The Effect of Adaptation to Periodic Hypobaric Hypoxic Stimulation on Allergic Inflammation in Childhood Bronchial Asthma

The dissertation of T.V. Dmitrieva is devoted to the study of the influence of adaptation to periodic hypobaric hypoxic stimulation on allergic inflammation in children with bronchial asthma. The work encompasses a literature review on the role of allergic inflammation in the development of bronchial asthma in children, the leading mechanisms of this inflammation, changes in cytokines, as well as the effect of periodic hypobaric hypoxic stimulation on the body of a child suffering from bronchial asthma. The study includes a clinical characterization of patients, an analysis of risk factors, and the clinical features of the course of the disease.

The main focus is placed on the study of immunological indicators — levels of IL-4, IL-6, IgE, IgG1–IgG4 — in children with atopic bronchial asthma of prepubertal and pubertal age, before and after the performance of non-pharmacological therapy in a multi-place barochamber. The study was conducted at the Orenburg State Medical Academy at the Department of Pediatric Diseases and was aimed at clarifying the mechanism of the therapeutic effect of the method, determining the criteria for its effectiveness, and developing an algorithm for predicting the outcome of treatment.

Bronchial asthma is among the most prevalent diseases in modern society, and in recent years a trend toward an increase in the incidence of bronchial asthma and its more severe course has been observed worldwide, including in Russia (Sokolova T.S., Studenikin M.Ya., 1986; Vel'tishch Yu.E., Svyatkina O.B., 1995; Gavalov S.M., Kondyurina E.G., Elkina T.N., 1998; Pytskiy V.I., Adrianova N.V., Artomasova A.V., 1999; Balabolkin I.I., 1999; Chuchalin A.G., 2001; Weiss S.T. et al., 1992; Busse W.W., Calhoun W.E., Segwick J.D. et al., 1999). Modern medicine regards bronchial asthma as a chronic inflammatory disease of the respiratory tract regulated by various cellular elements and mediators (Chernyushenko E.F., 1981; Stefani D.V., Vel'tishch Yu.E., 1996). Signs of bronchial inflammation persist even during the asymptomatic period of the disease and are the result of changes in the immune system, with their severity correlating with the degree of disease severity. The insufficient study of many aspects of the pathogenesis makes this problem highly relevant (Balabolkin I.I., 1999).

Changes in the immune system and cytokine dysregulation play a significant role in maintaining the chronic inflammatory process and hypoxic state in bronchial asthma. Cytokines regulate the intensity and duration of the inflammatory and immune response (Mikhailova Z.M. et al., 1987; Kozlik O.V., Balabolkin I.I., Reutova V.S., 2000; Totolyan A.A., Freydlin I.S., 2000; Prosenkova E.V. et al., 2002; Blalok J.E., 1984; Callard R., Gearing A., 1994; Chung K.F., 1999). The study of cytokine and immunoglobulin levels provides information on the functional activity of various types of immunocompetent cells, the severity of the inflammatory process, and the prognosis of the disease. Assessment of immune indicator levels allows a new approach to studying the state of the immune system in clinical practice (Kul'berg A.Ya., 1986; Reznik I.B., 1997; Petrov V.I., Smolenov I.V., 1998; Daser A., Meissner N., HerzU., 1995).

Anti-relapse therapy of bronchial asthma in children is indicated even during the remission period. In recent years, non-pharmacological methods of treating bronchial asthma have been employed. One such method, recommended during the remission phase, is adaptation to periodic hypobaric hypoxic stimulation in a multi-place barochamber. Adaptation to periodic barochamber hypoxia not only increases the body's resistance to hypoxia itself but also enhances resistance to other damaging factors, that is, it possesses numerous cross-protective effects (Sergeeva K.M. et al., 1989; Vol'yanik M.N., 1993; Meerson F.Z., 1993; Tverdokhlib V.P., Meerson F.Z., 1994; Tin'kov A.N., 1999; Prokof'ev A.B., 2005).

In this connection, it was of great interest to study the effect of periodic hypoxic hyperbarotherapy on immunological indicators and allergic inflammation in children with bronchial asthma during the remission period.

Goal and objectives of the study. The main goal of the work is to clarify the mechanism of the therapeutic action of periodic hypobaric hypoxic stimulation (APGGS) on allergic inflammation in children with the atopic form of bronchial asthma and to determine the criteria for the effectiveness of the planned therapy.

In accordance with the stated goal, the following tasks were defined:

1. To study the levels of IL-4, IL-6, IgE, IgG1, IgG2, IgG3, IgG4 at varying degrees of severity of the atopic form of bronchial asthma in children.

