СОСТАВ СООБЩЕСТВА МИКРООРГАНИЗМОВ В ДЫХАТЕЛЬНЫХ ПУТЯХ У ЗДОРОВЫХ ЛИЦ И БОЛЬНЫХ БРОНХИАЛЬНОЙ АСТМОЙ

This review summarizes the results of studies on the composition of microbial communities in the airways of healthy individuals and patients with asthma. Modern molecular genetic technology of the microbial identification, which are based on a sequence determination of encoding proteins genes conserved regions. These regions form the 16s-subunit ribosomal RNA in microorganisms of different species. These genes are detected by sequencing markers characteristic of individual microorganisms and their phylogenetic groups, and allow to perform a deep analysis of the microbiota in healthy volunteers and patients with chronic bronchoobstructive diseases. So, apparently healthy human bronchial tree is characterized by low bacterial contamination (most typical representatives here are the genera Pseudomonas, Streptococcus, Prevotella, Fusobacteria and Veilonella, much less potentially pathogenic Haemophilus and Neisseria are represented). In bronchial asthma patients the lower respiratory tract microbiota undergoes a qualitative transformation: as compared to healthy individuals the number of Proteobacteria increases and the number of Bacteroidetes decreases. Severe asthma in children is associated with significant respiratory tract Staphylococcus spp. insemination. Association between the asthma developing higher risk in young children and organisms such as Haemophilus, Moraxella and Neisseria spp. It is of considerable interest to determine the role of the microbiome in the development of human diseases of the bronchopulmonary system, and to understand the impact of the microbes communities as a course of disease and the important factor for the development of resistance to therapy.В обзоре обобщены результаты исследований по изучению состава сообщества микроорганизмов в дыхательных путях здоровых лиц и пациентов с бронхиальной астмой. Современные технологии молекулярно-генетической идентификации микроорганизмов основаны на определении последовательности консервативных участков генов, кодирующих белки, которые формируют 16s-субъединицу рибосомальной рибонуклеиновой кислоты микроорганизмов различных видов. Данные гены имеют выявляемые секвенированием маркеры, характерные для отдельных микроорганизмов и их филогенетических групп, и позволяют выполнить глубокий анализ микробиома как у здоровых добровольцев, так и у больных хроническими бронхообструктивными заболеваниями. Так, у практически здорового человека бронхиальное дерево характеризуется низкой бактериальной обсемененностью (наиболее типичными являются представители родов Pseudomonas, Streptococcus, Prevotella, Fusobacteria и Veilonella, значительно реже представлены потенциально патогенные Haemophilus и Neisseria). У больных брон-хиальной астмой микробиота нижних дыхательных путей подвергается качественной трансформации: по сравнению со здоровыми инди-видуумами количество Proteobacteria увеличивается, а Bacteroidetes — уменьшается. Тяжелая бронхиальная астма у детей ассоциирована со значимой обсемененностью дыхательных путей Staphylococcus spp. Также обнаружена ассоциация более высокого риска развития аст-мы у детей раннего возраста и такими микроорганизмами, как Haemophilus, Moraxella и Neisseria spp. Полученные данные представляют значительный интерес как для определения роли микробиома в развитии заболеваний бронхолегочной системы человека, так и для понимания влияния микробиотических сообществ на особенности течения болезни и формирование резистентности к терапии.

Прогностическое значение коморбидной патологии в прогрессировании хронической обструктивной болезни легких в зависимости от фенотипических особенностей заболевания

