Introduction . Cystic fibrosis is a severe systemic multiorgan exocrinopathy, the severity of the condition in 95% cases is caused by the depth of respiratory organ damage. Symptom management drugs that were developed over more than 50 years allowed to improve survival, but average life expectancy in cystic fibrosis (CF) remains well below the general population average. Targeted therapy is the most promising treatment, which restores the chloride channel function. Lumacaftor/ivacaftor is the first targeted therapy drug authorized in Russia. Aim . To evaluate the effect of lumacaftor/ivacaftor therapy on the respiratory function, microbiological profile, nutritional and oxygen status, as well as the rescue antibiotic therapy coverage in adult patients with CF. Materials and methods . 39 adult patients with CF received lumacaftor/ivacaftor for one year. The therapy effectiveness endpoints included the changes in indices of the pulmonary function tests: FEV 1 , FVC, FEV 1 /FVC, sweat test results, nutritional and oxygen status, antibiotic therapy coverage. The tolerability of the drug was assessed. The median age of patients was 28.9 (11.3) years. 6 patients (15.4%) discontinued therapy due to different adverse reactions. Results . The median increase in FVC was 2.9 (4.1)%, in FEV 1 – 3.1 (4.1)%, sweat chloride decreased by 21 (27) mmol/l during 1–1.5-month lumacaftor/ivacaftor therapy. After 12-month therapy, the median increase in FVC was 2.3 (3.6)%, in FEV 1 – 2.4 (3.8)%, BMI increased by 0.6 (0.6) kg/m 2 and the frequency of rescue antibiotic therapy decreased by half. The patients showed a significant increase in FVC and FEV 1 indices and a decrease in sweat chloride after 1-month therapy and an increase in FEV 1 indices, BMI vales as well as a reduced need for rescue antibiotic therapy after 12-month therapy. Conclusion . The first experience with a long-term pathogenetic therapy with lumacaftor/ivacaftor in adult patients with CF in Russia demonstrated the expected positive effect on the respiratory function and changes in nutritional status, a reduced need for rescue antibiotic therapy, and low rates of adverse reactions.

The aim of this investigation was to analyse the register of cystic fibrosis (CF) patients of Central Federal District (CFD) of Russian Federation (RF) in 2017. The register of CF patients includes data on 3096 people from 81 regions-entities of RF. CF patients in CFD represent 30% of total amount of patients included in the register. The full data presents 9 regions. The data of the rest 9 regions is presented partially. There is a list of genetically, clinical and microbiological peculiarities in comparison with RF in general and, at the same time, with other districts of CFD. The difference between adult patients and average age of patients by areas of received treatment, laboratory and instrumental indicators. There are obvious differences in infection indicators of the same age groups, there is difference in provided therapy. The analysis of the register data will enable to optimize aid to CF patients in CFD, to take over the experience of regions with the best indicators and criteria of the progress of the disease.

AIM:To compare auditory function during screening of children of different age groups who received ototoxic therapy.PATIENTS AND METHODS:Auditory function was studied in various categories of children receiving ototoxic drugs. Hearing was assessed by the registration of distortion product otoacoustic emission (DPOAE), short-latency evoked potentials (SLEP), tympanometry. Statistical processing was performed using the C program Statgraphics Centurion XV.RESULTS:In this study, screening of auditory function in children suffering from cystic fibrosis and receiving ototoxic treatment revealed pathologic conditions of the middle ear according to tympanometry in 15.4% of cases, impaired auditory function in 28.2% of cases according to DPOAE. Early ototoxicosis presented as a decrease in the amplitude of the response at a frequency of 4 kHz, and a change in the structure of the DP-gram in the form of a shift to the low-frequency area. Examination of the auditory function of premature infants receiving potentially ototoxic drugs in the early neonatal period demonstrated that the administration of ototoxic drugs does not affect the maturation of outer hair cells.CONCLUSION:Audiological control, such as tympanometry and registration of evoked otoacoustic remission should be included in the outpatient observation of children with a history of ototoxic drugs.

