BACKGROUND:Differential diagnosis of hypogonadotropic hypogonadism (HH) and constitutional delay of puberty (CDP) is extremely important since with the latter puberty begins and completes without any medical intervention and in the case of HH puberty does not occur or is incomplete. Failure to start treatment on time leads to medical and psychosocial maladjustment of the patient. AIM:Development of a method for differential diagnosis of hypogonadotropic hypogonadism and constitutional delay of puberty in boys 13.5-17 years old by scoring the levels of LH, FSH, testosterone and inhibin B. MATERIALS AND METHODS:The study group was formed by adolescent men 13.5-17 years old with delayed puberty including all observations. Anamnesis, stage of puberty, testicular volume were assessed; serum levels of LH, FSH, testosterone (T) were determined by chemiluminescent analysis and inhibin B, AMH by ELISA. Stimulation tests were performed with triptorelin and human chorionic gonadotropin (3 days). Patients were followed up for 6-24 months. RESULTS:The study included adolescent men at the age of 13.5-17 years with delayed puberty: 56 for the purpose of development a method of differential diagnosis, 30 for its control (control group). We`ve created a method that allows differentiate HH and CDP. Through the ROC-analysis the most sensitive and specific HH markers were identified. The basal levels of LH, FSH, T, and inhibin B were selected as most available for outpatient testing. Based on the results of our own research and scientific data we selected ranges of values and rated LH, FSH, T and inhibin B depending on them (marks). Then we assigned the coefficients (k) for each hormone. Scores were calculated by multiplying the marks by k then summed and normalized to the maximum amount the patient could get. To increase the accuracy of diagnosis an age coefficient was introduced. The result of the calculation was the result of the scoring (S). S for CDP (10.65 [3.13-14.91]) differed significantly from that for HH (76.46 [57.79-83.74]) (p< 0.001). Diagnoses based on S (<21.16 and ≥55.07) in the control group were confirmed by follow up data in 97% cases. An algorithm for the differential diagnosis of HH and CDP by using S has been developed. CONCLUSION:The result of scoring of LH, FSH, testosterone, inhibin B levels ≥55.07 makes it possible to diagnose hypogonadotropic hypogonadism, < 21.16 - constitutional delay of puberty with a high probability. In the case of score ≥21.16 but < 55.07, calculation of the inhibin B/AMH ratio and/or stimulation tests are required.

Idiopathic pulmonary hemosiderosis (IPH) is a rare disease of unclear etiology that belongs to interstitial lung diseases and is characterized by a triad of symptoms: hemoptysis, iron deficiency anemia, and diffuse interstitial changes on computed tomography (CT) of the chest cavity. IPH can occur at any age, but the disease develops in childhood in 80% of cases, more often before 10 years of age. A significant proportion of pulmonary hemosiderosis cases in this age group remain undiagnosed. The purpose of the study is to demonstrate a clinical case illustrating the features of differential diagnosis and therapy of IPH during the COVID-19 pandemic. Conclusion. An 8-year-old girl was diagnosed with IPH based on fever, shortness of breath, weakness, and severe iron-deficient anemia. The chest CT scan revealed diffuse interstitial ground-glass opacity in lungs. The lung biopsy revealed hemosiderin deposits and hemosiderophages in the alveolar lumens. Treatment with systemic glucocorticoids (SGC) and azathioprine was effective. The patient was followed for 3 years.

