Репозиторий Университета

Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology. Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) showed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.

Copyright © 2021 The Korean Academy of Asthma, Allergy and Clinical Immunology. Arginine kinase (AK) was first identified as an allergen in the Indian-meal moth and subsequently shown to occur as allergen in various invertebrates and shellfish. The cDNA coding for AK from the house dust mite (HDM) species Dermatophagoides pteronyssinus, Der p 20, has been isolated, but no recombinant Der p 20 (rDer p 20) allergen has been produced and characterized so far. We report the expression of Der p 20 as recombinant protein in Escherichia coli. rDer p 20 was purified and shown to be a monomeric, folded protein by size exclusion chromatography and circular dichroism spectroscopy, respectively. Using AK-specific antibodies, Der p 20 was found to occur mainly in HDM bodies, but not in fecal particles. Thirty percent of clinically well-characterized HDM allergic patients (n = 98) whose immunoglobulin E (IgE) reactivity profiles had been determined with an extensive panel of purified HDM allergens (Der f 1, 2; Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 18, 21, 23 and 37) showed IgE reactivity to Der p 20. IgE reactivity to Der p 20 was more frequently associated with lung symptoms. AKs were detected in several invertebrates with specific antibodies and Der p 20 showed IgE cross-reactivity with AK from shrimp (Litopenaeus vannamei). Thus, Der p 20 is a cross-reactive HDM allergen and may serve as a diagnostic marker for HDM-induced lung symptoms such as asthma.

© 2019 American Academy of Allergy, Asthma  &  Immunology Background: Mepolizumab is an anti–IL-5 antibody approved for the treatment of severe eosinophilic asthma. However, the prevalence of patients with severe asthma eligible for mepolizumab remains unknown, especially among children. Objective: To determine, in a population of patients with severe asthma from a tertiary referral center, the proportion of patients with an eosinophilic phenotype who would be eligible for mepolizumab, when stratified for the age of onset of asthma, and the prevalence of phenotypic features that favor mepolizumab therapy. Methods: An extensive database of 245 adults and children referred for severe asthma was used. The prevalence of severe asthma was estimated by using the European Respiratory Society/American Thoracic Society criteria. Patients with an eosinophilic uncontrolled phenotype qualified for mepolizumab. Results: In our cohort, 216 (88%) had severe asthma. Based on blood eosinophils of either greater than or equal to 150 cells/μL or greater than or equal to 300 cells/μL, 61%/41% had an eosinophilic phenotype, while 49%/34% were eligible for mepolizumab therapy. A greater percentage of adults (60%/47% of adults with asthma onset in adulthood [AoA] and 48%/26% adults with childhood-onset asthma [<18 years, CoA]) were eligible compared with children (33%/24%), for eosinophil counts of ≥150 and ≥300 cells/μL, respectively; P < .05. Compared with adults, children had a similar number of exacerbations while having better lung function (P < .05). Among adults, those with AoA were older, were more likely to have nasal polyps (28% vs 5%; P < .05), and had higher blood eosinophil counts (272 vs 150 cells/μL; P < .05) compared with those with CoA, with no difference in lung function noted between the 2 groups. Subjects showing greater than or equal to 500 eosinophils/μL, a strong indicator for mepolizumab therapy, had more nasal polyps, higher inhaled steroid dose, lower lung function, and AoA predominance than did those with less than 500 eosinophils/μL (P < .05). Conclusions: A smaller percentage of children with severe asthma were eligible for mepolizumab compared with their adult peers. Severe AoA has distinct phenotypic features that favor treatment with mepolizumab, including greater eosinophilia and nasal polyposis, in contrast to CoA, which appears to have fewer features of type 2 mucosal inflammation.

