Asthma remains the most common chronic non-infectious respiratory disease in children, affecting about 14 – 15% of the global pediatric population. Current research shows that asthma is not a single disease, but a spectrum of different endotypes and phenotypes. Phenotypes describe the observed demographic and clinical characteristics of asthma, while endotypes reflect the underlying pathogenetic mechanisms of the disease. The aim. The review systematizes current data on clinical phenotypes (allergic and non-allergic asthma, preschool-age asthma, severe asthma) and inflammatory endotypes (T2-high and T2-low) of asthma in children. Results. Biomarkers used to identify endotypes and their clinical significance are analyzed. The main problems in determining phenotypes and endotypes of asthma in children are highlighted, including the possibility of combining several phenotypes in one patient, temporal instability of biomarkers, and the influence of comorbid conditions. Particular attention is paid to insufficient study of non-allergic asthma and T2-low endotype in children. Conclusion. It is shown that the determination of phenotypes and endotypes of asthma is critical for personalizing therapy and improving the prognosis of the disease. However, further studies of their stability over time and validation in prospective studies are needed for more effective use in clinical practice.

Severe asthma is characterized by significant prevalence and unfavorable outcomes. Biological therapy with monoclonal antibodies significantly improves the prognosis of T2-phenotype of severe asthma. Features of allergic occupational asthma associated with the properties of industrial allergens determine the need to study its response to biological therapy. The aim of the study was to determine the effectiveness of biological therapy with monoclonal antibodies in patients with occupational or work-related asthma in real clinical practice. Methods. A prospective observational study was conducted involving patients with severe occupational and work-related asthma (n = 49) receiving therapy with monoclonal antibodies (omalizumab (n = 19), reslizumab (n = 3), mepolizumab (n = 8), dupilumab (n = 9), benralizumab (n = 11)). The diagnosis of asthma was confirmed by a positive bronchodilator test. The occupational and work-related nature of the disease was identified by allergy tests or return-to-work test. The primary endpoints were symptom control (ACQ-5 < 0.75) and asthma exacerbations. Statistical analysis was performed using descriptive statistics methods (median and interquartile range, proportions), Mann – Whitney test or χ2 criterion for comparison of independent groups, Wilcoxon test or McNemar criterion for interrelated groups. Cox proportional hazards method was used to search for factors associated with endpoints, Kaplan–Meier method was used for survival analysis. Results. The observation period was 12 – 60 months. Asthma control was achieved in 39 (79.6 %) patients. The following factors were associated with achieving asthma control (relative risk; 95% confidence interval): sensitization to a low-molecular allergen (2.30; 1.84–3.46), a decrease in the forced expiratory volume in 1 second (FEV1) after exercise (0.89; 0.50 – 0.97), and blood eosinophilia (1.02; 1.01 – 1.05). Exacerbations were noted in 49 (100%) subjects before treatment and in 16 (32.7%) during therapy (p = 0.0001). Sensitization to a low-molecular allergen and high baseline blood eosinophilia reduced the likelihood of exacerbations during treatment (0.27; 0.15 – 0.86 and 0.96; 0.92 – 0.99). In the Kaplan–Meier analysis, the probability of symptom control was 90.3% in patients with low-molecular-weight allergen-induced asthma and 61.1% in patients with high-molecular-weight allergens. The survival rate without exacerbations was 72.3% and 37.7%, respectively (p < 0.05). FEV1 increased, and blood eosinophilia decreased. Conclusion. In patients with occupational and work-related asthma, biological therapy prevents exacerbations, increases the probability of symptom control, and improves lung function, primarily in asthma caused by low-molecular-weight allergens.

