RU2484770C2 - Method of predicting frequency of exacerbations of chronic obstructive lung disease - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to pulmonology, and can be applied for predicting frequency of exacerbations of chronic obstructive lung disease (COLD) in men. For this purpose volume of forced inhalation for 1 second (VFI1) and value of general blood testosterone (T) are determined. After that coefficient of COLD exacerbations (C_exacerb.) is calculated by specific mathematical formula. If C_exacerb. value is less than 2.065, not more than two exacerbations per year are predicted. If C_exacerb. value equals or is higher than 2.065, three and more exacerbations per year are predicted.

EFFECT: method makes it possible to predict course of the disease in remote period of time and in correct performed therapy in case of necessity.

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Description

The invention relates to medicine, in particular to pulmonology, and is intended to predict the frequency of exacerbations of the disease over the next year in patients with chronic obstructive pulmonary disease (COPD).

There is a method of clarifying the diagnosis of exacerbation of chronic obstructive pulmonary disease (patent application RU No. 2009136764), namely, that blood counts are estimated by the cytolucogram of granulocyte-binding lymphocytes and calculate the index of rosette formation (IRO) as the ratio between LS-1 (lymphocyte +1 granulocyte) , LSH-2 (lymphocyte +2 granulocytes), LSH-3 (lymphocyte +3 granulocytes) and free-lying lymphocytes. With an increase in the RTI of LSH-1 more than 0.8, a decrease in the RTI of LSH-2 less than 0.11, patients are diagnosed with exacerbation of chronic obstructive pulmonary disease.

The disadvantages of the method are the low fitness for mass surveys and the inability to use to determine exacerbation at the current time.

A known method for predicting the progression of chronic obstructive pulmonary disease (application for US Pat. RU No. 2007113314 from 10.27.2008). The method consists in conducting immunological studies to determine the ability of immunocompetent cells (ICC) to produce transforming growth factor β (TGF-b) and fibroblast growth factor (FGF) and at a spontaneous level of TGF-b 1102.11 pg / ml and FGF 37.02 pg / ml predict a favorable course of COPD, a decrease in FEV1 of not more than 50 ml per year, and at a spontaneous level of TGF-b of 1008.8 pg / ml and FGF of 40.01 pg / ml, an unfavorable course of COPD with a decrease in FEV1 of more than 50 ml per year.

The disadvantage of this method is its low suitability for conducting mass examinations, both due to the complexity of the method and due to the high cost of laboratory studies necessary for its implementation. Using this method, it is impossible to predict the number of exacerbations during the year.

Closest to the proposed is a method for diagnosing disorders of bronchial obstruction described in patent RU No. 2240725, published December 27, 2004 "Method for predicting the progression of airway obstruction." The change in forced expiratory volume in the first second (FEV1) is determined in% of the initial value after a bronchial provocative test with a 0.1% solution of acetylcholine chloride, the smoking person index is calculated, the discriminant equation is solved, and coefficient D is obtained by which the progression of airway obstruction is predicted. The disadvantage of the prototype is that the use of a bronchial provocative test with a 1% solution of acetylcholine chloride can lead to the development of severe bronchospasm in patients with chronic obstructive pulmonary disease, provoke an exacerbation of the disease, while our method is minimally invasive and is not at risk of developing such complications. In addition, the disadvantages should also include the complexity of the methodology for its implementation, high economic value, the duration of its implementation and the inability to use in most medical institutions.

The purpose of the invention is to develop a method for predicting the frequency of exacerbation of chronic obstructive pulmonary disease over the next year, taking into account the individual characteristics of the patient, easy to use, inexpensive to perform. Prediction results using the proposed method allow individually approaching the correction of the course of treatment of patients with COPD.

The method is based on observations of the clinical condition of 115 patients with COPD and measurement of testosterone, functional lung capacity (FVC), FEV1 during the year.

Determination of total testosterone in blood serum is carried out by the immunochemiluminescent method, for example, using an Automated Chemiluminescence System analyzer (ACS-180). For analysis used a blood sample taken from nine to eleven o'clock in the morning, during the peak of secretion of sex hormones. A functional study of external respiration is performed by spirometry, for example, using the installation "Diamond RKS", Russia. FEV1, FVC are subject to registration, in addition, the ratio of FEV1 to FVC is calculated.

When developing a forecasting method, we measured the above parameters with a frequency of once every three months, and recorded the frequency of hospitalizations of patients for exacerbations of COPD. After a year of observations using a regression analysis, where the frequency of exacerbations of COPD was used as a dependent variable for a total of one year, and the level of testosterone in the blood serum of FEV1 to FVC was used as an explanatory variable after initial treatment, after three, six or nine months of observations it was found that significant for forecasting is the level of indicators in the initial treatment.

The formula for the dependence of the frequency of exacerbations of COPD on other measured parameters was:

To _{exacerbation.} = 5.27-0.029 * OFV1-0.111 * T, where:

To _exacerbation - the frequency coefficient of exacerbations of COPD; FEV1 is the volume of a fixed expiration in the first second, T is the level of testosterone in the blood.

Verification of the work of the obtained prediction formula was carried out on a training sample of 115 patients with COPD who performed the calculation of K _{exacerbation.} during the initial treatment and then the condition of these patients was monitored, including the frequency of hospitalizations for exacerbations of COPD, during the year.

