RU2796385C1 - Method for determination of bronchial destruction degree in patients with bronchial asthma - Google Patents

Abstract

FIELD: medicine; internal medicine; pulmonology.

SUBSTANCE: determine the level of physical activity according to the ODA23+ questionnaire, the level of activity of patients according to Lequesne scale and the level of the total antioxidant capacity ImAnOx. Then, calculate forced expiratory volume (FEV₁) based on the received data using a given formula. With a FEV₁ value of 80.0% to 100.0% determine mild degree of bronchial obstruction, with an FEV₁ of 60.0% to 79.9% - moderate bronchial obstruction, with an FEV₁ less than 60.0% - severe bronchial obstruction.

EFFECT: method allows to determine degree of bronchial obstruction by the value of FEV₁ due to the simultaneous accounting of indicators that are diagnostically significant for given determination of degree of obstruction summation.

1 cl, 2 tbl, 3 ex

Description

The field of technology to which the invention belongs

The invention relates to medicine, namely to therapy and pulmonology, and can be used to individually determine the degree of bronchial obstruction in patients with bronchial asthma (BA).

The level of technology.

Worldwide, there is currently a pandemic of chronic non-specific diseases (CNCD), which includes AD. In mortality from chronic NCDs, along with hyperglycemia (6.0%) after arterial hypertension (13.0%) and smoking (9.0%), a low level of physical activity (PA) makes a significant contribution (Balanova Yu.A., Shalnova S.A., Kutsenko V.A., Imaeva A.E., Kapustina A.V., Muromtseva G.A., Evstifeeva S.E., Maksimov S.A., Karamnova N.S., Yarovaya E.B., Kulakova N.V., Kalachikova O.N., Chernykh T.M., Belova O.A., Artamonova G.V., Indukaeva E.V., Grinshtein Yu.I., Libis R.A., Duplyakov D .V., Rotar O.P., Trubacheva I.A., Serebryakova V.N., Efanov A.Yu., Konradi A.O., Boytsov S.A., Drapkina O.M. Contribution of arterial hypertension and others risk factors in survival and mortality in the Russian population, Cardiovascular Therapy and Prevention, 2021; 20(5):3003, https://doi.org/10.15829/1728-8800-2021-3003). All over the world, including in the Russian Federation, there is a decrease in FA in all age groups (Global status report on physical activity 2022. Geneva: World Health Organization; 2022. License: CC BY-NC-SA 3.0 IGO https://www .who.int/publications/i/item/9789240059153). For BA, unlike other chronic obstructive diseases, the variability of respiratory symptoms of different duration, intensity, frequency, which is combined with reversible bronchial obstruction, is characteristic. The pathogenetic mechanisms of the development of asthma are heterogeneous, which is associated with the need to personalize diagnostic and therapeutic approaches in the management of patients with asthma (Global Strategy for Asthma Management and Prevention (2022 update), https://gunasthma.orn/wp-content/uploads/2022 /07/GINA-Main-Report-2022-FINAL-22-07-01-WMS.pdf). Quite often, FA causes symptoms that are associated with or mimic AD. Intuitively or intentionally, patients often avoid PA or increase it and lead a sedentary lifestyle. Literature reviews show that patients with asthma engage in PA less frequently than people without asthma (Hansen ESH, Pitzner-Fabricius A, Toennesen LL, et al. Effect of aerobic exercise training on asthma in adults: a systematic review and meta-analysis. Eur Respir J 2020; 56).

The imbalance of the prooxidant-antioxidant system with the formation of oxidative stress is a pathogenetic link not only in inflammatory processes of any origin, but also in oncological, cardiovascular, bronchopulmonary diseases. Oxidative stress plays the most important role in the pathogenesis of bronchopulmonary pathology, since anatomical and physiological features, exogenous (microorganisms, pollutants), endogenous (eosinophils, macrophages, neutrophils, gene mutations, mitochondrial and microsomal oxidation, xanthine oxidase, metabolites of arachidonic acid) act as activation factors for free radical processes. acids, etc.). Lung tissue is a source of oxidative stress. Directly in the lungs, tissues are in contact with oxygen, which is the initiator and participant in the oxidation processes. A large number of unsaturated fatty acids in the lung tissue act as a substrate for lipid peroxidation, and during inflammation, activated alveolar macrophages and other phagocytic cells begin to produce reactive oxygen species, initiating lipid peroxidation (Tseilikman V.E., Lukin A.A. Effect of oxidative stress on the human body International Research Journal 2022;3-1(117):206-211).

