Cystic fibrosis (CF) is the most common severe autosomal recessive disease in the Caucasoid population caused by mutations in the CF transmembrane regulator (CFTR) gene. However, the course of the disease may be modulated by genetic factors other than the CFTR gene and may be pleiotropically influenced by VDR (Vitamin D Receptor) gene. The aim of the study was to search for associations between genetic variants (c.1206T>C(A>G), c.152T>C, c.1174+283G>A) of VDR gene and clinically significant manifestations of CF, complications, and responses to therapy. Methods. Patients with CF (n = 283) and healthy children (n = 333), who formed the control group, were examined. Calcidiol levels were tested in all subjects. Polymorphic variants of VDR gene (c.1206T>C(A>G), c.152T>C, c.1174+283G>A) were tested by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. It was found that carriers of the TT genotype of the c.152T>C FokI variant of VDR gene are 6.3 times more likely to develop meconium ileus (odds ratio – OR – 6.375; p = 0.011), 3.2 times more likely – respiratory failure (OR – 3.253; p = 0.079), 3.4 times more likely – chronic lung infection (CIL) caused by Pseudomonas aeruginosa (OR – 3.432; p = 0.026), and 4 times more likely – CIL caused by non-fermenting gram-negative bacteria (OR – 4.056; p = 0.009). Carriers of the CC genotype of the c.1206T>C(A>G) TaqI genetic variant use systemic corticosteroids more frequently (66% vs 7%) (OR – 0.034; p = 0.001). It was shown that the AA genotype of the BsmlI polymorphism (c.1174 + 283G>A) is 4 times more likely to be detected in children with CF-associated liver diseases (OR – 4.300; p = 0.051). Conclusion. The contribution of all studied genetic variants c.1206T>C(A>G) TaqI, c.152T>C FokI, BsmlI (c.1174+283G>A) of the VDR gene to the clinical manifestations, complications and response to therapy in CF is described.

Bronchial asthma (BA) is one of the leading chronic non-communicable diseases in all age groups and has been noted by WHO and GINA due to the large socio-economic burden on society. Aim. The analysis of mortality rates (MR) and hospital mortality (HM) due to BA in the Russian population in 2014 and 2018. Methods. The statistical information of the Ministry of Healthcare of the Russian Federation and Federal State Statistics Service of the Ministry of Economic Development of the Russian Federation on the MR and HM associated with BA was used. Results. The mortality rate (MR) associated with BA in Russia was 1.2 per 100 thousand population in 2014 and 0.9 in 2018, which corresponded to 2% of mortality from all respiratory diseases. The maximum MR was registered in the Volga Federal District (in 2014 – 1.7, in 2018 – 1.1 per 100 thousand population). Among the working age population, the average MR due to BA was registered at the level of 0.4 per 100 thousand in 2014 and 0.3 in 2018. Among the population older than working age, MR was 4.2 in 2014. In 2018, MR due to BA decreased by 1.5 times to 2.7 per 100 thousand in the older age group (p = 0,026). MR due to BA in the urban population in 2018 was 2 times higher than in the rural population, and was 1.6 times higher in women than in men. Hospital mortality (HM) in the adult population in 2014 and 2018 stayed at the level of 0.3%. Conclusion. The early diagnosis and follow-up of patients with asthma and control of asthma among different age groups contribute to gradual decrease in MR.

The problem of long COVID-19 (COronaVIrus Disease 2019) has been highly relevant for the healthcare system in the last three years. The persistence of respiratory symptoms, radiological and functional changes in COVID-19 patients brings new challenges to the entire medical community. The aim of the study is to explore long-term clinical and functional changes in patients with severe COVID-19-associated lung injury, including assessment of functional and radiological abnormalities of the respiratory system, as well as persistent clinical symptoms a year after the acute phase of the disease. Methods. The study included 45 patients who were examined 3, 6 and 12 months after COVID-19 with severe lung damage (more than 50% according to chest CT in the acute phase of the disease). Patients underwent multispiral computed tomography of the chest organs, a comprehensive study of respiratory function (spirography, body plethysmography and diffusion test); the clinical symptoms were assessed. Results. Chest CT scans showed gradual regression of pathological changes during the follow-up. However, radiographic changes of varying severity persisted after 12 months of follow-up in 51% of patients. A year later, restrictive disorders persisted in 20% of patients and the diffusion capacity of the lungs was reduced in 69% of patients. At the same time, a statistically significant difference in the DL_СО level was observed between 3, 6 and 12 months. The severity of dyspnea decreased 1 year after hospitalization in 48% of patients. Conclusion. The obtained results demonstrate a gradual regression of both radiological and functional pathological changes during the 1st year. However, CT changes and deviations of the respiratory function persist in some patients, mainly in the form of a decrease in DL_СО, which necessitates further monitoring of this group of patients.

