Role of proteins MRP8 (S100A8) and MRP14 (S100A9) in the development of critical condition in patients with pneumonia with A/H1N1 influenza

Background. Today, the critical care medicine is actively developing, and rapid progress is closely related to the achievements of molecular biology, immunology, and pathological physiology. The study of the role of individual molecular structures in the realization of the reactions of innate and adaptive immunity, which underlie the pathogenesis of critical conditions, is an urgent scientific direction and is of interest.Aims. To assess the contribution of the protein complex MRP-8/14 to thedevelopment of systemic inflammation by determining its plasma  concentration in patients with pneumonia with influenza A/H1N1.Materials and methods. 85 patients with pneumonia associated with influenza A/H1N1 were examined. Of these, 30 patients with severe pneumonia, 55 with non-severe pneumonia. The plasma concentration of the S100A8/A9 protein complex (MRP-8/14) was determined by flow cytometry on an analyzer (Beckman Coulter, USA).Results. It was found that in patients with severe pneumonia with influenza A/H1N1, the concentration of MRP-8/14 increased in 1.9 times compared  with healthy. At the same time, in patients with severe pneumonia with influenza A/H1N1 with a fatal outcome, the concentration of MRP-8/14 increased in 2.1 times.Conclusion. An increase in the level of MRP-8/14 in patients with severe pneumonia associated with influenza A/H1N1, on the one hand, reflects the severity of the course of systemic inflammation, on the other hand, the molecules MRP-8 and MRP-14, acting as damage-associated molecular patterns (DAMPs) stimulate a pro-inflammatory response and contribute to the development of critical state. Thereby, the protein complex MRP-8/14 can be considered as a potential point of application of pharmacological action in the intensive care of critical conditions

Acute kidney injury in patients with pneumonia with A/H1N1 influenza

Background. A critical condition of any genesis may be accompanied by the development of multiple organ failure, one of the manifestations of which is acute renal injury. Often, the process is subclinical in nature and the «classical» approaches to diagnose renal damage by creatinine concentration, urea level and assessment of glomerular filtration rate may not fully reflect the degree of impaired renal function, while acute kidney injury is a well-known predictor of high hospital mortality among critically ill patients.Aims. The purpose of this study was to assess functional state of the kidneysby determining the serum concentration of the markers of kidney injury  NGAL and Cystatin C in patients with pneumonia associated with influenza A/H1N1.Materials and methods. 85 patients with pneumonia associated with influenza A/H1N1 were examined, 30 patients with severe pneumonia, 55 with non-severe pneumonia. The control group was formed by 15 healthy donors. The serum concentration of NGAL and Cystatin C molecules was determined by flow cytometry on a Beckman Coulter analyzer (USA), using a Human Immune Checkpoint Panel 1 multiplex assay kit (Biolegend, USA). The glomerular filtration rate was calculated using the CKD-EPI formula.Results. It was found that in patients with severe pneumonia with the influenza A/H1N1, the concentration of NGAL increased 3.8 times compared with the control group, the concentration of Cystatin C increased 1.4 times, the glomerular filtration rate did not change.Conclusion. Timely diagnosis of subclinical kidney injury makes it possible to  objectify the severity of the condition, make adjustments to therapy, which can help to an increase in the survival rate of critically ill patients

Активность системы негативной регуляции Т-клеточного ответа PD-1/PD-L1/PD-L2 у больных пневмониями на фоне гриппа A/H1N1

