Introduction. Guidelines on Biological Therapy for Bronchial Asthma of the European Academy of Allergy and Clinical Immunology (EAACI) identified a number of controversial issues for additional outcome analysis using randomized clinical trials and data from routine clinical practice. In particular, there is unmet need to clarify algorithms for prescribing biologicals using predictors of response and its timing, taking into account risk factors and multimorbidity. Omalizumab is a recombinant humanized monoclonal anti-IgE antibody of IgG1 class used for the treatment of severe refractory atopic bronchial asthma (BA) and a variety of IgE-mediated diseases. Among biological agents, this "pioneer molecule" has the greatest experience in the "allergology and immunology" profile. Detailed description of the "nonresponders" portraits will allow to perform the therapy response assessment on time and facilitate rational planning of individual therapy, which is a prerequisite for biologicals era. Using only routine methods, it is possible to perform initial and dynamic screening to phenotype a heterogeneous cohort of patients with severe asthma and chose the optimal strategy. Aim. To identify predictors of nonresponse to omalizumab anti-IgE therapy in patients with severe atopic BA and to establish optimal timing of efficacy assessment using retrospective analysis of data from the Biologic Therapy Registry of Allergology and Immunology in routine clinical practice. Materials and methods. A retrospective single-center registry study was conducted at the Allergy and Immunology Reference Center from June 2017 to August 2021. 135 patients with severe BA, with confirmed perennial sensitization, who received omalizumab according to the recommendations of the current version of GINA, were selected from the clinical and dynamic observational system (registry). Dosing regimen and administration frequency of omalizumab were determined in accordance with the instructions for the drug. Assessment of therapy efficacy was performed at the time point 4, 6 and 12 months. Patients were subgrouped into "responders" and "non-responders" according to the following criteria: ACT score less than 19 and/or difference between initial ACT score in dynamics less than 3 points; forced expiratory volume in the first second less than 80%; combination of these two criteria. Nonparametric methods of descriptive statistics were used in data processing: median, interquartile range. Differences were considered significant at p0.05. MannWhitney U-test, KruskalWallis one-way analysis of variance, and Fisher's 2 test were used to compare quantitative characteristics. Results. Heterogeneous subgroups of patients differing in reaching the criteria of "non-responders" to treatment were identified; the informativity of modifiable and unmodifiable factors differed at time-points of dynamic observation. In the differential analysis, two profiles of "nonresponders" were defined in combination with the most significant predictors of "nonrsponse" to omalizumab. According to the data obtained, one of the clinical phenotypes, namely the combination of severe asthma with the Samters triad, corresponded to the characteristics of the patient "nonresponders": age of onset is about 30 years, females, severe exacerbations of BA while taking non-steroidal anti-inflammatory drugs, accompanied with high levels of eosinophilia. Conclusion. The data obtained illustrates the hypothesis of pathogenetic heterogeneity of severe BA with the phenomenon of overlapping phenotypes and can serve as an additional orienteer for creating the individual plan of anti-IgE therapy in real clinical practice.
According to accumulated clinical data, one of the causes of severe damage to lung epithelial cells associated with SARS-CoV-2 (2019-nCoV) is an acute, timely underestimated "cytokine storm" (cytokine cascade, hypercytokinaemia) with characteristic signs of an expressed hyper-inflammatory syndrome with subsequent polyorganic failure. The study presents the results of the analysis of the effectiveness of tocilizumab therapy (TCZ) in patients (n = 181) of different age groups with developed pneumonia caused by SARS-CoV-2. The aim of the study was to evaluate the effectiveness of TCZ therapy in patients of different age groups with developed pneumonia in the frame of COVID-19. Methods. Patients (n = 181) with community-acquired pneumonia caused by coronavirus SARS-CoV-2 are included in a one-center, non-randomized, prospective study to evaluate the effectiveness of TCZ therapy conducted at the State Public Health Institution "City Clinical Hospital No.52" of the Moscow City Health Department. Patients were divided into 3 age subgroups – up to 50 years, 50–70 years and over 70 years. Patients with community-acquired SARS-CoV-2-induced pneumonia receiving non-invasive oxygen support and patients who had artificial lung ventilation (ALV) were given a single dose of 400 mg of TCZ in addition to basic therapy. Results. There are no significant differences between age groups in the severity of pneumonia according to the data of the computed tomography (CT), however, a more severe condition and a higher mortality rate (p < 0.001) were reliably observed in patients over 70 age compared to the other age groups. After TCZ treatment in patients of each age group, the severity of the condition assessed on the National Early Warning Score (NEWS2) has been significantly reduced compared to the baseline. Conclusion. According to the data of the pilot study the efficacy and safety of TCZ in patients of all presented age groups with COVID-associated pulmonary tissue lesion and signs of "cytokine storm" was demonstrated. At the same time, patients up to 50 years after the therapy of TCZ managed to achieve greater clinical efficiency compared to patients in other groups. According to the severity of the state and laboratory criteria, the lowest clinical efficacy of TCZ therapy was observed in patients over 70 years of age; as a consequence, the highest mortality rate was observed in the same group. At the same time, the TCZ therapy has not had a positive impact on the change of laboratory values and the severity of the disease in case of unfavorable outcome.