© 2018, EDRA S.p.A. All rights reserved. Background. Asthma is a common childhood respiratory disease, affecting around 20% of Irish children. In other populations, vitamin D receptor (VDR) polymorphisms have been associated with asthma risk. We aimed to investigate the association between 2 VDR polymorphisms and uncontrolled paediatric asthma. Methods. 44 asthmatic children and 57 healthy volunteers were studied. The VDR TaqI gene variant in exon 9 (T/C) (rs731236) and ApaI (rs7975232) in intron 8 (C/T) were determined, using TaqMan® Assays. The lung function, serum 25-hydroxyvitamin D (25OHD) levels and other biomarkers of allergy, immunity, airway and systemic inflammation were assessed. Results. The distribution of T and C alleles and genotype frequencies differed significantly between asthmatics and controls for both polymorphisms (p < 0.05). A significant association was found between both TaqI (OR = 2.37, 95% CI (1.27 - 4.45), p = 0.007) and ApaI polymorphisms, and asthma risk (OR = 2.93, 95% CI (1.62 - 5.3), p = 0.0004). No association was observed between genotypes and 25OHD levels, lung function and other biomarkers, with the exception of Interleukin-10 (IL-10) and white blood cells count (WBC). IL-10 levels were lower in asthmatics with TC genotype for TaqI polymorphism (p < 0.01) and were higher in patients with TT genotype for ApaI (p < 0.01). WBC were higher in patients with TC and CC genotypes for TaqI (p < 0.05) and lower in TT genotype for ApaI (p < 0.05). Conclusion. TaqI and ApaI polymorphisms are associated with asthma in Irish children. Further studies are warranted to investigate the importance of decreased IL-10 levels in paediatric asthmatics with specific genotypes.

© 2018 S. Karger AG, Basel. Asthma is a chronic disabling respiratory disease that can be triggered by a variety of factors, including allergens, respiratory infections, psychological factors, occupational agents, exercise, atmospheric pollutants, and drugs. The asthma syndrome has been treated for decades according to a "one-fits-all" treatment strategy based on bronchodilators and steroids. With the availability of new forms of treatment targeting the different pathomechanisms of the asthma syndrome, such as anti-immunoglobulin E and cytokine-targeting therapies, the interest in biomarkers that can dis criminate different forms of asthma according to their pathomechanisms has increased. This review attempts to provide an overview of protein biomarkers in asthma and how they might be used to discriminate different forms of asthma that may respond positively to sophisticated new targeted therapies.

© 2018, Pediatria Ltd. All rights reserved. Materials and methods: the study assessed safety and clinical efficacy of combined use of vaccine preparations against S. pneumoniae and H. influenzae type b, leading pathogens in bronchopulmonary diseases exacerbations development, in previously unvaccinated 38 children aged 2–17 years with chronic bronchopulmonary diseases: 19 with malformations of the bronchi and lungs (MBL); 10 with malformations of bronchi and lungs in combination with bronchial asthma (MBL+BA); 9 with bronchial asthma (BA). The control group consisted of 19 unvaccinated children of the same age with a similar pathology. Combined vaccination against these infections, as well as their separate administration, did not cause adverse effects. Results: a year after the introduction of Pneumo-23 vaccine, the incidence of acute respiratory infections (ARI) and exacerbations of the main disease decreased by 2,3 times; Act-HIB by 2,3 and 2,1 times respectively; by 1,7 and 1,5 times respectively with simultaneous administration of these preparations. In children with BA the duration of one exacerbation decreased by 3,4 times, the average duration of temperature reaction by 1,9 times and the systemic antibiotic therapy of one exacerbation episode by 2,4 times. In the group of children with MBL+BA these indicators decreased by 2,1, 1,8 and 1,6 times, respectively, and in patients with MBL by 1,6, 1,5 and 1,4 times, respectively. Conclusion: vaccination against pneumococcal and hemophilic type b infections using one or both vaccines in patients with MBL and with MBL+BA is safe and positively affects the clinical course of the main disease.

© 2018, Dynasty Publishing House. All rights reserved. The objective. To specify the duration of persistence of antigens and DNA of Mycoplasma pneumoniae (M. pneumoniae) and Mycoplasma hominis (M. hominis) cells in the free state and as part of circulating immune complexes in blood of children suffering from bronchial asthma. Patients and methods. In the University Children’s Clinical Hospital of the Sechenov University, 161 children aged 1 to 14 years were observed. Group 1 (treatment group) included 126 children with bronchial asthma. 55 children (43.7%) had a mild course of disease, 52 children – moderate (42.1%) and 19 children (15.1%) – severe. All children were in the exacerbation period. Group 2 (control) consisted of 35 children with ARVI. The mean age of children in group 1 – 5.4 ± 1.8 years (79 boys (62.7%) and 47 girls (37.3%)); in group 2 – 5.7 ± 1.9 years (20 boys (57.1%) and 15 girls (42.9%). Diagnostic methods used: cultivation of mycoplasmas, preparation of immune serums, aggregate-haemagglutination assays (AHAA), polymerase chain reaction (PCR), direct immunofluorescence (DIF), methods of detection of circulating immune complexes (CIC). Results. AHAA examination of 126 serum samples of children from group 1 with BA, M. pneumoniae and M. hominis antigens in the free state were found in 73 and 50% of cases, respectively. In children of group 2 AHAA detected M. pneumoniae and M. hominis significantly more rarely: M. pneumoniae was found in 3 (8.6%) children (p = 95.3), M. hominis – in 2 (5.7%) children (p = 97.1). Further examination of serum samples of children with BA found M. pneumoniae and M. hominis cell DNA in 7.14 and 16.6% of cases, respectively. The work has shown that M. pneumoniae antigens are found in the composition of CIC in 55.5% of cases, M. hominis antigens – in 46.8% of cases, DNA – in 26.98 and 46.8%, respectively. For treatment of mycoplasma infection, children with BA received three azitromicin courses in the dose 10 mg/kg for 3 days with a 4-day interval. Conclusion. These data are indicative of long-term persistence of mycoplasma cell antigens and DNA in the free state and in CIC in blood of children with BA. Mycoplasmas can be regarded as one of the factors of inducing BA exacerbations in children. Tests for mycoplasma infection are indicated in patients with BA. Addition of macrolides to standard BA therapy in children with mycoplasma infection, as a rule, yields positive results.