Interstitial lung disease (ILD) is a diverse and heterogenous group of chronic lung diseases affecting lung parenchyma and characterized by inflammation followed by pulmonary fibrosis that can progress and lead to hospitalization. The impact of hospitalizations on the clinical course of ILD is not fully understood. The aim was to analyze the causes of hospitalization related to the underlying disease and their relationship with the clinical and functional features of the disease course in patients with fibrosing ILD (f-ILD). Methods. This study was an open comparative non interventional study. We analyzed findings from two groups of patients with f-ILD, who had or did not have hospitalizations due to respiratory reasons during the previous 12 months. Additionally, we analyzed demographic and clinical data, severity of ILD according to Gender, Age, Physiology (GAP) scale, lung function and echocardiographic parameters, physical tolerance in 6-minute walk test (6MWT), and pharmacological therapy. Results. Ninety-five patients with f-ILD were involved in the study. Of them, 37 patients had one to four previous hospitalizations due to respiratory reasons during the previous 12 months, and 58 patients did not have any hospitalizations during this period. Most frequent reasons for hospitalization were progressing or exacerbation of f-ILD, less frequent reasons were community-acquired pneumonia and other respiratory infections, and pulmonary embolism. One third of the patients (n = 29) were hospitalized for elective procedures to verify the diagnosis. Patients with previous hospitalizations had more severe course of f-ILD according to GAP scale, lower parameters of lung function, oxygenation, and physical tolerance and more often were treated with pharmacological agents and supplemental oxygen. Conclusion. Most common reasons for hospitalization of f-ILD patients were progressing or exacerbation of f-ILD and the need in elective procedures to verify the diagnosis. Patients hospitalized for respiratory reasons during the previous 12 months had more severe clinical course of the disease with lower lung function and physical tolerance and more often required pharmacological therapy and supplemental oxygen as compared to the patients who had no hospitalizations in this time interval. Further studies are needed to investigate the prognostic value of hospitalizations in f-ILD.

Epidemiological studies show the detection rates of interstitial lung diseases (ILD) among individuals working in contact with dust and industrial aerosols. The authors suggest that exposure to fibrogenic dust and toxic aerosols in the workplace contributes to the development of other progressive ILD in addition to pneumoconiosis. The aim of this study was to evaluate the impact of occupational aerosol exposure on the risk of development and course of ILDs. Methods. 32 patients with diagnosed ILDs were followed for 3 – 5 years. 20 people worked in contact with dust and toxic aerosols for 8 to 30 years. The comparison group consisted of 12 patients with ILD who had no harmful occupational factors. ILD diagnoses were established in accordance with clinical guidelines (in some cases with histology). All patients underwent clinical-functional, laboratory, and radiological examinations. Comparative analysis was conducted using statistical processing of the data. The difference in indicators was considered statistically significant at p ≤ 0.05. Results. Progressive course of ILD in the first 1.5 – 3 years, together with patient disability, was noted in 14 (70%) individuals working with silica-containing, metallic, and organic dust. Negative dynamics of clinical and functional indicators and chest CT data were revealed after a year of observation with gradual worsening of the disease course by the 3rd year of examination. In the comparison group, significant negative changes in the course of ILD were absent for 5 years. Conclusion. The results showed the negative impact of industrial dust on the course of ILD and its potentially significant role in the development of diseases.

