RU2618469C1 - Method of treating and preventing chronic inflammatory diseases of nasopharynx associated with inhalation exposure to benzene and formaldehyde in children - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention can be used to treat and prevent chronic inflammatory diseases of nasopharynx (CIDN) in children aged 4 through 10 years old, living in area of industrial enterprises impact in conditions of atmospheric air pollution with benzene and formaldehyde. Treatment is carried out by combined administration of the following medicinal products to children: "Tonsilgon N" preparation orally in a dose for children aged 4 through 6 years old - 10 drops 3-4 times a day; for children over 6 years - 1 pill 3-4 times a day, for 21 days course; "Multi-Tabs Junior" 1 tablet once a day for 21 days; "Eslidine" 1 capsule twice a day before meals in the morning and evening for 21 days; "Zodac" preparation 5 mg once a day in a dose for children aged 4 through 6 years old; 10 mg once a day for children over 6 years old, for 21 days course, and simultaneously with children medical treatment, starting from the third day of drug administration, pulsed low-frequency magnetotherapy is employed for 10 minutes daily or every other day for 10 days course on nose sinuses or submandibular regions in the form of two-inductor technique with transverse arrangement of inductors and feedback sensor position at right supraclavicular region.

EFFECT: invention provides treatment and prevention of chronic inflammatory disease of nasopharynx associated with exposure to benzene and formaldehyde in children.

5 cl, 5 tbl

Description

The invention relates to medicine, namely to pediatrics, and can be used for the treatment and prevention of chronic inflammatory diseases of the nasopharynx (hereinafter - CVH) in children 4-10 years old, living in the influence zone of industrial enterprises in the conditions of atmospheric air pollution with benzene and formaldehyde. The toxic effect of benzene and formaldehyde is manifested in the form of diseases of the nasopharynx, according to ICD-10, to such diseases as: J35.0 - chronic tonsillitis, J35.1 - tonsil hypertrophy, J35.2 - adenoid hypertrophy, J35.3 - tonsil hypertrophy and adenoids.

The pathogenetic basis for the development of CVD associated with exposure to benzene and formaldehyde is the morphofunctional failure of the lymphoepithelial structures of the pharyngeal Pirogov-Valdeyer ring directly in contact with the external environment (the combined effect of exogenous antigenic material of biological origin and chemical compounds) and a decrease in the activity of humoral factors of local immunity.

In recent years, the problem of the occurrence of this disease in children is increasingly being considered in connection with the impact of environmental chemical factors of technogenic origin.

A number of technical solutions are known from the prior art that are relevant to the proposed method, which can be attributed to methods of treatment and prevention of specific manifestations of diseases of the nasopharynx, as well as to methods that implement a complex effect on the nasopharynx.

The technical solutions of the first group include the following inventions.

A known method of treating chronic tonsillitis (RF Patent No. 2240132), according to which a comprehensive immunocorrective therapy is carried out with simultaneous rehabilitation of the tonsils. As an immunomodulator, Vitagmal biologically active food supplement is used, which is administered once sublingually, 10-12 drops 40 minutes -1 hour before meals in the morning every day for 14 days. Remediation of the tonsils is carried out with activated infusion of celandine, followed by lubrication by spot application of the surface of the tonsils with a solution of the Vitagmal preparation once a day, for a course of 10 procedures. Such treatment is carried out at least once every six months. However, this method of treatment does not take into account the effects of chemical technogenic factors in urban settlements (benzene, formaldehyde) and is aimed primarily at stopping the infectious component.

Also known is a method of treating acute sore throat (acute tonsillitis) (RF Patent No. 2456896), in which, against a background of three times daily oral administration of mexidol (emoxipin succinate) in 0.125 g tablets and a daily single oral administration of vitamins D ₃ at a dose of 4000 ME (100 μg ) and B 12 in a dose of 200 μg prescribe a sequential throat rinse, first with a 0.1% hydrogen peroxide solution, and after 15 minutes, a repeated gargle with a 0.125% solution of novocaine in a 0.5% sodium thiosulfate solution. Rinses are repeated 3-4 times a day, and each rinse is carried out for 2-3 minutes. The course of treatment is 3-4 days, and treatment begins no later than 24 hours after the onset of symptoms of the disease. Its disadvantage is that the effectiveness of this method is confirmed only for the acute process, and is not applicable for chronic inflammatory diseases of the nasopharynx in children.

A known method of treating chronic adenoiditis (HA) in children (RF Patent No. 2294758). According to this method, groups of patients are distinguished: with CA with purulent exudate, with CA against the background of allergic rhinitis and with CA against the background of intracellular infections. Conservative treatment with rinsing of the nasopharynx and differential therapy are carried out for each group of patients. Treatment includes the use of mucoregulatory drugs, and differentiated therapy for patients with HA with purulent exudate additionally includes local antibiotic therapy with Bioparox for 7 days. For patients with CA on the background of allergic rhinitis - the use of local antihistamines or mast cell stabilizers. For patients with CA with intracellular infections - two courses of systemic antibiotic therapy with macrolides and topically Bioparox, followed by the introduction of interferonogens or interferon inducers. 7-8 days after the start of treatment, all patients undergo 10 sessions of quantum therapy with the Rikta apparatus with the use of antioxidants, 4 times a year they carry out rehabilitation of IRS-19, the biological product Narine endonasally 10 days, inside with bifidumbacterin for 3 weeks, alternating with Narine. The method provides an individual treatment program for patients with CA of various groups with a persistent clinical effect, reduction of pharyngeal tonsil hypertrophy to the first degree, restoration of microbiocenosis and indices of local immunity in the nasopharynx.