© 2018 Dynasty Publishing House. All rights reserved. The objective. To offer a characteristic of phenotypes of atopic bronchial asthma (BA) in children according to the level physical health (LPH). Patients and methods. Our observation included 359 children aged 4 - 14 years with atopic BA. We performed a questionnaire survey among parents, studied medical histories and took anthropometric parameters. The parameters of respiratory, muscular and cardiovascular systems, and LPH according to the method by G.L.Apanasenko (1992) were determined. Results. Using multiple factor analysis with the principal component method we selected parameters that characterize the level of physical health in BA: values of external respiratory function - ERF (VC, FEV1), hand muscle strength (HMS), body mass index (BMI), vital index (VI), Robinson index (IRob), muscular endurance (ME). In BA with low LPH no patient has full control over disease. Overweight is recorded in 37.9% of them, lower ERF parameters in 33.3%, lower HMS in 87.9%, deviations on the part of the cardiovascular system in 80.3%. In BA with higher LPH, full control over diseases is observed in almost half of children (48.7%), harmonious physical development - in 87.1% of cases. Parameters of ERF, muscular and cardiovascular system corresponded to the norm in 92.3; 61.5 and 100% of patients, respectively. Children with BA with average LPH take the intermediate position between these two groups. Conclusion. Physical health should be regarded as a factor of retaining control over BA. Phenotype determination according to the level of physical health and degree of disease control permits to personify rehabilitation programmes for children with atopic bronchial asthma.

© 2018 Dynasty Publishing House. All rights reserved. The objective: To give a characteristic of body composition in adolescents with atopic bronchial asthma combined with overweight, and to determine the impact of its disorders on the degree of disease control. Patients and methods: Bioimpedance analysis of the body composition was performed in 168 adolescents aged 12-17 years, including 68 patients with mild bronchial asthma in the remission stage and in combination with overweight, 50 overweight adolescents without asthma and 50 healthy same-age peers. Bioimpedance characteristics were compared with the degree of controlling the symptoms of disease. Results: As has been found, adolescents with atopic bronchial asthma combined with overweight are characterised by significant changes in the body composition, which is manifest by higher fat tissue (on average 156.8 ± 21.3% with respect to the norm), total body water and extracellular fluid (127.0 ± 8.1% and 112.3 ± 5.9%, respectively), lower active cell (to 92.8 ± 10.2%) and skeletal muscle mass (to 96.9 ± 6.2%). The degree of the above disorders of body composition was higher in patients with incomplete asthma control. Conclusion: Disorders of body composition in adolescents with bronchial asthma reflect a decreased physical activity, shifts in water-electrolyte balance and protein deficiency. Worsening of body composition is associated with loss of asthma control.

