4 research outputs found
Several features of inflammation at the patients with atopic bronchial asthma when exposed to respiratory viruses
No full textThe modern interpretation of the pathogenesis bronchial asthma (ВА) emphasizes the role of systemic inflammation at the BA, since its development under the influence of specific (allergens) and non-specific factors leads to an imbalance of pro- and anti-inflammatory cytokines in the airways. It has been established that most exacerbations of BA occur due to the influence of respiratory viral infection (RVI). The process of inflammation in the airways with virus-induced exacerbations of BA depends on the type of respiratory virus, and also phenotype and endotype of BA at the patient. Based on in vitro and in vivo studies, the role of interleukin-33 (IL-33) in the pathogenesis exacerbation of atopic BA in the mouse model is described. The aim of our work is to determine the IL33 gene expression and study its role during development of atopic BA and its virus-induced exacerbation in humans. Material and methods. All volunteers included in the study were divided into groups: «BA», «BA+RVI», «RVI», «healthy donors». All study participants underwent clinical, laboratory, instrumental (spirometry), allergological, immunological examination (determination the expression mRNA of the IL33 gene in peripheral venous blood and identification the mRNA of respiratory viruses (RSV, RV, coronaviruses, influenza virus type A and B, metapnevmoviruses, adenoviruses, bokaviruses, parainfluenza viruses type 1, 2, 3, 4) in smears from the nasal cavity by RT-PCR). Results. In the «BA» and «BA+RVI» groups were observed the decrease FEV , increased the ACQ-7 (more than 1.5 points), the blood eosinophilia (P = 0.000002), which characterizes the uncontrolled course and exacerbation of atopic BA from volunteers. The highest level of the expression mRNA IL-33 was found at the «BA+RVI» group (P = 0.003), and in the absence of RVI in volunteers with exacerbation of atopic BA the level of IL-33 not differs from healthy donors. According to the results of our study the more severe course of atopic BA was observed in the season with a predominance of RSV infection in 2017 compared to 2016 according to ACQ-7 (P = 0.00004 and P = 0.0002) and FEV (P = 0.006 and P = 0.008), respectively. Conclusions. The results of the study provide additional evidence of the role of pro-inflammatory IL-33 in the pathogenesis of RVI and virus-induced exacerbations of atopic BA (most often RSV and RV). Identification of new mechanisms of virus-induced exacerbations of atopic BA can be used in the selection and development of personalized basic therapy of asthma. 1
Allergic rhinitis – the actual problem of the XXI century
No full textAllergic rhinitis (AR) is one of the most common chronic diseases of the upper respiratory tract throughout the world. Despite advances in understanding the mechanisms of allergic inflammation, the symptoms of AR in most cases are not completely controlled by modern methods of treatment. AR is a precursor and a predisposing factor for the development of other respiratory diseases, one of which is bronchial asthma. Therefore, it is important to diagnose AR in time and select the most effective and modern drugs that will not only help control the course of AR, but also improve the quality of life of patients. Intranasal glucocorticosteroids are recommended as first-line therapy for patients with varying severity of AR. The experience of using intranasal fluticasone propionate in Russia and abroad testifies to the effectiveness of this drug in the treatment of various forms of AR, both as mono-therapy and in combination with antihistamines and decongestants
Dupilumab: basic aspects and applications to T2-mediated diseases
No full textThe asthma, chronic rhinosinusitis with nasal polyps (CRSwNP), atopic dermatitis (AD), eosinophilic esophagitis and other diseases based on T2-inflammation are a widespread in the world. It has led to the development of genetically engineered drugs aimed at individual and specific components of inflammation. One of the leading positions in the pathogenesis of T2-mediated diseases is occupied by interleukin (IL)-4 and IL-13, which explains the prospects of studying these cytokines for the creation of anti-IL-4/IL-13 monoclonal antibodies. The first immunobiological drug was registered to directe against the α subunit of the IL-4 receptor (IL-4Ra), common to both IL-4 and IL-4/IL-13 receptor complexes is dupilumab which is a fully human monoclonal antibody. Dupilumab targets the IL-4 receptor alpha chain (IL-4Rα), common to both IL-4R complexes: type 1 (IL-4Rα/γc; IL-4 specific) and type 2 (IL-4Rα/IL-13Rα1; IL-4 and IL-13 specific). Because the IL-4/IL-13/STAT6 signaling pathway plays a significant role in T2 inflammation. IL-4 and IL-13 are secreted by several cells and, along with other T2 cytokines, as well as with the participation of IL-33, IL-25 and TSLP can stimulate cells to further secrete pro-inflammatory cytokines, contributing to the maintenance of the inflammatory process. Currently, dupilumab has been studied in at least 3,000 patients with asthma, AD, CRSwNP and eosinophilic esophagitis. The results of investigation show an acceptable safety profile in placebo-controlled studies worldwide. In this article, we have highlighted the results of numerous clinical studies and observations that have proven the effectiveness and safety of the use of dupilumab in asthma, AD, CRSwNP, prurigo, eosinophilic esophagitis and eosinophilic pneumonia
