RU2765432C1 - Method for assessing the severity of bronchial asthma exacerbation using an integral indicator - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to immunology and allergology, pulmonology, and can be used to assess the severity of exacerbation of bronchial asthma. The integral indicator for assessing the severity of bronchial asthma exacerbation was developed on the basis of specialized clinical and functional characteristics. The invention makes it possible to determine the severity of exacerbation of bronchial asthma, which further contributes to the correct personalized selection of anti-asthmatic therapy that prevents subsequent exacerbations of asthma. This method can be used in clinical studies for comparative analysis of the course of BA in different groups of patients with different trigger factors and/or those on different therapy regimens.

EFFECT: method provides an increase in the reliability of the diagnosis of the severity of bronchial asthma.

1 cl, 4 tbl, 2 ex

Description

The invention relates to medicine, namely to immunology and allergology, pulmonology, and can be used in diagnosing the severity of an exacerbation of bronchial asthma.

Bronchial asthma (BA) is currently one of the most common inflammatory diseases of the respiratory tract [1]. The prevalence of BA in Russia among the adult population is 6.9%, and among children and adolescents - about 10% [2, 3].

Bronchial asthma is a heterogeneous disease characterized by chronic inflammation of the airways, the presence of respiratory symptoms such as wheezing, shortness of breath, chest congestion and cough, which vary in time and intensity, and manifest together with variable airway obstruction [1].

AD reduces the quality of life and working capacity of patients, and also leads to significant economic losses. One of the undesirable outcomes of the course of BA is exacerbation of the pathological process, in the event of which patients are forced to seek help from hospitals and emergency departments, remain disabled for a significant period of time. Each exacerbation of asthma reduces the functional reserve of the lungs of patients, requires an increase in the dose of inhaled glucocorticosteroids in basic therapy and the appointment of systemic steroids, which, in turn, have a number of side effects [4]. Moreover, exacerbations of asthma become the main cause of death from this disease. Therefore, it is necessary to develop a set of measures to reduce the number of BA exacerbations [1].

The main causes of asthma exacerbation are respiratory viral infections and exposure to a causally significant allergen [5].

The guidelines of the Global Strategy for the Treatment and Prevention of Bronchial Asthma (GINA) and the Federal Clinical Guidelines for the Diagnosis and Treatment of Bronchial Asthma fully describe the criteria for asthma control [1, 2] (Table 1).

In addition, the asthma conciliation documents contain detailed formulations of risk factors for the development of asthma and algorithms for providing medical care in case of exacerbation of asthma.

According to the Federal Clinical Guidelines, exacerbations of bronchial asthma are episodes of increasing shortness of breath, coughing, wheezing, or chest congestion, requiring changes in the usual treatment regimen [2]. The formation of an exacerbation of asthma is influenced by various triggers that induce inflammation of the airways or provoke acute bronchospasm. These triggers can vary significantly from patient to patient.

The main triggers are respiratory tract infections (mainly respiratory viruses [5]), causally significant allergens, aeropollutants, physical activity, meteorological factors, taking certain drugs (beta-blockers, in patients with "aspirin asthma" - non-steroidal anti-inflammatory drugs (NSAIDs)), emotional reactions and others. Additional factors that can lead to exacerbation of asthma are exacerbation of rhinosinusitis, gastroesophageal reflux, pregnancy, and insufficient therapy [2].

It should be noted that there are criteria according to which asthma exacerbations are divided into mild, moderate, severe, life-threatening. These criteria are based on clinical characteristics [2] (Table 2).

Currently, there is a known method for assessing the severity of bronchial asthma, its atopic and mixed (atopic and infection-dependent) variants, characterized in that it is prescribed to test the clinical signs of autonomic dystonia syndrome, secondary immunodeficiency, determine the content of class E immunoglobulin and, in the presence of a vagoinsular form of the syndrome vegetative dystonia, elevated levels of immunoglobulin class E diagnose mild severity of bronchial asthma; in the presence of a sympathoadrenal form of the syndrome of vegetative dystonia, T-cell or monocytic immunodeficiency, a moderate severity of bronchial asthma is diagnosed; in the presence of the sympathoadrenal form of the syndrome of vegetative dystonia, combined T-cell monocytic immunodeficiency, a severe form of bronchial asthma is diagnosed (RU 2268001 C1, 20.01.2006). This method makes it possible to identify in patients with varying degrees of severity of bronchial asthma the features of the frequency of occurrence and structure of secondary immunodeficiency, depending on the intensity of clinical manifestations of bronchopulmonary pathology, in which the form (sympathoadrenal or vagoinsular) of manifestations of the syndrome of autonomic dystonia and secondary immunodeficiency, as well as the level of class E immunoglobulin different.