Another known method of treating chronic adenoiditis and tonsillitis in children (RF Patent No. 2391108). With its implementation, sanitation and immunocorrection are carried out. Remediation is carried out with a 0.9% solution of sodium chloride at a temperature of 37-40 ° C daily according to one procedure for 7-10 days. Then, light therapy is additionally performed by exposing the bridge of the nose and / or the left and right sides of the neck to incoherent polarized light with a wavelength of 400-2000 nm, the light flux density per minute is 2.4 J / cm ^{2, and the} degree of polarization at the output is 95-98% in 5-10 minutes daily for 7-10 days. Immunocorrection is carried out by the drug tonsilotren sublingually 30-60 minutes before meals every day 3 times after 6-8 hours, 125-500 mg for 7-10 days.

A common drawback of these inventions is that they do not take into account the negative influence of chemical technogenic factors of urban settlements (benzene, formaldehyde), which are able to determine pathogenetic processes in the lymphoepithelial structures of the pharyngeal ring, have a general toxic, sensitizing, hepatotoxic and immunotropic effect.

A known method of treating chronic compensated tonsillitis through the use of a herbal preparation Tonsilgon N produced by the German pharmaceutical company "Bionorika" (Dergachev B.C. Change in the immune and endocrine status in the treatment of tonsilon N with patients with chronic compensated tonsillitis, 2002. - S. 104-110). The method consists in the use of complex therapy of chronic tonsillitis, including traditional sanitizing drainage of the tonsils with the antiseptic drug chlorhexidine and oral administration of the drug Tonsilgon N, which has immunostimulating, anti-inflammatory, antiviral effects.

Tonsilgon N is a combined preparation containing an extract of seven herbs. The active components of chamomile, marshmallow and horsetail stimulate the body's defense mechanisms by increasing the phagocytic activity of macrophages and granulocytes. Extracts from these plants also enhance the intracellular destruction of absorbed microbes due to increased formation of bactericidal oxygen metabolites. Polysaccharides, essential oils and flavonoids of chamomile, marshmallow and dandelion have an anti-inflammatory effect and reduce swelling of the mucous membrane of the respiratory tract. Oak bark, rich in tannins, has antiviral activity.

Lavage of palatine tonsil lacunae with chlorhexidine antiseptic is carried out daily, a course of 10-15 sessions. Tonsilgon N was taken orally daily in the morning on an empty stomach, 25 drops for 4 weeks. The course of treatment was 1 month, and dispensary observation was carried out for 1 year.

Under observation were 130 patients with a compensated form of chronic tonsillitis aged 18 to 42 years. The duration of the disease did not exceed 3-5 years.

Immediately after the complex of therapy, a good effect was observed in all patients. However, the main disadvantages of the method are the significant frequency of relapse (in every fifth patient) and the insufficient effectiveness of the treatment of compensated chronic tonsillitis, leading to decompensation in the form of recurring paratonsillitis and paratonsillar abscesses, severe tonsilogenic intoxication, diseases of distant organs and systems, resulting in the end of the observation period (1 year) in 3% of patients performed bilateral tonsillectomy.

The prior art method of improving psycho-emotional indicators in frequently ill children of primary school age (RF Patent No. 2535161). Children included in the dispensary group of frequently ill patients are given Multi-Tab Junior 1 tablet 1 time per day for 30 days - 3 courses with an interval of 1 month and glucosaminylmuramyl dipeptide 1 tablet 1 time per day sublingually for 10 days - 3 courses with an interval of 2 months (the appointment of multivitamins and minerals restores their deficiency and increases the body's resistance to infectious pathogens in children taking them). The known method allows to reduce the frequency of respiratory infections in frequently ill children by increasing the body's resistance to infectious pathogens while restoring a deficiency of vitamins and trace elements. The group of often sick includes children who suffer 4 or more infectious diseases of the upper respiratory tract per year. Using this method can reduce the frequency of respiratory infections and improve psycho-emotional indicators: reduce high levels of anxiety in the classroom (p <0.05) and extracurricular time (p <0.05), as well as high levels of negative emotions in the classroom (p <0.05) and in extracurricular time (p <0.05). In addition, the use of this method leads to an increase in the number of children with an “average” level that is most favorable for the normal development of the person, the level of negative experiences in the classroom (p <0.05) and extracurricular time (p <0.05), as well as the level of anxiety, as in lesson time (p <0.05), and extracurricular time (p <0.05). The disadvantage of this method is that without physiotherapeutic support, there is a high probability of recurrence of the pathogenetic process in the lymphoepithelial structures of the pharyngeal ring, followed by a worsening of psycho-emotional indicators.

A known method of treating patients with inflammatory and benign hyperplastic formations of the larynx, including microsurgical intervention, antibiotic therapy and physiotherapy (USSR Author's Certificate No. 466832).

Treatment with this method has several disadvantages, the main of which are relapses of the disease and, as a consequence, poor voice quality due to the development of cicatricial changes in the mucous membrane of the vocal folds. Sclerosis of the mucous membrane of the vocal folds is caused by both frequent inflammatory changes and inadequate surgical interventions - biopsies. As a result, the chronic inflammatory process of the mucous membrane in some cases leads to malignancy.

