Experience of long-term use of anti-IgE therapy in a patient with chronic spontaneous urticarial

Chronic spontaneous urticaria is an urgent health problem. Recurrent urticarial rashes, angioedema and severe itching reduce the quality of life of patients. The ineffectiveness of standard therapy requires the search for new modern methods of treating this disease. Taking into account the current data on the pathogenesis, the third line of therapy for chronic spontaneous urticaria is the addition of anti-IgE therapy (omalizumab) to antihistamines of the 2nd generation. The presented clinical case is devoted to the experience of long-term use of omalizumab in a patient with chronic spontaneous urticaria. Having a disease duration of about a year, the patient was thoroughly examined, all concomitant diseases were identified and compensated, parasitic invasion was treated, but this did not lead to a regression of symptoms. Antihistamines of the 2nd generation in standard and increased doses (up to 4 times) did not control the disease, systemic glucocorticosteroids stopped the symptoms for a short time, and therefore, in  the future, the  patient began to use them independently and uncontrollably. Almost daily use of  corticosteroids for 6 months caused the development of complications in the form of weight gain and Cushing’s syndrome. Omalizumab completely stopped all the symptoms during the first day, no side effects were detected. The clinical effect lasted from 3 to 4 weeks. Thus, omalizumab therapy allowed the patient to almost completely get rid of the symptoms of CSC, which significantly improved the quality of life and made it possible to cancel systemic glucocorticosteroids. The peculiarity of the presented case is the duration of the use of omalizumab (more than 2 years) with the inability to cancel due to the return of urticarial rashes and itching

Free-radical oxidation as a pathogenetic factor of metabolic syndrome

The medical and social significance of cardiovascular diseases remains high. One of the factors that determine cardiovascular risks is metabolic syndrome. As a result of excessive accumulation of lipid and carbohydrate metabolism products in metabolic syndrome, oxidative (oxidative) stress develops. The article considers both domestic and foreign scientific studies, which highlight various aspects of the influence of reactive oxygen and nitrogen species, as well as other free radicals on the formation of oxidative stress in pathological conditions that are part of the metabolic syndrome complex. This describes the mechanisms of the formation of chronic inflammation through excessive secretion of pro-inflammatory cytokines and adipokines, activation of the transcription factor NF-kB, as well as damage to the antioxidant system in obesity. Separately, a number of mechanisms of the stimulating effect of adipokines: leptin, adiponectin, chimerine, omentin 1, resistin, on the formation of oxidative stress have been noted. The ways of activating the polyol pathway, as well as diacyl-glycerol — protein kinase C — the signaling pathway of oxidative stress, the formation of mitochondrial dysfunction is described. As a result of which there is an excessive production of free radicals in insulin resistance, diabetes mellitus and macroand microvascular complications of diabetes. In addition, the influence of oxidative stress directly on the formation of cardiovascular diseases of atherosclerotic genesis, as well as arterial hypertension, has been shown

Experience with the triple fixed combination in patients with chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is one of the most important problems of modern medicine associated with a high mortality rate, high costs of treatment and relief of exacerbations of COPD. The main objectives of COPD treatment are symptom control, reduce the frequency of exacerbations and hospitalizations, and reduced risk of exacerbation in the future. The recommendations of the GOLD initiative propose a treatment approach based on the assessment of exacerbation rates external respiratory function indicators (spirometric classification of GOLD), the severity of symptoms assessed on the CAT test and mMRC. When choosing therapy, the physician must first of all take into account the effectiveness, safety of the drug, adherence to treatment in order to achieve the therapeutic goals of treating patients with COPD. The change in therapeutic approaches in COPD treatment is associated with the accumulation of knowledge in physiology, clinical pharmacology, and the isolation of new clinical phenotypes of COPD. Currently, the main classes of drugs for the treatment of COPD are long-acting beta-agonists (LABA), longacting anticholinergics (LAMA), and inhaled glucocorticosteroids (ICS). The evolution of therapeutic approaches in COPD treatment has led to the creation of new fixed inhalation combinations of the main groups of drugs for COPD treatment. The therapeutic strategies recommended by GOLD and the Russian Federal Guidelines determine the long-term goals of COPD treatment – the impact on the risk of exacerbations in the future. The presented clinical observation of a patient with severe COPD demonstrates the effectiveness of a triple fixed combination vilanterol/umeclidinium/fluticasone furoate 55/22/92 μg as a basic therapy. The  chosen treatment strategy not only reduces the  severity of  the  symptoms of  the  disease, but also reduces the  risk of exacerbations in the future

