[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.

[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.

Spectrum of PRSS1, SPINK1, CTRC, CFTR, and CPA1 Gene Variants in Chronic Pancreatitis Patients in Russia.

The aim of the study was to define the spectrum of genetic risk factors of chronic pancreatitis (CP) development in patients living in the European part of the Russian Federation. Materials and Methods: The study group included 105 patients with CP, with the age of the disease onset under 40 years old (the average age of onset was 26.9 years). The control group consisted of 76 persons without clinical signs of pancreatitis. The diagnosis of chronic pancreatitis in patients was made on the basis of clinical manifestations and the results of laboratory and instrumental investigations. Genetic examination of patients was conducted using the next-generation sequencing (NGS) technology and included targeted sequencing of all exons and exon-intron boundaries of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes. The genotyping of the rs61734659 locus of the PRSS2 gene was also conducted. Results: Genetic risk factors of the CP development were found in 61% of patients. Pathogenic and likely-pathogenic variants associated with the risk of CP development were identified in the following genes: CTRC (37.1% of patients), CFTR (18.1%), SPINK1 (8.6%), PRSS1 (8.6%), and CPA1 (6.7%). The frequent gene variants in Russian patients with CP were as follows: CTRC gene - c.180C>T (rs497078), c.760C>T (rs121909293), c.738_761del24 (rs746224507); cumulative odds ratio (OR) for all risk alleles was 1.848 (95% CI: 1.054-3.243); CFTR gene - c.3485G>T (rs1800120), c.1521_1523delCTT (p.Phe508del, rs113993960), and c.650A>G (rs121909046); OR=2.432 (95% CI: 1.066-5.553). In the SPINK1, PRSS1, and CPA1 genes, pathogenic variants were found only in the group of patients with CP. The frequent variants of the SPINK1 gene include c.101A>G (p.Asn34Ser, rs17107315) and c.194+2T>C (rs148954387); of the PRSS1 gene - c.86A>T (p.Asn29Ile, rs111033566); of the CPA1 gene - c.586-30C>T (rs782335525) and c.696+23_696+24delGG. The OR for the CP development for the c.180TT genotype (rs497078) CTRC according to the recessive model (TT vs. CT+CC) was 7.05 (95% CI: 0.86-263, p=0.011). In the CTRC gene, the variant c.493+49G>C (rs6679763) appeared to be benign, the c.493+51C>A (rs10803384) variant was frequently detected among both the diseased and healthy persons and did not demonstrate a protective effect. The protective factor c.571G>A (p.Gly191Arg, rs61734659) of the PRSS2 gene was detected only in the group of healthy individuals and confirmed its protective role. 12.4% of the patients with CP had risk factors in 2 or 3 genes. Conclusion: Sequencing of the coding regions of the PRSS1, SPINK1, CTRC, CFTR, and CPA1 genes allowed to identify genetic risk factors of the CP development in 61% of cases. Determining the genetic cause of CP helps to predict the disease course, perform preventive measures in the proband's relatives, and facilitate a personalized treatment of the patient in future.

Associations of Toll-like Receptor Gene Polymorphisms with NETosis Activity as Prognostic Criteria for the Severity of Pneumonia.

The aim of the study was to determine the molecular genetic prognostic criteria for the severity of the course pneumonia based on the analysis of the association of genetic polymorphism in toll-like receptors with the severity of NETosis. MATERIALS AND METHODS: The study included 38 patients with the main diagnosis of community-acquired pneumonia with a severe course. All the patients underwent standard clinical laboratory examinations, computed tomography of the thoracic organs, microbiological examination of blood and tracheobronchial aspirate. The level of neutrophilic extracellular traps (NETs) in blood smears was determined on the 1st-2nd and 5th-7th days of hospitalization. Genotyping of rs5743551 (TLR1), rs5743708 (TLR2), and rs4986790 (TLR4) polymorphic loci was performed by pyrosequencing. RESULTS: The level of NETs on the 1st day of admission was statistically significantly lower in heterozygous and homozygous carriers of rs4986790 (TLR4) polymorphism (AG and GG genotypes) compared with patients with the wild-type genotype (AA genotype) (p<0.05). When comparing the number of NETs with genotypes for rs5743708 (TLR2) and rs5743551 (TLR1) polymorphisms, no statistically significant correlation was found (p>0.05). The study of the NET level in dynamics demonstrated a decrease in the NETosis activity of neutrophils during the first week of hospitalization (p<0.05). The presence of the G allele in the patient's genotype for rs5743551 (TLR1) polymorphism increases the risk of a poor outcome of the disease (p<0.0001) (OR=20.3; 95% CI (4.3-135.0)). CONCLUSION: The obtained data suggest that level of NETs is a marker of the activity of neutrophils which are closely related to the studied genetic polymorphisms, and affects the prognosis of the pneumonia outcome.

[The late results of thrombocytapheresis in bronchial asthma patients]. / Otdalennye rezul'taty trombotsitafereza u bol'nykh bronkhial'noi astmoi.

A long-term follow-up (within 18 months) has been conducted of bronchial asthma (BA) patients (a total of 29 cases with atopic, aspirin and mixed BA forms) subjected to thrombocytapheresis. The examination performed in 1-2 month intervals included a berotec test, assessment of platelet aggregation, platelet intracellular calcium metabolism, external respiration function (ERF). The treatment resulted in remission of 4-18 month duration. It was characterized by ERF normalization, high sensitivity to sympathomimetics, platelet status improvement. The best results were achieved in the groups of atopic and aspirin asthma patients. The findings allow recommendation of thrombocytapheresis as a method of choice in combined therapy of BA.