A known method for predicting exacerbations of bronchial asthma (BA) over the next year in patients with concomitant obesity, including the definition of diagnostic indicators, characterized in that the following are determined as diagnostic indicators: body mass index (BMI), kg/m2, leptin level in venous blood , ng/ml, adiponectin level in venous blood, µg/ml, patient compliance using the “Compliance Scale for Patients with Chronic Nonspecific Lung Diseases”, presented in the description, to determine the compliance level, the scores obtained are summarized, the level of situational anxiety (ST) on the anxiety scale Spielberger, points, the level of depression on the Zung self-reported depression scale, points; based on the data obtained, the index of the probability of exacerbation of BA during 1 year of observation (ExBA) is calculated according to the formula:

ExBA=8.63042-0.0536544*ADIPONECTIN-0.134532*COMPLIANCE+0.0602315*ST+0.00909584*LEPTIN-0.0471218*BMI-0.0814472*DEPRESSION,

and with an ExBA value of less than 3, a low risk of developing BA exacerbations is predicted, with the number of exacerbations - 1 time per year, with an ExBA value of 3 or more, a high risk of exacerbations is predicted, with the number of exacerbations per year 2 or more times (RU 2655829 C1, 29.05. 2018). However, this method makes it possible to predict the development of BA exacerbations in patients with comorbidities, in particular obesity, due to the simultaneous accounting of a set of diagnostically significant indicators for this prognosis.

A known method for assessing the severity of the course of infectious-dependent bronchial asthma (RU 2182333 C2, 05/10/2002), including the determination of T-lymphocytes, B-lymphocytes and immunoglobulin A in a blood test, characterized in that, in addition, indicators of circulating immune complexes are determined in a blood test ( CEC) and eosinophils and calculate the severity index (SI) of the disease according to the formula

where the CEC is conventional units, B is lymphocytes - 109/l, eosinophils - 109/l, T-lymphocytes - 109/l, immunoglobulin-A - g/l, and with a severity index of up to 0.50 conventional units. units, diagnose the norm, from 0.51 to 0.80 - mild degree, from 0.81 to 0.95 - moderate degree and more than 0.95 - severe. This method assesses the severity of the course of bronchial asthma with the presence of an infectious component of the disease, and is also based only on the determination of immunological blood parameters.

Closest to the proposed method is a method for diagnosing the severity of bronchial asthma in children (RU 2355317 C2, 05/20/2009), including examination of patients, characterized in that the integral sensitization index (IIS) is calculated based on the determination of 4 reliable informative indicators: the level of total plasma IgE blood, eosinophilia in a smear of peripheral blood, eosinophilia in a smear from the nasal cavity, positive skin prick tests with any of the 6 allergens: house dust mites - 2 species; library dust mites; mold; the epidermis of animals - a cat, a dog, then the obtained indicators are evaluated in points: where the level of total IgE: normal values (less than 100 IU / ml) are evaluated as 1 point, moderately increased from 100 to 400 IU / ml - 2 points, significantly increased more than 400 IU/ml - 3 points; eosinophilia in a peripheral blood smear: normal values less than 5% - 1 point, elevated values more than 5% - 2 points; eosinophilia in a nasal swab: no cells - 1 point, presence of 1 or more cells - 2 points; positive skin tests with any of the 6 allergens: the severity of the reaction is less than "++" - 1 point, the severity of the reaction is more than "++" - 2 points, after which the scores are summarized and the value of the integral sensitization index (IIS) is obtained, with the value which from 4 to 6 diagnose intermittent BA, and with a value of 7 to 9 - persistent BA.

The disadvantages of this method is the verification of the severity of asthma in children without the use of anamnestic and spirographic data.

In addition, when characterizing the severity of BA exacerbation, it is necessary to take into account information about the required treatment (duration, volume of therapy with systemic glucocorticosteroids), the fact of the need for hospitalization, including in the intensive care unit.

Thus, at the moment there is no universal method for assessing the severity of an exacerbation of BA, the presence of which would allow a reliable and objective assessment of the severity of an exacerbation of BA, both in an individual aspect for each patient, and when analyzing groups of patients with BA.

