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Asthma is a chronic, heterogeneous inflammatory disease with a high variability of the flow caused by the trigger influence of genetic and environmental factors. The heterogeneity of asthma indicates the involvement of many components in the mechanism of the inflammation of the respiratory tract. Currently, the microbiotic concept of the pathogenesis of respiratory system diseases is studied, based on the existence of a bilateral relationship between the microflora lungs and the intestines. The key mechanism of these relationships is free fatty acids performing signal and regulatory functions in the body. The medium-chain and long-chain free fatty acids are synthesized by de novo or enter the body as a result of consumption of fats, while the short-chain free fatty acids are formed in the intestine as a result of partial digestion of soluble fibre. The mechanism connecting the free fatty acids and inflammatory reactions includes activation of their receptors (Free Fatty Acid Receptor, FFAR) expressed on the cells of the gastrointestinal and respiratory tract, as well as on immune cells. If the role of the medium-chain and long-chain fatty acids receptors (FFAR1, FFAR4) and their ligands in the pathogenesis of asthma is actively studied, the value of the short-chain receptors (FFAR2, FFAR3) only begins to attract the attention of researchers in connection with the emergence of numerous data on the interconnection of the respiratory microbiome paths and intestines and its possible role in the induction of broncho-pulmonary complications. This review includes modern knowledge of the microbiotic concept of asthma, the basic information about the nomenclature, metabolism and transport of the free fatty acids, the value of the individual classes of the free fatty acids in the regulation of immune processes is normal and at bronchopulmonary pathology. The latest data of the FFAR receptors are systematized, features of their activation and expression, the intended role of FFAR2 and FFAR3 in the development and asthma therapy. It is discussed that gastrointestinal microbiota correction can reduce the activity of chronic inflammation of the respiratory tract at asthma.

Background — The development of systemic inflammation is a key pathogenetic mechanism in progression of chronic obstructive pulmonary disease (COPD). Fatty acids (FAs) and their oxidized derivatives serve as essential regulators of inflammation. The relationship between systemic inflammation and FA metabolism in COPD is poorly understood. In our research, we focused on examining the FA composition of the leukocyte membrane in COPD and the FA metabolism in association with systemic inflammation. Objective — We examined 137 patients with mild, moderate, or severe COPD. The control group comprised 32 healthy non-smokers. Methods — Blood cytokines and immune cell subpopulations were evaluated by flow cytometry. The FA composition of the leukocyte membranes was analyzed by gas chromatography. The concentrations of eicosanoids (thromboxane B2 (TXB2), leukotriene B4 (LTB4)) in plasma were measured by ELISA. Results — Our results implied systemic inflammation in all patients with COPD. The analysis of the FA composition of leukocyte membrane demonstrated increased level of saturated FAs and n-6 polyunsaturated fatty acids (PUFAs), along with reduced levels of monounsaturated FAs and n-3 PUFAs, in patients with COPD. The TXB2 and LTB4 content was increasing in COPD patients. We established a significant correlation with n-6 PUFAs, immune cells, and cytokines, which was indicative of an important role of FAs in the progress of systemic inflammation in COPD. Conclusion — Thus, FA modification of immune cells in patients with chronic pathologies of the bronchopulmonary system leads not only to disruption of the cell membrane structure, but also to the pathology of immune response regulation, and contributes to the development of the inflammatory process. The latter is a decisive factor in the pathogenesis of COPD.

In the last decade, significant research has been focused on Toll-like reseptors (TLRs) in the pathogenesis of respiratory diseases. The presented data show that TLR-mediated signaling can be directed both at the successful alleviation of the inflammatory reaction in the respiratory tract, and at its development and aggravation. Asthma is a chronic inflammatory disease of the respiratory tract caused by genetic factors, allergens, or microbial agents. TLRs play an important role in the pathogenesis of asthma. TLRs recognize a wide range of microbial molecules, endogenous molecules, and air allergens and modulate the allergic sensitization. An important feature of TLRs is their participation in the development of an immune response to viral and bacterial infections that cause severe exacerbations of asthma. TLRs are expressed on hematopoietic and non-hematopoietic airway cells, which play an immunomodulatory role in the development of asthma when activated by TLRs agonists. Due to the involvement of TLRs in innate and adaptive immunity and the ability to regulate adaptive Th-response, these receptors are currently being used as possible targets for drug development. Therefore, understanding the mechanisms and ways in which TLRs are involved in the pathogenesis of asthma may suggest new strategies for controlling the disease.

Coronary artery disease (CAD) is defined as myocardial damage developing as a result of its organic and functional changes, and leading to impaired blood flow through the coronary arteries. An important pathogenetic component of CAD is atherosclerosis. Currently, key aspects of the molecular relationship between inflammation and atherosclerosis are being actively studied, the immunometabolic theory of atherosclerosis is being discussed, along with an involvement of perivascular adipose tissue in the pathogenesis of this pathology, due to its ability to respond to atherogenic stimuli via developing inflammatory reactions. Evidence has been accumulated that in patients with CAD, both in their blood and perivascular adipose tissue, the level of neurotrophic factors (in particular, brain-derived neurotrophic factor, BDNF) changes, which may be a promising area of research from the standpoint of studying this factor as a therapeutic target for atherosclerosis in CAD. Neurotrophic growth factors control the functioning of both immune and nervous systems, and the balance of energy metabolism and innervation of adipose tissue. They affect vascular homeostasis, and are also involved in causing and stopping inflammation. Currently, there are data on the role of BDNF in the pathogenesis of cardiovascular, neurodegenerative and metabolic diseases, and on the effect of polyunsaturated fatty acids and eicosanoids on the level of BDNF and, accordingly, the development and progression of coronary artery atherosclerosis. Our review summarizes published data (2019-2021) on the pathophysiological and pathogenetic mechanisms of the relationship between BDNF and CAD (atherosclerosis).

