Stepwise therapy of bronchial asthma. Treatment of bronchial asthma - principles of therapy. "aspirin" bronchial asthma

Sinusoidal cells (endothelial cells, Kupffer cells, stellate and pit cells), together with the section of hepatocytes facing the lumen of the sinusoid, form a functional and histological unit.

endothelial cells line the sinusoids and contain fenestrae, forming a stepped barrier between the sinusoid and the space of Disse. Kupffer cells are attached to the endothelium.

stellate cells liver are located in the space of Disse between hepatocytes and endothelial cells. Disse space contains tissue fluid that flows further into the lymphatic vessels of the portal zones. With an increase in sinusoidal pressure, lymph production in the space of Disse increases, which plays a role in the formation of ascites in violation of the venous outflow from the liver.

The Kupffer cell contains specific membrane receptors for ligands, including the immunoglobulin Fc fragment and the complement C3b component, which play an important role in antigen presentation.

Kupffer cells are activated during generalized infections or injuries. They specifically take up endotoxin and in response produce a number of factors, such as tumor necrosis factor, interleukins, collagenase, and lysosomal hydrolases. These factors increase the feeling of discomfort and malaise. The toxic effect of endotoxin, therefore, is due to the secretion products of Kupffer cells, since it is non-toxic in itself.

The Kupffer cell also secretes arachidonic acid metabolites, including prostaglandins.

The Kupffer cell has specific membrane receptors for insulin, glucagon, and lipoproteins. The carbohydrate receptor for N-acetylglycosamine, mannose, and galactose may mediate the pinocytosis of some glycoproteins, especially lysosomal hydrolases. In addition, it mediates the uptake of immune complexes containing IgM.

In the fetal liver, Kupffer cells perform an erythroblastoid function. The recognition and rate of endocytosis by Kupffer cells depend on opsonins, plasma fibronectin, immunoglobulins, and tuftsin, a natural immunomodulatory peptide. These "liver sieves" filter macromolecules of various sizes. Large, triglyceride-saturated chylomicrons do not pass through them, and smaller, triglyceride-poor, but cholesterol- and retinol-saturated residues can penetrate the space of Disse. Endothelial cells vary somewhat depending on their location in the lobule. Scanning electron microscopy shows that the number of fenestrae can decrease significantly with the formation of a basement membrane; these changes are especially pronounced in zone 3 in patients with alcoholism.

Sinusoidal endothelial cells actively remove macromolecules and small particles from the circulation using receptor-mediated endocytosis. They carry surface receptors for hyaluronic acid (the main polysaccharide component of connective tissue), chondroitin sulfate, and a glycoprotein containing mannose at the end, as well as type II and III receptors for FcIgG fragments and a receptor for a lipopolysaccharide-binding protein. Endothelial cells perform a cleansing function, removing tissue-damaging enzymes and pathogenic factors (including microorganisms). In addition, they cleanse the blood of destroyed collagen and bind and absorb lipoproteins.

stellate cells of the liver(fat-storing cells, lipocytes, Ito cells). These cells are located in the subendothelial space of Disse. They contain long outgrowths of the cytoplasm, some of which are in close contact with parenchymal cells, while others reach several sinusoids, where they can participate in the regulation of blood flow and thus affect portal hypertension. In a normal liver, these cells are, as it were, the main storage site for retinoids; morphologically, it appears as fat droplets in the cytoplasm. After the release of these droplets, stellate cells become similar to fibroblasts. They contain actin and myosin and contract when exposed to endothelin-1 and substance P. When hepatocytes are damaged, stellate cells lose fat droplets, proliferate, migrate to zone 3, acquire a phenotype resembling that of myofibroblasts, and produce type I, III, and IV collagen, and also laminin. In addition, they secrete cell matrix proteinases and their inhibitors, such as a tissue inhibitor of metalloproteinases (see Chapter 19). Collagenization of the space of Disse leads to a decrease in the intake of protein-bound substrates into the hepatocyte.

