Cytological and oxidant features of bronchial inflammation were investigated in 155 patients with severe obstructive pulmonary pathologies. The cytooxidative peculiarities of the bronchial inflammation found in the patients with different severe obstructive lung disorders can be applied as additional diagnostic markers. A differentiated approach to detection and treatment of severe bronchial asthma and severe chronic obstructive bronchitis considering the cytooxidative inflammatory features in bronchi allows control an exacerbation for the shortest period of time, optimizing the basic therapy, to reduce a cost of the treatment and to treat more patients need specialized pulmonologic care.
Цель: изучить ассоциацию однонуклеотидного полиморфизма rs6737848 гена SOCS5 с аллергической бронхиальной астмой (БА). Материалы и методы. Обследовано 59 пациентов (19 мужчин и 40 женщин) с аллергической БА и 50 здоровых лиц (29 мужчин и 21 женщина), составивших контрольную группу. Всем пациентам проведено клинико-инструментальное и лабораторное обследования на базе Красноярской межрайонной клинической больницы №20 им. И.С. Берзона и молекулярно-генетическое исследование на базах Российско-итальянской лаборатории медицинской генетики «MAGI» и лаборатории молекулярно-генетических исследований терапевтических заболеваний НИИТПМ - филиал ИЦиГ СО РАН (Новосибирск). Статистическая обработка материала осуществлялась с использованием программы Statistica for Windows 7.0. Результаты. По результатам исследования выявлено, что частота носителей гомозиготного генотипа СC гена SOCS5 по распространенному аллелю среди больных с аллергической БА была статистически значимо выше по сравнению с контрольной группой. Заключение. Гомозиготный генотип СС гена SOCS5 является фактором риска развития аллергической БА.
The purpose of this study was to investigate cytologic and chemiluminescence (ChL) parameters of phagocytes in induced sputum and bronchoalveolar lavage fluid (BALF) of patients with severe acute exacerbation of COPD (AECOPD). Methods: Eighty-eight patients aged 45 to 75 years (56 males and 32 females) with severe AECOPD were included in the study. The control group included 16 healthy individuals. Cytological examination of induced sputum was done. The luminol-dependent ChL of BALF phagocytes obtained during bronchoscopy was investigated. Results : Leukocyte cell count and neutrophil/eosinophil ratio were increased and macrophages/lymphocyte ratio was decreased in induced sputum (p < 0.05). Exacerbations of infectious etiology were characterized by higher eosinophil count. Leukocyte cell count has been still significantly increased after resolution of the exacerbation. Eosinophil/macrophage ratio was significantly higher in bronchitis phenotype and neutrophil/lymphocyte ratio was higher in emphysema phenotype (p < 0.05). Phagocyte ChL in patients with AECOPD of infectious etiology was significantly higher compared to that in patients with AECOPD of other etiologies, both in exacerbation (spontaneous ChL, 10,049 ± 1,828 vs 8,886 ± 2,672; induced ChL, 19,912 ± 4,037 vs 10,751 ± 1,354, respectively) and in stable state (spontaneous ChL, 3,878 ± 1,147 vs 2,335 ± 1,277; induced ChL, 4,804 ± 1,284 vs 4,253 ± 1,174, respectively). This could be due to a relatively high eosinophil count in AECOPD of non-infectious etiology and in the bronchitis phenotype of COPD; eosinophils could contribute to phagocytosis and oxidative mechanisms. Conclusion . Cytological and oxidant characteristics of the airway inflammation and phagocyte-related features of the local immunity are thought to be different in AECOPD of infectious compared to non-infectious etiology and in exacerbation compared to the stable state. The luminol-dependent ChL could reliably assess phagocyte functional activity in the airway material. This method could be proposed to distinguish between infectious vs non-infectious etiologies of AECOPD in patients with bronchitis phenotype or emphysema phenotype and to evaluate the efficacy of anti-inflammatory treatment.