With free radical damage to the lungs, inflammatory cell infiltration increases the secretion of biologically active substances, increases vascular permeability. The existing relationship between the increase in peroxidation, the activity of the inflammatory process, the severity of the clinical picture and the duration of the disease indicates a significant role of imbalance in the prooxidant-antioxidant system of the body in the pathogenesis of AD (Madieva L.S., Mamashalieva S.B., Bakirova R.E., Muravleva L.E., Ibraeva L.K. Some aspects of the pathogenesis of bronchial asthma: a review of the literature. Modern problems of science and education. 2020; 2: 4-9).

In patients with AD, alveolar macrophages and phagocytes excessively and uncontrollably generate reactive oxygen species, making a significant contribution to the formation of oxidative stress, which leads to the depletion of the body's antioxidant system. The development of oxidative stress is also supported by the harmful effects of the environment - air pollution, tobacco smoke. Against the background of oxidative stress, the balance between the expression of genes for pro-inflammatory mediators and antioxidant enzymes is shifted towards inflammatory mediators. The system of functionally interconnected antioxidants limits the accumulation and pathological effect of oxygen-dependent free radicals. The fact of participation of genetically determined deviations in the functioning of various antioxidant enzymes associated with the presence of functional polymorphisms in the structure of their genes in the development of AD has been established. Phenotypically, these deviations manifest themselves as an imbalance of prooxidant-antioxidant reactions with a shift in redox homeostasis towards increased free radical oxidation and the formation of oxidative stress in the respiratory tract. In patients with AD, there was a decrease in the activity of the enzymatic link of the antioxidant system with the accumulation of products of free radical oxidation of proteins and lipids, which confirms the presence of oxidative stress in AD (Michaeloudes C, Abubakar-Waziri H, Lakhdar R, Raby K, Dixey P, Adcock IM, Mumby S , Bhavsar PK, Chung KF Molecular mechanisms of oxidative stress in asthma Mol Aspects Med 2022 Jun 85:101026 doi: 10.1016/j.mam.2021.101026).

Thus, the imbalance of the prooxidant-antioxidant system is of great importance in the pathogenesis of AD.

This determines the feasibility of searching for new effective preventive measures, as well as determining the predictors of progression, insufficient control of asthma, taking into account the pathogenetic mechanisms of asthma, especially in patients with low physical activity.

Known "Method for diagnosing disorders of bronchial patency" (RF patent for invention No. 2291666; 04/25/2005), which allows recording and analysis of respiratory noise on the trachea during the execution of the forced exhalation maneuver by the subject. The total duration of the noise process (T) is determined, the chest circumference of the subject is additionally measured during quiet breathing (OG1) and maximum inspiration (OG2), the normalized duration of the noise process Tn is calculated equal to (a⋅T⋅OG1b/OG2c)d, where a, b, c, d - coefficients calculated by regression modeling for a representative sample of healthy individuals of the same sex as the subject and the same age group. If the value of Tn exceeds the threshold value, a decision is made about the presence of violations of bronchial patency.

The disadvantages of the method are: the determination of only the presence of violations of bronchial patency, the method does not give a conclusion about the severity of bronchial obstruction.

Known "Method for diagnosing the syndrome of bronchial obstruction", (RF patent for invention No. 2245550; 29.04.2002), which consists in diagnosing the syndrome of bronchial obstruction by recording respiratory sounds using a sensor inserted into the patient's oral cavity, and with their subsequent processing on computer, characterized in that forced expiratory breath sounds are recorded, and wavelet analysis is used to process the breath noise signal on the computer, and when frequent and uneven peaks are detected on the wavelet spectrogram in the low frequency range up to 300 Hz, as well as in the high frequency range from 2000 to 18000 Hz define bronchial obstruction syndrome.

The disadvantages of the method are: for the diagnosis of the syndrome of bronchial obstruction, a special device is needed - an audiofluograph, as well as a computer program for processing registered respiratory sounds; the method is designed only for children; the method does not give a conclusion about the severity of bronchial obstruction.

