RU2612861C1 - Method for diagnosis of myocardium morphofunctional disturbances for children older than 5 years with bronchopulmonary diseases associated with exposure to benzene, toluene, phenol and formaldehyde - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: concentration benzene, toluene, phenol and formaldehyde is determined in the chold's blood sample. If it exceeds the background value, functional and laboratory parameters are determined. The following is determined as the functional parameters: myocardium electrophysiological function, heart rate variability, heart contractile function and intracardiac hemodynamics, valvular function. The following is determined as laboratory parameters: white blood cells level, level of antioxidant activity AOA, malondialdehyde MDA, high-sensitive C-reactive protein, and apolipoproteins. In case of sinus bradycardia/tachycardia, eutonic initial vegetative tonus, accompanied by predominating activity of the autonomic nervous system parasympathetic division, asympathicotonic/hypersympathicotonic reactivity, increase in systolic blood pressure in the pulmonary artery, transient right ventricular diastolic dysfunction, as well as in case of white blood cell excess by 20% and more, MDA - 1.3 times or more, high-sensitivity C-reactive protein - 1.8 times or more, reduction of AOA 1.2 times or more and at increased apolipoprotein A1 and decreased "apolipoprotein B/apolipoprotein A1" factor relative to the physiological age norm, morphofunctional myocardium disorders are diagnised for children older than 5 years with bronchopulmonary diseases associated with exposure to benzene, toluene, phenol and formaldehyde.

EFFECT: method provides reliable and informative diagnosis of morphofunctional myocardium disorders, timely treatment and prevention of complications development by assessing the most significant functional and laboratory parameters.

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Description

The invention relates to medicine, namely to pulmonology, cardiology and toxicology, and can be used for early diagnosis of morphofunctional myocardial disorders in children over 5 years old with respiratory diseases, in particular with bronchial obstruction, living in a living environment with increased aerogenic exposure to toxic compounds : toluene, benzene, phenol, formaldehyde.

The invention can be used to detect myocardial disorders associated with the inhalation effect of these organic compounds, and is aimed at early detection of cardiac disorders, in order to prevent the progression of complications of chronic respiratory diseases.

The cardiovascular and respiratory systems are morphologically and functionally interconnected; therefore, changes in the heart play a role in the development of respiratory diseases. A variety of cardiovascular disorders during exacerbation of bronchopulmonary diseases in children has been studied by many researchers, but there are still some diagnostic difficulties.

Diseases of the respiratory organs of children consistently occupy a leading place in the structure of the general incidence rate and, for example, in 2013 amounted to 12,561.7 cases per 100,000 children in the Russian Federation. Over the past five years, there has been a slight decrease in the incidence of chronic bronchitis, chronic obstructive diseases, bronchial asthma in children from 1521.2 to 1325.6 cases per 100,000 children. According to the State Report in 2013, the tense situation regarding the level of atmospheric air pollution developed in the Siberian, Ural and Far Eastern districts. Common pollutants from industrial enterprises and vehicles were suspended solids, carbon monoxide, nitrogen dioxide, aromatic hydrocarbons, formaldehyde. At the same time, 5.6% of respiratory diseases are associated with air pollution.

Currently, the issues of the development of morphofunctional changes in the myocardium in children with chronic respiratory diseases, which are associated with the aerogenic impact of adverse environmental factors, remain insufficiently covered.

Currently, there are known methods for diagnosing myocardial lesions, including in patients suffering from pulmonary diseases, based on clinical, instrumental and laboratory data.

A known method for the diagnosis of non-coronarogenic myocardial damage in patients with pulmonary tuberculosis (RF patent No. 2475746), according to which the same patient before and during anti-tuberculosis therapy in the blood serum determines the concentration of heart protein that binds fatty acids (SBLC), and with an increase Concentrations of SBSS are diagnosed with non-coronarogenic myocardial damage. The known invention provides early preclinical diagnosis of non-coronarogenic myocardial damage in this group of patients.

However, its drawback is that SBLC, located in the free form of the cardiomyocyte, is rapidly released regardless of the acting factor as a result of myocardial ischemia leading to necrosis, which reduces the accuracy of the method. In addition, it does not take into account the modifying effect of environmental factors on the formation of lung diseases (tuberculosis).

The prior art method for the diagnosis of right ventricular hypertrophy in patients with chronic obstructive bronchitis (RF patent No. 2216270). When it is implemented in patients with chronic obstructive bronchitis, an electrocardiogram (ECG) is recorded according to a standard technique. The following indicators are analyzed: the amplitude of the S wave in the first standard lead, the sum of the amplitude of the R waves in the first chest and S in the fifth chest leads, the amplitude of the R wave in the strengthened lead from the right hand, the amplitude of the T wave in the first and second chest leads, take into account the patient’s age and the duration of the disease. The above parameters are substituted into the original mathematical formula. The presence of right ventricular hypertrophy is diagnosed by the value of the calculated indicator Z.