In addition to type 1 and 2 diabetes mellitus (DM), endocrine disorders in children include hereditary forms of diabetes, such as maturity onset diabetes of the young (MODY). Since pathogenic mechanisms of chronic hyperglycemia in MODY are different from those in DM1 and DM2, it requires other therapeutic approaches. The diagnosis of MODY is confirmed by expensive molecular testing, such as next generation sequencing (NGS). Therefore, the strategy of choosing candidates for NGS is very important. Objective. To optimize the algorithm of choosing patients for NGS testing for DM type verification. Patients and methods. This study included 97 patients aged 1–18 years suspected of having MODY. We used NGS to confirm the diagnosis and identify polymorphisms in MODY-associated genes. Results. Fifty-three patients were found to have polymorphisms in MODY-associated genes, including GCK gene (MODY2) (n = 44), NHF1A gene (MODY3) (n = 8), and PAX4 gene (MODY9) (n = 1). Comparison of family histories of patients with MODY-associated polymorphisms and those in whom clinical diagnosis of MODY was not confirmed by NGS demonstrated significant differences: children with verified MODY were more likely to have first-degree relatives with some carbohydrate metabolism disorder (CMDs). Clinical, laboratory, and anthropometric parameters, as well as levels of insulin secretion and carbohydrate metabolism were similar in both groups. However, patients with non-confirmed MODY received insulin therapy more frequently than those with verified MODY as the majority of them were on a diet. Conclusion. NGS confirms the diagnosis of MODY in patients with different CMDs. A tailored approach should be used to choose patients for NGS to confirm MODY. Key words: monogenic diabetes mellitus in children, diabetes mellitus, next generation sequencing, GCK, HNF1A, MODY

Cystic fibrosis (OF) is characterized by disorders of chloride secretion and sodium absorption in exocrine epithelium. A crucial location of these ion disorders is the respiratory epithelium. Such ion pathology forms a transepithelial electric potential difference. It is hard to measure tracheobronchial electric potential difference, so a method for measuring nasal potential difference (NPD) was created. We measured baseline values of NPD in 100 patients (including 45 OF patients) and in 15 healthy volunteers. More significant negative values of the average baseline NPD were registered in the OF patients (42.2±1.4 mV) compared with healthy and COPD persons (-18.3±1.8 and 19.2±0.6 mV accordingly, p <0.0001). NPD values in 6 (13%) OF patients with typical clinical features, normal or boundary sweat test results and CF gene confirmation were compatible with CF bioelectric profile. Meantime 3 COPD patients had increased sweatiest results and a low NPD level. Under amiloride hydrochloride blocking sodium channels the basal NPD was inhibited greatly (up to 66%) in CF patients, whereas the same value in COPD patients was 36.7%.Therefore, the NPD reflects the principal CF disorder. Its increase under the amiloride influence more than 60% is thought to be used as an additional diagnostic test.

Based on the long-term surveillance of 127 patients older than 15 yrs and 173 children aged 3 months to 15 yrs we concluded of the survival age of cystic fibrosis patients in Russia (16.9 ±1.1 yrs). Patients older than 15 yrs take 30.1 % of all the investigated patients. Under the adequate surveillance and treatment conditions 82.4 % of adult patients keep their social activity and only 17.6 % of the patients do not work and do not study.

25 patients with CF and 20 with others of COPD were examinated. Ciliary beat was measured by a lifetime TV microscopy of bioptates of respiratory mucous. Material was obtained with the help of brush biopsy during fiberoptic bronchoscopy. The image of ciliary beat from a light microscope was recorded on the hard disk of the personal computer. The specially created program estimated ciliary beat frequency (CBF) and amplitude of ciliary beating. CBF into bronchi of the CF patients have made at impact phase – 6.3+0.33 Hz, raising phase – 5.7+0.36 Hz; in the patients with COPD: 6.5+0.32 Hz and 6.2+0.33 Hz accordingly. The precise tendency to a drop of CBF and amplitude of ciliary beating in the patients with CF on a comparison with the patients with COPD and literary datas was marked. Also, the drop of indexes of beating in the patients with Ps.aeruginosae mucoid were marked.

We studied 21 children with cystic fibrosis (CF). W e carried out bronchial challenge tests with methacholine and histamine and revealed hyperreactivity in 18 patients. A comparative study was performed of the bronchial reactivity depending on the CF severity, the patients' phenotype, course of inflammatory respiratory process and co-existing allergic pathology, nose and digestive diseases.

