Современные представления о диагностике и лечении детей с муковисцидозом

The issue of contemporary diagnosis and correct management of patients with cystic fibrosis is relevant not only for Russia, but for the entire world. Despite achievements of the contemporary medical science, underdiagnosis of this systemic genetic disorder leading to severe incapacitation and death of pulmonary and heart failure in the vast majority of cases is still observed. The burden induced by this disease is so severe that neonatal screening has been introduced to suspect and detect disease and start pathogenetic treatment capable of stopping or slowing progression of the disease as soon as possible. Apart from the contemporary classification and diagnostic criteria, the article presents treatment goals and components requiring a multidisciplinary approach in detail. Specific attention is given to methods of kinesitherapy, use of antibacterial drugs and enzyme replacement therapy, which primarily determine prognosis of the disease. Проблема своевременной диагностики и правильного ведения пациентов с муковисцидозом актуальна не только в нашей стране, но и во всем мире. Несмотря на достижения современной медицинской науки, продолжается гиподиагностика этой генетической болезни, которая носит системный характер, приводит к тяжелой инвалидизации и смерти в преобладающем большинстве от легочной и сердечной недостаточности. Бремя болезни настолько тяжело, что введен скрининг среди новорожденных, который позволяет как можно раньше заподозрить и выявить болезнь и начать патогенетическое лечение с целью остановить или замедлить прогрессирование болезни. Помимо современной классификации и критериев диагностики, подробно представлены цели и компоненты лечения, требующие мультидисциплинарного подхода. Особое внимание уделено методикам кинезитерапии, применению антибактериальных средств, ферментозаместительной терапии, во многом определяющим прогноз болезни.

INFLUENCE OF NEONATAL SCREENING FOR CYSTIC FIBROSIS BY THE EXAMPLE OF PATIENTS OF THE MOSCOW REGION

Study objective: comparative evaluation of clinical status of patients with cystic fibrosis (CF) 6–9 years, the diagnosis of which was established before the start of neonatal screening (NS) for MV in the Moscow region and in same age group since the start of the NS according to the register 2012 and 2015. Patients and methods. The patients were divided into 2 groups: I – 45 children aged 6–9 years, diagnosed before the beginning of the NS, II – 86 children aged 6–9 years, identified after the start of the NS. Results. A comparative assessment of the age of diagnosis had a significant difference between groups I and II. The average age of diagnosis in group I was 2.29 (±2.29) years, in group II the average age of diagnosis – 0.66 (± 1.13) years (p = 0.0000). According to the microbiological status diagnosed according to the NS program (group II), chronic infection of the respiratory tract by Ps. aeruginosa was less frequent in this group (37.78% of patients in group I vs. 14,10 % in group II) (p = 0.0026). In the group of patients identified by the newborns screening program directed at newborns (group II) a statistically significant decrease of the ongoing intravenous (p = 0.0000) and inhaled antibiotic therapy (p = 0.0139) and reduced compared with group I patients receiving bronchodilators (p = 0.0322). Conclusion. A positive impact of neonatal screening for MV at the age of diagnosis and a number of important indicators of the disease was demonstrated

Contemporary Understanding of Diagnosis and Treatment of Children with Cystic Fibrosi

The issue of contemporary diagnosis and correct management of patients with cystic fibrosis is relevant not only for Russia, but for the entire world. Despite achievements of the contemporary medical science, underdiagnosis of this systemic genetic disorder leading to severe incapacitation and death of pulmonary and heart failure in the vast majority of cases is still observed. The burden induced by this disease is so severe that neonatal screening has been introduced to suspect and detect disease and start pathogenetic treatment capable of stopping or slowing progression of the disease as soon as possible. Apart from the contemporary classification and diagnostic criteria, the article presents treatment goals and components requiring a multidisciplinary approach in detail. Specific attention is given to methods of kinesitherapy, use of antibacterial drugs and enzyme replacement therapy, which primarily determine prognosis of the disease

MICROFLORA OF THE RESPIRATORY TRACT IN PATIENTS WITH CYSTIC FIBROSIS AND SENSITIVITY TO ANTIBIOTICS BASED ON A 15-YEAR FOLLOW-UP (2000–2015 YEARS)

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 <0.001). The proportion of B. cepacia complex increased from 1.1 to 7.3%, up to 11.3% in 2008–2011, and a rise in the proportion A. xylosoxidans was registered from 2.9 to 4.9% (p <0.001). During the follow-up period, the diversity of isolated species has grown.ABM such as colistin (active against 100% of strains), carbapenems (imipenem is active against 70.3–72.2% of strains, and meropenem against 75.8 and 78.9%) remain active against P. aeruginosa. The effect of piperacillin/tazobactam is similar to that of carbapenems. Cefepime is less effective than ceftazidime. Fluoroquinolones and tobramycin also remian active

ИСТОРИЧЕСКИЕ И СОВРЕМЕННЫЕ АСПЕКТЫ МУКОВИСЦИДОЗА В РОССИИ

The article is dedicated to historical and modern trials in the sphere of mucoviscidosis in Russia, peculiarities of clinical manifestations, pathophysiological and pathomorphological disorders and of the disease course with the analysis of the first results of the register of patients in the Moscow region. The aggregate result of this evaluation is the survival rate in the Moscow region that has become almost equal to the one in the USA and Europe and is considerably higher than in the other regions of the Russian Federation. Such a result reflects many components of specialized care rendered to mucoviscidosis patients in the Moscow region: special centers for children and adults have been founded, patients are actively and regularly checked and may be examined in detail during each visit, while pharmacological support is up to world standards; this is not yet present or is developed insufficiently in many RF subjects. The article also dwells upon the genetic peculiarities of mucoviscidosis important both for diagnosing the disease (including neonatal screening) and creation of a panel for DNA-diagnostics and for determining the disease course to a considerable extent. It also presents information on the prospects of gene therapy development and the first results of clinical studies.Статья посвящена историческим и современным исследованиям в области муковисцидоза в нашей стране; особенностям клинических проявлений, патофизиологических и патоморфологических нарушений, течения заболевания с анализом первых результатов регистра пациентов Московского региона. Суммирующим результатом этой оценки является показатель выживаемости, который практически сравнялся по Московскому региону с таковым в США и Европе, и существенно отстает по регионам Российской Федерации. Это стало отражением многих компонентов специализированной помощи больным муковисцидозом в Московском регионе: созданы специальные центры для детей и взрослых, проводится их активное диспансерное наблюдение с возможностью детального обследования в каждый визит, лекарственное обеспечение — на уровне мировых стандартов, что пока отсутствует или недостаточно развито во многих субъектах РФ. В статье отражены также генетические особенности муковисцидоза, которые важны как для диагностики заболевания (включая неонатальный скрининг) и создания панели для ДНК-диагностики, так и для определения в значительной мере течения заболевания. Приводится информация о перспективах разработки генотерапии и первые результаты клинических исследований

Диетотерапия и заместительная ферментотерапия при муковисцидозе

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ANDROLOGY EXAMINATION OF PATIENTS WITH PANCREATIC-SUFFICIENT AND PANCREATIC-INSUFFICIENT CYSTIC FIBROSIS

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