RU2625028C1 - Method for forecasting the duration of ischemia of myocardium in patients with copd with copd and related chd - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: assessing the acute period when entering the clinic level of markers of inflammation in the blood, IL-6, CRP, TNF-α and instrumental studies of spirography, Holter monitoring of ECG. Then calculating the forecasting coefficient by the formula: Kprogn Dlit=1.19532-0.171896*lechen-0,00392163*CRB+0.000232908*IL_6-0.00328536*FNO-0.00626344*OFB_1+0.00898338*prist_1+0.00282975*dlit_1-0.00522293*kachel+0.000463957*mokrota, where lechen is the type of treatment (1 - standard therapy, 2 - therapy with roflumilast supplementation), CRB - C-reactive protein, measured in venous blood, mg/L, IL_6 - interleukin-6, measured in venous blood, pg/ml, FNO - tumour necrosis factorα, Measured in venous blood, pg/ml, OFB_1 - FEV-1 by spirography, %, prist_1 - the number of attacks of angina pectoris per week on the diary of self-control, dlit_1 - duration of myocardial ischemia per day according to Holter ECG monitoring, kachel - the number of cough pushes per day on the self-monitoring diary; Mokrota - the amount of sputum produced per day by self-monitoring diary, ml, and at KprognDlit 0.63 or more the effectiveness of standard therapy including berodual, dexamethasone, ceftriaxone, euphyllin, high and additional prescription of medications is not required; When detecting KProGnDlit less than when KprognDlit is detected, less than 0.63 standard therapy will not give the proper effect and it will be necessary to add roflumilast.

EFFECT: use of the method makes it possible to predict the effectiveness of the anti-inflammatory therapy scheme with high accuracy even before its practical application in patients with COPD in combination with IHD.

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Description

The invention relates to medicine, namely to pulmonology, and can be used in the treatment of patients with chronic obstructive pulmonary disease and concomitant coronary heart disease.

Known methods for treating chronic obstructive pulmonary disease, in particular a method for predicting the clinical effect of inhaled glucocorticosteroid drugs in patients with chronic obstructive pulmonary disease [RF patent No. 2424522] by determining the concentration of hemoglobin in the patient’s peripheral blood, the systolic pressure in the pulmonary artery and the end-diastolic size right ventricle of the heart. Then calculate the indicator F by the formula: F = 175-27.3 × PZhd-4.35 × SDLA + 0.5 × G,

where G is the hemoglobin content in peripheral blood, g / l; ПЖд - end-diastolic size of the right ventricle of the heart, cm; SDLA - the value of systolic pressure in the pulmonary artery, mmHg At F> 0, a positive clinical effect is predicted, and at F <0, a negative clinical effect or its absence is predicted. The application of the method allows the administration of IHC therapy individually only to those patients for whom a positive clinical effect can be achieved, thereby contributing, on the one hand, to improving the quality of medical care for patients with COPD, and on the other, to reducing the undesirable steroid load on the patient.

The disadvantages of the method: not in all patients the use of steroids gives a positive clinical effect, there are undesirable side effects that can be associated with the regular administration of IHC (oropharyngeal candidiasis, dysphonia, steroid osteopenia and osteoporosis).

There is a method of complex treatment of chronic obstructive pulmonary disease in remission [RF patent No. 2386438] by intravenous drip of a 1.5% reamberin solution in a volume of 400 ml every other day (5 infusions in total). Addition of treatment with reamberin in a regimen specially developed for this allows improving the function of external respiration and pulmonary-cardiac hemodynamics in this category of patients and achieving a significant increase in the duration of remission due to the manifestation of antihypoxant activity of reamberin.

The disadvantages of the method: reambirin does not have anti-inflammatory activity, it is inappropriate to use during exacerbation of COPD.

Known drugs for the treatment of respiratory diseases [RF patent No. 2395284] by using theophylline and a steroid for the manufacture of a composition for the treatment of chronic obstructive pulmonary disease (COPD), where theophylline is administered at a dose that reaches plasma levels lower than 5 mg / l (t ie, administered orally at a dose of 3 mg / kg or less) and the steroid dose below 0.5 mg / kg, as well as the corresponding treatment method, pharmaceutical composition in unit dosage form and kit for the same purpose. The synergism of the action of this combination in doses that are separately ineffective for the treatment of COPD, and plasma concentrations are lower than those that are usually associated with anti-inflammatory activity, is shown.

However, theophylline is undesirable in patients suffering from cardiovascular diseases.

Known drug that affects IL-6 - Tocilizumab. Tocilizumab is a humanized monoclonal antibody (IgG1) that, when bound to membrane and soluble IL-6 receptors, inhibits both signaling pathways of IL-6-dependent cellular activation.

