The use of monoclonal antibodies against interleukin-6 (IL-6) receptors is considered as a potential method of treatment and prevention of complications of the new coronavirus infection 2019 (COVID-19), based on reducing the intensity of the cytokine storm. The aim. To assess the relationship between the use of IL-6 blockers and the risk of tracheal intubation in patients with severe pneumonia associated with COVID-19. Methods. The retrospective cohort study included patients over 18 years of age admitted to the intensive care unit (ICU) with confirmed COVID-19 infection, lung tissue damage of at least 25% between November 4, 2020 and December 25, 2020. All patients underwent standard therapy in accordance with the current recommendations of the Ministry of Health of the Russian Federation, including IL-6 blockers in some patients. The primary endpoint was tracheal intubation and initiation of mechanical ventilation (MV). Data on the use of IL-6 inhibitors, baseline demographic, clinical and laboratory characteristics, as well as information on tracheal intubation, fatal outcomes and length of hospitalization were obtained from the unified medical information and analytical system of the city of Moscow. To analyze the relationship between the use of IL-6 blockers and endpoints adjusted for baseline characteristics, a multivariate Cox proportional hazards model was used. Results. The study included 242 patients, in 120 (49.5%) of them IL-6 blockers were used. The independent predictors of tracheal intubation were the degree of lung tissue damage, ferritin and diabetes, while the use of IL-6 blockers was not associated with a decrease in the risk of intubation: hazard ratio (HR) 0.96 (95% confidence interval [CI] 0.63 – 1.48) and death: HR 1.05 (95% CI 0.69 – 1.62). Subgroup analysis showed that, among surviving patients, the use of IL-6 blockers was associated with an average decrease in hospital stay by 3 days (95% CI 1 – 6 days). Conclusion. The use of IL-6 blockers was not associated with a decrease in the risk of tracheal intubation or death. Among surviving patients, the use of IL-6 blockers was associated with a decrease in the length of hospital stay. These findings may contribute to medical decision making during COVID-19 pandemic associated high hospital workload.

This document provides clinical recommendations for the management of severe asthma. Comprehensive evidence syntheses, including metaanalyses, were performed to summarise all available evidence relevant to the European Respiratory Society/American Thoracic Society Task Force’s questions. The evidence was appraised using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach and the results were summarised in evidence profiles. The evidence syntheses were discussed and recommendations formulated by a multidisciplinary Task Force of asthma experts, who made specific recommendations on six specific questions. After considering the balance of desirable and undesirable consequences, quality of evidence, feasibility, and acceptability of various interventions, the Task Force made the following recommendations:

• suggest using anti-interleukin (IL)-5 and anti-IL-5 receptor α for severe uncontrolled adult eosinophilic asthma phenotypes;
• suggest using a blood eosinophil cut-point ≥150 μL⁻¹ to guide anti-IL-5 initiation in adult patients with severe asthma;
• suggest considering specific eosinophil (≥260 μL⁻¹) and exhaled nitric oxide fraction (≥19.5 ppb) cut-offs to identify adolescents or adults with the greatest likelihood of response to anti-IgE therapy;
• suggest using inhaled tiotropium for adolescents and adults with severe uncontrolled asthma despite Global Initiative for Asthma (GINA) step 4 – 5 or National Asthma Education and Prevention Program (NAEPP) step 5 therapies;
• suggest a trial of chronic macrolide therapy to reduce asthma exacerbations in persistently symptomatic or uncontrolled patients on GINA step 5 or NAEPP step 5 therapies, irrespective of asthma phenotype;
• suggest using anti-IL-4/13 for adult patients with severe eosinophilic asthma and for those with severe corticosteroid-dependent asthma regardless of blood eosinophil levels.

These recommendations should be reconsidered as new evidence becomes available.

