RU2523651C2 - Method for differentiated control of basic anti-inflammatory treatment of bronchial asthma in children and adolescents - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention refers to medicine, namely to pulmonology and allergology, and can be used for treating bronchial asthma (BA) in children and adolescents. That is ensured by determining clinical, functional, cytological, biochemical, immunological allergic inflammation activity markers (AIAMs). These markers are evaluated according to the developed scales. The total score is calculated according to each scale separately. Allergic inflammation activity indices (AIAIs) are calculated by the certain formulas taking into account the calculated total scores according to each scale. An integrative AIAI is calculated. An allergic inflammation activity degree (AIAD) is determined depending on the integrative AIAI. If the AIAD is 0, therapy required for the stage I basic anti-inflammatory therapy of BA is conducted. The 1^st AIAD requires therapy corresponding to the stage II basic therapy. The 2^nd AIAD requires therapy corresponding to the 3^rd stage therapy; the 3^rd AIAD provides therapy corresponding to the 4^th stage basic anti-inflammatory therapy of BA.

EFFECT: method provides a differentiated approach to selecting a volume of basic therapy of the given disease by accurate diagnosing of a degree of activity of the allergic inflammatory process in the airway walls that in its turn provides reducing a rate of attacks and length of aggravations in prolonging BA remission.

2 ex, 10 tbl

Description

The invention relates to medicine, namely to pulmonology and allergology of childhood and adolescence and can be used to treat bronchial asthma (BA) in children and adolescents.

In the available literature, there are known ways to control the treatment of AD in children and adolescents (National Program "Bronchial Asthma in Children. Treatment and Prevention Strategy." - 3rd ed., Rev. And add. - M.: Atmosphere Publishing House, 2008 . - 108 p.) To evaluate the control of asthma, criteria are proposed for its complete or good control (Batemane) in children over 12 years of age. It is used in children over 12 years old and in adolescents (table 1).

It is known that the morphofunctional basis of bronchial hyperreactivity (BHR) is an allergic (non-infectious) chronic inflammation of the wall of the airways, characterized by the presence of mucus in the lumen of the bronchi containing various cellular elements, dysplasia and desquamation of the ciliary epithelium, an increase in the number of goblet cells, a thickening of the basement membrane, and infiltration mucosal membranes by lymphoid cells and granulocytes, with a predominance of eosinophils in infiltrate and secretion. These changes can be traced, starting from the early stages of the disease and further in the interictal period, both in the mild and severe cases of the course of the disease.

The inflammatory process affects all the structures of the wall of the bronchi: epithelial cover, basement membrane, broncho-associated lymphoid tissue (nodules), blood vessels, smooth muscles. This morphological picture is largely specific for AD and indicates that persistent inflammation is the basis of the disease. Moreover, in patients with AD who are in stable remission, the morphological changes characteristic of the disease are preserved. However, there is no correlation between clinical manifestations and morphological changes.

Table 1 CRITERIA FOR BA CONTROL IN CHILDREN 12 years (by Batemane) Indicators Disease control levels Good Full 2 or more of the following All of the following Daytime symptoms ≤2 with a rating on a scale of> 1 no Use of beta-2 agonists ≤2 days and ≤4 times total no Morning peak expiratory flow rate ≥80% of the due value every day ≥80% of the due value every day All of the following: All of the following: Awakening at night no no Exacerbations no no Emergency Calls no no Side effects of treatment not requiring a change in therapy not requiring a change in therapy The patient must meet the specified criteria for at least 7 out of 8 weeks

Based on the pathogenesis of AD, modern therapy is aimed at eliminating allergic inflammation of the bronchial mucosa, reducing GHB, restoring bronchial obstruction and eliminating bronchospasm, preventing structural adjustment of the bronchial wall (Geppe N.A., Misernitsky Yu.L., Revyakina V.A. O the new (third) version of the national program "Bronchial asthma in children. Strategy and prevention" // Pulmonology of childhood: problems and solutions / under the editorship of Yu.L. Mizernitsky and AD Tsargorodtsev. - M., 2009. - Issue 9. - S.183-185).

The prototype was taken as a basic anti-inflammatory therapy, which is the basis for the treatment of AD, in which drugs that relieve allergic inflammation in the mucous membrane of the respiratory tract are regularly and continuously used (National Program “Bronchial Asthma in Children. Treatment and Prevention Strategy.” - 3rd ed., Rev. and add. - M .: Publishing house "Atmosphere", 2008. - 108 p.).

The inflammatory process in the bronchi is detected not only during exacerbation, but also in the phase of remission, in connection with this, it is necessary to use anti-inflammatory drugs for the prevention of exacerbations of AD. The duration of therapy is determined by the ability to achieve a stable state and can be several months, and if necessary, several years.