The technical solutions of the second group that implement a complex effect on the nasopharynx include the following inventions.

Known methods of treating inflammatory diseases of ENT organs are usually complex and include antibacterial, antihistamine, mucoregulatory, immunomodulatory therapy, physiotherapy and biologics. This requires the use of various antiseptic drugs, which are often ineffective due to the low antimicrobial activity, the mismatch of the spectrum of the drug to the nature of the microflora of the inflammatory focus, and also due to the resistance of microorganisms to antibacterial agents.

There is a method of treating inflammatory diseases of ENT organs, in particular rhinopharyngitis, adenoiditis, sinusitis, granulosa pharyngitis, chronic tonsillitis and otitis media (RF Patent No. 2307657). To do this, use 0.5-2% aqueous solutions of colloidal silver. These solutions are a complex of silver and polyvinylpyrrolidone (protargol). Moreover, silver in them is 7-8%, polyvinylpyrrolidone 92-93%. Or use these solutions in water-soluble polymer gels. The method provides effective treatment through the use of smaller silver particles, creating a large total surface for maximum contact with pathogenic flora, and a high rate of silver entry into the pathological focus in the absence of allergic reactions. The disadvantages of using protargol include side effects in the form of allergic reactions caused by the stabilizer, and insufficient therapeutic effect.

The prior art method of nonspecific etiological antiviral therapy for inflammatory and hyperplastic diseases of the nasopharynx in children (RF Patent No. 2504374). During the acute clinical manifestations of the disease, cycloferon is used in clinically effective daily doses, selected taking into account the weight and age of the patients, in short five- or ten-day courses, in combination with topical administration of a 20% aqueous solution of sulfacyl sodium-2-3 drops in both halves of the nose with head thrown back 3 times a day in ten-day courses. In this case, cycloferon is used in rarely ill patients with acute respiratory viral infections five-day courses. In often ill patients and against the background of hyperplastic phenomena in the nasopharynx, with chronic nasopharyngitis, chronic adenoiditis and lymphopharyngeal ring hyperplasia - repeated ten-day courses for each exacerbation of clinical manifestations, to reduce the frequency of acute clinical manifestations and exit into persistent clinical remission.

The disadvantage of these methods is that they do not take into account the general toxic, prooxidant, sensitizing, hepato- and immuno-toxic effects of chemical compounds together with viral and bacterial factors, as a result of which the effectiveness of these methods is reduced.

The technical result of the invention is to provide effective treatment and prevention in children of a chronic inflammatory disease of the nasopharynx associated with exposure to benzene and formaldehyde, and is achieved due to the high degree of restoration of antioxidant defense activity, local homeostasis and immune barriers at the level of lymphoepithelial structures of the pharyngeal ring, and an increase in non-specific body resistance to viral and bacterial flora, increased biotransformation processes uu chemical compounds, and in the improvement of medical care provided to children living in areas with prolonged exposure of exogenous chemical factors of anthropogenic origin.

The specified technical result is achieved by the proposed method for the treatment and prevention of chronic inflammatory diseases of the nasopharynx in children associated with an inhalation exposure to benzene and formaldehyde, which consists in the fact that the treatment is carried out by the combined use of the following drugs by children: the drug Tonsilgon N is taken orally in children from 4 up to 6 years - 10 drops 3-4 times a day; children over 6 years old - 1 tablet 3-4 times a day, a course of 21 days; "Multi-tabs Junior" 1 tablet 1 time per day for 21 days; "Eslidine" 1 capsule 2 times a day before meals in the morning and evening for 21 days; “Zodak” preparation, 5 mg once a day in a dosage for children from 4 to 6 years old; 10 mg once a day for children over 6 years old, a course of 21 days, and simultaneously with medical treatment of children, starting from the third day of taking medicines, pulsed low-frequency magnetotherapy is used for 10 minutes daily or every other day with a course of 10 days for sinuses or submandibular regions in the form of a two-inductor technique with a transverse arrangement of inductors and placing the feedback sensor in the right supraclavicular region.

Pulse low-frequency magnetotherapy is carried out on the device ANEb-01 - "Hephaestus".

Along with medicines, the child is prescribed diet therapy, which includes products with a high content of protein and amino acids, water- and fat-soluble vitamins, omega-3 unsaturated fatty acids, trace elements: zinc, selenium, iodine, lacto- and bifidobacteria, phytoncides, pectins and dietary fiber, as well as products with pronounced antioxidant and immunomodulating properties, as well as products with cytoprotective properties.

Along with medicines, the child is prescribed physiotherapy exercises, breathing exercises and hardening procedures.

Treatment and prevention is carried out once or twice a year by courses for 21 days.

The technical result is achieved due to the following.

To understand the essence of the issue, it should be clarified that in the territories of industrial cities, the recorded incidence of CVD (ICD10: J35.0-35.3) is 1.5 times higher than that of children in rural areas (2014: 54.1% versus 37, 0%), and 1.2 times higher than the average regional incidence - 45.7%. Based on the risk assessment carried out in the Perm Territory with unsatisfactory air quality in terms of the content of aromatic hydrocarbons (benzene) and formaldehyde (up to 1.5-2.0 MPC.s.), the risk of developing respiratory diseases exceeds the acceptable level (risk assessment HI = 1.48-13.7, while the norm is considered to be HI≤1.0).

