Bronchial asthma is a disease that is characterized by periodically occurring attacks of suffocation or expiratory dyspnea caused by allergic reactions that occur in the tissues of the bronchial tree. The incidence of children with bronchial asthma in our country is 0.2 – 0.4%. More often, the disease begins in the first years of life (more than 50% of cases). In recent decades, there has been a tendency to a more severe course of the disease, the appearance of the first signs of it at an earlier age, and the increase in hormone-dependent forms of the disease. Separate deaths at the height of an asthmatic attack are described. In connection with the polymorphism of the clinical manifestations of bronchial asthma, many foreign scientists consider it as a syndrome. Domestic scientists (A.D. Ado, P.K. Bulatov, etc.) believe that bronchial asthma is an independent allergic disease.
Etiology of bronchial asthma
In the occurrence of bronchial asthma, in most cases exoallergens are important – substances that enter the body from the external environment and cause its sensitization. According to the classification of A. D. Ado and A. A. Polener (1963), allergens of infectious and non-infectious origin are distinguished. Accordingly, two forms of bronchial asthma are distinguished: infectious-allergic and non-infectious-allergic (allergic, atopic). With a combination of infectious and non-infectious factors, they speak of a mixed form of the disease.
Allergens of infectious origin include bacterial (hemolytic streptococcus, hemolytic staphylococcus, neisseria, E. coli, Proteus and their metabolic products), viral (influenza, parainfluenza, adenovirus, rhinovirus, etc.), fungal. To allergens of non-infectious origin – household (home, library dust, feather pillows), pollen (pollen of timothy flowers, fescue, team hedgehogs, ragweed, poplar fluff, etc.), epidermal (fluff, wool, dandruff, hair of various animals and humans) food (strawberries, chicken protein, chocolate, citrus fruits, etc.), medicinal (antibiotics, sulfonamides, acetylsalicylic acid, etc.), chemical (preservatives, washing powders, toxic chemicals, etc.), vaccines. Extremely adverse effects of smoking (active and passive).
Pathogenesis of bronchial asthma
An asthmatic attack is based on allergic reactions that unfold in the mucous membrane of the respiratory tract.
Bronchial asthma, and primarily non-infectious-allergic, proceeds predominantly as an immediate allergy. In the mechanism of development of allergic reactions of an immediate type, three stages are distinguished. In the immunological stage, in response to the initial exposure to the antigen (allergen), special allergic antibodies are formed – reagins (by the immunological nature they belong to the IgE class). The formation and accumulation of specific reagents is the essence of sensitization. There are no clinical signs of the disease at this time. Subsequently, in 15 – 25 minutes after repeated contact with the allergen, antigen is combined with antibodies fixed on basophils and mast cells in the bronchial mucosa. In the second stage – pathochemical (biochemical), under the influence of the antigen-antibody immune complex, the cell membranes of mast cells are damaged, their enzyme systems (proteases, complement, histidine decarboxylase,) are formed and biologically active substances are formed (“shock poisons”, mediators of an allergic reaction) – histamine, a slow-reacting substance of allergy (MRSA), serotonin, bradykinin, acetylcholine, etc. The third stage is pathophysiological. Allergic reaction mediators and products of incomplete proteolysis, as well as the direct action of the antigen – antibody immune complex on target cells lead to spasm of the muscles of the bronchi (in severe asthmatic attacks and asthmatic status – bronchial dyskinesia), swelling of the mucous membrane, hypersecretion of thick viscous sputum, which is significantly violates the ventilation function of the lungs and is clinically manifested in the form of an asthma attack. At the same time, the elastic resistance of the lungs increases, the aerodynamic resistance on the exhale increases several times in comparison with normal values. Gas exchange is sharply disrupted. All indicators of external respiration worsen: the residual volume (OO) increases, the vital capacity of the lungs (VC) decreases, the forced vital capacity of the lungs. (FVC), breath limit. Breathing becomes superficial, ineffective. Under the action of proteolytic enzymes and tissue thromboplastin released from mast cells, blood coagulation is enhanced, which leads to intravascular coagulation. From the side of the cardiovascular system, there is an overload of the right heart, stagnation of blood in the pulmonary circulation, increased blood pressure (vasospasm due to biologically active substances). The acid-base balance of the blood is disturbed, respiratory and metabolic acidosis develops. With an infectious-allergic form of bronchial asthma, the reactions of delayed hypersensitivity are of leading importance. In the mechanism of development, they are also distinguished by three stages. In the immunological stage, with the initial exposure to an allergen, sensitized T-lymphocytes appear in the body and accumulate (sensitization process). Upon repeated contact with the allergen, T-lymphocytes interact with it. The reaction unfolds 5 to 6 hours after the body meets the allergen, reaching a maximum after 24 to 48 hours. In the second stage, pathochemical, T-lymphocytes release biologically active substances – lymphokines (mediators of delayed hypersensitivity): transfer