[PHARMACOGENETIC MARKERS OF THE EFFECTIVENESS OF TREATMENT OF CHILDREN WITH ATOPIC BRONCHIAL ASTHMA.]

Data on the pharmacogenetic markers of the effectiveness of treatment of children with atopic asthma are presented, which reveal a variability of the response to treatment with glucocorticosteroids, leukotriene receptor antagonists, and b2-adrenoreceptor agonists in children with bronchial asthma. The association of genotype Gly/Glyl6 gene b2-adrenergic receptor with insufficient effect of the therapy with short-acting b2-agonists is demonstrated. The Glyl6 allele, CYP2D6 - 1934GGd contributes to the formation of a phenotype with severe asthma and tolerance to therapy with b2-agonists and inhaled corticosteroids.

[Genetic aspects of atopic diseases in children].

Atopic diseases is a group of pathologic conditions with polygenic inheritance the development of which is governed by familial predetermination to allergy. This review summarizes results of research on pathogenetic mechanisms of atopic diseases and their clinical features. Analysis includes the structure of hereditary predetermination to allergic reactions and diseases, risk of their development in subsequent generations, the role of age, sex, and ethnic background in pathogenesis of atopic diseases and formation of allergic constitution governed by genotype and environment. Polymorphisms of candidate genes responsible for atopic diseases are considered along with their response to basal pharmacotherapy.

[Bronchial asthma in children and adolescents].

Modern concept of the development of bronchial asthma (BA) is discussed based on original and reported findings with reference to specific features of its etiology, pathogenesis, clinical course, and drug therapy. Special emphasis is laid on the methods of allergen-specific immunotherapy of atopic BA. Up-to-date staged treatment of different forms of BA in children by inhalation of glucocorticosteroids is described.

[Polioxidonium in comprehensive therapy of recurrent herpetic stomatitis in children with allergic diseases].

In the study with participation of 96 children of 1-7 years age with recurrent herpetic stomatitis and allergic diseases therapeutic efficacy of Polioxidonium was investigated. Polioxidonium was used in combination with traditional methods and with He-Ne-laser irradiation. Local oral cavity immunity, indexes of cellular immunity (in the reaction of lymphocytes blast-transformation with phytohemagglutinin), indexes of humoral immunity (IgG and IgE) were studied, complement C(3)-component was determined. Polioxidonium in combination with traditional methods and with laser therapy for recurrent herpetic stomatitis treatment in children with allergic diseases influenced favourably upon clinical course of allergic diseases, let achieve stable remission, increased efficacy of their treatment, promoted immunological status and shorten the terms of medical rehabilitation.

Effect of Nasal Obstructive Disorders on Sinonasal Symptoms in Children with Different Levels of Bronchial Asthma Control.

Allergic rhinitis (AR) and allergic rhinosinusitis (ARS) are typical upper airway pathologies (UAP) in children with bronchial asthma (BA) frequently accompanied with nasal obstructive diseases (NOD). In order to establish the effect of NOD on correlations between nasal and synonasal symptoms with clinical assessments of asthma control, 82 children, 9.8 [8.9; 10.7] years old, with atopic BA were assessed using ACQ-5 for the BA control level, TNSS for nasal symptoms, and SNOT-20 for synonasal quality of life in combination with rhinovideoendoscopy for NOD. All patients had AR/ARS; in 76.3% (63/82) of children, UAP had a multimorbid character with the presence of NOD. Significant correlations were found between ACQ-5 and TNSS (R=0.40, p < 0.0001) and ACQ-5 and SNOT-20 (R=0.42, p < 0.0001). Correlations between TNSS/ACQ-5 and SNOT-20/ACQ-5 were higher in patients who do not have a combination of AR/ARS with NOD (R=0.67, p=0.0012; R=0.50, p=0.022, resp.) than in patients who have AR/ARS combined with NOD (R=0.30, p=0.015; R=0.26, p=0.04, resp.). Thus, the association of BA control level with the expression of nasal and synonasal symptoms is higher in children who do not have multimorbid UAP.

