Clinicopathogenetic Characteristics of Chronic Bronchoobstructive Diseases in Children

The dissertation by I.N. Gaimolenko is devoted to the clinicopathogenetic characteristics of chronic bronchoobstructive diseases in children — one of the leading problems of pulmonology and pediatrics. The research substantiates the necessity of clarifying the terminology and grouping of chronic bronchoobstructive diseases in childhood, taking into account the absence of a unified approach to their classification and diagnosis. The prevalence of bronchial asthma symptoms among children of the city of Chita was studied using the international ISAAC program, the clinical-functional features of the course of chronic bronchoobstructive diseases depending on the nature of the inflammatory process were analyzed, and pathogenetic mechanisms associated with disorders of the immune system and the hemostasis system were identified. The results of the research are aimed at the development of new diagnostic criteria of disease severity and pathogenetically based approaches to treatment and rehabilitation of children, including immunomodulating therapy, laser blood irradiation, and educational programs for parents.

Relevance.

To date, among bronchopulmonary pathology in children, a significant proportion is occupied by recurrent and chronic diseases of the respiratory system. The structure of chronic bronchopulmonary pathology is very diverse — these are hereditary and acquired, infectious and allergic diseases, as well as congenital anomalies and developmental defects. It is known that chronic obstructive pathology of the lungs, beginning in childhood, often continues into adulthood and is one of the leading causes of the number of days of disability and invalidism. Chronic bronchoobstructive diseases occupy the fourth place among the causes of death in adults [195, 317].

The structure of diseases of the bronchi and lungs in children accompanied by an obstructive syndrome is sufficiently diverse. Morphofunctional features of the bronchopulmonary system in children predispose to the development of obstruction against the background of diseases of diverse etiology. The most common bronchoobstructive allergic disease in children is bronchial asthma, which is increasingly diagnosed at an early age. Studying its prevalence in specific eco-geographical conditions presents an especially urgent task. However, there exists a group of obstructive lung diseases of non-allergic etiology, the differential diagnosis of which is an important problem determining the tactics and strategy of treatment. Despite a sufficient number of works devoted to this problem, there is no clarity in the definition of chronic bronchoobstructive diseases in children, in the methods of diagnosing pathogenetic mechanisms, and in the approaches to treatment.

According to modern concepts, chronic obstructive pulmonary disease (COPD) is a collective concept that unites a group of chronic diseases of the respiratory system. The criterion by which the group of COPD in adults is formed is slowly progressive irreversible bronchial obstruction with increasing manifestations of respiratory insufficiency [309]. However, to this day there is no consensus in the world as to which diseases should be included in this group. In Russia, COPD in adults unites chronic obstructive bronchitis, emphysema of the lungs, and severe bronchial asthma. In the United States and Great Britain, the concept of "chronic obstructive pulmonary diseases" also includes cystic fibrosis, obliterative bronchiolitis, and bronchiectatic disease. In recent years, a view has become established in therapeutic practice that chronic obstructive pulmonary disease is a separate nosological form characterized by the presence of a chronic progressive inflammatory process of the airways and lung parenchyma regardless of the degree of severity [195]. In pediatrics, there is no consensus on the grouping of chronic bronchoobstructive diseases. This is associated with the features of the child's organism and the difficulties of predicting the course of the disease in children. Among chronic lung diseases in children, the most common are bronchial asthma and chronic pneumonia (primary or secondary). However, common risk factors for the formation of chronic lung pathology are indicated both in children and in adults. Diseases are formed against the background of hereditary and genetic defects. The main provocateurs of the realization of the disease are: active and passive smoking, contamination of inhaled air, occupational hazards in adults, and the infectious factor in children. A significant share of the causes of the formation of chronic lung pathology in children is occupied by congenital developmental anomalies, aspiration syndrome, and bronchopulmonary dysplasias. Thus, the uncertainty of the concept and the absence of a clear grouping of chronic bronchoobstructive diseases in children determine the relevance and necessity of studying this problem.