Features of cellular structure of the induced sputum and profile of cytokines at sintropiya of bronchial asthma and obesity at young patients

Aim. To estimate changes of cellular structure of the induced sputum at young patients with bronchial asthma at interrelations with BMI and level of cytokines in blood plasma. Materials and methods. 164 patients with bronchial asthma were divided into 2 groups taking into BMI: the 1st group included patients with bronchial asthma and BMI from 18 to 25 kg/m2, patients with bronchial asthma and BMI from 30 to 40 kg/m2 entered into the 2nd group. The group of control was made by 40 almost healthy volunteers. Estimated existence of excess weight and defined obesity degree according to recommendations of World Health Organization. Studied the level of control of bronchial asthma, cellular structure of the induced sputum, the IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, INF-γ levels in plasma of peripheral blood. Results. There are presented the results of the research of cellular profile of the induced sputum and profile of cytokines at patients with bronchial asthma depending on BMI and severity of the disease. The received results testify to prevalence of eosinophilic type of an inflammation in the group of patients with BMI less than 25 kg/m2 whereas at patients mainly paucigranulation inflammation decided on obesity. The highest content of the Il-17 was registered at patients with bronchial asthma and obesity as in comparison with indicators of patients with normal BMI, and with almost healthy that, perhaps, is the reason of low effect of steroid therapy at these patients. Conclusion. Endotype assessment before basic antiinflammatory therapy at patients with the first time diagnosed bronchial asthma, will be able to help with selection of the most optimum treatment to each specific patient

Роль катепсина S в патофизиологии бронхиальной астмы

To date, the study of the role of proteases in the pathogenesis of various diseases remains relevant. The variety of cathepsin functions is associated with the peculiarities of their localization, expression, and regulation, due to which cathepsins are involved in development of many pathologies. Dysregulation of proteases, their inhibitors, and substrates can lead to the development of multiple organ dysfunction.The review presents data on the characteristics of the entire family of cathepsins and cathepsin S, in particular. The pathophysiological role of cathepsin S in the formation of bronchopulmonary pathologies, as well as in bronchial asthma is described, and intraand extracellular implementation mechanisms are considered. The authors believe it is this enzyme that could be targeted in targeted asthma therapy to prevent airway wall remodeling at the earliest stages of the disease. The literature search was carried out in the search engines Medline, eLibrary, Scopus, the Cochrane Library, and RSCI.До настоящего времени сохраняет свою актуальность изучение роли ферментов – протеаз в патогенезе различных заболеваний. Многообразие функций катепсинов обусловлено особенностями их локализации, экспрессии и регуляции, благодаря чему они принимают участие в развитии многих патологических процессов. Дисрегуляция активности протеаз, их ингибиторов и субстратов может привести к развитию полиорганных заболеваний.В обзорной статье представлены данные о характеристике всего семейства катепсинов и катепсина S в частности; описаны его патофизиологические роли при формировании бронхолегочных патологий, а также при бронхиальной астме; освещены внутрии внеклеточные механизмы реализации. Авторы считают, именно этот фермент может стать мишенью для таргетной терапии астмы с целью предотвращения ремоделирования бронхиальной стенки на самых ранних этапах заболевания. Поиск литературы осуществлялся в поисковых системах Medline, еLibrary, Scopus, The Cochrane Library, РИНЦ

Значение остеопонтина в формировании диастолической дисфункции правого желудочка у больных атопической бронхиальной астмой

The purpose of this study was to investigate a role of osteopontin for development of right heart diastolic dysfunction in patients with atopic bronchial asthma (ABA). This is important for early diagnosis of pulmonary hemodynamic disorders. Methods. The study involved 188 subjects: 148 ABA patients who were divided into 3 groups according to asthma severity and 40 healthy volunteers as controls. We measured right ventricle functional parameters and blood osteopontin concentration. Results. While increasing ABA severity blood osteopontin concentration increased and the right ventricle diastolic function decreased in comparison to the healthy controls. Osteopontin concentration was higher in patients with right heart dysfunction. Conclusion: More severe course of ABA was associated with higher blood osteopontin concentration. More significant right heart dysfunction was seen in patients with moderate to severe ABA. Right heart dysfunction in ABA was associated with systemic inflammation, particularly with osteopontin concentration.Целью исследования была оценка значения остеопонтина в формировании ремоделирования правых отделов сердца у больных атопической бронхиальной астмой (АБА) для выявления ранних признаков нарушения гемодинамики малого круга кровообращения. Материалы и методы. В исследовании приняли участие 188 пациентов: 148 больных АБА различной степени тяжести, которые были разделены на 3 группы соответственно степени тяжести заболевания, и 40 практически здоровых добровольцев, составивших группу контроля. Изучались функциональные параметры правого желудочка и уровень остеопонтина. Результаты. Выявлено повышение уровня остеопонтина в плазме крови и снижение диастолической функции правого желудочка (ПЖ) параллельно тяжести течения заболевания по сравнению с показателями практически здоровых. Показано, что уровень остеопонтина выше у больных с нарушенной функцией ПЖ.Заключение. С возрастанием тяжести течения АБА увеличивается содержание ОП. Наиболее значимые функциональные нарушения выявлены при среднетяжелом и тяжелом течении заболевания. Функциональные изменения правых отделов сердца при АБА различной степени тяжести ассоциированы с активностью системного воспаления, а именно с уровнем остеопонтина