The optimal interval for initiating tocilizumab therapy in patients with COVID-19 (COronaVIrus Disease 2019) has not been determined. The aim of the study was to evaluate the effectiveness of prescribing tocilizumab depending on the duration of persistent hyperthermia > 38 °С in patients with SARS-CoV-2 (Severe Acute Respiratory Syndrome-related CoronaVirus 2) associated pneumonia who received tocilizumab according to the Interim Guidelines of the Ministry of Health of the Russian Federation (version at the time of inclusion in the study). Methods. A retrospective cohort study was conducted in hospitalized patients (n = 163) with SARS-CoV-2-associated pneumonia from May 2020 to May 2021. Patients were retrospectively divided into 2 groups depending on the time of tocilizumab administration: ≤ 7 days (n = 61) or ≥ 8 days (n = 102) from the disease onset. Results. Patients who received tocilizumab in the first 7 days had the lower need for CPAP (Continuous Positive Airway Pressure) therapy on day 3 after tocilizumab therapy (HR (Hazard Ratio) – 0.129 (0.039 – 0.430); p = 0.001), a higher probability of a decrease in the volume of lung lesions on computed tomography > 25% a week after the use of tocilizumab (HR – 1.065 (1.036 – 1.093); p = 0.001), the lower probability of hemoglobin oxygen saturation below 92% on day 3 (HR – 0.807 (0.750 – 0.869); p = 0.001), and day 7 (HR – 0.825 (0.772 – 0.883); p = 0.001) after tocilizumab therapy. If CPAP therapy was required on day 3 after administration of tocilizumab, each day of delay in prescribing the drug increased the risk of an adverse outcome 18-fold (HR – 18.24 (5.328 – 62.438); p = 0.001). The duration of hospitalization was significantly lower in the early group than in the late group (10 (8.5 – 15) vs 13.5 (10 – 18) days, respectively; p = 0.02). The mortality was similar (5 (8.2%) vs 6 (5.9%) patients, respectively; p = 0.748). Conclusion. The administration of tocilizumab in the first seven days from the onset of the disease in patients with COVID-19 who developed systemic inflammation and lung damage may prevent the need for escalation of respiratory support and accelerate recovery compared with the later tocilizumab administration.

The main cause of death in patients with cystic fibrosis (CF) is infectious process in the lungs, in particular, chronic lung infections caused by various pathogens, most often a combination of bacteria, fungi, or viruses. Data on mixed bacterial and viral-bacterial infections from domestic and foreign sources are fragmentary and sparse. The dominant associations of bacterial and viral pathogens in patients with cystic fibrosis have not been studied properly, and data on their epidemiological significance are lacking. The aim of this study was to assess the prevalence of bacterial and viral infections in patients with cystic fibrosis and to substantiate the need for the development of virological monitoring. Methods. Biomaterials from the respiratory tract of CF patients (409 children and 160 adults with CF) examined from 2006 to 2022 were used. The study was carried out using bacteriological methods, molecular genetic methods (RT-PCR) and MALDI-TOF mass-spectrometry. Results. Microflora of the respiratory tract was shown to be mixed in 2/3 patients with CF. The microflora of the lungs of children with CF is a dynamic community of microorganisms with high diversity and variability. In adult patients, associations of microorganisms are more common than in children, but the composition of associations is less diverse. We isolated about 40 species of bacteria from adult patients and more than 85 species from children in our sample. NFMO prevailed, including Burkholderia cepacia complex, Pseudomonas aeruginosa, Achromobacter xylosoxidans, Achromobacter ruhlandii, Stenotrophomonas maltophilia, and Staphylococcus aureus, Candida albicans, Aspergillus spp. Real-time PCR showed the presence of rhinovirus RNA in 10% of samples obtained from children and 12.9% from adults with cystic fibrosis. Conclusion. Our results indicate the need for continuous monitoring of the lung microflora in patients with CF, including testing for viruses.