Background: Chronic obstructive pulmonary disease (COPD) is characterized by progressive limitation of airflow rate, hyperergic inflammatory response of the respiratory tract, and systemic manifestations. Prognosis of the disease depends on the severity of these pathogenetic components. FEV1 which characterizes the speed limit airflow do not allow predicting the rate of COPD progression. Aims: comparison of the prognostic significance of such clinical parameters as frequency of exacerbations and the development of comorbid diseases to assess the nature of COPD progression by using different classification approaches. Materials and methods: The prospective comparative study included 98 patients with COPD. In the framework of the study protocol, 2 visits were required when a practitioner recruited patients who met inclusion/exclusion criteria, obtained the signed informed consent, collected the anamnestic data, and performed basic procedures of the study: spirometry, 6-minute stepper test, assessment of dyspnea on questionnaire mMRC, body plethysmography, lung diffusion capacity study, dopplerechocardiography, tomography of the chest. Visit 2 was conducted in 12 months after the first one to assess the dynamics of the disease. The dynamics of the disease was considered negative if, upon repeated examination, the patient was referred to the group with more severe COPD. Results: Our study demonstrates that comprehensive assessment of such factors as the frequency of COPD exacerbations in the preceding 12 months and the presence of comorbid diseases in a patient is reasonable for assessment of disease severity and determination of disease prognosis. At the same time the frequency of COPD exacerbations as one of the evaluated factors is most strongly associated with disease progression. Conclusions: Thus, a practitioner is recommended to use the proposed additional clinical criteria to assess the severity and degree of progression of COPD.Обоснование. Хроническая обструктивная болезнь легких (ХОБЛ) — хроническое заболевание с прогрессирующим ограничением скорости воздушного потока, гиперергическим воспалительным ответом дыхательных путей и системными проявлениями. От степени выраженности этих патогенетических компонентов зависит прогноз течения заболевания. Показано, что характеристика ограничения скорости воздушного потока (объем форсированного выдоха за первую секунду) не позволяет с высокой вероятностью предсказать скорость прогрессирования ХОБЛ.Цель исследования: сравнение прогностической значимости таких клинических показателей, как частота обострений и развитие коморбидных заболеваний, для оценки характера прогрессирования ХОБЛ при использовании различных классификационных подходов.Методы. На основании единого протокола в проспективное сравнительное исследование включены 98 больных ХОБЛ. В рамках протокола предусмотрено 2 визита, включающих оценку соответствия пациента критериям включения/исключения, подписание информированного согласия, сбор анамнестических данных и выполнение основных процедур исследования (оценка функции внешнего дыхания, 6-минутный шаговый тест, оценка одышки по опроснику mMRC, бодиплетизмография, исследование диффузионной способности легких, допплерэхокардиография, компьютерная томография органов грудной клетки). Второй визит проводился через 12 мес после первого с целью оценки динамики заболевания, которая считалась отрицательной, если по прошествии одного года наблюдения пациента переводили в группу ХОБЛ с более тяжелым течением. Коморбидными заболеваниями считались снижение индекса массы тела менее 21, наличие остеопороза, анемии, сердечно-сосудистых заболеваний, язвенной болезни желудка, сахарного диабета 2-го типа.Результаты. Проведенное нами исследование свидетельствует о целесообразности комплексной оценки таких факторов, как частота обострений ХОБЛ за предшествующие 12 мес и наличие коморбидных заболеваний у больного при оценке текущей тяжести течения заболевания и определении его прогноза. При этом частота обострений ХОБЛ среди оцениваемых факторов наиболее сильно связана с прогрессированием заболевания.Заключение. Таким образом, практическому врачу предложены дополнительные клинические критерии для комплексной оценки тяжести и степени прогрессирования ХОБЛ

Сравнительный анализ орофарингеальной микробиоты у больных хронической обструктивной болезнью легких и бронхиальной астмой различной степени тяжести

