Some patients with severe community-acquired pneumonia develop fatal complications in the form of acute respiratory distress syndrome and/or septic shock despite the timely adequate antibacterial therapy and presumably due to an excessive uncontrolled systemic inflammatory response and inadequate adrenal response to infection due to the critical illness-related corticosteroid insufficiency (CRICI). Therefore, the additional use of systemic corticosteroids can significantly improve the survival of patients with severe community-acquired pneumonia.

Aim. To present the most current preclinical and clinical studies and meta-analyses assessing the effectiveness and safety of the use of systemic corticosteroids for communityacquired pneumonia.

The results of these studies demonstrate that the most optimal regimen for the use of systemic corticosteroids in terms of risk and benefit is early (the first 3 days), low-dose (the dose equivalent of 6 mg/day dexamethasone) short-course (5 – 7 days) therapy with immediate withdrawal of the drugs. This regimen produces the best effect in patients with severe community-acquired pneumonia who require ventilation (invasive or non-invasive) with PEEP ≥ 5 cm H₂O or high-flow oxygen therapy with FiO₂ ≥ 50% and a PaO₂/FiO₂ ratio less than 300 and/or vasopressor support.

Conclusion. Currently, the federal clinical guidelines do not recommend the routine use of corticosteroids in adult patients with community-acquired pneumonia, with the exception of patients with refractory septic shock. However, this narrative review presents evidence supporting the use of adjunctive corticosteroid therapy in adult patients with severe community-acquired pneumonia, particularly when complicated by septic shock, acute respiratory distress syndrome, comorbid asthma and/or chronic obstructive pulmonary disease, provided there is no pulmonary suppuration, severe influenza or mycotic infection. Undoubtedly, this is a compelling argument in favor of revising existing domestic clinical guidelines regarding the use of systemic corticosteroids. Thus, further research is needed to identify subgroups of patients who may benefit from or potentially be harmed by corticosteroids. In addition, it is necessary to determine the optimal regimen for the use of corticosteroids in terms of specific drugs, their dose, routes of administration, frequency and duration of therapy, as well as the withdrawal.

Currently, the most effective approach to treating patients with severe uncontrolled asthma is the use of biologicals. These treatments are highly effective and safe, but not universal. Different biologicals block various parts of asthma pathogenesis. Also, biologicals have different effectiveness in relation to comorbidities. In this regard, the targeted therapy selection should be personalized, endotypeand phenotype-oriented.

The aim of this review was to analyze the literature data on methods for personalized biologicals’ selection in patients with severe asthma that are currently used in clinical practice, as well as new prospects in this area.

Conclusion. Laboratory and instrumental examination methods currently used for endoand phenotyping of severe asthma help in identifying the key pathogenetic factor in the disease development that serves as a basis for selection of the biological. However, biomarkers identified during routine examination are not absolute and are prone to exceptions. Also, the targeted therapy selection is based on a subjective determination of the prevailing pathogenetic mechanism when a patient with severe asthma has a mixed disease phenotype and meets the criteria for prescribing all available biologicals. Therefore, the search for biomarkers that predict the effect of a particular biological remains a relevant direction for future studies. The combined use of clinical, molecular-genetic examination results and evaluation of epigenetic markers can help in solving this problem. This review provides current data on the biologicals used in severe asthma treatment, the phenotyping and endotyping tools used in real practice, and also describes promising areas of the epigenetic biomarkers research.

High incidence of respiratory diseases (RD) makes monitoring of the associated morbidity and mortality in the Russian population important for the public health.

The aim was to study the incidence, disability and mortality rates associated with RD in 2016 – 2021 by federal districts of Russian Federation.

Methods. Statistical data from the Ministry of Healthcare of the Russian Federation and Federal State Statistics Service was used.