The study is devoted to the challenge of interpreting the lung damage associated with COVID-19 in children and the necessity for antimicrobial therapy in this disease. The aim of the research was a comparative analysis of clinical, radiological and laboratory signs in children with COVID-19 and community-acquired pneumonia (CAP). Methods. The observational comparative study included medical records of 53 children with the lung damage at the age of 1 year 4 months up to 17 years old, hospitalized for the period from June to August 2020. All children were tested for Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) by polymerase chain reaction (PCR). 34 patients with SARS-CoV-2⁺ were diagnosed with COVID-19 and 19 children with SARS-CoV-2^– were diagnosed with CAP. The assessment included medical history, clinical, laboratory and radiological changes. Results. Distinctive reliable clinical, laboratory, and X-ray signs of lung damage in COVID-19 compared to CAP were olfactory impairment (26%), bilateral lung damage (23%), erythrocytosis, leukopenia (20.6%), granulocyto- and monocytopenia, lower levels of reactive protein (CRP). Irrational prescribing of antibiotics (94%) was detected in the group of patients with COVID-19. Conclusion. We established the reliable clinical, laboratory and radiological features of COVID-19 in children, which indicate the viral nature of lung damage.

Aim. To assess the prevalence and clinical and functional features of a new coronavirus infection (COVID-19) in patients who underwent pulmonary thromboendarterectomy (PTE) using data from a single-center registry. Methods. This study included 127 patients with chronic thromboembolic pulmonary hypertension who underwent PTE from January 2016 to March 2020 and were included in a follow-up group. The follow-up after surgery was 6 or more months. The prevalence of COVID-19 and clinical and functional properties of the cardiorespiratory system were assessed in the study group. Results. The average follow-up period after PTE in the study group was 2.5 ± 0.9 years. 14 (11%) deaths not associated with COVID-19 were reported during this period. 5 cases of COVID-19 were detected among the remaining 113 patients. In one case, the infection was asymptomatic, while other patients had the typical clinical symptoms and developed bilateral polysegmental pneumonia. No patients required mechanical ventilation or died of COVID-19. All patients who underwent PTE were compliant with anticoagulation therapy and PAH-specific therapy for residual pulmonary hypertension. No adjustment of PAH-specific and anticoagulation therapy was required during COVID-19. Conclusion. The prevalence of COVID-19 in patients who underwent PTE was 4.4%, no deaths were recorded. Outpatient follow-up and timely informing of patients undergoing PTE allow keeping the COVID-19 morbidity and mortality in the studied group at the general population level. Evaluation of the impact of chronic anticoagulants and PAH-specific therapy on the outcome of COVID-19 deserves further research.

Aim. Assessment of the role of cytokine-mediated changes in the development of respiratory muscle (RM) dysfunction in patients with community-acquired pneumonia (СAP). Methods. 84 men aged 18 – 26 years with a median of age 19.5 [18.4; 22.8]. Mild to moderate CAP (MCAP) was diagnosed in 62 (73.8%) patients and severe (SCAP) in 22 (26.2%). The expiratory (MEP, MRPD_out) and inspiratory (MIP, MRPD_in. SNIP) strength indices of RM were recorded on a MicrоRPM apparatus (CareFusion, UK). The severity of endogenous intoxication was verified using the following indices: hematologic (HII), leukocyte (LII), and nuclear. Serum concentrations of interleukins-2, -8, -10, basic fibroblast growth factor, transforming growth factor-beta, tumor necrosis factor-alpha (TNF-α), and a soluble receptor for TNF-α. Data processing was performed by cluster and correlation analysis methods. Results. Three clusters of patients with CAP were identified by the characteristic combinations of indicators of RM strength, endogenous intoxication, and cytokine status. The first cluster had MCAP, the second – both MCAP and SCAP, the third – SCAP. In the first cluster, dysfunction of expiratory RM prevailed, and in the second and third – dysfunction of inspiratory RM. In the midst of CAP, significant negative correlations of RM strength indicators with LII, HII, TNF-α, IL-10, IL-8, and IL-2 levels were recorded. The endogenous intoxication indices reached control values in all patients during recovery. The first cluster showed a decrease in the level of analyzed cytokines against isolated dysfunction of expiratory RM. The second cluster showed a tendency toward restoration of TNF-α and IL-8 levels, and only their SNIP index was normal. The third cluster showed minimal medians of RM strength against the continuing imbalance in the profile of pro- and anti-inflammatory cytokines during recovery. Conclusion. RM dysfunction in CAP is associated with cytokine-mediated dysfunction. The degree of cytokine involvement in this process depends on the severity of endogenous intoxication and the volume of alveolar inflammation.