[Goiter transformation as a risk factor of the development of bronchial asthma in children under the influence of natural and technogenic factors of the environment].

The paper deals with the comparative characterization of the prevalence of goiter transformation in children with bronchial asthma (BA) in relation to the level of a technogenic load and natural iodine deficiency in case of the Perm Region. There was a wide distribution of goiter transformation in children, which did not correspond to natural iodine supply in the Perm Region, suggesting the contribution of anthropogenic strumogenic factors to the formation of goiter endemia. There was a high prevalence of thyromegaly in children with BA as compared with those with another disease and its high the incidence as man-made pollution increased particularly in the areas exposed to a combination of natural and technogenic factors as compared in relatively pure areas. The findings suggest that goiter transformation is a marker of ecological ill-being and an additional serious risk factor of the development and prolonged course of BA in predisposed children.

[Atopic disease in children: present-day concepts of pathogenesis and therapy]. / Atopicheskie zabolevaniia u detei: sovremennaia kontseptsiia patogeneza i terapiia.

A contemporary understanding of evolution mechanisms and of therapy related with allergic diseases in children is defined on the basis of published data and independent research. A concept predetermining the significance of atopy in pathogenesis of allergic pathologies is outlined; an essential role of environmental factors and a genetic contribution to the role promotion are pointed out. Issues pertaining to the onset of both early and late phases of the allergic response and of allergic inflammation are touched upon. Finally, modern approaches towards therapy of allergic diseases in children are described.

[Immunologic reactivity of children with allergic diseases during the measles vaccinal process]. / Immunologicheskaia reaktivnost' detei s allergicheskimi zabolevaniiami pri korevom vaktsinal'nom protsesse.

Children immunized with live measles vaccine, especially those immunized at the period of short-term remission and having had systemic or allergic reactions after the administration of the vaccine, have been found to develop more pronounced changes in the content of IgE. A high concentration of IgE is supposed to inhibit phasic changes in the content of IgM and IgG, which negatively affects the intensity of the formation of specific immunity.

[The vaccinal prevention of diphtheria and tetanus in children suffering from bronchial asthma and asthmatic bronchitis]. / Vaktsinoprofilaktika difterii i stolbniaka u detei, stradaiushchikh bronkhial'noi astmoi i astmaticheskim bronkhitom.

The course of the vaccinal process was studied in 69 children with bronchial asthma and asthmatic bronchitis after the injection of adsorbed diphtheria-tetanus (DT) toxoid with reduced antigen content. After immunization all these children were found to form protective levels of anti-diphtheritic and antitetanus antibodies irrespective of the severity and duration of the remission of the main disease prior to vaccination; at the same time no obstructive changes in bronchial ventilation were observed after immunization with adsorbed DT toxoid with reduced antigen content. The schemes of the preparatory medicinal treatment of patients at the period of vaccination are given with due regard for the duration of the remissions of bronchial asthma and asthmatic bronchitis.

[The adsorbed-DTP-m vaccination of children with allergically altered reactivity]. / AKDS-m vaktsinatsiia detei s allergicheski izmennoi reaktivnost'iu.

Immunization and booster immunization with adsorbed DPT-m vaccine was carried out, respectively, in 45 and 15 children with different severity of the course of an allergic disease, each child receiving simultaneously individually prescribed complex drug therapy. The postvaccinal period took a relatively favorable course. General and allergic reactions and complications observed after the injection of the preparation did not hinder the continuation of the course of immunization, while the appearance of neurological reactions provoked doubts on the expediency of the repeated injection of this preparation. A decrease in the content of diphtheria and tetanus toxoids in one immunization dose did not lead to the decreased synthesis of specific antibodies. The present investigation showed the possibility of using adsorbed DPT-m vaccine with reduced antigen content in cases of both the remission of an allergic disease and the subacute course of such disease.

[Mucous membrane of the jejunum in allergy to cereal protein]. / Slizistaia obolochka toshchei kishki pri allergii k belku zlakovykh.