Особенности молекулярных механизмов патогенеза бронхиальной астмы в сочетании с полипозным риносинуситом
No full textThe combination of bronchial asthma (BA) and chronic rhinosinusitis with nasal polyps (CRSwNP) is currently considered a separate phenotype wit1 dysregulation of pro- and anti-inflammatory cytokines as one of t1e leading causes of inflammation. The aim of this study was to investigate the local and systemic inflammatory process in patients with BA associated with CRSwNP. Methods. The study enrolled 96 volunteers divided into 4 groups: the 1st was healthy control (Normal); the 2nd had allergic BA associated with CRSwNP; the 3rd had nonallergic BA associated with CRSwNP; the 4th had CRSwNP without BA. All participants of the study underwent clinical, laboratory, instrumental, and histological examinations. The expression of il-1β, il-4, il-,5 il-6, il-13, il-37, il-17f, ifn-γ, tnf-α and tgf-β genes was assessed in the peripheral blood mononuclear cells - PBMC and in the polyp tissue using RT-PCR. We also estimated the expression of tslp, il-25 and il-33 in the polyp tissue and expression of GATA3 and RORgt transcription factors in PBMC. Results. The pathogenesis of BA associated with CRSwNP is characterized by the dys-regulation of the local pro- and anti-inflammatory cytokines of the Th1-, Th2-, Th17- immune response. Moreover, the high expression of il-37 gene in patients with BA associated with CRSwNP, and especially in patients with not-allergic BA associated with CRSwNP, probably indicates the «inclusion» of the compensatory mechanism. In addition, BA associated with CRSwNP is characterized by severe course of both diseases. A nonallergic BA associated with CRSwNP is characterized by more pronounced eosinophilic inflammation, which is an unfavorable prognostic factor. Conclusion. Thus, a comparison of the levels of local and systemic cytokine expression in patients with BA associated with CRSwNP led to the conclusion that CRSwNP affects the local immunity more than systemic immunity. However, the latter is affected to some extent in the long-term as well.В настоящее время бронхиальная астма (БА) в сочетании с полипозным риносинуситом (ПРС) рассматривается как отдельный фенотип, где дизрегуляция про- и противовоспалительных цитокинов играет ведущую роль в развитии воспаления. Целью исследования явилось изучение особенностей воспаления при сочетании БА и ПРС на основе данных о локальной и системной экспрессии генов цитокинов. Материалы и методы. В исследование включены добровольцы (n = 96), которые были распределены в 4 группы: 1-я («Норма») — здоровые лица; 2-я — лица с аллергической БА (аБА) в сочетании с ПРС («аБА + ПРС»); 3-я — неаллергической БА (нБА) в сочетании с ПРС («нБА + ПРС»); 4-я — «ПРС без БА». У всех участников выполнены клинико-лабораторные, инсаруме’наальные’ и аллергологические обследования, а также гистологическое исследование ткани полипа. Полученные образцы мононуклеарных клеток периферической крови (peripheral blood mononuclear cells (PBMC) и ткань полипа) изучались на предмет экспрессии генов il-1β, il-4, il-5, il-6, il-10, il-13, il-17f, il-37, ifn-γ, tnf-α, tgf-β, при этом экспрессия генов tslp, il-25 и il-33 изучалась только в ткани полипа. Также изучена экспрессия факторов транскрипции (GATA3 и RORgt) в PBMC. Результаты. Патогенез БА в сочетании с ПРС характеризуется локальной дизрегуляцией про- и противовоспалительных цитокинов Th1-, Th2- и Тh17-иммунного ответа. При этом высокая экспрессия гена il-37, в особенности при нБА в сочетании с ПРС, возможно, свидетельствует о «запуске» противовоспалительного компенсаторного механизма. Полученные результаты также коррелировали с данными экспрессии генов-факторов транскрипции в стимулированных PBMC. Показано также, что сочетание БА и ПРС способствует утяжелению течения обоих заболеваний, а при сочетании нБА и ПРС имеет признаки более выраженного эозинофильного воспаления, что является неблагоприятным прогностическим фактором. Заключение. Таким образом, по данным сравнения уровней локальной и системной экспрессии цитокинов у пациентов с БА в сочетании с ПРС, сделан вывод о том, что локальный иммунный ответ в большей степени изменен при ПРС, в дальнейшем эти изменения происходят также на системном уровне, но в меньшей степени