The disadvantage of this method is the ability to diagnose only in the adult population with a long history of chronic obstructive bronchitis; and also the exclusion from examination of patients with the presence on the ECG of signs of blockade of the legs of the bundle of His and / or myocardial infarction of any location.

Also known is a method for diagnosing coronary heart disease (CHD) in patients with chronic obstructive pulmonary disease (COPD) (RF patent No. 2187240). A patient with COPD is given a provocative pharmacological test. The test consists in the inhalation of salbutamol in a dose of 5 mg or fenoterol 1 mg through a nebulizer. ECG is monitored for an hour after inhalation. If there is a clinic of angina pectoris and / or registration of electrocardiographic signs of myocardial ischemia lasting more than 1 min, the sample is considered positive. The method allows to identify concomitant coronary heart disease in patients with COPD and at the same time improve bronchial conduction.

However, this known method is not without drawbacks, namely: the identification of signs of angina pectoris, which in childhood does not occur; conducting pharmacological provocative tests in children is limited.

In the known method for the early diagnosis of angina pectoris of a typical and atypical course in chronic obstructive pulmonary disease (RF patent No. 2414847), the implementation is carried out by laboratory testing of blood of patients with COPD. The cytoleukogram of granulocyte-binding lymphocytes is evaluated. The Rosette Index (IRO) is calculated as the ratio between LSH-1 (lymphocyte + 1 granulocyte), LSH-2 (lymphocyte + 2 granulocyte), LSH-3 (lymphocyte + 3 granulocyte) and free-lying lymphocytes. With an increase in the RTI of LSH-3 more than 0.03, a decrease in the RTI of LSH-2 less than 0.11, patients with COPD are diagnosed with angina pectoris. Its disadvantage is invasiveness, the possibility of multidirectional shifts of granulocyte-binding lymphocytes due to more pronounced immunodeficiency and autoimmune mechanisms, as well as the presence of a pronounced inflammatory process in the body, which leads to insufficient specificity, as a number of factors affect the formation of rosettes.

The prior art also known a number of technical solutions aimed at establishing cardiological changes in children.

For example, there is a method for diagnosing disorders of the cardiovascular system in the acute period of bronchial obstruction in children (Gnusaev SF. The value of small cardiac abnormalities (MARS) in healthy children and cardiovascular disease according to clinical and echocardiographic studies. Abstract of dissertation Doctor of Medical Sciences - Moscow, 1996. - 53 pp.), including conducting an echocardiographic (ECHO) study using ultrasonic diagnostic devices "SSD-600 ALOKA" in M and B modes. Based on the assessment of the ultrastructure of the heart muscle during its visualization, small abnormalities of the development of the heart (MARS) are determined. The study of systolic and diastolic functions of the left heart and the measurement of certain indicators allows you to evaluate: end-diastolic and end-systolic volume of the left ventricle (BWW and CSR LV, ml) according to the formula 1. TEICHHOLS; shock volume (UO): KDO-KSO (ml); minute volume of blood circulation (IOC): UOCHCHSS (l / min); EO emission fraction: BWW (%). By the presence of MARS, functional changes in the heart are judged, and with a decrease in systolodiastolic indices, a violation of the contractile activity of the myocardium and cardiac dysfunction in the acute period of bronchial obstruction is judged.

The disadvantage of this known method is that:

- it is not pathogenetically substantiated and allows you to diagnose only the presence of dysfunction of the left heart;

- the lack of objective indicators for assessing the topical features of its damage does not make it possible to differentiate the options for myocardial damage;

- pathological changes, as a rule, are detected by this method in the acute period of the disease or in severe cases of the disease;

- the method is not accurate, even with severe pathology, indicators may not have deviations from the norm.

Another known method for the differential diagnosis of myocardial lesions in newborns (RF patent No. 2089900). It can be used for the differential diagnosis of myocardial lesions in newborns after a perinatal lesion of the central nervous system. In newborns, a biochemical study of blood serum is carried out, the activity of the cardiospecific creatine phosphokinase isoenzyme (KFK-MV) is determined, and with an increase in KFK-MV activity from 10 to 50%, posthypoxic cardiopathy is diagnosed, over 51% ischemic myocardial damage. The disadvantages of this diagnostic method include the fact that in children undergoing perinatal hypoxia, in the neonatal period, an increase in the activity of cardiospecific enzymes is due to a restructuring of myocardial metabolism (V.A. Tabolin, N.P. Kotlukova, L.V. Simonova, N.V. Gaidukova, N.A. Chernyavskaya, 2001). In addition, this method lacks preclinical diagnostic markers of cardiovascular dysfunction in newborns.