Bronchial asthma (BA) and obesity are common diseases with a tendency towards a steady and progressive increase in the number of patients. A combination of these diseases is one of the major problems of modern medicine, requiring close attention due to a decrease in the quality of life, poor control over the course of the primary disease, and an increase in the frequency and duration of hospitalization. The association between asthma and obesity is obvious. However, detailed mechanisms underlying it require further investigation. In the last decade, in the formation of the phenotype of BA combined with obesity, much attention has been paid not only to the immune, but also to the neurogenic mechanisms of inflammatory response. It is known that the functioning of all parts of the nervous system can be controlled by neurotrophic growth factors due to their ability to influence many signalling mechanisms. Currently, there is evidence that neurotrophic factors are involved in the pathogenesis of bronchopulmonary and metabolic diseases. The review is devoted to detailed investigation of the mechanisms of neurogenic inflammation in obesity and asthma with participation of neurotrophic factors that may play a significant role in the formation of the BA phenotype associated with obesity. The study of new mechanisms involved in the pathogenesis of asthma and obesity will make it possible to find common therapeutic targets for this asthma phenotype.

The combined course of bronchial asthma (BA) and obesity is one of the urgent medical and social problems that requires a comprehensive and careful study in connection with a decrease in the quality of life of such patients, an increase in the frequency, duration of hospitalization and a high economic burden for the state as a whole. The relationship between BA and obesity is now confirmed by numerous studies, at the same time, despite the variability of the proposed mechanisms of pathogenetic effects of obesity on asthma, metabolic aspects of the relationship of these diseases need further study. Adipose tissue hormones are responsible for the energy homeostasis of the body therefore, excessive accumulation of adipose tissue is accompanied by the development of an imbalance in metabolic processes in various organs and tissues. Due to the emergence of new scientific data on the role and function of adipokines in the body, metabolic effects of adipokines are considered in the focus of their pathophysiological association with obesity and asthma. This literary review highlights the current understanding of the role of metabolic effects of the most studied adipokines (resistin, retinol-binding protein, leptin and adiponectin) in the development of obesity and BA. Gender and age-dependent features of adipokine levels in BA and obesity are described. Data on the confirmed role of adiponectin and leptin in the progression of BA combined with obesity are presented. It has been shown that the role of resistin and retinol-binding protein in the development of BA combined with obesity has not been studied. It is demonstrated that further study of metabolic activity of adipokines in BA is an actual and perspective direction of researches which will allow to develop new diagnostic and therapeutic strategies in patients with BA with obesity.Сочетанное течение бронхиальной астмы (БА) и ожирения представляет собой одну из актуальных медико-социальных проблем, требующих всестороннего и пристального изучения в связи со снижением качества жизни таких больных, повышением частоты, длительности госпитализации и высоким экономическим бременем для государства в целом. Взаимосвязь БА и ожирения в настоящее время подтверждена многочисленными исследованиями, в то же время, несмотря на вариабельность предложенных механизмов патогенетического действия ожирения на течение БА, метаболические аспекты взаимосвязи данных заболеваний нуждаются в дальнейшем изучении. Гормоны жировой ткани ответственны за энергетический гомеостаз организма, поэтому избыточное накопление жировой ткани сопровождается развитием дисбаланса метаболических процессов в различных органах и тканях. В связи с появлением новых научных данных о роли и функции жировой ткани в организме метаболические эффекты адипокинов рассматриваются в фокусе их патофизиологической ассоциации с ожирением и БА. В данном обзоре освещены современные представления о роли метаболических эффектов наиболее изученных адипокинов (резистин, ретинолсвязывающий белок, лептин и адипонектин) в развитии ожирения и БА. Описаны гендерные и возрастзависимые особенности уровней адипокинов при БА и ожирении. Представлены данные о подтвержденной роли адипонектина и лептина в прогрессировании БА, сочетанной с ожирением. Показано, что роль резистина и ретинолсвязывающего белка в развитии БА, сочетанной с ожирением, не изучена. Продемонстрировано, что дальнейшее изучение метаболической активности адипокинов при БА является актуальным и перспективным направлением исследований, позволит разработать новые диагностические и терапевтические стратегии у больных БА с ожирением.

Toll-like receptors (TLRs) are important players in innate and adaptive immune responses involved in the initiation of the inflammatory process in response to the stimulating influence of endogenous (аllarmine) and exogenous ligands (pathogens viruses, bacteria, fungi). It has now become apparent that not only viral and bacterial infections but non-infectious inflammatory diseases are accompanied by the activation of inflammatory response systems and the development of chronic inflammation associated with disorders in the regulation of the TLRs system. In this regard, the ligand-independent activation of TLRs, which occurs with the participation of lipids, is actively studied. Their signalling functions of TLRs implemented in unique microdomains does membrane lipid rafts that coordinate many cellular processes. The ability to activate TLRs has been found for saturated fatty acids (SFAs), both exogenous and endogenous. On the other hand, TLRs can be inhibited by omega-3 polyunsaturated fatty acids (PUFAs), which can block the inflammatory process. The activation of TLRs triggers a signal cascade that induces the production of reactive oxygen and nitrogen species. The development of oxidative stress is accompanied by the formation of oxidized forms of phospholipids (Ox-PLs), which also induce the development of chronic inflammation. At the same time, Ox-PLs is characterized not only by pro-inflammatory but also anti-inflammatory activity, which necessitates in-depth studies of their role in the implementation of these processes. This review article discusses the mechanisms by which SFAs, PUFAs, and Ox-PLs modulate TLRs activation in lipid rafts. Research into the details of these mechanisms will contribute to the development of a strategy to reduce the risk of chronic diseases caused by inflammatory reactions mediated by TLRs.