The pathogenetic basis for the development of CVD in children associated with exposure to benzene and formaldehyde is the morphofunctional failure of the lymphoepithelial structures of the pharyngeal Pirogov-Valdeyer ring directly in contact with the external environment (the combined effect of exogenous antigenic material of biological origin and chemical compounds) and a decrease in the activity of humoral factors of local immunity.

The high incidence of CVD in children under conditions of chronic aerogenic exposure to aromatic hydrocarbons (benzene) and formaldehyde is due to the specific effects of chemicals on the respiratory system and immune system. Having a local irritant, dehydrating and sensitizing effect, formaldehyde causes the development of a local chronic inflammatory process (including immuno-allergic) with hypofunction of the mucous glands. The multilayer ciliated epithelium of the respiratory tract is replaced by a multilayer flat one, a large number of collagen fibers are formed in the own layer of the mucous membrane, mucociliary clearance is impaired, degenerative processes develop, which reduces the level of mucosal resistance and forms the morphological basis of chronic inflammatory diseases of the nasopharynx. The development of local inflammatory, lymphoproliferative and dystrophic processes is accompanied by a general resorptive action of formaldehyde, characterized by prooxidant, sensitizing, hepatotoxic and immunosuppressive effects, leading to a decrease in the detoxification and elimination mechanisms of the body against the background of the development of specific sensitization and immunosuppression.

The pathogenetic feature of the combined aerogenic effects of formaldehyde and benzene is the initiation of immuno-allergic inflammatory proliferative reactions in lymphoid formations, primarily the oral and nasopharynx, with the development of a secondary transient immunodeficiency state, a decrease in the production of humoral factors of the immune response and impaired activity of phagocytic resistance with non-specific lymphoid tissue and a decrease in barrier function to viral-bacterial flora.

The clinical manifestation of CVZN (J35.0-35.3) associated with the aerogenic exposure of benzene and formaldehyde is characterized by a persistent recurrent course with the development of local lymphatic-hyperplastic / dystrophic processes and immunoallergic reactions, a persistent decrease in rhinomanometric indicators, moderate intoxication, or general non-specific sensory dysfunction oxidative and antioxidant processes.

Immune disorders that develop in children under conditions of chronic exposure to benzene and formaldehyde at the first stage are characterized by a decrease in the functional activity of nonspecific resistance indicators (percentage of phagocytosis, phagocytic number) and the relative content of humoral immunity factors (immunoglobulins A, D, G). Subsequently, against the background of continued exposure to formaldehyde and benzene, more significant immune disorders develop (a decrease in absolute phagocytosis, a violation of the normative ratio of T and B lymphocytes, an increase in general and specific sensitization). The combination of pathofunctional and pathomorphological changes in the immune system leads to a decrease in adaptation reserves and the effectiveness of the functioning of the natural protective barriers of the child’s body, i.e. a decrease in resistance to the action of various kinds of etiological factors (including infectious).

Thanks to the combined use of drugs and at the same time the physiotherapeutic method recommended by the proposed method, the treatment and prevention are highly effective in children aged 4-10 years with inflammatory diseases of the nasopharynx associated with exposure to benzene and formaldehyde, due to the high degree of recovery of antioxidant activity, local homeostasis and immune barriers at the level of lymphoepithelial structures of the pharyngeal ring, increased nonspecific resistance ntnosti organism to viral and bacterial flora, enhancing the processes of biotransformation of chemical compounds.

Recommended frequency of specialized preventive programs: 1-2 times a year, courses for 21 days.

Specialized preventive programs are intended for children who are in the stage of subcompensation / compensation of the main pathological process.

During the implementation of specialized prevention programs, children should be monitored daily by paramedical personnel with a weekly examination by a pediatrician.

Moreover, in the proposed method, it is recommended to use the following drugs in combination:

"Tonsilgon N", pharmacotherapeutic group: antiseptic and immunomodulating agent of plant origin. ATX Code: R02AA20. Pharmacological properties are due to biologically active substances that make up the drug. Tonsilgon® N has anti-inflammatory and antiseptic effects. The active components of chamomile, marshmallow and horsetail included in the preparation contribute to an increase in the activity of nonspecific defense factors of the body. Polysaccharides, essential oils and flavonoids of chamomile, marshmallow and yarrow, tannins of oak bark have an anti-inflammatory effect and help to reduce swelling of the mucous membrane of the respiratory tract.

