Comorbidity is a common condition in medical practice. The presence of comorbid conditions in a patient makes a great contribution to the course and prognosis of the underlying disease, as well as the development of complications [12]. At the same time, diseases occurring with broncho-obstructive syndrome and arterial hypertension syndrome are widespread throughout the world [13, 14]. The aim of this study was to assess the degree of endothelial dysfunction associated with impaired nitric oxide synthesis, based on the state of the NO/NOS/ADMA system and genetic polymorphisms of the nitric oxide synthetase gene in patients with bronchial asthma combined with essential hypertension. Materials and methods Three groups of patients, 96 people each, were formed, corresponding in age and gender structure with a diagnosis of bronchial asthma (BA group), essential hypertension (EH group) and their joint course (BA+EH group). Serum concentrations of asymmetric dimethylarginine, symmetric dimethylarginine, genetic polymorphisms of nitric oxide synthase (synthases NOS3 786T/C and NOS3 894G/T) were determined. To determine the role of other factors in increasing the concentration of ADMA and SDMA, multiple linear regression analysis was performed. Results: according to the results of the study, for a group of patients with a combination of bronchial asthma and hypertension, there are increased levels of ADMA and SDMA, the T allele NOS3 786C/T is more common in hypertension, in multiple linear regression significant factors in increasing ADMA are the presence of hypertension, bronchial asthma, body mass index and glomerular filtration rate, for SDMA - the presence of hypertension, asthma and glomerular filtration rate. Conclusions: The comorbidity of bronchial asthma and arterial hypertension is associated with an increased serum concentration of ADMA and SDMA. The presence of the TT genotype of the NOS3 786C/T polymorphism is associated with an increased incidence of arterial hypertension in patients with asthma.

Clinical efficacy of inhalation therapy by Onbrez (R) Breezhaler (R) and examination of the effect on the leading clinical symptoms, quality of life (COPD Assessment Test), lung function, heart rate, QTc interval and the potassium level in blood in hospital patients with COPD were under study. Based on the found evidence we can conclude that once daily administration of indacaterol at a dose of 150 mcg is an effective treatment for patients with COPD. It provides significant bronchodilation, reduces clinical manifestations, improves the quality of life of patients and has a favorable cardiovascular safety profile.

The lung provides not only respiration, but also the functioning of innate immunity mechanisms. The hydrophilic proteins SP-A and SP-D are responsible for the regulation of the latter. In the literature, there is evidence for elevated serum SP-A and SP-D levels in respiratory diseases accompanied by enhanced mucosal inflammation of the lung or its parenchymal injury and their association with age and cardiovascular diseases has been recently found. Studies of the efficiency of using SP-A and SP-D as specific markers for inflammatory lung diseases are presently worthwhile.

Бронхиальная астма (БА) представляет собой муль тифакториальное заболевание, в развитии которого, наряду с внешнесредовыми факторами, важную роль играет генетическая предрасположенность. Ис ходя из современных представлений о патофизиоло гических механизмах БА, можно выделить группы генов, нарушения структуры и функционирования которых могут вносить вклад в развитие БА. К ге нам кандидатам будет правомерно отнести гены врожденного иммунного ответа и иммунорегуляции; гены, связанные с дифференцировкой и функцио нированием Th2; гены иммунитета слизистых обо лочек; гены легочной функции и др. [1]. Однако многие гены, имеющие отношение к патогенезу БА, недостаточно исследованы. Среди большого числа генов, которые могут принимать участие в формиро вании предрасположенности к развитию БА, внима ние привлекает ген хемокинового рецептора CCR5. Этот ген ответственен за направленную миграцию и выход из сосудистого русла в ткани иммуноком петентных клеток [2]. Ген CCR5 занимает около 6 тыс. пар нуклеотидов (п. н.) на хромосоме 3р21. Делеция 32 п. н. в кодирующей области гена CCR5 (del32CCR5) приводит к трансляции укороченного варианта белка, который адгезируется на поверхно сти клеток [3]. Частота делеционного аллеля гена CCR5 составляет 15,5–16 % в различных популяци ях и зависит от этнического состава населения [4]. По данным литературы известно, что нарушение функции рецептора CCR5 в результате делеции 32 п. н. может выступать патогенетически значимым фактором в развитии заболеваний [5–7]. Сведения об ассоциации CCR5del32 с риском заболевания БА нем ногочисленны и демонстрируют противоречивые ре зультаты [8–12]. Известно, что инфильтрация тканей легких эозинофилами у больных БА ассоциирована И.И.Черкашина 1, С.Ю.Никулина 1, Н.И.Логвиненко 2, В.Н.Максимов 3, М.И.Воевода 3, В.А.Шульман 1, В.А.Шестовицкий 1, В.А.Чупахина 1, А.А.Чернова 1, А.В.Талаевская 4 Полиморфные варианты гена хемокинового рецептора ССR5 и особенности морфологической конституции как маркеры предрасположенности к бронхиальной астме

