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Cystic fibrosis (CF) is one of the most common autosomal-recessive inherited diseases. The primary genetic defect in CF is aligned CFTR gene mutation which encodes a membrane protein functioning as cAMP-depended chloride channel. Classic phenotypical manifestations of CF include chronic obstructive pulmonary disease with bronchiectasis, persisting infection (St. aureus, Ps. aeruginosa, B. cepacia) and aberrant inflammatory response, as well as exocrine pancreatic insufficiency with malabsorption, hypotrophy and growth retardation. CFTR deficiency is also accompanied by β-cell pancreatic dysfunction, causing glucose metabolism disturbances and CF-related diabetes. The aim of the study was the comparison of inflammatory markers dynamics in patients with normal and disturbed glucose metabolism during pulmonary exacerbation treatment. The study included 10 patients with impaired glucose tolerance (Group 1) and 24 patients with normal carbohydrate metabolism (Group 2). Patients of the two groups did not significantly differ in demographic characteristics, pulmonary function test and body mass index parameters, as well as in the number of F508del mutation carriers and in the number of those who were infected with Ps. aeruginosa and B. cepacia complex. Blood sampling was performed twice: before and after a routine course of antibiotic therapy. Plasma levels of biomarkers including the antibodies to single- and double-stranded DNA (ss-DNA-IgG, ds-DNA-IgG, respectively), the hormones (dehydroepiandrosterone (DHEA) and DHEA sulfate), C-reactive protein (CRP), Mn-dependent superoxide dismutase (Mn-SOD), and the cytokines (tumor necrosis factor-α (TNFα), interferon-γ (IFNγ), IFNα, tissue growth factor-β1 (TGF-β1), interleukin-4 (IL-4), IL-6, IL-10, IL-17A) were assessed using commercial immunoassay kits. Our study shows that antibiotic treatment did not have a sufficient influence on levels of inflammatory markers in patients with disturbances of glucose metabolism while patients with normal glucose tolerance demonstrated a significant reduction in inflammatory marker values after the therapy. The data may suggest both impaired effectivity of antibiotic treatment and aberrant inflammatory response in patients with glucose intolerance.

BACKGROUND: In recent decades, the life expectancy of patients with CF has increased, which leads to an increase in the frequency of conditions associated with impaired carbohydrate metabolism.AIM: to analyze the impact of cystic fibrosis-associated diabetes mellitus (CFDM) in children and adolescents on the course of cystic fibrosis according to the 2021 register of patients with cystic fibrosis of the Russian Federation (RF).MATERIALS AND METHODS: the data of the register of patients with cystic fibrosis of the Russian Federation for 2021 were analyzed. The study included 122 patients with diabetes mellitus requiring the use of insulin — 33 children (27%) and 89 adults (73%), the average age of children was 13.5±4.1, the average age of adult.patients aged 18 years and older was 27.4±6.6. To compare the course of cystic fibrosis in patients with and without diabetes mellitus, groups were formed that were comparable in age, gender, genotype — the group of patients without diabetes included 827 patients, 33 patients made up the group of patients with CFRD using insulin. Diagnostic criteria, indicators of respiratory function, microbiological status, nature of complications, volume of therapy were compared.RESULTS: Patients with CFRD have a lower FEV1 compared to children without diabetes mellitus — M±SD FEV1 (%) 85.2±27.5 in the group of patients without diabetes mellitus and M±SD FEV1 (%) 72.4±26.0 in patients with diabetes mellitus (p < 0.016), compared in the microbiological seeding groups — a trend towards more frequent chronic growth of Pseudomonas aeruginosa 54.50% versus 39.4% in the group without CFRD. An increase in MRSA was also more often detected — 9.1% compared with the group of children without diabetes — 3.1%. Antibacterial therapy is more commonly used — inhaled in 54.6% of patients without diabetes mellitus while children with CFRD received inhaled antibiotic therapy in 75.8% (p=0.017). There was a significant difference in the used antibacterial tablet therapy (p=0.013). A significant difference in the number of patients on oxygen therapy in the group with CFRD — 12.1%, versus 3.4% without CFRD (p=0.01) confirms a more severe course of cystic fibrosis in patients with CFRD.CONCLUSION: The prevalence of CFDM with the need for insulin therapy among children in the Russian Federation is 1.3%. Cystic fibrosis-associated diabetes mellitus significantly worsens the course of cystic fibrosis in terms of lung function, the growth of gram-negative and resistant flora, the presence of severe complications and the frequent use of antibiotic therapy, which is obviously associated with frequent exacerbations of the bronchopulmonary process in cystic fibrosis in patients with developed cystic fibrosis-associated diabetes mellitus.

