RU2652550C1 - Method for predicting exacerbations of chronic obstructive pulmonary disease in obese patients - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine, namely to therapy, and can be used to individually predict exacerbations of chronic obstructive pulmonary disease (COPD) in obese patients during the next year of follow-up. Body weight index (BWI) is calculated. 6-minute walking test (TSH) and a COPD Assessment Test (CAT) for measuring the effect of COPD on patient quality of life are performed. Levels of thyroid-stimulating hormone (TTG), leptin, adiponectin, melatonin are determined. Based on the obtained data, using the original regression equation, the COPD probability index is calculated for 1 year of observation. Based on obtained data, a low risk of developing exacerbations of COPD with the number of exacerbations per year to 2 times or a high risk of exacerbations with the number of exacerbations per year 2 or more is predicted.

EFFECT: method allows to obtain reliable prognosis of the development of exacerbations of COPD in patients with obesity.

1 cl, 2 ex, 1 tbl

Description

The invention relates to medicine, namely to therapy, and can be used for individual prognosis of exacerbations of chronic obstructive pulmonary disease (COPD) in patients with obesity during the next year of observation.

At the present stage, much attention is paid to the issue of prevention and treatment of one of the most common chronic lung diseases - COPD. This is primarily due to the tendency to increase the number of severe forms of the disease, the number of people with disabilities and the mortality rate from COPD (A.G. Chuchalin, S.N. Avdeev, Z.R. Aisanov et al. Russian Respiratory Society: Federal clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease (Pulmonology. 2014; 3: 15-54). In the main COPD management document - “Global Initiative for Chronic Obstructive Lung Disease Diagnosis, Treatment and Prevention of Chronic Obstructive Pulmonary Disease” (GOLD, revision 2017), it is emphasized that COPD is characterized by comorbidity. Concomitant diseases affect the aggravation of COPD, quality of life (QOL), the nature of progression and prognosis (http://www.goldcopd.org). Among the many concomitant diseases, obesity is considered, and the presence of complex pathogenetic relationships between the two pathologies is associated with the phenomenon of mutual complication, which, in turn, serves as a limiting factor in achieving stabilization of COPD, reducing the likelihood of a favorable prognosis of working capacity and life (Yu.V. Samuleeva, BC Zadionchenko, VV Lee et al. Obesity and metabolic disorders in patients with chronic obstructive pulmonary disease: the possibility of phenotyping. Pulmonology. 2014; 5: 32-38).

This determines the need to search for new effective preventive measures and to determine predictors of COPD progression in patients with concomitant obesity.

In recent years, studies of systemic effects in COPD have been particularly actively developing, when patients with COPD already have signs of a cardiovascular disease and signs of a metabolic syndrome, the main criterion of which is obesity (SN Avdeev. Clinical symptoms and quality of life of patients with chronic obstructive pulmonary disease: subjectively assessed indicators or factors determining the prognosis Pulmonology. 2016; 2: 231-237; SK Park, JL Larson. Metabolic syndrome and associated factors in people with chronic obstructive pulmonary disease. West J. Nurs. Res. 2014; 36 (5): 620-642).

Obesity is a complex metabolic condition that affects many physiological systems. Adipose tissue is often considered as a source of pro-inflammatory mediators. Adipocytes produce high concentrations of adipocytokines, among which the most studied are leptin, adiponectin, which aggravate progradient systemic inflammation and aggravate intermittent hypoxia (N. Hosogai, A. Fukuhara, K. Oshima et al. Adipose tissue hypoxia in obesity and its impact on adregipocy Diabetes Apr. 2007; 56 (4): 901-911). At the same time, chronic systemic inflammation is characteristic of COPD, and elevated levels of pro-inflammatory mediators are recorded in patients with COPD (WQ Gan, SF Man, A. Senthilselvan, DD Sin. Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax. 2004; 59 (7): 574-80).

The overall prevalence of obesity in patients with COPD is about 18.0%. Obesity is associated with a 20.0-34.0% increase in the relative risk of mortality from all causes in patients with mild to moderate COPD compared with patients with COPD and normal weight with comparable disease severity (BD James, AV Jones, RE Trethewey, RA Evans Obesity and metabolic syndrome in COPD: is exercise the answer? Chron Respir Dis. 2017. DOI: 0.1177 / 1479972317736294).

Obesity is seen as the main factor responsible for airway obstruction in COPD. Several mechanisms have been proposed linking obesity and airflow rate limitation: decreasing chest volume and lung tissue elasticity, dysfunction of the bronchi of medium and small caliber, expiratory limitation of airflow velocity, decreasing ventilation ability, enhanced breathing (K.V. Lam, RE Jordan , CQ Jiang et al. Airflow obstruction and metabolic syndrome. The Guangzhou Biobank Cohort Study. Eur Respir J. 2010; 35: 317-323).