Asthma is one of the most common and socially significant human diseases. To date, spirometry is included in most recommendations as the gold standard for the diagnosis of obstructive disorders. However, in real clinical practice, this procedure does not always reveal signs of bronchial obstruction, not only in the early stages of the disease but also in more severe controlled bronchial asthma. Tests of oscillatory mechanics are increasingly being used to detect early violations of the pulmonary ventilation function. These tests are based on the forced oscillation technique, and the latest modification is impulse oscillometry system. The aim of this study was to investigate the capabilities of impulse oscillometry in diagnosing early changes in the function of the respiratory system in patients with asthma and identifying the most informative parameters of the method. Methods. A total of 146 patients with an established diagnosis of mild and moderate asthma were examined during remission. The patients were divided into 2 groups by the severity of asthma. The comparison group included 40 people with no signs of lung abnormalities. Results. Disorders of the pulmonary ventilation function were found in 23% of patients with asthma by spirometry, in 42% by bodypletismography in 42%, and in 72% of patients by impulse oscillometry. Impulse oscillometry system revealed obstructive changes localized in the central respiratory tract in 11% of patients, and obstruction of mixed localization was found in 6% of respondents. Peripheral respiratory tract disorders were diagnosed in 56 % of patients. Most respiratory tract lesions were located in the small bronchi in both groups. The obstructive disorders in large bronchi and generalized obstruction were observed more often in the 2^nd group. Among impulse oscillometry parameters, the increase in Delta (R_rs5 – R_rs20) was most often recorded in both examined groups of patients with asthma. Conclusion. Compared to standard methods, impulse oscillometry system is more sensitive. Therefore, it has advantages in diagnosing respiratory system dysfunctions both in the early stages of asthma and in more severe cases during remission.

Obstructive sleep apnea (OSA) is a common disease. The incidence is higher in patients with chronic obstructive pulmonary disease with moderate to severe bronchial obstruction or hypoxemia. OSA is associated with increased risks of fatal outcomes of acute cardiovascular diseases in such patients. Objective. To assess the effect of long-term non-invasive ventilation of the lungs in the spontaneous breathing mode with positive airway pressure (CPAP) on the indicators of systemic inflammation, insulin resistance, and thrombogenic risk together with clinical outcomes during the rehabilitation period after an exacerbation in patients with concomitant chronic obstructive pulmonary disease and obstructive sleep apnea who do not need long-term oxygen therapy. Methods. The effects of long-term CPAP therapy as a part of complex treatment were analyzed in an openlabel, prospective, comparative six-week study that enrolled 65 patients with concomitant chronic obstructive pulmonary disease and obstructive sleep apnea. The main group included 26 people who received CPAP therapy as a part of complex treatment. The comparison group included 39 people who did not use non-invasive ventilation of the lungs. The patients’ age was 55.5 ± 2.1 years in the main group and 57.1 ± 1.5 years in the comparison group (p > 0.1). Men prevailed in both groups – 92.3% in the main group and 100.0% in the comparison group (p > 0.1). Results. The clinical efficacy of CPAP therapy was confirmed by an improvement in the quality of life of patients on the SF-36 questionnaire, a decrease in the degree of daytime sleepiness on the Epworth scale (Johns, 1991). CPAP-therapy was associated with a drop in the serum levels of tumor necrosis factor α and the blood level of endothelin 1, a more pronounced decrease in the levels of C-reactive protein, interleukin 8, C-peptide, vascular endothelial growth factor, homocysteine versus the comparison group. Conclusion. The use of CPAP-therapy in patients with concomitant chronic obstructive pulmonary disease and obstructive sleep apnea who do not need long-term oxygen therapy during the rehabilitation period after an exacerbation is associated with a decrease in systemic inflammation, vascular endothelial dysfunction, and hyperhomocysteinemia.