The objective of the invention is to create an informative method for an objective assessment of the severity of BA exacerbation based on an integral indicator, including a retrospective analysis of clinical and functional characteristics used in clinical practice.

The invention is based on the creation of a method for diagnosing the severity of bronchial asthma, in which patients are examined and an integral indicator is calculated based on clinical and functional characteristics: duration of exacerbation of BA (number of days), duration of use of systemic glucocorticosteroids (GCS) (number of days), FEV1 (% ), hospitalization - yes / no, degree of blood oxygen saturation (%), stay in the intensive care unit - yes / no, which are evaluated in points from 0 to 3, where the duration of exacerbation of BA and the duration of the use of systemic corticosteroids: 0 days are evaluated as O points , 1-3 days as 1 point, 4-7 days - 2 points, 8 days or more - 3 points; with FEV1 of > 80%, 0 points are scored, with FEV1 of 70 - 79% - 1 point, FEV1 of 60-69% - 2 points, FEV1 < 60% - 3 points; with a degree of blood oxygen saturation of ≥ 95%, 0 points are determined, with values of 92-94% - 1 point, with 90-91% - 2 points, < 90% - 3 points; in the absence or presence of hospitalization, stay in the intensive care unit, 0 points or 3 points are determined, respectively, after which the scores are summed up and the value of the integral indicator is obtained, and at a value of which 0 - no exacerbation is diagnosed, from 1 to 4 mild exacerbation of BA, with a value of 5 to 9 - moderate exacerbation, and ≥10 - severe exacerbation.

The technical result of the claimed invention is the development of an integral indicator for assessing the severity of an exacerbation of bronchial asthma, including a retrospective analysis of the clinical and functional characteristics of an exacerbation of asthma, taking into account spirographic data and treatment data - duration, volume of therapy with systemic glucocorticosteroids. This diagnostic method based on the developed integral indicator allows to reliably distinguish the absence of exacerbation, mild manifestations from moderate and severe, and the average degree from the severe form of bronchial asthma, which contributes to the correct selection of therapy for the relief of asthma exacerbation, a personalized approach when choosing anti-asthmatic basic therapy.

Description of the invention

The generally accepted criteria for an exacerbation of asthma, in addition to an increase in symptoms, a deterioration in external respiration, an increase in the need for the use of fast-acting inhaled bronchodilators, signs of tachypnea and tachycardia, a decrease in blood oxygen saturation, is the need to prescribe systemic glucocorticosteroids (GCS) for at least three days in a row or at least a twofold increase in the volume of systemic corticosteroid therapy for patients who were initially on oral corticosteroids [1].

When assessing the severity of an exacerbation of asthma, the duration of an exacerbation of asthma, the duration of corticosteroid therapy, the need for hospitalization and emergency medical attention, and the severity of obstructive changes in breathing are of decisive importance.

The development of an integral indicator for assessing the severity of BA exacerbation was carried out on study participants with exacerbation of atopic BA against the background of exposure to a causally significant allergen and the triggering effect of respiratory viruses.

Taking into account the above definitions, we have developed an integral indicator for assessing the severity of BA exacerbation, which includes six characteristics, each of which is estimated from 0 to 3 points (Table 3).

List of considered characteristics:

• duration of asthma exacerbation (measured in days);

• duration of use of systemic corticosteroids (measured in days);

• the smallest forced expiratory volume in 1 second recorded during an exacerbation of BA, FEV ₁ (measured as a percentage (%), relative to the proper values);

• hospitalization (yes / no);

• the degree of blood oxygen saturation (the lowest indicator determined by the method of pulse oximetry during an exacerbation of BA, measured as a percentage (%);

• stay in the intensive care unit (yes / no).

The integral criterion is formed as the sum of points obtained for each characteristic of BA exacerbation.

Based on the Integral indicator, three degrees of severity of an exacerbation of BA can be distinguished (Table 4):

• 0 points - no exacerbation of BA;

• 1-4 points - slight exacerbation of BA;

• 5-9 points - exacerbation of BA of moderate severity;

• 10 or more points - severe exacerbation of BA.

A slight exacerbation of BA manifests itself in the form of a lack of BA control, a decrease in FEV ₁ (70-79%), requiring the appointment of systemic corticosteroids in a short course (parenteral or oral), while the degree of blood oxygen saturation is within normal values (more than 95%) and there is no need hospitalization of the patient for inpatient treatment.

