Bronchial asthma – the most common lung disease, which is based on eosinophilic inflammation, but other cells also take part, and the exact significance of each type of cell and mediator in its pathogenesis is unknown. With bronchial asthma, a variety of inflammatory changes in the bronchi are noted. The international agreement “Global Strategy for Asthma Management”, adopted in 1993, defines bronchial asthma as “a chronic inflammatory disease of the respiratory tract, in which many cells play a role, including mast cells and eosinophils.” Only in patients with bronchial asthma, the intraepithelial presence of eosinophils and the presence of an increased amount of degranulated eosinophils under the basement membrane were found, however, a correlation was found between the content of degranulated eosinophils, damage to the bronchial epithelium and the severity of the course of bronchial asthma. Eosinophils in the contents of bronchoalveolar lavage persist in patients with bronchial asthma in the interictal period and a direct relationship was found between the level of eosinophils in lavage fluid and the severity of the course of bronchial asthma. The preservation of inflammatory changes in the bronchi in patients with bronchial asthma in the interictal period, which is manifested by an increased content of eosinophils and neutrophils in the lavage fluid, as well as a permanent state of increased bronchial reactivity, makes it possible for any external and internal agents that play the role of a trigger to mobilize these cells inflammation and cause exacerbation of the disease.
Damage to the epithelium by the “major protein” of eosinophils plays an important role in the development of nonspecific bronchial hyperreactivity (GBS) and bronchial asthma, which some authors even call “epithelial disease,” since bronchial epithelial cells secrete substances that can modulate the activity of brooch smooth muscles and secrete arachidonic derivatives acids, and also contain sensitive nerve endings, the irritation of which leads through the reflex mechanisms to the release of neuropeptides, in particular, neuro kin, substance P, playing an important role in the development of bronchial obstruction. The eosinophil’s “major core protein” as well as the eosinophilic cationic protein and eosinophilic neurotoxin cause epithelial damage, desquamation and destruction of ciliary cells, which is typical in bronchial asthma. The concentration of eosinophilic cationic protein in sputum and in peripheral blood correlates with the degree of bronchial obstruction. As a rule, there is a direct correlation between an increase in the number of eosinophils in the contents of bronchoalveolar lavage and in peripheral blood. The number of eosinophils in peripheral blood allows us to judge the general (systemic) allergization, and it is proposed to judge the severity of bronchial asthma and the severity of the exacerbation of the disease by the degree of eosinophilia in the blood. It was found that HGB correlates with an increase in the number of eosinophils in the peripheral blood even in individuals without clinical signs of bronchial asthma. Sometimes there are deviations from the usual correspondence between the number of eosinophils of peripheral blood and lavage fluid.
This can be explained by the existence of independent chemotactic factors acting in the capillaries of the great circle and in the alveoli.
Experimental models of bronchial obstructive syndrome in animals as well as inhalation provocations of various allergens in patients with bronchial asthma showed that it is possible to develop one or two phases of the pathological process: early asthmatic reaction, characterized by rapid bronchoconstriction with a maximum of 10-30 minutes after provocation and a gradual weakening over the next 2 hours, and a late asthmatic reaction that occurs 6-8 hours after provocation in 60% of patients with bronchial asthma, with a maximum of bronchoconst iktsii another 2-4 hours. If the mast cell is the main cell responsible for the development of the early asthmatic reaction, the late asthmatic reaction is associated with the involvement of various types of cells in the lungs, primarily eosinophils, and the occurrence of chronic inflammation in IgE-mediated reactions. The development of a late asthmatic reaction is accompanied by a transient decrease in the number of eosinophils in the peripheral blood with an increased content in bronchial swabs, which indicates the selective involvement of these cells from bronchial vessels and is accompanied by an increase in GBS. However, as it is now believed, in patients with chronic persistent course of bronchial asthma, the differences between early and late asthmatic reactions are not so pronounced and mast cells and their mediators are actively involved in the development of chronic inflammation.
