Introduction. Cystic fibrosis (CF) is a hereditary disease with genetic heterogeneity and clinical polymorphism. Expanding the range of knowledge about the characteristics of the course of the disease in different regions is important to achieve the goal of improving the quality and life expectancy.Purpose. Comparative analysis of the features of the course of CF in the subjects of the Southern Federal District, Stavropol Territory.Methods. Data from the National Register of Patients of the RF MV 2016 were used. Results: there are clinical and genetic features between the regions of the Southern Federal District and the Stavropol Territory of the North Caucasus Federal District and in general with the Russian Federation. Analysis of the data showed differences in indicators: the proportion of patients aged ≥ 18 is the lowest in the Republic of Crimea (14.9%), in the Rostov region the lowest average age of patients (9.0 ± 6.3), and the lowest age of diagnosis 2.2 ± 3.1 years. Late terms of diagnosis were revealed in the Stavropol Territory (4.0 ± 8.0 years), but here there is one of the highest average age of CF patients (14.1 ± 11.5), the proportion of adult patients (23.3%) and the lowest allelic frequency of F508del, which is determined by the high number of patients with a “soft” genotype. There is a high proportion of patients with an undetermined genotype. A low proportion of two identified genetic variants of the CFTR gene is registered in patients of the Republic of Crimea. A low frequency of Burkholderia cepacia complex and Achromobacter spp was revealed, and a high infection with non-tuberculous mycobacteria was revealed in the Rostov region. FEV1 in children and adults was lower in Rostov Region and Stavropol Territory. In all regions, there is a discrepancy between the seeding of flora and azithromycin therapy and the severity of the genotype with the use of pancreatic enzymes.Conclusions. Analysis of the data of the registry, which allows substantiating the need to study the regional characteristics of the course of CF in order to differentiate the planning of measures to improve the quality of medical care for patients with CF.

Study of efficacy, safety, and patient satisfaction with inhaled tobramycin (Tobramycin-Gobbi) in children with cystic fibrosis and pseudomonas infectionAim of the study was to assess efficacy and safety of Tobramycin-Gobbi in CF, as well as the patients’ satisfaction with the treatment.Methods. 35 children from 6 to 18 years with CF were enrolled in this non-interventional prospective cohort multicenter study. All children had P. aeruginosa in the respiratory tract (newly diagnosed, recurrent, or chronic infection). The children received inhalation treatment with Tobramycin-Gobbi in the following cycles: 28-day treatment/28-day break, for 6 months. The studied parameters included respiratory function, bacterial cultures of the respiratory tract with a bacterial count, growth and body weight, antibiotic therapy for the respiratory episodes. The children and parents filled in a questionnaire “Treatment satisfaction assessment” and assessed their state of health on the visual-analog scale before and after each treatment cycle.Results. P. aeruginosa was eradicated in 17.7% of cases (6 patients, including 2 newly diagnosed, 3 recurrent infections, and 1 chronic infection), reduced bacterial count, decreased number of courses of antibiotic therapy, improvement of FEV1. Adverse reactions were reported by one patient.Conclusion. The efficacy, safety, and tolerability of Tobramicine Gobbi were confirmed in the patients with newly diagnosed, recurrent, and chronic infection caused by P. aeruginosa.

Муковисцидоз – тяжелое моногенное заболевание, характеризующееся ухудшением качества и сокращением жизни больного. Липиды обеспечивают нормальное течение процессов клеточного метаболизма, стимулируют неспецифический иммунитет и являются предшественниками стероидных и половых гормонов. Исследование липидного обмена у детей Ставропольского края, страдающих муковисцидозом, выявило выраженную дислипидемию, при форме с панкреатической недостаточностью – обратную, статистически значимую зависимость между эластазой кала и ЛПВП, временную дисфункцию надпочечников и уменьшении расходов холестерина на синтез стероидов, что, в свою очередь, может усугублять обструктивный синдром.

Cistic fibrosis (CF) is the hereditary disease, presenting the important medical social problem, related with timely diagnostics, the early disablement of patients, short duration of their life, need for a constant performing therapeutic measures and active clinic observation. In 2008 in the North-Caucasian Federal Region (NCFR), there was introduced the register of СF patients, in 2015 the data about patients residing in the Stavropol territory were sent for the introduction into the register of CF cases of the Russian Federation. The executed analysis showed the register of СF cases of the Russian Federation to be is insufficiently used in all NCFR regions, which makes impossible the processing of data about the special features of the course, the clinical manifestations, epidemiology, genetic inspection, microbiological monitoring and treatment of the disease in the region. The implemented analysis of the management of СF patients in NCFR, determines the need of creating the united regional center for the improvement of the centralized aid for considered patients.