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.

Obesity is a complex and relevant global medical and social problem. The adipose tissue is not only a place of deposition of energy substrates but also a source of secretion of pro-inflammatory and anti-inflammatory mediators involved in the development of the chronic latent systemic inflammatory process in the organism with obesity. The metabolic signal in obesity contributes to the polarization of macrophages in the M1 direction and triggers the Th1 immune response, causing the development of adipose tissue inflammation. A chronic inflammatory condition plays a key role in the pathophysiology of obesity-induced insulin resistance. Toll-like receptors (TLRs) may be a possible pathophysiological link in the development of insulin resistance in inflammation. At the same time, inflammation-induced lipolysis is necessary for the release of energy resources during the development of the infectious process. Thus, low-grade inflammation is important to protect against adipocyte dysfunction. These results suggest that pro-inflammatory signaling is not exclusively pathogenic in obesity. In this regard, the study of inflammatory signaling pathways involved in the modulation of chronic inflammation of adipose tissue is particularly relevant. This review summarizes current views on the structure, function of TLRs and their involvement in the pathogenesis of chronic inflammation in obesity. The possibility of using TLRs as a therapeutic target in this pathology is discussed. Obviously, further study of inflammatory signaling pathways involving TLRs initiating the development of chronic inflammation of adipose tissue will allow the development of new and effective therapeutic strategies for obesity and its metabolic complications.

PURPOSE: To identify the formation of meteopathic reactions in patients with respiratory diseases under the influence of extreme weather changes in Vladivostok. METHODS: The short-term meteopathic reaction in patients with respiratory diseases to the impact of “Weather Complex”, consisting of nine weather parameters, on the day of patient’s examination and on 1 and 2 days before the examination, was assessed. 146 acclimatized residents of Vladivostok (29 patients with chronic bronchitis, 51 patients with controlled asthma, 39 patients with uncontrolled asthma and 27 healthy volunteers) were examined. Pulmonary function (PF) was studied by spirography and by body plethysmography. RESULTS: The adaptive-compensatory response of PF in patients with respiratory diseases to weather decreases depending on the disease severity, resulting in the development of meteodependence. The impact of “Weather Complex” on a human body is primarily reflected in PF, and the reaction of metabolic parameters is manifested with a 1–2 days time lag. Glutathione peroxidase and glutathione reductase, key factors in maintaining oxidative cell balance, play the most important role in the formation of a compensatory response to weather. In the light of the global health implication, recommendations are suggested to adjust the treatment of patients with respiratory pathology in specific conditions of abruptly changeable weather. CONCLUSIONS: The maritime monsoon climate creates an additional strain on both respiratory system and systems that ensure the peroxidation balance worsening bronchopulmonary pathology.

Overweight, obesity, type 2 diabetes mellitus, metabolic syndrome, cardiovascular diseases, and non-alcoholic fatty liver disease are common chronic ailments associated with lipid metabolism disorders. One of the mechanisms of these disorders is related to the deficiency and/or change in the balance of essential fatty acids (FAs). At the same time, the provision of ω3 and ω6 polyunsaturated fatty acids (PUFAs) depends, besides sufficient dietary intake, on efficiency of their endogenous biosynthesis by desaturation and elongation processes regulated by FA elongases and FA desaturases. Desaturases are encoded by PUFA desaturase genes (FADSs): FADS1 and FADS2. Alteration of FA desaturase activity and single nucleotide polymorphisms (SNPs) in the FADS1 and FADS2 gene cluster are associated with lipid metabolism dysfunction and may affect the pathogenesis of lipid-related diseases. People of different ages, from different ethnic backgrounds and countries may exhibit varying degrees of response to dietary supplements of ω3 and ω6 PUFAs. The study of the relationship between lipid metabolism disorders and genetic factors controlling FA metabolism is an important research area since the health effects of alimentary ω3 and ω6 PUFAs can depend on genetic variants of the FADS genes. This review summarizes the literature data on the association of FADS gene polymorphisms with lipid metabolism disorders and their role in the development of chronic non-communicable pathologies associated with changes in lipid metabolism.

Bronchial asthma (BA) and obesity are one of the major modern problem, requiring the development of an effective therapeutic strategy. The frequent combination of these diseases in one patient indicates the general pathophysiological mechanisms and future study for targeted drug exposure are needed. The endocannabinoid system is involved in a variety of physiological and pathological processes and can be considered as a general mechanism and a potential therapeutic target in asthma and obesity, the receptors of the system are expressed in many central and peripheral tissues. This signal system modulates the functions of the autonomic nervous system, immune system and microcirculation, plays an important role in the regulation of energy balance, metabolism of carbohydrates and lipids. The main research aimed at studying the functioning of this system was focused on neurology and psychiatry, while numerous scientific data demonstrate the importance of the participation of this system in the pathogenesis of other diseases. In particular, this system is involved in the mechanisms of obesity. The role of the endocannabinoid system in the pathogenesis of asthma is actively studied. The wide prevalence of the endocannabinoid signaling system and its regulatory role in the body opens up prospects for therapeutic effects in the treatment of asthma and obesity, as well as the possible phenotype of asthma, combined with obesity. The review is devoted to modern ideas about endocannabinoids, their receptors, mechanisms of action and their role in the pathophysiology of asthma and obesity. The therapeutic prospects and difficulties associated with the use of endocannabinoids and phytocannabinoids in medicine are discussed.