A known method for the diagnosis of ischemic myocardial lesions in children (ed. Certificate of the USSR No. 1749833), according to which blood serum is examined biochemically, determining the activity of the pyrophosphatase enzyme, reflecting changes in energy metabolism, spectrophotometrically and with values of activity indicators exceeding 11.92 mmol / l relatively normal, diagnosed with early ischemic myocardial damage in children with rhythm and cardiac conduction. Its disadvantages are that pyrophosphatase is present in different cell structures and performs a control function in many important metabolic processes of the body, so its use does not make the method selective. In addition, the known method involves the study of children with rhythm and conduction disorders and does not take into account the influence of technogenic environmental factors.

From the prior art, only one technical solution was found to diagnose myocardial impairment from toxic environmental effects. In auth. testimonial. USSR No. 1784923 "A method for the diagnosis of cobalt myocardiopathy" describes an invention that allows you to diagnose professional damage to the heart muscle when exposed to cobalt and its compounds. Its essence lies in the fact that the concentration of the hormone calmodulin is determined in the patient’s blood and, with its value of 300 mg / ml or more, pathology is diagnosed. Its disadvantages are that a variety of factors can influence the calmodulin concentration, since it is involved in all processes regulated by calcium ions, including the striated skeletal muscle. Therefore, such a diagnostic criterion does not ensure the accuracy of the diagnosis.

Moreover, the known methods for diagnosing myocardial disorders in children with respiratory diseases associated with the toxic effects of aromatic compounds and formaldehyde have not been identified from the prior art; therefore, it is not possible to choose the closest analogue to the claimed object.

The technical result achieved by the present invention is to create an informative and evidence-based method for the diagnosis of morphofunctional disorders of the myocardial system in children with bronchopulmonary diseases caused by exposure to phenol, toluene, benzene and formaldehyde, which allows prescribing adequate therapy in the early stages of the disease and preventing the development of complications .

The technical result is achieved by the proposed method for the diagnosis of morphofunctional myocardial disorders in children older than 5 years with bronchopulmonary diseases associated with exposure to benzene, toluene, phenol and formaldehyde, including determining the concentration of benzene, toluene, phenol and formaldehyde in a child’s blood sample, and if it is exceeded the background carry out the determination of functional and laboratory parameters, while the following are determined as functional indicators: electrophysiological function myocardial lumen by electrocardiography; heart rate variability under the influence of the autonomic nervous system according to cardiointervalography, and contractile function of the heart and intracardiac hemodynamics with determination of the main parameters of blood flow in the heart chambers and valve function during echocardiography; and as laboratory indicators establish: the level of leukocytes; the level of antioxidant activity of AOA; MDA malondialdehyde level; level of highly sensitive C-reactive protein; and the state of anti-atherogenic defense - apoliproteins; and in the presence of sinus bradycardia / tachycardia during electrocardiography; with an ejtonic initial vegetative tone, accompanied by a predominance of activity of the parasympathetic department of the autonomic nervous system, asymptaticotonic / hypersympathicotonic reactivity according to cardiointervalography; in the presence of an increase in systolic pressure in the pulmonary artery, transient diastolic dysfunction of the right ventricle with echocardiography; as well as when the relative physiological norm is exceeded, the level of leukocytes is 20% or more, MDA is 1.3 times or more, highly sensitive C-reactive protein is 1.8 times or more, and AOA is reduced by 1.2 times or more and when the anti-atherogenic defense factors change, which consists in increasing the relative physiological norm of Apoliprotein A1 and decreasing the Apoliprotein B / Apoliprotein A1 coefficient, morphofunctional myocardial disorders in children older than 5 years with bronchopulmonary diseases associated with exposure to benzene, toluene, phenol and formaldehyde.

The specified technical result is achieved due to the following.

To understand the essence of the issue, it should be clarified that the cardiovascular and respiratory systems are morphologically and functionally interconnected, therefore, changes in the heart play a role in the development of respiratory diseases. It was established that the chronic aerogenic combined effect of benzene, toluene, phenol and formaldehyde causes the development of a local chronic inflammatory process in the mucous membrane of the respiratory tract with impaired mucociliary clearance and the development of dystrophic processes.

Along with the respiratory system, the cardiovascular system is also involved in the pathological process, which is associated both with the direct cardiotoxic effect of benzene and phenol, as well as indirect, due to impaired respiratory function and a change in the functioning of the autonomic nervous system under the influence of technogenic chemical factors. In addition, prolonged exposure to benzene, toluene, phenol and formaldehyde disrupts the processes of tissue metabolism, which subsequently leads to chronic intoxication. As a result, in children with bronchial obstruction, hypoxic vasoconstriction occurs, leading to increased resistance in the pulmonary vessels and pressure in the lung tissue with the development of further pulmonary hypertension.