The aim of the study was to evaluate a role of transforming growth factor"β1 (TGF"β1) gene rs1800470 single nucleotide polymorphisms (SNPs), cytotoxic T"lymphocyte"associated protein 4 (CTLA4) gene rs231775 SNPs and hedgehog"interacting protein (HHIP) gene rs1828591 SNP for predisposition to bronchial asthma (BA) in Krasnoyarsk residents. Methods. The study involved 100 asthma patients and 338 control subjects. The control group included a representative population sample of Siberian urban residents without respiratory diseases who had participated in the WHO MONICA (Multinational Monitoring of Trends and Determinants in Cardiovascular Disease) and the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) projects. Results. There was a significant difference in genotype and allele frequency distribution of the TGFβ gene in patients with non"allergic BA vs controls. Therefore, A allele carriers with heterozygous genotype AG and homozygous genotype AA of rs1800470 polymorphism of the TGF"β1 gene were at high risk of non"allergic BA. We also found an increase in the GG genotype frequency in BA group compared to the control group. The GG genotype of CTLA4 gene rs231775 polymorphism was associated with high risk of allergic BA (ОR = 2.036; 95% CI = 1.16–3.58; р = 0.012). Genotype and allele frequency distribution of HHIP gene rs1828591 polymorphism did not differ significantly between BA patients and the control group. Conclusion. An association was revealed between BA, TGF"β1 gene rs1800470 SNPs and CTLA4 gene rs231775 SNPs. An association between BA and HHIP gene rs1828591 SNPs was not found.
The aim of the research. Analysis of the frequency of genotype polymorphism rs231775 gene STLA4 in patients with asthma, residents of Krasnoyarsk, as well as assessing the relationship of the studied polymorphisms and asthma. Materials and methods. Genomic DNA was isolated from 10 ml of venous blood by phenol-chloroform extraction. DNA testing was conducted using the polymerase chain reaction in real time. A group of patients with bronchial asthma -100 persons, the control group 338 persons. Results. It was studied the frequency of polymorphism rs231775 gene CTLA4 separately in patients with allergic and nonallergic bronchial asthma (BA). A comparative analysis revealed that in patients with allergic asthma the frequency of genotype G / G was 1.7 times higher as compared with the control group and was amounted in allergic asthma patients 36.4% in the control group -21.9% (p = 0.031). Frequency of genotype G / G and A / A + A / G polymorphism rs231775 CTLA4 gene in AD patients was 36.4% and 63.6%, while in the control group 21.9% and 78.1% respectively. Conclusion. In the study of frequency polymorphism rs231775 gene CTLA4 was revealed the increasing the frequency of genotype G / G in the group of patients with allergic asthma. Considering these results, we can conclude that the genotype G / G (OR = 2.036; 95% CI -1,16-3,58, r1-3 = 0.012) determine increased risk of allergic asthma.
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
The purpose of the study. To conduct the comparative analysis of cytological and chemiluminescent markers of phagocytic cells of the bronchial washout at inflammation of respiratory tract in patients with bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). Materials and methods. The study included ii7 patients with bronchial asthma (BA) under control and 53 patients with chronic obstructive pulmonary disease (COPD) in phase of aggravation of the disease under the age of 75 years old. In the fluid of bronchial washout were studied cytological and chemiluminescent indicators of phagocytic cells. Rating (CL) of chemiluminescence was carried out on chemiluminometer (Russia). Results. In cytological examination of bronchial washout fluid in patients with COPD was revealed significantly higher level of neutrophils in contrast to the eosinophilic inflammation in asthma. It was found that spontaneous CL activity of phagocytic cells of the bronchial washout in patients with COPD is different from the same in patients with asthma and healthy persons. Conclusion. The study of cytology the bronchial washout fluid and chemiluminescent activity of phagocytic cells improves the quality of the differential diagnosis of asthma and COPD in cases of combined pathology.
Study of the influence of polymorphism rs 4129267 of IL6R gene on the susceptibility to the development of bronchial asthma among the population of Krasnoyarsk is discussed in present article. Genome DNA was extracted from 10 ml of venous blood with phenol-chloroform extraction technique. Mononucleotide gene polymorphism was tested with the help of polymerase chain reaction in real time in accordance with the firm producer protocol (probes TaqMan, Applied Biosystems, USA) on the apparatus ABI 7900HT. The group of bronchial asthma patients consisted of 108 people; the control group included 282 people. While studying the polymorphism rs 4129267 of gene IL6R genotype distribution among men and women suffering from allergic and non-atopic bronchial asthma and the control group we have revealed some statistically valid differences. The group of allergic bronchial asthma male patients showed the absence of rare homozygotes GG (CR0,88; 95%-CI 0,84-0,92; р=0,023). The number of genotype GG carriers among non-atopic bronchial asthma female patients was less than in the control group (2,9% and 10,9% accordingly, р=0,032), which can be the evidence of protective significance of the genotype GG SNP rs4129267 IL6R gene in the development of bronchial asthma. The above-mentioned facts say about the necessity of further investigations of genetic mechanisms of bronchial asthma development for assessing the individual susceptibility of a particular patient to the development of the disease, which is the basis of personalized medicine.