Known "Method for diagnosing the severity of bronchial asthma" (RF patent for invention No. 2348352; 7.11.2006), including an assessment of the patency of the bronchial tree according to the peak flow curve, characterized in that for at least one month of regular basic therapy, patency is monitored of the bronchial tree in combination with the determination of the reversibility of bronchial obstruction by measuring the peak expiratory flow rate (PEF) before (first curve) and 30 minutes after the use of a bronchodilator (second curve), the obtained indicators are compared with the average statistical norms of healthy people and determine the amount of increase in PSV in% - the difference between PSV before and after the use of a bronchodilator, referred to the initial PSV and expressed in%, and then after one month, the obtained peak flow indicators are evaluated, and the severity is set as follows: with normal initial PSV values, at least 80% of the average statistical indicators of healthy and in the absence of the dynamics of this indicator under the influence of a bronchodilator, the PSV of the second peak flow curve - increases by less than 15% in relation to the PSV of the first curve, a mild severity of bronchial asthma is diagnosed; with low initial values of PSV of the first curve less than 80% of the average statistical indicators of healthy people and their increase by 15% or more in relation to the initial values under the influence of a bronchodilator with the achievement of normal bronchial patency - 80% or more in relation to the average statistical indicators of healthy people, a moderate degree of severity is diagnosed ; with stably recorded low PSV values of the first peak flow curve less than 80% in relation to the average statistical parameters of healthy people and their increase after the use of a bronchodilator by less than 15% in relation to the initial values of bronchial patency that does not reach normal values - less than 80% of the average statistical parameters of healthy people are diagnosed severe degree of the disease. The effectiveness of the method lies in the appointment of the appropriate severity of the disease, the most effective treatment.

The disadvantages of the method are: the need for a long, for at least one month on the background of regular basic therapy, monitoring of the patency of the bronchial tree according to the peak flow curve to assess the patency of the bronchial tree and determine the severity of asthma; correction of therapeutic and preventive measures for patients with asthma is possible only after one month of observation.

Known "Method for diagnosing bronchial obstruction" (RF patent for the invention No. 2368307; 06/16/2008), intended for non-invasive diagnosis of bronchial obstruction. The circumference of the chest is measured with calm breathing. The following parameters of forced expiratory sounds (EF) are measured: the total duration of the EF sound (Ttot), the rise time of the amplitude (Tnast), the frequency of the maximum sound energy of the EF (Fmax), the coefficient (Qvyd) - the ratio of the total energy of low (LF) and medium (MF) frequencies to the energy of high frequencies (HF), the shares of the relative energy of HF, MF and LF in percent. In addition, body mass index (BMI), peak expiratory flow rate (PSV), "smoker" index (IC), and the presence of occupational hazard are determined. According to a certain formula, the degree of bronchial obstruction is determined. If the obstruction coefficient is in the range from 100 to 86.456, then there is no bronchial obstruction, if in the range from 86.455 to 80.887 the diagnosis is mild bronchial obstruction, if in the range of 80.886 to 43.684 the diagnosis is moderate bronchial obstruction, if in the range from 43.683 to 0 - severe bronchial obstruction. The method allows to increase the efficiency of diagnosis of bronchial obstruction.

The disadvantages of this method are: the diagnosis of bronchial obstruction only in patients with chronic obstructive pulmonary disease; the method is not applicable for patients with BA.

Previously, we developed a “Method for determining the degree of bronchial obstruction in patients with bronchial asthma and concomitant obesity” (RF patent No. 2692229 dated June 21, 2019), which consists in determining the diagnostic indicators of venous blood: leptin level, resistin level, 25-OH vitamin level D, interferon-γ level, interleukin-4 level, neuropeptide Y level, degree of total oxidative damage to biological molecules (PerOx), tumor necrosis factor alpha level. The method allows to calculate the forced expiratory volume (FEV1) using the developed formula. The disadvantages of this method is the need for laboratory examination of patients, the presence of obesity in patients.

The technical problem we solved was a personalized approach to patients with asthma in order to identify factors that affect the degree of bronchial obstruction, since low physical activity and imbalance of the prooxidant-antioxidant system are considered as factors responsible for the aggravation of the clinical course of asthma and the difficulty in controlling the disease.

Disclosure of the essence of the invention

Achievable technical result is a reliable determination of the degree of bronchial obstruction in patients with BA in terms of forced expiratory volume (FEV ₁ ), due to the simultaneous accounting of a set of diagnostically significant indicators for this determination of the degree of obstruction.

The technical result is achieved through the following methods.