A stepwise approach to basic anti-inflammatory therapy is its fundamental principle. A step-by-step approach to treatment involves matching the volume of therapy with the severity of the disease. In children older than 5 years, basic therapy is carried out under the control of external respiration function. Basic therapy is determined taking into account the initial severity of the disease at the time of examination of the patient; It is carried out for a long time, taking into account the specific clinical situation and is corrected depending on the degree of disease control. Basic treatment agents include: inhaled glucocorticosteroids (GCS) - both as monotherapy, and in combination with prolonged β2 - agonists (long-acting); systemic corticosteroids, cromoglycic acid (sodium cromoglycate, cromon), sodium subcromyl, antileukotriene preparations (Montelukast and Zafirlukast), extended release theophyllines, some anti-allergic drugs (ketotifen), and allergen-specific immunotherapy (ASIT). The volume of basic therapy is determined by the severity of AD, the age and nature of the concomitant pathology.

The essence of a stepwise approach to basic medical treatment of AD is to increase or decrease the volume of therapy, depending on the control of the symptoms of the disease. With insufficient control, the volume of therapy increases by a step. 3 months after achieving clinical and functional remission, the volume of therapy can be reduced by a step. The control criterion along with clinical symptoms is the need for short-acting β2-agonists.

1st stage: BA is light intermittent. Patients with mild intermittent AD do not need basic therapy. If necessary, inhaled β2-agonists of fast action are used. An alternative may be inhaled M - anticholinergics, oral short-acting β2-agonists or short-acting theophyllines.

2nd stage: BA is light persistent. Basic therapy with cromons is prescribed for a period of at least 3 months. Fast β2 agonists are used on demand. Long-acting β2 agonists or slow release theophylline can be added to cromons. With insufficient effect of cromonum, low or medium doses of inhaled GCS are prescribed.

Stage 3: BA of moderate severity. Low and medium doses of inhaled GCS and their combination with long-acting β2-agonists are preferred. A combination of inhaled corticosteroids with oral medications (antileukotriene drugs, theophylline slow release) is possible.

4th stage: BA is heavy. Use of inhaled GCS in medium and high doses is required. As a starting therapy, combined preparations with fixed combinations of GCS and β2-agonist (Budesonide + Formoterol, Flixotide + Salmeterol) can be used. The addition of β2 agonists is more preferable than increasing the dose of corticosteroids. A combination of high doses of inhaled corticosteroids with antileukotriene preparations and delayed release theophyllines is prescribed. Systemic corticosteroids for long-term treatment are rarely prescribed, only in extremely severe cases. Therefore, to control the treatment of AD it is recommended to use a wide range of clinical presentation and external respiration functions, evaluated in the dynamics of the disease.

However, the prototype has several disadvantages.

Monitoring of basic anti-inflammatory therapy is carried out only at the level of clinical symptoms of the disease and indicators of the function of external respiration. At the same time, the absence of a correlation between clinical manifestations and morphological changes in the bronchi was proved. However, there are available methods (cytological, biochemical, immunological) that can be used to determine locally the activity of inflammation in the bronchi and more reasonably resolve the issue of basic anti-inflammatory therapy. The duration of therapy, ranging from several months to several years, is not determined. In this case, the main reference point of the basic anti-inflammatory therapy is the onset of a stable state, but there is no definition or clear criteria for this stable state. It is recommended that therapy be appropriate for the condition, which also has no definition. There are no recommendations focusing on the activity of inflammation, as the basis of the pathological process, when determining the duration of basic anti-inflammatory therapy.

The volume of basic anti-inflammatory therapy is determined by the severity of the disease, taking into account the initial severity of the condition at the time of examination of the patient, the age of the patients and the nature of the associated pathology. In this case, the following parameters are the clinical parameters characterizing the severity of an exacerbation of AD:

- respiratory rate and heart rate;

- the participation of auxiliary muscles in the act of breathing and retraction of the jugular fossa;

- the intensity of wheezing, bloating;

- change in behavior, degree of restriction of physical activity;

forced position;

- functional indicators (FEV-1, PSV, PaO ₂ , PaCO ₂ , SaO ₂ ) and their degrees of deviation,

- the amount of therapy used to relieve exacerbation.

However, this list of clinical parameters characterizing the severity of an exacerbation of AD does not contain indicators of the activity of local inflammation in the bronchi. Since there is no correspondence between the above clinical and local inflammatory signs, this inevitably can lead to the wrong choice of basic anti-inflammatory therapy. Only local criteria for inflammation, reflecting the pathomorphological and pathophysiological nature of the disease, can determine the entire tactics of choice and amount of anti-inflammatory drugs.

The indications of the transition of basic therapy from one stage to another stage are only clinical and functional criteria, and there are no main more sensitive criteria for the local inflammatory process in the bronchi. It is recommended to increase or decrease the volume of therapy depending on the control of the clinical symptoms of the disease, which can lead to undesirable therapeutic effects without taking into account the activity of the inflammatory process. The failure to use the criteria for the activity of local inflammation in determining the volume of basic therapy in some cases is the reason for the insufficiently effective treatment of AD.

