Kozhyna O. Improvement of children bronchial asthma course prognostication in view of the thymic stromal lymphopoietin associated phenotype.

Українська версія

Thesis for the degree of Candidate of Sciences (CSc)

State registration number

0420U100895

Applicant for

Specialization

  • 14.01.10 - Педіатрія

24-06-2020

Specialized Academic Board

Д 64.609.02

The Kharkiv Medical Academy of Postgraduate Education, Ministry of Health of Ukraine

Essay

The study is aimed to improve prognostication of bronchial asthma (BA) in children on the basis of children health in the population studying with the use of epidemiological methods, determining of the features of disease phenotype associated with thymic stromal lymphopoietin (TSLP). 5926 pupils of Kharkiv and 6330 pupils of Kharkiv Region districts (12256 children in total) were questioned in accordance with standardized ISAAC (International Study of Asthma and Allergy in Childhood) methods. Additionally, the children answered 15 questions about their life and disease history. Among the pupils who had surveys, the percentage of affirmative answers to all 8 questions of the international ISAAC survey was analyzed. BA symptomatic manifestations prevalence in Kharkiv and Kharkiv Region districts among children is 10.9 %; for 6 7 and 13-14 years old children respectively were as follows: 12.0 % and 9.5 %. The clinical and paraclinic characteristics of BA were conducted among 185 children aged from 6 years old to 17 years. 20 randomized by age healthy children were made up a control group. In the Kharkiv region BA was not diagnosed in time in the most of patients. Among bronchial asthma and recurrent wheezing mild cases of disease prevail. Severe strokes are registered in 14.2 % of cases. In 81.7 % of cases there was a comorbidity of BA with other allergic diseases: with allergic rhinitis in 54.8 %; with atopic dermatitis in 16.5 %; with both rhinitis and dermatitis in 10.4 %. For the most of patients (74.3 %) a mixed form of BA is characteristic; atopic form was revealed in 7 (10.0 %) patients; infectious dependent form was revealed in 11 (15.7 %) patients. Only 22.9 % of patients had typical cases of dyspnea on the background of modern BA therapy. 77.1 % of patients suffering from BA have positive and hyperergic sensitization reactions to respiratory allergens. Among them the allergens of domestic dust and cat are the first ranked ones; pollen allergens include ambrosia, sunflower and alder tree allergens. Severity of asthma correlates with sensitization to household but not pollen allergens. Study of pathogenetic BA features revealed the probably increased level of TSLP in blood serum in school-aged children suffering from bronchial asthma in the case of severe course of disease (81.84 (62.60; 98.90) pg/ml in comparison with the control group 17.39 (6.13; 40.52) pg/ml). Statistical analysis of TSLP correlation relationships with clinical and asthma symptoms showed only one probable difference - the correlation with tainted allergy heredity (P=0.027). Correlation relationships of TSLP levels and IgE were not revealed. Possible inverse correlation of TSLP level with FEV1 (P=0.040,), absolute lymphocyte CD8 count (P=0.030), absolute lymphocyte CD25 count (P=0.040) was defined as well as positive correlation with stimulated NBT test (P=0.040). The study allowed to characterize high serum TSLP associated phenotype of BA in children. For the phenotype the following aspects are specific: severe persistent BA (P=0.050) with male prevalence (P=0.050), long disease duration (more than 9 years; P=0.045), allergic rhinitis (P=0.028), allergic family history (P=0.015), decrease of relative lymphocyte count (P=0.050), absolute CD4 count (P=0.020) and increase of spontaneous NBT (P=0.050) as compared with low TSLP patients. To create a model of BA course prognosis by means of binary logistic regression analysis, 10 of the most significant factors were selected from 142 ones used in the model for definition of possible severe BA in children. The mathematical model for prognostication of severe BA was created. This allows to do a reliable forecast with classification accuracy (according to Hosmer-Lemeshow test) of 65.5%; specificity of 0.85; sensitivity of 0.90.

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