An exacerbation of moderate BA is characterized by severe symptoms, a moderate decrease in FEV ₁ (60-69%), a decrease in blood oxygen saturation (less than 95%), the need for inpatient treatment and, possibly, a stay in the intensive care unit due to signs of severe respiratory failure and / or a violation of vital signs with a mandatory and pathophysiologically justified long-term course of systemic corticosteroids (4-7 days).

Directly, a severe exacerbation of BA is a course of BA with severe manifestations of respiratory failure, a significant decrease in FEV ₁ (less than 60%), a decrease in blood oxygen saturation (less than 90%), the relief of which is carried out only in a hospital and intensive care for several days before stabilization of the state of vital signs with the use of a long course of systemic corticosteroids in high doses (more than 8 days).

Example 1

The Integral indicator developed by us was used to assess the severity of BA exacerbation in a clinical study for a comparative analysis of exacerbations in patients with various trigger factors.

The study included 54 patients with atopic BA. All patients were treated for relief of exacerbation in a hospital setting.

The diagnosis of atopic BA was confirmed by the anamnesis, the results of screening, clinical, allergological, instrumental (spirometry, pulse oximetry) examination. The course of BA of moderate and severe severity was determined. In all patients, exacerbation of atopic asthma occurred under the influence of various trigger factors - respiratory viruses or the action of a causally significant allergen.

To stop the exacerbation, all patients received systemic corticosteroids parenterally (dexamethasone or prednisolone) and nebulizer therapy (budesonide nebules, salbutamol nebules), the duration of which depended on the objective condition of the patient and the severity of the exacerbation of atopic BA. Some patients, based on vital signs (respiratory rate, pulse oximetry, blood pressure, pulse, FEV ₁ or peak expiratory flow rate, symptoms of respiratory failure, etc.), were in the intensive care unit for monitoring and treatment, then after an objective assessment of their condition, they continued treatment in the allergology department.

In the process of monitoring the course of exacerbation of atopic asthma in hospital patients, data were obtained on a more severe course of exacerbation against the background of trigger exposure to respiratory viruses that were detected in this group of patients in nasal discharge.

It was necessary to reliably mathematically confirm this hypothesis.

We analyzed 38 patients with an exacerbation of atopic asthma against the background of exposure to a causally significant allergen and with the exclusion of the presence of a respiratory viral infection (respiratory viruses were not detected in the discharge from the nasal cavity).

We determined the Integral Index for each patient, and during statistical data processing, we obtained an average value for the described group of patients 7.2±1.8 (P<0.05), which corresponded to an exacerbation of atopic BA of moderate severity.

These data allowed us to objectively and reliably assess the course of asthma in patients with atopic asthma without manifestations of a respiratory viral infection.

Next, we analyzed 16 patients with an exacerbation of atopic asthma under the trigger influence of respiratory viruses. The Integral criterion was determined for each patient, and during statistical data processing, the average value for the described group of patients was 13.6±2.4 (P<0.05), which corresponded to a severe exacerbation of atopic BA.

Statistical analysis of the obtained data was carried out using the statistical software package Statistica 12.0. Sample data were given as medians, and the maximum and minimum values were also indicated. The use of the Integral indicator for assessing the severity of asthma exacerbation made it possible to reliably assess that the severity of atopic asthma exacerbation under trigger exposure to respiratory viruses was more significant than under the influence of a causally significant allergen (13.6±2.4 vs 7.2±1.8 (P <0.05)).

Example 2

The proposed method was used by us to assess the severity of BA exacerbation in some clinical situations.

A 42-year-old male patient was hospitalized due to an exacerbation of bronchial asthma.

During an objective examination, the patient's blood oxygen saturation was measured by pulse oximetry, which corresponded to 94%.

The patient was confirmed to have atopic asthma based on complaints, medical history, allergic history, and skin allergy testing.

According to the results of spirometry, the patient was diagnosed with mild bronchial obstruction, where FEV1 was equal to 73%.

To stop the exacerbation of asthma, the following treatment was carried out: parenteral anti-inflammatory (dexamethasone IV 4 mg 1 time per day for five days) and bronchodilator therapy; nebulizer therapy (budesonide nebula 1000 mcg per day and salbutamol nebula 2500 mcg per day for five days).