Asthma and obesity are serious medical and social world problems, and their combined course is characterized by a decrease in the quality of life, an increase in the frequency and duration of hospitalization. The present review summarizes the current views on the mechanisms of formation of asthma phenotype combined with obesity, role of leptin and adiponectin imbalance in the development of systemic inflammation in obesity in the pathophysiology of asthma, its interrelations with metabolic syndrome. We present data that shows that syndrome is closely related not only to the debut of asthma, but also to a decrease in its control. Along with obesity, the role of other components of metabolic syndrome, in particular insulin resistance, as a predictor of asthma development is considered. Insulin resistance may be the most likely factor in the relationship between asthma and obesity, independent of other components of the metabolic syndrome. Insulin resistance associated with obesity can lead to disruption of nitric oxide synthesis. We reveal common mechanism of metabolic disorders of nitric oxide and arginine in metabolic syndrome and asthma and show that insulin resistance treatment can be therapeutically useful in patients with asthma in combination with obesity.

Currently, in parallel with the increase in the prevalence of asthma, there is an increase in the number of obese patients. The results of numerous studies indicate that the asthma phenotype in combination with obesity has well-defined clinical features – a more severe course with frequent exacerbations and reduced control of the disease. The article considers the main pathogenetic mechanisms that determine the development of the asthma phenotype in combination with obesity. The influence of excess adipose tissue in the chest on respiratory mechanics, the correlation of gastroesophageal reflux disease and respiratory depression in sleep are described. It is shown that the phenotype of asthma with obesity is characterized by inflammation of adipose tissue, adipokine imbalance, insulin resistance, and disturbance of vitamin D metabolism. Gender peculiarities and genetic condition of asthma associated with obesity are considered. Understanding general mechanisms underlying the formation of asthma and obesity will undoubtedly contribute to the development of new therapeutic strategies.

The prevalence of bronchial asthma and obesity has grown in the recent decades worldwide. The urgency of this problem due to its medical and social significance for the society in connection with a reduction of patients ‘ quality of life and considerable economic damage to the health system. The relationship of these diseases, there are gender-related, age-related characteristics no doubt. Growing clinical-epidemiological evidence indicates that obesity might be an independent risk factor for bronchial asthma. On the other hand, the clinical data of bronchial asthma is a consequence of obesity remain indicative. The presence of concomitant obesity, bronchial asthma is considered as a state, significantly worsens its course. Etiology the causal relationship between obesity and asthma, despite the proposed mechanical, immunological, genetic and hormonal concepts still remains unclear. The underlying mechanism for this association is still unclear although several theories have been postulated in an attempt to describe it. Many studies demonstrate that bronchial asthma and obesity have some common mechanisms, including chronic systemic inflammation. In the review, we outline the current understanding of the role of systemic inflammation linked to obesity in the pathophysiology of bronchial asthma. An important role in the pathophysiology of systemic inflammation is given to changing levels of key adipose tissue hormones - leptin and adiponectin, respectively, having proinflammatory and anti-inflammatory activity. '/'his review article will focus on the leptin and adiponectin. Understanding the mechanisms of correlation between the metabolic activity of adipose tissue and the functional status of the respiratory tract with the development of systemic inflammation with comorbid asthma and obesity will review a number of existing provisions for the diagnosis and treatment of associated course of these diseases, to expand understanding the phenotypes of asthma and to develop new treatment strategies.

The dynamics of parameters of cytokine status in patients with allergic rhinitis in view of efficiency of allergen-specific immunotherapy (ASIT) was studied in this work. 62 subjects with moderate persistent rhinitis at the age of 18-40 years old were included in the study. For specific diagnosis and treatment there we used standard allergens. ASIT was performed by the classical scheme. The concentrations of IL-4, IL-5, IL-6, IL-8 in the blood serum were measured by the enzyme immunoassay. A good or excellent effect of treatment with ASIT was achieved in 62.9% of cases, and satisfactory one in 37.1% of cases. The analysis of the dynamics of IL-4, IL-5, IL-6, IL-8 concentrations showed that the efficiency of ASIT in patients with allergic rhinitis depends on the ability of the immune system to activation by low doses of the allergen, quite fast suppression of proinflammatory cytokines induced by them, and active functioning of the system of anti-inflammatory cytokines.

The study goal was to identify specificities of small airways dysfunction development (SAD) in patients with mild asthma. Material and Methods — The study involved 114 patients with mild asthma. Depending on the condition of their small airways, the patients were split among two groups: Group 1 of 94 patients with asthma without SAD (82.5%); Group 2 of 20 patients with asthma and SAD (17.5%). The control group consisted of 25 volunteers. SAD was diagnosed by the presence of air trapping and hyperinflation. Results — SAD was diagnosed in 17.5% of patients with mild asthma. The development of SAD was observed in 80% of asthma patients with ailment duration of over 5 years and family history of asthma. Obesity was diagnosed 1.7 times more often in patients with SAD compared with those without it. Food allergy, allergic rhinitis, allergic conjunctivitis, urticaria and bronchial obstruction were identified two or more times more often in patients with SAD compared with those without it. Among all patients with mild asthma and SAD, bronchial obstruction was detected in 55% of cases. Conclusion — The development of SAD in the presence of mild asthma is characteristic for patients with ailment duration over 5 years, family history of asthma, obesity, predominant sensitization to food allergens, and concomitant non-pulmonary allergic diseases. Bronchial obstruction is not the obligatory feature of SAD development in presence of mild asthma.