Results. There was an increase in the RD morbidity by 12.0% from 2019 to 2021 (from 40,694.7 to 45,560.7 per 100 thousand population, p < 0.001), and a 3-fold increase in the incidence of pneumonia. The RD incidence increased in all federal districts, with the maximum in the Northwestern Federal District (2021 – 55,680.9 per 100 thousand population). An increase in the RD-associated mortality rates (MR) by 95.8% was recorded from 2019 to 2021: from 40.3 to 78.7 deaths per 100,000 population. In 2021, the proportion of pneumonia in the structure of MR was 65.3%, and the hospital mortality due to RD increased. The proportion of people with primary disability due to RD decreased in 2021. The COVID-19 (COronaVIrus Disease 2019) incidence rate has been registered since 2020 (2020 – 3,391.1, 2021 – 8,085.7 cases per 100 thousand population). The MR associated with COVID-19 reached 98.8 per 100,000 population in 2020 and 319.1 per 100,000 population in 2021.

Conclusion. In the period 2019 – 2021, there were an increase in the RD incidence in the Russian population, mostly due to pneumonia. The RD incidence and pneumonia incidence reached the maximum in 2021, which required expansion of the healthcare capacities at short notice.

Lipopolysaccharide (LPS) from gram-negative bacteria is considered a pathogenetic factor of many diseases. It is also known to include exacerbations of chronic obstructive pulmonary disease (COPD), but this effect has been little studied in stable COPD.

The aim of the study was to evaluate the relationship between serum LPS levels and inflammatory markers, clinical and functional characteristics of COPD without exacerbation.

Methods. The pilot study included 29 patients with COPD who did not have any exacerbations requiring antibacterial therapy or systemic steroids for 3 or more months and 27 patients without respiratory diseases, matched by age and gender (63.9 ± 6.3 years, 69% men). All patient data were taken from the database of National Medical Research Center for Therapy and Preventive Medicine. The differences were considered statistically significant at p < 0.05; and a trend (change of variables in one direction requiring further investigation) at p ≥ 0.05 – 0.075.

Results. The COPD group showed a tendency towards a lower LPS level (p = 0.062). The levels of TMAO and CRP were significantly lower in the control group (p < 0.05), and the fibrinogen and leukocyte levels did not differ. In the COPD group, a direct correlation was found between the LPS level and quality of life according to the CAT (COPD Assessment Test™) (r = 0.43; p = 0.019), an inverse correlation with the spirometry parameters (p < 0.05), and a trend towards an association between LPS and age (r = –0.34; p = 0.075), body mass index (r = 0.34; p = 0.072), waist circumference (r = 0.35; p = 0.064), and smoking status (r = 0.35; p = 0.061). No such relationships were seen in the control group. No relationship with exacerbations of COPD was found during the prospective follow-up (12 months).

Conclusion. The level of LPS tends to differ between patients with stable COPD and patients without COPD, and correlates with severity of symptoms and lung function impairment in COPD patients. Further larger studies in this area are advisable.

Aim. To conduct a comparative assessment of clinical, functional and laboratory parameters in patients with COPD and pulmonary tuberculosis with and without HIV infection.

Methods. 160 patients with COPD and pulmonary tuberculosis were examined, including 80 with HIV infection and 80 without HIV infection. The patients were hospitalized in the State Budgetary Healthcare Institution “City Anti-Tuberculosis Dispensary” (Saint Petersburg). The clinical symptoms (shortness of breath according to the mMRC, CAT), laboratory parameters, the viral load (the number of virus copies and CD4 cells in 1 ml of blood and as a percentage of lymphocytes) and the lung function were assessed.

Results. All examined patients had severe COPD with 2 or more exacerbations per year. More than 90% of the patients were current or former smokers. The HIV-positive patients with COPD and tuberculosis were younger than the HIV-negative (the mean age was 44 (41; 48) years versus 53 (45; 63) years, p < 0.001). The body mass index in the HIV-negative patients was higher than in the HIV-positive (22.15 (19.85; 25.13) kg/m² vs 21.2 (19.3; 22.95) kg/m², p = 0.050). The HIV-positive patients with low viral load (40 copies/ml and below) statistically significantly differed from the HIV-positive patients with high viral load (above 40 copies/ml) in the CD4 cell count (p < 0.001). Both the “younger” (aged 50 years or less) and “older” (aged over 50 years) HIV-positive patients with COPD and tuberculosis had more severe dyspnea compared to the HIV-negative patients (p < 0.001). COPD symptoms according to the CAT test were more severe in both “younger” and “older” HIV-positive patients (p < 0.001), and the score was higher in the HIV-positive patients compared to the HIV-negative patients (p < 0.05). The severity of COPD according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria was significantly higher in both “younger” and “older” HIV-positive patients compared to the HIVnegative patients (p < 0.05).