Backgraund: The result of comparative study of oropharyngeal microbiota taxonomic composition in patients with different severity level of bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD) is presented in this paper. Aims: To compare oropharyngeal microbiota composition in case of bronchial asthma and chronic obstructive pulmonary disease in different severity levels. Metods: 138 patients, 50 with BA and 88 with COPD were studied. For each patient was collected anamnesis vitae, swab from the back of the throat and performed physical examination. High-throughput 16S ribosomal RNA gene sequencing and bioinformatic analysis was employed to characterize the microbial communities. Results: As a result of the study was found a number of differences on various taxonomic levels in microbiota’s composition within group of patients with different severity level of BA and group of patients with different severity level of COPD and between those groups. COPD patients with GOLD 1–2 in comparison with GOLD 3–4 patiens are marked by prevalence of species Brevibacterium aureum, genus Scardovia, Coprococcus, Haemophilus, Moryella, Dialister, Paludibacter and decrease of Prevotella melaninogenica species. BA patients with severe uncontrolled asthma in comparison with patients which have mild persistent asthma are marked by decrease of Prevotella and increase of species Bifidobacterium longum, Prevotella nanceiensis, Neisseria cinerea, Aggregatibacter segnis and genus Odoribacter, Alloiococcus, Lactobacillus, Megasphaera, Parvimonas, Sneathia. Patient’s microbiota in BA group in comparison with COPD group is characterized by the prevalence of Prevotella melaninogenica and genus Selenomonas, Granulicatella и Gemella, and decrease of Prevotella nigrescens, Haemophilus influenza and genus Aggregatibacter, Alloiococcus, Catonella, Mycoplasma, Peptoniphilus и Sediminibacterium. There are no differences between microbiota composition in case of severe uncontrolled BA and very severe COPD. Conclusion: Lack of differences in oropharyngeal microbiota taxonomic composition between patients with severe uncontrolled BA and very severe COPD allow us to suggest a similarity of bronchopulmonary system condition in case of diseases' severe stages.Обоснование. Характеристика орофарингеальной микробиоты при хронической обструктивной болезни легких (ХОБЛ) и бронхиальной астме (БА) в зависимости от тяжести течения заболеваний является актуальной задачей, решение которой позволит уточнить роль микробиоты в их патогенезе. Цель исследования: сравнительный анализ состава орофарингеальной микробиоты при ХОБЛ и БА разной степени выраженности симптомов. Методы. В исследование включены 138 больных, из них 88 с ХОБЛ, 50 — с БА. Для каждого пациента был собран анамнез жизни, проведено физикальное исследование и получен мазок из орофарингеальной области. Определение таксономического состава проводилось секвенированием генов бактериальной 16S рРНК с последующим биоинформатическим и статистическим анализом. Результаты. При сравнительном анализе были найдены различия в представленности микроорганизмов. Для микробиоты больных ХОБЛ 1–2-й степени тяжести в сравнении с образцами ХОБЛ 3–4-й степени на фоне снижения представленностиPrevotella melaninogenica характерно более высокое содержание Brevibacterium aureum и представителей рода Scardovia, Coprococcus, Haemophilus, Moryella, Dialister и Paludibacter. Микробиота пациентов с тяжелой БА в сравнении с таковой при легкой персистирующей форме на фоне более низкого содержания бактерий рода Prevotella характеризуется более выраженным присутствием Bifidobacterium longum, Prevotella nanceiensis, Neisseria cinerea, Aggregatibacter segnis, а также представителей рода Odoribacter, Alloiococcus, Lactobacillus, Megasphaera, Parvimonas и Sneathia. При сравнении микробиоты больных БА и ХОБЛ для пациентов с БА отмечалась более высокая представленность P. melaninogenica и микроорганизмов рода Selenomonas, Granulicatella, Gemella, а также снижение Prevotella nigrescens, Haemophilus influenzae и Aggregatibacter, Alloiococcus, Catonella, Mycoplasma, Peptoniphilus, Sediminibacterium. При этом различия в составе орофарингеальной микробиоты у больных тяжелой неконтролируемой БА и ХОБЛ очень тяжелого течения не выявлены.Заключение. Отсутствие различий в бактериальной композиции орофарингеальной микробиоты у больных с тяжелыми формами ХОБЛ и БА позволяет высказать предположение о сходстве состояния бронхолегочной системы при тяжелых стадиях развития данных заболеваний

The airways microbial community composition in healthy individuals and bronchial asthma patients

This review summarizes the results of studies on the composition of microbial communities in the airways of healthy individuals and patients with asthma. Modern molecular genetic technology of the microbial identification, which are based on a sequence determination of encoding proteins genes conserved regions. These regions form the 16s-subunit ribosomal RNA in microorganisms of different species. These genes are detected by sequencing markers characteristic of individual microorganisms and their phylogenetic groups, and allow to perform a deep analysis of the microbiota in healthy volunteers and patients with chronic bronchoobstructive diseases. So, apparently healthy human bronchial tree is characterized by low bacterial contamination (most typical representatives here are the genera Pseudomonas, Streptococcus, Prevotella, Fusobacteria and Veilonella, much less potentially pathogenic Haemophilus and Neisseria are represented). In bronchial asthma patients the lower respiratory tract microbiota undergoes a qualitative transformation: as compared to healthy individuals the number of Proteobacteria increases and the number of Bacteroidetes decreases. Severe asthma in children is associated with significant respiratory tract Staphylococcus spp. insemination. Association between the asthma developing higher risk in young children and organisms such as Haemophilus, Moraxella and Neisseria spp. It is of considerable interest to determine the role of the microbiome in the development of human diseases of the bronchopulmonary system, and to understand the impact of the microbes communities as a course of disease and the important factor for the development of resistance to therapy

Microbiological oropharyngeal patterns in patients with different phenotypes of chronic obstructive pulmonary disease