Common variable immune deficiency is the most common form of a group of primary immunodeficiencies in adult patients. Pulmonary complications occupy leading positions. It is the development of recurrent bronchopulmonary inflammatory diseases that is considered to be one of the main causes of death and disability in patients with this disease. By presenting two clinical cases with long diagnostic delays, the authors try to attract the attention of specialists of related professions, which will minimize the development of irreversible complications in the patients.
Современный взгляд на терапию пациентов с бронхи альной астмой (БА) характеризуется развитием пер сонализированного подхода и попытками выделить отдельные клинические фенотипы болезни с после дующей разработкой индивидуального лечебного плана (GINA, 2014) [1]. В настоящее время ведется активный поиск связей между фенотипом, геноти пом, механизмом развития заболевания, сопутствую щей патологией и ответом на проводимую терапию. В дальнейшем это позволит разработать алгоритм на значения лекарственных препаратов в зависимости от варианта течения заболевания [2,3].У пациентов с неконтролируемым вариантом БА отмечается высокий уровень распространенности со путствующего ожирения. Значимость этой проблемы хорошо иллюстрируется имеющейся статистикой. По данным Всемирной организации здравоохране ния (ВОЗ), ожирение и БА приблизились к рубежам пандемии: в мире насчитывается 300 млн больных БА, а к 2025 г. ожидается увеличение этого числа еще на 100 млн; кроме того, БА ежегодно является причи ной преждевременной смерти 250 тыс. пациентов. Избыточная масса тела (МТ) отмечается у ≈ 1 билли она взрослого населения планеты, а у 475 млн -ожи рение. Согласно статистике Министерства здраво охранения Российской Федерации, у 40 % трудоспо собного населения России установлена избыточная МТ, данные по БА аналогичны. Распространенность БА среди взрослых с ожирением выше, чем среди лиц без избыточной МТ (соотношение составляет 9 : 5 % соответственно) [4]. Сочетание БА и ожирения тяже лым бременем ложится и на педиатров. Так, > 60 % детей с ожирением после 12 лет страдают БА [5].В настоящее время неоспоримо доказано, что при ожирении повышается риск развития БА и ухуд шается контроль над ней, при этом формируется трудноконтролируемый фенотип с проявлениями до зозависимости или резитентности к ингаляционным глюкокортикостероидам (иГКС) [6]. Взрослые и де ти, страдающие БА на фоне ожирения, чаще госпи тализируются и дольше пребывают в стационаре, имеют больше дней нетрудоспособности и нуждают ся в завышенных объемах лекарственной терапии, чем пациенты с БА и нормальной МТ [7]. При име ющихся вариабельности клинической картины, анамнеза, ответа на терапию у детей и взрослых дан ного клинического фенотипа необходим поиск при чин и улучшения тактики терапии этого сочетания.С клинической точки зрения комбинация БА + ожирение -проблема междисциплинарная, требую РезюмеВсе большее внимание экспертов уделяется фенотип обоснованному подходу к лечению пациентов с бронхиальной астмой (БА). Одним из основных клинических фенотипов является сочетание БА и избыточной массы тела, а в некоторых случаях -ожирения. Ряд клинических особенностей этого тандема объясняется результатами молекулярно генетических исследований. Активный поиск взаи мосвязей между фенотипом, генотипом и механизмом развития заболевания позволит разработать эффективный терапевтический алго ритм, наиболее прогностически оправданный у данной подгруппы пациентов. Ключевые слова: бронхиальная астма, ожирение, фенотип. SummaryA phenotype based approach to treatment of bronchial asthma dr...
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