The aim of the study was to evaluate various methods of osteoporosis diagnostics (FRAX® and Dual-energy Х-Ray absorptiometry – DXA) and the sequence of their application in the diagnostic algorithm in COPD patients without a history of large bone fractures. Methods. Cross-sectional study of 115 COPD patients without exacerbation (93 men and 22 women, mean age 67.2 ± 7.1 years). The study included clinical examination, FRAX®  estimation and comparison of the 10-year probability of a major osteoporotic fracture (MOF) with the Russian intervention threshold, spirometry, DXA of lumbar spine and proximal femur, semi-quantitative radiographic morphometry by Genant. All patients were examined using several methods that are possible in clinical practice: 1) FRAX® without DXA; 2) FRAX® + DXA in patients with intermediate 10-year probability of MOF and recalculation of FRAX® probability including femoral neck bone mineral density (BMD); 3) FRAX® + DXA in patients with intermediate 10-year probability of MOF. Take into account DXA results; 4) DXA without FRAX® ; 5) DXA + recalculation of FRAX ® for individuals with normal BMD or osteopenia. Results. In the whole sample of patients 1 – 5 diagnostic methods revealed 5.1, 7.0, 15.7, 44.3, 45.2% of individuals with osteoporosis, respectively. In men, the methods using FRAX ® (1 – 3) gave unsatisfactory results – the number of patients requiring treatment did not exceed 4.3%, while DXA revealed osteoporosis in 43%. FRAX® + DXA analysis in patients with intermediate 10-year probability of MOF (3 th method) was the best for women. The main independent predictors of low bone mineral density were post-bronchodilator FEV 1 ≤ 30% predicted and/or long-term oral glucocorticoid use. Asymptomatic vertebral fractures were detected in 11 patients. Before the radiographic morphometry, treatment would have been prescribed only 1 patient for the 1^th or 2^th methods; 5 patients – 3^th method and 9 patients using 4^th or 5^th methods. Conclusion. The use of the Russian FRAX® model in men with COPD revealed a very low percentage of people who need osteoporosis treatment; DXA was the optimal diagnostic method. If it`s not possible to perform DXA in the most COPD patients, it should be prescribed to people with very severe bronchial obstruction and/or taking long-term oral glucocorticoid therapy. Regardless of the BMD parameters, semi-quantitative X-ray morphometry should be performed to diagnose asymptomatic vertebral fractures.

In the last decade, significant research has been focused on Toll-like reseptors (TLRs) in the pathogenesis of respiratory diseases. The presented data show that TLR-mediated signaling can be directed both at the successful alleviation of the inflammatory reaction in the respiratory tract, and at its development and aggravation. Asthma is a chronic inflammatory disease of the respiratory tract caused by genetic factors, allergens, or microbial agents. TLRs play an important role in the pathogenesis of asthma. TLRs recognize a wide range of microbial molecules, endogenous molecules, and air allergens and modulate the allergic sensitization. An important feature of TLRs is their participation in the development of an immune response to viral and bacterial infections that cause severe exacerbations of asthma. TLRs are expressed on hematopoietic and non-hematopoietic airway cells, which play an immunomodulatory role in the development of asthma when activated by TLRs agonists. Due to the involvement of TLRs in innate and adaptive immunity and the ability to regulate adaptive Th-response, these receptors are currently being used as possible targets for drug development. Therefore, understanding the mechanisms and ways in which TLRs are involved in the pathogenesis of asthma may suggest new strategies for controlling the disease.

The new coronavirus infection COVID-19 has highlighted the importance of ongoing support for innate antiviral immunity systems. The aim. Conduct a systematic review of publications on the research of the use of B vitamins to support immunity and rehabilitation of patients with COVID-19. Methods. Intelligent analysis of so-called Big Data and special computational methods for analyzing Big Data of biomedical publications, based on the topological theory of sentiment analysis of medical texts from PubMed/MEDLINE. Results. Low levels of B vitamins contribute to chronic comorbidities and aggravate the clinical course of COVID-19 significantly. Increasing the supply of B vitamins in COVID-19 patients is essential for the maintenance of energy and oxygen metabolism; the direct antiviral effects of vitamins (reduction of SARS-CoV-2 replication); compensation of chronic comorbidities (thromboembolism, impaired liver and kidney functions, diabetes mellitus, polyneuropathy), which aggravate the course of COVID-19; reducing hyperhomocysteinemia and chronic aseptic inflammation; inhibiting carbonic anhydrases to improve oxygen metabolism in the lungs, and increasing the clearance of lactate from the blood and preventing sepsis. Conclusion. By improving myelination of the olfactory sensory neurons, vitamin B₁₂ can help overcome anosmia, which occurs in 80% of COVID-19 patients. Short courses (up to 2 – 3 weeks) of high-dose parenteral therapy with thiamine, pyridoxine, and cyanocobalamin can be used as a part of a complex of therapeutic measures to improve clinical outcomes in patients with COVID-19, especially in elderly patients with polyhypovitaminosis, diabetes mellitus, hyperhomocysteinemia, thrombophilia, and high risk of sepsis. Oral therapy with thiamine, pyridoxine, and cyanocobalamin is justified as a part of rehabilitation measures after COVID-19 in patients who have faced its consequences in the form of clinical signs of vitamin B vitamin deficiency.