Chronic lung infections are a consequence of the disturbance of mucociliary clearance process in cystic fibrosis. For most patients with cystic fibrosis, chronic lung infection is associated with a poor prognosis. The impact of chronic Pseudomonas aeruginosa infection on progressive deterioration of lung function and nutritional status has been established. Timely and effective antibiotic therapy aimed at eradication or control of gram-negative flora affects the duration and quality of life. The purpose of the study. To investigate the safety and efficacy of inhaled administration of sodium colistimethate (Colimistin®). Methods. The study enrolled 42 patients (27 patients aged 5 to 17 years and 15 patients over 18 years) with an established diagnosis of cystic fibrosis, 38 with monoculture of P. aeruginosa or various associations, 4 with Achromobacter spp. culture. Microbial status, external respiratory function, nutritional status, assessment of well-being, adverse reactions, exacerbations, and use of antibiotic therapy during colimistin inhalations were recorded in all patients at baseline and at 3 months. Results. A significant improvement in nutritional status in terms of weight (p < 0.007) and height (p < 0.001) was shown in the general patient group and the children’s group. In the group of children, there was a significant increase in weight (p < 0.034) and height (p < 0.0001). In the group of patients older than 18 years, there was a significant increase in weight (p < 0.045) and BMI three months after therapy (p < 0.013). There were no significant improvements in FVC and FEV1. The treatment efficacy was shown by the assessment of well-being in the general patient group (p < 0.001) and in the children’s group (p < 0.002). No significant difference was found in the adult patient group (p < 0.067). Two patients dropped out of the study due to ADR at the start of therapy. Conclusion. Sodium colistimethate showed efficacy and safety in bronchopulmonary infections caused by P. aeruginosa in monoculture and in association with Achromobacter spp. and may be recommended for use in children and adults with cystic fibrosis.

Early and adequate antibacterial therapy of airway infections in patients with cystic fibrosis (CF) may lead to decrease in chronic inflammation, delay the worsening of pulmonary function, and prevent the selection of resistant bacteria. Inhaled forms of antibiotics, which can help to achieve high concentrations of drug in airways and minimize systemic adverse reactions, are particularly important when treating children under 6 years of age. Purpose. To evaluate effectiveness of combined therapy and tolerability of therapy with inhaled colistimethate sodium when treating exacerbations of infectious process in children with cystic fibrosis under 6 years of age. Methods. A retrospective analysis of medical records of patients with CF and infections caused by Pseudomonas aeruginosa who were admitted to pulmonology department of Federal State Autonomous Institution “National Medical Research Center for Children’s Health” of the Ministry of Health of the Russian Federation from June of 2021 to March of 2023 and who were treated with inhaled colistimethate sodium. Results. 20 courses of therapy in 17 patients with cystic fibrosis under 6 years of age were recorded. Mean duration of treatment was 10.4 days (4 – 19 days). There were no adverse reactions that led to discontinuation of the treatment. Clinical and microbiological effectiveness of the combined therapy was 60%. Conclusion. Therapy of exacerbations of airway infections caused by P. aeruginosa with inhaled colistimethate sodium was well tolerated by patients under 6 years of age. No adverse drug reactions were reported.

An expert analysis of existing organizational approaches at different levels of pulmonological medical care is needed to develop measures to improve pulmonological care for patients with chronic obstructive pulmonary disease. Aims: To conduct a multicenter medical and sociological study among pulmonologists to find priority areas and optimal ways to improve the organization of medical care for patients with chronic obstructive pulmonary disease (COPD). Methods. 181 pulmonologists from 23 regions of the Russian Federation were surveyed. Results. Pulmonologists believe that the actual prevalence (59.7%), disability rate (49.7%) and mortality rate (39.2%) associated with COPD are higher than official statistics in Russia. The most significant problems of the organization of pulmonological care are: defects in the organization of medical care at different levels, including insufficient quality of medical care (95.6%); lower quality of outpatient medical care compared to the inpatient care (p < 0.001); insufficient subsidized drug provision (69.6%); lack of dispensary follow-up (58.1%); insufficient rehabilitation measures (56.4%); diagnostic errors (53.4%); insufficient preventive measures (52.3%); long distance between specialized medical institution and the patient’s place of residence (41.4%); lack of continuum between the pre-hospital and hospital care (39.2%); lack of effective patient routing (37.1%); the high need of the regions in the medical and social programs to reduce morbidity and mortality from COPD (92.8%); insufficient contribution of the medical community to the adherence of COPD patients to prevention, treatment and rehabilitation; inadequate legal framework governing pulmonary care for COPD patients (29.3%). According to 97.7% of pulmonologists, COPD should be classified as a socially significant disease. This will allow for upscaling the programs aimed at prevention of COPD and reduction of the mortality rate and disability rate associated with COPD. Conclusion. The priority direction in the development of pulmonological care in Russia is improvement of regulatory and legal support with the development of more effective approaches to the provision of medical care to patients with COPD at all levels.

