Bronchial asthma and microcirculatory disorders

Microcirculatory disorders in patients with bronchial asthma can develop in a wide range: from increased microfiltration of the fluid, protein output and the development of edema without visible changes in the ultrastructure of the pulmonary endothelium to the occurrence of immune vasculitis. In case of immune (allergic) inflammation of the endothelium of microvessels, one of the targets of the action of cytokines (FAT, interleukins, etc.), which in themselves worsen microcirculation, as well as the target of the action of anti-endothelial antibodies, immune lymphocytes and CEC. There is experimental evidence of IgE-mediated immune responses that contribute to the deposition of immune complexes in the vascular wall and the development of immune vasculitis. As shown now, the development of local vasculitis in the target organ is possible.

The possibility of eosinophilic microvasculitis in some patients with bronchial asthma is also confirmed by our data obtained at the Department of Hospital Therapy. Acad. N.V. Chernorutsky St. Petersburg State Medical University. Acad. I.P. Pavlova.

Based on the study of the cellular composition of bronchial swabs in 416 patients with bronchial asthma (BA), chronic bronchitis (CB) and in the state of pre-asthma (PA), we distinguished various variants of bronchial inflammation depending on the type of cells, the percentage of which in the bronchial flush exceeded the upper limits of normal . The state indicators obtained as a result of the examination of patients (two databases, a total of 687 comprehensive studies, including 239-241 indicators characterizing the clinical picture of the disease, biochemical, immunological, instrumental and other parameters) were processed using a new mathematical method: COMOD technology proposed by St. Petersburg employees Electrotechnical University T.L. Kachanova and B.F. Fomin (1992) and designed to process large amounts of data that differ in difficult to detect and non-linear relationships.

The capabilities of this system modeling method for the study of patients have been described by us previously. Using COMOD technology, on the basis of a set of statistically reliably related signs of the condition, which include immunological, biochemical parameters, genetic markers, signs of impaired PVD and microcirculation, a conceptual model of pulmonary microvascular vasculitis in patients with bronchial asthma with eosinophilic inflammation and eosinophilia of blood is built.

The significance of eosinophilic allergic inflammation is most clearly revealed by the example of a group of patients with bronchial asthma isolated by COMOD technology on the basis of the principle of dynamic change in the indicator “eosinophils of bronchial flushing” (ES): eosinophils appear in flushing in a minimal amount (1-3%). This immediately leads to a change in the sign of the relationship between the ES indicator and a number of reliably associated indicators that determine the severity of the disease compared with the sign of the connection that was with ES = 0; at the same time, bronchial patency significantly worsens and the severity of the disease increases. The phenomenon of a change in the sign of the statistical relationship after the appearance of eosinophils in bronchial flushing can be described in terms of the theory of self-organization (synergetics), which considers the behavior of nonlinear systems and, in particular, biological objects. Synergetics suggests that for complex systems, there are several alternative development paths. Almost all life processes in the body are chaotic (the so-called “dynamic chaos”), moreover, for normal functioning of physiological systems, moderate chaos is required, and too “strong” or too “weak” chaos is evidence of pathology. One of the reasons for the occurrence of too “strong” chaos in a nonlinear system may be the realization of the principle of “overgrowing” (or the principle of “amplification of fluctuations”), when the nonlinearity makes a small difference large, macroscopic in its consequences.

Small random fluctuations qualitatively change all the details of the ongoing processes, and sometimes the process of avalanche-like growth occurs in the so-called “blow up” mode, when the quantities under consideration change for at least part of the time according to the law of unlimited increase over a finite time. The mechanism of superfast development of processes is based on nonlinear positive feedback, which can lead to instability, buildup, and destruction of systems. In this way, for example, the rapid development of asthmatic status in patients with AD, as well as a number of other acute conditions, occurs. In other cases, when a parameter that is significant for the functioning of the system exceeds a certain critical value (in this case, this parameter is “ES” and critical ES = 1-3%), the system’s motion mode changes qualitatively, it falls into the attraction region of a new attractor (in in this case – eosinophils flushing) and begins to function at a different level of homeokinesis. Clinically, this level is manifested by a more severe course of AD. Until this time, until the ES indicator = 0, the system functioned in a different mode, not determined by eosinophils.

The increased content of eosinophils in bronchial flushing in the patients examined by us was most often combined with an increase in the number of neutrophilic leukocytes. Among the variants of eosinophilic inflammation, eosinophilic and eosinophilic-neutrophilic inflammation was detected with a frequency of 0.50-0.68 (depending on the initial database).

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