In patients with late asthmatic reactions , the number of eosinophils does not just change, but their qualitative changes are determined: low density eosinophils (density less than 1.095 g / ml), which are more active, express more IgE receptors on their membrane and secrete more BAS, moreover, an increase in the number of active eosinophils correlates with the severity of the course of bronchial asthma found in the biopsy material of the bronchial mucosa, even in patients with mild bronchial asthma The number of active eosinophils, mast cells, and cells comprising tumor necrosis factor and cytokine, similar to their action with interleukin-1 and is a primary mediator of inflammation.
Some authors emphasize that eosinophil is a powerful effector cell, mainly in the late phase of an asthmatic reaction, manifested by allergic inflammation of the predominantly distal parts of the bronchi. It is possible that this is especially true for atonic bronchial asthma Attraction, activation and support of the long-term existence of eosinophils in the mucous and submucosal layers of the bronchial tree is caused by the action of many biologically active substances, among which interleuken 3 and 5, granulocyte-macrophage colony-stimulating factor and tumor necrosis factor are especially distinguished.
Currently, it is believed that one of the key points in the pathogenesis of bronchial asthma is the interaction of eosinophil and platelet aggregation factor (FAT). The fact is that eosinophils are cells that produce FAT and at the same time are the objects of its action: FAT causes activation and degranulation of eosinophils and causes their chemotaxis. It has been shown that FAT induces an increase in the expression of Fc receptors for IgC on unactivated eosinophils in patients with bronchial asthma, involving these cells in immune responses. FAT is considered as a common effector substance of anaphylaxis, it also induces platelet aggregation with the release of serotonin, histamine, 3 and 4 platelet factors, which leads not only to bronchospasm, but also to microcirculation disorders. FAT can directly increase the permeability of the microvasculature of the respiratory tract, which leads to the release of plasma, neutrophils, monocytes and eosinophils. Through all these mechanisms, FAT causes a state of bronchial hyperreactivity with respect to a wide range of specific and nonspecific stimuli and, as a modulator of inflammatory reactions, together with other inflammatory mediators, causes desensitization of adrenergic receptors in AD patients. The role of FAT as the only substance causing an increase in nonspecific bronchial hypersensitivity and hypersensitivity in healthy individuals is shown. With atopic bronchial asthma, the main producers of FAT are eosinophils and macrophages, with infection-dependent bronchial asthma neutrophils attach to these cells.
There is evidence of the effect of FAT on the proliferation of B-lymphocytes and the stimulation of IgE production: thus, FAT acts as a mediator of GNT. FAT has the action of an endogenous pulmonary vasodilator and is involved in maintaining a low level of vascular resistance in the pulmonary artery system, which may be associated with the rarity of high pressure in the pulmonary artery system in patients with chronic lung disease (unlike patients with primary pulmonary hypertension and recurrent small branch thromboembolism) pulmonary artery). On the other hand, in some patients with bronchial asthma, with the possible development of pulmonary eosinophilic microvasculitis, this protective vasodilating action is not enough, in any case, it has been shown that in a number of patients with bronchial asthma, as blood eosinophilia increases and the level of circulating immune complexes (CIC) increases, pulmonary artery. Eosinophils and the biologically active substances secreted by them are responsible for structural changes in the epithelium of the bronchi, basement membrane, mucous glands, smooth muscles of the bronchi and nerve endings, and FAT, in addition to the bronchoconstrictor effect and the effect on GBS, can increase the number of small vessels of the bronchial mucosa and cause its edema. In the literature, there are indications of a violation of microcirculation in patients with bronchial asthma, and violations of blood rheology correlate with the severity of bronchial obstruction. However, even in the early stages of the development of bronchial asthma and even in some patients with a state of pre-asthma, blood rheology disorders are detected, platelet and erythrocyte aggregation increases, and these changes increase in parallel with impaired bronchial patency. Scintigraphic studies conducted in patients with bronchial asthma showed disorders in capillary circulation: in many patients, the uneven distribution of the radiopharmaceutical in the arterial-capillary bed of the lungs was determined, sometimes focal circulatory disorders up to areas with complete shutdown of capillary blood flow.