Introduction. The group of gluten-dependent diseases currently comprises 3 pathological conditions: celiac disease, non-celiac gluten intolerance and wheat allergy. Celiac disease is a chronic, immune-inflammatory disease that occurs in genetically predisposed individuals in response to exposure to the main cereal protein - gluten. It is characterised by damage to the small intestinal mucosa, leading to its atrophy with corresponding intestinal and extraintestinal clinical manifestations. The treatment is a lifelong gluten-free diet. Gluten intolerance is a condition characterised by the onset of irritable bowel syndrome-like symptoms within hours or days of eating gluten-containing foods. These symptoms disappear quickly when the consumption of gluten-containing products is stopped. The causes of gluten intolerance are amylase inhibitors, trypsin and fructans (FODMAPS), which are present in wheat and other gluten-containing and gluten-free foods. New recommendations from the European Society of Paediatrics, Gastroenterology, Hepatology and Nutrition (ESPGHAN) for the diagnosis of celiac disease in children were published in 2020. The diagnosis of gluten intolerance requires the exclusion of celiac disease and wheat allergy.The aim of the study was to determine the characteristics of the clinical course of celiac disease and gluten intolerance (analysis of intestinal and extraintestinal symptoms), serological and morphological features for differential diagnosis and management.Material and methods. Thirty children aged 9 months to 11 years were included in the study for the period 2016-2023. Distribution by gender: 13 (43.3%) boys and 17 (56.6%) girls, p=0.1391. Patients were divided into two groups according to the diagnosis of celiac disease and gluten intolerance. The study included a detailed medical history, assessment of the child's examination and physical development. Determination of titer of IgA antibodies, IgA to tissue transglutaminase (tTG-IgA), endomysial IgA (EMA-IgA), gliadin IgG, wheat IgE antibodies, endoscopy and morphological examination of duodenal mucosal biopsies. Descriptive analysis and comparison of two proportions were used. Non-parametric methods were used to test hypotheses. Logistic regression analysis using the relative risk index (RR) and its 95% confidence interval (CI). Differences in parameters were considered statistically significant when p<0.05.The study was approved by the Commission on Biomedical Ethics for Compliance with Moral and Legal Rules of Medical-Scientific Research of the Kharkiv National Medical University. It was confirmed that the research does not contradict the basic bioethical norms and complies with the main provisions of the Good Clinical Practice (1996), the Convention of the Council of Europe on Human Rights and Biomedicine (04.04.1997), the Declaration of Helsinki of the World Medical Association on the ethical principles of research involving human subjects (1964-2008), and the Order of the Ministry of Health of Ukraine No. 690 (23.09.2009) with amendments according to the Order of the Ministry of Health of Ukraine No. 523 (12.07.2012). Both parents of the patients were informed about the purpose and procedures of the research and signed the informed consent for their children's participation in this study.Statistical analysis was performed using Statistica 7.0 StatSoft Inc.1984-2004, (serial number 12255555555, USA) and MedCalc version 14.8-© 1993-2014 MedCalc Software bvba (Acacialaan 22 B-8400 Ostend, Belgium). The procedures, logic and interpretation of the statistical parameters obtained in the mathematical and statistical analysis were based on generally accepted rules of medical and biological statistics. Descriptive analysis and comparison of two proportions were used. Non-parametric methods were used to test hypotheses: Logistic regression analysis using the relative risk index (RR) and its 95% confidence interval (CI). Differences in parameters were considered statistically significant if p<0.05. Patients in the study were divided into two groups according to the diagnosis of celiac disease and gluten intolerance.The presented article is a fragment of the scientific research of the Department of Paediatrics No.1 and Neonatology of the Kharkiv National Medical University: topic "Medical and social adaptation aspects of children with somatic pathology in modern conditions"; state registration No.0120U102471.Results. 66.6% of children from the general cohort were diagnosed with celiac disease and 33.3% of children with gluten intolerance, p=0.0053. The mean age of the children with celiac disease was 8.4±1.0 years. Gender distribution of children with celiac disease - 50.0% boys, 50.0% girls, p=1.0000. The mean age of the children with gluten intolerance was 9.1±1.0 years. The gender distribution of children with gluten intolerance was 70.0% boys and 30.0% girls, p=0.0001. In 65.0% of children with celiac disease, the diagnosis was confirmed at an earlier stage than in children with gluten intolerance, p=0.0350. A family history of autoimmune pathology was found in 40% of children with celiac disease. All patients with celiac disease were seropositive for serological biomarkers. IgA to tissue transglutaminase tTG-IgA was detected in 95.0% of children with celiac disease (RR=20.4; 95% CI 1.4-307.2; p=0.0292).Diarrhoea and abdominal pain were found in 18/30 children from the general cohort (RR=0.8; 95% CI 0.4-1.4; p=0.5050), loss of appetite - in 17/30 children (RR=0.7; 95% CI 0.4-1.3; p=0. 2695), 15/30 children had constipation and poor weight gain (RR=0.7; 95% CI 0.3-1.5; p=0.4209), 14/30 children had delayed physical development and weakness (RR=0.9; 95% CI 0.4-1.9; p=0.7929). One third of the children had hyperactivity and attention deficit syndrome, sleep disturbances. All children with celiac disease had various stages of small intestinal mucosal atrophy according to the Marsh-Oberhuber classification. No atrophic changes in the small intestinal mucosa were found in children with gluten intolerance (normal structure of villi and crypts), but infiltrative changes were found in 60% of these patients (increase in intraepithelial lymphocytes).Conclusion. Comparative analysis showed no significant differences in the clinical presentation of celiac disease and gluten intolerance. Autoimmune pathology was not found in the family history of children with celiac disease, whereas it was found in 40% of patients with celiac disease. The diagnosis of gluten intolerance is made in case of exclusion of family history of autoimmune nosology; absence of autoantibodies to tissue tranglutaminase and deaminated gliadin peptides, endomysial autoantibodies, which should be determined on a gluten-containing diet, and absence of specific IgE to wheat. All children with celiac disease had various stages of atrophy of the small intestinal mucosa according to the Marsh-Oberhuber classification, whereas no atrophic changes were found in children with gluten intolerance, but 60% of patients with gluten intolerance had infiltrative changes in the small intestinal mucosa.

