CLINICAL IMMUNOLOGICAL PECULIARATIES OF ATOPIC BRONCHIAL ASTHMA DEPENDING FROM THE LEVEL OF CONTROL OVER THE DISEASE IN CHILDREN

The formation of definite phenotype in atopic bronchial asthma is associated with interaction between environment factors and peculiarities of endogenous constitution. We have carried out the analysis of peculiarities of immunological status, cytokine regulation of cellular interactions collectively with environment factors. We have revealed the predictors of non-controllable course of atopic bronchial asthma in children

Microbiota of the upper respiratory tract in children with chronic adenoiditis

Background. Routine application of the GC-MS method to assess the URT microbiota can potentially improve the efficacy and safety of treatment for chronic respiratory diseases. Aim. To perform a comparative analysis of the microbiota from the surface of the pharyngeal tonsil, from the deep parts of the nose, and saliva in children with chronic adenoiditis. Materials and methods. The study included 90 patients with chronic adenoiditis (CA) and/or pharyngeal tonsil hypertrophy (PTH). All study participants had swabs taken from the surface of the pharyngeal tonsil, from the deep parts of the nasal cavity, and saliva as a biological fluid of the oral cavity. Microorganisms were identified by specific fatty acids using GC-MS to assess the composition of the microbial community on the surface of the pharyngeal tonsil. Results. The study showed that the microbiota of the nasopharynx is identical in its qualitative composition to microorganisms from the deep parts of the nose. However, according to the results of the analysis of microbial markers of saliva, the oral microbiota showed significant differences in the quantitative and qualitative composition of microorganisms compared with the nasopharyngeal microbiota. Conclusion. The introduction of the GC-MS method for assessing the URT microbiota enables its monitoring in clinical practice for the treatment of chronic respiratory system diseases without disturbing the ecology of the mucous membranes and the whole body

Этиологическая диагностика внебольничной пневмонии у детей

The paper represents a systematic review of current etiological diagnostic methods in childhood communityacquired pneumonia based on studies and guidelines of recent years. The authors compare sensitivity and specificity of different diagnostic methods, advantages and limitations of different routine microbiological diagnostic approaches. According to most opinions molecular methods are very valuable, quick and easy to use but should be combined with culturing and other routine tests for better interpretation of results.Представлен обзор современных методов этиологической диагностики внебольничной пневмонии у детей по результатам проведенных в последние годы исследований. Приведены данные о чувствительности и специфичности различных методов диагностики. Проанализированы достоинства и недостатки традиционных методов микробиологической диагностики. Представлены возможности применения молекулярных методов исследования как наиболее информативных, быстрых и простых в применении

Этиологическая роль и молекулярно-генетические особенности Streptococcus pneumoniae при инфекционных заболеваниях у детей

Objective: To study the etiological role, serotype distribution and prevalent Streptococcus pneumoniae genotypes (sequence types) in 459 children hospitalized with acute purulent otitis media, acute tonsillitis, community-acquired pneumonia, and purulent bacterial meningitis. Pneumococcal cultures isolated from patients were tested for sensitivity to antimicrobials, and presence of resistance genes.Materials and Methods: The cultural and molecular methods (PCR, sequencing) were used. Statistical analysis was carried out using Microsoft Excel 2007 and Statistica 6.0. Results: S. pneumoniae was detected in 16,8%. The prevalent serotypes were 19F (39.7%) and 19A (13.2%) — representatives of multidrug-resistant clonal com-plex 320. Isolates of serogroup 6 (6AB, 8.82%) belonged to clonal complex 315, and characterized by resistance to macrolides, clindamycin and tetracycline.From 70.6% to 88.2% of S. pneumoniae serotypes isolated from patients corresponded to «vaccine»-types.Цель: выявление этиологической роли, исследования серотипового пейзажа и определения преобладающих генотипов (сиквенс-типов) Streptococcus pneumoniae у 459 детей, госпитализированных по поводу острого гнойного среднего отита, острого тонзиллита, внебольничной пневмонии, гнойного бактериального менингита. Материалы и методы: Использовался культуральный (бактериологический) метод, молекулярные методы (ПЦР, секвенирование). Статистическая обработка проводилась с помощью программ Microsoft Excel 2007 и Statistica 6.0.Результаты: S. pneumoniae был выявлен в 16,8% случаев. Преобладали серотипы 19F (39,7%) и 19A (13,2%), относящиеся к мультирезистентному клональному комплексу 320. С меньшей частотой (8,82%) встречались пневмококки 6 серогруппы (6АВ) — представители клонального комплекса 315, характеризующиеся устойчивостью к макролидам, клиндамицину и тетрациклину.Соответствие выявленных серотипов антигенному составу пневмококковых вакцин составило от 70,6% до 88,2%.