The main stepwise principle of the basic anti-inflammatory therapy of AD is not correctly implemented in the following: at the first stage, basic anti-inflammatory therapy is not recommended, at the same time, morphological (i.e. local) signs of inflammation in the bronchi are always present and even in clinical and functional remission. In this case, evidence of the presence or absence of inflammation activity is not required, which could objectively and reasonably resolve the issue of the appropriateness of basic anti-inflammatory therapy; at the second stage, basic therapy with cromons is recommended for a period of at least 3 months, which is not pathogenetically substantiated and determined simply empirically without taking into account any individual characteristics of the inflammatory process; at the 3rd and 4th stages of basic therapy, the treatment terms are not indicated at all. Therefore, the subjective approach to the appointment of predominantly inhaled glucocorticosteroids can be either insufficiently long or redundant, since no guidelines are given for determining the duration of their use. It is for anti-inflammatory inhaled glucocorticosteroids that the main criteria can only be indicators of the activity of the local inflammatory process, otherwise the use of glucocorticosteroids becomes pathogenetically insufficiently substantiated in each individual case.

The task of the invention is to develop a method for monitoring the basic anti-inflammatory treatment of bronchial asthma, which allows to increase the accuracy and effectiveness of the prescribed therapy.

The problem is solved by the method of differential control of the basic anti-inflammatory treatment of bronchial asthma in children and adolescents, including clinical and functional criteria for diagnosing bronchial asthma, which consists in the fact that clinical and functional criteria for diagnosis are carried out by three-stage diagnosis, in which at the first stage activity markers are determined allergic inflammation (MAAB), followed by their assessment on the developed scales and the calculation of the total points for each scale e separately, at the second stage, the allergic activity indices (IAAW) are calculated according to the developed mathematical formulas with the subsequent calculation of the integrative allergic inflammation activity index (IAAW), at the third stage, it is supposed to determine the degree of allergic inflammation activity (SAAI) in accordance with the characteristics of the signs: depending on the severity of each marker of the activity of allergic inflammation (MAAB) is evaluated by one of 4 ratings (0, 1, 2, 3 points), the diagnosis of the degrees of activity of allergic the inflammatory process in children and adolescents with this pathology is carried out according to the proposed clinical, functional, cytological, biochemical and immunological markers of the activity of allergic inflammation (MAAB) on the basis of a 4-point scale with the subsequent calculation of the integrative index of activity of allergic inflammation (IAAW): clinical (IAAW wedge .), functional (IAAV funct.), cytological (IAAV cytol.), biochemical (IAAV biochem.) and immunological (IAAA immun.) according to the following formulas:

1. IAAW wedge. = Σ points: n, where n is the number of evaluated MAAI (there are 8 of them);

2. IAAF funct. = Σ points: n, where n is the number of MAAI (there are 2);

3. IAAV cytol. = Σ points: n, where n is the number of MAAU (there are 7 of them);

4. IAAV biochemical. = Σ points: n, where n is the number of MAAV (there are 2);

5. IAAA immun. = Σ points: n, where n is the number of MAAI (there are 1),

this allows you to determine the degree of activity of allergic inflammation (SAAV) in accordance with the value of the integrative index of activity of allergic inflammation (IAAV):

0th SAAV with IAAV from 0 to 0.1 points,

I-SAAV with IAAV from 0.1 to 1.1 points,

II SAAV with IAAV from 1.2 to 2.1 points,

III-rd SAAV with IAAV from 2.2 to 3.0 points.

Moreover, each SAAV indicates the intensity of the allergic inflammatory process:

0-th SAAV - on its absence,

I-th SAAV - for minimal severity,

II-nd SAAB - for moderate severity,

III-th SAAV - for maximum severity, depending on the degree of activity of allergic inflammation (SAAV), determine the volume of therapeutic measures depending on the degree of activity of allergic inflammation (SAAV) (0-I, I-I, II-I, III-I ), namely: when establishing the 0th SAAV, treatment is prescribed in the volume of the 1st stage, respectively, the 1st - SAAV - the 2nd stage, the 2nd SAAV - the 3rd stage and the 3rd SAAV - the 4th steps.

The technical result of the proposed method is as follows: the availability of technical performance and its application in clinical practice; improving the accuracy of diagnosing the activity of allergic inflammation; providing an integrated and individual approach to the diagnosis of the activity of allergic inflammation; the use of not only general (clinical, functional, immunological), but also local (cytological indicators of bronchial secretions, biochemical indicators of expired air vapor) markers as criteria for diagnosing the activity of allergic inflammation, reducing subjectivity and possible errors in diagnosing the activity of allergic inflammation (AAV) for due to the introduction of developed scales with gradation of the severity of markers of the activity of allergic inflammation (MAAV) and the calculation of integrative activity indices of alle rgic inflammation (IAAW), including clinical, functional, cytological, biochemical and immunological, a differentiated approach to determining the intensity of inflammation according to the degree of activity of allergic inflammation (SAAI) depending on the value of the integrative IAAA; the use of SAAV as indicators for the choice of the volume of therapeutic measures according to the stages of basic therapy of AD; the achievement of a greater degree of reduction in the activity of allergic inflammation, expressed in a decrease in clinical, functional, cytological, biochemical, immunological IAAVs by 21.6-35.6% and integrative IAAVs by 27.5%, as well as in an increase in the frequency of absence of AAS (0- i) and the 1st SAAV by 1.3-2.0 times and in the decrease in the occurrence of the second and third SAAVs by 1.9 and 2.9 times; a reduction in the frequency of asthma attacks and the duration of exacerbations by 1.5-1.6 times with an increase in the duration of remission by 1.2 times, a decrease in hospitalization rates, visits to the clinic and VUT on sheets of temporary disability in cases and days of 1.5-2, 4 times.