Systemic inflammation is an integral pathophysiological component of many critical illnesses. The systemic inflammatory response is based on a cascade of interactions leading to hypercytokinemia and, as a consequence, multiple organ failure, which is one of the main causes of mortality in intensive care units.Aim of the study. To evaluate the activity of the negative regulation system of T-cell response by determining the plasma levels of PD-1, PD-L1 and PD-L2 molecules in pneumonia patients with influenza A (H1N1).Materials and methods. 85 patients with pneumonia and underlying influenza A (H1N1) were examined. Among them there were 30 patients with severe pneumonia, and 55 patients with non-severe pneumonia. Plasma levels of PD-1, PD-L1, PD-L2 molecules was determined by flow cytofluorometry method.Results. In patients with severe pneumonia and underlying influenza A (H1N1), the plasma level of PD-1 receptor increased 4.6-fold, while the concentration of its ligands PD-L1 and PD-L2 increased 10.6 and 2.2-fold, respectively.Conclusion. Significant increase in levels of PD-1 and its ligands PD-L1 and PD-L2 in patients with pneumonia and underlying influenza A (H1N1) indicates the involvement of negative regulation system of T-cell response in the cascade of immunological reactions and is associated with the severe disease. Possible correction of immune reactions realized through PD-1/PD-L1/PD-L2 complex in critically ill patients is a promising research avenue.Системное воспаление является неотъемлемой патофизиологической составляющей многих критических состояний. В основе системного воспалительного ответа лежит каскад взаимодействий, приводящий к гиперцитокинемии, и, как следствие, к полиорганной недостаточности, которая является одной из основных причин летальности в отделениях интенсивной терапии.Цель работы. Оценить активность системы негативной регуляции Т-клеточного ответа, определив плазменную концентрацию молекул PD-1, PD-L1 и PD-L2 у больных пневмониями на фоне гриппа A/H1N1.Материалы и методы. Обследовали 85 больных пневмонией на фоне гриппа A/H1N1. Из них 30 пациентов с тяжелой пневмонией, 55 — с нетяжелой пневмонией. Методом проточной цитофлуометрии определяли плазменную концентрацию молекул PD-1, PD-L1, PD-L2.Результаты. Установили, что у больных тяжелой пневмонией на фоне гриппа A/H1N1 плазменная концентрация рецептора PD-1 повышалась в 4,6 раза, при этом концентрация его лигандов PD-L1 и PD-L2 увеличивалась в 10,6 и в 2,2 раза, соответственно.Заключение. Статистически значимое увеличение концентрации PD-1 и его лигандов PD-L1 и PD-L2 у больных пневмонией на фоне гриппа A/H1N1 свидетельствует о вовлечении в каскад иммунологических реакций системы негативной регуляции Т-клеточного ответа и ассоциировано с тяжестью состояния. Возможная коррекция иммунных реакций, реализуемых через комплекс PD-1/PD-L1/PD-L2 у пациентов в критическом состоянии — это перспективное научное направление

Изменение состояния гемодинамики на фоне курса сурфактант-терапии у пациентов с гормонально-зависимой бронхиальной астмой

Non-specific hyperresponsiveness of the respiratory tract mucosa makes one of the important pathophysiological mechanisms for asthma development; it is characterized by the increased active response of the efferent system to stimuli. When this occurs, it damages the alveoli surfactant which ensures the viability of local immunity of lung tissue. Chronic respiratory failure induces changes in the cardiovascular system. The course of inhalations with a native surfactant reduces the dependence on inhalation corticosteroid.The objective of the study: to assess the effect of the course of inhalations with surfactant on the cardiovascular system in patients with hormone-dependent asthma. Materials and methods: 15 patients with asthma underwent a 70-day course of inhalation with natural surfactant based on a certain regimen (25 mg per inhalation, 21 inhalations in total) in addition to the basic therapy (inhaled corticosteroids and bronchodilators). On the 1st and 70th days of the surfactant therapy course, oscillometry was performed in order to assess macrohemodynamic parameters.Results. After the course of treatment, pulse pressure was found to increase by 26% compared to the initial level (p <0.05), the cardiac index increased by 16% (p <0.05) and the linear blood flow rate went up by 20% (p <0.05). At the same time, the pulse wave velocity decreased by 15% (p <0.05), while specific vascular resistance went down by 24% (p <0.01). This suggests that clinical remission during surfactant therapy in asthma patients is accompanied by changes in the functional state of the cardiovascular system.Одним из важных патофизиологических механизмов развития бронхиальной астмы является наличие «неспецифической» гиперреактивности слизистой оболочки дыхательных путей, которая характеризуется повышенным активным ответом эфферентной системы на действие раздражителей. При этом происходит повреждение сурфактанта альвеол, обеспечивающего состоятельность локального иммунитета ткани легкого. Хроническая дыхательная недостаточность индуцирует изменения состояния сердечно-сосудистой системы. Использование курса ингаляций препарата нативного сурфактанта уменьшает зависимость от приема ингаляционного кортикостероида.Цель исследования: оценить влияние курса ингаляций препарата сурфактанта на состояние сердечно-сосудистой системы у больных гормонально-зависимой бронхиальной астмой.Материалы и методы: 15 пациентов с бронхиальной астмой проходили 70-дневный курс ингаляций природного сурфактанта по схеме (доза 25 мг на ингаляцию, всего 21 ингаляция) дополнительно к базисной терапии (ингаляционные кортикостероиды и бронходилататоры). На 1-й и 70-й день курса сурфактант-терапии с помощью метода осциллометрии оценивали макрогемодинамические параметры.Результаты. После курса лечения обнаружено увеличение пульсового давления на 26% по сравнению с исходным уровнем (p < 0,05), сердечного индекса на 16% (p < 0,05) и возрастание линейной скорости кровотока на 20% (p < 0,05). Одновременно зарегистрировано снижение скорости пульсовой волны на 15% (p < 0,05), а также удельного сосудистого сопротивления на 24% (p < 0,01). Это свидетельствует о том, что клиническая ремиссия на фоне сурфактант-терапии у пациентов с бронхиальной астмой сопровождается изменениями функционального состояния сердечно-сосудистой системы