The novel coronavirus infection caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome-relate CoronaVirus 2) is a serious disease often associated with cardiovascular complications. The combination of acute respiratory distress syndrome, invasive ventilation, thromboembolic complications, and direct myocardial injury creates conditions that increase likelihood of right ventricular (RV) dysfunction due to pulmonary hypertension (PH). The aim of the work was to search for literature sources in the PubMed, Google Scholar and eLibrary databases and analyze these sources to elucidate the main pathophysiological mechanisms that underly the onset and progression of PH in COVID-19 (COronaVIrus Disease 2019). Viral damage to the myocardium and pulmonary vascular endothelium in hospitalized patients with COVID-19 may contribute to the development of PH, which is associated with signs of a more severe course of the disease and the development of RV failure in the future. Results. It was concluded that the routine echocardiography protocol should be expanded with additional indicators of the right ventricular function, since these data can be used can be used to predict course of the disease. Conclusion. Based on the literature data, COVID-19 can lead to the development of clinically significant PH in some cases.

The constant increase in the level of resistance of Streptococcus pneumoniae to antimicrobial drugs significantly affects the algorithms for the pharmacotherapy of pneumococcal infection, reduces the effectiveness of the therapy and increases the healthcare costs. In this regard, specific vaccine prevention of pneumococcal diseases is a socially significant and economically promising and profitable area. The aim of the study is to analyze the current status of antimicrobial resistance of S. pneumoniae in healthy carriers and patients with non-invasive and invasive pneumococcal infections, as well as specific vaccine prevention of pneumococcal infection. Conclusion. An increase in the number of pneumococcal strains resistant to macrolides and tetracycline has been noted, as well as a trend toward an increase in resistance to beta-lactam antibiotics. Given the spread of resistant strains of S. pneumoniae, a continuous epidemiological surveillance of pneumococcal infection with an assessment of the dynamics of pneumococcal serotype resistance and the effectiveness of vaccination is needed on a global scale.

Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare systemic necrotizing vasculitis of small to medium-sized vessels associated with antineutrophil cytoplasmic antibodies (ANCA). EGPA is usually diagnosed in patients with bronchial asthma (BA) and is characterized by a predominant lesion of the lungs, skin, and peripheral nervous system. ANCAs to myeloperoxidase are detected in 1/3 of patients with EGPA. Presence or absence of ANCAs differentiates 2 disease phenotypes with different clinical characteristics and prognosis. New opportunities for the treatment of EGPA appeared after identification of the key role of eosinophils in EGPA and development of targeted drugs for the treatment of eosinophilic BA that are being studied now. Aim of the review is to highlight modern approaches to the diagnosis and treatment of patients with EGPA, primarily through the use of targeted biological therapy. Conclusion. EGPA is a multisystem disease with ambivalent manifestations associated with eosinophilic or ANCA-mediated small vessel injuries. Currently, there is no “gold standard” for the diagnosis of EGPA, although the efficacy of pharmacological therapy is directly related to early detection and timely initiation of treatment. Monoclonal antibodies targeting interleukin-5 (IL-5) are an effective alternative to conventional systemic corticosteroids used alone or in combination with immunosuppressants (cyclophosphamide for induction and azathioprine for maintenance therapy) in patients with severe/refractory disease and unfavorable prognosis. The clinical benefits of the targeted anti-IL-5 drug mepolizumab were confirmed in a randomized controlled trial, and this drug was approved for the treatment of patients with EGPA. Currently, new drugs, including targeted ones, are being tested for induction and maintenance therapy. Pulmonologists and rheumatologists should coordinate patient management to improve the results of treatment and the prognosis of the disease.

For clinical medicine the problem of complications associated with the metabolic syndrome is significant and requires a multidisciplinary approach, since the metabolic syndrome itself has long since moved from the sphere of interest of endocrinologists and cardiologists to general medical practice. Most commonly, the metabolic syndrome leads to cardiovascular and cerebrovascular complications. One of the topics currently under discussion is the question of the influence of the components of the metabolic syndrome on the condition of the respiratory system. An epidemiological association between visceral obesity and insulin resistance with chronic obstructive pulmonary disease, bronchial asthma, and obstructive sleep apnea/hypopnea syndrome has been established. Although respiratory disorders are common in patients with clinical equivalents of the metabolic syndrome, their pathogenesis is not well understood. Aim of the study was to analyze the role of individual most significant components (pathogenetic factors) of the metabolic syndrome in the pathogenesis of respiratory disorders. Conclusion. Clinical and laboratory equivalents of the metabolic syndrome, such as obesity, hyperglycemia, and hyperinsulinemia, contribute to respiratory function impairment. The most discussed process that combines the components of the metabolic syndrome and its associated complications is chronic systemic inflammation. The review presents a conceptual scheme of the pathogenesis of respiratory disease in the metabolic syndrome and highlights the role of its factors in the development of qualitative changes in the air-blood barrier and a decrease in the diffusion capacity of the lungs. The authors pointed out a number of unresolved issues in the pathogenesis of respiratory disorders in the metabolic syndrome and also emphasized the relevance of experimental studies of early mechanisms of lung disease development using animal models.