The essence of the proposed method.

First, the degree of activity of allergic inflammation (SAAV) is determined and, in accordance with this, the volume of therapeutic measures is prescribed. Diagnosis of the degrees of activity of the allergic inflammatory process in children and adolescents with this pathology is carried out according to the proposed clinical, functional, cytological, biochemical and immunological markers of the activity of allergic inflammation (MAAB) based on a 4-point scale, followed by the calculation of the integrative index of the activity of allergic inflammation (IAAV) and the definition of SAAV.

A method for diagnosing the activity of allergic inflammation in children and adolescents with AD is carried out in 3 stages:

Stage 1 - assessment of markers of the activity of allergic inflammation (MAAB);

Stage 2 - counting the activity indices of allergic inflammation (IAAV);

3rd stage - determination of the degree of activity of allergic inflammation (SAAV).

Stage 1 includes the determination of informative clinical, functional, cytological, biochemical and immunological MAAV. MAAV assessment is carried out according to the developed scales (tables 2-6). Scales have gradations of 4 points:

0 points - no sign

1 point - a mild sign,

2 points - a moderate symptom,

3 points - a very pronounced sign.

Depending on the severity, each marker of allergic inflammation activity (MAAB) is evaluated by one of 4 ratings (0, 1, 2, 3 points).

table 2 SCALE OF CLINICAL MARKERS OF ALLERGIC INFLAMMATION ACTIVITY (MAAB) IN CHILDREN AND ADOLESCENTS WITH BRONCHIAL ASTHMA (BA) Clinical MAAB Criteria for the activity of inflammation, (points) 0 points 1 point 2 points 3 points Behavior pattern Common behavior Slightly modified Moderately changed Drastically changed Physical activity Saved Slightly reduced Moderately reduced Significantly reduced Dry spastic cough Absent Weak, fickle Moderate, more permanent Sharp, frequent Expiratory dyspnea Absent Appears during physical exertion. Detected at rest intermittently Detected at rest constantly Involvement of ancillary muscles Absent Rarely occurs Inconsistently determined Constantly determined Boxed percussion sound over the lungs Not determined It is determined to a small extent, rarely Moderately expressed, often determined Significantly expressed, often determined Elongated and labored exhalation Absent Occurs during exercise Appears at rest intermittently Detected at rest constantly Wheezing Absent Insignificant Moderately expressed Significantly expressed

Table 3 SCALE OF FUNCTIONAL MARKERS OF THE ACTIVITY OF ALLERGIC INFLAMMATION (MAAV) IN CHILDREN AND ADOLESCENTS WITH BA Functional MAAB Criteria for the activity of inflammation, points 0 points 1 point 2 points 3 points OFV-1 (according to computer spirography), l / s Corresponds to the age norm Obstructive type I ventilation deficiency Obstruction type II ventilation failure Obstruction type III insufficiency PSV (according to peak flowmetry data), l / s Corresponds to the age norm Reduced by 20-30% Reduced by 31-40% Reduced by 41-60% or more

Table 4 SCALE OF CYTOLOGICAL MARKERS OF ACTIVITY OF ALLERGIC INFLAMMATION (MAAB) OF THE MUCOSURES OF THE LOWER RESPIRATORY WAYS IN CHILDREN AND ADOLESCENTS WITH BA Cytological MAAV Criteria for the activity of inflammation, points 0 points 1 point 2 points 3 points Etz,% 78.22-72.58 72.57-67.88 67.87-63.18 63.17-58.48 E% 1.12-1.66 1.67-2.11 2.12-2.56 2.57-3.01 N% 9.27-12.85 12.86-15.65 15.66-18.55 18.56-21.45 Lf,% 1.22-1.88 1.89-2.43 2.44-2.98 2.99-3.53 AM,% 7.10-10.10 10.11-12.60 12.61-15.10 15.11-17.60 Etz / Lts 5.97-5.13 5.12-4.43 4.42-3.73 3.72-3.03 Etz / Am 10.50-7.50 7.49-5.00 4.99-2.50 2.49-0

Table 5 SCALE OF BIOCHEMICAL MARKERS OF ALLERGIC INFLAMMATION ACTIVITY (MAAB) IN CHILDREN AND ADOLESCENTS WITH BA Biochemical MAAV Criteria for the activity of inflammation, points 0 points 1 point 2 points 3 points The content of nitric oxide (NO), μm / ml 2.56-3.28 3.29-3.88 3.89-4.48 4.49-5.08 The content of αl-acid glycoprotein (αl-KGP), ng / ml 1.41-1.95 1.96-2.40 2.41-2.85 2.86-3.30

Table 6 SCALE OF IMMUNOLOGICAL MARKERS OF ALLERGIC INFLAMMATION ACTIVITY (MAAB) IN CHILDREN AND ADOLESCENTS WITH BA Immunological MAAV Criteria for the activity of inflammation, points 0 points 1 point 2 points 3 points Ig E total, IU / ml The indicator is within the age norm 2-3 times increased Increased 4-6 times Raised 7-10 times or more

Upon completion of the IAAA assessment on five scales, the total score for each scale is calculated separately.