Common variable immunodeficiency disorder: a clinical case

Primary immunodeficiency is a rare congenital pathology associated with failure of immune system, manifested by disturbances of its functions. These defects lead to increased susceptibility of patients to various infectious agents, as well as the development of autoimmune, malignant and other diseases. Primary immunodeficiency is classified as a rare disease, which was previously associated with a poor prognosis with a high risk of mortality in childhood. To date, the emergence of highly effective treatment methods has changed the course and prognosis of these diseases. Clinicians of various specialties increasingly meet with this pathology in everyday practice, including adult age cohorts. In this regard, early diagnosis of primary immunodeficiency in adults becomes relevant, being associated with choosing optimal therapy, prevention of severe internal organ damage, determination of management strategy for the patient, as well as the need to identify inherited disorders and provide information to the patient’s family. Delayed verification of the diagnosis may cause disability of the patient and development of irreversible, often fatal complications. This article presents our own clinical case with a newly diagnosed clinical condition: Common variable immunodeficiency disorder (CVID), the most common form of primary immunodeficiency in adults. The symptoms of common variable immunodeficiency disorder appear in these patients in adulthood, but a high-quality collected history of the disease will allow you to trace symptoms in the patients even since early childhood. There is a common gap for several years between the onset of the disease and clinical diagnosis, since erroneous diagnosis is often made due to non-specific clinical symptoms that resemble other, more frequent diseases. The prognosis of patients with CVID depends on several factors: frequency of infections, structural disorders in the lungs, the occurrence of autoimmune diseases and the success of infection prevention. Thus, a variety of clinical forms of primary immunodeficiency, lack of awareness of doctors about this pathology, complexity of immunological examination in the general medical network lead to the fact that CVID is not diagnosed for long terms, and patients do not receive the necessary pathogenetic therapy. There is a need for drawing attention of doctors of various disciplines to the fact that the recurrent inflammatory processes of various localization, which are difficult to respond to adequate traditional therapy, may be caused by changes in the immune system, including congenital, genetically determined immunodeficiency

Особенности апоптоза и блеббинга цитоплазматической мембраны лимфоцитов при бронхиальной астме

 Given a persistent global trend towards an increase in the number of patients with bronchial asthma (BA) over the past decades, researchers are facing challenges related to a comprehensive study of the pathogenesis of BA. Numerous studies have shown that BA is associated with long-term persistence of leukocytes (lymphocytes, macrophages, and eosinophils) in the bronchial tissues. However, the causes of this phenomenon remain understudied. The article provides an overview of modern research on the mechanisms of disorders of lymphocyte apoptosis in patients with BA.Our study considers the main mechanisms of molecular regulation of  lymphocyte apoptosis, including transcription factors, the Fas/FasL system, and bcl-2/bcl-XL factors. We present the data on the role of reduced lymphocyte apoptosis in the formation of a severe BA phenotype. Taking into account high  prevalence of obesity among patients with BA, we analyzed a few existing articles on the apoptosis of immunocompetent cells in obesity. In addition, the article highlights the key mechanisms of development of lymphocyte plasma membrane blebbing (PMB) with formation of microvesicles, as well as their influence on the course of pathological processes in BA. The authors believe that further in-depth study of apoptosis, lymphocyte  necrosis, and plasma membrane blebbing can help improve the principles of diagnosis and treatment of BA.  С учетом стойкой общемировой тенденции к нарастанию численности больных бронхиальной астмой (БА) за последние десятилетия перед исследователями встает  задача всестороннего изучения патогенеза бронхиальной астмы. В многочисленных исследованиях доказано, что течение БА сопряжено с длительной персистенцией лейкоцитов (лимфоцитов, макрофагов, эозинофилов) в тканях бронхов. Однако остается открытым вопрос о причинах данного явления. В данной статье представлен обзор современных научных исследований, посвященных изучению механизмов нарушения апоптоза лимфоцитов у  больных бронхиальной астмой.Рассматриваются основные механизмы молекулярной  регуляции апоптоза лимфоцитов, например  транскрипционные факторы, система Fas/FasL, факторы bcl- 2/bcl-XL и др. Приводятся данные об участии снижения  апоптоза лимфоцитов в формировании фенотипа с тяжелым течением бронхиальной астмы. Учитывая высокую  распространенность ожирения среди больных  бронхиальной астмой, проанализированы немногочисленные статьи, касающиеся апоптоза  иммунокомпетентных клеток при ожирении. Кроме того, в статье освещаются ключевые механизмы развития  блеббинга цитоплазматической мембраны (ЦПМ) с формированием лимфоцитарных микровезикул, а также их  влияние на течение патологических процессов при астме.Авторы считают, что дальнейшее углубленное изучение  процессов апоптоза и некроза лимфоцитов, а также блеббинага ЦПМ сможет помочь в улучшении принципов диагностики и  лечения бронхиальной астмы.