Smoking-related lung diseases are diverse, but the most difficult to diagnose remain diseases that involve interstitial changes, in some pathologies combined with emphysema. The aim of the research is to compare the X-ray and morphological features of smoking-related interstitial fibrosis (SRIF). Methods. A histological analysis of surgical samples from 119 patients (smokers and ex-smokers) who underwent lobectomy for lung cancer or other focal lesions in the lungs was performed. Results. Twenty seven patients (18 men, 9 women, 4 ex-smokers) with histological signs of SRIF were identified based on the pathology results; the mean age was 69.1 ± 8.9 years, the smoking index (SI) was 42.06 ± 11.8 pack-years. Results. The prevalence of fibrosis, assessed semi-quantitatively by histological examination, was significantly associated with the SI (r = 0.44; p < 0.05). Fibrosis of the interalveolar septa was observed in areas of emphysema; in addition, signs of chronic bronchiolitis were detected in a third of patients, and constrictive bronchiolitis in 2/3 of patients. The presence of emphysema was correlated with the presence of constrictive bronchiolitis (r = 0.67; p < 0.05). In 11 of 27 patients, fibroblastic foci were found in the walls of the respiratory bronchioles, and their presence also correlated with emphysematous changes (r = 0.40; p < 0.05). CT scans revealed signs of emphysema in 80% patients. In addition; polysegmental areas with ground glass opacities were detected in 12/20 patients, reticular and/or cord-like attenuations were detected in 14 patients, and interlobular interstitial thickening was detected in 8 patients. These signs were assessed as “fibrous” when localized in the emphysema zone. When conducting a correlation analysis, a relationship was found between radiologically detected emphysema and fibrotic changes detected by histological examination (r = 0.50), and the prevalence of CT signs of fibrosis correlated with the presence of fibroblastic foci in the bronchiolar wall (r = 0.51). Conclusion. SRIF is more common in individuals with a smoking history of more than 20 pack-years. CT examination does not always identify the signs of SRIF. In our study, signs of emphysema were detected in 80% patients, and signs possibly associated with fibrosis – in less than half of the cases. Histological results suggest that SRIF is the end stage of the respiratory bronchiolitis of smokers.

Sarcoidosis is an epithelioid cell granulomatosis of unknown etiology. Its course varies from spontaneous remission to the development of fibrosis. The aim of the work was to evaluate the subjective and objective state of patients with sarcoidosis in the years following the detection of pulmonary fibrosis. Methods. 47 patients with sarcoidosis were examined at detection, during the transition to stage IV, and later. Results. One year after the detection of fibrosis, 46.3% of patients assessed their condition as unchanged, 39.0% as improved, and 12.2% as worsened. One patient died. HRCT did not change in 65.8%, improved in 24.5%, and worsened in 9.7%. FVC did not change in 36.6%, improved in 39.0%, and worsened in 24.4%. 22.0% of patients had saturation < 95% at baseline, and 17.1% after one year. After 2 – 3 years, the condition did not change in 53.7%, improved in 22.0%, and worsened in 24.4%. HRCT did not change in 28 (68.3%), improved in 7 (17.0%), and worsened in 6 (14.6 %). FVC did not change in 8 (19.5%), improved in 12 (29.3%), and worsened in 21 (51.2%). SpO2 was < 95% in 6 (14.6%) patients at baseline and in 11 (26.8%) after 2 – 3 years. After ≥ 4 years, the condition remained unchanged in 10 (62.5%), improved in 1 (6.3%), and worsened in 5 (31.3%). HRCT remained unchanged in 12 (75.0%) and worsened in 4 (25.0%). FVC did not change in 3 (18.8%), improved in 4 (25.0%), and worsened in 9 (56.2%). Saturation was < 95% in 2 (12.5%) at baseline and in 6 (37.5%) after 4 years. In all cases, the changes depended on compliance with the doctor’s recommendations and concomitant pulmonary diseases. Conclusion. Sarcoidosis progresses slowly in most patients with established fibrosis and may depend on both the correct initial therapy upon detection and concomitant bronchopulmonary diseases. We believe that further research should be directed towards developing criteria for prescribing antifibrotic therapy, the experience of using which in sarcoidosis is minimal.