A non-interventional prospective cohort study was conducted on adult patients with cystic fibrosis, who received mucolytic therapy with 7% NaCl solution combined with 0.1% hyaluronic acid (medical product Hyaneb) and 7% NaCl solution for 4 and 8 weeks. Materials and methods: A total of 24 CF patients over 18 years old were enrolled in the study. A comparative analysis of respiratory function, therapy satisfaction, efficacy and safety of treatment was conducted following 4 weeks of therapy in 7% NaCl Solution Group (n = 12) and MP Hyaneb Group (n = 12), and the dynamics of these parameters was assessed against the background of the use of MP Hyaneb for 8 weeks (n = 12). Results: At week 4 of treatment, a significantly smaller number of patients complained of nasal congestion, ears and or accumulation of mucus in the throat and chest, irritation of the throat and unpleasant taste in the MP Hyaneb Group. No significant differences in the onset and increase in the intensity of cough were achieved. No significant differences between the groups in terms of spirometry parameters were identified. Findings: MP Hyaneb showed the best tolerability compared to 7% NaCl solution in adult patients with cystic fibrosis. The use of MP Hyaneb reduces the frequency and severity of irritation of the pharyngeal mucosa, cough and nasal congestion following administration for one month.

Российский национальный исследовательский медицинский университет им.Н. И

НИИ Пульмонологии, Москва 115682, Российская Федерация 2 Медико-генетический научный центр, Москва 115478, Российская Федерация 3 Российский национальный исследовательский медицинский университет им.Н. И. Пирогова, Москва 117997, Российская Федерация Цель исследования.Оценка динамики показателей национального регистра больных МВ за 2011-2017гг

Background: Evaluation of the main clinical and functional indicators and their relationship with the treatment and diagnostic care at different time periods can contribute to the development of further effective medical strategies and globally lead to improved care for cystic fibrosis patients. Aim: An assessment of the dynamics of some clinical and functional indicators in adult CF patients, who have been observed ed Research Institute of Pulmonology during the last 15 years(2003–2018). Methods: The comparative analysis was performed on the data of adult patients with cystic fibrosis, observed at 31.12.2003 and at the end of October of 2018. The group of patients in 2003 consists of 80 and in 2018 — of 667 patients. The comparative analysis between the groups was carried out according to the following indicators: age, survival, lung function, nutritional status, proportion of infection with pathogenic microflora, identification of mutations in the cystic fibrosis gene and diagnosis in adult patients. Results: An increase in patient’s age, survival rate, the proportion of identified mutations in cystic fibrosis gene and infection of Burkholderia cepacia complex in the group of patients in 2018 was revealed. There were no differences in the state of lung function, nutritional status, the ratio of the living and dead patients and proportion of patients diagnosed in adulthood between groups. Conclusion: The progress in the treatment through the introduction of modern methods and therapeutic programs leads to improved survival and an increase in the number of adult patients with cystic fibrosis.

The aimof this study was to analyze drug therapy of patients with cystic fibrosis (CF) in Russia.Methods.Findings of the Russian National Register of CF patients, 2014, were used in this study. The 2014 Register included data for 2,131 patients (2,092 alive and 39 died) from 74 regions of Russia. The median age was 10.2 (15.2) years, 29.2% of patients were aged 18 years and older. We analyzed administration of bronchodilators, inhaled corticosteroids (ICS), systemic steroids, dornase alfa, hypertonic saline solution, macrolides, systemic and inhaled antibiotics, pancreatic enzymes, ursodeoxycholic acid, and fat-soluble vitamins.Results.Drug administration rates were as follows: bronchodilators, 65.9%; ICS, 21.7%; systemic steroids, 5.5%; macrolides, 32.4%; dornase-alfa, 92.8%; hypertonic saline solution, 45.9%; intravenous antibiotics, 62.3%; oral antibiotics, 73.3%; inhaled antibiotics, 41.3%; pancreatic enzymes, 93.3%; ursodeoxycholic acid, 91.4%; and fat-soluble vitamins, 88.3%.Conclusion. Compared to treatment of CF patients in the Western Europe, there is higher rate of administration of pancreatic enzymes, ursodeoxycholic acid, dornase alfa, hypertonic saline solution and intravenous antibiotics in Russia. Compared to treatment strategy in USA, there is higher rate of administration of pancreatic enzymes and lower rate of administration of bronchodilators, hypertonic saline solution and inhaled antibiotics in Russia.

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.