The aim of the present study was to investigate the influence of TRPM8 single-nucleotide polymorphisms (SNP) on cold airway hyperresponsiveness in patients with chronic obstructive lung diseases. 140 patients with persistent bronchial asthma and chronic obstructive pulmonary disease were examined. All of them were genotyped for c.750G>C, c.1256G>A, c.3048C>T, c.3174C>G SNPs and underwent spirometry testing before and after 3-minute isocapnic cold air hyperventilation. We found that GC genotype and C allele carriers for SNP c.750G>C prevailed among subjects who reacted positively on the cold air bronchoprovocation. Affected heterozygotes had substantial fall of FEV₁ after the cold challenge while response in GG homozygotes was less prominent. There were no statistically significant associations with cold hyperresponsiveness status for the rest of studied SNPs. However, CC homozygotes for SNPs c.3048C>T and c.3174C>G appeared also to be predisposed to bronchoconstriction in response to cold air hyperventilation. Thus, the discovered associations prove the contribution of TRPM8 thermoreceptors into the development of airway response to low temperatures.

The analysis of exhaled breath temperature is one of non-invasive methods of the estimation of inflammatory process activity in patients with bronchial asthma. To develop quantitative criteria of diagnostically important changes of exhaled breath temperature, daily and two-week variability of this parameter was determined. The exhaled breath temperature was measuredby «X-halo» (Delmedica) in 39 patients with bronchial asthma during three visits: initially, the next day and in two weeks after treatment. During dynamic observation patients with bronchial asthma with cold airway hyperresponsiveness had a high day-to-day variability of the exhaled breath temperature, which diminishes the possibility of its use for the estimation of disease severity control in such patients.

To estimate the interrelationship between life quality and compliance of patients with bronchial asthma, 113 patients divided in two groups depending on the compliance level were examined. The patient compliance was defined with the help of the questionnaire specially developed for that purpose. The state of emotions was estimated by Hospital Anxiety and Depression Scale. Life quality was evaluated by SF-36 and AQLQ questionnaires. It was found out that asthmatics with low compliance have a significantly lower level of general and specific life quality associated with the disturbance of distal bronchi patency and intensive cold airway hyperresponsiveness. A high frequency of occurrence and a high degree of anxiety and depression intensity are one of the factors of low patient compliance. The developed discriminant model allows to identify the patients with low compliance with a high degree of accuracy on the basis of cold bronchoconstriction intensity, the level of mental health according to the questionnaire SF-36 and estimation of the environmental influence on the specific life quality by the questionnaire AQLQ.

The features of vascular stiffness and glomerular filtration rate (GFR) depending on the severity degree and the control level of the diseases were studied in 48 patients with bronchial asthma (BA). The state of the vascular stiffness was studied with the method of sphygmomanometry and sphygmography (Pulse Wave Velocity (PWV) was found), Ankle-Brachial Index (ABI) and GFR were identified with the help of Cockroft-Gault formula. According to the severity of the disease the first group included 8 patients with mild persistent BA, the second group had 23 patients with the moderate BA and 17 patients with severe BA were in the third group. According to the level of control the patients were divided into the group with partly controlled BA (8 patients) and uncontrolled BA (40 patients). It was found out that PVW in the first group didn't differ from the values that were in the group of healthy volunteers (7.4±0.6 and 6.1±03 m/s, respectively), but in the second and the third groups it increased reliably till 10.9±1.7 m/s (р<0.01) and 12.7±3.3 m/s (р<0.05), respectively. At controlled and uncontrolled BA the values of PVW grew till 9.3±2.5 m/s (p<0.05) and 11.3±1.6 m/s (р<0.01), respectively. This fact may point to the increase of cardiovascular risk at BA. The parameters of ABI did not have statistically significant differences with the control group. The values of GFR dropped in all the groups, most significantly at severe BA (64.24±1.98 ml/min, р<0.05) and uncontrolled BA (76.43±3.37 ml/min, р<0.001). The direct dependence of GFR decrease on the length of the disease was revealed. So, at severe uncontrolled long course of BA there is a significant drop of GFR, which is the result of attrition of kidneys compensatory possibilities about the maintenance of effective filtration pressure in consequence of persistent disturbances of renal blood flow. The worsening of glomerular filtration conditions in the future may lead to a significant disturbance of kidney's function and poor prognosis in patients with severe BA.