Conclusion. Patients with COPD, tuberculosis, and HIV infection have decreased body weight, more pronounced dyspnea and symptoms of COPD and obstructive pulmonary ventilation disorders compared to the patients without HIV infection.

Registry is a unique and universal mechanism for group and individual approaches to managing patients, including those with severe asthma (SA) who require targeted therapy.

The aim is to evaluate the clinical and organizational potential of the SA patient registry as a tool for group and individual approaches to patient management, as a way to describe and systematize the signs of bronchial asthma, comorbid diseases, and monitoring immunobiological therapy (using anti-IgE therapy as an example) in patients with SA in Sverdlovsk region.

Methods. The subject of the study was the Territorial Registry of Patients with SA of the Sverdlovsk region. The registry effectiveness was assessed based on the clinical and organizational indicators, including monitoring the effectiveness of 3-year anti-IgE therapy in patients with SA with an allergic component.

Results. From 2016 to 2023, both inclusive, 198 patients with SA were entered into the registry. Analysis of the registry data allowed us to develop a scheme for SA phenotyping and selecting the 1st and 2^nd line targeted drugs and a scheme for phenotyping and selecting a targeted drug for T2 inflammatory nasal diseases. Over 3 years of anti-IgE therapy with omalizumab, the ACT test increased from 9.00 to 19.50 points, the proportion of patients with partial and good asthma control increased by 13.89 times, the frequency of exacerbations decreased by 71.43%, FEV1 increased by 17.91%, and the proportion of patients requiring systemic corticosteroids decreased by 83.32%.

Conclusion. The registry of SA patients has high clinical and organizational potential to describe and systematize the signs of bronchial asthma, comorbid diseases, and monitor the effectiveness and safety of immunobiological therapy. The 3-year anti-IgE therapy demonstrates statistically significant effectiveness in patients with SA with an allergic component.

The initial efforts to describe the inflammatory mechanisms associated with SARS-CoV-2 have revealed upregulation of circulating proinflammatory cytokines as well as activation of innate immune cells.

The aim of the study was to investigate the phagocytic activity of leukocytes in hospitalized patients with COVID-19 (COronaVIrus Disease 2019).

Methods. The phagocytic activity of leukocytes was studied in admitted patients with COVID-associated lung disease (n = 105). The mean age of the studied patients was 43.5 (37; 51) years; 69 for men, and 36 for women; the mean duration of the disease before hospitalization was 6 (4; 8) days. Using cluster analysis, two groups of patients (clusters) were formed according to the severity of COVID-19: Group 1 with the moderate course (n = 34) and Group 2 with the mild course (n = 71). Flow cytofluorimetry with determination of neutrophil (NI) and monocyte index (MI) was used to determine the phagocytic activity of neutrophils and monocytes in the peripheral blood.

Results. The median NI in the studied patients was 97.9% (96.3; 99); the mean median MI was 91.2% (84.6; 95). The correlation analysis revealed statistically significant direct correlation of MI with SpO2 level (r = 0.21; 95% CI: 0.005 – 0.39; p = 0.04); inverse correlation of MI with CRP level (r = –0.31; 95% CI: –0.11 to –0.48; p = 0.003) and degree of lung damage by CT (r = –0.2; 95% CI: –0.11 to –0.48); p = 0.05). MI in the group with moderate course was statistically significantly lower than in the group with mild course of COVID-19 (86.7 (81.4; 91.7) and 92.6 (86.5; 95.4), p = 0.01). The blood MI of the initially more severe patients statistically significantly increased.

Conclusion. Complicated forms of SARS-CoV-2 infection lead to a decrease in phagocytic activity of the monocytic-macrophage link of innate immunity. The degree of decrease in monocyte phagocytic activity is directly related to the severity of COVID-19, and the MI is comparable in the patients with severe and mild course after 30 days of treatment.

About 13% of all variants causing cystic fibrosis are splice variants of the CFTR gene; at the moment, such variants are not well studied.

The aim was to investigate the effect of the splicing variant 2789+5G>A on the phenotypic manifestations of cystic fibrosis and the effectiveness of targeted therapy in an intestinal organoids model in the patients with genotypes 2789+5G>A/L732X and 2789+5G>A/CFTRdele2,3.