Ассоциации гена VDR с клиническими проявлениями и осложнениями муковисцидоза

Cystic fibrosis (CF) is the most common severe autosomal recessive disease in the Caucasoid population caused by mutations in the CF transmembrane regulator (CFTR) gene. However, the course of the disease may be modulated by genetic factors other than the CFTR gene and may be pleiotropically influenced by VDR (Vitamin D Receptor) gene. The aim of the study was to search for associations between genetic variants (c.1206T>C(A>G), c.152T>C, c.1174+283G>A) of VDR gene and clinically significant manifestations of CF, complications, and responses to therapy. Methods. Patients with CF (n = 283) and healthy children (n = 333), who formed the control group, were examined. Calcidiol levels were tested in all subjects. Polymorphic variants of VDR gene (c.1206T>C(A>G), c.152T>C, c.1174+283G>A) were tested by polymerase chain reaction and restriction fragment length polymorphism analysis. Results. It was found that carriers of the TT genotype of the c.152T>C FokI variant of VDR gene are 6.3 times more likely to develop meconium ileus (odds ratio – OR – 6.375; p = 0.011), 3.2 times more likely – respiratory failure (OR – 3.253; p = 0.079), 3.4 times more likely – chronic lung infection (CIL) caused by Pseudomonas aeruginosa (OR – 3.432; p = 0.026), and 4 times more likely – CIL caused by non-fermenting gram-negative bacteria (OR – 4.056; p = 0.009). Carriers of the CC genotype of the c.1206T>C(A>G) TaqI genetic variant use systemic corticosteroids more frequently (66% vs 7%) (OR – 0.034; p = 0.001). It was shown that the AA genotype of the BsmlI polymorphism (c.1174 + 283G>A) is 4 times more likely to be detected in children with CF-associated liver diseases (OR – 4.300; p = 0.051). Conclusion. The contribution of all studied genetic variants c.1206T>C(A>G) TaqI, c.152T>C FokI, BsmlI (c.1174+283G>A) of the VDR gene to the clinical manifestations, complications and response to therapy in CF is described.Муковисцидоз (МВ), или кистозный фиброз, является наиболее частым тяжелым аутосомно-рецессивным заболеванием в европеоидной популяции, вызываемым мутациями гена трансмембранного регулятора МВ (CFTR). Однако течение заболевания может модулироваться генетическими факторами, отличными от гена CFTR, и подвергаться плейотропному влиянию гена VDR (Vitamin D Receptor – рецептор к витамину D). Целью исследования явился поиск ассоциаций между генетическими вариантами (c.1206T>C(A>G), c.152T>C, c.1174+283G>A) гена VDR и клинически значимыми проявлениями МВ, осложнениями и ответами на терапию. Материалы и методы. Обследованы пациенты с МВ (n = 283) и здоровые дети (n = 333), составившие контрольную группу. У всех обследованных определялось содержание кальцидиола. Тестирование полиморфных вариантов гена VDR (c.1206T>C(A>G), c.152T>C, c.1174+283G>A) проводилось методами полимеразной цепной реакции и анализа полиморфизма длины рестрикционных фрагментов. Результаты. Выявлено, что у носителей генотипа ТТ генетического варианта c.152T>C FokI гена VDR в 6,3 раза чаще реализуется мекониевый илеус (отношение шансов (Odds Ratio – OR) – 6,375; p = 0,011), в 3,2 раза чаще – дыхательная недостаточность (OR – 3,253; p = 0,079), в 3,4 раза чаще – хроническая инфекция легких (ХИЛ), вызванная Pseudomonas аeruginosa (OR – 3,432; p = 0,026), в 4 раза чаще – ХИЛ, вызванная неферментирующими грамотрицательными бактериями (OR – 4,056; p = 0,009). У носителей генотипа СС генетического варианта c.1206T>C(A>G) TaqI чаще (66 % vs 7 %) применяются системные глюкокортикостероиды (OR – 0,034; p = 0,001). Показано, что генотип АА полиморфизма BsmlI (c.1174+283G>A) в 4 раза чаще выявляется у детей с МВ-ассоциированными заболеваниями печени (OR – 4,300; p = 0,051). Заключение. Показан вклад всех изучаемых генетических вариантов c.1206T>C(A>G) TaqI, c.152T>C FokI, BsmlI (c.1174+283G>A) гена VDR в формирование клинических проявлений, осложнений и ответа на терапию при МВ