ОСОБЕННОСТИ РЕСПИРАТОРНОЙ ПОДДЕРЖКИ ПРИ ТЯЖЕЛЫХ ФОРМАХ ГРИППА A/H1N1/09 В 2019 Г.

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Сурфактант-терапия в комплексном лечении больных бронхиальной астмой. Влияние на клинические симптомы и показатели функции внешнего дыхания

The objective of the study: to study the impact of inhalation with natural pulmonary surfactant on clinical signs and changes in external respiration rate in the patients with partially controlled and uncontrolled persisting asthma, and to assess the chances to reduce dependence of the patients on inhalation glucocorticosteroid (iGCS).Subjects and methods. 29 patients with partially controlled and uncontrolled persisting asthma were followed up Persisting asthma was diagnosed as per GINA, 2016. The duration of asthma in the patients varied from 1 to 24 years. All patients received iGCS and long-acting bronchodilators or combination drugs containing them. By the enrollment into the study, patients had been receiving this therapy for at least 6 months. According to the study protocol, after examination patients started to receive inhalation with natural pulmonary surfactant and continued the above therapy. Totally, each patient received 21 inhalations (25 mg per inhalation) in accordance with the schedule during 70 days; after the first inhalation with a surfactant, the patients were followed up for 340 days. No adverse events caused by surfactant and other drugs have been registered during this study.The patients came to see the doctor and to be examined 9 times: on day 1, 8, 15, 29, 41, 70, 160, 250 and 340 of the follow-up. During each visit, the clinical state and external respiration were assessed: FVC, FEV1, FEV1/FVC, and PEF.Results. The positive impact of surfactant therapy was found out: reduction of the frequency of asthma attacks, cessation or reduction of bronchial spasm frequency under moderate physical load. Two-fold and more reduction of iGCS dose was achieved in 19 out of 29 patients (65.5%; 95%CI 47.4-80.1%), and 3 out of 29 (10.3%; 95% CI 3.6-26.4%) patients fully stopped taking iGCS. The subjective data on the state of patients and objective data on the changes in external respiration function showed a confident improvement of the bronchial functions while taking surfactant therapy (day 1-70 of follow-up), and after it (day 71-340 of follow-up).Цель исследования: изучение влияния ингаляций препарата природного легочного сурфактанта на клинические проявления и динамику параметров функции внешнего дыхания у больных с частично контролируемой и неконтролируемой персистирующей бронхиальной астмой (БА), а также оценка возможности уменьшения зависимости пациентов от приема ингаляционных глюкокортикостероидов (иГКС).Материалы и методы. Под наблюдением находились 29 больных с частично контролируемой и неконтролируемой персистирующей БА. Диагноз персистирующей БА устанавливался согласно руководству GINA версии 2016 Продолжительность БА у пациентов колебалась от 1 года до 24 лет. Все пациенты получали иГКС и бронходилататоры продленного действия или комбинированные препараты, их содержащие. К моменту включения в данное исследование пациенты получали эту терапию не менее 6 мес. Согласно протоколу исследования, на фоне этой терапии пациенты после обследования начали прием ингаляций природного препарата легочного сурфактанта. Всего каждый пациент получил 21 ингаляцию (25 мг на ингаляцию) по графику в течение 70 дней, наблюдение за состоянием пациентов осуществляли в течение 340 дней после приема первой ингаляции сурфактанта. Нежелательных явлений на прием сурфактанта и других препаратов в этом исследовании не зафиксировано.Осмотр и обследование пациентов проводили в рамках девяти визитов к врачу: в 1, 8, 15, 29, 41, 70, 160, 250 и 340-й день наблюдения. Во время каждого визита оценивали клиническое состояние пациента и функцию внешнего дыхания: ФЖЕЛ (FVC), ОФВ1 (FEV1), ОФВ1/ФЖЕЛ (FEV1/FVC), а также ПОС выд. (PEF).Результаты. Установлено позитивное влияние сурфактант-терапии: снижение частоты приступов удушья, прекращение или уменьшение частоты бронхоспазма при умеренной физической нагрузке. Двукратное и более снижение дозы иГКС удалось провести у 19 из 29 больных (65,5%; 95%-ный ДИ 47,4-80,1%), при этом из них у 3/29 (10,3%; 95%-ный ДИ 3,6-26,4%) пациентов удалось полностью отказаться от приема иГКС. Субъективные данные состояния пациентов и объективные данные изменения параметров функции внешнего дыхания показали достоверное улучшение функционального состояния бронхов как на фоне сурфактант-терапии (1-70-й день наблюдения), так и после ее завершения (с 71-го по 340-й день наблюдения)