Pit cells. These are very mobile lymphocytes - natural killers, attached to the surface of the endothelium facing the lumen of the sinusoid. Their microvilli or pseudopodia penetrate the endothelial lining, connecting with microvilli of parenchymal cells in the space of Disse. These cells do not live long and are renewed by circulating blood lymphocytes that differentiate into sinusoids. They show characteristic granules and vesicles with rods in the center. Pit cells have spontaneous cytotoxicity against tumor and virus-infected hepatocytes.

Sinusoidal Cell Interactions

There is a complex interaction between Kupffer cells and endothelial cells, as well as between sinusoid cells and hepatocytes. Activation of cells by Kupferalipolysaccharides inhibits the uptake of hyaluronic acid by endothelial cells. This effect is possibly mediated by leukotrienes. Cytokines produced by sinusoid cells can either stimulate or inhibit hepatocyte proliferation.

Asthma is a well-known pathology of the respiratory system, the mechanisms of which are still being studied. Treatment of this disease is carried out by various methods. There are several approaches to the treatment of asthma. The complex of measures is aimed at eliminating the causes that cause asthma attacks, blocking the pathogenesis of the disease and combating the symptoms. Currently, there is a step therapy for bronchial asthma, which is common throughout the world. The essence of this treatment is the gradual addition of drugs and an increase in their dosages with the progression of the pathology.

The concept of disease

Asthma is an acute problem in pulmonology. Despite the fact that scientists have an idea about the etiology of this disease, it is almost impossible to eliminate it completely. Drugs that are used to treat this disease are addictive and affect the hormonal background. In this regard, a stepped pathology was developed. Symptoms of the pathology can be pronounced or, on the contrary, appear rarely and do not affect the patient's well-being. This is the basis of therapy. Drugs and their doses are selected depending on the severity of the patient's condition. In addition to the clinical picture, data from instrumental studies are also taken into account. This is the only way to assess the severity of the disease.

In most cases, the disease is allergic in nature. In almost all patients, the trigger for the development of symptoms is hypersensitivity to certain exogenous factors. Among them are food, animal, chemical, dust and plant allergens. Less often - bronchial asthma does not depend on the presence of hypersensitivity. In such cases, bacterial and viral microorganisms that cause irritation of the respiratory system are considered to be etiological factors. Often bronchial asthma has a mixed mechanism of development. Step therapy, developed by the Association of Physicians, helps to influence the main links of pathogenesis.

Symptoms of the disease in adults and children

To understand how the stepwise therapy of bronchial asthma works, it is necessary to know the symptoms of the pathology and stages. The severity of the pathological process is assessed according to the following criteria:

1. The frequency of nocturnal and daytime asthma attacks.
2. Duration of exacerbation and remission.
3. The indicator of PSV (peak expiratory flow rate) during peak flowmetry.
4. The presence of symptoms of chronic pathology of the broncho-pulmonary system.
5. Forced expiratory volume.

According to these indicators, the severity of the disease is determined. Based on this, there is a selection of medicines. Stepwise therapy of bronchial asthma in adults and children is based on this.

According to the nature of the course of the pathology, there are intermittent and persistent forms of the pathological process. The first is characterized by the fact that asthma symptoms appear rarely and do not affect breathing parameters (FEV1 and PSV). At the same time, there is no tendency to progression of the disease. According to the rules of the stepwise therapy of bronchial asthma according to Gina, in the intermittent course of the pathology, only short-acting inhalants are prescribed to help quickly eliminate airway spasm.

The mild persistent stage of the disease is characterized by the systematic manifestation of symptoms. During the day, asthma attacks can occur more than once a week. They interfere with normal human activity. Night attacks develop more than 2 times during the month, but not every week. At the same time, PSV and FEV1 indicators remain normal and amount to more than 80%. According to the stepwise therapy of bronchial asthma, with a mild persistent course, short-acting beta-2-agonists and low doses of inhaled glucocorticosteroids (IGCS) are prescribed. Hormonal drugs can be replaced with a drug that is part of the antileukotriene receptor group.