Multi-Tabs Junior, pharmacotherapeutic group: multivitamins in combination with microelements, antihypoxants and antioxidants. ATX code: ATX A11AA04, ATX С01ЕВ Preparations that reduce the activity of lipid peroxidation processes, increase the antioxidant protection of cells, and replenish the need for vitamins and minerals (zinc, iodine, selenium). The effect of the drug is determined by the properties of vitamins and minerals that make up the complex. Vitamin plays an important role in the formation of the immune system, increases the body's resistance to various infections. It is an essential component of the antioxidant defense of the body. Vitamin C is vital for the immune system and the functioning of white blood cells, helps increase the body's resistance to various infections. Ascorbic acid promotes the absorption of inorganic iron from the digestive tract. It is an important antioxidant. Vitamin E stimulates and improves the state of the immune system. Vitamin B1 is a necessary component of carbohydrate metabolism as an integral part of coenzyme for decarboxylation of keto acids; plays an important role in carbohydrate, protein and fat metabolism, is involved in the conduct of nervous excitation in synapses. Vitamin B2 is of great importance in the metabolism of carbohydrates, proteins and fats, and the synthesis of hemoglobin. Promotes the good functioning of the skin, tissue regeneration during wounds and cuts, maintains the normal structure and function of the mucous membranes. Vitamin B6 is involved in the synthesis of neurotransmitters, therefore it is important for the normal function of the central and peripheral nervous system. Nicotinamide regulates higher nervous activity and functions of the digestive system. Improves microcirculation. Pantothenic acid plays a large role in the regulation of oxidation and acetylation. Participates in the metabolism of carbohydrates and lipids. Folic acid is involved in the reproduction of genetic material, in normal cell division, including blood cells, in the synthesis of amino acids, nucleic acids, pyrimidines, is important in the formation of hemoglobin in red blood cells. Iron is involved in blood formation processes. Promotes the full functioning of cellular and local immunity. Zinc is necessary for the formation of red blood cells and other formed elements of the blood. Stabilizes the body's immune processes. Not synthesized in the body. Copper is a vital trace element. It plays a large role in metabolic processes. Selenium, due to its antioxidant properties, has a protective effect on the immune system, preventing the formation of free radicals, which have a damaging effect on the body. Not synthesized in the body. Iodine is part of the thyroid hormones that perform vital functions: they regulate the activity of the brain, nervous system, sex glands, and the growth and development of the body. Not synthesized in the body.

"Eslidine", pharmacotherapeutic group: a drug for the treatment of liver diseases. A drug that has a hepatoprotective effect, normalizes metabolism (fatty, protein, carbohydrate). ATX Code: A05C. The combined drug. It has a hepatoprotective effect, normalizes all types of metabolism (fatty, protein, carbohydrate).

Methionine, one of the active components of the drug, is an essential amino acid that is a source of mobile methyl groups. Methionine is also necessary for the neutralization of xenobiotics. Essential phospholipids are indispensable factors for the development and functioning of liver cells. The main fraction of essential phospholipids in the preparation is represented by phosphatidylcholine (73%), which is the main component of biological membranes. Once in the body, phosphatidylcholine restores the integrity of the membranes of the affected liver cells and activates the phospholipid-dependent enzymes located in the membrane, thereby normalizing the permeability and enhancing the detoxification and excretory potential of the liver cells. Methionine and essential phospholipids enhance each other's action, being a source of endogenous (internal) and exogenous (entering the body) phospholipids, respectively, improve the functional state of liver cells and have a hepatoprotective (protective) effect.

Methionine is also involved in the exchange of sulfur-containing amino acids, in the synthesis of epinephrine, creatinine and other biologically active compounds, converts the action of hormones, vitamins (B12, ascorbic acid, folic acid), enzymes, proteins, and participates in the reactions of methylation, deamination, decarboxylation.

Eslidine® restores liver function, increases its detoxification ability, and also normalizes fat, carbohydrate and protein metabolism in the body.

Zodak, pharmacotherapeutic group: antihistamines. Drugs that prevent the development and facilitate the course of allergic reactions have anti-inflammatory and anti-exudative effects. ATX Code: R06AE07. The active substance of the drug - cetirizine, is a metabolite of hydroxyzine, belongs to the group of competitive histamine antagonists and blocks H1-histamine receptors. It prevents the development and facilitates the course of allergic reactions, has antipruritic and antiexudative effects. It affects the early histamine-dependent stage of allergic reactions, limits the release of inflammatory mediators in the late stage of an allergic reaction, and also reduces the migration of neutrophil and basophil eosinophils, stabilizes mast cell membranes. Reduces the permeability of capillaries, prevents the development of tissue edema, relieves spasm of smooth muscles. Eliminates the skin reaction to the introduction of histamine, specific allergens.

Along with the combined use of drugs, physiotherapeutic methods are used, namely: pulsed low-frequency magnetotherapy for the sinuses of the nose or submandibular regions, 2-inductor technique; the location of the inductors is transverse, the feedback sensor in the supraclavicular right region. The device for controlled bioelectromagnetic therapy ANEb-01 - "Hephaestus" (hereinafter referred to as the device), is intended for the treatment of patients using a pulsed complex modulated electromagnetic field, the characteristics of which vary depending on the impedance of the patient’s tissues. The dynamics of the passive electrical properties of the patient’s tissues reflects changes in the functional properties of the patient’s tissues subjected to medical treatment and can serve as a diagnostic criterion for their condition. The device can be used in physiotherapy departments and offices of medical and preventive and outpatient facilities, health centers and other medical institutions. The carrier frequency range of magnetic field pulses is not more than 200 Hz. The modulation frequency is from 0.5 to 0.8 Hz. The frequency deviation of the pulse modulated electromagnetic field is ± 10%. Induction of the magnetic field on the surface of the inductors at a pulse frequency of 100 Hz is not more than 12 mT. The rated supply voltage is 12 V.

Recommended by the proposed method, bioregulated low-frequency electrotherapy, normalizes local blood flow, provides lymphatic drainage of the nasopharynx and paranasal sinuses, stimulates the metabolism of all layers of the skin, reduces general fatigue of the body. It has a stable decongestant, anti-inflammatory and analgesic effects.