Against the background of ongoing anti-asthma therapy, improvement was noted - exacerbation of atopic BA was stopped. The patient continued to receive basic anti-asthma therapy - inhalation of budesonide/formoterol 320/9 μg 2 times a day endobronchially, daily.

According to the clinical data and the time of the patient's response to the treatment, the doctor assessed that this exacerbation of atopic BA can be considered as moderate severity.

When analyzing this clinical case “inpatient treatment of exacerbation of atopic BA”, we applied the Integral criterion developed by us.

The patient was admitted to the hospital - 3 points.

Duration of BA exacerbation - 5 days - 2 points.

The duration of the use of systemic corticosteroids (dexamethasone IV) - 5 days - 2 points.

Forced expiratory volume in 1 second, FEV1 - 73% - 1 point.

The degree of blood oxygen saturation - 94% - 1 point.

For the entire period of treatment in the hospital, there were no indications for staying in the intensive care unit - 0 points.

Thus, the total score of the Integral indicator for assessing the severity of exacerbation of atopic BA in this patient was 9 points. According to the total score of the Integral indicator, it is possible to objectively and reliably interpret the exacerbation of atopic asthma described above as an exacerbation of asthma corresponding to moderate severity.

When comparing the conclusion about the severity of BA exacerbation by the patient's attending physician and the data of the Integral indicator, we obtained a correspondence between the clinical subjective and mathematically reliable substantiation of the severity of BA exacerbation.

Bibliography

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention (2020 update). Gina. 2020. https://ginasthma.org/reports/ Link available 11/16/2020.

2. Federal clinical guidelines for the diagnosis and treatment of bronchial asthma. 2019. https://spulmo.ru/upload/kr_bronhastma_2019.pdf (Link active as of 11/16/2020). [Federal clinical guidelines for the diagnosis and treatment of bronchial asthma. 2019 (In Russ.)]

3. National program “Bronchial asthma in children. Treatment strategy and prevention”. 2012 (IV edition). [Nacional'naya programma "Bronhial'naya astma u detej. Strategy lecheniya i profilaktika. 2012 (IV edition) (In Russ.)]

4. Heffler E. Strategies to reduce corticosteroid-related adverse events in asthma. / Heffler E., Bagnasco D., Canonica G.W. // Curr Opin Allergy Clin Immunol. - 2019. - Vol. 19(1). - P. 61-67.

5. Jackson D.J. The role of viruses in acute exacerbations of asthma. / Jackson D.J., Johnston S.L. // Journal of Allergy and Clinical Immunology. - 2010. - Vol. 125(6). - P. 1178-1187.

6. Galitskaya M.A. Some features of inflammation in patients with atopic bronchial asthma when exposed to respiratory viruses. / M.A. Galitskaya, O.M. Kurbacheva, I.P. Shilovsky, A.A. Nikolsky, A.A. Nikonova, M.E. Dyneva, M.R. Khaitov // Immunology. - 2020 - T. 41. - No. 2 - S. 154-163.

Claims (1)

A method for assessing the severity of an exacerbation of bronchial asthma (BA), including a survey of patients and the calculation of an integral indicator based on clinical and functional characteristics: the duration of an exacerbation of asthma - the number of days, the duration of the use of systemic glucocorticosteroids (GCS) - the number of days, FEV1 in%, the presence of hospitalization, the degree blood oxygen saturation in%, stay in the intensive care unit, then evaluate the characteristics in points, where the duration of exacerbation of BA and the duration of the use of systemic corticosteroids: 0 days are rated as 0 points, 1-3 days as 1 point, 4-7 days - 2 points, 8 days or more - 3 points; with FEV1 of more than 80%, 0 points are scored, with FEV1 of 70-79% - 1 point, FEV1 of 60-69% - 2 points, FEV1 of less than 60% - 3 points; at a degree of blood oxygen saturation of 95% or more, 0 points are determined, at values of 92-94% - 1 point, at 90-91% - 2 points, less than 90% - 3 points; the presence of hospitalization, stay in the intensive care unit is assessed as 0 points in the absence and 3 points in the presence, respectively, after which the scores are summed up and the value of the integral indicator is obtained, at a value of which 0 diagnoses the absence of an exacerbation, from 1 to 4 - a mild exacerbation of BA, at a value of 5 to 9 - an exacerbation of moderate severity and at 10 or more - a severe exacerbation.