Objective: To study an association of CVD risk factors (smoking, hypertension, obesity) аnd аirflow obstruction (АO). Materials and methods. In frames of the population-based cross-sectional study (project HAPIEE, total sample 9360 persons aged 45–69) spirometry parameters were investigated in subsample 6875 persons (73,5 %). Forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC) were fixed. Ао was registred at FEV1/FVC < 70 % and (or) FEV1 < 80 %. Two variants АO allocated for analysis: 1) АO (FEV1 / FVC < 70 % FEV1 ≥ 80 % and FEV1 < 80 %) – typical for chronic obstructive pulmonary disease – АO (COPD), 2) АO (FEV1 < 80 %; FEV1 / FVC ≥ 70 %) typical for asthma – АO (asthma). Number of smoking pack years (PY) was calculated using the formula: (number of cigarettes smoked per day × number of years smoked) / 20 (1 pack has 20 cigarettes). All respondents divided to 3 groups depending on the PY: 1 – < 10 p / y, 2 – 10–24 p / y, 3 – ≥ 25 p / y. Hypertension registered if systolic blood pressure (SBP) ≥ 140 mm. Hg and diastolic blood pressure (DBP) ≥ 90 mm. Hg. Overweight and obesity determined by BMI WHO criteria. Results. Significant negative correlation was determined between PY and FEV1 in men and women (p < 0.01), between PY and FEV1/FVC in males (p < 0.01) and in women (p < 0.05); between SBP, DBP and FEV1 in men and in women (p < 0.01), SBP and FEV1 / FVC in women (p < 0.05). A positive correlation was determined between BMI and FEV1 / FVC in women and in men (p < 0.001), negative – between BMI and FEV1 in women (p < 0.01). When using the binary logistic regression (independent variables: age, sex, BMI, PY, SBP, DBP) increased relative risk (RR) of AO (COPD) found in males in 2.1 times PY 10–24 p / y, 3.8 times at PY ≥ 25 p/y. Increased RR of AO (COPD) was found in women-smokers in 3 times compared to the never smokers. Increased RR of АO (asthma) was detected in men 1.9 times with obesity and increased 2 times with PY 10–24 p / y versus never smokers. RR of АO (asthma) in women increased 2.1 times with PY 10–24 p / y, 4 times with PY ≥ 25 p / y. Influence of blood pressure on the risk of both variants of АO had not revealed. Conclusions. Higher prevalence of coronary heart disease among patients with AO compared with the general population, most likely due to the presence of associations of cardiovascular risk factors and АO.