In connection with terminological uncertainty, there are no reliable and accurate data on the prevalence of COPD. In the 1990s, national and international standards began to be created on this problem. In 1999, in Russia, the Federal Program "Chronic Obstructive Lung Diseases" was created, which states that, based on calculations using epidemiological markers, hypothetically about 11 million patients have COPD. However, according to official statistics, their number is approximately 1 million. Diagnosis of the disease at late stages, the imperfection of diagnosis and treatment in childhood, is the main cause of high mortality among patients with COPD. This confirms the socio-economic significance of chronic bronchoobstructive diseases both in children and in adults.

Bronchial asthma is the most common chronic obstructive disease in children. Its mild forms often run under the guise of recurrent obstructive bronchitis. The true prevalence of bronchial asthma does not correspond to official statistics data. This leads to late diagnosis, an increase in the severity of the course, irreversibility, and ineffectiveness of traditional therapy. Studying the prevalence of bronchial asthma in children in accordance with the International Study of Asthma and Allergies in Children (ISAAC) program allows for early diagnosis of mild forms of the disease, timely prescription of basic therapy, and prevention of disease progression.

Regardless of the cause of the development of chronic lung pathology in children, the consequences are considerable for the child's organism. Damage to one of the life-support systems leads to a constant intoxication syndrome, hypoxia, and changes in the immune system and hemostasis system. The immune system is one of the most important mechanisms of organism adaptation and a powerful factor directed toward preserving antigenic homeostasis. Any chronic disease is accompanied by various variants of disorders in the immune system. Chronic lung diseases are one of the causes of the formation of secondary immunodeficiency states in children and adults.

The traditional assessment of the immunogram by comparing absolute values of healthy and sick children reveals diverse disorders in the system of cellular and humoral immunity, intercellular relationships. However, the existence of fluctuations in the identified parameters depending on the time, age, and influence of external factors makes this method of assessment insufficiently informative in clinical practice. "Since all elements of the immune system are interconnected, functional changes more often manifest as a change in the direction and degree of coupling of individual indicators rather than in a change in their absolute values" [290]. This testifies to immune imbalance, the diagnosis of which is carried out by methods of calculating various indices.

The leading role of immunological mechanisms in the development of any type of inflammation at the present time is beyond doubt. The chronic course of the disease is to a significant extent conditioned by disorders in the functioning of the immune system of the organism. It has been proven that in the main pathological processes the immune system and the hemostasis system function together, linked by numerous common mechanisms of the realization of their functions through formed elements of blood and humoral factors. These two systems are united by a common task — the preservation of homeostasis of the internal environment of the organism. The fine regulation of these numerous cooperation schemes is ensured by lymphocytes, which, through the production of lymphokines, regulate cellular and humoral mechanisms of hemostasis and immunity [290, 149]. Therefore, establishing the role of immunological disorders in interrelation with changes in the blood coagulation system in the development of chronic obstructive diseases of the lungs in children has important theoretical and practical significance.

Effective programs for the treatment of chronic bronchoobstructive pathology in adults and children have been developed. However, their influence on certain pathogenetic mechanisms of impairment of immunity and hemostasis is unknown. Traditional therapy is not always effective in cases of severe disease course, which requires the development of new methods for diagnosing pathogenetic disorders and treating patients, including pathogenetically justified methods of medication and non-medication therapy. Given the prolonged course of the disease, which requires mutual understanding between the child's parents and the physician in observing long-term treatment programs, an important stage of comprehensive rehabilitative therapy is the education of parents. Effective use and implementation of teaching methods in Asthma Schools will allow achieving better treatment results and improving the quality of life of sick children.

Objective: on the basis of a comprehensive study of the prevalence, clinical-functional characteristics, changes in the immune system in interrelation with disorders of the blood coagulation system, to develop new approaches to the diagnosis of pathogenetic disorders, the severity of the disease course, and pathogenetically based therapy of chronic bronchoobstructive diseases in children.

Tasks:

1. To study the prevalence of bronchial asthma symptoms in children of the city of Chita.

2. To study the clinical-functional features of the course of chronic bronchoobstructive diseases in children depending on the nature of the inflammatory process.

3. To determine the pathogenic significance of impairment of cellular and humoral immunity in children with chronic bronchoobstructive diseases of various etiologies.