Background/Aims: Diagnosis of growth hormone deficiency (GHD) in children requires the use of provocative growth hormone (GH) stimulation tests, which can have limited reliability and are potentially contraindicated in some patients. This is the first paediatric study to test the safety, tolerability, and pharmacokinetics (PK)/pharmacodynamics (PD) of macimorelin, an oral GH secretagogue, approved for diagnosis of adult GHD. Methods: In this open-label, group comparison, single-dose escalation trial (EudraCT 2018-001988-23), sequential cohorts of patients (C1–C3) received ascending single doses of macimorelin: 0.25 (C1), 0.5 (C2), and 1.0 (C3) mg/kg. Primary endpoints were safety and tolerability, and secondary endpoints were PK/PD. Results: Twenty-four patients aged between 2 and <18 with suspected GHD participated in the study. No macimorelin-related adverse events were reported, and macimorelin was well tolerated. Plasma macimorelin concentrations increased with dose: mean areas under the curve were 6.69 (C1), 18.02 (C2), and 30.92 (C3) h × ng/mL; mean maximum concentrations were 3.46 (C1), 8.13 (C2), and 12.87 (C3) ng/mL. GH concentration increased following macimorelin administration: mean times of maximum measured concentration were 52.5 (C1), 37.5 (C2), and 37.5 (C3) min. Conclusion: All 3 doses of macimorelin had excellent safety and tolerability with PK/PD profiles in expected ranges. These results support the use of 1.0 mg/mL macimorelin in a Phase 3 test validation trial in children.