Changes in hemodynamics during the course of surfactant therapy in patients with hormone-dependent asthma

Non-specific hyperresponsiveness of the respiratory tract mucosa makes one of the important pathophysiological mechanisms for asthma development; it is characterized by the increased active response of the efferent system to stimuli. When this occurs, it damages the alveoli surfactant which ensures the viability of local immunity of lung tissue. Chronic respiratory failure induces changes in the cardiovascular system. The course of inhalations with a native surfactant reduces the dependence on inhalation corticosteroid.The objective of the study: to assess the effect of the course of inhalations with surfactant on the cardiovascular system in patients with hormone-dependent asthma. Materials and methods: 15 patients with asthma underwent a 70-day course of inhalation with natural surfactant based on a certain regimen (25 mg per inhalation, 21 inhalations in total) in addition to the basic therapy (inhaled corticosteroids and bronchodilators). On the 1st and 70th days of the surfactant therapy course, oscillometry was performed in order to assess macrohemodynamic parameters.Results. After the course of treatment, pulse pressure was found to increase by 26% compared to the initial level (p <0.05), the cardiac index increased by 16% (p <0.05) and the linear blood flow rate went up by 20% (p <0.05). At the same time, the pulse wave velocity decreased by 15% (p <0.05), while specific vascular resistance went down by 24% (p <0.01). This suggests that clinical remission during surfactant therapy in asthma patients is accompanied by changes in the functional state of the cardiovascular system

Surfactant therapy as a part of comprehensive treatment of asthma patients. Impact on clinical signs and external respiration rates

The objective of the study: to study the impact of inhalation with natural pulmonary surfactant on clinical signs and changes in external respiration rate in the patients with partially controlled and uncontrolled persisting asthma, and to assess the chances to reduce dependence of the patients on inhalation glucocorticosteroid (iGCS).Subjects and methods. 29 patients with partially controlled and uncontrolled persisting asthma were followed up Persisting asthma was diagnosed as per GINA, 2016. The duration of asthma in the patients varied from 1 to 24 years. All patients received iGCS and long-acting bronchodilators or combination drugs containing them. By the enrollment into the study, patients had been receiving this therapy for at least 6 months. According to the study protocol, after examination patients started to receive inhalation with natural pulmonary surfactant and continued the above therapy. Totally, each patient received 21 inhalations (25 mg per inhalation) in accordance with the schedule during 70 days; after the first inhalation with a surfactant, the patients were followed up for 340 days. No adverse events caused by surfactant and other drugs have been registered during this study.The patients came to see the doctor and to be examined 9 times: on day 1, 8, 15, 29, 41, 70, 160, 250 and 340 of the follow-up. During each visit, the clinical state and external respiration were assessed: FVC, FEV1, FEV1/FVC, and PEF.Results. The positive impact of surfactant therapy was found out: reduction of the frequency of asthma attacks, cessation or reduction of bronchial spasm frequency under moderate physical load. Two-fold and more reduction of iGCS dose was achieved in 19 out of 29 patients (65.5%; 95%CI 47.4-80.1%), and 3 out of 29 (10.3%; 95% CI 3.6-26.4%) patients fully stopped taking iGCS. The subjective data on the state of patients and objective data on the changes in external respiration function showed a confident improvement of the bronchial functions while taking surfactant therapy (day 1-70 of follow-up), and after it (day 71-340 of follow-up)