The 2nd stage consists in calculating the indices of the activity of allergic inflammation (IAAW): clinical (IAAW wedge), functional (IAAW funct.), Cytological (IAAW cytol.), Biochemical (IAAW biochemical) and immunological (IAAA immun.) the following formulas:

1. IAAW wedge. = Σ points: n, where n is the number of evaluated MAAI (there are 8 of them);

2. IAAF funct. = Σ points: n, where n is the number of MAAI (there are 2);

3. IAAV cytol. = Σ points: n, where n is the number of MAAU (there are 7 of them);

4. IAAW biochem. = Σ points: n, where n is the number of MAAW (there are 2);

5. IAAA immun. = Σ points: n, where n is the number of MAAI (there are 1).

(Osin A.Ya., Matveeva L.I., Schegoleva E.B. Degrees of activity of allergic inflammation in bronchial asthma in children and adolescents // Joint Immunological Forum - 2008 (St.-Petersburg, 30.06.2008 - 05.07. 2008). - Russian Immunological Journal. - RAS: Nauka, 2008. - Volume 2 (11). - No. 23. - p. 222; Osin A.Ya., Uskova A.V. ”Shchegoleva EB and other activity of the inflammatory process in bronchopulmonary diseases in children and adolescents // Actual problems of pediatrics, pediatric surgery and orthopedics at the present stage: Materials of a scientific-practical conference with international participants thiem (Khabarovsk, October 8-10, 2009) .- Khabarovsk, 2009.- p. 78-81; Osina T.D., Schegoleva E.B., Matveeva L.I., Osin A.Ya. Criteria for the activity of allergic inflammation in asthma in children and adolescents // Actual issues of allergology and pediatrics: Materials of the 5th regional scientific-practical conference (Vladivostok, May 17, 2007). - Vladivostok, 2007, - p.31- 36 .; Osin A.Ya., Schegoleva E.B., Osin A.Ya., Matveeva L.I. A method for diagnosing the activity of chronic allergic inflammation in children with respiratory allergies // Modern technologies in pediatrics and pediatric surgery: Materials of the VI Russian Congress (Moscow, October 23-25, 2007). - M., 2007, - p. 39-40).

Possible values of the activity indices of allergic inflammation (IAAV) can fluctuate in the theoretically acceptable range from 0 to 3.0 points. After calculating the IAAW data, the integrative IAAV is calculated by the formula:

Integrative IAAW = (IAAW wedge + IAAW funct. + IAAW cytol. + IAAW biochemical + IAAA immun.): N (5).

The 3rd stage allows you to determine the degree of activity of allergic inflammation (SAAV) in accordance with the value of the integrative index of activity of allergic inflammation (IAAV):

0th SAAV with IAAV from 0 to 0.1 points,

I-SAAV with IAAV from 0.1 to 1.1 points,

II SAAV with IAAV from 1.2 to 2.1 points,

III-rd SAAV with IAAV from 2.2 to 3.0 points.

Moreover, each SAAV indicates the intensity of the allergic inflammatory process:

0-th SAAV - on its absence,

I-th SAAV - for minimal severity,

II-nd SAAB - for moderate severity,

III-th SAAV - for maximum severity.

To study the diagnosis of the degrees of activity of allergic inflammation, 450 patients with asthma in children and adolescents aged 3 to 18 years were included in the study volume. Of these, the number of boys and boys was 240 (53.3 ± 3.2%) and girls and girls - 210 (46.7 ± 3.4%). Children aged 3 to 10 years old were 145 (32.2 ± 3.9%) and adolescents 10 to 18 years old - 305 (67.8 ± 2.7%). For diagnosis, the classification of bronchial asthma (BA) was used. Along with clinical methods for examining patients, chest x-ray was used according to the generally accepted method, computed spirography using a Spiro Vision-2 PC spirograph using the Low Radiation program, peak flow measurement using a Pulmot peak flow meter with PSV determination (l / min) , a clinical analysis of peripheral blood according to the generally accepted methodology, bacteriological and bacterioscopic studies of smears from the nose and throat, sputum, studies of the immune status (if indicated), allergological studies (carrying out scarification skin and local scarification tests, determination of IgE content in blood serum by ELISA), cytoimmunological studies of tracheobronchial secretion (or sputum) according to A.Ya. Aspen (2000), the study of exhaled air vapor condensate (CPVV) with the determination of the total content of nitric oxide (NO) metabolites using Grace's reagent (1988) and the level of α-1 acid glycoprotein (α-1 KGP) by ELISA by E. Engvall ( 1980).