The aim: Matrix metalloproteinases (MMP) play an important role in the architecture and remodeling of the lungs. There are 2 gene families of MMP among significantly different genes – MMP-1 and MMP-12, which are closely related to the pathophysiological processes of allergic inflammation, damage and restoration of tissues and the body’s defense against pathogens. Materials and methods: 70 examined children were divided into 2 groups: 37 children who had acute recurrent bronchitis complicated by wheezing syndrome, the comparison group included 33 children with acute bronchitis. The determination of gene polymorphism was carried out using ELISA analysis. Results: In the dominant model, carriers of the 2G allele genotypes had 3,45 times lower risk of wheezing syndrome compared with patients with the 1G/1G genotype (OR = 3,45, 95% CI: 1,07-11.15, p<0,05). In the dominant model, carriers of G-allele genotypes had a 4,2-fold lower risk of wheezing syndrome compared with patients with the AA genotype (OR = 4,2; 95% CI (CI) = 1,09- 16,09; p <0,05). Conclusions: Polymorphism rs1799750 in the MMP-1 gene increases the risk of developing the wheezing syndrome among children with acute recurrent bronchitis in 3,5 times. The rs2276109 polymorphism in the MMP-12 gene reduces the risk of wheezing syndrome by 4,2 times among children with acute recurrent bronchitis.

The article considers the problem of renal arterial hypertension as one of the frequent manifestations of secondary arterial hypertension in childhood, which contributes to an increase in the rate of disease progression. Symptoms of renal hypertension are due to the level of blood pressure, manifestations of cardiovascular disease and the presence of proteinuria. Blood pressure indicators were analyzed in 86 children with chronic kidney disease. According to the results of diurnal monitoring of blood pressure in 58.1 +/- 5.3 % (50/86) children, violations of the circadian rhythm of daily fluctuations in blood pressure were revealed. Renal arterial hypertension was diagnosed in 41.8 +/- 5.3 % (36/86) children. For doctors who observe pediatric patients, especially with kidney pathology, approaches to non-pharmacological and pharmaceutical treatment of renal hypertension in children are offered. These include physical activity correction, nutrition in accordance with the child's basic age needs, in combination with the appointment of renoprotective therapy. For initial treatment, it is recommended to use drugs from the group of inhibitors of angiotensin converting enzyme and blockers of angiotensin receptors.

OBJECTIVE The aim of the study to evaluate the peculiarities of the aortic wall structure at the place of coarctation. PATIENTS AND METHODS Materials and methods: Studying of the aortic sections removed during operative correction at the place of constriction. 10 children at the age between 1 to 6 months were undergone the operation. Intraoperative aortic biopsy specimens were observed in 10% neutral formalin. Histologic sections were prepared in a conventional way followed by staining them with hematoxylin-eosin. RESULTS Results: Histological examination in the areas of constriction revealed that the endothelium in all the preparations had poor expressiveness. The most significant changes were recorded in the middle layer of the aorta in the form of reduced development of elastic fibers, their fragmentation and chaotic arrangement. Angiomatosis with the formation of thin-layer small vessels by capillary type was found out. In all the preparations, areas of emptying of cells and fibers of the middle cover with the formation of cystic structures were revealed. CONCLUSION Conclusions: The histological examination has revealed changes in the structure of the aorta wall, which may indicate the systemic nature of the lesion and make it possible to consider coarctation of the aorta to be a manifestation of systemic vasculopathy. The above-mentioned facts determine the need for a more detailed examination of children with the specified pathology at different stages of observation.