4. To conduct a comprehensive study of the immune system, cytokines, and hemostasis in children with chronic bronchoobstructive diseases.

5. To study the influence of immunomodulating therapy, laser blood irradiation on the clinical picture of the disease, indicators of immunity and hemostasis in comparison with traditional methods of treatment.

6. To develop and evaluate the effectiveness of medical-educational programs for parents of sick children in conditions of an Asthma School.

Propositions to be defended:

1. The prevalence of bronchial asthma symptoms (wheezing, nocturnal dry cough, decreased tolerance of physical exertion over the last 12 months) in children of the city of Chita is 8.8%. In two-thirds of children, symptoms of mild bronchial asthma predominate. Screening by peak flowmetry with physical exertion makes it possible to identify a risk group of children with bronchial hyperresponsiveness.

2. A comparative characterization of risk factors, the clinical picture, and data of instrumental and functional methods of investigation of the cardiorespiratory system in patients with chronic bronchoobstructive pathology reveals features of the course of diseases of allergic and infectious origin. Differential diagnosis of the nature of the inflammatory process in the bronchopulmonary system and the causes of its formation determine the tactics of basic therapy and the prognosis of the disease.

3. Imbalance of cellular and humoral immunity is a link in the pathogenesis of chronic lung diseases in children. In interrelation with immunological disorders, a hypercoagulable syndrome was revealed, accompanied by increased expression of tissue factor, an increase in the concentration of pro-inflammatory and anti-inflammatory cytokines, and a decrease in lymphocyte-platelet adhesion.

4. The use of immunomodulators, laser blood irradiation in complex with traditional therapy contributes to the normalization of the main parameters of immunity, the level of cytokines, and the blood coagulation system against the background of a positive clinical effect. Medical-educational programs for training parents and patients in the Asthma School are an effective method of rehabilitative therapy, allowing improvement of the quality of life of children with bronchial asthma.

Scientific novelty. For the first time in the city of Chita, the prevalence of bronchial asthma symptoms was studied in accordance with the International Study of Asthma and Allergies in Children (ISAAC) program. A new method for the diagnosis of bronchial hyperresponsiveness by peak flowmetry during physical exertion was proposed, aimed at identifying children at risk group for the development of bronchial asthma.

A comparative clinical-instrumental characterization of chronic bronchoobstructive diseases in children depending on the genesis of the disease was conducted, and a differential diagnostic algorithm was proposed. A collective group of chronic bronchoobstructive diseases in children was determined, which included bronchial asthma, chronic inflammatory diseases of the lungs manifesting as primary or secondary bronchiectasis and/or deformative bronchitis. Objective criteria for the assessment of immunity by relative indices reflecting the imbalance of the immune system and the degree of severity of the disease course were proposed (the index of allergic inflammation, the ratio of B-lymphocytes and the level of immunoglobulins).

A comprehensive study of the immune system, cytokine levels, and hemostasis made it possible to establish that in severe cases of chronic bronchoobstructive diseases in children, there is suppression of cellular and depression of humoral immunity, a decrease in the number of lymphocytes capable of adhering to platelets. In chronic bronchoobstructive pathology in children, the content of the main classes of cytokines increases, and indices characterizing the ratio of pro-inflammatory cytokines to the anti-inflammatory cytokine IL-4 increase.

In a significant proportion of sick children, a chronic form of DIC syndrome develops, accompanied by increased expression of tissue factor and a decrease in the hemocoagulation index, characterizing the ratio of APTT to total euglobulin fibrinolysis.

Mathematical analysis (correlation and multiple regression) was applied in the assessment of pathogenetic correlations and the severity of the disease course, on the basis of which clinical and instrumental-laboratory diagnostic criteria of the severity of chronic bronchoobstructive diseases in children were identified.

The use of vilon in children with chronic diseases of the lungs results in improvement of the parameters of cellular and humoral immunity and normalization of the number of lymphocyte-platelet coaggregates. The criterion of successful therapy is a more rapid decrease in the concentration of the studied cytokines and the restoration of equilibrium between pro- and anti-inflammatory cytokines. During treatment with vilon, the expression of tissue factor is inhibited and the hemocoagulation index is normalized. Laser blood irradiation contributes to the normalization of coagulogram parameters and lymphocyte-platelet adhesion in children with severe forms of chronic diseases of the lungs.