The article shows the results of prospective research of clinical and functional course of chronic obstructive pulmonary disease combined with ischemic heart disease in 39 patients. The standard therapy of 21 patients was supplemented with Crestor^® (rosuvastatin calcium), the inhibitor of HMG-CoA-reductase of the fourth generation and the therapy of 17 patients did not include Сrestor^®. The observations were made throughout the year. It was found out that the combination of crestor with the standard therapy of chronic obstructive pulmonary disease and ischemic heart disease contributes to the control over the symptoms of the combined pathology (it decreases the intensity of short breath, sputum production, the frequency and intensity of the cough, the frequency of angina attacks) and 1.9 times reduces the frequency of exacerbations and the severity of comorbid pathology. Long application of Crestor^® combined with the standard therapy leads to the increase of FEV₁ by 7.04±1.86%, FEV₁/FVC by 7.16±1.62% and to the decrease of arterial stiffness and the activity of laboratory parameters of the systemic inflammation. The research proves the significant anti-inflammatory effect of Crestor^® and the feasibility of its application while treating chronic obstructive pulmonary disease.

The possibilities of prognostication of frequent exacerbation of chronic obstructive pulmonary disease (COPD) combined with the ischemic heart disease (IHD) by the estimation of parameters of system inflammation in blood plasma (С-reactive protein, TNF-α, IL-6, IL-8, leukocytes, fibrinogen) and anti-inflammatory IL-4 were studied. Complex clinical and laboratory examination of 88 COPD patients with IHD was done. 36 patients during 12 months were found to have an acute form of COPD for no more than 2 times (the first group), and 52 patients had it for more than two times (the second group). It was found out that in the patients of the second group the concentration of biomarkers of system inflammation was significantly higher than in the patients of the first group. Statistically important differences were revealed in the content of C-reactive protein (3.78±0.14 and 3.21±0.11 g/l, respectively, р<0.05), TNF-α (7.64±0.32 and 4.92±0.22 pg/l, respectively, р<0,001), IL-8 (19.73±1.19 and 15.90±1.21 pg/l, respectively, р<0.05). At the same time the level of IL-4 in the second group was lower than in the first group (6.12±0.10 and 8.23±0.65 pg/l, respectively, р<0.01). On the basis of the revealed regularities the method of prognostication of frequent COPD exacerbation combined with IHD was offered with the help of integral estimation of the mentioned parameters by doing the discriminant equation. This mathematical model of prognostication is a simple and accessible method which allows to make a decision about individual treatment and prophylaxis in such-like patients.

The examination of 1933 men aged 18 to 60 was done for the purpose of studying respiratory symptoms prevalence among railway transportation workers. The main group consisted of 1038 people working in hazardous conditions for more than a year, and the group of comparison involved 895 people without occupational hazards in the form of dust pollutants. The respondents were interviewed by the main questionnaire «Burden of major Respiratory Diseases WHO Survey»; the intensity of smoking was identified by the index of packs/years; the study of lung function (LF) was carried out with the spirometry. It was found out that among the men who were exposed to industrial aerosols there was a big number of people with respiratory complaints: 21.5% was among the respondents working in hazardous conditions, and 14.5% was from the group of comparison. The men who work in the dust pollution smoke more than the men without professional risk factors. The frequency of respiratory symptoms increases proportionally the intensity of smoking. The absence of respiratory complaints does not exclude the presence of pathological changes in the spirogram in the study of LF. Approximately identical frequency of LF pathological changes can be observed both among men working in harmful conditions and men who do not have professional risk factors. Smoking has a more significant impact on the development of chronic bronchopulmonary diseases in workers of railway transportation than the inhalation of industrial aerosols. Chronic obstructive pulmonary disease among railway transportation workers is more often diagnosed in men exposed to occupational hazards such as welding fumes than in men working in other occupational hazards.

