Clinical Features and Indicators of Secretory Immunity in Children with Bronchial Asthma

The dissertation is devoted to the study of clinical features and indicators of secretory immunity in saliva in children with bronchial asthma residing in the cities of the Southern Urals. The research focuses on the assessment of non-invasive markers of local immunity, including sIgA, IgE, complement components, cytokines, and lactoferrin, with the aim of refining diagnostic criteria for mild bronchial asthma in children. Special attention is given to the role of housing ecological factors in the formation of secretory immunity dysbalance.

In the work, a comprehensive analysis of secretory immunity indicators in saliva in children with bronchial asthma and a control group was conducted, a correlational relationship of these indicators with external respiratory function was established, and a discriminant analysis of diagnostic criteria was developed. The obtained results allow secretory immunity indicators in saliva to be regarded as a potential tool for non-invasive immunological screening in population studies in children.

The relevance of studying bronchial asthma in children is determined by the widespread prevalence of the disease, its frequent clinical manifestation in childhood, the significant role of immunologically mediated mechanisms in this age group, the insufficient study of topical pathogenetic mechanisms of immune origin, and the underdiagnosis of this disease in children. It is known that the diagnostic criteria for mild-grade bronchial asthma are imprecise; therefore, there is a need to identify specific diagnostic laboratory and functional indicators [14,55, 56, 57, 70, 91, 93, 159].

Certain contradictions exist in the study of the pathogenesis of bronchial asthma. Existing approaches to analyzing the problem are based on the study of systemic immune disorders [5, 19, 23, 42,44, 46, 55, 97, 120, 122, 124, 133, 140, 141, 145, 147, 148, 249], whereas considerably less attention from researchers has been devoted to the characteristics of local immunity in bronchial asthma. At the same time, pathogenetically significant events occur precisely at the topical level and are associated with inflammatory changes in the mucous membranes of the respiratory tract and the predominant involvement of bronchus-associated lymphoid tissue (BALT) elements, while changes in immunological blood indicators are secondary [25, 70, 98, 147]. Furthermore, the modern arsenal of pharmaceutical preparations for the treatment of bronchial asthma and their dosage forms (inhalers, solutions for nebulization) are also primarily directed at eliminating the local inflammatory response, which makes it logical that in the assessment of the immunological efficacy of topical-action drugs, greater attention should be paid not to blood immunological indicators but to markers of BALT function [1, 2, 4, 33, 60, 76, 88, 105, 111, 134, 138, 168, 172].

In the opinion of several authors [14,147], it remains difficult to determine to what extent the increase in cytokine concentrations and other molecular products of the peripheral blood immune system in patients with bronchial asthma may reflect the development and severity of the inflammatory process in the airways; rather, these changes appear to be a consequence of local pathological processes. An optimal approach to studying the problem of bronchial asthma, in the opinion of many specialists, is the use of non-invasive methods for assessing mucosal immunity indicators and inflammatory factors in lavage fluid, sputum, saliva, and exhaled air condensate [1, 2, 88, 95, 138, 156, 163, 164, 169, 192, 193, 219, 260, 265].

The diagnostic use of saliva is attractive not only because of the non-invasive method of obtaining the test fluid but also because of the high sensitivity of immunological indicators to the effects of various stressors, accurately reflecting the function of the neuro-immune-endocrine complex, the dysregulation of which is of fundamental importance in bronchial asthma [51, 104, 138, 162, 170, 186, 189, 211, 214].

The systemic organization of local immunity allows, to a certain extent, the extrapolation of data obtained from the study of local immunity in any compartment of the system [160]. Despite this, only a few clinical studies devoted to salivary cytokine levels have been conducted, and these are related to pathology of the oral mucosa [1, 2, 86]. Most researchers limit their analysis to the content of secretory immunoglobulin A [101, 107, 219]. The ratio and content of other biologically active substances, cytokines, and other components in saliva remain a less-studied issue.

Many researchers have demonstrated the high informativeness and substantiated the prospectiveness of studying secretory immunity for the purposes of ecological health monitoring of different population groups [4, 30, 86, 91, 92, 111, 118, 119, 138, 164]. Conducting such studies in children is associated with the fact that the adverse effects of the external environment on immunity are particularly pronounced at the early stages of postnatal ontogeny due to the age-related immaturity of tissue barriers and the insufficient maturity of protective immune mechanisms, which makes the task of developing comprehensive reference values for local immunity highly relevant.

Research objective: To determine the clinic-immunological features and additional criteria for early diagnosis of mild bronchial asthma in children residing in large and small cities, based on a comprehensive analysis of secretory immunity indicators in saliva.