High population frequency with the prevalence of connective tissue dysplasia, the unique role of connective tissue in the exercise of various functions of organs and systems of the body significantly affects the clinical course of bronchopulmonary diseases in children. The relationship between the presence of tracheobronchial dyskinesia and other phenotypic signs of "weakness" of connective tissue is noted. The clinical significance of tracheobronchial dyskinesia is that it is one of the causes of bronchial obstruction and chronic cough. Through mechanisms of hyperventilation and local inflammation, bronchial obstruction can lead to the development of emphysema, chronic bronchitis, and pulmonary heart. The study included 72 inpatients (the 1 group comprised 41 children with acute obstructive bronchitis and the 2 group had 31 children with acute bronchitis simple). To assess the status of connective tissue metabolism, the daily excretion of the metabolite of connective tissue – oxyproline in the daily urine sample was determined. The metabolism of glycosaminoglycans was studied by the level of uronic acids in the urine. The level of blood glycosaminoglycans was determined. In establishing the presence of connective tissue dysplasia, the levels of stigmatization (a conditional index that includes the total number of connective tissue dysplasia points with the allocation of low, medium and high levels) were taken into account using the table "Indicators in the severity of connective tissue dysplasia". During the analysis of connective tissue metabolism in the serum of children with acute bronchitis complicated by broncho-obstructive syndrome with connective tissue dysplasia we observed phenotypic changes in the form of a decrease in the total level of the glycosaminoglycans, 2 and 3 fractions of the glycosaminoglycans, as well as an increase in the concentration of chondroitin sulfates of urine. Phenotypic portrait of children of the first group was characterized by dysplastic disorders of the skeleton, skin and its appendages, eyes, ears. From the list of external manifestations of dysmorphogenesis of children of this group, including 55 dysplastic signs, 24 (43.6%) were absent in children of the second group. The unfavorable factors of the formation of a syndrome of bronchial obstruction include the age of a mother older than 30 years and father's age older than 36 years, children born of the 3 or more pregnancies and childbirth, and burdened with an antenatal period of development of the fetus (anemia in pregnant women, manifestations of pregnancy gestosis, threat of premature abortion) and bad habits (including smoking) of mothers during this pregnancy. Connective tissue dysplasia causes prolongation of cough symptoms and physical changes (in the form of box shades of percussion sound, hard breathing, dry and damp mid-rash wheezing), which lead to the need of longer usage of mucolytic drugs.

Abstract Objectives GX-H9 is a long-acting form of recombinant human GH under clinical development for both adults and children with GHD. In this report, 24-month efficacy and safety of once weekly and every other week (EOW) administration of GX-H9 were evaluated, in addition to Genotropin® switch-ability to GX-H9 after 12-month of treatment. Methods Subjects were randomly assigned to receive either one of three doses of GX-H9 (0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week) or 0.03 mg/kg/day of Genotropin®. Treatment duration is 24-month for all patients in GX-H9 arms while patients in Genotropin® arm were re-randomized to one of three doses of GX-H9 at the completion of the first 12-month of treatment. Doses of GX-H9 were adjusted throughout the treatment period whenever necessary, based on IGF-1 levels. Results Out of 56 randomized, 54 received either GX-H9 or Genotropin®. Fifty subjects completed the 12-month treatment period. Of 50, 45 subjects completed the next 12-month, comprising 33 patients from GX-H9 and 12 patients who switched from Genotropin®. First year/second year mean±SD annualized height velocity (aHV) for 0.8 mg/kg/week, 1.2 mg/kg/week or 2.4 mg/kg every other week of GX-H9 were 10.50±2.54/9.14±1.96, 11.76±1.96/9.88±1.92 and 11.03±2.92/9.72±1.90 cm/year, respectively. First year mean±SD aHV for Genotropin® was 9.14±3.09 cm/year. Patients switched to one of the three doses of GX-H9 in the second year showed comparable aHV in the second year (8.73±2.69/7.60±0.90/9.13±1.07 cm/year for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg/EOW GX-H9, respectively). No significant slow-down of the growth was observed in the second year from patients who received GX-H9 throughout and patients who switched from Genotropin®. Mean change in height SDS after 12 months/24 months of GX-H9 treatment throughout from baseline treatment improved continuously (+1.10/+1.61 and +1.31/+1.89 and +1.15/+1.69 for 0.8 mg/kg/week, 1.2 mg/kg/week and 2.4 mg/kg EOW GX-H9, respectively). First year mean change in height SDS for Genotropin® was +0.92 SDS, and showed comparable improvement in height SDS after switching to GX-H9 weekly arms (+0.76 and +0.79 SDS for 0.8 mg/kg/week and 1.2 mg/kg/week, respectively). Most treatment-emergent adverse events were evaluated as unrelated to the study drug and were mild or moderate in severity. No new safety concerns were observed throughout 24 months of long-term GX-H9 treatment or after switching to GX-H9 from Genotropin®.Conclusions Growth response and safety profile of GX-H9 in children with GHD is comparable to those of daily GH, achieving robust growth rates after 24-month treatment. Subjects switched from Genotropin® in the second year, also showed substantial catch-up growth indicated by improvement in height SDS. GX-H9 has a unique potential to be a convenient long-term GH providing not only weekly but also twice-monthly treatment.

