[Burden and management of severe asthma in Russia: results from international observational study].

AIM: To assess clinical and demographic characteristics of severe asthma (SA) patients and their management in Russian Federation. MATERIALS AND METHODS: This publication provides data for Russian part of population of the international observational study. In Phase I, retrospective analysis of medical records of patients with SA was performed with assessment of clinical and demographic data, medical history, comorbidities, treatment approaches and healthcare utilization. Phase II was a cross-sectional collection of patient-reported outcomes: level of asthma control assessed by ACT (Asthma Control Test) and health-related quality of life (HRQoL) measured using the EQ-5D-5L questionnaire. Phase I patients were enrolled into Phase II if they signed a written consent form. RESULTS: A total of 315 patients were included in Phase I of the study, 106 (33.6%) of them entered Phase II. Majority of study participants were either obese (n=103; 39.8%) or overweight (n=94; 36.3%). The most common comorbidities were cardiovascular diseases (n=217; 71.4%), followed by chronic respiratory diseases (n=198; 68.8%). There were 268 (85.1%) patients who had at least one exacerbation during last 12 months. Data for blood eosinophil count were available in 176 patients; 81.3% of them (n=143) had only one test in the last 12 months. The mean (SD) last available blood eosinophil count was 161.2 (181.2) cells/mm3. Serum Immunoglobulin E (IgE) value was known for 88 patients, and the mean (SD) last measured IgE value was 254.3 (249.7) ng/mL. Only 4.7% of Phase II participants had ACT scores indicative of controlled asthma (>20). As much as 74.5% had scores ≤15 suggesting uncontrolled disease. Most patients also had impaired HRQoL. CONCLUSION: Most SA patients had poor disease control with frequent exacerbations and high number of comorbidities. Blood eosinophils and IgE level measurements were not evaluated routinely which might be a barrier for appropriate phenotyping and treatment selection.

Antibiotic prescribing practices and perceptions on antimicrobial resistance among healthcare practitioners in Russia.

OBJECTIVES: Antimicrobial resistance (AMR) is a growing global health threat. The misuse of antibiotics is the main factor contributing to the development of AMR. Healthcare practitioners (HCPs) play a crucial role in the use of antibiotics. There are limited data available on antibiotic prescribing patterns among physicians in Russia. The aim of this study was to explore antibiotic prescribing practices and perceptions of AMR among HCPs in the Russian Federation. STUDY DESIGN: A cross-sectional, multi-centre study was used. METHODS: A survey using an online questionnaire was conducted among HCPs. A qualitative study was conducted before the questionnaire was developed. The online questionnaire was distributed via email addresses obtained from the Consilium Medicum database, a specialised educational resource for healthcare professionals in Russia. RESULTS: In total, 746 HCPs from 74 regions of the Russian Federation were included in the study. Physicians who participated in this study did not frequently prescribe antibiotic drugs: 40.6% of participants recommended antibiotics less than five times per week. Gynaecologists, paediatricians, family doctors, and surgeons were the least likely study participants to prescribe antibiotics, whereas clinical pharmacologists, otolaryngologists, urologists, and infectious disease specialists prescribed antibiotics more often. Amoxicillin and amoxicillin/clavulanic acid were the most frequently prescribed antimicrobials. The majority of HCPs in Russia who took part in this survey reported relying on national guidelines for information on antibiotic prescribing. Only 67.8% of study participants perceived AMR as a challenge for their practice. CONCLUSIONS: Health authorities should regularly provide up-to-date reliable information on AMR in the region. Antimicrobial stewardship programmes are important for specialised medical professionals, such as urologists, gynaecologists, and otolaryngologists, since they are responsible for prescribing second-line antibiotics, which carries with it a greater responsibility.

[Efficacy of dupilumab in real practice in the treatment of severe forms of asthma and atopic dermatitis (comparative retrospective study)].

