Asthma is a heterogeneous and often difficult to treat condition that results in a disproportionate cost to healthcare systems. Children with severe asthma are at increased risk for adverse outcomes including medication-related side effects, life-threatening exacerbations, and impaired quality of life. An important therapeutic focus is to achieve disease control, which is supposed to involve a personalized approach to treatment of asthma of any severity. Asthma is a multifactorial disease with a significant genetic determinant, however, the inheritance of asthma has not been fully elucidated. Polymorphic genes of inflammatory mediators, including cytokines, play an important role in developing various disease forms. In the current study, large-scale original data on the prevalence of cytokine gene genotypes (IL2, IL4, IL5, IL6, IL10, IL12, IL13, IL17A, IL31, IL33, IFNG, TNFA) among Russian children with asthma in Krasnoyarsk region have been obtained. Genotyping was carried out using real-time PCR. We identified markers predisposing to the development of different variants of the course of childhood asthma: the CT genotype and T allele of IL4 rs2243250 are associated with asthma (p < 0.05), especially in mild asthma and in controlled asthma. The TT genotype and allele T of IL13 rs1800925 are associated with severe and uncontrolled asthma (p < 0.05). The AA genotype of IL17A rs2275913, the TT genotype of IFNG rs2069705 and allelic A variants of TNFA rs1800629 are associated with mild asthma, and the TT genotype of IFNG rs2069705 is additionally associated with controlled asthma. The results obtained will supplement information on the prevalence of polymorphic variants of the cytokine genes in the Russian population and in asthma patients with different disease courses, which is likely to be used in order to shape a plan for Public Health Authority to prevent the development of severe uncontrolled asthma and to optimize personalized therapy.
Chronic respiratory diseases are among the most common non- infection diseases. In particular, it is bronchial asthma (BA), characterized by bronchial hyperreactivity and varying degrees of airway obstruction that is the cause of morbidity and mortality. The methods available for the information about the presence of inflammation in the airways, such as bronchoscopy and bronchial biopsy to be obtained have currently been invasive and difficult in everyday clinical practice, especially for children and seriously ill patients. In this regard, recently there has been an increase in the development of non-invasive methods for diagnosing the respiratory system, being comfortable and painless for trial subjects, especially children, also providing the inflammatory process control in the lungs, the severity assessment and monitoring the treatment process. The exhaled breath condensate (EBC) is of great attention, which is a source of various biomolecules, including nitric oxide (NO), leukotrienes, 8-isoprostane, prostaglandins, etc., being locally or systemically associated with disease processes in the body. Of particular interest is the presence of cytokines in EBC, namely the specific proteins produced by various cells of the body that play a key role in inflammatory processes in AD and provide cell communication (cytokine network). Thereby, it becomes possible for the severity and control level of childhood bronchial asthma using only the EBC analysis to be assessed. In addition, the non-invasiveness of this method allows it to be reused for monitoring lung diseases of even the smallest patients, including infants. Thus, the field of metabolite analysis in EBC has been developing and, in the near future, the given method is likely to be the most common for diagnosing the respiratory system diseases in both children and adults.
Bronchial asthma is a multifactorial disease, with both environmental factors and genetic predisposal affecting its development. A number of gene associations have been obtained between polymorphisms of cytokine genes produced by different types of immune cells and asthma development. Interleukin-13 is involved in allergic inflammation, increased bronchial hypersensitivity, regulation of eosinophil levels and IgE production by B cells, thus making it promising for studying IL13 gene polymorphisms in bronchial asthma coupled to development of the disease. The aim of this study was to investigate possible association between asthma and IL13 rs1800925 polymorphism in the children of Caucasian origin in Eastern Siberia. Four groups of patients with asthma were examined (mean age 12.8±1.2 years): with a controlled (n = 95) and uncontrolled course (n = 107), with severe (n = 71) and moderate severity (n = 131) diseases. The control group consisted of healthy individuals: children (n = 33) and adults (n = 102). DNA was isolated with sorbent method; genotyping was carried out using RT-PCR using specific oligonucleotide primers and fluorescent TaqMan probes. The allele and genotype frequencies were compared by the χ-square test using an online calculator. The odds ratio (OR) with a 95% confidence interval (CI) was performed to link genetic markers with pathological phenotypes. The CT IL13 rs1800925 genotype was shown to be associated with moderate asthma and cases of uncontrollable clinical course, whereas the TT genotype was associated with severe asthma. Thus, rs1800925 polymorphism of IL13 gene (the T* variant is known to be associated with increased IL-13 expression) may be associated with bronchial asthma in children. Our data are consistent with results of other authors. E.g., Liu Z. et al. revealed an association between rs1800925 IL13 and the risk of developing asthma in children, with CT and TT genotypes being more common in the patient group. Radhakrishnan A. et al., was studied rs1800925 IL13 in adult population of Malaysia and found that the T* allele frequency in the group of patients significantly exceeds the frequency of this allele in the control group. Thus, the results of our study showed that IL13 rs1800925 polymorphism is associated with bronchial asthma in children, especially, with level of its control and severity of the disease.
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