Physiological responses to exercise during the growth and development of children-athletes haven’t been established much. The aim of the study was to compare the results of pulmonary function test in children of middle childhood engaged in football and in sedentary children. Materials and Methods: The study included data from 66 male children aged 10-11 years, of which 50 children attended football sections; for more than 4 years (17); 2 to 4 years (19); less than 2 years (14). The control group consisted of 16 boys of the same age which do not have regular physical activity. We performed anthropometric evaluation that includes height and weight measurement; pulmonary function test was performed in accordance to ATS/ERS Guidelines. Statistical analysis performed with nonparametric tests. Results: The data of anthropometry had no significance difference in boys of different groups (increased BMI had the same prevalence in all groups). When football players and non-athletes are compared, pulmonary function test results such as VC, FVC, FEV1, MEF25-75 did not show any significant changes. Sings of bronchial obstruction were not found in both groups. The tidal volume difference was found in 1st and 4th groups [Mann-Whitney (MW), p=0,0059], 3rd and 4th groups [MW, p=0,0010]. The difference in minute respiratory volume was found in 1st and 4th groups [MW, p =0,0012], 2nd and 4th groups [MW, p=0,0074], 3rd and 4th groups [MW, p=0,0016]. This fact may be the evidence of fast respiratory system adaptation in boys of middle childhood during football training. Conclusion: Authors suggest that the respiratory pattern adaptation to a physical activity happens on early stages of the regular trainings

Changes in cardiorespiratory complex of adult athletes are the subject of scientific researches. However, there is a lack of researches that would assess such changes in children and adolescents involved in intensive physical training. The purpose of the study was to evaluate functional and morphological changes of cardiovascular and respiratory systems in boys of primary school age engaged in football. Materials and methods. 109 male children aged 10-11 years were enrolled in the study, among which 81 children have been attending sports football schools, 28 children didn’t have regular physical activity. The study design included a general clinical examination, a spirometry, the condition of cardiovascular system was assessed with echocardiography, and ambulatory blood pressure monitoring (ABPM). Results. The boys 10-11 years of age who play sports have higher values of minute respiratory volume and cardiac indices, which may support the hypothesis of the myocardial hypertrophy development, although they correspond to normal Z-score values. According to ABPM results the duration of physical activity may influence on transition from vasodilation to vasoconstriction. Conclusions. We obtained statistically significant quantitative differences in the functional state of the cardiovascular and respiratory systems in children-athletes. The changes found in young athletes may result to further supervision of a pediatric cardiologist, but decision should be made individually.