Therapeutical options for the treatment of chronic obstructive pulmonary disease (COPD) have significantly expanded in recent years, primarily due to market entry of new combination drugs. One of the commonly used therapeutic options for patients with frequent exacerbations of COPD is a triple combination, including LABA, LAMA and ICS, however, prescribing such therapy, doctors often face a decrease in treatment adherence, which ultimately leads to lack of effectiveness, as well as with an increased risk of adverse events. This article presents the current information on the clinical efficacy and safety profile of a fixed triple combination of beclomethasone dipropionate, glycopyrronium bromide and formoterol fumarate, available as extrafine aerosol inhaler, allows to optimize inhalation treatment for patients with frequent exacerbations of COPD.

Among the extensive list of manifestations of post COVID syndrome, cough is often found. Most researchers interpret its character as post infection. In some patients, post infection cough becomes productive, and combined mucoactive therapy is required for effective treatment. Since the onset of the pandemic, clinical descriptions of spontaneous pneumothorax have accumulated in the literature. The risk of this complication is present even in patients who are not burdened with chronic lung diseases, as well as those who are breathing spontaneously. The study of the mechanisms of development of spontaneous pneumothorax in COVID-19 is necessary for the development of further therapeutic and preventive measures. Traction bronchiectasis occurs in 27 – 52.5% of cases of new coronavirus infection. Changes in the structure of the bronchi predispose to chronic cough and recurrent infections. Respiratory viral infection has been considered in the past as a trigger for bronchial asthma. There is controversy over the new coronavirus. Asthma has been suggested as a protective factor in COVID-19, due to the specific inflammation profile that protects patients. In some patients who have had COVID-19, the cough is due to hyperventilation syndrome. To explain it, a hypothesis of impaired respiratory control was proposed. The paper presents clinical examples illustrating a wide range of pathological conditions accompanied by cough. Possible relationships between cough and previous coronavirus infection are discussed.

The described clinical case shows the challenges in the differential diagnosis of primary diffuse large B-cell lymphoma of the lung. It has been shown that the diagnosis can be made only by a morphological examination of a biopsy specimen, and the specimen should be representative and allow for full histological and immunohistochemical testing. A correct diagnostic algorithm, an interdisciplinary approach, the use of new technologies, particularly radiation imaging methods, to reliably determine the primary localization and spread of the pathological process, biopsies for the morphological confirmation shorten the time to diagnosis. A quick diagnosis improves the treatment outcomes and affects the quality of life and life expectancy of patients.

Systemic scleroderma is a systemic autoimmune disease that affects multiple organs, including the bronchopulmonary system. The disease leads to progressive pulmonary fibrosis, which is the most common cause of death. Hence, standard therapy of systemic sclerosis should be supplemented with antifibrotic therapy. The article describes a clinical case of the efficacy of a combination of standard therapy with the tyrosine kinase inhibitor nintedanib in a patient with systemic scleroderma and a progressive phenotype ILD. The patient was taking nintedanib in combination with standard therapy (methylprednisolone, mycophenolate mofetil) for 7 months and showed improvement on CT in the form of a significant decrease in the ground glass lesions. In addition, bodyplethysmography showed a decrease in restrictive changes in the external respiration (an increase in the total lung capacity from 49 to 57%), an improvement in the lung diffusion capacity (an increase in total diffusion from 47 to 53%). This clinical case demonstrates the high efficacy of antifibrotic drug nintedanib in the complex therapy of patients with systemic scleroderma and progressive pulmonary fibrosis. Nintedanib increases the efficacy of basic therapy and improves the prognosis.