© 2018 Medical Education. All rights reserved. The aim of this study was to assess long-term effects of pneumococcal vaccination with 23-valent polysaccharide vaccine (PPV23) and 13-valent conjugate vaccine (PCV13) in patients with bronchial asthma. Methods. One hundred and three patients with mild to severe asthma were involved. They were randomly assigned to vaccination with PCV13, or PPV23, or PPV23 followed by PCV13, or vice versa. Clinical efficacy of vaccination was evaluated using number of asthma exacerbation a year before and 1 and 4 years after the vaccination; need in antibiotics a year before and 1 and 4 years after the vaccination; and number of hospitalizations due to asthma exacerbation a year before and 1 and 4 years after the vaccination. Results. In a year after vaccination, number of patients who had not experienced asthma exacerbation increased significantly in PPV23, PPV23/PCV13, and PCV13/PPV23 groups (p < 0.01 to p < 0.001). In 4 years after vaccination, number of patients without exacerbations increased significantly in PCV13/PPV23 group only (48.1%; p < 0.01). Number of patients who did not require hospitalization due to asthma exacerbation increased significantly in PCV13 group only (81.8%; p < 0.05). Conclusion. The authors proposed a hypothesis of impact of pneumococcal vaccines on immunopathogenesis of bronchial asthma. The authors consider vaccination against pneumococcus using PCV13 followed by PPV23 should be a part of the basic therapy of asthma.

© 2018, Pleiades Publishing, Ltd. Interleukin-33 (IL-33) belongs to the IL-1 cytokine family and plays an important role in modulating immune system by inducing Th2 immune response via the ST2 membrane receptor. Epithelial cells are the major producers of IL-33. However, IL-33 is also secreted by other cells, e.g., bone marrow cells, dendritic cells, macrophages, and mast cells. IL-33 targets a broad range of cell types bearing the ST2 surface receptor. Many ST2-positive cells, such as Th2 cells, mast cells, basophils, and eosinophils, are involved in the development of allergic bronchial asthma (BA). This suggests that IL-33 directly participates in BA pathogenesis. Currently, the role of IL-33 in pathogenesis of inflammatory disorders, including BA, has been extensively investigated using clinical samples collected from patients, as well as asthma animal models. In particular, numerous studies on blocking IL-33 and its receptor by monoclonal antibodies in asthma mouse model have been performed over the last several years; IL-33-and ST2-deficient transgenic mice have also been generated. In this review, we summarized and analyzed the data on the role of IL-33 in BA pathogenesis and the prospects for creating new treatments for BA.

© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.

© 2018 Medical Education. All rights reserved. The article provides a review on prevalence, phenotypes, endotypes, and the control of severe bronchial asthma. Severe asthma is a widespread, heterogeneous disease that affects 5 - 20% of patients with bronchial asthma. Prevalence of severe asthma in Russia significantly exceeds the official statistics data, therefore it is necessary to maintain a national register of patients with severe asthma. The conventional therapy for severe asthma is not always effective due to the uncontrolled course of the disease and eosinophilic airway inflammation. The identification of asthma phenotype/endotype is reasonable to develop a personalized approach to treatment. This approach allows to achieve better control of the disease and to minimize the risk of asthma exacerbations, fixed airway obstruction and adverse effects of the pharmacological therapy. The main changes in the Global Strategy for Asthma Management and Prevention (GINA, 2018) concerning severe asthma therapy are highlighted in this article. It is also emphasized that the use of monoclonal IL-5 and IgE-antibodies could contribute to successful treatment of patients with uncontrolled severe asthma. Currently, two immunobiological drugs have been registered in Russia, omalizumab (anti-IgE antibody) and reslizumab (anti-IL-5 antibody).

© 2018 Medical Education. All rights reserved. The aim of this study was pharmacoeconomic evaluation of treatment with reslizumab compared to omalizumab in severe eosinophilic asthma. Methods. The study was based on indirect comparison between omalizumab and reslizumab in patients with severe asthma using published data. Costs of treatment with omalizumab, reslizumab, combinations of inhaled corticosteroids and long-acting beta-agonists (ICS/LABA), outpatient treatment, treatment of exacerbations and adverse events were also compared. Сost-effectiveness analysis and budget impact analysis were used. Results. According to results of cost-effectiveness analysis, therapy with reslizumab dominated over therapy with omalizumab in patients with severe asthma in term of exacerbation rate requiring treatment with systemic steroids. According to results of budget impact analysis, switching of 100 patients from omalizumab to reslizumab could save RUB 51.99 million per year that corresponds to 36.6% reduction in general direct costs for treatment of severe asthma. Conclusion. The results of this study demonstrated economic advantage of reslizumab over omalizumab in patients with severe eosinophilic asthma.