Training parents in the Asthma School according to the developed educational program has a positive effect and improves the quality of life of children with bronchial asthma.

Practical value. Conducting questionnaire surveys of children according to the ISAAC program with screening control of peak flowmetry during physical exertion makes it possible to identify a risk group of children threatened by the development of bronchial asthma. Dispensary observation of this group of children contributes to early diagnosis of mild forms of the disease and prevents disease progression.

The use of a differential diagnostic algorithm for chronic obstructive diseases of the lungs in children contributes to qualitative diagnosis, the appointment of timely and correct basic therapy, which improves the results of treatment and the prognosis of the disease.

For a more reliable assessment of the immune status of sick children, in practical activity, it is necessary to use relative coefficients reflecting the imbalance in the immune and blood coagulation systems — relative production of immunoglobulins, the number of B-lymphocytes synthesizing a conditional unit of immunoglobulins, the index of allergic inflammation, the ratio of the main pro-inflammatory cytokines to the anti-inflammatory cytokine IL-4, lymphocyte-platelet adhesion, expression of tissue factor, hemocoagulation index.

Diagnostic criteria of the severity of the course of chronic bronchoobstructive diseases in children are a complex of clinical and laboratory-instrumental data, which makes it possible to assess the degree of severity of the disease and conduct adequate therapy.

It is proposed to use the immunomodulator vilon in complex treatment of children with chronic diseases of the lungs. Restoration of the parameters of lymphocyte-platelet adhesion, expression of tissue factor by monocytes, as well as the proposed immunoregulatory and coagulation indices, is an objective criterion of successful therapy.

As non-medication therapy in children with severe forms of diseases of the lungs, the use of laser blood irradiation is recommended, which improves the clinical condition of children and normalizes the parameters of the coagulogram and the functional activity of lymphocytes.

The effectiveness of training parents of sick children in the Asthma School has been proven. The educational program contributes to a decrease in the number of disease exacerbations due to a correctly chosen plan and method of treatment, the use of additional methods of self-monitoring. Complex rehabilitative therapy contributes to improvement of the quality of life of children with bronchial asthma.

Implementation. The results of the work were introduced into the treatment process of the pulmonology department of the Oblast Clinical Children's Hospital. Methods for diagnosing pathogenetic disorders and treating chronic bronchoobstructive diseases in children were introduced into the clinic. The application of immunomodulating therapy and laser blood irradiation is widely used. Effective work of the Asthma School according to the proposed plan is carried out in the Oblast Therapeutic and Consultative Center for Children. The results of the work were introduced into the educational process at the departments of normal physiology with a course of clinical physiology, pathological physiology, and the department of pediatrics of the Chita State Medical Academy.

Dissertation defense. The materials of the dissertation were reported at the All-Russian Scientific and Practical Conference "Allergic Diseases in Children," Moscow, 1998; at a Scientific and Practical Conference dedicated to the 5th anniversary of the formation of the Institute of Pediatrics of the Chita Oblast, Chita, 2000; at the All-Russian Scientific Conference with International Participation "Problems of Health Preservation," Krasnoyarsk, 2001; at the IX Congress of Pediatricians of Russia, Moscow, 2001; at a meeting of the regional division of the Union of Pediatricians of Russia, Chita, 2002; at the Fifth Far Eastern Regional Conference with All-Russian Participation "New Medical Technologies in the Far East," Khabarovsk, 2002; at the 11th and 12th National Congresses on Diseases of the Respiratory Organs, Moscow, 2001, 2002; at the All-Russian Conference "Infocom-Municative and Computing Technologies and Systems," Ulan-Ude, 2003.

Structure and volume of the dissertation. The dissertation is presented on 297 pages of typed text, contains 60 tables, 13 figures, 4 diagrams, an algorithm, and appendices. The list of cited literature includes 456 items, of which 340 are domestic and 176 are foreign.