It was experimentally established that only the use of the integrated regimen for the use of the above drugs and the specified physiotherapeutic effect provides synergies in achieving the technical result due to the restoration of antioxidant defense activity, local homeostasis and immune barriers at the level of lymphoepithelial structures of the pharyngeal ring, and an increase in the nonspecific resistance of the body to viral and bacterial flora, enhancing chemotransformation processes eskih compounds.

Studies have shown that when using these drugs individually or with a regimen of one, two, or three drugs, the treatment of CVD associated with the inhaled exposure to benzene and formaldehyde is not achieved in children.

In the treatment and prevention of CVI, along with medications and a physiotherapeutic procedure, diet therapy can also be prescribed to restore the activity of factors of non-specific resistance and immune defense, to increase the rate of metabolism of benzene and formaldehyde, to reduce the activity of peroxidation processes, increase the functional activity of systems antioxidant protection, to reduce sensitization and the provision of cytoprotective effects. Diet therapy is a balance in the content of proteins, fats and carbohydrates; the inclusion in the diet of foods rich in vitamins and minerals, as well as products with pronounced antioxidant and cytoprotective properties; expansion of the product range due to vegetable and fruit juices, berries, fruits, vegetables, fruit purees.

In addition to diet therapy, physiotherapy exercises, respiratory gymnastics and hardening are also recommended. This will help restore optimal functional state, improve non-specific immune defense, stimulate activation of reserve and adaptive capabilities, and increase the effectiveness of pharmaceuticals. At the same time, it is necessary to consult a doctor of exercise therapy, classes with an instructor of exercise therapy (small-group - 2-3 people and group of 10-15 people), rubdown, dousing, bathing, contrast shower.

When implementing the proposed method, the following operations are carried out in the following sequence:

1. In an environmentally disadvantaged area with a high level of chemical stress (chronic aerogenic exposure to benzene and formaldehyde), which forms an unacceptable risk level (HI≥1.0) for the development of chronic inflammatory diseases of the nasopharynx, children with CVD are identified through traditional anamnestic and clinical examinations (ICD -10: J35.0 - chronic tonsillitis, J35.1 - hypertrophy of the tonsils, J35.2 - hypertrophy of the adenoids, J35.3 - hypertrophy of the tonsils and adenoids);

2. Next, the child is diagnosed with CVD associated with an inhalation exposure to benzene and formaldehyde, as follows:

a) for each child, a venous blood sample is taken and the content of benzene and formaldehyde is established in it.

b) if the content of benzene and formaldehyde in the blood of the child is exceeded above the background level, further biomedical studies are carried out, consisting in the establishment of certain functional and laboratory parameters.

c) as functional indicators determine:

- volume-velocity indicators of rhinomanometry;

- adenoid vegetation according to x-ray of the nasopharynx;

- with ultrasound, signs of diffuse liver damage;

g) as laboratory indicators establish:

- the content in the nasal secret of eosinophils and the eosinophilic lymphocytic index;

- the content of immunoglobulins IgE, IgA, IgG;

- indicators of phagocytic blood activity: absolute phagocytosis, percentage of phagocytosis, phagocytic number and phagocytic index;

- the number of B-lymphocytes in the blood and their functional activity; ratio of T and B lymphocytes;

- total antioxidant activity of blood and blood levels of superoxide dismutase, glutathione peroxidase, catalase, lipid hydroperoxides, malondialdehyde (MDA), the number of reticulocytes, the number of red blood cells and the level of aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT).

e) the presence of chronic inflammatory diseases of the nasopharynx in children associated with exposure to benzene and formaldehyde is diagnosed if there are the following deviations of the indicators (diagnostic criteria) from the physiological age norm:

- a decrease in volume-velocity indicators of rhinomanometry by 15% or more;

- the presence of increased adenoid vegetation according to x-ray of the nasopharynx;

- ultrasonic signs of reactive diffuse liver damage and an increase in its size by 10% or more;

- increase in the content in the nasal secret of eosinophils by 15% or more;

- increase in eosinophilic-lymphocytic index by 10% or more;

- an increase in the content of total IgE by 20% or more;

- an increase in blood levels of specific IgE to formaldehyde;

- decrease in the number of IgA by 15% or more;

- reduction in the number of IgE by 15% or more;

- increase the level of IgG to benzene by 15% or more;

- decrease / increase in indicators of phagocytic activity of blood (any of): absolute phagocytosis by 15% or more, percentage of phagocytosis by 15% or more, phagocytic number by 15% or more, phagocytic index by 15% or more;

- a decrease in B-lymphocytes in the blood in absolute numbers and percentage by 10% or more;

- violation of the functional activity of B-lymphocytes;

- violation of the normative ratio of T- and B-lymphocytes;

- increase / decrease in the total antioxidant activity of blood by 10% or more;

- increase / decrease of superoxide dismutase by 20% or more;

- increase / decrease of glutathione peroxidase by 20% or more;

- increased catalase by 20% or more;

- increase in the level of lipid hydroperoxides by 20% or more;

- increase in MDA by 20% or more;

- increase in the number of reticulocytes by 10% or more;

- reduction of red blood cells by 10% or more;

- increase in ASAT and / or ALAT by 15% or more;

f) moreover, the indicated diagnosis of CVD associated with exposure to benzene and formaldehyde is made if the child has 2/3 or more of these diagnostic criteria (table 3).

When a diagnostic examination of the proposed method use the equipment specified in table 1.

