Dynamics of the cytokine profile in achieving the therapeutic effect of allergen-specific immunotherapy in children with allergic rhinitis and bronchial asthma

Allergen-specific immunotherapy is a pathogenetic method for the treatment of IgE-mediated allergic diseases.Objective. To evaluate effectiveness of allergen-specific immunotherapy in 471 children with allergic rhinitis and bronchial asthma, as well to analyze the dynamics of the cytokine profile at baseline and 1 year after the start of treatment in 86 children. The research was supported by a grant from the International Scientific Council for Young Scientists of Kazan State Medical University.Results. Analysis of the data obtained demonstrated that allergen-specific immunotherapy is a highly effective method of treating children with allergic rhinitis and atopic bronchial asthma. The dynamics of the level of the studied cytokines during treatment indirectly indicates an increase in the functional activity of adaptive subpopulations of regulatory T-lymphocytes (T-reg) and B-lymphocytes (B-reg) with a decrease in the activity of Th2 lymphocytes, which may indicate the reconstruction of the immune response and possible disease-modifying effect.

ECONOMIC ASPECTS OF APPLICATION OF THE RUSSIAN BIOSIMILAR OMALIZUMAB IN PATIENTS WITH ATOPIC BRONCHIAL ASTHMA OF MODERATE TO SEVERE CLINICAL COURSES

A certain success in the treatment of bronchial asthma is associated with the introduction of monoclonal antibodies into the treatment process. They made it possible to improve the control of the disease. A number of original genetically engineered biological drugs, such as benralizumab, reslizumab, dupilumab, mepolizumab and omalizumab, are currently registered in Russia. In 2020, this list was supplemented by the first Russian biosimilar drug omalizumab – Genolar® (JSC Generium, Russia). High rates of the development of modern medicine are closely related to the use of biosimilars. The prescription of biosimilars today often makes it possible to provide a larger number of patients with modern drugs at lower costs.The aim of the study was a comprehensive pharmacoeconomic assessment of the application of the domestic biosimilar drug omalizumab in the treatment of patients suffering from moderate and severe atopic bronchial asthma.Materials and methods. At the first stage, an information search in the available databases (Cochrane Library, MedLine, Embase, eLIBRARY) was carried out. According to the results obtained, a meta-analysis (Agache I. et al.) was found out; within its framework, the efficacy and safety of the use of several monoclonal antibodies was assessed. Dupilumab was chosen as the reference drug. Pharmacoeconomic analyses were carried out using a “Cost-Minimization Analysis” (CMA) and a “Budget Impact Analysis” (BIA). Taking into account various options of bronchial asthma, the developed algorithm for providing medical care to adult patients with atopic asthma made it possible to assess the costs, including direct medical and indirect costs.Results. The cost analysis demonstrated the advantage of using the Russian biosimilar omalizumab in patients with atopic asthma compared to dupilumab due to financial savings of up to 40%. The Budget Impact Analysis showed that the use of the domestic biosimilar omalizumab, even taking into account the annual increase in the number of patients (8%), will save up to 109,641,409.64 rubles (or 3%) compared to the current practice.Conclusion. The use of the domestic biosimilar omalizumab in patients with moderate to severe atopic bronchial asthma is a clinically effective and economically justified approach to organizing medical care for adult patients in Russia.

Initial vegetative tone in mild atopic asthma in children

Background. In most industrialized countries, allergic diseases affect up to 20% of the population. This pathology belongs to the most common in children: according to the World Health Organization, more than 15% of the world's child population suffers from it. In recent years, there has been a significant increase in the frequency and more severe course of these diseases, in connection with which they are considered in modern society as a major medical and social problem. Thus, the prevalence of bronchial asthma, according to domestic and foreign authors, ranges from 0.2 to 8.1%. Purpose. In order to clarify the role of the autonomic nervous system in the genesis of the mild course of atopic bronchial asthma in childhood, the features of the interaction of the sympathetic and parasympathetic divisions of the autonomic nervous system in the examined children were clarified. Materials and methods. 126 children aged 10 to 14 years were examined. Atopic bronchial asthma was diagnosed in 91 children. At the same time, 61 of them were diagnosed with an intermittent course, 30 a mild persistent course of the disease. The control group consisted of 35 healthy children also aged 10 to 14 years. Complaints, anamnesis data were studied in all children, an objective and generally accepted laboratory and instrumental examination was carried out. All examined children underwent daily monitoring of the electrocardiogram, according to the results of which, based on the analysis of time and frequency indicators of heart rate variability, a variant of the initial autonomic tone was established. Results. In children with atopic bronchial asthma, both with intermittent and mild persistent course, an absolute or relative dominance of sympathetic influences was revealed against the background of varying degrees of decrease in parasympathetic activity, which was interpreted as a compensatory reaction of the body in response to chronic allergic inflammation.