The average severity of the disease is characterized by daily attacks of suffocation. At night, symptoms occur more than once a week. The indicator of the respiratory system (PSV or FEV1) is from 60 to 80%. In this case, 1 of the following treatment regimens is selected:

1. Low-dose inhaled glucocorticosteroids and long-acting bronchodilators (beta-2-agonists).
2. IGCS and a drug from the group of antileukotriene receptors.
3. Medium or high doses of a hormonal drug and short-acting beta-2 agonists.
4. IGCS and theophylline.

In severe asthma, frequent attacks of suffocation are noted both during the day and at night. This affects the decline in performance and quality of life. Exacerbations of the disease become more frequent, and remissions become shorter. PSV and FEV1 are less than 60%. Prescribe long-acting bronchodilators and ICS in medium and high dosages. If necessary, theophylline or an antileukotriene drug is added to therapy.

If, despite the ongoing treatment, the patient's condition worsens, this is regarded as an extremely severe degree of bronchial asthma. Antibodies to immunoglobulin E and glucocorticosteroids in tablet form are prescribed.

Preparations for the relief of bronchospasm

The standard of treatment for bronchial asthma according to the Gina classification includes several groups of drugs that are the main ones. Currently, many combinations of these drugs are used. This helps reduce the frequency of drug use and improve well-being. The main group of drugs needed for bronchial asthma are beta-2 receptor agonists. They are short and long acting. The former include the preparations "Salbutamol", "Fenoterol". Among the long-acting beta-2 receptor agonists, the drugs Formoterol and Salmeterol are distinguished. The main action of these drugs is the relaxation of the muscles of the bronchi, that is, the relief of spasm.

The use of hormonal drugs

The use of steroid hormones is one of the main principles of the treatment of bronchial asthma. Step therapy includes several types of glucocorticoids. With mild to moderate persistent severity, low doses of hormones are prescribed. In order to avoid the systemic effects of steroids, medications are prescribed in the form of inhalation. With the progression of the disease, the dosage of the drug increases. Aerosols "Beclomethasone", "Budesonide", "Fluticasone" are referred to hormonal anti-asthma drugs. Hormones in the form of tablets are used only in cases of extremely severe asthma.

Glucocorticosteroids can be replaced with drugs from the antileukotriene group. These include tablets "Zafirlukast" and "Montelukast". Like hormones, they belong to pathogenetic therapy. The main effect of these medicines is to block the inflammatory process and eliminate swelling of the respiratory muscles.

Stepwise therapy of bronchial asthma: treatment standards

Asthma medications have been used for many years. At the end of the last century, a special group was organized. The main task of the team of doctors and scientists was to develop standardized methods for the treatment and diagnosis of bronchial asthma. The working group included major pharmaceutical companies, experienced doctors and experts. Thanks to this, a stepwise therapy for bronchial asthma was developed, which is currently used. It includes standards for the diagnosis and treatment of the disease. Step therapy is applicable for adults and children from 5 years of age.

Types of combination drugs

In order to improve the general condition of patients and reduce the frequency of inhalations, many combination medications for asthma have been developed. These preparations include the active substances that are included in the standard stepwise therapy. The most commonly used drugs are Seretide Multidisk, Symbicort. They include a beta-2 agonist and an inhaled glucocorticosteroid.

Alternative medicines

Despite the fact that doctors from all countries are guided by the recommendations of Gina, it is allowed to approach the treatment of each patient individually. Doctors have the right to prescribe additional groups of drugs that are not included in the stepwise therapy. These include: M-cholinomimetics, cromon substances. The most commonly used drugs are Ipratropium bromide, Spiriva, Intal. These drugs are combined with beta-2 agonists and steroids. Stepwise therapy of bronchial asthma in children should be combined with the use of antihistamines and antitussives. In addition, the primary measure to eliminate seizures is the exclusion of all possible allergens and provoking factors.

Treatment of asthmatic disease should be based on a systematic approach. The recommendations developed by the Gina Association are the basic therapy for this disease. In addition, each state has its own protocols for the treatment of this pathology. They are based on global recommendations and include additional groups of medications, as well as other therapies.