Bronchial asthma (BA) is a multifactorial disease, genetic factors play an important role in its etiopathogenesis. At the same time, data on associations of polymorphic variants of the estrogen receptor gene with BA are quite contradictory. Objective of this research was to study the peculiarities of allele polymorphism frequencies of ER1 and TNF-α genes and their combinations in patients with atopic BA depending on the disease severity. Materials and methods: in the course of a retrospective single-center comparative pilot study by PCR/RFLP analysis, the frequencies of alleles and genotypes for the ER1 and TNF-α genes were determined in 78 prepubertal children (9 [6–13] years) with atopic BA. The population comparison group included 115 people. Results: the study revealed that in BA patients with moderate severity, genotypes Xx (48% and 14%; OR=6,067 CI=[1,653–22,268]), and Pp (94% and 47%, respectively; OR=18,074 CI=[2,319–140,854]) of the ER1 gene were statistically significantly more common than in the comparison group. A statistically significant difference was found in the distribution of genotype combinations for the XbaI and PvuII polymorphisms of the ER1 and –308A genes>G of TNF-α gene polymorphism in patients with BA and in the comparison group (2=31,761, p=0,0043). The frequency of the combined a-PpXx genotype in BA patients was higher than in the comparison group (22% and 3%, OR=11,09, p<0,0001). Conclusion: associations were found between the severity of BA and the genotype of the ER1 gene. The revealed absence of associations of polymorphism of the ER1 gene and BA with gender is probably due to the fact that we observed the direct influence of genetic factors without the influence of hormonal background.

This article demonstrates high clinical efficacy of long-term treatment of bronchial obstructive syndrome in cystic fibrosis (CF) patients with N-acetylcysteine (Fluimucil, Zambon Group). Lung function parameters, oxygen saturation, sputum viscosity, biochemical parameters of inflammation activity in sputum (elastase, sialic acid and α 1 -antitripsin concentrations) were evaluated. Oral Fliumucil was combined with inhaled N-acetyl-Lcysteine. The therapy resulted in reduction of the sputum viscosity, recovering of the mucociliary clearance, improvement in the lung function, antiinflammatory and antioxidative effects of Fliumucil. This allows to recommend the drug for the long-term basic therapy of bronchoobstructive syndrome in CF patients.

The present prospective study was carried out to assess the contribution of polymorphisms of the genes that code for the enzymes of the second phase of detoxication of xenobiotics and for antioxidant enzymes of the GSTT1 glutathione-S-transferase family to the development of bronchial asthma phenotypes in childhood. The study group comprised 238 children having bronchial asthma diagnosed according to GINA criteria valid at the time of examination. The children were categorized into groups according to the following phenotypes: atopic asthma (AA, 128 subjects), asthma associated with limited allergic lesions of the respiratory tract in children whose parents suffered from allergies (RA_H+, 88 subjects), and the same as in the latter group but without hereditary predisposition to allergy (RA_H-, 22 subjects). It has been shown that, despite the absence of differences in the rates of homozygous deletion polymorphisms of GSTT1 and GSTM1 genes between virtually healthy people living in Saint Petersburg and bronchial asthma patients, different asthma phenotypes show significant differences between them and upon comparison of any of them with the general population. In children having asthma associated with limited allergic lesions of the respiratory tract without hereditary predisposition to allergic diseases, the key determinants of the pathogenesis of their disease are genetically determined defects in the enzymes of GSTT1 and GSTM families involved in the detoxication of xenobiotics.

The objective: To develop a method for predicting exacerbation of chronic illness in children with asthma and cystic fibrosis, patients with influenza, based on the study of the dynamics of cytokines. Materials and methods: Were examined 52 patients with bronchial asthma and 45 children with cystic fibrosis at the age from 1 year to 12 years, located in infectious pulmonary Department at the planned treatment of underlying pathology, in which influenza was in-hospital infection. Control group observations included 40 patients with the flu, without concomitant pulmonary disease. The etiology of viral infection was established by detection of viral RNA in nasopharyngeal swabs by PCR. Among the influenza viruses were identified influenza АH1N1, АH3N2, influenza B, and in 2009–2010 the predominant antigen was the pandemic influenza virus АH1N1pdm09. Determination of the concentration of serum interleukins IL-1β, IL-4, IL-8, IL-10, ТNF-α, IFN-γ was performed in the 1st and 3rd day of hospitalization cytokines by the solid-phase immune-enzyme assay. Analysis of the results performed using statistical package SPSS 17.0 EN for Windows. Results: The flu caused the aggravation associated bronchopulmonary pathology in 2/3 of children, as MV patients, and patients with BA (65,4%-66,7%, respectively). With an increase of the ratio of IL-4 / IFN-γ and IL-10/IFN-γ, at least 5-6 times, influenza can be considered a trigger of exacerbation of chronic bronchopulmonary pathologies that require amplification of the therapy of bronchial asthma and of сystic fibrosis. The growth of prognostic coefficients in 2-3 times allows using for treatment of influenza in these patients only antiviral agents. Conclusion: The study has shown a method for predicting exacerbation of bronchial asthma and cystic fibrosis in children at an early stage of influenza by calculating the ratio of IL-4/IFN-γ and IL-10/IFN-γ in children aged from 1 year to 12 years.