Due to the expansion in the proposed method of information indicators (the simultaneous use of functional and laboratory) associated with the cardiovascular system and at the same time with the amount of chemical toxicant - toluene, benzene, phenol and formaldehyde in the blood, the accuracy of the diagnosis of the impact of these compounds on development will be ensured specified pathology.

Due to the fact that in the proposed method, along with the results of this diagnosis, information on the content of benzene, toluene, phenol and formaldehyde in the blood of the child and the claimed specific aggregate indicators (functional: electrophysiological function of the myocardium, heart rate variability under the influence of the autonomic nervous system, contractile cardiac function and intracardiac hemodynamics with determination of the main parameters of blood flow in the heart chambers and valve function; factor indicators: leukocyte levels; AOA; MDA; highly sensitive C-reactive protein and the state of anti-atherogenic defense - apoliproteins), the clinical significance of which has been proved by the method of correlation and regression analysis, provides additional information linkage of changes in these aggregate indicators with excess above the background level in blood levels of these aromatic compounds and formaldehyde, which makes the proposed method accurate and reliable.

Based on the foregoing, we can conclude that the technical result is achieved due to the totality of all operations of the proposed method, their sequence and modes of implementation.

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

- choose an ecologically unfavorable territory for a high load of chemical environmental factors with unsatisfactory atmospheric air quality for sanitary and chemical indicators (excess of benzene, toluene, phenol and formaldehyde in excess of 1.0 MPC m.r., MPC s.s.).

The results of a study of atmospheric air quality are obtained on the basis of socio-hygienic monitoring data in the framework of the Decree of the Government of the Russian Federation of 02.02.2006 No. 60 "Regulation on the conduct of socio-hygienic monitoring" (as amended on 04.09.2012), taking into account the requirements of GN 2.1 .6.1338-03 "Maximum allowable concentrations (MPC) of pollutants in the atmospheric air of populated areas" (as amended on November 3, 2005, February 4, 2008, January 27, 2009).

Data on the presence of a risk of respiratory pathology in a population exposed to benzene, toluene, phenol and formaldehyde are evaluated according to a standardized method in accordance with the Guidelines for assessing the risk to public health when exposed to chemicals polluting the environment (R 2.1.10.1920 -04):

- carry out the selection of children over 5 years old, living in the territory with atmospheric air pollution with benzene, toluene, phenol and formaldehyde, with a diagnosis of bronchial asthma (ICD10: J45.0) and recurrent bronchitis (ICD10: J44.8) without exacerbation; conduct their clinical examination;

- take a blood sample from each child and determine the concentration of benzene, toluene, phenol and formaldehyde in it;

- and when it is exceeded above the background level, further biomedical studies of the child are carried out, consisting in the establishment of certain functional and laboratory indicators.

Moreover, as functional indicators determine:

- electrophysiological function of the myocardium by conducting electrocardiography;

- heart rate variability under the influence of the autonomic nervous system according to cardiointervalography;

- and contractile function of the heart and intracardiac hemodynamics with the determination of the main parameters of blood flow in the heart chambers and the function of the valve apparatus during echocardiography.

As laboratory indicators establish:

- white blood cell count;

- serum AOA level;

- the level of MDA in blood plasma;

- the level of highly sensitive C-reactive protein in blood serum;

- state of anti-atherogenic defense - apoliproteins;

- and morphofunctional myocardial disorders in a child with a bronchopulmonary disease associated with exposure to benzene, toluene, phenol and formaldehyde are diagnosed if at the same time the child has deviations in both functional and laboratory parameters, namely:

- the presence of sinus bradycardia / tachycardia during electrocardiography;

- aytonic initial vegetative tone, accompanied by an increase in the activity of the parasympathetic department of the autonomic nervous system,

- increase in asymptaticotonic / hypersympathicotonic reactivity;

- increased systolic pressure in the pulmonary artery, transient diastolic dysfunction of the right ventricle;

- excess of the age-related physiological norm of the level of leukocytes by 20% or more; MAD - 1.2 times or more; highly sensitive C-reactive protein - 1.8 times or more,

- reduction of AOA by 1.2 times or more,

- change in lipid metabolism, which consists in increasing Apoliprotein A1 and lowering the coefficient "Apoliprotein B / Apoliprotein A1".

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 functional and laboratory parameters, and background levels are used for the content of benzene, toluene, phenol, formaldehyde.