IMMUNOLOGICAL MARKERS OF UNCONTROLLED ATOPIC BRONCHIAL ASTHMA IN CHILDREN

Bronchial asthma is a prevalent chronic allergic disease of lungs at early ages. A priority  task in allergology  is to search  biological  markers  related  to uncontrolled atopic  bronchial asthma. Cytokines fulfill their distinct function in pathogenesis of atopic  bronchial asthma, participating at the initiation, development and persistence of allergic inflammation in airways, causing different  variations of clinical course of the disease (with  respect  to its acuteness, severity, frequency of exacerbations). The  present  work has studied  indices  of cellular  and  humoral links of immunity, as well as levels of some  pro and  anti-inflammatory cytokines in peripheral blood serum (IL-4, IL-10, IL-2 and TNFα), aiming to determine potential markers of uncontrolled atopic bronchial asthma in children. A group of Caucasian (European) children was involved into the research: Cohort 1, moderate atopic  bronchial asthma with controlled course during the last 3 months (n = 59); Cohort 2, severe/moderate-severe atopic bronchial asthma with uncontrolled course of the disease within last 3 months (n = 51),  Cohort 3 – control, practically healthy  children without signs of atopy  (n = 33). All the  children included in the group with atopic  bronchial asthma underwent regular mono/combined basic therapy  at high/ intermediate therapeutic doses.  We performed a comparative analysis  of cell  population indices  reflecting certain cellular  immunity links,  and  determined significantly  lower  levels of CD3+   lymphocytes, as well as decrease in relative  and  absolute  contents of CD4+  and  CD8+  cells in the  cohort with  uncontrolled course of atopic  bronchial asthma, as compared with controlled-course cohort. When  evaluating concentrations  of cytokines in peripheral blood serum of the patients with controlled and uncontrolled atopic  bronchial asthma, we revealed  significantly  higher  levels of IL-2, IL-4, and  IL-10, as compared to control group.  It was found that TNFα concentration is considerably higher in both cohorts of the patients, being 2to 3-fold higher than the levels of this cytokine in control group.  When comparing the cohorts with different  control of the disease course, we have found that TNFα concentration in the cohort with uncontrolled bronchial asthma is statistically higher  than  among  children with  controllable course  of the  disease.  Hence, the  following  parameters may serve as potential markers  of pediatric atopic  bronchial asthma with uncontrolled course:  low levels of total Т lymphocyte numbers in peripheral blood,  and decreased counts  of CD4+, CD8+ cells; IgE hyperproduction; low contents of common IgA, and high concentration of TNFα in peripheral blood serum

Etiological role and molecular-genetic features of <i>Streptococcus pneumoniae</i> in children’s infectious diseases

Objective: To study the etiological role, serotype distribution and prevalent Streptococcus pneumoniae genotypes (sequence types) in 459 children hospitalized with acute purulent otitis media, acute tonsillitis, community-acquired pneumonia, and purulent bacterial meningitis. Pneumococcal cultures isolated from patients were tested for sensitivity to antimicrobials, and presence of resistance genes.Materials and Methods: The cultural and molecular methods (PCR, sequencing) were used. Statistical analysis was carried out using Microsoft Excel 2007 and Statistica 6.0. Results: S. pneumoniae was detected in 16,8%. The prevalent serotypes were 19F (39.7%) and 19A (13.2%) — representatives of multidrug-resistant clonal com-plex 320. Isolates of serogroup 6 (6AB, 8.82%) belonged to clonal complex 315, and characterized by resistance to macrolides, clindamycin and tetracycline.From 70.6% to 88.2% of S. pneumoniae serotypes isolated from patients corresponded to «vaccine»-types