The results of the studies showed differences between the IAAV at different periods of the disease (table 7.). The average values of IAAV differed 2.1-4.5 times, and the integrative IAAV 2.8 times during periods of exacerbation and remission.

According to the results of the integrative IAAA, SAAW was calculated (table 8.). During the period of exacerbation and remission of asthma, significant differences in the frequency of occurrence of SAAW were determined. During the period of exacerbation, the 0th and 1st SAAWs were not met, and during the period of remission, the 0th and 1st SAAWs were determined in 50.0% and 41.6% respectively. In the period of BA exacerbation, II-nd SAAV was found 4.0 times more often than in the period of remission (p <0.001). During the period of exacerbation, the third SAAV was found in 2/3 of the patients, but was not determined during the period of remission (0%). The data obtained correspond to the level of evidence “B”, i.e. moderate certainty in accordance with uniform international criteria. According to the WHO classification, data obtained from at least one randomized controlled trial qualifies as Category IIa (Smolkin Yu.S., Balabolkin II, Markova TP, etc. Primary prevention of allergies in children: Conciliation document of the Association of Children's Allergologists and Immunologists of Russia (ADAIR) - Moscow, 2010. - 72 p.).

Table 7 ALLERGIC INFLAMMATION ACTIVITY INDICES (IAAV) IN CHILDREN AND ADOLESCENTS WITH BRONCHIAL ASTHMA (BA) (X ± m _x ) IAAB IAAV values (points) Aggravation (n = 240) Remission (n = 240) p Vibrations X ± m _x Vibrations X ± m _x IAAW wedge. 1.5-3.0 1.8 ± 0.2 0-1.0 0.4 ± 0.1 <0.001 IAAW Functions 1.7-3.0 2.1 ± 0.2 0.1-1.5 0.6 ± 0.1 <0.001 IAAW cytol. 1.7-3.0 2.2 ± 0.3 0.2-2.0 0.9 ± 0.1 <0.001 IAAW biochem. 1.6-3.0 1.9 ± 0.2 0.2-2.0 0.9 ± 0.1 <0.001 IAAW Immune. 1.6-3.0 2.0 ± 0.2 0.2-1.8 0.8 ± 0.1 <0.001 IAAW integrate. 1.8-3.0 2.0 ± 0.2 0.2-1.7 0.7 ± 0.1 <0.001 Note: p is the degree of reliability of differences in IAAV values during the period of exacerbation and remission

Table 8 ACTIVITY DEGREES OF ALLERGIC INFLAMMATION (SAAV) IN CHILDREN AND ADOLESCENTS WITH BRONCHIAL ASTHMA (BA) (Abs. Number, P ± m _p ) SAAV Frequency (%) Aggravation (n = 240) Remission (n = 240) P Abs. P ± m _p ,% Abs. P ± m _p ,% 0th 0 0 120 50.0 ± 3.2 - II 0 0 one hundred 41.6 ± 3.2 - II 80 33.3 ± 3.0 twenty 8.3 ± 1.8 <0.001 III 160 66.6 ± 3.0 0 0 - Note: p is the degree of reliability of differences in the values of IAAV during the period of exacerbation and remission of AD

Examples of the method.

Example 1. Child V., 9 years old, was hospitalized in the pulmonology department of the Municipal Clinical Hospital "Children's Clinical Hospital" in Vladivostok during an exacerbation of moderate asthma. A clinical examination of the patient revealed: the child is moderately excited in behavior (2 points), physical activity is moderately reduced (2 points), moderately expressed dry spastic cough (2 points), expiratory dyspnea during physical exertion (1 point), the participation of auxiliary muscles is determined intermittently (2 points), moderate percussion box sound above the lungs (2 points), elongated and difficult exhalation during physical exertion (1 point), moderate wheezing (2 points).

IAAW wedge. = 14 points: 8 MAAW = 1.75 points.

When considering functional studies, functional MAABs were determined: during computer spirography, ventilation insufficiency of the II degree (2 points) was determined, during peak flowmetry, a decrease in the peak expiratory rate by 35% (2 points) was determined. IAAF funct. = 4 points: 2 MAAB = 2, 0 points.

In the tracheobronchial secretion, an increasing cell content was detected: E 2.34% (2 points), H 16.24% (2 points), Lf 2.52% (2 points), AM 14.98% (2 points) and a decreasing number ETs up to 66.34% (2 points), ETs / Lts ratio of 3.93 (2 points) and ETs / AM 3.24 (2 points).

IAAV cytol. = 14 points: 7 MAAB = 2 points.

In the condensate of expired air vapor (CPVV), the content of NO metabolites was 4.24 μM / ml (2 points) and α1 - CHP - 2.84 ng / ml (2 points).

IAAW biochem. = 4 points: 2 MAAW = 2 points.