The purpose of the research was to study the influence of single-nucleotide polymorphisms rs1800470 of TGFВ1 gene and rs231775 of CTLA4 gene on the susceptibility to the development of bronchial asthma among the population of Krasnoyarsk. The group of patients with bronchial asthma were 100 people; two control groups, respectively, for each polymorphism 282 and 338 people. Genome DNA was extracted from 10 ml of venous blood with phenol-chloroform extraction technique. Single nucleotide gene polymorphism was tested with the help of polymerase chain reaction in real time in accordance with the firm producer protocol (probes TaqMan, Applied Biosystems, USA) on the apparatus ABI 7900HT. While studying the polymorphism rs1800470 of gene TGFВ1 for a group of patients with non-allergic asthma the absence of rare homozygous GG was demonstrated. Development of non-allergic asthma significantly associated with genotype AA and AG, in comparison with both the control group (p=0.025) and a group of patients suffering from allergic forms of asthma (p=0.006). If there is evidence of genotypes, non-allergic asthma risk increases compared with the control group (ОR=1.631; 95% CI=1.37-1.94) and with a group of patients with allergic asthma (ОR = 1.128; 95% CI=1.08-3.17). When studying polymorphism rs231775 CTLA4 gene, increased frequency of genotype GG in the group of patients with allergic asthma, including women, was revealed. Taking into consideration the results obtained, it can be concluded that the presence of the genotype GG (ОR=2.036; 95% CI=1.16-3.58) causes an increased risk of allergic asthma in comparison with the control group.
It was studied the distribution of genotypes and alleles of the gene CCR5 chemokine receptor and constitutionally-morphological phenotypes in the group of patients with asthma, their relatives, and in the group of healthy controls. The study was conducted on the material of 62 Russian families of patients with bronchial asthma (total 232 people) citizens of city Krasnoyarsk. It was found that the polymorphism gene CCR5 chemokine receptor in the coding area is associated with allergic asthma and is an important component of genetic predisposition to asthma. In patients with bronchial asthma, the greatest number of correlation refers to the fat component of body weight. Taking into account that we have found the association of asthma with genotype II gene CCR5, there is a reason to believe that fat dimorphism is a factor contributing to polymorphism of the gene responsible for the development of allergic asthma.
The aim of the study was to investigate cytological features and chemo luminescent activity of bronchial lavage phagocytic cells in 58 patients (28 of them are over 60 years old and 25 patients younger than 60 years) with bronchial asthma (BA) before and after achievement of medicinal disease control. Bronchial inflammation process in elderly patients (> 60 years) was characterized by significant higher content of neutrophils and lymphocytes as well as lower proportion of alveolar macrophages. Chemo luminescent responses of bronchial lavage phagocyte cells in patients with BA were unidirectional in two comparative aging groups, albeit with quantitative differences. In conclusion, respiratory tract inflammatory process in elderly patients with BA is characterized by less pronounced involvement of effector cells, lower chemo luminescent activity of phagocytes in comparison with similar parameters in the patients younger than 60 years old.
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.
The authors have studied cytological peculiarities and processes of free radical oxidation by chemiluminescent indices of phagocytizing inflammatory cells in breathing passages of patients suffering from bronchial allergy and chronic obstructive lung disease. Having examined 128 patients, they proved firm differences, which may be used as additional criteria for differential diagnostics of these diseases. Based on study materials, they received a patent of Russian Federation for invention Nr. 2262095 dated 10.10.2005.
The paper presents the results of clinical and genealogical analysis of 72 genealogies of patients with bronchial asthma (BA). It was defined the family accumulation of asthma in families of probands with the same pathology, it was done segregation analysis on "sibsovom" method by Weinberg, were studied constitutional features of patients with asthma and their relatives of I, II and III relation degree. The results indicate the inherited predisposition to BA, an autosomal-dominant type of inheritance of this disease, the prevalence of asthma among patients with breast somatotype in men and leptosomnoy constitution in women.
Severe pneumonia is characterized by acute inflectional inflammation with respiratory insufficiency, sings of severe sepsis and septic shock. The modern view for this process describes it as a system inflammation to inflectional loci which formally takes place in every case of severe pneumonia. However sepsis in severe pneumonia is diagnosed only when the organic insufficiency develops. To enhance the treatment efficiency we need to unify the definitions of sepsis, severe sepsis, and septic shock in pneumonia.