The most studied biomarkers of progressive pulmonary fibrosis (PPF) are matrix metalloproteinases (MMP) types 1, 7 and 9 and surfactant proteins A and D (SP-A and SP-D). The aim was to study the levels of MMP-1, MMP-7, MMP-9, SP-A and SP-D in the context of diagnosis of idiopathic pulmonary fibrosis (IPF) and hypersensitivity pneumonitis (HP) and the relationship of these indicators with the PPF criteria. Methods. The study included 65 patients with ILD. Analysis of computed tomography (CT) scans, spirometry, and lung diffusion capacity data were performed. PPF was established based on the diagnostic criteria of the American Thoracic Society (2022). Quantitative determination of serum SP-A levels was performed using Cloud-Clone Corp. kits. (China), SP-D and MMP-7 levels using RDS kits (USA), MMP-1 and MMP-9 levels using RayBiotech kits (USA) on the Hydro Flex enzyme immunoassay (TECAN, Austria). Statistical data processing was performed using Statistica 10.0 software. Results. A relationship between elevated MMP-7 and SP-D levels in HP and PPF criteria was found. No statistically significant differences were found between MMP-7 and SP-D levels in IPF and HP with PPF (9.03 ± 3.1 and 8.47 ± 2.61 ng/ml, respectively; p = 0.42), as well as SP-D (34.51 ± 6.12 ng/ml in IPF and 33.22 ± 8.91 ng/ml in HP with PPF; p = 0.45). Negative correlation was noted between elevated levels of SP-D and MMP-7 with FVC and DLCO during the year. Conclusion. An increase in the levels of MMP-7 and SP-D in the blood serum allows us to consider these indicators for the diagnosis of PPF in HP.

A review of existing international and Russian data on registries and studies was conducted to identify key variables for effective patient monitoring, as part of the development of a regional registry of patients with chronic obstructive pulmonary disease (COPD) in the Tomsk region. The aim. The primary goal of this review is to identify the most significant and informative variables to be included in the registry, as well as to determine reliable information sources for their collection, enabling a more comprehensive understanding of COPD progression and adaptation of treatment approaches according to local conditions and patient needs. Conclusion. Registries play a crucial role in COPD management by allowing the collection and analysis of data that contribute to improving the quality of healthcare and scientific research. Creating and maintaining a registry in Russia will enhance the quality of diagnosis and treatment, as well as optimize medical care costs for COPD patients.

Lesions of the skin and its appendages against the background of respiratory diseases are fairly common in routine clinical practice. Abnormal changes in the skin and its appendages can manifest as signs of a multisystem genetic disease, chronic lung diseases, or acquired syndromes with combined lesions of the skin, its appendages, and respiratory organs. Abnormal changes in the skin and its appendages against the background of respiratory diseases can be linked to a severe systemic condition (Bazex syndrome, granulomatosis with polyangiitis, Löfgren’s syndrome), but at the same time can be the only clinical sign of the disease (yellow nail syndrome). The aim of this work is to describe the clinical features of acquired skin-pulmonary syndromes, including Bazex syndrome, granulomatosis with polyangiitis, Löfgren’s syndrome, yellow nail syndrome, eosinophilic granulomatosis with polyangiitis, and Sjogren syndrome, with an emphasis on the known clinical manifestations in the skin, its appendages and respiratory organs. Conclusion. Identification of distinct symptoms and syndromic nature of a specific disease is a very complex task, requiring deep academic and clinical knowledge of the physician. The variety of clinical lesions of the skin, its appendages, and respiratory organs associated with skin-pulmonary syndromes may create challenges during a routine appointment. In this article, the authors attempted to describe the main acquired skin-pulmonary syndromes encountered in the routine practice of both a pulmonologist and a dermatologist, with an emphasis on the clinical manifestations of these syndromes in the skin, its appendages, and respiratory organs.

The problem of multidrug resistant pathogens has significantly limited the capabilities of tuberculosis chemotherapy, reinstating the need for pathogenetic treatment methods in phthisiology. The practitioner is faced with a difficult choice between the expediency and even necessity of prescribing drugs for pathogenetic therapy and the risk of prescribing drugs whose effectiveness and safety have not been proven. The aim of the work was to familiarize doctors with the principles of prescribing pathogenetic therapy included in the current version of the clinical recommendations “Tuberculosis in adults”. Conclusion. Today, the phthisiological service has drugs of various pharmacological groups in its toolkit that can influence the pathogenesis of tuberculosis and have a high level of evidence from pre-clinical and clinical studies. The new data should be reflected in future versions of the clinical guidelines.