After a year of observation, it was found that when the coefficient K _{exacerbation was} less than 2.065, patients had no more than two exacerbations per year. A coefficient equal to or greater than 2.065 corresponded to three or more exacerbations per year.

The values observed and predicted using this equation, as well as their difference (residuals) are presented in the table.

Table. The ratio of the frequency of exacerbations of COPD per year and the proposed estimated indicator K _exacerbation Patient group Average Maximum Minimum No more than one exacerbation of COPD per year 1.351895 2,149853 -0.05184 No more than 2 exacerbations of COPD per year 2,0656 3,222389 -0.051842 Three or more exacerbations of COPD per year 3.052559 3,85087 2,420106

The resulting model was tested for performance, that is, its stability and effectiveness were evaluated using the results of other patients with COPD from the newly recruited control group. As a control, not intersecting with the training, the samples were used the results of measurements of 55 people. Of these, 15 healthy people aged 37-64 years, 12 patients with mild COPD, 17 patients with moderate COPD and 11 patients with severe COPD. The groups were comparable by age, severity of COPD.

Testing the model in the control sample showed a coincidence of the observed and predicted values of 94%, which makes it possible to predict the frequency of exacerbation of COPD over the next year using just two easily obtained parameters.

Moreover, the specificity of the proposed forecasting method was 94%, sensitivity - 98%.

The proposed method has shown great efficiency for detecting the frequency of exacerbation with moderate severity and severe course.

The following are examples of the use of the claimed method.

Example 1

Man L., 52 years old, does not smoke, works as a manager, height - 178 cm, weight - 62 kg, BMI - 19.6 kg / m ² , waist circumference - 91 cm. FEV - 1 - 66%; FVC - 70%; Tifno index - 65%. The level of testosterone (T) is 15.2 nmol / L.

From the anamnesis, it is known that COPD has been suffering for more than six years, the last three years have noted 1-2 hospitalizations due to exacerbation of the disease.

Over the past two years, ipratropium bromide has been continuously taken by inhalation - 2 doses of an aerosol (40 mcg) 4 times a day (up to 12 inhalations if necessary).

The coefficient K _exacerbation is 1.67, since the calculated value does not exceed 2.065 - a forecast of no more than two exacerbations per year. It is recommended to continue the course of basic therapy without changes. During the year, dynamic monitoring of the patient was carried out. During the observation, the patient was found to have one exacerbation per year.

Example 2

Male R., 56 years old, smokes for 35 years, does not work, height - 177 cm, weight - 95 kg, BMI - 30.3 kg / m ² , waist circumference - 105 cm .; FEV - 1 - 49%; FVC - 71%; Tifno index - 70%; T - 6.2 nmol / L.

From the anamnesis it is known that COPD has been suffering for more than six years, the last three years have noted 3-4 hospitalizations due to an exacerbation of the disease, ipratropium bromide is inhaled - 2 doses of aerosol (40 mcg) 4 times a day (if necessary, up to 12 inhalations); theophylline inside 0.1-0.2 g 2-4 times a day; fenoterol (Berotek) 1-2 inhalation doses per dose, if repeated inhalations are required, then no more than 8 inhalations per day.

The coefficient K _exacerbation is 3.16, which corresponds to the probability of three or more exacerbations per year. The correction of basic therapy is recommended - the addition of andriol in a dose of 80 mg once a day in the morning. After 2 months, the level of total testosterone in the blood increased to 15.4 nmol / L, after which the dose was adjusted downward to 40 mg once a day. During the year, one exacerbation was registered in the patient.

Conclusion: this formula allows us to predict the frequency of exacerbations per year, on the basis of which to adjust treatment and reduce the number of hospitalizations per year.

Example 3

Man Z., 61 years old, smokes 35 years, does not work. Height - 178 cm, weight - 88 kg, BMI - 27.8 kg / m ² , waist circumference - 112 cm; FEV -1 - 41%; FVC - 64%; Tifno index - 42%; T - 5.9 nmol / L.

From the anamnesis, it is known that COPD has been suffering for more than eight years, the last three years have noted at least 4 hospitalizations due to an exacerbation of the disease.

Ipratropium bromide was prescribed inhalation treatment - 2 doses of aerosol (40 mcg) 4 times a day (if necessary, up to 12 inhalations); theophylline inside 0.1-0.2 g 2-4 times a day; fenoterol (Berotek) 1-2 inhalation doses per dose, if repeated inhalations are required, then no more than 8 inhalations per day.

The coefficient K _exacerbation is 3.43 - corresponds to the forecast of three or more exacerbations in the next year. It is recommended that to reduce the number of exacerbations, add to the basic therapy andriol in a dose of 80 mg once a day in the morning. The patient refused to comply with the recommendations and take andriol. During the observation over the next year, the patient was registered 4 hospitalizations for exacerbation of COPD.

Claims (1)

A method for predicting the frequency of exacerbation of chronic obstructive pulmonary disease in men with measuring forced expiratory volume in 1 s (FEV1) and total blood testosterone (T), characterized in that they use the formula
To _{exacerbation.} = 5.27-0.029 · OFV1-0.111 · T,
where K _exacerbation is the coefficient of the frequency of exacerbations of COPD; FEV1 - volume of a fixed expiration in the first second, T - level of testosterone in the blood;
when the value of K _{exacerbation.} less than 2.065 predict no more than two exacerbations per year; when the value of K _{exacerbation.} equal to or greater than 2.065, predict three or more exacerbations per year.