The physiological levels are used as criteria for assessing deviations of clinical and laboratory parameters, and background levels are used for the content of benzene and formaldehyde (N. Tits, 2003).

3. Carry out complex treatment of children with CVD identified in this way, associated with exposure to benzene and formaldehyde, by the combined use of drugs and the physiotherapeutic method listed in table 2.

In the treatment and prevention of CVI, along with medications and physiotherapy, diet therapy, physiotherapy exercises, physical therapy, breathing exercises and hardening can be additionally prescribed.

Diet therapy provides to some extent the elimination of benzene and formaldehyde through the gastrointestinal tract, an increase in the rate of benzene metabolism, a decrease in the activity of peroxidation processes, and an increase in the functional activity of antioxidant defense systems. The inclusion of foods with pronounced antioxidant properties rich in fiber and pectins in the diet may be recommended.

Moreover, as criteria for the effectiveness of the specialized treatment and prevention program for children with CVD take:

- restoration of patency of the upper respiratory tract,

- normalization of the broken links of the immune defense,

- reduction of general and specific sensitization,

- a decrease in the activity of lipid peroxidation processes,

- increase the antioxidant protection of cells,

- activation of tissue respiration processes,

- and stabilization of cell membranes.

The proposed method was tested in 124 children (age 4-10 years, 54% of boys; 46% of girls) with CVI (J35.0-35.3) associated with the aerogenic exposure of benzene and formaldehyde. The territory of these children was characterized by unsatisfactory air quality in terms of benzene and formaldehyde content (up to 1.5-3.4 MPCs), the risk of developing respiratory pathology, including respiratory organs, exceeded the permissible level (H1 = 1.48-1 , 94); the incidence rate of respiratory diseases in children is 1.6-1.8 times higher than the national average; secondary immunodeficiency states 5.5-7.3 times, diseases of the tonsils and nasopharynx 1.5-2.0 times. Causal relationships were established between the level of atmospheric air pollution with benzene and formaldehyde and the incidence rates of children with chronic respiratory infections (odds ratio ratio OR = 1.2-1.4).

Diagnostic indicators indicating that children suffer from CVD associated with exposure to benzene and formaldehyde were as follows:

Anamnestic - the age of children from 4 to 10 years, the presence of CVI (ICD-10: J35.0-35.3) with a frequency of more than 3 times a year and lasting more than 7-10 days, with a persistent and recurrent course, signs of local sensitization of the upper respiratory tract symptoms of general intoxication and prolonged subfebrile condition, weighed down by an allergic history and heredity (OR = 1.2-2.0; p = 0.04-0.05); there may be anomalies in the development of ENT organs and anemia; resistance to basic therapy (OR = 1.7-1.9; p = 0.03-0.05).

Clinical - features of the manifestation of the pathological process (persistent nasal congestion, episodic reflex dry cough, viscous mucopurulent discharge from the nose, swelling of the mucous membranes, hyperemia with a cyanotic hue, enrichment and lubrication of the vascular pattern of the mucous membranes, persistent narrowing of the nasal passages, thickening of the nasal mucosa, nasal mucosa) sinuses of the nose, palatine arches and vocal cords) (OR = 1.2-2.3; p = 0.03-0.04); hyperplasia of the lymphoid elements of the nasopharynx - tonsils, adenoids; less often signs of dystrophic processes in the nasopharynx mucosa (thinning, pallor, atrophy) (OR = 1.6-2.4; p = 0.02-0.05), signs of moderate intoxication (pallor of the skin and mucous membranes, periorbital shadows), persistent enlargement, adhesion, lack of mobility, soreness of the regional lymph nodes; a change in the timbre of the voice, hearing impairment, circulatory disturbance in the cranial cavity is possible, headaches are possible (OR = 1.3-2.1; p = 0.04-0.05), a characteristic sluggish and indifferent facial expression (the so-called adenoid face ): constantly open mouth, drooping lower jaw, smooth nasolabial folds; abnormal development of the chest (chicken breast), nighttime urinary incontinence (OR = 1.9-3.0; p = 0.02-0.05) are often observed.

Functional indicators - a decrease in volume-velocity indicators of rhinomanometry by 15% or more; the presence of an enlarged pharyngeal tonsil (adenoid) II-III art. according to the R graph of the nasopharynx (OR = 1.5-1.8; p = 0.03-0.05); the presence of ultrasonic signs of moderate diffuse liver damage (structural damage and an increase in size by 10% or more), a causal relationship between the concentration of benzene in the blood and the reactive changes in the liver (R ² = 0.32; F = 38.42; p = 0.01);

