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 1 st -2 nd and 5 th -7 th 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 1 st 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.
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.
The aim of the investigation was to study the impact of prematurity and severe infections of lower respiratory tract suffered in early childhood on the occurrence of chronic bronchopulmonary pathology in young adults.Materials and Methods. 25 men took part in the study: 16 adult patients born prematurely (n=10) or suffered infections of lower respiratory tract in early childhood (n=6), and 9 healthy volunteers as a control group. All patients filled in British Medical Research Council (mMRC scale) questionnaires of breathlessness rating, underwent spirometry with bronchodilatation test, 6-minute walk test with determination of blood oxygen saturation level, body plethysmography and examination of lung diffusion capacity.Results. Post-bronchodilator reversible obstruction of the peripheral airways (p<0.05), signs of static hyperinflation (p<0.05), and fibrous changes in the lung parenchyma (p<0.05) were revealed in all participants with bronchopulmonary pathology. Though no statistically significant differences in the influence of prematurity and infections of lower respiratory tract on the function of the respiratory system have been established, structural and functional alterations in the peripheral airways were more marked in the group of prematurely born patients. Statistically significant positive correlations (p<0.05) were revealed between gestation age and body mass at birth and parameters characterizing the function of the peripheral airways, as well as between the indices of static hyperinflation and the intensity of changes in the bronchi.Conclusion. The processes affecting the growth and development of the lungs, such as prematurity and severe infection of the lower respiratory tract suffered in early childhood, result in formation of structural and functional changes of the respiratory system, which promote the development of chronic obstructive pulmonary disease.Key words: infection of the lower respiratory tract; pulmonary consequences of prematurity; chronic obstructive pulmonary disease.For contacts: Dmitriy Yu. Ovsyannikov, e-mail: mdovsyannikov@yahoo.com Pediatric Predictors of the Development of Chronic Obstructive Bronchopulmonary Pathology in AdultsChronic obstructive pulmonary disease (COPD) is a multiple-factor illness characterized by actually irreversible restriction of the air flow velocity. A chronic hyperergic inflammatory response of the lung parenchyma to the effect of air pollutants and infection agents underlie its development [1]. According to the WHO data, about 600 million people with COPD are living in the world at present, and nearly 11 million of them in Russia. COPD is likely to become the third cause of mortality [2].The main etiologic factor of COPD in people over 40 years is tobacco smoking. However, in 3-11% of cases disease manifestation occurs at a younger age in non-smoking persons [3][4][5]. The causes of chronic bronchopulmonary pathology in the given group of patients are supposed to be such pathological factors as prematurity and a heavy course of lower respirato...
Background: The progression of infectious diseases depends on the characteristics of a patient’s innate immunity, and the efficiency of an immune system depends on the patient’s genetic factors, including SNPs in the TLR genes. In this pilot study, we determined the frequency of alleles in these SNPs in a subset of patients with pneumonia. Methods: This study assessed six SNPs from TLR genes: rs5743551 (TLR1), rs5743708, rs3804100 (TLR2), rs4986790 (TLR4), rs5743810 (TLR6), and rs3764880 (TLR8). Three groups of patients participated in this study: patients with pneumonia in 2019 (76 samples), patients with pneumonia caused by SARS-CoV-2 in 2021 (85 samples), and the control group (99 samples). Results: The allele and genotype frequencies obtained for each group were examined using four genetic models. Significant results were obtained when comparing the samples obtained from individuals with pneumonia before the spread of SARS-CoV-2 and from the controls for rs5743551 (TLR1) and rs3764880 (TLR8). Additionally, the comparison of COVID-19-related pneumonia cases and the control group revealed a significant result for rs3804100-G (TLR2). Conclusions: Determining SNP allele frequencies and searching for their associations with the course of pneumonia are important for personalized patient management. However, our results need to be comprehensively assessed in consideration of other clinical parameters.
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