Детская клиническая больница № 1, ярославль 150003, Российская Федерация 36 Клиническая больница № 2, ярославль 150010, Российская Федерация Цель исследования.Изучить особенности и разнообразие спектра патогенных генетических вариантов гена CFTR (ABCC7) у российских пациентов с МВ, представленных в Регистре больных муковисцидозом (МВ) Российской Федерации (РФ) 2017г.Материал и методы.Проанализированы результаты генотипирования, включавшего анализ частых патогенных генетических вариантов, секвенирование кодирующей последовательности, поиск генных перестроек гена CFTR, 3096 больных из 81 региона-субъекта Российской Федерации, представленных в Регистре больных МВ в РФ 2017 г.Результаты.Выявлено 196 патогенных генетических вариантов гена CFTR.Суммарная доля 11 генетических вариантов c.1521_1523delCTT (F508del), c.54-5940_273+10250del21kb (CFTRdele2,3), c.274G>A (E92K), c.2012delT (2143delT), c.3718-2477C>T (3849+10kbC->T), c.3846G>A (W1282X), c.2052_2053insA (2184insA), c.1545_1546delTA (1677delTA), c.3909C>G (N1303K), c.1624G>T (G542X), c.413_415dupTAC (L138ins) составляет 75,6 %. 102 редких вариантов обнаружены однократно, 29 -дважды.Как в спектре, так и по частоте у пациентов в РФ преобладают варианты, приводящие к серьезным нарушениям функции белка CFTR (I, II, III классы).44 генетических варианта не внесены в базы CFTR1 и CFTR2.Заключение.На основании данных Регистра 2017 года определены спектр и относительные частоты патогенных вариантов последовательности гена CFTR у российских больных МВ; описано их распределение в зависимости от класса и типа.Выявлены генетические варианты, ранее не описанные в базах CFTR1 и CFTR2.Полученные результаты могут использоваться для оптимизации генетического консультирования и клинической работы с семьями, отягощенными МВ, а также для дальнейших исследований патогенетической значимости ранее не описанных генетических вариантов гена CFTR.

The aim of this study was to investigate genetic features of patients with cystic fibrosis (CF) according to the National Register findings in Russia. Methods. The study involved 2,131 CF patients living in 74 regions of Russia who were included in the National Register of CF patients in 2014. Results . Genetic testing was performed in 89% of patients. The total mutant allele frequency was 81.2%. One hundred and twenty two mutations were found which comprised 173 genotypes; «mild» mutations took 23%. The most common mutant allele frequencies in the descending order were as follows: F508del, 51.53%; СFTRdele2,3, 5.93%; E92K, 2.62%; 3849+10kbC>T, 2.14%; 2184insA, 1.80%; W1282X, 1.80%; 2143delT, 1.69 %; N1303K, 1.43%; G542X, 1.16%; 1677delTA, 0.98%; L138ins, 0.95%; R334W, 0.85%; 394delTT, 0.85%; 3821delT, 0.42%; 2789+5G>A, 0.37%; S466X, 0.37%; S1196X, 0.37%; 3272-16T>A, 0.34%; W1282R, 0.29%; 3944delGT, 0.21%. Typical features of CFTR mutation distribution in Russian CF patients were lower frequency of mutations which are predominant worldwide, such as F508del, G542X, N1303K, and scarce G551D, 1717-1G>A, 2183AA>G mutations. On contrary, СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins mutations which are quite rare in Western Europe were encountered more often in Russia. «Mild» mutations were more common in Russian population of CF patients compared to European countries and have being increasing last years. Conclusion. Genetic features of Russian CF patients could be provided by Slavic, Turkic and Finno-Ugric genetic influence on Russian population.