To prove the validity of the diagnostic criteria used in the proposed method, a correlation analysis was used between the obtained functional and laboratory parameters and the content of benzene, toluene, phenol and formaldehyde in the child’s blood using the logistic regression model, according to which the probability of a negative change in the response marker of the body is calculated (the above indicators) when exposed to an exposure marker (specified toxicants received by inhalation eat). The identification and assessment of the relationship between changes in functional and laboratory parameters in children and the concentration of benzene, toluene, phenol and formaldehyde in the blood is performed based on the calculation of the odds ratio (OR) indicator and its confidence interval (DI). The criterion for the presence of the relationship "the concentration of benzene, toluene, phenol and formaldehyde in the blood - an indicator of the response" is OR≥1. The justification of response markers is based on the assessment of the parameters of the dependence of the odds ratio on the concentration of benzene, toluene, phenol and formaldehyde in the blood, described by the regression model in the form of an exponential function. The Fisher test (F) is used as a criterion for testing statistical hypotheses. Differences are considered statistically significant with a probability of p≤0.05.

An example of a specific implementation of the proposed method

1. Choose an ecologically unfavorable territory for a high load of chemical environmental factors with unsatisfactory atmospheric air quality for sanitary and chemical indicators (excess of benzene, toluene, phenol and formaldehyde in excess of 1.0 MPC MP, MPC SS). MPC - maximum permissible concentration.

2. To substantiate the criteria for the diagnosis of cardiac disorders in children with chronic respiratory diseases associated with exposure to benzene, toluene, phenol and formaldehyde, an in-depth clinical, functional, instrumental and laboratory examination was carried out.

The observation group consisted of 43 people with bronchial asthma and recurrent bronchitis without exacerbation at the age of 6-13 years (average age 9.8 ± 0.53 years; 47.6% of boys and 52.4% of girls) living in the Perm Territory with unsatisfactory air quality for sanitary and chemical indicators (excess of benzene, toluene, phenol and formaldehyde more than 1.0 MPC MP, MPC SS).

The comparison group consisted of 39 children (average age 9.3 ± 0.55 years; 53.5% of boys and 46.5% of girls) with bronchial asthma and recurrent bronchitis in remission, living in conditions of sanitary and hygienic well-being.

When analyzing medical and social questionnaires, there were no significant differences between groups by social indicators.

3. In the course of a chemical-analytical study in children of the observation group, the presence in the blood of benzene (0.013 ± 0.0024 mg / dm ³ ) and toluene (0.025 ± 0.0047 mg / dm ³ ), which were absent in children of the compared group (p = 0.001) (table. 1). The phenol concentration in the blood of children in the observation group was 3.2 times significantly higher than the comparison group (0.013 ± 0.005 mg / dm ³ and 0.0041 ± 0.004 mg / dm ^3, respectively, p = 0.01). The formaldehyde content in the blood was determined at the level of 0.0057 ± 0.0016 mg / dm ³ , which statistically significantly exceeded the indicator of the comparison group (0.0025 ± 0.0011 mg / dm ³ , p = 0.001). Data on the content of toxicants in the blood of the examined children are shown in table 2.

4. During clinical trials, it was found that a comparative analysis of the frequency of complaints showed that the parents of the children in the observation group reliably more often indicated previous pneumonia (27.9% and 10.3% in the comparison group, p = 0.034), colds 4-6 times a year or more (25.6% and 12.8%, respectively, OS = 2.4, p = 0.08, while OS is the odds ratio, characterizes the ratio of the probability that the event will occur to the likelihood that the event will not happen). In 23.3% of the children of the observation group there was an episodic dry cough at night (in the comparison group 12.8%, OS = 2.14, p = 0.23); 13.9% had a persistent cough for three months (in the comparison group 5.1%, OS = 2.72, p = 0.16); 27.9% had noisy breathing (in the comparison group 12.8%, OR = 2.63, p = 0.08).

In addition, in children of the observation group, complaints of a vegetative nature in the form of rapid fatigue were significantly more common (46.5% and 23.1%, respectively, p = 0.027); headaches (37.2% and 17.9%, respectively, p = 0.03); weaknesses (37.2% and 15.4%, respectively, p = 0.02); increased irritability (34.8% and 20.5%, respectively, OSH = 1.59, p = 0.07) and anxiety (16.3% and 7.7%, respectively, OSH = 2.33, p = 0, fourteen). The relative risk of vegetative complaints was 2.9 times higher in the observation group (OR = 2.9; DI = 1.11-7.54; p = 0.047).

At the same time, 23.3% of children living in the territory with atmospheric air pollution with benzene, toluene, phenol, and formaldehyde were worried about pain in the heart or rhythm interruptions during physical activity, which is 2.2 times more often in relation to the compared group (10 , 3%, OR = 2.72, p = 0.07).

In the history of every third child living on the territory of the aerogenic exposure to formaldehyde, allergic rhinitis was noted (30.2% versus 10.3% in the comparison group, p = 0.025).

An objective examination of children in the observation group showed pale skin with a marble pattern (48.8% and 20.5% in the comparison group, p = 0.007), dark circles around the eyes (30.2% and 12.8%, respectively, p = 0.04).