The inflammation is a key mechanism for the development of asthma. The initiation and the resolution of inflammation are mediated by n-3 and n-6 polyunsaturated fatty acids (PUFAs) and their metabolites. The violation of PUFA metabolism is accompanied by an imbalance in the regulatory mechanisms of the inflammatory process and contributes to its chronicity. The desaturase enzymes are of great importance in the chemical structure and functions of PUFAs. There are ∆5 desaturase (D5D or FADS1) and ∆6 desaturase (D6D or FADS2). It is known that the influence of desaturase enzymes on fatty acids is an essential factors in many diseases. The aim is to evaluate FADS1 and FADS2 activity in the blood in patients with mild and moderate asthma. Methods. This study included 19 patients with mild asthma, 21 patients with moderate asthma and 24 healthy people. PUFA levels were quantified by liquid chromatography-mass spectrometry. The enzyme activities were estimated as the product-to-substrate ratio: 20:4n-6/20:3n-6 for FADS1; 18:3n-6/18:2n-6 for FADS2. Results. A decrease in FADS1 and FADS2 activities in mild and moderate asthma patients has been shown. In mild asthma, FADS1 and FADS2 activities were 1.36 and 2 times lower, than in the control group. In moderate asthma, FADS1 and FADS2 activities were decreased in 1.8 and 4 times. Conclusion. Thus, asthma progression is accompanied by the decrease in the activity of FADS1 and FADS2. It may be a cause of the violation of PUFA metabolism and pro-resolving lipid mediator synthesis. One of the reasons of the reduction in desaturase activity may be FADS1 and FADS2 gene polymorphism. Further detailed research, including the gene studies, is needed.

Asthma is a chronic heterogeneous disease characterized by chronic inflammation and bronchial hyperreactivity. Neurogenic inflammation is one of the important causes of hyperreactivity. Dysfunction of transient receptor potential (TRP) ion channels underlies the development of neurogenic inflammation, bronchial hyperreactivity and respiratory symptoms of asthma such as bronchospasm and cough. TRP channels are expressed in the respiratory tract. Their activation is mediated by endogenous and exogenous factors involved in the pathogenesis of asthma. The study of functioning and regulation of TRP channels is relevant, as they could be important therapeutic targets for asthma. The aim of the review is to summarize modern ideas about the mechanisms of functioning and regulation of members of the TRP channel superfamily, the role of which in lung pathology and physiology are the best studied.

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

To assess the anti-inflammatory effect of millimeter therapy in the treatment of partially controlled asthma, the fatty acid composition of erythrocyte membranes and their oxygenase derivatives were studied. Eighty-five subjects aged 18 to 45 years old were examined, 60 of them were diagnosed with partially controlled asthma and 25 were a control group, which consisted of conditionally healthy subjects without bronchopulmonary pathology. Two study groups were formed. Patients of the 1st group (n=30) received only basic medical treatment: inhalation glucocorticosteroid and β2-agonists of short action on demand. Patients of the 2nd group (n=30) underwent complex treatment: basic medical treatment in combination with millimeter therapy according to the developed technique. Clinical symptoms (frequency of nocturnal and daily asthma attacks per week, severity of cough, need for short-acting bronchodilators during the day), results of the asthma symptom control questionnaire (ACQ-5 test), lung function, composition of fatty acid (FA) in erythrocyte membranes, level of eicosanoids were assessed. The dynamics of clinical-functional and laboratory indicators in patients was evaluated one month after the start of treatment. The study established a modification of FA erythrocyte membranes composition, characterized by an increase in the proportion of some representatives of saturated and monounsaturated FA, increased production of arachidonic acid and its cyclooxygenase and lipoxygenase metabolites (thromboxane B2, leukotriene B4) against the background of deficiency of eicosapentaenoic and docosapentaenoic acids. A significant decrease in the level of oxygenated derivatives of fatty acids in the blood plasma of patients was revealed against the background of positive dynamics of clinical course of the disease in the 2nd group receiving complex treatment, which indicates the normalization of metabolic transformations of oxygenated derivatives of fatty acids, and as a consequence the extinction of allergic inflammation under the influence of electromagnetic waves of the millimeter range of extremely high frequency.

Objective: to study the composition of fatty acids (FA) and mitochondrial membrane potential (MMР) of blood cells in patients with chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD); to establish the role of the Mitochondrial dysfunction in the formation of respiratory diseases. Material and methods. The study involved 26 patients with chronic bronchitis, 27 - with mild COPD, 21 - with moderate COPD steady flow, 29 healthy people. MMР leukocytes was assessed by flow cytometry. The composition of the FA mitochondrial membranes was studied by gas-liquid chromatography. Results and discussion. With the worsening of the disease (moderate COPD) increases the number of white blood cells with reduced MMP, appears deficit of the saturated, monoenic (14: 0, 16: 0, 18: 0) and n-3 polyunsaturated fatty acids (18: 3n-3 20: 5n-3, 22: 5n-3, 22: 6n-3) in the membrane of the mitochondria. Identified imbalance in the composition of fatty acids verifies the changes in the physicochemical properties of subcellular membrane malfunction membrane transport systems, enzymes and receptors, processes of oxidative phosphorylation. Conclusion: The imbalance in the composition of the LCD mitochondrial membranes lead to the development of mitochondrial dysfunction and the formation of cell hypoxia.