Methods. The medical history data, intestinal current measurement (ICM), and forskolin-induced swelling assay in the intestinal organoids were used.

Results. The clinical features of the course of CF in 2 patients, carriers of the 2789+5G>A variant in a heterozygous state with genetic variants of the CFTR gene of classes I and VII, are presented. Clinical picture: the disease is of moderate severity; the pancreas is sufficient. The ICM method demonstrated the preservation of the chloride channel function. Assays on the cultured organoids obtained from the intestinal tissue showed moderate residual functional activity of the chloride channels. In addition, the 2789+5G>A variant is sensitive to all tested CFTR modulators.

Conclusions. The splicing variant 2789+5G>A is characterized by moderate residual functional activity of the CFTR channel and is sensitive to all targeted treatments. However, the most effective CFTR modulator for this genetic variant is tezacaftor.

The severe course of infectious and inflammatory diseases of the respiratory system, high rates of morbidity and mortality among the elderly and senile aged people may be associated with respiratory sarcopenia, a new nosological form that describes age-related changes in the strength and structure of the respiratory muscles.

The aim of the review is to update the data of open access scientific sources on aspects of pathogenesis and diagnostic approaches to respiratory sarcopenia. Foreign and domestic scientific publications on this topic were analyzed from 2019 to the present. The mechanisms of respiratory sarcopenia pahogenesis were assessed in the light of its relationship with whole body sarcopenia, age-related mechanisms of aging of the respiratory system as a whole, risk factors and lifestyle aspects of the elderly. The currently proposed diagnostic algorithm for respiratory sarcopenia is considered in detail.

Conclusion. Age-related changes in muscle tissue also affect the respiratory muscles. Whole-body sarcopenia, according to some authors, may be accompanied by respiratory sarcopenia. The proposed terminology and algorithm for diagnosing this pathology require additional data accumulation and further discussion.

Cough is a serious problem of practical pulmonology. The mechanisms of cough occurrence are diverse and numerous diseases are associated with chronic cough syndrome. The diagnosis can be challenging because of a “perplexing”, “unexplained”, or “idiopathic” cough.

The aim of the review was to consider the main underlying mechanisms of the “perplexing” cough, its potential course, an algorithm for managing patients with the persistent cough, and new treatment methods.

Conclusion. Chronic “perplexing” cough disrupts the patient’s quality of life and reduces their performance. Unveiling the mechanisms of its development may increase the treatment efficacy.

Pulmonary hypertension (PH) is a polyetiological disease characterized by an increase in mean pulmonary artery pressure (MPP) by more than 20 mm Hg at rest. Idiopathic pulmonary arterial hypertension (PAH), which is assigned to the first group according to the 2018 PH classification, is the most studied in terms of optimal therapy selection. This is a rare but fatal disease that occurs as a result of vascular remodeling of the distal pulmonary arteries. Currently, PAH treatments target three major metabolic cascades: prostacyclin, endothelin, and nitric oxide. The available therapies improve the symptoms and quality of life of patients with PAH, but, unfortunately, none of them directly affect the pathogenesis or allow to achieve complete control of the disease.

The aim of the review was to analyze the literature and demonstrate of the most promising methods and potential targets for the treatment of PAH.

Conclusion. At the moment, PAH therapy is a serious clinical problem, and therefore, it is essential to study new therapeutic targets and develop the corresponding drugs.

Hypersensitivity pneumonitis (HP) is an inflammatory immune-mediated interstitial lung disease that develops in response to repeated inhalation exposures to various low molecular weight compounds in susceptible individuals. The current guidelines distinguish non-fibrotic and fibrotic phenotypes of HP, with fibrotic HP associated with progression and worse prognosis. The differential diagnosis of HP can be complex and requires careful historytaking, multidisciplinary discussion of clinical and radiological findings, evaluation of lymphocytosis in bronchoalveolar lavage (BAL), and histopathological examination. Differentiating HP from other interstitial lung diseases (ILDs), including fibrotic HP from idiopathic pulmonary fibrosis (IPF), can be difficult, as the clinical, radiological, and histopathological features of HP are highly variable and similar to those of other ILDs.