Background. To detect sixteen cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations most common to Russian populations in children with severe asthma (SA). Patients and Methods. S A group included 59 children aged 4-17 years old (43 boys and 16 girls). Cystic fibrosis (CF) group included 27 children aged 5-17 years old with a primary diagnosis of CF (15 boys and 12 girls). We used two kits developed by Center for M olecular Genetics (Moscow): «CF-5» kit (G542X, W1282X, N1303K, 3849+10kbC>T, R334W) and «CF-11» kit (del21 kb, F508del, I 507del, 1677delTA, 2143delT, 2184insA, 394delTT, 3821delT, L138ins, 604insA, 3944delTG). Results. I n the group of children with CF, the frequency a major mutation F508del was 85% (41% with genotype F508del/ F508del, 29% with genotype F508del/nomal and 15% with compound genotype F508del/others). I n 15% of the cases, there were identified some other mutations of the CFTR gene: N1303K, 394delTT, 2143delT, CFTRdele2, 3 (21kb). The rest 7% of the cases were not clarified. We have found neither «mild» nor «severe» the mutations of CFTR gene in the S A group. Conclusion. This study failed to show an association of mutations of CFTR gene with severe asthma in children.

TNFA, связанный с наиболее низкой экспрессией гена, приводит к значительному уменьшению риска заболевания БА (OR = 0,097).Atopic bronchial asthma (ABA) is a complex genetic disease characterized by increased airway responsiveness to a variety of stimuli, reversible airway obstruction, and airway inflammation. The genetic polymorphisms -238 A/G and -308 A/G of the TNFA gene were studied by PCR-RFLP analysis in the group of asthmatic patients with age of manifestation before 18 years (83) and the population group (117). According to obtained data the frequency of -238A allele of the TNFA gene was significantly lower in the group of patients with ABA (1,2%) as compared to the population group (5,6%). The analysis of distribution of the G -308A polymorphism of the TNFA gene revealed significant increase of the frequency of -308A allele in the patients with ABA (9,0%) as compared to the population (4,0%). According to odds ratio the careers of -308A allele of the TNFA gene have 2-fold increased risk of the development of ABA (OR = 2,48; CI: 1,06-5,82). The frequency of -308A allele of the TNFA gene in the group of patients was significantly higher in women (14,8 %) as compared to men (2,6 %, p = 0,0064, df = 1). After comparing the distribution of genotypes of -238 and -308 polymorphisms of the TNFA gene together significant difference between patients with ABA and population was observed. Combined genotype -238A/G + -308G/G of the TNFA gene associated with the lowest level of gene expression resulted in considerable decrease of ABA risk (OR = 0,097). Different hypotheses of the role of polymorphic variants of the TNFA gene in pathogenesis of ABA were discussed.

It’s well known that neutrophils being fundamental effectors of the host protective from bacteria infection can generate various oxidants and proteins with antibacterial functions such as myeloperoxidase (MPO) and lactoferrin (LF). The aim of our study was to determine the MPO and LF concentrations in serum, sputum and lavage of patients with cystic fibrosis in minimum activity and exacerbation periods of disease, with and without Ps. aemginosa. High levels of MPO and LF had been determined in blood, sputum and lavage fluid in minimum activity of disease. There were no difference in MPO and LF serum concentrations between minimum activity and exacerbation periods of disease, but at the same time concentrations of these proteins were significantly higher (p