In the last decade, the attention of scientists in the field of biomedicine is focused on studying the relationship between the immunological and neurogenic components of the inflammatory response and their contribution to the pathophysiology of allergic inflammation in asthma. The review is devoted to detailing the mechanism of neurogenic inflammation involving regulatory neuropeptides (substance P, vasoactive intestinal peptide, calcitonin gene-related peptide) in the pathogenesis of bronchial hyperreactivity in asthma. The role of neurotrophic growth factors (nerve growth factor, brain-derived neurotrophic factor) in the regulation of remodeling of bronchi in asthma has been analyzed. The study of neuroimmune mechanisms in the pathophysiology of asthma will it possible to find new therapeutic targets in this research area.

Aim. To assess the functional status of the small Airways in patients with bronchial asthma associated with obesity, by body plethysmography. Materials and methods. 65 patients with bronchial asthma of mild severity, partially controlled course, including 30 patients with normal body weight and 35 patients with obesity of I degree were examined. Control group-30 healthy volunteers. Examined forced vital capacity (FVC), forced expiratory volume in first second (FEV1) ratio of FEV1 to FVC (FEV1/FVC), maximum volumetric exhalation rate after 25.50 and 75% FVC (MEF75, MEF50, MEF25), average flow velocity in the exhalation interval 25-75% of FVC (MMEF25-75). Method bodyplethysmography was evaluated in bronchial resistance, functional residual capacity (FRC), residual volume of the lungs (RV), total lung capacity (TLC), the percentage of RV/TLC. Results. Patients with bronchial asthma with obesity showed a reduction of indicators of bronchial obstruction: FEV1 of 14% (p=0.02), FEV1/FVC by 14% (p=0.001), MEF75 30% (p=0.001), MEF50 by 35% (p=0.001), MEF25 by 44% (p=0.003), MMEF25-75 by 38% (p=0.001). The increase of bronchial resistance on inhalation in 2 times (p=0.001), on exhalation in 3.3 times (p=0.003) was found, which is typical for generalized bronchial obstruction at the proximal level. An increase in RV by 24% (p=0.03), TLC - by 9% (p=0.03), RV/TLC - by 18% (p=0.03), indicating the presence of "air traps" and dysfunction of the small respiratory tract. Conclusion. In patients with asthma of mild severity associated with obesity, both the central bronchis and the distal lung are affected, which are manifested by generalized bronchial obstruction, the formation of "air traps" and dysfunction of the small respiratory tract.

A control group included seventeen conditionally healthy people (Group 1). Eighty-eight patients with proven bronchial asthma (BA) at the age of 22 to 48 were enrolled into the study. I.e., Group 2 included nine patients with well-controlled BA. Group 3 included persons with partially controlled BA (n=79). There were 8 people with easily treated BA in group 2, and 57 such cases in Group 3. The levels of interleukins (IL-4, IL-10, IL-17A), interferon-γ (IFNγ), and tumor-α necrosis factor (TNFα) were monitored by means of flow cytometry technique. The parameters of cellular immunity were registered by flow cytofluorimetry assays. Phagocytosis indicators were studied by means of D. Mayansky method, metabolic activity of neutrophils, by the B.Park method, as modified by E.Shmelev. Evaluation of cellular immunity did not reveal statistically significant differences for distinct CD subpopulations between healthy controls and BA patients. The patients with controlled and partially controlled BA exhibited some changes in cytokine concentrations, i.e., increased IL-4, IL-17А, IL-10 and TNFα levels; changes in phagocytosis and oxygen dependent bactericidal activities of neutrophils. We have revealed higher concentrations of IL-4, IL-17А in the less controlled BA (group 3) , as compared with group 2. TNFα induction remained at significantly higher level in both groups of BA patients, exceeding mean control values by 2.3 times. The degree of IL-10 production in group 2 with controlled BA was significantly higher than in group with partial disease control (group 3, p < 0.001), thus suggesting application of IL-10 levels as an index of active inflammation control. Patients with BA (groups 2, 3) exhibited a decrease of basal IFNγ, as compared to healthy people (p < 0.001). In group 3 (partial control), this parameter was 3-fold lower than in healthy persons. Evaluation of monocyte/phagocyte functions showed statistically significant differences between BA patients and healthy persons. Functional reserve of granulocyte activity and oxidative metabolism were decreased to a similar degree in the patients with well-controlled and partially resistant BA, thus showing their independence on the quality of disease control.

The aim of the research is to examine the relationship between the integral parameters of respiratory function, the values of LPO-AOD system and NO level at bronchopulmonary pathology in individuals living in different ecological areas of the city of Vladivostok. 206 patients living in different ecological conditions (healthy individuals, patients with respiratory disorders) were examined. Lung function and the state of LPO-AOD system were studied; the concentration of NO metabolites was assessed in blood serum. The nature and strength of the impact of environmental factors on respiratory function, the state of LPO-AOD, NO level were studied by the method based on correlation analysis. There was calculated power index (D) which was differentiated into power within the system (Ds) which in its turn reflects the in-system interrelationship tension (LPO-AOD, respiratory) and power between systems (Dm) characterizing the activity of interconnections and response to an external stimulus. Intra-system dependences typical for the unfavorable zone were viewed in relation to the favorable zone. It was found out that in ecologically unfavorable regions in individuals with different bronchopulmonary pathologies the value of Ds increases. This indicates that the pathogenic influence of environmental factors increases. In healthy people living in ecologically unfavourable area physiological adaptive-compensatory reaction of the body was revealed, which was proved by high power interconnections (Dm). In the patients with chronic bronchitis there was maintained an adequate level of functioning of the body systems studied. In patients with COPD living in an unfavourable zone there were found strong links between the indicators of the system of LPO-AOD and of NO, and in patients with bronchial asthma - supplementary relationship between lung function and NO. At the same time pathologic changes in the system of LPO-AOD and NO depend on the general pollution, metal and gas components contained in the air. Thus, the people with respiratory diseases being in environmentally unfavorable conditions have the most negative influence. The analysis of the activity of relationships proved that violations of interaction of LPO-AOD systems and NO in ecologically unfavorable regions may contribute to the occurrence and progression of bronchopulmonary diseases.