According to experts, 2 billion people in the world are infected with the causative agent of tuberculosis. A priority task in the diagnosis of tuberculosis infection is the use of accurate, accessible and scalable tools. The tuberculin skin test (TST), or Mantoux test, and the interferon gamma release assay (IGRA) are currently used to diagnose tuberculosis infection. In 2022, the World Health Organization (WHO) identified a fundamentally new class of skin tests for the early detection of tuberculosis infection, the so-called Mycobacterium tuberculosis antigen-based skin tests (TBST). These tests include Diaskintest (Russia), C-Tb (India), and C-TST (China) and pose an alternative to the tuberculin skin test and the IGRA. The aim of this work was to conduct a systematic review of domestic and foreign literature sources on the use of a new skin test based on M. tuberculosis antigens (ESAT-6 and CFP-10) to detect tuberculosis infection (Diaskintest) in world practice. Conclusion. According to the literature data, including the published results of meta-analyzes on the use of skin tests, it has been shown that recombinant tuberculous allergen test, as a new skin test based on M. tuberculosis antigens (ESAT-6 and CFP-10), or TBST, has high sensitivity and specificity for the detection of tuberculosis infection. Its sensitivity and specificity are significantly higher than those of the tuberculin test. TBST skin test results are comparable to those of IGRA, have a favorable safety profile, combined with high laboratory test specificity and ease of performance and assessment of the result in one cut (cut-off > 0 mm – any size papule is considered positive). Thus, TBST is a valuable tool for early detection of TB infection. Taking into account the volume of scientific clinical studies on recombinant tuberculous allergen test in the world practice, more than 10 years of experience in clinical practice in Russia and the CIS countries, it can be concluded that recombinant tuberculous allergen test is currently the leading test for mass diagnosis of tuberculosis infection not only in Russia, but also in the world.

Despite the obvious and simple diagnosis, in practice we meet patients who do not respond to standard therapy. Why does drug resistance occur? The answer to this question is not unambiguous and requires careful investigation in each clinical case. Here we present a clinical case of a patient with bronchial asthma, who had no bad habits and occupational hazards and received adequate drug therapy. However, her condition worsened from attack to attack. Whole exome sequencing by NGS allowed us to determine the spectrum of pathogenic mutations which contribute to the pathological process and drug resistance. Atopy due to dysfunction of filaggrin gene (FLG) triggered the disease and supported the pathological process that led to bronchial asthma. Furthermore, the patient’s body is not able to neutralize the bacterial flaggelin. The inflammatory response is reduced due to а Toll-like receptor 5 (TLR5) deficiency. This is one of the mechanisms underlying development of allergic bronchial asthma. In addition, the patient has reduced cross-presentation of antigens by dendritic cells, that is, a reduced immune response in the absence of infection, due to the complete loss of UNC93B1 gene function. Conclusion. Thus, an atopic reaction based on reduced adaptive immunity led to severe IgE allergy and torpid course of bronchial asthma. This conclusion supports atopic sensitization as the target for therapeutic action and the main core of pathological processes. For this purpose, we used a monoclonal antibody omalizumab that is capable of binding and reducing the amount of IgE. Targeted treatment of bronchial asthma made it possible to interrupt the symptoms and achieve complete remission.

Pediatricians and neonatologists often deal with a variety of causes of respiratory failure. Most algorithms for the diagnosis and treatment of such conditions are well developed. However, the diagnosis of some rare causes of respiratory disorders is still challenging. The aim of this review is to present current literature data on a very rare autosomal dominant disorder – congenital central hypoventilation syndrome (Ondine’s curse). This syndrome is manifested by the absence of spontaneous breathing due to a congenital genetic defect, namely the expansion of the polyalanine tract in the PHOX2B gene on chromosome 4p12. Conclusion. Issues of pathogenesis, diagnosis, clinical variants, treatment, and prognosis of this disease are discussed.