According to spirography data, it was found that the indicators of lung capacity were within the normative values, but had a significant decrease to 95.46 ± 13.22% in children of the observation group relative to the comparison group (118.36 ± 13.07%, p = 0.012) . The data on this are shown in Table 3. These data show that a significant decrease in volumetric speed indicators was obtained, reflecting patency of the middle and small bronchi (MEF 50, MEF 25, MEF 25-75) in children of the observation group in relation to the compared group (p = 0.001-0.002).

It was noted that in 25.4% of the children in the observation group, obstructive or mixed breathing disorders were detected, which were recorded 1.5 times less often in the comparison group (16.7%, p = 0.27).

The results of pulsed oscillometry showed a significant increase in respiratory impedance (Zrs), resistance (R5), which indicates the presence of obstruction at the level of small and medium bronchi in the children of the observation group relative to the comparison group (p = 0.04) (table 4).

It was revealed that every fourth child living under the conditions of aerogenic exposure to benzene, toluene, phenol and formaldehyde had signs of peripheral airway obstruction during the remission of chronic respiratory diseases (23.8% and 7.5% in the comparison group, p = 0.028 ) The relative risk of developing peripheral obstruction was 3.84 times higher in the observation group (OR = 3.84; DI = 1.04-14.31; p = 0.06).

5. When conducting functional studies of the heart, it was found that for all the children examined, the physiological parameters of the time parameters of the electrocardiogram (P wave, PQ interval, QRS complex, Q-T interval) were within the age norm (table 5). A direct correlation was established for shortening of the P wave in the presence of an increased phenol content in the blood (r = -0.29, p = 0.027). In 17.2% of children in the observation group, a deviation of the electrical axis of the heart to the right was registered, which was 3.4 times more often than the comparison group (5.1%, p = 0.05).

Sinus rhythm disturbances occurred in more than half of all examined children (table 6). Moreover, the data shown in table 6 show that violations of the automatism of the sinus node in children of the observation group in the form of sinus tachycardia and sinus bradycardia were found 3.1-1.6 times more often than in the compared group (p = 0.14-0.001 )

Analysis of heart rate variability showed that eutonia was the predominant type of initial vegetative tone in children of the observation group, and vagotonia was in the examined group (table 7).

However, in children of both groups there was an increase in the activity of the parasympathetic link of autonomic regulation (Dx, RMSSD, pNN50), more pronounced in children of the comparison group (p = 0.83-0.0002) (table 8). At the same time, children living under the aerogenic effects of benzene, toluene, phenol and formaldehyde showed a decrease in the power of high-frequency waves (HF%) and an increase in the power of the very low-frequency component of the spectrum (VLF%), which indicates a decrease in the activity of the parasympathetic department of the autonomic nervous system and increasing the role of central regulatory influences (neuro-humoral and metabolic levels) on the activity of the heart. While in the children of the comparison group the parasympathetic type of autonomic nervous regulation of the heart rhythm prevailed (HF% and LF%).

Assessment of vegetative reactivity according to the clinostatostatic test data showed that in the observation group in 60.5% of cases there was a sympathicotonic type of response (table 9). Moreover, the data presented show that asymptaticotonic reactivity, characterized by a strain of adaptive-compensatory mechanisms and a violation of the response of all parts of the autonomic regulation, was detected only in 5.3% of children living under the conditions of aerogenic exposure to benzene, toluene, phenol and formaldehyde.

A spectral analysis of the autonomic rhythm regulation in a clino-orthostatic test revealed a decrease in vagal activity (HF) with an increase in the sympathetic autonomic nervous system (LF) and humoral-metabolic mechanisms of heart rhythm regulation (VLF) in children of the observation group (table 10), and in the comparison group the level of central ergotropic influences and humoral regulation was 1.2 times significantly higher (p = 0.023).

Thus, in children with high blood levels of benzene, toluene, phenol and formaldehyde, violations of the regulatory-compensatory mechanisms of the autonomic nervous system in the form of a decrease in the functioning of the humoral-metabolic links upon activation of the parasympathetic link of the autonomic regulation are revealed, which indicates the tension of adaptive-compensatory body reactions to changes in the conditions of the external and internal environment.

When analyzing echocardiography data, the indicators of the left and right ventricles in the examined children were within the physiological standards (table 11). However, an increase in systolic pressure in the pulmonary artery was revealed in children of the observation group relative to the comparison group (9.78 ± 1.09 mm Hg and 8.35 ± 1.07 mm Hg, respectively, p = 0, 05), which indicated an increased load in the pulmonary circulation.

