis of HP is usually based on the characteristic clinical picture, high-resolution computed tomography (HRCT) data, bronchoscopy, lung biopsy, and evidence on the antigen. HRCT plays a central role in the diagnosis of HP. The most common finding on HRCT in HP is ground-glass opacities, which can be associated with centrilobular nodules and air trapping. In some cases, the fibrotic HP signs are very similar to those of idiopathic pulmonary fibrosis (IPF), and most changes are found in the lower regions and subpleurally. Therapy for HP usually includes avoiding exposure to the antigen, considering corticosteroids (CS) and/or immunosuppressive therapy to suppress the active inflammatory/immune response, and treating comorbidities. Nintedanib therapy in patients with progressive fibrotic HP results in a slower decline of lung function compared to placebo.

The scientific review provides current information on the current epidemiological status of tuberculosis in our country and the world, genetic adaptability and the evolution of Mycobacterium tuberculosis. The well-known and recently discovered molecular targets of aggression of this microorganism are described, and possible methods of circumventing the resistance of the Office to existing and developed drugs are presented. Objective: to create a scientific analytical review, which allows you to form an idea of the basic principles of development of the mechanisms of drug resistance of M. tuberculosis, as well as ways to overcome them with the possibility of further development of the chosen direction with the involvement of reputable scientific groups and practical implementation. Methods. scientific analysis of international reports, highly indexed scientific articles and clinical protocols. Results. Ihanks to the conducted analytical work, critical biological markers of M. tuberculosis immunity to anti-tuberculosis therapy were identified, which protect it from pharmacological intervention by the person and do not adequately sanitize the centers of inflammation in the patient's body. Methods have been proposed for disintegrating the mechanisms of drug resistance, which will bring the algorithms for treating tuberculosis infection to a new level. Conclusion. The analyzed information will contribute to deepening and expanding the knowledge of specialists involved in the fight against tuberculosis about the importance of implementing a personalized approach in the provision of medical care to TB patients, taking into account the studied molecular indicators of resistance to standardized and developed drugs.

Treating dyspnea in patients with idiopathic pulmonary fibrosis is a challenge. The foreign experience of using low doses of opioids to relieve dyspnea in patients with progressing diseases is controversial among Russian specialists. The presented clinical case is an 83-year-old patient with idiopathic pulmonary fibrosis in the terminal stage and refractory dyspnea, progressive respiratory failure of II - III degrees, and concomitant exertional angina II FC and organic anxiety disorder. The patient was offered low-dose morphine injections (2 mg 5 times a day subcutaneously) to relieve the shortness of breath. The patient, who had not previously received opioids, and his relatives gave prior consent to the use of morphine. Within a week from the moment of hospitalization, the general and psycho-emotional state of the patient improved, dyspnea decreased, and night sleep was partially normalized. However, а week later, being in a severe but relatively stable condition, the patient died from a massive nosebleed. Shown, that the traditional approach to reducing dyspnea and the associated agitation in patients with interstitial lung disease is the use of corticosteroids and psychotropic therapeutics in increasing doses. The use of low doses of opioids to relieve dyspnea in patients with non-cancer disease meets many organizational, medical, and psychological barriers. At the same time, this therapy is recognized as successful and safe in the foreign palliative practice. Overcoming the existing barriers based on the evidence from clinical trials, as well as the domestic and foreign clinical practice of the safe use of low doses of opioids would expand the arsenal of effective treatments for refractory dyspnea.

This article discusses voluntary informed consent (VIC), a prerequisite for any medical intervention. The article touches upon the history of this issue in modern health care and medical science. The role of the Nuremberg Code is emphasized, which is the basis for the Universal Declaration of Human Rights, the Code of Medical Ethics of the World Medical Association, and the Declaration on Bioethics and Human Rights. These documents helped define the world order after the end of World War II. The first part of the article reflects the history of the concept of VIC, while the second outlines the modern ethical views on this issue.