Although currently smoking cigarettes recognized as the most common and important risk factor for chronic obstructive pulmonary disease, there is a view that this is not the only factor in the development of airflow obstruction (AO). Objective: to study the effect of smoking on the development of AO in the open population of the city of Novosibirsk. We used population-based cross-sectional study materials obtained in the framework of the project <HAPIEE> in 2002-2005. ("The determinants of cardiovascular disease in Eastern Europe: a cohort study"). At 73.2% (6875) from a total sample of persons aged 45-69 studied lung function: a three-fold measurement of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC). Conducted individual calculation of indices FEV1, FEV1/FVC, without defining test for reversibility of AO to identify those with FEV1/FVC < 70% and FEV1 < 80%. Depending on the groups of smoking status: 1 - "smokers", 2 - "periodically smokers" 3 - "exsmokers", 4 - "never smokers." With AO registered 42.5% of smokers (among men - 64.2%, among women - 14,3%); 0,8% periodically smokers (among men - 0.5%, among women - 1,2%); 15,5% ex -smokers (among men - 22.2%, among women - 6,7%); 41,2% never smokers (among men - 13.1%, among women - 77,8%). In the study of the possibility of forming AO for persons with the smoking anamnesis relative to never smokers, it was found that AO is formed 3.2 times more often in male smokers, 1.7 times more often in female smokers than nonsmokers; AO is formed 2 times more often in male ex-smokers, 2.1 times more often in female ex-smokers than never smokers; chance of developing AO was not greater in periodically smokers. Analysis of indices population showed negative correlation of AO components (FEV1, FEV1/FVC) with the number of smoking pack years. The results showed that the presence of smoking history, intensity and duration of smoking affect the development of AO.

Bronchial obstruction syndrome (BOS) is the most common manifestation of chronic obstructive pulmonary disease and asthma. Spirometry is a necessary and most objective method of assessing chronic bronchial obstruction.Purpose of study: To study the prevalence of BOS in the open population of Novosibirsk.Materials and method: We used population-based cross-sectional study materials obtained in the framework of the project 'HAPIEE' in 2002-2005. ("The determinants of cardiovascular disease in Eastern Europe: a cohort study"). At 73.2% (6875) from a sample of persons aged 45-69 studied lung function: a three-fold measurement of FEV1, FVC. Respondents were divided into three age groups: 45-54 years, 55-64 years, 65-69 years. Conducted individual calculation of indices FEV1, FEV1 / FVC, without defining test for reversibility of airflow limitation to identify those with FEV1 / FVC < 70% and FEV1 < 80%.Results: Reduced FEV1 / FVC < 70% in 8.26% found (568). At 2.5 times more likely to decline in FEV1 / FVC < 70% found among men - 12.06% (389) than among women - 4.91% (179) (p = 0.0001). FEV1 / FVC ( >= 70%) of normal FEV1 ( >= 80%) reported in 87.03% (2469) of men and 88.39% (3067) of women; moderate disturbances in FEV1 (50-79%) - at 12.41% (352) of men and 11.15% (387) of the women, severe disturbances in FEV1 (30-49%) - at 0.53% (15) males and 0.43% (15) women, with very severe BOS (FEV1 < 30%) - at 0.04% (1) in men and 0.03% (1) of the women. There were no significant gender differences in the degree of disturbance of FEV1 in FEV1 / FVC >= 70% were found (p > 0,05). BOS detected in the following rates: 1 - FEV1 / FVC < 70%; 2 - FEV1 < 80%, FEV1 / FVC >= 70%. In the total sample of BOS was detected in 19.48% of the 6875 patients (in the group of 45-54 years - at 14.80%, 55-64 years - at 20.8%, 65-69 years - at 25.49%). BOS was detected in 23.47% of all surveyed 3,226 men and 15.95% of the 3649 women (p < 0.001). Among men aged 45-54 years the prevalence of BOS was 17.33%, 55-64 years 24.79%, 65-69 years - 32.05%. The women in the age group of 45-54 years BOS was found in 12.63% of cases, 55-64 years - 17.26%, 65-69 years - 19.69%.Conclusions: The results showed a fairly high prevalence of BOS in a large industrial center of Western Siberia. In the total sample of BOS was diagnosed in 19.48% of the 6875 patients irrespective of gender (45-54 years - 14.80%, 55-64 years - 20.85%, 65-69 years - 25.49%). Among men, the airflow obstruction was detected in 23.47% of cases (of 3226 patients), among women (3649 patients) - in 15.95%.