Indicators of diastolic function of the left ventricle in the groups were within normal limits and did not have significant differences (table 12). At the same time, in children of the observation group, an increase in the maximum speed of early diastolic filling of the right ventricle with respect to the indicator of the compared group was noted (0.56 ± 0.036 m / s and 0.52 ± 0.03 m / s, respectively, p = 0.08). The E / A index (the ratio of the rates of diastolic filling and atrial systole) was significantly higher in the observation group (1.68 ± 0.22 cu against 1.42 ± 0.096 cu of the comparison group, p = 0.031), which testified to functional changes in the right ventricle of the heart during clinical remission.

In addition, in 17.9% of the children of the observation group, transient diastolic dysfunction of the right ventricle was revealed, which was absent in the comparison group (p = 0.046).

6. When conducting laboratory tests, the following indicators were established: white blood cell count; the level of antioxidant activity of serum AOA; the level of MDA in blood plasma; the level of highly sensitive C-reactive protein in serum and the state of lipid metabolism.

A comparative analysis of the results of a laboratory study showed that for children in the observation group, in contrast to the comparison group, an increase in the total blood count of leukocytes is characteristic (6.7 ± 0.42⋅10 ⁹ / L versus 5.69 ± 0.50⋅10 ⁹ / L, p = 0.001), 62.3% revealed lymphocytosis (46.3 ± 1.46%). A direct correlation was established between the increase in the blood leukocyte count with an increase in phenol in the blood (r = 0.253, p = 0.05). Excess leukocyte count was 20% of the physiological norm.

Analysis of biochemical blood parameters of children in the observation group showed an intensive accumulation of products of enhanced peroxidation, for example, the MDA content in blood plasma was 3.31 ± 0.37 μmol / cm ³ , which is 1.3 times higher than the physiological limit (norm) and the group indicator comparison (2.73 ± 0.17 μmol / cm ³ , p = 0.005). Moreover, a direct correlation dependence of the increase in the content of MDA with an increase in the blood phenol (r = 0.397, p = 0.004) was obtained.

Assessment of redox reserves found that the average level of AOA in the blood serum of children in the observation group was 33.30 ± 1.89%, which was significantly lower than the value of the comparison group (36.28 ± 1.74%, p = 0.02) and physiological norms are 1.2 times.

During the study of lipid metabolism in children of the observation group, a significantly higher indicator of apoliprotein A1 was established relative to the comparison group (1.65 ± 0.18 g / cm ³ versus 1.37 ± 0.1 g / dm ³ , p = 0.01 ) At the same time, in children living under the aerogenic effects of benzene, toluene, phenol and formaldehyde, a significant decrease in the Apoliprotein B / Apoliprotein A1 coefficient (0.39 ± 0.05 cu versus 0.47 ± 0.06 c. e., p = 0.05), which indicated an increase in the synthesis of cardioprotective protective factors in the presence of an external chemical load.

In addition, in the observation group, the highly sensitive C-reactive protein in serum, which is an indicator of chronic sluggish vascular inflammation, was 5.32 ± 0.5 mg / dm ³ , which was 1.8 times higher than the physiological norm and level of the comparison group ( 2.74 ± 0.55 mg / dm ³ , p = 0.001). The correlation dependence of the increase in the amount of highly sensitive C-reactive protein with an increase in the blood phenol, formaldehyde, toluene (r = 0.275-0.462, p = 0.048-0.001) was established.

Thus, the studies showed that in children with chronic respiratory diseases associated with exposure to benzene, toluene, phenol and formaldehyde, morphofunctional heart disorders are manifested by autonomic disorders (increased fatigue, irritability, headaches, weakness, anxiety, pain in the heart or interruptions in rhythm during physical exertion; the presence of sinus brady, tachycardia; changes in the regulatory and compensatory mechanisms of the autonomic nervous system in the form of a decrease in functions of the humoral-metabolic and sympathetic links upon activation of the parasympathetic division of autonomic regulation), increased systolic pressure in the pulmonary artery, transient diastolic dysfunction of the right ventricle and are accompanied by an inflammatory reaction in the form of an increase in the level of leukocytes in the blood with relative lymphocytosis, an increase in the highly sensitive C-reactive protein; violation of anti-atherogenic defense factors (increased apoliprotein A1, decreased coefficient "Apoliprotein B / Apoliprotein Al"); an imbalance of oxidative and antioxidant reactions (an increase in the content of MDA in blood serum against the background of a decrease in serum AOA).

Example

Patient E., 9 years old, with a diagnosis of Asthma, atopic, lung, without exacerbation. Allergic rhinitis, remission.

A chemical-analytical study of the content of chemical compounds in the blood established the presence of benzene (0.003 mg / dm ³ ), toluene (phenol concentration was 0.015 mg / dm ³ , the formaldehyde content was determined at the level of 0.004 mg / dm ³ .

In the general blood test, the leukocyte count was 7.4⋅10 ⁹ / L (physiological norm 4.5-6.5⋅10 ⁹ / L).