Respiratory damage in cystic fibrosis (CF) is the result of a vicious circle of chronic infection, severe inflammation, and rapidly progressing bronchial obstruction. These processes are the main cause of high mortality associated with the disease. With age, the number of patients infected with non-fermenting gram-negative microflora increases. Pseudomonas aeruginosa is the most common gram-negative pathogen infecting the respiratory tract of patients with CF. The introduction of inhaled antipseudomonal antibiotics has changed the course of the disease and improved the lives of patients. The aim. The objective of the review was to study the role of aztreonam lysine for inhalation (AZLI) in the treatment of patients with CF based on an analysis of literary sources. Methods. A search for publications on AZLI was conducted in the Cochrane Database of Systematic Reviews, as well as in the PubMed and ClinicalTrials.gov databases using the queries “inhaled aztreonam” and “cystic fibrosis”. Results. The results of pre-registration clinical placebo-controlled phase 3 studies that led to AZLI’s Food and Drug Administration (FDA) approval were found and analyzed. The review also included reports of post-marketing studies comparing AZLI with the existing “gold standard” of inhaled antibacterial therapy for CF – inhaled Tobramycin. The role of the adapted AZLI delivery device, which creates an innovative drug-delivery device combination to achieve the maximum therapeutic effect, is separately noted. Conclusion. It is concluded that the inclusion of AZLI in the treatment program for CF accompanied by P. aeruginosa infection can further improve the clinical and functional characteristics and quality of life of the patients.

Adult-onset Still’s disease (AOSD) is a rare polygenic systemic autoinflammatory disease of unknown etiology, characterized by neutrophilic leukocytosis and the absence of rheumatoid factor and antibodies to cyclic citrulline-containing peptide in the blood serum. Lung damage in AOSD is a rare but serious complication. Bronchiolitis, bronchitis, nonspecific interstitial pneumonia, and organizing interstitial pneumonia have been described as patterns of lung damage in AOSD. Pulmonary manifestations of AOSD remain poorly understood. The aim of the article was to demonstrate a clinical case of AOSD, the main manifestation of which was the development of cryptogenic organizing pneumonia with respiratory failure. The article presents in detail the stages of the diagnostic search. An interesting feature of this clinical case was the absence of the most common symptoms of AOSD (sore throat, arthritis/arthralgia). Conclusion. This clinical case emphasizes the importance of clinicians’ awareness of possible pulmonary complications in AOSD.

The recommended methods for obtaining biopsy material for the differential diagnosis of mediastinal lymphadenopathy (ML), such as transbronchial or transesophageal needle biopsy under the control of intraluminal ultrasound (ultrasound transbronchial fine-needle biopsy – US-FNB), require expensive equipment and consumables, while the availability of US-FNB for routine use is currently limited. The aim of the study is to evaluate the safety and efficacy of forceps transbronchial lymph node biopsy (FTLB) as one of the main methods for verifying the etiology of ML. Methods. A study was conducted in 2024 – 2025, which included patients (n = 91) with radiologically confirmed ML. The experience of using an alternative endoscopic approach to diagnosing the causes of ML using widely available equipment is presented. Results. The following diagnoses were confirmed based on the obtained histological material – sarcoidosis of intrathoracic lymph nodes (77 (85%)), cryptococcosis (2 (2%)), squamous cell lung cancer (G2) (1 (1%)), and poorly differentiated lung adenocarcinoma (3 (3%)). The biopsy material was uninformative in 7 (8%) cases. Conclusion. The presented method of PTBL can be used in centers where equipment for ultrasound-FBI is not available or in cases where ultrasound-FBI was ineffective.