The character of lung function (LF) changes - lung vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume at the first second (FEV₁) were studied in inhabitants of Yamal-Nenets autonomous region in its different climatic and geographic zones. Cross screening examination of 1090 non-smoking inhabitants of the region was done. All the inhabitants in the settlements were compared by sex, age, ethnicity and occupation. The inhabitants were interviewed with questionnaires «GOLD 2006»; spirometry, electrocardiography and pulmonologist examination were also done. Severe somatic pathology in all the examined patients was excluded. It was found out that mean values (M±SD) of VC in the inhabitants were within the limits of 100.6±13.4% from predicted values, and in the newly arrived they were 96.0±12.6% (p<0.001). Those people who worked in cold conditions in comparison with the participants of the study whose work was not connected with the influence of cold on the body had statically reliable decrease of VC values (93.5±15.7 and 100.3±16.2%, respectively, p<0.01), of FVC values (90.0±16.3 and 95.6±15.3%, respectively, p<0.01) and of FEV₁ values (86.3±16.6 and 92.2±14.5%, respectively, p<0.01). The study of LF in inhabitants of the settlements of different climatic and geographic zones of Yamal-Nenets autonomous region showed that at the increase of intensity of climatic factors effect mean values of FEV₁ reliably dropped in the direction of the study from the South to the North (from 98.0±16.0 till 94.0±15.0%, p<0.05), at the same time the values of VC increased from 94.0±12.0 till 100.0±15.0% (p<0.05). The results of the research can be used for the development of the prognostic model of airways adaptation to extreme conditions.

The aim of the research is to study the peculiarities of changes of central hemodynamics and respiratory function in patients at neuroaxial anesthesia. 122 patients who were subjected to elective surgical, urologic and gynecologic operative interventions were studied upon the parameters of central hemodynamics and gas composition of arterial blood at neuroaxial anesthesia as monoanesthesia with the possibility of separate breathing. The dependence between the disturbance of central hemodynamics and respiratory dysfunction development was found out. The changes of central hemodynamics are prognostically unfavorable for the development of arterial hypoxemia and acute respiratory failure. They include the decrease of heart index, heart beating index, the fraction of heart left ventricle output, the index of heart left ventricle capacity, and the increase of general peripheral vascular resistance. Central hemodynamics controlled with the method of echocardiography at inotropic and vasopressor support allows to retain the gas composition of the arterial blood at neuroaxial anesthesia within physiological limits.

The aim of the research is to find out a three-dimensional spatial organization of ciliated epithelium of intact rats trachea. It is demonstrated that solid electronic microscopy or scanning electronic microscopy with the application of focused ion beam is a perspective method of biological objects study. Layer-by-layer etching of transverse section of fixed and contrasted preparation of biological tissue by the focused ion beam with the further visualization of the structure with the detector of back-reflected electrons in the double-beam system FIB/SEM allows to restore a three-dimensional structure of the object out of a big range of electronically microscopic images of successive transverse sections. Obtained structural information allows to visualize a complex microanatomy of tissues at the subcellular level. As a result of these 3D-reconstructions the information about the topology of compartments of ciliated epithelial cells of rats trachea mucosa and spacious geometry of ultrastructures was obtained, intracellular structures were visualized, and a thin texture of submicroscopic details of trachea epithelium surface (cilia and microvilli) was reconstructed.

The mechanism of direct influence of bioflavonoids on the tissue homeostasis of respiratory apparatus at organism hypothermia has not been studied enough. Complex histochemical characteristic of the vein channel of lungs respiratory part of experimental rats which during three months were subjected to hypothermia in climate camera at 15ºС one hour a day was done. At the same time bioflavonoid dihydroquercetin in a dose of 50 mg/kg of the body mass was given to the part of animals as a food additive. It was found out that constant influence of cold temperatures on the body of experimental animals leads to local pulmonary hemosiderosis, which proves the development of respiratory apparatus tissue dystrophy. There is also the deposition of argyrophilic substance typical for ascorbic acid in the cytoplasm of cells that are near the outer membrane of veins of the respiratory part of experimental animals' lungs. The granular coloring of erythrocytes by Alizarin red S is identified in the veins of lungs respiratory part of experimental rats which had dihydroquercetin in their meals.