Analysis of biochemical parameters showed an increase in the content of MDA in blood plasma to 2.8 μmol / cm ³ , a decrease in the average level of AOA in blood serum to 23.16%. A high apoliprotein A1 value (2.67 g / cm ³ with a physiological norm of 0.93-1.72 g / dm ³ ) and a decrease in the Apoliprotein B / Apoliprotein A1 coefficient to 0.26 cu were established. (0.52-0.73 cu standard values). The level of highly sensitive C-reactive protein in blood serum was 3.97 mg / dm ³ (physiological norm 0-3 mg / dm ³ ).

According to spirography data, the ventilation ability was within the conventional norm (FVC - 88.5%; FEV1 - 89.7%; PEF - 80.4%; MEF50 - 66.1%; MEF25 - 72.6%; MEF25-75 - 80.7%).

Oscillometry with an assessment of bronchial resistance showed an increase in bronchial resistance and signs of peripheral obstruction (Rocc - 286.8%; Frs - 16.70%; Z - 137.1%; R5 - 70.6%; R20 - 122.8%; X5 - 254.9%).

The performed electrocardiography revealed mild sinus bradycardia (heart rate of 72 beats per minute, angle alpha - 67 °, P wave - 0.08 sec, PQ interval - 0.12 sec, QRS complex - 0.12 sec, QT interval - 0.35 sec).

According to cardiointervalography, a vagotonic initial vegetative tone was recorded (IN = 25.3 cu). The structure of heart rate variability reflected the predominance of waves of a slow period (LF component) and is due to an increase in the sympathetic effect on heart rate modulation. The total power of the neurohumoral modulation spectrum is high. Assessment of vegetative reactivity according to the clinostatic test showed a hypersympathicotonic type of response (IN2 / IN1 = 3.29).

When analyzing the data of echocardiography, the indicators of the left and right ventricles were within physiological standards (Ao - 21 mm; CRD of the LV - 43 mm; CSR of the LV - 29 mm; BWC of the LV - 83 ml; CSR of the LV - 31 ml, MML - 118 g; UO - 52 ml; PV - 62%; RV - 15 mm).

Indicators of diastolic function of the left ventricle were within normal limits (Em 0.8 m / s, Am 0.37 m / s, Em / Am 2 cu). At the same time, diastolic dysfunction of the right ventricle was noted (Etr 0.5 m / s, Apr 0.37 m / s, Etr / Apr 0.82 cu).

In this case, the patient revealed deviations of both functional and laboratory parameters, which are proposed by the claimed method.

Echocardiography revealed signs of morphofunctional myocardial disorders in the form of diastolic dysfunction of the right ventricle. The data obtained indicated the presence of a cardiac type of vegetative dysfunction in a patient with bronchial asthma and allergic rhinitis. So, this confirms the accuracy of the proposed method.

The developed diagnostic method allows you to obtain reliable data, does not require scarce reagents, expensive instruments (the Doppleroechocardiograph is an expensive device with special sensors), it is simple to perform, economical and has no contraindications.

Claims (1)

A method for diagnosing morphofunctional myocardial disorders in children older than 5 years with bronchopulmonary diseases associated with exposure to benzene, toluene, phenol and formaldehyde, which includes determining the concentration of benzene, toluene, phenol and formaldehyde in a child’s blood sample, and, if it exceeds the background, the functional and laboratory indicators, while the following are determined as functional indicators: electrophysiological function of the myocardium by means of electrocardiography; heart rate variability under the influence of the autonomic nervous system according to cardiointervalography, and contractile function of the heart and intracardiac hemodynamics with determination of the main parameters of blood flow in the heart chambers and valve function during echocardiography; and as laboratory indicators establish: the level of leukocytes; the level of antioxidant activity of AOA; MDA malondialdehyde level; level of highly sensitive C-reactive protein; and the state of anti-atherogenic defense - apoliproteins; and in the presence of sinus bradycardia / tachycardia during electrocardiography; with an ejtonic initial vegetative tone, accompanied by a predominance of activity of the parasympathetic department of the autonomic nervous system, asymptaticotonic / hypersympathicotonic reactivity according to cardiointervalography; in the presence of an increase in systolic pressure in the pulmonary artery, transient diastolic dysfunction of the right ventricle with echocardiography; as well as when the relative physiological norm is exceeded, the level of leukocytes is 20% or more, MDA is 1.3 times or more, highly sensitive C-reactive protein is 1.8 times or more, and AOA is reduced by 1.2 times or more and when the anti-atherogenic defense factors change, which consists in increasing the relative physiological norm of Apoliprotein A1 and decreasing the Apoliprotein B / Apoliprotein A1 coefficient, morphofunctional myocardial disorders in children over 5 years old with bronchopulmonary diseases associated with exposure to benzene, toluene, phenol and formaldehyde.