Research tasks:

1. To analyze the clinical features of mild bronchial asthma in children residing in large and small cities of the Southern Urals.

2. To determine a comprehensive set of secretory immunity indicators in saliva in children of the control group and those with bronchial asthma.

3. To provide a comparative assessment of secretory immunity indicators in saliva in children with bronchial asthma and the control group depending on living conditions.

4. To identify intra- and inter-system correlational relationships between parameters of the secretory immunity system in saliva and indicators of external respiratory function (ERF).

5. To determine, using discriminant analysis, the most informative diagnostic markers of mild bronchial asthma in children.

Scientific novelty:

The features of the clinical course and secretory immunity indicators in saliva of children with mild bronchial asthma have been determined. For the first time, it has been proven that children with mild bronchial asthma during remission are characterized by a dysbalance of the secretory immunity system and the cytokine profile of saliva, marked by elevated salivary levels of IgE, IL-4, and pro-inflammatory factors IL-8 and CH50, as well as alterations in intra-system correlational relationships.

Ecologically determined features of secretory immunity in children of the control group and those with bronchial asthma have been identified.

For the first time, correlational relationships between components of secretory immunity in saliva and the diurnal variability of peak expiratory flow (PEF), as well as other ERF indicators in children with bronchial asthma, have been established.

Practical significance:

The possibility of using secretory immunity indicators in saliva as a non-invasive method of immunological screening in population studies in children of different ages has been demonstrated. Reference values for an extensive complex of secretory immunity indicators in children have been determined, and the influence of environmental factors on their levels has been shown.

The informative mathematical model developed using discriminant analysis makes it possible to mathematically predict bronchial asthma in a child with a probability of 83%, based on the consideration of anamnestic data, assessment of functional respiratory indicators, and the levels of inflammatory mediators in saliva (IL-8 and CH50).

Implementation of research results in practice:

The research results have been implemented in population studies of children in the Southern Urals; in the work of the children's allergological department of City Clinical Hospital No. 1, and children's polyclinics in Chelyabinsk and Magnitogorsk; they are addressed during the educational process in the teaching of diseases of the respiratory organs and immunopathology at the departments of immunology and allergology, and children's diseases No. 1 at Chelyabinsk State Medical Academy; and have been recommended for use as additional criteria for assessing immune status by the Children's Scientific and Practical Pulmonological Center of the Ministry of Health of the Russian Federation.

Main provisions of the dissertation for defense:

1. Children with bronchial asthma are characterized by changes in the secretory immunity system and a dysbalance of salivary cytokines.

2. Changes in secretory immunity in saliva substantially depend on ecological factors of housing (presence of insect and mold allergens, passive smoking).

3. Parameters of secretory immunity in saliva (sIgA, IgE, pro-inflammatory cytokines) correlate with the diurnal variability of peak expiratory flow and other ERF indicators in children with bronchial asthma.

4. Secretory immunity indicators in saliva can be used as a non-invasive method of immunological screening in population studies in children of different ages.

Dissertation material verification:

Thirteen papers on the dissertation topic have been published, including four in central press.

The main provisions of the dissertation work have been reported at the All-Russian Conference "Current Issues of Diseases of the Respiratory Organs in Children" (Krasnoyarsk, 2004), the IV Congress of Pulmonologists of the Ural Federal District "Current Problems of Pulmonology in the Urals" (Chelyabinsk, 2004), the X Congress of Pediatricians of Russia "Ways to Improve the Effectiveness of Medical Care for Children" (Moscow, 2005), the III All-Russian Scientific and Practical Conference "Methodological and Medical-Psychological Aspects of Health and a Healthy Lifestyle" (Smolensk, 2005), the III Final Scientific and Practical Conference of Young Scientists of Chelyabinsk State Medical Academy (Chelyabinsk, 2005), the IV Russian Congress "Modern Technologies in Pediatrics and Pediatric Surgery" (Moscow, 2005), and the All-Russian Scientific and Practical Conference "Current Problems of Pediatric and Adolescent Pulmonology" (Chelyabinsk, 2006). The work was awarded a special prize at the All-Russian Young Scientists' Competition in Pediatrics (Moscow, 2005).

Structure and volume of the dissertation: The dissertation is set out on 191 pages of typescript and consists of an introduction, a literature review, a description of the groups of examined children and the methods used, five chapters of original research results, a conclusion, findings, practical recommendations, and a reference list. The work is illustrated with 34 tables and 22 figures. The reference list contains 265 sources, of which 164 are by domestic and 101 by foreign authors.