Организация биологической терапии пациентов с тяжелой эозинофильной бронхиальной астмой в Красноярском крае

Patients with severe bronchial asthma, which remains uncontrolled despite the optimal basic therapy, carry a significant healthcare burden and require substantial financial investments. Severe asthma is a heterogeneous airway disease with complex pathophysiological mechanisms that can be broadly divided into inflammatory pathways with eosinophilic and non-eosinophilic inflammation.Aim. This study aimed to analyze the literature data on the use of targeted genetic engineering therapy in patients with severe bronchial asthma, as well as to analyze the organization of immunobiological therapy in the Krasnoyarsk Territory. The addition of targeted drugs for severe eosinophilic bronchial asthma based on phenotyping has proven to be effective and is recommended by all current guidelines. Today, several biologics targeting specific endotypes and phenotypes has been approved for the treatment of severe eosinophilic asthma worldwide. These are antibodies binding immunoglobulin E (omalizumab), antagonists of interleukin-5 (mepolizumab, reslizumab) and its receptor (benralizumab), as well as antibodies selectively binding to the IL-4 and IL-13 receptors (dupilumab). Eosinophilic inflammation therapy is a relatively new direction of asthma treatment, and understanding its long-term efficacy and safety is important.Conclusion. It is essential to differentiate patients with severe eosinophilic asthma from the general cohort of asthma patients, timely refer them to specialists who can prescribe this therapy and have experience with it, select the drug correctly, and monitor the patients during the treatment. This article describes organization of biological therapy for patients with severe eosinophilic bronchial asthma in the Krasnoyarsk Territory.Бремя тяжелой бронхиальной астмы (БА), которая остается неконтролируемой, несмотря на использование оптимальной базисной терапии, весьма существенно, при этом заболевании требуется значительное вложение денежных средств. Тяжелая БА (ТБА) представляет собой гетерогенное заболевание дыхательных путей, патофизиологические механизмы воспаления при этом весьма сложны и в целом подразделяются на 2 типа: эозинофильное и неэозинофильное.Целью работы явился анализ данных литературы по применению таргетной генно-инженерной терапии у больных ТБА и организации иммунобиологической терапии на территории Красноярского края. При лечении тяжелой эозинофильной БА (ТЭБА), установленной на основе фенотипирования, доказана эффективность таргетных препаратов, рекомендуемых всеми современными руководствами по лечению ТБА. В настоящее время в мире одобрено несколько биологических препаратов для лечения ТЭБА, нацеленных на конкретные эндотипы и фенотипы. Это антитела, связывающие иммуноглобулин Е (омализумаб), антагонисты интерлейкина-5 (меполизумаб, реслизумаб) и его рецептора (бенрализумаб), а также антитела, избирательно связывающиеся с рецепторами IL-4 и IL-13 (дупилумаб). Терапия эозинофильного воспаления представляет собой относительно новое направление лечения БА, при этом важно понимать их долгосрочную эффективность и безопасность.Заключение. Важным является выявление пациентов с ТЭБА из общей когорты больных БА, своевременное направление их к специалистам, у которых имеется возможность и опыт назначения данной терапии, правильный выбор препарата и динамическое наблюдение в процессе лечения. В статье приведены данные об организации биологической терапии пациентов с ТЭБА в Красноярском крае

Современные представления о роли CD38 в патогенезе бронхиальной астмы

Current view on a role of CD38 for pathogenesis of bronchial asthma.Современные представления о роли CD38 в патогенезе бронхиальной астмы