The aim is to establish interrelations between levels of cytokines and adipokines in blood serum of patients with asthma; to reveal the features of cytokine and adipokine regulation in asthma associated with obesity. Material and Methods ― We examined 71 patients with partially controlled mild asthma: 24 normal-weight patients (group 1), 24 overweight patients (group 2), 23 patients with grade I and II obesity (group 3). The control group consisted of 25 healthy volunteers. Blood serum levels of Tumour necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10, and IL-17A were studied by flow cytometry. The concentrations of leptin and adiponectin were measured by an enzyme immunoassay. Results ― Increase levels of TNF-α, IL-6, IL-17A and IL-4 have been found in asthma patients regardless of body weight. At the same time, IL-6 level in the groups 2 and 3 was 1.4 times higher than in group 1. IL-17A level in patients with asthma and obesity was 1.2 times higher than in the groups 1 and 2. The elevation of IL-10 level in 1.8 and 2.3 times in patients of groups 2 аnd 3 in comparison with the group 1, respectively, has been determined. Hyperleptinemia was detected in the groups 2 and 3. A positive correlation between the body mass index and the levels of leptin, IL-4, IL-6, IL-10, IFN-γ and an invert correlation between this index and adiponectin concentration has been established. The interrelations between the levels of leptin, pro- and anti-inflammatory cytokines, depending on the body weight, have been revealed. Conclusion ― The production of pro-inflammatory cytokines IL-6 and IL-17A, as well as anti-inflammatory cytokine IL-10 enhances in asthma patients as the body weight increases and the obesity develops. The features of cytokine and adipokine imbalance indicate the prevalence of neutrophilic inflammation in asthma with obesity and demonstrates pathogenetic link between obesity and asthma.

Asthma is a common allergic pathology of the respiratory tract that requires the study of mechanisms underlying it, due to severe forms of the disease, which are refractory to therapy. The review is devoted to the search for molecular targets of fatty acid ethanolamides in asthma, in particular palmitoylethanolamide (PEA), which has been successfully used in the treatment of chronic inflammatory and neurodegenerative diseases, in the pathogenesis of which the nervous and immune systems are involved. Recently, the potentially important role of neuro-immune interactions in the development of allergic reactions has been established. Many of the clinical symptoms accompanying allergic airway inflammation are the result of the activation of neurons in the airways, so the attention of researchers is currently focused on neuro-immune interactions, which can play an important role in asthma pathophysiology. A growing number of scientific works confirm that the key molecule in the implementation of these inter-systemic interactions is nerve growth factor (NGF). In addition to its classic role in nervous system physiology, NGF is considered as an important factor associated with the pathogenesis of allergic diseases, particularly asthma, by regulating of mast cell differentiation. In this regard, NGF can be one of the targets of PEA in asthma therapy. PEA has a biological effect on the nervous system, and affects the activation and the degranulation of mast cells.