Among diseases of ENT organs at patients with the CF prevails chronic rhinosinusitis. Stagnation of the infected dense slime in the paranasal sinus and violation of nasal breath aggravates weight of a course of lung pathology. Timely inspection and treatment of pathology of the top airways at patients with CF is necessary. In surgical treatment method of a choice is expanded FESS. This technique allows to keep anatomy of a facial skeleton and to provide a drainage the paranasal sinus. Supervision by the ENT specialist and conservative treatment of a chronic rhinosinusitis has to is carried out during all life of the patient with CF. Continuous use of local mukolitichesky and antibacterial therapy is necessary. As method of delivery of medicines the compressor inhaler with the mode for the chronic rhinosinusitis can serve.

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.

Introduction. Cystic fibrosis (CF) is common monogenic disease resulted from CFTR gene mutations. A most of CF male patients are infertile due to the obstructive azoospermia, however, the mechanisms of the reduced fertility in male patients without the obstruction of seminal ducts, also as the influence of CFTR genotype on their development is understudied.Objective is to assess an influence the effect of CFTR genotype, clinical form of CF and age on men reproductive system organs, fertility, and testosterone level and semen parameters in male patients with CF. Materials and methods. We examined 71 Russian men (17–39 years old, mean 24.9 ± 5.3) with CF (pancreatic-sufficient, n = 34, and pancreatic-insufficient, n = 37). Clinical, andrology, laboratory and instrumental examination, including scrotal ultrasonography, biochemical semen, and hormonal analyses were performed.Results. Testicular hypoplasia was reveled in 40,5 % CF patients. Diffuse alterations of epididymis, of epididymal and/or testicular cysts were detected in 62 % patients; 10 % of the patients presented symptoms of hypogonadism. As many as 88 % patients showed spermiological signs of bilateral obstruction of seminal ducts at the level of the vas deferens and epididymis, aplasia of the seminal vesicles (azoospermia, oligospermia, low pH and fructose level of the ejaculate). Pancreatic-insufficient CF is an unfavorable prognostic sign for the obstruction of vas deferens, morphological changes in the scrotum. Patients until 25 years (23 %) as 3849+10kb C>T mutation’s carriers (72 %) significantly more frequently presented preserved vas deferens.Conclusion. Pancreatic-sufficient CF, young age and 3849+10kbС>T mutation are favorable factors presented preserved vas deferens and the possible fertility in men with CF.

Introduction. Cystic fibrosis (CF) is a common genetic disorder associated with male infertility. Almost all men with CF are infertile due to obstructive azoospermia.The objective is to evaluate semen parameters, excretion of seminal fluid, and spermatogenesis in CF patients.Materials and methods. We examined 44 male CF patients with pancreatic sufficiency (n = 20) and pancreatic insufficiency (n = 24). Standard semen analysis, quantitative karyological analysis of immature germ cells from ejaculate sediment, biochemical semen analysis (fructose, α-glucosidase, citric acid) were performed.Results. Semen analysis diagnosed azoospermia in 77.3 % patients, severe oligozoospermia (< 1 million/ml) and other diagnoses (oligozoospermia, asthenozoospermia, normozoospermia) in 13.6 % and 9.1 % patients, respectively. The signs of obstruction of the vas deferens and aplasia of seminal vesicles were observed in 91 % patients. Azoospermia, oligospermia, pH

Creation of the Russian register of patients with cystic fibrosis and participation in the program European register is essential for patients in the region and in the country. Result of creating and analyzing annual data register should be the understanding of the following fundamental epidemiological indicators: number of patients, including deaths, number, patient age, their sex distribution. Analysis of the register of patients showed that the proportion of children and adolescents dominates adults (58 children and 14 adults), the average age of the patients below the other regions of the country and the world. Clinical-laboratory features of cystic fibrosis in the Krasnodar region showed an increase in complications of the disease and Pseudomonas aeruginosa infection with age. Total number of mutations have been identified 7, which was 75%. Results register landmark adoption of adequate institutional, medical and social measures when working with patients suffering from cystic fibrosis.