In the immunogram, the content of total Ig E is doubled (1 point).

IAAV immunol. = 1 point: 1 MAAB = 1 point.

Integrative IAAV = (1.75 + 2.0 + 2.0 + 2.0 + 1.0 points): 5 = 1.75 points, which corresponds to the II-nd IAAV.

Therefore, the II-nd SAAV was diagnosed, which indicates a moderately pronounced activity of the allergic inflammatory process, and the treatment volume corresponding to the III-rd stage is shown.

Example 2. Teenager S., 12 years old, was undergoing routine treatment at the Children's Clinical Hospital of Vladivostok in the period of remission of moderate asthma. A clinical examination revealed: the child’s behavior was not changed (0 points), physical activity was slightly reduced (1 point), there was no cough (0 points), expiratory dyspnea was not determined during physical activity (0 points), there was no involvement of auxiliary muscles (0 points) ), boxed percussion sound is not detected (0 points), elongated and difficult exhalation only during physical exertion (1 point), wheezing is absent (0 points).

IAAW wedge. = 2 points: 8 MAAW = 0.25 points.

When considering functional studies, functional MAABs were determined: during computer spirography, ventilation insufficiency of the first degree was determined (1 point), during peak flow measurement, a decrease in the peak expiratory flow rate by 25% (1 point) was determined.

IAAB funct. = 2 points: 2 MAAB = 1.0 points.

In the tracheobronchial secretion, an increasing cell content was detected: E 1.67% (1 point), H 12.76% (1 point), Lph 1.91% (1 point), AM 12.1% (1 point) and a decreasing number ETs up to 72.58% (1 point), the ratio ETs / Lts 5.14 (1 point) and ETs / AM 7.52 (1 point).

IAAV citol. = 7 points: 7 MAAB = 1 point.

In CPVP, the content of NO metabolites was 3.31 μM / ml (1 point) and α1 - CHP - 1.98 ng / ml (1 point).

IAAW biochemical. = 2 points: 2 MAAW = 1 point.

In the immunogram, the content of total Ig E is doubled (1 point).

IAAV immunol. = 1 point: 1 MAAB = 1 point.

Integrative IAAV = (0.25 + 1.0 + 1.0 + 1.0 + 1.0 points): 5 = 0.85 points, which corresponds to the 1st SAAU.

Therefore, the 1st SAAV was diagnosed, which indicates a minimally pronounced activity of the allergic inflammatory process, and the volume of treatment corresponding to the second stage is shown.

A comparative assessment of the effectiveness of control methods for the basic anti-inflammatory treatment of AD in 150 patients taking into account the activity of allergic inflammation (the claimed method) in 150 patients without taking into account the activity of allergic inflammation and (prototype method based on the step principle only) at the end of the treatment period for patients in groups during 1 year (table 9). From the presented results of the study, significant differences in the influence of control methods on the activity of allergic inflammation follow.

A comparative analysis of the proposed method and the prototype method shows that the claimed method is characterized by lower activity indices of allergic inflammation (IAAW). Clinical IAAI decreased by 23.1%, functional IAAV by 21.6%, cytological IAAV by 35.6%, biochemical IAAV by 33.3%, immunological IAAV by 27.1% and integrative IAAV, by 27 ,5%. Confirmation of the positive impact of the proposed method on the activity of allergic inflammation in comparison with the known method is also the structure of the degrees of activity of allergic inflammation (CAAB). In this case, the frequency of absence of AAA (0-SAAV) increased by 2.0 times and I-SAAV - 1.3 times, and the frequency of occurrence of II - and SAAV decreased by 1.9 times and III - and SAAV - by 2 9 times.

Therefore, the method of differential control of the basic anti-inflammatory treatment of AD taking into account the activity of allergic inflammation is characterized by higher efficiency, which is expressed in a decrease in the studied IAAV by 21.6% -35.6% and integrative IAAV by 27.5%, as well as in an increase in the frequency of absence AAV (0-th SAAV) and I-SAAV 1.3-2.0 times and a decrease in the occurrence of the II-nd SAAV and III-th SAAV by 1.9-2.9 times.

In addition, a clinical and medical-social comparative characteristic of the effectiveness of control methods for the basic anti-inflammatory treatment of bronchial asthma is given in 150 patients taking into account the activity of allergic inflammation (the proposed method) and in 150 patients without taking into account the activity of allergic inflammation (prototype method) based on only a stepwise principle at the end of the treatment period for patients in groups for 1 year (table 10).