Patient with polymorbid pathology. Possibilities of therapy with monoclonal antibodies

With the widespread increase in the number of patients with allergic pathology, doctors in clinical practice increasingly have to observe the simultaneous development of several nosological forms in the same patient. Frequent occurrence of a combination of lesions of the skin and respiratory tract in patients with atopy (atopic dermatitis, allergic rhinitis, and atopic bronchial asthma) is traditionally considered within the framework of comorbidity and suggests a number of therapeutic interventions given the similarity of the pathogenesis. However, phenotypic or endotypic differences exist between patients (e.g., triggers, age, persistence of manifestations, degree and type of inflammation, severity of symptoms, and response to treatment), for which it is more correct to use the term multimorbidity. The strategy of precision medicine for patients with several immune-mediated diseases should focus on identifying not only the general features of the disease, but also the pathogenetic mechanisms in the target organs. Because of these differences, the sensitivity to therapeutic interventions by target organs can vary. Herein, a clinical case of a patient with comorbid pathology ― chronic spontaneous urticaria, allergic rhinitis, and bronchial asthma ―was analyzed. Respiratory manifestations (rhinitis and asthma) were mild to severe. Chronic urticaria had the most severe disease course and resistant to antihistamines, which are considered first and second lines of drugs according to federal and international clinical guidelines that required the use of monoclonal antibodies. Anti-IgE therapy with omalizumab had a rapid and complete effect on urticaria symptoms, but respiratory symptoms were less responsive to treatment. In patients with multimorbid pathology, therapy should be individualized in terms of targeted drugs and their dosage.

INFLUENCE OF SUBLINGUAL SPECIFIC IMMUNOTHERAPY ON THE DYNAMICS OF SENSITIZATION INDICATORS IN ATOPIC BRONCHIAL ASTHMA IN CHILDREN

Of all the currently existing methods of treating atopic asthma, the most vivid example of a systemic approach is sublingual allergen-specific immunotherapy (SL ASIT). Allergen-specific immunotherapy (ASIT) is the only method of antiallergic treatment that affects all pathogenetic links of the allergic process and has a long-term preventive effect (Gushchin I.S., 1998).Keywords:atopic bronchial asthma, sensitization, epidemiology, specific immunotherapy

Enzymatic characterization of blood lymphocytes in various clinical and pathogenetic variants of respiratory allergy

Allergy is a sufficient social and economic issue of modern times. Altered immunity in allergic disorders is based, mainly, on the lymphocyte disturbances.Immune characteristics depend both on populations and subpopulational profile of immune cells, and on intrinsic intensity and specific features of theirintracellular metabolism. Interest to studies of intracellular metabolism of lymphocytes id determined by high-scale energetic and plastic processes aimed for support of immune homeostasis. The aim of this study was to evaluate the state of intracellular metabolism in peripheral blood lymphocytes from the patients with respiratory allergies of different genesis and respiratory affection.The study included patients with various clinical variants of respiratory allergy (n = 152) at the age of 21 to 63 years old, and virtually healthy blood donors (n = 209), comparable for age and sex. Within these cohorts, we have separately analyzed, e.g., respiratory atopy (atopic rhinosinusitis and atopic bronchial asthma), as well as respiratory pseudoatopy (polypous rhinosinusitis and asthmatic triad). Allergic disorders of upper respiratory ways were diagnosed in a complex clinical examination by allergologist/immunologist and otorhinolaryngologists. Bronchial asthma verification was based on current GINA criteria (2014). We used m standard common clinical methods and specific allergological diagnostics, e.g., allergological anamnesis, skin prick tests, with different non-infectious allergens, measurement of total and specific IgE’s with ELISA method. The parameters of intracellular metabolism of peripheral blood lymphocytes were determined with bioluminescent technique with bacterial luciferase. Actifity of NAD(P) and NAD(P)H enzymes was measured.Dehydrogenase activities in lymphocytes were expressed as enzyme un its (EU, 1 unit = 1 mcmol/min) per 104 cells.Certain changes of intracellular activities in peripheral lymphocytes are revealed, dependent on genesis and origin of allergic inflammation, and affection level of respiratory ways. In respiratory atopy (atopic rhinosinusitis and atopic bronchial asthma), irrelevant on the level of respiratory affection, the activities of intracellular enzymes suggest increased plastic processes that are maximally pronounced in atopic bronchial asthma. In respiratory pseudoatopy (polypous rhinosinusitis and asthmatic triad) the metabolic changes of lymphocytes presume activation of both plastic and energetic processes, with decreased intensity in asthmatic triad condition. Independent on genesis of respiratory allergic inflammation, we have determined low activity of NAD(P)-dependent glutamate dehydrogenase, and NAD(H)-dependent lactate dehydrogenase in allergic inflammation of upper respiratory ways (atopic rhinosinusitis and polypous). Its activity is statistically higher in bronchial asthma (atopic bronchial asthma and asthmatic triad.

Experience in Course of Anti-IgE Therapy of Bronchial Asthma in Children

The results of the clinical approbation of Patient-specific therapy of bronchial asthma in children using the course method of application of the monoclonal antibodies (anti-IgE-therapy) by the Ministry of Health are summarized in order to assess the effect of this type of treatment on the disease exacerbation rate, including those associated with the seasonal acute respiratory infections. The conclusion was made regarding the high clinical efficiency in relation to all parameters studied and safety of this type of the treatment. It was determined that the monitoring of the level of specific IgE receptors on basophils using the cytoflowmetry method, which is concomitant to anti-IgE therapy, makes it possible to predict the efficiency and individual duration of anti-IgE therapy for uncontrolled atopic bronchial asthma in children.