Strelkova M. Prediction of acute bronchitis course among children on the background of undifferentiated connective tissue dysplasia, taking into account genetic factors

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0821U100409

Applicant for

Specialization

  • 228 - Педіатрія

24-02-2021

Specialized Academic Board

ДФ 64.600.013

Kharkiv National Medical University

Essay

An important issue Pediatric Pulmonology and Allergology is the problem of acute bronchitis in children, due to its diversity and the difficulties in conducting a differential diagnosis. Every fifth child who turns to a general practitioner or pediatrician, suffers from the disease, and about half of children suffering from acute bronchitis with complications as a syndrome wheezing. As new knowledge is gained about the formation of complications that may accompany acute bronchitis among children, it becomes increasingly clear that the variability of pathological traits in individuals depends largely on the genetic basis. Given the scientific evidence on the mechanisms of genetic control of the predisposition to chronic bronchopulmonary pathology, the solution to this problem will likely be to study the relationship of control genes and products of the genetic program at different levels of the organization, which can predict the development of chronic diseases of the bronchopulmonary system stages. In this regard, the purpose of the study is study is to improve the prediction of the risk of wheezing syndrome in children with acute bronchitis, by studying the role of connective tissue, taking into account genetic factors. In accordance with the aims and objectives of the study it was conducted a comprehensive examination of 103 children with acute bronchitis complicated by wheezing and uncomplicated acute bronchitis. The scientific novelty is to develop a concept for optimizing the prediction of the risk of wheezing syndrome in children with acute bronchitis based on the study of genetic and phenotypic features with the involvement of biochemical and immunological parameters. Clinical-anamnestic, genetic, biochemical and immunological parameters in patients with acute bronchitis depending on the presence of a complicated course in the form of wheezing were evaluated. Genetic variants of polymorphic gene loci associated with the risk of complications in the form of wheezing – single polymorphisms of genes of the matrix metalloproteinase (MMP) family: collagenase-1 (MMP1) and 1607lasta (MMP12) (A-82G); microsomal epoxy hydrolase (EPHX1) (Tyr113His), aquaporin-5 (AQP5) (A2254G) - and their contribution to the possible advancement of chronic bronchopulmonary pathology in children was evaluated. For the first time, allelic variants-candidates have been identified regarding the risk of developing complications of acute bronchitis in the form of wheezing. Predictors that can influence the prediction of the development of the wheezing syndrome in children with acute bronchitis have been identified and a prognostic model of the possibility of the formation of the wheezing syndrome in children with acute bronchitis up to five years of age has been built. The practical value of the work is to develop a step-by-step model of examination of a child under 5 years of age suffering from acute bronchitis in order to optimize the diagnosis of the threat of wheezing syndrome, as well as reduce the time and cost of examination of the child: 1. With the help of "Family history questionnaire pulmonological profile for parents of a child with acute bronchitis" the doctor can determine the presence or absence of perinatal risk factors for the development of wheezing syndrome (threat of abortion in the first trimester and birth by cesarean section), and also a burdensome family allergy history. 2. If the questionnaire detects significant risk factors for the development of the wheezing syndrome with the help of a questionnaire, the doctor may continue the laboratory examination of the child to determine the level of total IgE serum and the level of uronic acids in the urine. 3. In the presence of significant anamnestic risk factors for the development of wheezing syndrome, increased serum total IgE levels above 52 IU/ml and urinary uronic acid levels above 5.5 mg/day, the doctor may continue laboratory examination of the child and conduct SNP polymorphism 1607insG in the MMP1 gene , A-82G in the gene MMP12, Tir113His in the gene EPHX1, A2254G in the gene AQP5. 4. Using our developed expert system (taking into account perinatal and family allergy history, total serum IgE levels and urinary uronic acid levels, SNP polymorphisms 1607insG in the gene MMP1, A-82G in the gene MMP12, Tir113His in the gene EPHG1, A2 genes AQP5) the doctor can analyze the risk of developing wheezing syndrome in acute bronchitis in children under five years (Block diagram for the doctor to identify significant risk factors for wheezing syndrome in children under 5 years is attached).

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