Chronic lower respiratory tract infection in patients with cystic fibrosis (CF) is the major factor determining the severity of the clinical course and prognosis of the disease. The purpose of the study was to investigate the prevailing respiratory microflora in patients with CF and changes in the activity of antibacterial medicines (ABM) during the period 2000–2015 in order to optimize guidelines for antibiotic therapy. Bronchial secretion was evaluated in CF patients from 2000 till 2015. 9774 samples were studied, 16.703 microbial strains were obtained. In 2000–2015, P. aeruginosa (smooth and mucoid morphological types) was the most widespread gram-negative strain. Typical strains of P. aeruginosa were isolated more often than mucoid morphotypes. In 2000–2015, isolation rates for P. aeruginosa decreased from 41.2 to 20.0% (p

Cystic fibrosis (CF) is the third most common indication for lung transplantation. The recipients with CF have shown the best early and late survival rates after surgery. The special group of CF patients consists of those, whose airways were infected with Burkholderia cepacia (B. cepacia), since the recurrence of B. cepacia infection after transplantation are coupled with extremely high risk of death. Up to the present, the question whether the patients in such conditions should be included onto the lung transplant waiting list is still unanswered. We describe a case of lung transplantation in the patient with late postoperative complication in the form of severe pyoseptic infl ammatory process caused by the recurrence of B. cepacia infection. The success of the treatment of this patient was achieved thanks to combined multidisciplinary approach. This therapeutic approach could be considered as a standard treatment protocol in case of its validation by further clinical experience.

Cystic fibrosis is multiple organ pathology that requires a complex treatment. Its standardization and pharmacoeconomic analysis are absolutely necessary. We performed a retrospective analysis of the trends in life expectancy of cystic fibrosis patients who lived inMoscow in 1993, 1998, 2003, 2008, and 2013. It was found that the survival rate of these patients depended on the choice of drug therapy (pancreatic enzymes, dornase alfa, intravenous and inhaled antipseudomonal antibiotics), changes in diet, active dispensary observation at a specialized center for cystic fibrosis, and neonatal screening. We determined the cost of drug therapy per patient. From 1993 to 2013, the survival rate of patients who lived in Moscow increased by more than 20 years (from 16 to 39 years, respectively). The average cost of therapy increased more than 10 times (from USD 1.8 to 21.9 thousand, respectively).

In order to optimize the therapy, the functional state of the pancreas (P) and the peculiarities of metabolic activity of intestinal microbiota in adults with cystic fibrosis (CF) were assessed. Materials and methods. 14 CF patients (20-34 years, 7 men, 7 women) were enrolled. In 8 patients, the diagnosis was confirmed in the first year of life on the basis of clinical data, positive sweat test, 5 had genetic confirmation. In 4 patients, the diagnosis was confirmed at the age of 8-13 years and 2 patients aged 18, 27 years. In this group, genetic confirmation was in 4 subjects. In addition to general clinical studies, the level of C-peptide in blood, elastase and the concentration of short chain fatty acids in feces was determined. Results and discussion. Of elastase feces in 9 patients was 5.5±4.7 icg/g, that is revealed severe exocrine insufficiency of the pancreas and in 5 patients the elastase level was normal and amounted to 402±124 icg/g. Deployed the clinical picture of diabetes mellitus was observed in 3 patients. Metabolic activity of the colon microflora as a whole was reduced, the sum of the concentration of short-chain fatty acids (ΣCn) was 6.03±4.11 mg/g at a rate of 10.61±5.11 (p