The results of the study of clinical and epidemiologic features of сhlamydia infection in children with bronchopulmonary diseases are given in the article. From 2008 till 2010 two groups of children were examined: the first group consisted of 155 children of the first year of their life, the second group had 1048 children from 1 to 14 years old. With the method of polymerase chain reaction the detection of Chlamydia trachomatis (the first group) and Chlamydophyla pneumonia (the second group) was done in the induced sputum, throat swab and bronchoalveolar lavage. It was found out that Chlamydia trachomatis was the cause of out-patient pneumonia and bronchitis in children of early age in 7-35% of cases in different years. At long, recurrent and chronic diseases of bronchopulmonary system in children at the age from 1 till 14 years old there is Chlamydophyla pneumonia in 0.5-1.8% of cases and it is oftener in children older than 7 (68% of all infected ones). The comparative estimation of clinical, roentgenological, laboratory parameters in children with bronchopulmonary diseases of chlamydial and pneumococcal etiology was done. «Atypical» character of pneumonia caused by Chlamydia and the differences from the most spread pneumococcal pneumonias are presented by slower and gradual development of infection, by increase of before hospital and in hospital stages, and by slow dynamics of roentgenological data.

The aim of the research is the study of neuro-humoral-hormonal regulation of the immune response in pregnant women with exacerbation of herpes virus infection. 55 pregnant women at the age of 18-35 with exacerbation of herpes-virus infection at different stages of gestation (the main group) and 30 practically healthy pregnant women (the control group) were examined. In the peripheral blood by the method of solid phase immune-enzyme analysis the antibodies to the virus of simple herpes of the first type, interferons (IFN-α, γ), interleukins (IL-1, 2, 4, 8), tumor necrosis factor (TNF-α), placental hormones, as well as biologically active substances (serotonin) were identified. At the exacerbation of herpes-virus infection the quantity of serotonin in the peripheral blood is high at the beginning of pregnancy which is three times higher than in healthy pregnant women and this level does not change during all the period of gestation. In the main group there is the decrease of lymphocytes with suppressor activity at all stages of gestation especially if the exacerbation occurs in its first half (СD8⁺Т-lymphocytes drop till 6-9% (in the control group 20-25%), and subpopulation of СD4⁺Т-lymphocytes drops by 10-15%. Even at low activation of infection (antibody titer 1:3200) the activity of NK-lymphocytes increases in 1.5 times, and at the growth of antibody titer there is six times rise of the percentage of CD25⁺-cells in comparison with the control group, which proves a high differentiation of B-lymphocytes in plasmatic cells. The dependence of the parameters of cell and humoral responses of the immunity on hormonal changes at different antibody titer to herpes virus (1:1600-1:12800) is revealed. The lack of estradiol and estriol becomes the basic criterion of immune system consistency risk in the peripheral blood of pregnant women. The rise of the anti-inflammatory cytokines level (IL-1, IL-8, TNF-α) leads to the change of cytokine balance and to the disturbance of immunologic regulation mechanism which is revealed through the drop of immune suppressive activity.