factors; chemotaxis; lympholysis; macrophage migration inhibiting factor; a factor that blocks blast formation and mitosis, etc. The pathophysiological stage is characterized by the development of allergic inflammation of the mucous membrane of the bronchial tree, accompanied by spasm (or dyskinesia) of the muscles of the bronchi, swelling of the tissues, hypersecretion of viscous mucus, which is clinically manifested in the form of an asthmatic attack. The ratio of immediate and delayed reactions in the pathogenesis of various forms of bronchial asthma determines the clinical features of the disease in children. Of great importance in the development of allergic processes in patients with bronchial asthma are congenital or acquired disorders of the barrier function of the mucous membrane of the respiratory tract. Any inflammatory diseases of the respiratory apparatus are accompanied by dysfunction of the ciliated epithelium, vasomotor disorders, which creates the conditions for the penetration of inhaled allergens into the body and the development of sensitization. A specific role is played by the characteristics of the antigen – the allergen. For the occurrence of hypersensitivity, a sufficient amount of antigen and its high allergenic activity are necessary. A number of allergens (pollen of some plants) have the so-called “permeability factor”, which ensures the active penetration of antigen through an intact mucous membrane. Inhibition of nonspecific protection factors (phagocytosis, complement, properdin, chemotaxis, etc.) exacerbates defects in the barrier function of the mucous membrane of the respiratory tract and leads to disruption of the destruction and elimination of antigen, which also contributes to the development of hypersensitivity reactions. The most important direction in the study of the pathogenesis of bronchial asthma is to elucidate the role and importance of the autoallergic mechanism. In addition, neurogenic and endocrine factors play an important role in the development of bronchial asthma, which in some cases can be of leading importance, relegating allergic manifestations to the background. Changes in the nervous system are multifaceted. Under the influence of allergic processes, the threshold of excitability of nerve structures in relation to non-allergic stimuli is significantly reduced. This explains the occurrence of attacks of pungent odors, changes in atmospheric pressure, air humidity, and solar radiation. On the basis of primary allergic mechanisms, pathological reflexes occur. Therefore, an asthma attack can develop in the absence of an allergen when exposed to a conditioned reflex stimulus. Under the influence of the flow of pathological impulses, the formation of a focus of stagnant excitation in the cerebral cortex (pathological dominant) is possible, which supports dyskinetic phenomena in the bronchi and causes a protracted course of an asthmatic attack. Importance is also given to hereditary or acquired blockade of p2-adrenergic receptors (Szentivanyi, 1968). B2-adrenergic receptors are an enzyme adenylcyclase, which provides the conversion of ATP to cAMP. Under physiological conditions, cAMP reduces the tone of the smooth muscles of the bronchi, inhibits the release of histamine from mast cells, and promotes the reabsorption of biologically active substances by mast cells. With the blockade of B2-adrenergic receptors, the tone of the muscles of the bronchi increases significantly, which creates conditions for bronchospasm. But, as A. D. Ado (1976) points out, “one should not forget that any reflexes die out if they are not periodically reinforced by the initial stimulus, which in our case is an allergic reaction. Thus, it can hardly be assumed that even in the later stages of the disease, the role of the allergic reaction is completely reduced to zero. ” Changes in the endocrine system at the onset of the disease are expressed in an increase in the level of glucocorticosteroids, adrenaline, norepinephrine in the blood at the height of an asthmatic attack, which, however, is ineffective due to the blockade of B2-adrenergic receptors and a decrease in the sensitivity of the bronchial receptor apparatus to catecholamines. In the future, adrenal function is inhibited, their glucocorticoid activity decreases under the influence of allergens (steroidogenesis disturbance), which is associated with alternative processes in the tissues of the adrenal glands. In addition, the ability of blood plasma proteins (transcortin) to bind cortisol increases, and the sensitivity of tissues to it decreases (V. I. Pytsky, 1975). A certain role in the development of bronchial asthma is played by a hereditary predisposition to allergic diseases, which is manifested in the ability to enhanced IgE synthesis (5-15 times higher than normal), a decrease in the barrier function of the mucous membranes, in particular the bronchial receptor apparatus, and a decrease in blood histamine kinemia (blood plasma ability bind histamine), etc. Great attention is drawn to the role of prostaglandins in the mechanism of development of an asthmatic attack. It was found that prostaglandin E1 causes relaxation of the smooth muscles of the bronchi (enhances the formation of cAMP), and prostaglandin F, on the contrary, causes its spasm. Recently, the role and importance of the kinin system in the development of bronchial asthma in children has been studied. In addition, with bronchial asthma, a violation of the exchange of vitamins, amino acids, electrolytes is detected. Thus, the pathogenesis of bronchial asthma is extremely complex, multifaceted and has not yet been fully studied.