to investigate the composition of plasma fatty acids (FA) and red blood cells and the level of eicosanoids in patients with metabolic syndrome (MS) and to assess whether metabolic disturbances may be corrected during a cycle use of an ω-3 polyunsaturated fatty acid (PUFA).Examinations were made in 46 patients, including Group 1 (a control group) of 15 persons without MS components; Group 2 of 31 patients with MS, Group 3 of 16 MS patients who had taken an ω-3 PUFA for 6 months, and Group 4 of 15 MS patients who had received the drug for 12 months. The composition of plasma FA and red blood cells was analyzed on a gas-liquid chromatograph. An enzyme immunoassay was used to measure the serum levels of tumor necrosis factor-α (TNF-α) and eicosanoids (thromboxane B2, 6-keto-prostaglandin F1α, leukotriene B4). A biologically active additive from the king crab (Paralithodes camtschatica) hepatopancreas was used as a source of ω-3 PUFA.Having a higher proportion of linoleic and α-linolenic acids in the plasma, the patients were found to have decreased levels of ω-3 and ω-6 PUFAs (linoleic and α-linolenic, arachidonic, and eicosapentaenoic acids) and a larger proportion of Mead acid and saturated FAs (myristic and stearic acids) in the red blood cells, suggesting that that cellular blood FA transfer was impaired and FAs were absorbed by cells. Their serum samples showed the high levels of leukotriene B4, 6-keto-prostaglandin F1α, and thromboxane A2. The long-term (6- and 12-month) use of ω-3 PUFA from the king crab hepatopancreas had a positive impact in modifying the lipid FA composition of red blood cells and in eliminating deficiencies of physiologically important ω-3 and ω-6 PUFAs in the blood cells.The findings suggest that FAs and their metabolites play an important role in the pathogenesis of MS and that dietary ω-3 PUFA should be incorporated into a package of preventive and therapeutic measures for MS.Цель исследования. Изучить состав жирных кислот (ЖК) плазмы, эритроцитов и уровень эйкозаноидов у пациентов с метаболическим синдромом (МС) и оценить возможность коррекции метаболических нарушений при курсовом применении препарата ω-3 полиненасыщенных жирных кислот (ПНЖК). Материалы и методы. Обследовали 46 человек, из них 1-ю группу (контрольная) составили 15 человек без компонентов МС, 2-ю группу - 31 человек с МС, в 3-ю группу вошли 16 человек с МС, получавшие препарат ω-3 ПНЖК в течение 6 мес, в 4-ю группу - 15 человек с МС, принимавшие ω-3 ПНЖК в течение 12 мес. Анализировали состав ЖК плазмы крови и эритроцитов на газожидкостном хроматографе. Методом иммуноферментного анализа определяли содержание α-фактора некроза опухоли (TNF-α), эйкозаноидов (тромбоксан В2, 6-кето-простагландин F1α, лейкотриен В4) в сыворотке крови. В качестве источника ω-3 ПНЖК использовали биологически активную добавку (БАД) из гепатопанкреаса камчатского краба. Результаты. У пациентов с МС на фоне повышения доли линолевой и α-линоленовой кислот в плазме крови выявлено снижение уровня ω-3 и ω-6 ПНЖК (линолевая, α-линоленовая, арахидоновая, эйкозапентаеновая), увеличение доли кислоты Мида и насыщенных ЖК (миристиновая, стеариновая) в эритроцитах крови, что указывает на нарушение переноса в крови и поглощение клетками ЖК. В сыворотке крови установлено высокое содержание лейкотриена В4, 6-кето-простагландина-F1α, тромбоксана А2. Пролонгированное применение препарата ω-3 ПНЖК из гепатопанкреаса камчатского краба (6 и 12 мес) положительно влияло на модификацию состава ЖК липидов эритроцитов, устраняло дефицит физиологически важных ω-3 и ω-6 ЖК в клетках крови. Заключение. Полученные результаты свидетельствуют о важной роли ЖК и их метаболитов в патогенезе МС и целесообразности включения алиментарных ω-3 ПНЖК в комплекс профилактических и терапевтических мероприятий при МС.

The aim is to study structural and functional condition of cell mitochondrial apparatus for evaluating the mitochondrial membrane potential (MMР) and the fatty acids (FA) composition of mitochondrial membranes of blood cells in patients with COPD; to establish the role of mitochondrial dysfunction in the mechanism of COPD. The study involved 27 patients with mild COPD, 21 with moderate COPD of a stable course, and 20 healthy people. MMР of leukocytes was assessed with cytofluorimetry. The composition of FA of mitochondrial membranes was studied with gas-liquid chromatography. As a result of the study it was found out that the worsening of the disease (moderate COPD) leads to the increase of the number of white blood cells with reduced MMP and appearance of deficit of the saturated monoenic and n-3 polyunsaturated fatty acids in the membrane of mitochondria. The revealed changes in the structural and functional state of mitochondria show a violation in energetic activity, membrane permeability and transport of substances, which is a sign of the formation of mitochondrial dysfunction and cell hypoxia development at respiratory diseases.

Background Environmental pollution, local climatic conditions and their association with the prevalence and exacerbation of asthma are topics of intense current medical investigation. Materials and methods Air pollution in the area of Vladivostock was estimated both by the index of emission volumes of "air gaseous components" (nitrogen oxide and nitrogen dioxide, formaldehyde, hydrogen sulfide, carbon monoxide) in urban atmosphere and by mass spectrometric analysis of precipitates in snow samples. A total of 172 local asthma patients (101 controlled-asthma patients–CAP and 71 non-controlled asthma patients – nCAP) were evaluated with the use of spirometry and body plethysmography. Airway obstruction reversibility was evaluated with the use of an inhaled bronchodilator. Using discriminant analysis the association of environmental parameters with clinical indices of asthma patients is explored and thresholds of impact are established. Results CAP presented high sensitivity to large-size suspended air particles and to several of the studied climatic parameters. Discriminant analysis showed high values of Wilks’ lambda index (α = 0.69–0.81), which implies limited influence of environmental factors on the respiratory parameters of CAP. nCAP were more sensitive and susceptible to the majority of the environmental factors studied, including air suspended toxic metals particles (Cr, Zn and Ni). Air suspended particles showed higher tendency for pathogenicity in nCAP population than in the CAP, with a wider range of particle sizes being involved. Dust fractions ranging from 0 to 1 μm and from 50 to 100 μm were additionally implicated compared to CAP group. Considerably lowest thresholds levels of impact are calculated for nCAP.

Asthma is one of the most important medical and social problems of our time due to the prevalence and the complexity of its treatment. Chronic inflammation that is characteristic of asthma is accompanied by bronchial obstruction, which involves various lipid mediators produced from n-6 and n-3 polyunsaturated fatty acids (PUFAs). The review is devoted to modern ideas about the PUFA metabolites—eicosanoids (leukotrienes, prostaglandins, thromboxanes) and specialized pro-resolving lipid mediators (SPMs) maresins, lipoxins, resolvins, protectins. The latest advances in clinical lipidomics for identifying and disclosing the mechanism of synthesis and the biological action of SPMs have been given. The current views on the peculiarities of the inflammatory reaction in asthma and the role of highly specialized metabolites of arachidonic, eicosapentaenoic and docosahexaenoic acids in this process have been described. The possibility of using SPMs as therapeutic agents aimed at controlling the resolution of inflammation in asthma is discussed.