Persistent bronchial inflammation in chronic obstructive pulmonary disease (COPD) is considered the cause of ventilation disorders and related contamination with conditionally pathogenic microorganisms; the latter can proceed and transform into a full infection, which can aggravate and exacerbate COPD. The aim of the study was to evaluate the relations between the oropharyngeal microbiota in patients with COPD and the clinical, functional, and prognostic parameters of the disease. Materials and Methods. 64 patients with COPD were included in the study; the participants were scheduled to visit our clinic on two occasions. In the first visit, their medical history was studied in detail and the major examination procedures were conducted. Those included an assessment of the respiratory function, the 6-minute walk test, the degree of dyspnea by the Medical Research Council scale, body plethysmography, the diffusion capacity of the lungs, and a chest CT scan. The second visit took place 12 months after the first one to assess the changes in the course of the disease. The result was considered negative if, in the second examination, the patient‘s condition was found more severe. Oropharyngeal samples of all patients were sequenced to identify the V3–V4 variable sites of the 16S rRNA gene. Results. It is found that the microbiological oropharyngeal patterns in COPD patients depend on the source of micro-aspiration. In addition, the changes in the oropharyngeal microbiota correlate with the severity and prognosis of the disease, as well as the patient phenotype. Based on the data obtained by sequencing parts of the 16S rRNA gene, the role of oropharyngeal microbiota in determining the course and prognosis of COPD has been elucidated. Conclusion. The presented clinical and functional characteristics associated with oropharyngeal microbiota indicate that microaspirations from other body compartments not only affect the composition of oropharyngeal microbiota in patients with COPD but also have an important prognostic significance. © 2018, Nizhny Novgorod State Medical Academy. All rights reserved

Microbiological oropharyngeal patterns in patients with different phenotypes of chronic obstructive pulmonary disease

Persistent bronchial inflammation in chronic obstructive pulmonary disease (COPD) is considered the cause of ventilation disorders and related contamination with conditionally pathogenic microorganisms; the latter can proceed and transform into a full infection, which can aggravate and exacerbate COPD. The aim of the study was to evaluate the relations between the oropharyngeal microbiota in patients with COPD and the clinical, functional, and prognostic parameters of the disease. Materials and Methods. 64 patients with COPD were included in the study; the participants were scheduled to visit our clinic on two occasions. In the first visit, their medical history was studied in detail and the major examination procedures were conducted. Those included an assessment of the respiratory function, the 6-minute walk test, the degree of dyspnea by the Medical Research Council scale, body plethysmography, the diffusion capacity of the lungs, and a chest CT scan. The second visit took place 12 months after the first one to assess the changes in the course of the disease. The result was considered negative if, in the second examination, the patient‘s condition was found more severe. Oropharyngeal samples of all patients were sequenced to identify the V3–V4 variable sites of the 16S rRNA gene. Results. It is found that the microbiological oropharyngeal patterns in COPD patients depend on the source of micro-aspiration. In addition, the changes in the oropharyngeal microbiota correlate with the severity and prognosis of the disease, as well as the patient phenotype. Based on the data obtained by sequencing parts of the 16S rRNA gene, the role of oropharyngeal microbiota in determining the course and prognosis of COPD has been elucidated. Conclusion. The presented clinical and functional characteristics associated with oropharyngeal microbiota indicate that microaspirations from other body compartments not only affect the composition of oropharyngeal microbiota in patients with COPD but also have an important prognostic significance. © 2018, Nizhny Novgorod State Medical Academy. All rights reserved

Practical recommendations for choosing an immunobiological preparation for the treatment of severe bronchial asthma of T2-endotype

© 2020 Medical Education. All rights reserved. Biological therapy of bronchial asthma (BA) is a modern method of treating severe forms of the disease, that are uncontrolled by traditional pharmacotherapeutic approaches. Currently, 5 monoclonal antibody (AT) preparations are registered in the world for the treatment of severe bronchial asthma (SBA) of the T2 endotype (T2-SBA) - antibodies, binding to immunoglobulin (Ig) E (anti-IgE - omalizumab), interleukin antagonists (IL)-5 (anti-IL-5 - mepolizumab, resizumab) and its receptor (anti-IL-5Rα - benralizumab), as well as antibodies, that selectively bind to the IL-4 and -13 receptor (anti-IL-4 /13Rα - dupilumab). The article presents data on the effectiveness of these drugs in relation to the key characteristics of SBA, formulates clinical and laboratory criteria, the study of which in real practice can potentially predict the likelihood of a clinical response to a particular type of biological therapy. An algorithm is proposed for choosing a targeted therapy strategy for patients with SBA, clinically associated with allergies, for patients with severe non-allergic eosinophilic BA and for patients with eosinophilic BA of a combined phenotype