The aim of this review is to systematize the available evidence on predictors of HP for the use in diagnosis.

Conclusion. Making the diagnosis is crucial for selecting treatment strategies and prognosis. Indicators such as genetic predictors, serum biomarkers, and BAL can be used to diagnose HP, predict its development and course. Several biomarkers, such as BAL lymphocytosis and specific IgG – precipitating antibodies, are already widely used in clinical practice. Other indicators are still under investigation and may be implemented in the routine patient evaluation in the future.

Bacterial complications of the respiratory tract are negative prognostic factors leading to a decrease in pulmonary function, duration, and quality of life of patients with cystic fibrosis. To date, a sufficient number of studies have not been accumulated to reliably prove or reject microbiological improvement during targeted therapy.

The aim of the study was to collect continuous microbiological data from patients with cystic fibrosis in the Samara region receiving treatment with elexacaftor/tezacaftor/ivacaftor + ivacaftor from November-December 2021. The article presents eight clinical observations. At the time of therapy initiation, seven patients had chronic respiratory tract infection associated with Burkholderia cenocepacia ST 208, combined with chronic Pseudomonas aeruginosa infection in two of them. One patient had a chronic P. aeruginosa infection in association with Aspergillus fumigatus.

Conclusion. An expansion of the species composition in the respiratory samples was demonstrated in all cases. The majority of patients showed microbiological improvement. Thus, biochemical and, as a result, microecological changes in the lungs against the normalization of chlorine channel function allow suggesting that key pathogens may be eradicated during the therapy with elexacaftor/tezacaftor/ ivacaftor + ivacaftor.

With the narrow action of immunobiological drugs, it is necessary to understand the pathogenetic mechanisms of severe asthma (SA) in a particular patient.

The aim of the work was to demonstrate the importance of determining the endotype and phenotype of SA to select a targeted drug using the example of cases of anti-IL5R treatment failure in patients with allergic SA (ASA). Patients (n = 2) with ASA onset in childhood, identified causative allergens, and high eosinophilia before the start of targeted therapy are presented. The use of the anti-IL5 drug benralizumab in such cases is permitted by the Guidelines for Biological Therapy (The European Academy of Allergy and Clinical Immunology – EAACI, 2020), but the therapy was ineffective. The patients were switched to the anti-IL4R drug dupilumab, which indirectly blocks IgE production, with a positive outcome.

Conclusion. The considered cases of ASA demonstrate the necessity of determining the endotype and phenotype of SA to select the targeted drug. The inefficiency of the anti-IL5R drug in patients with ASA is shown, despite the pronounced initial blood eosinophilia. In case of Th2-mediated eosinophilia in ASA, preference should be given to anti-IgE or anti-IL4R drugs.

The problem of timely diagnosis of interstitial lung diseases (ILD) remains relevant today.

The aim. To describe the aspects of diagnosis, treatment, and providing care for ILD in a specialized center.

Results. During 2023, a panel of specialists examined 438 patients with ILD out of 2 373 (18.4%) at the prehospital stage who were referred for consultation to a specialized center. In the end, 181 patients with ILD were hospitalized for invasive diagnostic procedures and the decision upon prescribing antifibrotic therapy. The characteristics of patients with various clinical forms of ILD included in the register (n = 134) and the distribution of antifibrotic drugs are presented. The clinical and functional and computed tomography (CT) patterns in the patients receiving antifibrotic therapy (AFT) were analyzed.

Conclusion. The organizational, diagnostic and therapeutic algorithm and routing of patients with ILD on the basis of a specialized federal institution allows solving the problems of ILD diagnosis with high professionalism and successfully monitoring the patients on AFT.

Pulse oximeter is a simple non-invasive equipment used to determine patient’s arterial blood oxygen saturation (SpO₂). However, in some people, arterial blood gas measures (SaO₂) are normal and low SpO₂ values are related to hemoglobin variant rather than cardiac or pulmonary illnesses.

Aim. We present a case of thalassemia that manifested with low SpO₂ and discordant SaO₂.

Conclusion. When examining a patient with an unusually low SpO₂, the differential diagnosis of a suspected hemoglobin variant should be investigated. Establishing an accurate diagnosis as soon as possible may help avoid unnecessary tests.