The disadvantages of the method: the drug is used to treat patients with rheumatoid arthritis (Modern targets for the targeted treatment of rheumatoid arthritis: from monoclonal antibodies to blockers of signal molecules. Kovalenko V.N., Golovach I.Yu., Bortkevich O.P. Ukrainian rheumatological journal No. 49 ( 3) 2012)

The technical result is an increase in the effectiveness of treatment of patients with combined pathology - coronary heart disease and chronic obstructive pulmonary disease by predicting the duration of myocardial ischemia, which in turn will allow for timely and personalized correction of the course of therapy.

The technical result was achieved by prolonged clinical observation of patients with exacerbation of COPD and concomitant coronary artery disease undergoing treatment at the clinical bases of the Voronezh State Medical University. N.N. Burdenko at the Higher Educational Institution of Higher Education “VGKBSMP No. 1”. The level of markers of inflammation in the blood was evaluated - IL-6, CRP, TNF-α, instrumental studies - spirography, Holter ECG monitoring. Patients kept diaries of self-control, which indicated the number of cough shocks per day, the amount of sputum excreted, the number of angina attacks. In patients with COPD in the acute stage, with FEV1 less than 50%, in combination with IHD, basic anti-inflammatory therapy was used, which included NSAIDs, glucocorticosteroids, antibiotics, M-anticholinergic drugs for ten days of treatment in a hospital.

During the observation, it was found that the addition of roflumilast to the basic anti-inflammatory therapy improves the cardiovascular system. The method was tested in 34 patients with exacerbation of COPD in combination with coronary artery disease on hospitalization. Patients were divided into 2 groups: the main - 16 patients and the control - 18 patients.

16 patients with exacerbation of chronic obstructive pulmonary disease in combination with coronary artery disease in addition to basic anti-inflammatory therapy, including M-anticholinergics, glucocorticosteroids, NSAIDs, antibiotics, were given roflumilast at a dose of 500 mcg once a day.

Table 1.

Clinical efficacy of anti-inflammatory therapy with roflumilast in patients with COPD and IHD.

Indicators Known method The proposed method Before treatment After Before treatment After The number of angina attacks per week 10.61 ± 2.36 7.44 ± 1.95 12.37 ± 2.22 * 6.38 ± 1.75 * Duration of myocardial ischemia per day, min 43.61 ± 7.78 31.39 ± 7.11 49.38 ± 12.66 * 28.06 ± 8.44 * The number of cough shocks 43.83 ± 4.83 * 31.39 ± 5.0 * 47.19 ± 7.04 * 28.69 ± 5.8 * The amount of sputum, ml 90.83 ± 8.95 * 69.72 ± 9.15 * 89.06 ± 8.98 * 55.31 ± 9.03 * FEV1,% of due 45.22 ± 2.57 * 54.89 ± 2.92 * 45.22 ± 2.39 * 65.20 ± 3.34 *

* p <0.01

According to the results of observations, the percentage of changes in the duration of myocardial ischemia after treatment relative to the duration of myocardial ischemia before treatment was estimated. It was noted that the improvement results had a significant spread from more than 80% reduction in the duration of myocardial ischemia to less than 40% of the decrease in the duration of myocardial ischemia. This fact served as a prerequisite for calculating the prediction coefficient for the duration of ischemia, which allows with high accuracy to determine the likely percentage reduction in the duration of ischemia depending on the treatment regimen.

The prediction coefficient for the duration of myocardial ischemia was calculated by the formula:

Cprognolit = 1.19532 - 0.171896 * lechen - 0.00392163 * CRB + 0.000232908 * IL_6- 0.00328536 * FNO - 0.00626344 * OFB_1 + 0.00898338 * prist_1 + 0.00282975 * dlit_1 - 0, 00522293 * kachel + 0,000463957 * mokrota,

where lechen is the type of treatment (1 - standard therapy, 2 - therapy with the addition of roflumilast);

CRB - C-reactive protein, measured in venous blood, mg / l;

IL_6 - interleukin-6, measured in venous blood, PG / ml;

FNO - tumor necrosis factor α, measured in venous blood, pg / ml;

OFB_1 - FEV-1 according to the results of spirography,%;

prist_1 - the number of angina attacks per week according to the diary of self-control, pcs .;

dlit_1 - the duration of myocardial ischemia per day according to the results of Holter ECG monitoring, min;

kachel - the number of cough shocks per day on the diary of self-control, pcs .;

mokrota - the amount of sputum excreted per day according to the diary of self-control, ml.

The results are presented in table 2:

Table 2.