The bloodflow in the uterine arteries, echo structure of fetoplacental complex, biochemical and hormonal parameters in 121 women in the second trimester of pregnancy at influenza A(H3N2) at the height of the disease were studied. 58 women had antibody titer to the pathogen 1:8-1:32 (the first group), 63 women had the titer 1:32-1:128 (the second group). The control group had 40 women with physiological course of pregnancy. It was found out the patients of the second group in comparison with the patients of the first group had a reliable increase of resistance in the right uterine artery (2.52±0.052 and 2.34±0.063 standard units, respectively, р<0.05), statistically reliable increase of the detection frequency of uterine hypertonus (20.6 and 5.2%, respectively, р<0.05), placenta thickening (22.2 and 6.9%, respectively, р<0.05) and cord entanglement around the neck of the fetus (19.1 and 2.2%, respectively, р<0.05). These changes in the patients of the second group were diagnosed against the growth of mean molecular peptides content in the blood plasma and activation of the process of lipid peroxidation which leads to the increase of malonic dialdehyde concentration and to the decrease of ά-tocopherol content. At the higher titer of anti-influenza antibodies the depression of hormonopoiesis in fetoplacental complex was confirmed with the decrease of concentration of chorionic gonadotropin, placental lactogen, progesterone, estriol, dehydroisoandrosterone, which was diagnosed at the growth of serotonin and cortisol concentration. It was found out that the growth of antivirus antibody titer, endotoxins, the products of lipid peroxidation reaction and serotonin as well as the imbalance of sex hormones causing the change of the vascular tonus and alternative changes of the wall of uterine -placental blood vessels plays an important role in the change of blood flow at the level of uterine arteries and ultrasound picture of fetoplacental system.

The features of gestational period and of labour as well as morphofunctional state of placenta in women with chronic viral hepatitis B and C were studied. Retrospective analysis of 1336 labour histories including 534 pregnant women with viral hepatitis B and 788 pregnant women with viral hepatitis C and 14 pregnant women with the combination of viral hepatitis B and C was done. 1004 labour histories of pregnant women whose gestational period and labour were without complications were included in the group of comparison. All pregnant women had general clinical examination, identification of markers (antigens/antibodies) of hepatitis B and C in the blood serum; histological study of 100 placentas in pregnant women with viral hepatitis and 100 placentas in healthy pregnant women was done. The study proves convincingly that viral hepatitis B and viral hepatitis C have a negative influence on the course of pregnancy, labour and fetus development. The course of pregnancy with viral hepatitis unlike healthy pregnant women is statistically oftener complicated with gestosis (in 43.68±1.35 and 19.52±1.25%, respectively, р<0.0001), miscarriage threat (in 48.02±1.37 and 20.72±1.28%, respectively, р<0.0001), fetoplacental insufficiency (in 49.96±1.37 and 10.05±0.95%, respectively, р<0.0001). Histological signs of fetoplacental insufficiency were found in all pregnant women with viral hepatitis B and C, a severe form of placental insufficiency was revealed in 32% of pregnant women. Pregnant women with chronic viral hepatitis B and C had perinatal morbidity statistically oftener than the women in the control group.

The aim of the research is to study the local specific protection and system inflammatory response at chronic bronchitis of virus etiology in pregnant women. 158 pregnant women in the second trimester of gestation including 123 patients with chronic bronchitis and 35 with physiologic course of pregnancy were examined. The study of specific humoral immunity to influenza virus А(Н3N2) and to viruses of respiratory group and of the content of secretory immunoglobulin A and cytokines in the blood serum was done. It was found out that pregnant women with chronic obstructive bronchitis (COB) at exacerbation and without it oftener have lower values of secretory immunoglobulin content in the blood serum in comparison with women with chronic non-obstructive bronchitis (CNB). This proves the decrease of local specific protection of their respiratory system, predominantly at high titers of antiviral antibodies to influenza А(Н3N2), parainfluenza of 1-3 types and respiratory-syncytial virus as well as against four-time growth of antibodies to pathogens at exacerbation of chronic inflammatory process. Women at COB in remission in comparison with patients with CNB in the second trimester of pregnancy have lower content of IFN-γ, which demonstrates the worsening of their antivirus immunity. Pregnant women with COB exacerbation in comparison with the patients with the acute form of CNB have the signs of disturbance of T-cell immunity regulation and endothelial dysfunction development, which is proved by the imbalance of cytokines being characterized by higher parameters of IL-4 and TNF-ά at simultaneous decrease of IFN-γ level.