Summary. A distribution of alleles and genotypes of chemokine receptor CCR5 gene and constitutional and morphological phenotypes of asthma patients and their relatives in comparison with healthy persons have been studied. Findings of 62 Russian families of patients with asthma (n = 232) living in Krasnoyarsk city were used in this study. The polymorphism of a coding region of chemokine receptor CCR5 gene was associated with allergic asthma and also was an important component of congenital susceptibility for asthma. In patients with asthma, most relationships were associated with fat body mass. Given an identified association between asthma and genotype II of CCR5 gene there could be a consideration that fat dismorphism could contribute to gene polymorphism responsible for the development of allergic asthma.

Summary . The aim of this study was to investigate prevalence of genotypes and CCR2 gene alleles in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). We examined 90 BA patients, 72 COPD patients and healthy subjects as controls using standard diagnostic tools for these diseases and molecular analysis. CCR2 chemokine receptor gene polymorphism was investigated in patients with BA and COPD in comparison with healthy subjects. There was not any significant difference in prevalence of genotypes and CCR2 gene alleles in patients with BA or COPD, or in controls. The results have shown an association between rare allele 641 in the CCR2 gene and COPD and a protective role for homozygous genotype 64V/64V of this gene in COPD development. The comparative analysis allowed extension our knowledge about some genetic features of these diseases. The CCR2 chemokine receptor gene polymorphism was associated with COPD but not with BA.

Was analyzed the polymorphism in the 3'non-transmittable gene region of receptor macrophage-colony stimulating factor (c-fms) in patients with bronchial asthma (BA) and their families. The study was conducted on the material of 62 Russian families of patients with asthma ( 232 total) residents of city Krasnoyarsk. Polymorphism analysis of the gene c-fms showed a statistically significant prevalence of heterozygous genotype PQ c-fms gene among patients with non-allergic asthma compared to the control group. Frequency of genotypes and alleles of polymorphic locus gene c-fms in groups of relatives was not significantly different from the control group. Considering these results, the genotype pq gene c-fms can be regarded as a genetic predictor of formation of non-allergic asthma. Relatives of patients with various manifestations of allergy and genotype pq can be attributed to the risk group of developing the disease.

Family examination of 70 probands with bronchial asthma (BA) and 162 their relatives I, II, III degrees of relationship (the mainc group) was carried out. Healthy people were included in the control group (n=263). During the examination the standard complex of inspection of people with BA, molecular genetic methods of research, and also methods of statistical data processing were used. Results of research of polymorphism of a gene of chemokine receptor ССR5 in coding area in BA patients and their relatives in comparison with control group are presented. It is established that polymorphism of a gene of chemokine receptor CCR5 in coding area is associated with BA and is an important component of BA hereditary predisposition.

Проведено семейное обследование 62 пробандов, у которых была диагностирована бронхиальная астма (БА), и их 172 родственников I, II, III степени родства (основная группа). В контрольную группу вошли лица без заболеваний бронхолегочной системы. В работе использовался общепринятый комплекс обследования лиц, страдающих БА, молекулярно-генетические методы исследования, а также методы статистической обработки данных. Был изучен полиморфизм генов хемокиновых рецепторов ССR5 и CCR2 у больных БА и их родственников в сравнении с группой контроля. Установлено, что полиморфизм гена хемокинового рецептора CCR5 в кодирующей области ассоциирован с БА и является важной компонентой наследственной предрасположенности к этому заболеванию. Обнаружены статистически значимые различия в распределении частот аллелей гена CCR2 между группами родственников с аллергией и здоровыми родственниками. Можно предположить, что носительство аллеля 64I гена CCR2 является предрасполагающим фактором развития аллергии.

Проведено семейное обследование 81 пробанда, у которых диагностирована бронхиальная астма (БА), и 183 их родственников I-III степеней родства (основная группа). В группу сравнения были включены практически здоровые люди - 263 человека. Выявлено семейное накопление БА в семьях пробандов с данной патологией. Установлен аутосомно-доминантный тип наследования БА. Гетерозиготный вариант генотипа гена рецептора макрофаг-колониестимулирующего фактора с-fms (РМКСФ) можно рассматривать как один из генетических предикторов возникновения БА. Предиктором возникновения БА может служить также гомозиготный генотип по редкому аллелю гена РМКСФ.