CLINICAL AND ANAMNESTIC FEATURES OF THE COURSE OF ACUTE BRONCHITIS IN CHILDRENStrelkova M., Senatorova G. The purpose of the study wasto detect clinical and anamnestic features of the course of acute obstructive bronchitis in children with a background of undifferentiated connective tissue dysplasia. Dynamic examination of 42 children with acute obstructive bronchitis was performed. The registration card for all children was developed and filled, it consisted of several sections: general information, family history, allergic history, life and past medical history, phenotypic assessment of undifferentiated connective tissue dysplasia. The results indicate that compromised allergic and genealogical history, as well as burdened obstetric history of the mother (threatened preterm delivery and gestosis) is significant risk factors. Assessment of clinical manifestations of acute obstructive bronchitis in children showed that the severity of the disease, which is determined by the degree of severity and duration of symptoms, was associated with the number of signs ofUCTD.Keywords: acute obstructive bronchitis, children, undifferentiated connective tissue dysplasia, wheezing, phenotypic assessment. РезюмеКЛИНИЧЕСКИЕ И АНАМНЕСТИЧЕСКИЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ОСТРОГО БРОНХИТА У ДЕТЕЙСтрелкова М., Сенаторова Г.Метою дослідження було виявити клінічні та анамнестичні особливості перебігу гострого обструктивного бронхіту (ГОБ) у дітей на тлі недиференційованої дисплазії сполучної тканини. Проведено динамічне обстеження 42 дітей з гострим обструктивним бронхітом. Розроблено і заповнено реєстраційну картку для всіх дітей, вона складалася з кількох розділів: загальна інформація, сімейний анамнез, алергологічний анамнез, анамнез життя та хвороби дитини, фенотипічні оцінки недиференційованої дисплазії сполучної тканини. Результати свідчать про наявність факторів ризику - наявність обтяженого алергологічного та генеалогічного анамнезу, а також обтяжений акушерський анамнез матері (наявність загрози передчасних пологів та гестозів). При аналізі клінічних проявів ГОБ у дітей було встановлено, що ступінь тяжкості та тривалості симптомів захворювання була пов'язана з кількістю ознак недиференційованої дисплазії сполучної тканини.Ключові слова: гострий обструктивний бронхіт, діти, недиференційована дисплазія сполучної тканини, фенотипічні ознаки. Резюме.КЛИНИЧЕСКИЕ И АНАМНЕСТИЧЕСКИЕ ОСОБЕННОСТИ ТЕЧЕНИЯ ОСТРОГО БРОНХИТА У ДЕТЕЙСтрелкова М., Сенаторова Г.Целью исследования было выявить клинические и анамнестические особенности течения острого обструктивного бронхита у детей на фоне недифференцированной дисплазии соединительной ткани. Проведено динамическое обследование 42 детей с острым обструктивным бронхитом (ООБ). Разработаны и заполнены регистрационную карточку для всех детей, она состояла из нескольких разделов: общая информация, семейный анамнез, аллергологический анамнез, анамнез жизни и болезни ребенка, фенотипическая оценка признаков недифференцированнойдисплазиисоединительной ткани. Результаты свидетельствуют о наличии факторов риска - наличие отягощенного аллергологического и генеалогического анамнеза, а также отягощенный акушерский анамнез матери (наличие угрозы преждевременных родов и гестозов). При анализе клинических проявлений ГОБ у детей было установлено, что степень тяжести и продолжительности симптомов заболевания была связана с количеством признаков признаков недифференцированнойдисплазиисоединительной ткани.Ключевые слова: острый обструктивный бронхит, дети, недифференцированная дисплазия соединительной ткани, фенотипические признаки.

There is insufficient number of researches dedicated to cardiorespiratory adaptation in various physical activities in general, and especially in children and adolescents for certain types of sport. The objective: to determine the cardiorespiratory adaptation features in boys of primary school age engaged in football. Material and method. The study involved data from 92 male children aged 10-11 years, of which 68 children attended sports football schools. The study design included a general clinical examination, a spirometry, condition of cardiovascular system assessed with echocardiography, exercise stress test with cycle ergometer (VEM), 24-hours electrocardiogram (Holter - ECG) monitoring, and ambulatory blood pressure monitoring (ABPM). Results. Boys 10-11 years of age who play sports have increased values of minute respiratory volume and heart morphology indices, which reflect the myocardial hypertrophy development, although they correspond to normal Z-score values. The frequency of subjective complaints in boys who do not practice football is significantly more frequent when performing the exercise test. According to VEM, Holter-ECG and ABPM results in 57 (83.8%) of 68 football players (p=0.00393) changes were registered. Conclusions. We obtained statistically significant quantitative differences in the functional state of the cardiovascular system in children-athletes. Satisfactory cardiorespiratory adaptation of boys-athletes is documented during various stages of physical activity with the help of VEM and Holter-ECG and ABPM. The changes found in young athletes may result to further supervision of a pediatric cardiologist, but decision should made individually.

Mycoplasma pneumoniae посідає провідне місце в етіології пневмонії у дітей. У статті наведено особливості перебігу резистентної до макролідів мікоплазмової пневмонії і сучасної тактики лікування на прикладі клінічного спостереження дитини шкільного віку. Авторами описані особливості епідеміології захворювання, акцентовано увагу на механізмах резистентності до макролідів Mycoplasma pneumoniae. У роботі детально описані механізми надмірної імунної відповіді, а також сучасні світові стандарти діагностики і тактики лікування пневмонії.