The study shows changes in primary infection of the eye and its appendage apparatus in the Amur region among urban and rural population in different age groups for the past 12 years. From 1999 to 2010, the incidence of ophthalmopathology among population in the region increased by 35% (from 23.9 to 32.4‰). There are significant differences in the incidence among urban and rural population. The rate of primary ophthalmopathology morbidity among urban population of the Amur region increased from 1999 to 2010 by 17% (from 32.8 to 38.3‰). Among the rural population the overall morbidity increased over this period by 99% (from 10.3 to 20.5‰), which is the result of the lack of ophthalmologists, the reduction of the number of beds and low organizational work.

Modern conceptions about P-glycoprotein (Pgp) which is a big transmembrane protein transporting a variety of cytotoxic substances are presented in the literature review. Pgp belongs to the protein family of ABC transporters and is a product of MDR1 gene. Pgp is located on the surface of epithelium of small and large intestine, pancreatic duct, in the bile canaliculuses of the liver, bronchi, in the renal and adrenal gland proximal ducts, as well as in the endothelial cells of histohematogenous barriers (blood-brain, blood-testicular and blood-ovarian barriers) and of placenta. The physiological role of Pgp is the protection of cells from different toxic substances and metabolites. It transports the variety of compounds. The level of Pgp activity may influence the efficiency of the therapy significantly because a lot of drugs (glucocorticosteroids, anti tumor drugs, macrolides, statins, etc.) are the substrates of Pgp. A number of drugs can inhibit or induct the Pgp activity. At simultaneous application of Pgp inhibitors and drugs the concentration of the latter may increase and so the risk of unfavorable reactions also grows. On the other hand, the therapy by standard drugs doses may be not effective enough at combination with P-glycoprotein inductors as some of the substrates can inhibit it. P-glycoprotein is one of the most important mechanisms of multidrug resistance development

Almost all differentiated cells in the body have a limited life, their death and replacement occur with different speed. The renewal may happen as a result of duplication or multiplication of undifferentiated precursors. Stem cells in the respiratory tract can stay in the quiescent state for a long time, at the same time they are rarely divided and have a significant interval of a cellular cycle. Their specific behavior usually depends on the total of factors that provide vitality and differentiation. It is determined by inner signals which are controlled by the genes of the cell as well as by outer factors including the presence of basal membrane, territorial matrix, the presence of neighboring cells producing different regulators. The results of personal experimental study of stem cells state and «niches» that surround them in the trachea mucosa at cold exposure against intensive cold oxidative stress are given. It was shown that long exposure of trachea mucosa to cold decreases the speed of cellular elements differentiation and changes interrelations with the cellular surrounding of stem cells («niches»). While using cellular markers of stem cells (E-сadherin and alkaline phosphatase) it was demonstrated that an important cellular element of «niche» affecting the differentiation of stem cells is mast cells that migrate into epithelium at the exposure to cold. The growth of mast cells migration at the exposure to cold in this case is conditioned by the transfer of information influence on the stem cells through the liquid that decreases the quantity of little differentiated cells in epithelium. The identification of specific signal molecules stimulating differentiation of lungs cells can help find new ways of control over differentiation of cells and the possibility of application of stimulators of cambial and stem cells for cellular therapy at different pathologies of respiratory system.

Progressive pulmonary dystrophy («disappearing lung») is a rare disease of unknown etiology. It is characterized by intensive dystrophic pulmonary changes revealed through the transformation of normal lung tissue into huge air bullas taking 1/3 of lungs volume. This disease is characterized by progressive clinical course, predominantly one-sided character of affection, inconsistency between the scope of affection and bareness of clinical presentations. Personal experience of diagnostics and dynamic examination of 5 patients with progressive pulmonary dystrophy during several years was analyzed. The clinical outcome without surgical correction (the operation of the volume reduction, lung transplantation) is fatal in most cases. The work illustrates different methods of radiodiagnostics, ranging from widely-spread routine ones to modern high-technological ones. The results of exclusive development, namely the method of three dimensional volumetry for quantitative estimation of lungs ventilation function at multispiral computer-aided tomography with the use of inspiratory and expiratory test are presented.