The aim of this study was to investigate genetic features of patients with cystic fibrosis (CF) according to the National Register findings in Russia. Methods. The study involved 2,131 CF patients living in 74 regions of Russia who were included in the National Register of CF patients in 2014. Results . Genetic testing was performed in 89% of patients. The total mutant allele frequency was 81.2%. One hundred and twenty two mutations were found which comprised 173 genotypes; «mild» mutations took 23%. The most common mutant allele frequencies in the descending order were as follows: F508del, 51.53%; СFTRdele2,3, 5.93%; E92K, 2.62%; 3849+10kbC>T, 2.14%; 2184insA, 1.80%; W1282X, 1.80%; 2143delT, 1.69 %; N1303K, 1.43%; G542X, 1.16%; 1677delTA, 0.98%; L138ins, 0.95%; R334W, 0.85%; 394delTT, 0.85%; 3821delT, 0.42%; 2789+5G>A, 0.37%; S466X, 0.37%; S1196X, 0.37%; 3272-16T>A, 0.34%; W1282R, 0.29%; 3944delGT, 0.21%. Typical features of CFTR mutation distribution in Russian CF patients were lower frequency of mutations which are predominant worldwide, such as F508del, G542X, N1303K, and scarce G551D, 1717-1G>A, 2183AA>G mutations. On contrary, СFTRdele2,3, E92K, 2184insA, 2143delT, 1677delTA, L138ins mutations which are quite rare in Western Europe were encountered more often in Russia. «Mild» mutations were more common in Russian population of CF patients compared to European countries and have being increasing last years. Conclusion. Genetic features of Russian CF patients could be provided by Slavic, Turkic and Finno-Ugric genetic influence on Russian population.

A survey of 203 children with diseases, flowing with bronchial obstruction syndrome aged 1 month to 18 years in the period from 1999 to 2013 years (81 patients with a mixed form of cystic fibrosis (CF), 54-atypical pneumonia (AP), 68-obstructive bronchitis (OB) with recrudescent). The incidence of CF in the Stavropol region in 2013 was 0,89 per 10000 population of children. In 2007 the neonatal screening identified risk group of 3 children, 2009 – 2 child, 2010 – 3 children, 2011 – 2 child, 2012 – 6 children. In 2013 neonatal screening held of 37452 children; the 250 it was questionable, and 10 patients diagnosed with CF confirmed genetically. The prevalence of CF on the specified data neonatal screening in the Stavropol region amounted to 1 at 3745, in the Russian Federation – 1 on 10498 newborns. Monitoring the health status of patients with CF has identified the need to find new, more modern markers to improve diagnostics, which investigated the lipid profile and elements status of patients. The comparative analysis of changes in lipid metabolism and elements in children suffering from a mixed form of CF, AP and OB to recommend lizofosfotidilholin of erythrocyte membranes, hilomikrons, pre-β-lipoprotein, B+3, Na+ and Pb+4 as additional tokens when making a diagnosis of cystic fibrosis.

Изучены изменения липидного обмена у детей Ставропольского края, страдающих легочной патологией, сопровождающейся бронхообструкцией: атипичной пневмонией (I основная группа), обструктивным бронхитом (II основная группа) и смешанной формой муковисцидоза (III основная группа). Выявлено: при АП происходит повышенное расходование энергии (уменьшение уровня ФТЭА), увеличение липолиза (нарастание НЭЖК) и повышение нестабильности клеточных мембран, дислипидемия у детей ОБ носит преходящий характер. Нарушение относительной стабильности концентрации фракций фосфолипидов при смешанной форме МВ как до, так и после лечения свидетельствует о глубоких дезадаптационных процессах, так как изменения в структуре и составе фосфолипидов, как и нарушения взаимоотношений важнейших липидных метаболитов в сыворотке крови, могут привести к нарушению фазового состояния мембраны клетки, ее проницаемости, уменьшению обмена веществ в ней, снижению энзиматических функций.

Изучены перинатальный анамнез и характер сопутствующей патологии у детей Ставропольского края, страдающих атипичной пневмонией (I основная группа), обструктивным бронхитом (II основная группа) и смешанной формой муковисцидоза (III основная группа). Беременность и роды у матерей детей основных групп протекали с большим количеством осложнений, особенно у матерей III основной группы. В структуре сопутствующей патологии у изучаемого контингента детей чаще всего диагностировались патология нервной системы, детские инфекции, гипотрофия и рахит; 100% ОРВИ во всех основных группах предполагает снижение иммунитета, высокий процент пищевой аллергии во II основной группе свидетельствует об аллергической составляющей обструкции, а гипотрофии в III основной группе можно расценить как проявление основного заболевания.