Biopsies of the jejunum from 61 children, 6 months-4 years of age, including 35 with allergy to corn protein, 18 with celiac disease and 8 children without stomach and intestine pathology were studied. Biopsies were fixed in 10% formalin or in Carnois fixative, the sections were stained with hematoxylin and eosin, 0.5% toluidine blue (pH 0.5), and immunoperoxidase method was used for revealing IgA. The structure of the mucosa was not changed in the allergic patients, the content of the granulated and ungranulated labrocytes was increased, their number being decreased in the elimination diet. The number of plasma cells was diminished, and in only few of them IgA was found in children with severe alimentary malabsorption. A selective deficiency of IgA was diagnosed which determines the therapy of such children. Hyperregenerative atrophy of the mucous membrane and predominance of degranulated cells over undergranulated were noted in celiac disease.

[The immunotherapy of bronchial asthma with a multicomponent vaccine administered intranasally and orally]. / Immunoterapiia bronkhial'noi astmy polikomponentnoi vaktsinoi pri intranazal'no-oral'nom vvedenii.

Multicomponent vaccine prepared from opportunistic bacteria, when administered intranasally and orally to patients with bronchial asthma and chronic bronchitis, was well tolerated by the patients. Side effects induced by the vaccine in a few patients lasted for a short time and were mainly local. Immunotherapy with the vaccine led to a decrease in the severity of the course of the disease, as well as in the frequency and severity of exacerbations. In 26 out of 35 adult patients (74.3%) good and excellent effect was noted; during the observation of 20 sick children aged up to 3 years for a period of 1 year similar effect was noted in 60% of cases. Vaccinal therapy, in addition to its main effect, also contributed to a considerable drop in the morbidity rate of acute respiratory diseases among susceptible children.

[Glycosaminoglycans in leukocytes of children with bronchial asthma]. / Glikozaminoglikany leikotsitov pri bronkhial'noi astme u detei.

Content of hexuronic acids, hexoses and hexosamines was studied in lymphocytes and polymorphonuclear leukocytes of 56 children with bronchial asthma. The disease step-dependent alterations of the patterns studied were detected. Treatment of these children with bronchospasmolytic drug clenbuterol and with immunomodulator taktivine affected positively the bronchial asthma attack, which was followed by specific alterations in the carbohydrates content. Structural modifications of glycosaminoglycans in lymphocytes and phagocytes appear to be of importance for formation and development of allergic reactions in children with bronchial asthma.

[Lysosomal leukocyte glycosidases in childhood bronchial asthma]. / Lizosomnye glikozidazy leikotsitov pri bronkhial'noi astme u detei.

Activity of lysosomal glycosidases beta-galactosidase, N-acetyl-beta-D-galactosaminidase and N-acetyl-beta-D-glucosaminidase was studied in lymphocytes and neutrophils of children with bronchial asthma. Alterations of the enzymatic activity were found to depend considerably on the disease stage, form, severity, duration and on the sensitization efficiency. Activity of these enzymes was markedly decreased after glucocorticoid treatment while clenbuterol did not affect their activity. The status of leukocyte lysosomal glycosidases appears to be of importance for development of bronchial asthma in children.

[Correlations between lysosomal enzymes and cyclic nucleotides during allergies in children]. / Korreliatsionnye vzaimootnosheniia lizosomnykh fermentov i tsiklicheskikh nukleotidov pri allergicheskikh zabolevaniiakh u detei.

Correlation between activity of beta-galactosidase, N-acetyl-beta-D-glucosaminidase and content of cAMP and cGMP was studied in lymphocytes and polymorphonuclear leukocytes obtained from 20 children with atopic form of bronchial asthma and 9 patients with dermorespiratory syndrome. Activity of the lysosomal hydrolases studied correlated distinctly with the content of cyclic nucleotides in the leukocytes and lymphocytes of children with bronchial asthma and dermorespiratory syndrome. The most distinct relationship was found between the eosinophilia, the enzymatic activity and the cGMP content in lymphocytes and neutrophils under conditions of dermorespiratory syndrome. The data obtained suggest the dissimilarity of regulatory effects of cyclic nucleotides on functional activity of lysosomes in leukocytes of children with atopic form of bronchial asthma and dermorespiratory syndrome.