The effectiveness of standard therapy.

Dynamics of positive changes in relation to the level before treatment CprogDuration more than 70% 0.734821 from 70 to 50% 0.625256 less than 50% 0.520031

In patients whose CprognDlit was 0.63 or more, the effectiveness of standard therapy was high, additional prescriptions of drugs were not required.

If Kprognlit was less than 0.63, then standard therapy did not give the proper clinical effectiveness.

Clinical example 1. Patient VI, 63 years old with a diagnosis of COPD, severe course, exacerbation. KprognDlit was 0.54. In addition to the basic anti-inflammatory therapy, which included berodual, dexamethasone, ceftriaxone, aminophylline for ten days, the patient additionally received roflumilast at a dose of 500 mcg orally once a day for the entire time of hospitalization and the next three months after discharge from the hospital. Three months after discharge from the hospital, the number of cough shocks decreased from 45 to 22 per day, the amount of sputum excreted decreased from 80 ml to 50 ml per day, the number of angina attacks decreased from 8 per week to 3, the duration of myocardial ischemia decreased from 42 minutes to day to 17, FEV1 increased from 43.35% to 67.38%. The patient did not have exacerbations of COPD, there were no hospitalizations for coronary artery disease.

Clinical example 2. Patient I.V., 58 years old, with a diagnosis of COPD, severe course, exacerbation. KprognDlit was 0.67. For ten days, the patient received basic anti-inflammatory therapy, which included berodual, dexamethasone, ceftriaxone, aminophylline. Three months after discharge from the hospital, the number of cough shocks decreased from 39 to 22 per day, the amount of sputum excreted decreased from 80 ml to 60 ml per day, the number of angina attacks decreased from 8 per week to 5, the duration of myocardial ischemia decreased from 35 minutes to day to 24 minutes, FEV1 increased from 49.57% to 60.25%. Over the next three months, he was hospitalized for the progression of coronary heart disease.

Thus, we have developed a method based on the assessment of indicators that are standardly determined in the clinic and the calculation of the coefficient for predicting the duration of myocardial ischemia (KprognDlit). The value of CprognDlit 0.63 or more indicates a sufficient effect of standard therapy, including berodual, dexamethasone, ceftriaxone, aminophylline.

If Cprognolit is less than 0.63, then roflumilast at a dose of 500 mcg once a day should be added to standard therapy when planning a course of treatment.

After treatment, spirometric measurements were repeated, Holter ECG monitoring allowed to obtain a new result unknown from the prior art, namely, the additional inclusion of Roflumilast in the treatment regimen, in the case of a prognosis of insufficient clinical efficacy of standard therapy, can reduce the duration of episodes of myocardial ischemia during the day. These effects are not shown in the instructions for the drug Roflumilast, in textbooks and guidelines for the treatment of COPD and IHD.

A method of treating COPD patients in the acute stage and CHD allows determining the effectiveness of the anti-inflammatory therapy regimen even before its practical use in patients with COPD in combination with CHD. The method is personalized, can be used for a differentiated approach to the treatment of patients with COPD and IHD.

Claims (4)

A method for predicting the effectiveness of treatment of myocardial ischemia in patients with COPD and CHD, including an acute assessment of the level of blood inflammation markers, IL-6, CRP, TNF-α and instrumental studies, spirography, Holter ECG monitoring, which are calculated prediction coefficient according to the formula: Cprognolit = 1.19532 - 0.171896 * lechen - 0.00392163 * CRB + 0.000232908 * IL_6- 0.00328536 * FNO - 0.00626344 * OFB_1 + 0.00898338 * prist_1 + 0.00282975 * dlit_1 - 0, 00522293 * kachel + 0,000463957 * mokrota, where lechen is the type of treatment (1 is standard therapy, 2 is therapy with roflumilast), CRB is C-reactive protein measured in venous blood, mg / l, IL_6 is interleukin-6 measured in venous blood, pg / ml, FNO - tumor necrosis factor α, measured in venous blood, pg / ml, OFB_1 - FEV-1 according to spirography results,%, prist_1 - the number of angina attacks per week according to the self-monitoring diary, dlit_1 - duration of myocardial ischemia per day according to the results of Holter ECG monitoring , kachel - the number of cough shocks per day according to the diary of self-control, pcs., mokrota - the amount of sputum excreted per day according to the diary of self-control, ml, and with Cprognolit 0.63 and more, the effectiveness of standard therapy, including berodual, dexamethasone, ceftriaxone, aminophylline, high and additional prescriptions of medicines is not required; if Cprognolit is detected less than 0.63, standard therapy will not give the desired effect and roflumilast should be added.