Table 9 Comparative evaluation of the effectiveness of control methods for the basic anti-inflammatory treatment of bronchial asthma in children and adolescents (Abs. Number, X ± m _x , P ± m _p ,%) Allergic inflammation activity indicators Groups surveyed The inventive method (n = 150) Method - prototype (n = 150) R 1. The activity indices of allergic inflammation (IAAW): - IAAA Clinical 1.82 ± 0.05 2.24 ± 0.05 <0.001 - IAAA functional 1.53 ± 0.05 1.86 ± 0.05 <0.001 - IAAV cytological 1.15 ± 0.03 1.56 ± 0.03 <0.001 - IAAV biochemical 1.20 ± 0.03 1,60 ± 0,03 <0.001 - IAAV immunological 1.40 ± 0.05 1.78 ± 0.05 <0.001 - IAAV integrative 1.42 ± 0.05 1.81 ± 0.05 <0.001 2. The degree of activity of allergic inflammation (SAAV): - 0 th SAAV,% (43) 28.7 ± 3.7 (21) 14.0 ± 2.8 <0.01 - I-th SAAV,% (74) 49.3 ± 4.1 (56) 37.3 ± 3.9 <0.01 - II-nd SAAV,% (23) 15.3 ± 2.9 (44) 29.3 ± 3.7 <0.01 - III-th SAAV,% (10) 6.7 ± 2.5 (29) 19.3 ± 3.2 <0.01 - SAAV average 1.00 ± 0.05 1.54 ± 0.05 <0.001

Table 10 Clinical and medical-social characteristics of the effectiveness of the methods of basic anti-inflammatory treatment of AD in children and adolescents (x ± m _x ) Indicators Groups surveyed The inventive method (n = 150) Prototype method (n = 150) P The frequency of asthma attacks (amount per year) 2.60 ± 0.18 4.10 ± 0.39 <0.001 The duration of exacerbations, days 91.25 ± 8.20 141.66 ± 13.05 <0.01 Duration of remission, days 274.75 ± 15.02 223.34 ± 10.06 <0.01 Hospitalization rates: - number of cases 0.75 ± 0.06 1.30 ± 0.11 - number of days of illness 9.00 ± 0.82 17.55 ± 1.55 Outpatient clinic rates: - number of cases 1.85 ± 0.16 2.80 ± 0.24 <0.001 - number of days of illness 22.2 ± 2.05 37.80 ± 3.35 <0.001 Indicators of temporary disability (VUT) on sheets of temporary disability: - number of cases 1.05 ± 0.09 2.15 ± 0.20 <0.001 - number of days of work loss 12.60 ± 1.10 29.02 ± 2.74 <0.001

The frequency of asthma attacks decreased by 1.6 times, the duration of exacerbations of asthma decreased by 1.5 times, and the duration of remission increased by 1.2 times. Hospitalization rates by the number of cases and the number of days of illness decreased by 1.9-2.0 times, the number of cases in the clinic by the number of cases and the number of days of illness by 1.5-1.7 times and indicators of temporary disability (VUT) by sheets of temporary disability in cases and days of loss of work - 2.0-2.4 times.

Therefore, the method of differential control of the basic anti-inflammatory treatment of AD taking into account the activity of allergic inflammation differs from the prototype in higher efficiency and is expressed in a reduction in the frequency of AD attacks and the duration of exacerbations by 1.5-1.6 times with an increase in the duration of remission by 1.2 times, and also in reducing the rates of hospitalization, visits to the clinic and the high-level medical center on sheets of temporary disability in cases and days by 1.5-2.4 times.

Claims (1)

The method of differential control of the basic anti-inflammatory treatment of bronchial asthma in children and adolescents, including the determination of clinical and functional criteria for the diagnosis of asthma, characterized in that at the first stage they determine 8 clinical, 2 functional, 7 cytological, 2 biochemical and 1 immunological markers of the activity of allergic inflammation (MAAV ) in patients, then these markers are evaluated according to the corresponding scales presented in tables 4-6, then the total score for each scale is calculated separately; at the second stage, the activity indices of allergic inflammation are calculated: clinical (IAAW wedge), functional (IAAW funct.), cytological (IAAW citol.), biochemical (IAAW biochem.) and immunological (IAAA immun.) according to the formulas:
IAAW wedge. = Σ points / 8;
IAAF funct. = Σ points / 2;
IAAV cytol. = Σ points / 7;
IAAW biochem. = Σ points / 2;
IAAV immun. = Σ points / 1;
then calculate the interactive IAAW = (IAAW wedge + IAAH funct. + IAAH cytol. + IAAH biochemical. + IAAA immun.) / 5;
at the third stage, determine the degree of activity of allergic inflammation (SAAV) in accordance with the value of the interactive IAAV:
O-th SAAW is determined with an interactive IAAV from 0 to 0.1 points;
1st SAAV with interactive IAAV from 0.1 to 1.1 points;
II-nd SAAW with interactive IAAU from 1.2 to 2.1 points;
III-th SAAW is determined with an interactive IAAV from 2.2 to 3.0 points;
then, depending on the value of SAAV, the volume of subsequent therapeutic measures is determined according to the stepwise principle: at 0 SAAV, treatment is carried out corresponding to the 1st stage of the basic anti-inflammatory therapy of BA, at 1 SAAV, treatment is carried out corresponding to the 2nd stage of basic therapy, II-nd SAAV is given treatment corresponding to the III-rd stage of therapy, and at the III-rd stage of SAABs, treatment corresponding to the IV-th stage of the basic anti-inflammatory therapy of AD is carried out.