BACKGROUND: Dupilumab, a fully human monoclonal antibody directed against the common α-subunit of interleukin (IL)-4 receptors and blocking signaling from both IL-4 and IL-13, may be recommended for the treatment of moderate to severe atopic dermatitis (AD) and bronchial asthma (BA). AIM: To perform a comparative assessment of the effectiveness of maintenance therapy with dupilumab in patients with severe BA as the main indication for genetically engineered biological drugs and in patients with severe asthma with concomitant severe AD as the indication for targeted therapy. MATERIALS AND METHODS: A 6-month retrospective comparative study was performed at the specialized reference center for allergology and immunology. The study included 115 adult patients of both sexes treated with dupilumab for uncontrolled severe asthma as the main indication for targeted therapy (BA group; n=65) or for a combination of severe uncontrolled asthma and severe AD (BAAD; n=50). Dupilumab was administered subcutaneously for 6 months. The first dose was 600 mg once and then 300 mg Q2W. Evaluation of the effectiveness of dupilumab therapy at 6 months of treatment in both groups included achieving asthma control (ACT, ACQ5), improving pulmonary function test, reducing the risk of exacerbations and the need for systemic glucocorticosteroids (SGCS), improving quality of life (AQLQ), change of biomarkers (FeNO, eosinophil count) and the course of comorbid diseases, including improvement in the AD (SCORAD, EASI) and rhinosinusitis polyposa (SNOT-22). RESULTS AND CONCLUSION: During dupilumab therapy, in a significant proportion of patients, regardless of the presence or absence of other T2-associated diseases (e.g., AD or rhinosinusitis polyposa), an improvement in asthma was demonstrated as early as in the first 6 months of treatment with dupilumab in all recommended domains for assessing the response to targeted therapy: improving asthma control and respiratory function, reducing the frequency of moderate and severe exacerbations associated with the use of SGCS and/or hospitalization, a positive effect on the quality of life and the comorbid diseases, as well as a cumulative reduction in the need for SGCS.

[Clinical and economic analysis of Reslizumab use in the treatment of patients with severe allergic eosinophilic asthma].

Asthma is a heterogeneous chronic disease of airways. One of its endotypes is eosinophilic asthma, accompanied by both peripheral blood and airway eosinophilia, where severe eosinophilia is usually associated with more severe asthma. Anti - interleukin-5 (IL-5) monoclonal antibodies (MAb) can reduce eosinophil counts in peripheral blood and tissues in asthma patients. The first drug of this class registered in Russia was reslizumab. AIM: Comparative clinical and economic analysis of reslizumab use in patients with allergic asthma and eosinophilia. MATERIALS AND METHODS: Omalizumab was chosen as a reference drug, because until now it was the only MAb for the treatment of severe asthma in Russia. The study population included patients with allergic asthma with both high levels of IgE and high eosinophil counts in peripheral blood, i.e. individuals eligible for both omalizumab and reslizumab treatment. A decrease in the number of exacerbations requiring prescription of systemic corticosteroids and an increase in QALY index was used as efficacy criteria. An indirect comparative study was used, because no direct comparison has been conducted to date. As a result, reslizumab demonstrated a statistically significant reduction in the frequency of clinically significant asthma exacerbations compared with omalizumab. The utility of the both asthma treatment strategies was compared using Markov models, taking into account the frequency of exacerbations, their severity, as well as decrease in QALYs due to exacerbations. The time horizon was 12 months. RESULTS: Reslizumab treatment was 37.2% less expensive compared with omalizumab for the patients who are equally eligible for the both drugs. The calculated cost - effectiveness and cost - utility ratios were in favor of reslizumab. Budget impact analysis showed a significant effect of reslizumab on reducing budget costs. If reslizumab is used in 4250 patients (an estimated number of patients with severe allergic asthma and eosinophilia in Russia), this would reduce the costs for their treatment by up to 4896 million rubles per year. CONCLUSIONS: For patients with severe allergic eosinophilic asthma who are equally eligible for the both drugs, reslizumab can be considered a more reasonable medical technology in terms of pharmacoeconomics when compared with omalizumab.

[Clinical and Functional Phenotypes of Chronic Obstructive Pulmonary Disease, the Effect on the Severity of the Disease and Prognostic Value in Assessing the Risk of Disease Progression].

Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive limitation of airflow rate, hyperergic inflammatory response of the respiratory tract, and systemic manifestations. Prognosis of the disease depends on the severity of these pathogenetic components. FEV1 which characterizes the speed limit airflow do not allow predicting the rate of COPD progression. Aims: Comparison of the prognostic significance of such clinical parameters as frequency of exacerbations and the development of comorbid diseases to assess the nature of COPD progression by using different classification approaches. Materials and Methods: The prospective comparative study included 98 patients with COPD. In the framework of the study protocol, 2 visits were required when a practitioner recruited patients who met inclusion/exclusion criteria, obtained the signed informed consent, collected the anamnestic data, and performed basic procedures of the study: spirometry, 6-minute stepper test, assessment of dyspnea on questionnaire mMRC, body plethysmography, lung diffusion capacity study, dopplerechocardiography, tomography of the chest. Visit 2 was conducted in 12 months after the first one to assess the dynamics of the disease. The dynamics of the disease was considered negative if, upon repeated examination, the patient was referred to the group with more severe COPD. Results: Our study demonstrates that comprehensive assessment of such factors as the frequency of COPD exacerbations in the preceding 12 months and the presence of comorbid diseases in a patient is reasonable for assessment of disease severity and determination of disease prognosis. At the same time the frequency of COPD exacerbations as one of the evaluated factors is most strongly associated with disease progression. Conclusions: Thus, a practitioner is recommended to use the proposed additional clinical criteria to assess the severity and degree of progression of COPD.

[Clinico-functional phenotypes of chronic obstructive pulmonary disease, their influence on the severity of the disease, and prognostic value for risk evaluation].

Attempts at optimizing classification of chronic obstructive pulmonary disease (COPD) reflect clinical heterogeneity of this pathology and provide a basis for the search of new phenotypic markers (especially at the early stages of the disease) that could be useful for prognostication of its severity in individual patients. One of the potential makers is phenotyping of COPD with distinguishing bronchitic, emphysemic, and mixed phenotypes. This paper presents results of analysis of functional characteristics of the patients with these phenotypes. They are shown to reflect clinical and functional features of the disease that may be of value for diagnostic purposes, the choice of the treatment strategy and prognosis of the outcome in individual patients.

[Comparison Study of Oropharyngeal Microbiota in Case of Bronchial Asthma and Chronic Obstructive Pulmonary Disease in Different Severity Levels].

BACKGRAUND: The result of comparative study of oropharyngeal microbiota taxonomic composition in patients with different severity level of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is presented in this paper. AIMS: To compare oropharyngeal microbiota composition in case of bronchial asthma and chronic obstructive pulmonary disease in different severity levels. METODS: 138 patients, 50 with BA and 88 with COPD were studied. For each patient was collected anamnesis vitae, swab from the back of the throat and performed physical examination. High-throughput 16S ribosomal RNA gene sequencing and bioinformatic analysis was employed to characterize the microbial communities. RESULTS: As a result of the study wasfound a number of differences on various taxonomic levels in microbiota's composition within group of patients with different severity level of BA and group of patients with different severity level of COPD and between those groups. COPD patients with GOLD 1-2 in comparison with GOLD 3-4 patiens are marked by prevalence of species Brevibacterium aureum, genus Scardovia, Coprococcus, Haemophilus, Moryella, Dialister, Paludibacter and decrease of Prevotella melaninogenica species. BA patients with severe uncontrolled asthma in comparison with patients which have mild persistent asthma are marked by decrease of Prevotella and increase of species Bifidobacterium longum, Prevotella nanceiensis, Neisseria cinerea, Aggregatibacter segnis and genus Odoribacter, Alloiococcus, Lactobacillus, Megasphaera, Parvimonas, Sneathia. Patient's microbiota in BA group in comparison with COPD group is characterized by the prevalence of Prevotella melaninogenica and genus Selenomonas, Granulicatella u Gemella, and decrease of Prevotella nigrescens, Haemophilus influenza and genus Aggregatibacter, Alloiococcus, Catonella, Mycoplasma, Peptoniphilus u Sediminibacterium. There are no differences between microbiota composition in case of severe uncontrolled BA and very severe COPD. CONCLUSION: Lack of differences in oropharyngeal microbiota taxonomic composition between patients with severe uncontrolled BA and very severe COPD allow us to suggest a similarity of bronchopulmonary system condition in case of diseases' severe stages.