[The intracellular second messenger system and its regulatory effects in children with a bronchial asthma attack complicated by heart failure]. / Sistema vtorichnykh vnutrikletochnykh posrednikov i ee reguliarognye éffekty u detei v pristupnom periode bronkhial'noi astmy, oslozhnennoi serdechnoi nedostatochnost'iu.

Components of the intracellular mediators system: calmodulin in leukocytes, Ca2+ and cyclic nucleotides in leukocytes and blood plasma were studied in children with attack of bronchial asthma and heart failure. Alterations in content of these biologically active substances correlated with clinical manifestations of bronchial asthma: severity of the disease, duration of the attack, contractile activity of myocardium. Calmodulin, Ca2+ and cyclic nucleotides were demonstrated to be involved in development of the asthmatic attack. Alterations in the system calmodulin-Ca2+ were related to adaptation and contributed to realization of regulating effects responsible for a decrease of impairments in tissues.

[Use of vitamins in allergic illnesses in children]. / Primenenie vitaminov pri allergicheskikh zabolevaniiakh u detei.

Therapeutic efficacy of vitamins B6, P and E was studied in children with allergic diseases. Bronchial asthma and atopic dermatitis were treated more effectively if maximal doses of vitamin B6 were used. Quercetin was found to be useful for treatment of children with pollinosis in order to correct impairments in metabolism of lymphocyte membrane lipids. Only slight efficacy of vitamin E was detected in atopic dermatitis of children.

[Ebastine in the treatment of seasonal allergic rhinitis]. / Ebastin pri lechenii sezonnogo allergicheskogo rinita.

AIM: To test the efficiency and tolerance of the second generation antihistamine drug ebastin (kestine) in patients with seasonal allergic rhinitis (SAR). MATERIALS AND METHODS: Kestin was given for 3 weeks in doses 10 and 20 mg/day to 226 patients with SAR running for 6.8 +/- 6.1 years. SAR symptoms relief, subjective effects, side effects were studied. RESULTS: The total index of rhinitis symptoms diminished from 11.6 to 1.2 scores. Subjective response was registered in 82% of the patients, objective in 77%. Neither treatment aggravations nor serious side effects occurred. 2 patients had drowsiness, head aches, dizziness and discontinued treatment. CONCLUSION: Kestin is effective in SAR, had no serious side effects, is well tolerated.

[New way in dietotherapy of infants with food allergy]. / Novyi podkhod k dietoterapii detei s pishchevoi alergiei.

The authors followed up (in outpatient conditions) a total of fifty 1-to-9-mounth-old infants with the diagnosis of atopic dermatitis, disseminated form, of subacute course. The infants were followed up for 3-12 months, with 83% of the 113 examined patients 1-3 weeks after the beginning of treatment having shown clinical improvement of cutaneous inflammatory processes. Of the 172 infants subjected to immunological examination, in 100--the level of total IgE in blood serum was significantly elevated. These children also had elevated level of the specific IgE antibodies to cow's milk proteins. The outcomes of the carried out dietotherapy using mixture "Nanny" showed that this therapeutic product resulted in remission in the majority of the followed up infants suffering from allergy to cow's milk proteins.

[The absorption function of the small intestine and the effect on it of diet therapy in food allergy in children]. / Absorbtsionnaia funktsiia tonkoi kishki i vliianie na nee dietoterapii pri pishchevoi allergi u detei.

Small intestine absorption function was studied in 46 children with food allergy basing on the results of D-xylose test and estimating protein absorption by blood serum ovalbumin assay in circulating immune complexes. Decreased carbohydrate and increased protein absorption was recorded in the small intestine of the patients and the normalizing effect of the elimination diet on these changes was shown.