In a patient with AD, such indicators as the level of motor activity according to the ODA23+ questionnaire, the level of activity of patients according to the Lequesne scale, and the level of the total antioxidant capacity of ImAnOx are determined.

Then, based on the data obtained, the forced expiratory volume (FEV1) is calculated using the formula:

FEV ₁ =79.5541+0.237103×ODA23-1.33917×LEKEN-0.0556527×ImAnOx,

where ODA23 is the result according to the motor activity questionnaire ODA23+ in points,

LEKEN - the result of assessing the dynamics of the activity of patients on the Leken scale in points,

ImAnOx - level of total antioxidant capacity, µmol/l.

And when the value of FEV ₁ is less than 100% and at the same time equal to and more than 80.0%, a mild degree of bronchial obstruction is determined, when the value of FEV ₁ from is simultaneously equal to and less than 79.9% and from is simultaneously equal to and more than 60.0% - bronchial obstruction of medium severity, when the value of FEV ₁ from both equal to and less than 59.9% severe bronchial obstruction.

Implementation of the invention.

We have developed a formula for calculating FEV ₁ to determine the degree of bronchial obstruction in patients with asthma.

To calculate the parameters of the model, we analyzed the data of 237 patients with asthma aged 18 to 78 years: men - 51 (21.5%), women - 186 (78.5%), mean age 52.6±1.3 years. Clinical and laboratory examination of patients was performed at the stage of inclusion in the study.

The diagnosis of asthma was established in accordance with the GINA 2022 criteria.

All patients underwent a comprehensive examination, which included the collection of complaints and anamnesis, an assessment of the objective status, and laboratory testing.

The level of motor activity was assessed using the ODA23+ motor activity questionnaire developed at the Federal State Budgetary Institution “GNITsPM” of the Ministry of Health of Russia (Aronov D.M., Krasnitsky V.B., Bubnova M.G., 2013). Motor activity was assessed as "Very high" at ≥ 109 points, "High" at 85-108 points, "Moderate" at 62-84 points, "Low" at 39-61 points, "Very low" at ≤38 points.

The assessment of the dynamics of the activity of patients in everyday life was carried out using the Leken's functional index. With a result of 0 points - there was no disability, the degree of disability was assessed as "Mild" at 1-4 points, "Moderate" at 5-7 points, "Severe" at 8-10 points, "Sharply pronounced" at 11-13 points, "Extremely pronounced" at ≥ 14 points (Lequesne M. Indices of severity and disease activity for osteoarthritis. Semin Arthritis Rheum. 1991; 20(6(2)):48-54).

The assessment of the activity of free radical processes and the state of antioxidant defense systems was carried out according to the level of total antioxidant capacity by enzyme immunoassay (ELISA) using the Immanox (ImAnOx) kit from Immundiagnostik (USA). Overall antioxidant status/capacity was rated "Low" at <280 µmol/L.

Statistical data processing was carried out using the STATGRAPHICS 18 for Windows software package. To analyze dependencies, we used logistic regression analysis. The adequacy of the model was considered statistically significant at p <0.05.

Using the apparatus of multivariate regression analysis, the factors influencing FEV1 in patients with BA were determined.

Thus, forced expiratory volume (FEV1) in % is selected as a predictive variable, using quantitative variables the result of the motor activity questionnaire (points), the result of patients' activity on the Lequesne scale (points), the level of total antioxidant capacity (µmol / l), using of the original regression equation, a model is obtained for determining the degree of bronchial obstruction in patients with BA by the volume of forced

In table. 1 shows the parameters of the model that affect FEV ₁ in patients with BA.

The regression model looks like:

FEV ₁ =79.5541+0.237103×ODA23-1.33917×LEKEN-0.0556527×ImAnOx

where the diagnostic indicators are:

ODA23 - result on the motor activity questionnaire,

LEKEN - the result of an assessment of the dynamics of the activity of patients on the Leken scale,

ImAnOx - the level of total antioxidant capacity.

FEV ₁ "from 80.0% to 100.0%" indicates a mild degree of bronchial obstruction,

FEV ₁ "from 60.0% to 79.9%" indicates moderate bronchial obstruction,

FEV ₁ "from 59.9% or less" indicates a severe degree of bronchial obstruction.

As follows from Table 2, the model is statistically significant at the 99.99% confidence level.

The practical feasibility of the proposed method is illustrated by examples from clinical practice.