[Genetic determinants of antibiotic resistance in oropharyngeal streptococci in patients with chronic obstructive pulmonary disease and in those with asthma]. / Geneticheskie determinanty ustoichivosti orofaringeal'nykh streptokokkov k antibakterial'nym sredstvam u patsientov s khronicheskoi obstruktivnoi bolezn'yu legkikh i bol'nykh bronkhial'noi astmoi.

AIM: To identify oropharyngeal Streptococcus species and to analyze the genetic determinants of antibiotic resistance in patients with asthma and in those with chronic obstructive pulmonary disease (COPD). MATERIAL AND METHODS: An experimental diagnostic Streptopol+ (Lytech Co. LTD) panel based on a multiplex real-time PCR was applied to investigate the representation of antimicrobial resistance genes (mef and ermB) and the species composition of streptococci isolated from oropharyngeal swab samples from 89 patients with stable COPD and from 51 patients with asthma. RESULTS: In the stable disease period, the oropharyngeal swabs were found to contain Streptococcus pneumoniae in 7.8% of the patients with asthma and in 6.74% of those with COPD; the common feature of these groups was a tendency towards a severe disease course and recurrent exacerbations requiring antibiotics. S. pyogenus was detected in 42.9% of the oropharyngeal swabs from COPD and asthma patients without exacerbations. The oropharyngeal swabs showed the mef gene in 100% of the patients with asthma and in 100% of those with COPD; the ermB gene was encountered in 91% of the patients with COPD and in 82.4% of those with asthma. The COPD patients displayed a direct correlation between the representation of the ermB gene and sputum production and smoking index. The mef and ermB genes were directly correlated with the frequency of exacerbations in patients with COPD. CONCLUSION: The identified streptococci are a reservoir of antimicrobial resistance genetic determinants - the mef and ermB genes encoding the mechanisms of streptococcal macrolide resistance. The representation of the above genes directly correlates with the frequency of exacerbations and the number of antimicrobial drug uses.

[The airways microbial community composition in healthy individuals and bronchial asthma patients].

This review summarizes the results of studies on the composition of microbial communities in the airways of healthy individuals and patients with asthma. Modern molecular genetic technology of the microbial identification, which are based on a sequence determination of encoding proteins genes conserved regions. These regions form the 16s-subunit ribosomal RNA in microorganisms of different species. These genes are detected by sequencing markers characteristic of individual microorganisms and their phylogenetic groups, and allow to perform a deep analysis of the microbiota in healthy volunteers and patients with chronic bronchoobstructive diseases. So, apparently healthy human bronchial tree is characterized by low bacterial contamination (most typical representatives here are the genera Pseudomonas, Streptococcus, Prevotella, Fusobacteria and Veilonella, much less potentially pathogenic Haemophilus and Neisseria are represented). In bronchial asthma patients the lower respiratory tract microbiota undergoes a qualitative transformation: as compared to healthy individuals the number of Proteobacteria increases and the number of Bacteroidetes decreases. Severe asthma in children is associated with significant respiratory tract Staphylococcus spp. insemination. Association between the asthma developing higher risk in young children and organisms such as Haemophilus, Moraxella and Neisseria spp. It is of considerable interest to determine the role of the microbiome in the development of human diseases of the bronchopulmonary system, and to understand the impact of the microbes communities as a course of disease and the important factor for the development of resistance to therapy.

[Composition of microorganism community in the airways of patients with chronic obstructive pulmonary disease].

This review summarizes results of research on the composition of microorganism community in the airways of patients with chronic obstructive pulmonary disease. Modern technologies for molecular genetic identification of microorganisms provide a deep insight into the microbiota of patients with chronic broncho-obstructive diseases for the better understanding of bronchopulmonary pathology in man and effect of microbiotic communities on the clinical course of diseases and formation of resistance to antibiotics.

[Molecular and pharmacogenetic mechanisms of severe asthma].

This review summarizes the results of studies to identify the dominant mechanisms of development and persistence of inflammation in severe asthma and results of pharmacogenetic studies of determination response to drugs. These mechanisms could potentially be used for diagnostic purposes and become the new targets of asthma therapy. Pharmacogenetic information will enable the use of a personalized approach to the asthma management which will adjust the therapy technology and increase the possibility of achieving disease control.