© 2018 Medical Education. All rights reserved. Mild asthma is characterized by infrequent and slight clinical manifestations and, therefore, is paid lack of attention both from patients and physicians. Physicians tend to underestimate risk of severe exacerbations including asthmatic status in patients with mild asthma. Patients with mild asthma are often poorly adherent to treatment. Also, certain difficulties are related to timely and correct diagnosis and the choice of the optimal treatment by primary care physicians who are first physicians encountering such patients. The paradoxus of asthma and use of short-acting β2-agonists (SABA) to treat chronic airway inflammation lead to excessive dependence on rescue inhalers and insufficient adherence to maintenance anti-inflammatory therapy. This could trigger acute exacerbations and even fatal outcomes in patients with mild asthma. Therefore, SABA monotherapy has to be limited. Easy-to-use questionnaires, algorithms and treatment protocols accessible for primary care physicians could improve detection of mild asthma. Favorable results of clinical trials on as-needed use of budesonide/formoterol Turbuhaler® could change the management paradigm for mild asthma regarding risk of exacerbations, control of asthma symptoms, airway inflammation, and cost-efficacy.

Бронхиальная астма (БА) является хроническим воспалительным заболеванием дыхательных путей. Основной целью терапии БА является достижение и поддержание полного контроля болезни. Контроль заболевания включает в себя снижение частоты обострений и частоты госпитализаций или полное их отсутствие, нормализацию показателей функции внешнего дыхания на фоне правильно подобранной базисной (противовоспалительной) терапии. Ингаляционные глюкокортикостероиды (ИГКС) обладают противовоспалительной активностью, воздействуя на основу заболевания, и высокой клинической эффективностью у детей всех возрастных групп. Если течение астмы не контролируется ИГКС, необходимо повысить их дозу или использовать их в комбинации с другими препаратами, чаще всего с бета-2-агонистами длительного действия (ДДБА). Существует вариант проведения длительной терапии при лечении БА - это интермиттирующая схема дозирования препаратов базисной терапии (ИГКС или комбинации ИГКС/ДДБА). В этом случае доза выбирается в зависимости от выраженности симптомов и течения БА с подбором минимальной поддерживающей дозы и возможностью временного увеличения ингаляций во время периодов обострения.

Бронхиальная астма - мультифакторное заболевание, в основе которого лежат генетическая предрасположенность и агрессивное воздействие различных аллергенов. Заболевание сопровождается такими симптомами, как кашель, дистанционные свистящие хрипы, одышка. Однако данные симптомы сопровождают и бронхообструктивный синдром (БОС), который наблюдается у детей в возрасте 5 лет и младше в связи с инфекциями верхних дыхательных путей, которые часто встречаются в этой возрастной группе. При оказании помощи ребенку с бронхиальной обструкцией необходимо оценить тяжесть БОС до лечения. В педиатрии для купирования остро возникающих нарушений бронхиальной проходимости используют ß2-агонисты, антихолинергические препараты и их комбинацию.

Бронхиальная астма (БА) является хроническим воспалительным заболеванием дыхательных путей. Основной целью терапии БА является достижение и поддержание полного контроля болезни. Контроль заболевания включает в себя снижение частоты обострений и частоты госпитализаций или полное их отсутствие, нормализацию показателей функции внешнего дыхания на фоне правильно подобранной базисной (противовоспалительной) терапии. Ингаляционные глюкокортикостероиды (ИГКС) обладают противовоспалительной активностью, воздействуя на основу заболевания, и высокой клинической эффективностью у детей всех возрастных групп. Если течение астмы не контролируется ИГКС, необходимо повысить их дозу или использовать их в комбинации с другими препаратами, чаще всего с бета-2-агонистами длительного действия (ДДБА). Существует вариант проведения длительной терапии при лечении БА - это интермиттирующая схема дозирования препаратов базисной терапии (ИГКС или комбинации ИГКС/ДДБА). В этом случае доза выбирается в зависимости от выраженности симптомов и течения БА с подбором минимальной поддерживающей дозы и возможностью временного увеличения ингаляций во время периодов обострения.

Бронхиальная астма - мультифакторное заболевание, в основе которого лежат генетическая предрасположенность и агрессивное воздействие различных аллергенов. Заболевание сопровождается такими симптомами, как кашель, дистанционные свистящие хрипы, одышка. Однако данные симптомы сопровождают и бронхообструктивный синдром (БОС), который наблюдается у детей в возрасте 5 лет и младше в связи с инфекциями верхних дыхательных путей, которые часто встречаются в этой возрастной группе. При оказании помощи ребенку с бронхиальной обструкцией необходимо оценить тяжесть БОС до лечения. В педиатрии для купирования остро возникающих нарушений бронхиальной проходимости используют ß2-агонисты, антихолинергические препараты и их комбинацию.