Aim. To evaluate the efficiency of nocturnal hyperalimentation in adult patients with cystic fibrosis (CF) and respiratory failure. Subjects and methods. The investigation enrolled 17 patients older than 18 years (mean age, 25.6±4.2 years) diagnosed with very severe CF (forced expiratory volume in one second (FEV), < 30%; body mass index (BMI), < 18.5 kg/m); all the patients were on the waiting list for lung transplantation. Nutritional status and pulmonary function parameters, such as body weight, height, BMI, and FEV, were measured at baseline, before and 6 and 9 months after tube feeding. Results. The study group showed a considerable increase in body weight and BMI after 6 and 9 months. The change in lung function was statistically insignificant. Lung transplantation was successfully conducted in 5 patients; 4 died while on the waiting list; the cause of death was respiratory failure. Conclusion. Supplemental PEG tube feeding improves the nutritional status (BMI, body weight) of patients with very severe CF.

The major risk factor for death in cystic fibrosis (CF) is a progressive lung injury; however, low nutritional status (NS) remains an important and underestimated problem in the management of these patients. The NS of a patient with CF is impaired by many factors, such as chronic malabsorption, pancreatic failure, chronic inflammation, and recurrent pulmonary infection – they all lead to higher energy demand in the presence of lower intake of nutrients. The NS of those with CF plays an important role in maintaining lung function. The patients with higher NS have longer life expectancies. According to the Russian National Registry, both pediatric and adult patients with CF have shorter life expectancies. The article discusses various nutritional support regimens and their impact on lung function parameters.

Aim. To estimate survival median and its changes, number of patients over 18 years of age for 1991—2000 and 2001-2010 for 20-year period (1991-2010), to elucidate factors affecting survival for 2001—2010 in mucoviscidosis children living in Moscow and Moscow Region and treated outpatiently in specialized medical centers. Material and methods. Case records were analysed for mucoviscidosis patients registered in specialized clinics of Moscow on 01.01.01 and 01.01.11. Survival was assessed with Kaplan-Mеier curve. Results. Survival medians for 1991 — 2000 and 2001 — 2010 was 25.7 and 35.1 years, respectively. In the group of mucoviscidosis patients with Staphylococcus aureus infection survival was significantly higher than in those infected with gram-negative microflora. Longer survival was reported in patients with "soft" mutation (p = 0.06927). Conclusion. The survival median for mucoviscidosis patients for 2001-2010 was 35.1 years. The percentage of adult patients in the last decade significantly rose from 19.5 to 32%. Gram-negative microflora significantly reduces survival, while "soft" mutation prolongs survival. Creation of National Register will specify survival of mucoviscidosis patients in all regions of the Russian Federation.

Aim. Study the spectrum of resistance to antibiotics and its variability of Staphylococcus aureus, Pseudomonas aeruginosa and Вurkholderia cepacia complex (BCC), persisting in lungs of MV patients. Materials and methods. 312 strains of S. aureus, 213 strains of P. аeruginosa, 186 strains of BCC were studied. Monitoring of antibiotics sensitivity was carried out in strains, isolated from 30 patients with chronic S. aureus infection, from 22 patients with chronic BCC infection and from 21 patients with chronic pseudomonas infection. Interval of monitoring was from 14 days to 5 years 7 months. Results. Study of S. aureus, P. aeruginosa and ВCC strains has shown, that 35 and 33.3% of cases of staphylococcus infection, 37 and 46% of pseudomonas infection in children and adults, respectively, 100% of BCC infections were determined by multiresistant clones. Study of genotypically identical strains, isolated from a single patient at different stages, has shown a change in antibiotics sensitivity as a result of persistence. Conclusion. Persistent infection of lungs in patients with MV is determined by exchanging clones with varying antibiotics sensitivity or prolonged circulation of a single clone with a high degree of phenotypical and genotypical variability, that determine alteration of seeding of sensitive and resistant strains from the same patient during monitoring. This confirms the necessity of study of antibiotics sensitivity of strains for prescription of antibacterial therapy.

The pulmonary drug administration for the treatment of a pulmonary affection in cystic fibrosis is highly effective. This consensus document summarizes data on inhalation intake of bronchodilators, mucolytics, anti-inflammatory drugs, including glucocorticoids, recommended for use in cystic fibrosis patients of all age groups in the territory of the Russian Federation