Severe asthma (SA) is asthma that requires stage V therapy according to the Global Initiative for Asthma (GINA) criteria to achieve control. Attempts to reduce the amount of controller therapy invariably lead to loss of control of asthma symptoms, or asthma remains uncontrolled despite this treatment. Patients with SA have the highest rate of loss of control and exacerbations, making the search for new approaches to SA therapy relevant. Targeted therapy with genetically engineered biological products (biologics) is available for patients with T2-SA (allergic or late eosinophilic). This therapy is aimed at suppressing excessive immune signaling pathways associated with T2 cytokines (IL-5 and IL-5R, IL-4/IL-13) or IgE. This therapy is effective with the correct identification of the patient’s phenotype and selection of biologic agent. However, anti-cytokine biological agents do not produce the expected effect in all patients, which may be due to multiple signaling pathways mediated by different cytokines that may be involved in the pathogenesis of SA. So, a single biologic agent targeting a specific cytokine is insufficient. The phenotypes and endotypes of asthma are known to change over time in some patients, which can make it difficult to determine the phenotype for selecting a specific biologic agent in routine clinical practice. Some patients with SA may simultaneously exhibit features of T2- and non-T2-type inflammation. Therefore, there is a need for a biologic agent capable of targeting multiple cytokine signaling pathways and independent of, or less dependent on, the phenotypes and SA biomarker levels. The aim of this study was to observe the manifestations of severe asthma in patients receiving tezepelumab, a first-in-class biologic agent that inhibits thymic stromal lymphopoietin (TSLP), a key alarmin that plays a central role in the pathogenesis of SA. Conclusion. We present our experience with tezepelumab in adult patients. Its effectiveness in controlling various phenotypes of SA is demonstrated, which may be related to the suppression of the immune cascade at the early stages of inflammation via cytokine signaling pathways.

Morphological verification is not always required to make a definitive diagnosis of lymphangioleiomyomatosis (LAM) with a typical picture of cysts in the lungs using high-resolution computed tomography. Vascular endothelial growth factor D – VEGF-D (vascular endothelial growth factor D) is used worldwide as a laboratory marker of LAM with a diagnostic threshold of 800 pg/ml and higher in the blood [1]. There was no such possibility in the Russian Federation until April 2023. The aim of the study was to evaluate the diagnostic value of the serum levels of vascular endothelial growth factor D (VEGF-D) in patients with LAM in the Russian Federation. Methods. Blood serum samples were prospectively collected in the laboratory of the State Budgetary Institution of Healthcare of the city of Moscow “Moscow Clinical Scientific and Practical Center named after A.S.Loginov of the Department of Healthcare of the City of Moscow” from 71 patients with multiple air cavities in the lungs using high-resolution computed tomography of the chest organs. VEGF-D levels were measured using enzyme immunoassay, and diagnostic value was assessed using performance curve analysis (ROC-curve). Results. Patients with identified LAM accounted for 48 (68%) of all the included patients (n = 71) with cystic lung disease, with the average age of 48.2 ± 12.9 years. The group of patients with lung cysts not associated with LAM and the group of patients with LAM significantly differed in VEGF-D levels: 552 ± 276.5 pg/ml vs 1,425 ± 872.1 pg/ml, respectively (p < 0.0001). The level of VEFG-D was higher in women with LAM and extrapulmonary manifestations of the disease than in women without extrapulmonary changes: 1,510 ± 968.6 pg/ml vs 1,328.5 ± 761.0 pg/ml, respectively. However, the difference was not statistically significant (p < 0.06). The level of VEFG-D was higher than 800 pg/ml in 75% of patients with LAM. The area under the ROC curve for VEFG-D in LAM was 0.866 (95% CI – 0.783 – 0.950; p < 0.0001). The threshold value of VEFG-D of 738 pg/ml had a sensitivity of 81% and a specificity of 79% for the diagnosis of an identified LAM. Conclusion. Our data indicate that measurement of VEGF-D blood serum levels allows diagnosing LAM in 75% of cases with clinical and radiological suspicion of LAM without morphological examination of lung tissue.