Laboratory - the development of local immunoallergic reactions (an increase in the content of eosinophils in the nasal secretion, an increase in the eosinophilic-lymphocytic index); the development of general nonspecific sensitization (an increase in the content of total IgE); decrease in blood phagocytic activity (absolute phagocytosis, percentage of phagocytosis, phagocytic number and phagocytic index) (OR = 1.2-1.7; p = 0.03-0.04), decrease in B-lymphocytes in the blood (in absolute numbers and percentage), impaired functional activity of B-lymphocytes; decrease in the number of immunoglobulins (IgA, IgG), the presence of nonspecific (increase in total IgE) and specific sensitization (increased blood levels of specific IgE to formaldehyde, IgG to benzene) (OR = 1.3-2.4; p = 0.01 -0.05); a causal relationship between the concentration of benzene and formaldehyde in the blood with a decrease in B-lymphocytes in the blood, a decrease in the phagocytic activity of leukocytes (R = 0.29-0.56; F = 27.54-53.12; p = 0.04- 0.05); increase / decrease in the total antioxidant activity of the blood and in the blood content of superoxide dismutase, glutathione peroxidase, catalase, lipid hydroperoxides, malondialdehyde; a causal relationship was established between the concentration of formaldehyde and benzene in the blood with an increase in the antioxidant activity of serum (R ² = 0.31-0.43; F = 32.57-47.12; p = 0.01-0.04); the excess of formaldehyde and benzene in the blood compared to the background concentration with an increase in the content of superoxide dismutase, glutathione peroxidase and lipid hydroperoxides (R ² = 0.22-0.51; F = 61.47-78.143; p = 0.02-0.05) ; an increase in the number of reticulocytes, a decrease in red blood cells, the development of cytolysis syndrome (increased ASAT and ALAT) (OR = 1.6-2.2; p = 0.03-0.05).

Children were treated with the proposed method (table 2).

Data on the effectiveness of the proposed method for the treatment of children of the observation group with a diagnosis of CVD associated with the combined effects of benzene and formaldehyde according to the dynamics of the indicators are shown in table 4.

The data shown in table 4 show that after the treatment by the proposed method, there was an improvement in all the main groups of indicators in children suffering from CVD under the influence of benzene and formaldehyde.

In addition, after treatment, the processes of biotransformation improved and the body's resistance to the accumulation of benzene and formaldehyde in children with the indicated CVD increased (the benzene content decreased by 2.1 times after 12 months; formaldehyde by 2.0 times, despite the fact that children treated, continued to live in the environment of the external effects of these toxicants).

The data obtained during the studies showed that the proposed method of drug treatment and prevention in children with CVD due to the chronic exposure to benzene and formaldehyde combined with the use of the proposed drugs and physiotherapeutic method is pathogenetically substantiated and shows high efficiency in relation to the clinical manifestations of the disease, antioxidant and immunological protection, reduction of toxic load level.

To prove the synergism of the effect in the claimed method of exactly the four proposed drugs in the indicated dosage and the need for physiotherapy, we present below Table 5, which reflects the clinical efficacy in the follow-up history (after 12 months) with various medication regimens for treatment and prevention.

As studies and the data shown in table 5 showed, the effect of the proposed method is not a consequence of the simple action of the drugs and procedures used, but there is a pronounced positive synergy of drugs for the treatment and prevention of CVD due to exposure to benzene and formaldehyde in children (the sum of the effects of individual preparations in the same doses gives an effect significantly less pronounced than with the combined use of the four drugs recommended in the present method and the proposed drug ioterapevticheskogo method).

The complex of specialized medical and preventive care for children with this disease expands the standard approaches to treatment, includes an additional set of medical measures based on a pathogenetically sound combination of membrane-stabilizing, immunocorrecting, hepatoprotective, antioxidant, multivitamin and physiotherapeutic therapy.

Thus, the proposed method of treatment and prevention has a pronounced clinical effect and contributes to the restoration of antioxidant and immunological protection, reduction of toxic load, and can be recommended for the treatment and prevention of children with this disease, living in industrialized territories for a long time and having an increased level in biological media of benzene and formaldehyde.

Evaluation of the effectiveness of specialized medical and preventive measures at the individual level 1 year after their implementation showed a 25-30% decrease in the number of reported cases of children seeking medical help for CVD (J35.0-35.3).

Claims (5)

1. A method for the treatment and prevention of chronic inflammatory diseases of the nasopharynx in children associated with an inhaled exposure to benzene and formaldehyde, characterized in that the treatment is carried out by the combined use of the following drugs by children: the drug "Tonsilgon N" orally at a dosage of children from 4 to 6 years - 10 drops 3-4 times a day; children over 6 years old - 1 tablet 3-4 times a day, a course of 21 days; "Multi-tabs Junior" 1 tablet 1 time per day for 21 days; "Eslidine" 1 capsule 2 times a day before meals in the morning and evening for 21 days; “Zodak” preparation, 5 mg once a day in a dosage for children from 4 to 6 years old; 10 mg once a day for children over 6 years old, a course of 21 days, and simultaneously with medical treatment of children, starting from the third day of taking medicines, pulsed low-frequency magnetotherapy is used for 10 minutes daily or every other day with a course of 10 days for sinuses or submandibular regions in the form of a two-inductor technique with a transverse arrangement of inductors and placing the feedback sensor in the right supraclavicular region. 2. The method according to p. 1, characterized in that the pulsed low-frequency magnetotherapy is carried out on the device ANEb-01-Hephaestus. 3. The method according to p. 1, characterized in that at the same time as the medicinal product, the child is prescribed diet therapy, including products with a high content of protein and amino acids, water and fat-soluble vitamins, unsaturated fatty acids of the Omega-3 class, trace elements: zinc, selenium , iodine, lacto- and bifidobacteria, phytoncides, pectins and dietary fiber, as well as products with pronounced antioxidant and immunomodulating properties, as well as products with cytoprotective properties. 4. The method according to p. 1, characterized in that at the same time as the medicinal products, the child is prescribed physiotherapy exercises, breathing exercises and hardening procedures. 5. The method according to p. 1, characterized in that the treatment and prevention is carried out once or twice a year by courses for 21 days.