Example 7

Patient V., aged 46, diagnosis: Bronchial asthma of mixed origin, mild severity, partially controlled by DN0.

Comprehensive examination data: the result of ODA23+ was 95 points, the result of the activity of patients on the Lequesne scale was 1 point, the level of the general antioxidant status/ability (ImAnOx) was 291.42 µmol/l.

The degree of bronchial obstruction, determined using our original regression equation, was:

FEV ₁ =79.5541+0.237103×95-1.33917×1-0.0556527×291.42=84.52134951%

That is, FEV ₁ "from 80.0 to 100.0%", which indicates a mild degree of bronchial obstruction.

According to spirometry, the patient's FEV ₁ value was 82.1% of the predicted value. Thus, our calculation was confirmed.

Example 2

Patient M., aged 52, diagnosis: Bronchial asthma of mixed genesis, moderate severity, partially controlled by VNO. Obesity 2 degrees, exogenous-constitutional genesis. Generalized osteoarthritis: with a predominant lesion of the small interphalangeal joints of the hands, nodular form (Heberden's, Bouchard's nodes), bilateral osteoarthritis of the knee joints 1 tbsp. right and 2 tbsp. left. FN 2. Comprehensive examination data: the result of ODA23+ was 74.5 points, the result of the activity of patients on the Lequesne scale was 8.5 points, the level of the general antioxidant status/ability (ImAnOx) was 224.37 µmol/l.

The degree of bronchial obstruction, determined using our original regression equation, was:

FEV ₁ =79.5541+0.237103×74.5-1.33917×8.5-0.0556527×224.37=73.34864351%

That is, FEV ₁ "from 60.0 to 79.9%" indicating moderate bronchial obstruction.

According to spirometry, the patient's FEV ₁ value was 72.7% of the predicted value. Thus, our calculation was confirmed.

Example 3

Patient K., 45 years old, with a diagnosis of severe allergic bronchial asthma, uncontrolled DN0, moderate allergic rhinitis. Obesity 2 degrees, exogenous-constitutional genesis. Generalized osteoarthritis: involving the joints of the spine, bilateral osteoarthritis of the hip joints 1st degree, bilateral gonarthrosis 2nd degree. right and 2 tbsp. left. FN 2. Comprehensive examination data: the result of ODA23+ was 49 points, the result of the activity of patients on the Lequesne scale was 13 points, the level of the general antioxidant status/ability (ImAnOx) was 279.45 µmol/l.

The degree of bronchial obstruction, determined using our original regression equation, was:

FEV ₁ =79.5541+0.237103×49-1.33917×13-0.0556527×279.45=58.21051478%

That is, FEV ₁ "from 59.9% or less", which indicates a severe degree of bronchial obstruction.

According to spirometry, the patient's FEV ₁ value was 48.7% of the predicted value. Thus, our calculation was confirmed.

The developed method allows to calculate the forced expiratory volume (FEV ₁ ) in patients with BA and to determine the degree of bronchial obstruction: if the value of FEV ₁ is less than 100% and at the same time equal to and more than 80.0% - mild degree; when the value of FEV ₁ from is simultaneously equal to and less than 79.9% and from is simultaneously equal to and more than 60.0%, the average severity; when the value of FEV ₁ from is simultaneously equal to and less than 59.9% severe.

Claims (1)

A method for determining the degree of bronchial obstruction in patients with bronchial asthma, including the determination of diagnostic indicators, characterized in that the level of motor activity according to the ODA23+ questionnaire, the level of activity of patients according to the Lequesne scale, the level of total antioxidant capacity ImAnOx are determined as diagnostic indicators; Based on the data obtained, the forced expiratory volume (FEV ₁ ) is calculated using the formula: FEV ₁ =79.5541+0.237103×ODA23-1.33917×LEKEN-0.0556527×ImAnOx, where ODA23 is the result of motor activity assessment according to the questionnaire ODA23+ in points, LEKEN - the result of assessing the dynamics of the activity of patients on the Leken scale in points, ImAnOx - the level of total antioxidant capacity, µmol/l; with a FEV ₁ value of less than 100% and more than 80.0%, a mild degree of bronchial obstruction is determined, with a FEV ₁ value in the range from less than 79.9% to 60.0% - moderate bronchial obstruction, with a FEV ₁ value of equal to or less than 59.9% - severe degree of bronchial obstruction.