2. To determine the dynamics of the studied immunological indicators under the influence of periodic hypoxic hyperbarotherapy.

3. To compare the clinical effectiveness of periodic hypoxic hyperbarotherapy with the dynamics of immunological indicators during treatment, identifying the most significant indicators for predicting the effectiveness of treatment of bronchial asthma in children.

Scientific novelty. New data have been obtained on the mechanism of the therapeutic action of APGGS on allergic inflammation in childhood bronchial asthma.

It has been established that during the remission of bronchial asthma in prepubertal and pubertal children, an imbalance of immunological indicators is observed, which is corrected by the APGGS method.

On the basis of the obtained data, criteria for predicting the effectiveness of hyperbarotherapy and differentiated indications for this method of treatment in children suffering from bronchial asthma have been developed.

Practical significance. As a result of the conducted studies, it has been proven that the treatment method based on adaptation to periodic hypoxic hyperbarotherapy is highly effective and can be used at the rehabilitation stage for children suffering from bronchial asthma.

Studies of immune indicators in children with bronchial asthma during remission revealed deviations in their levels compared with the normal levels of these indicators in blood serum. Differences in immunological disorders have been shown between boys and girls of different ages with varying degrees of disease severity.

The recommended method of non-pharmacological treatment in children suffering from bronchial asthma, possessing a number of direct and cross effects, allows for a reduction of the main clinical symptoms of the disease.

The presented results of examining children before and after barochamber treatment have allowed the conclusion that the adaptation process occurs through changes in immune system indicators, and the effectiveness of baroadaptation depends on the degree of their correction. An algorithm for predicting the effectiveness of treatment by the APGGS method in children suffering from bronchial asthma during the remission period has been developed.

Implementation of research results in practice. As a result of the study, in 2005 an information letter entitled "Hypoxic Hyperbarotherapy in the Treatment of Atopic Bronchial Asthma in Children" was published. The materials of the work have been used in the rehabilitation of prepubertal and pubertal children suffering from atopic bronchial asthma of varying severity and presenting an imbalance of immune indicators. The obtained data are applied in the barotherapy department of the rehabilitation center, in the educational process at the Department of Pediatric Diseases of Orenburg State Medical Academy, and in the clinical work of the regional children's center of allergology and clinical immunology.

Presentation of the work. The main provisions of the dissertation were presented and discussed at the Russian Scientific and Practical Conference "Current Issues of Allergology and Immunology in Pediatrics" (Orenburg, 2003); the Interregional Conference of Biochemists of the Urals, Western Siberia, and the Volga Region "Biochemistry: From the Study of Molecular Mechanisms — to Implementation in Clinical Practice and Production" (Orenburg, 2003); the XIII National Congress on Diseases of the Respiratory Organs (Moscow, 2003); the II All-Russian Congress on Pediatric Allergology (Moscow, 2003); the III Russian Congress "Modern Technologies in Pediatrics and Pediatric Surgery" (Moscow, 2004); the Jubilee Scientific Session Dedicated to the 60th Anniversary of the Orenburg Medical Academy (Orenburg, 2004); the X Congress of Pediatricians of Russia (Moscow, 2005); the IV Conference of Immunologists of the Urals (Ufa, 2005); the VI Interregional Scientific and Practical Conference of Physicians of the Volga-Ural Military District "Current Issues of Military and Practical Medicine" (Orenburg, 2005); the II Regional Scientific and Practical Conference of the Volga Federal District "Pediatrics and Surgery in the Volga Federal District" (Kazan, 2005); the XV National Congress on Diseases of the Respiratory Organs (Moscow, 2005).

Based on the dissertation materials, 14 scientific works have been published, including 2 journal articles.

Main provisions presented by the author for defense:

1. During the remission period in children suffering from bronchial asthma, there is an imbalance of immune system indicators.

2. The use of the method of adaptation to periodic hypobaric hypoxia in children suffering from bronchial asthma exerts a significant therapeutic effect and leads to a predominant normalization of immune status indicators.

3. The clinical effectiveness of adaptation to hypobaric barochamber hypoxia correlates with the degree of changes in immunological indicators.

Scope and structure of the dissertation. The dissertation is set out on 162 pages of typescript and consists of an introduction, a literature review, a chapter on materials and methods, three chapters of original results, conclusions, recommendations, and a bibliography. The work is illustrated with 16 tables, 45 figures, and 1 scheme. The reference list includes 223 sources, of which 150 are domestic and 73 are foreign. The work was carried out at the Orenburg State Medical Academy (rector — D.M.S., Professor S.A. Pavlovichev), at the Department of Pediatric Diseases (head of the department — D.M.S., Professor M.N. Vol'yanik).