The presence of common pathogenetic factors causes in obese patients a more severe course of COPD with frequent exacerbations, hospitalizations, severe clinical symptoms of the underlying disease with low FEV ₁ , requiring high-dose inhaled glucocorticosteroids (M.S. Belsner, G.L. Ignatova, EV Blinova et al. External respiration function in patients with severe chronic obstructive pulmonary disease in combination with obesity. Ural Medical Journal. 2014; 4 (118): 85-87). Obese patients with COPD have a higher level of leptin, low adiponectin and pronounced insulin resistance (N. A. Sukaterina, I. S. Shpagin, O. N. Gerasimenko. New markers of nutritional status in arterial hypertension and chronic obstructive pulmonary disease. Journal of Siberian Medical Sciences. 2015; 6: 23-30).

A known method for predicting exacerbations of chronic obstructive pulmonary disease (COPD) in patients with concomitant type 2 diabetes mellitus (DM) within the next year of observation, including measuring systolic blood pressure (SBP), calculating body mass index (BMI), conducting a test with 6 minute walking (TLC) and the COPD Assessment Test (CAT) for assessing the degree of influence of COPD on the quality of life of patients. In addition, levels are determined: glycated hemoglobin (HbA), low-density lipoprotein cholesterol (LDL), triglycerides (TG). Based on the data obtained, the probability index of COPD exacerbation is calculated using the original regression equation (RU 2625270, publ. 12.07.17 - prototype).

Our clinical observations have revealed the effect on the risk of exacerbation of COPD in obese individuals with levels of thyroid stimulating hormone (TSH), leptin, adiponectin, melatonin.

For example, it is known that melatonin has a number of physiological effects: hypnogenic, rhythm-regulating, immunomodulating, reproductive, antioxidant and mitochondrial-protective, pleiotropic, metabolic (A.Yu. Molchanov, M.G. Ivanovskaya, S.I. Rapoport, E . S. Molchanova. Determination of melatonin in biological fluids. Clinical and laboratory diagnostics. 2011; 6: 3-7). Against the background of melatonin secretion, glucose concentration decreases, insulin levels in blood serum increase, triglycerides and low density lipoproteins decrease, high density lipoproteins increase, and melatonin deficiency is accompanied by obesity, insulin resistance, and the risk of developing cardiovascular diseases (P. Guaraldi, E. Sancisi, S. La Morgia et al. Nocturnal melatonin regulation in post-traumatic vegetative state: a possible role for melatonin supplementation? Chronobiol. Int. 2014.31 (5): 741-745).

The technical problem that we were solving was expanding the arsenal of tools for predicting COPD exacerbations in obese patients, allowing timely identification of patients who need correction of the treatment and preventive measures system, since obesity is considered as the main factor responsible for airway obstruction in COPD.

The technical result achieved is to obtain a reliable prognosis of the development of exacerbations of COPD in obese patients.

As a result of our studies, we developed a prognostic model of the frequency of exacerbations of COPD in obese patients. To calculate the parameters of the model, a clinical and laboratory study of the data of 90 patients with COPD and obesity was performed, of which 38 women (42.2%) and 52 men (57.8%). The age of patients ranged from 40 to 70 years, averaging 59.14 ± 0.78 years. The diagnosis of "chronic obstructive pulmonary disease" is clinically confirmed on the basis of complaints of progressive shortness of breath, aggravated by physical exertion, chronic cough with a small amount of viscous sputum, chest tightness, the presence of common dry inspiratory or expiratory wheezing during auscultation and anamnesis data - exposure to risk factors, including tobacco smoking, indications of burdened heredity, partially reversible nature of bronchial obstruction according to the GOLD (2017) criteria. The duration of the disease was determined anamnestically by the time of the onset of the first symptoms characteristic of COPD. She ranged from 5 to 20 years. The majority of patients had a COPD duration of up to 15 years. Patients were observed for 1 year, clinical and instrumental and laboratory examination was carried out at the stage of inclusion in the study.

The diagnosis of central obesity was established if the ratio of waist to hip volume exceeded 0.8 for women or 0.95 for men, as well as the result of calculating body mass index (BMI).

All patients underwent a comprehensive clinical and instrumental examination with an analysis of complaints, anamnesis data and objective research methods, as well as laboratory examinations, including the determination of venipolar adiponectin level, venous blood leptin level, venous blood melatonin level, venous blood thyroid stimulating hormone level.

Body mass index was calculated by the formula: BMI = weight / height ² .

The degree of COPD impact on quality of life (QOL) of patients was evaluated using the COPD Assessment Test (CAT) (Jones PW, Harding G., Berry P. et al. Development and first validation of the COPD Assessment Test. Eur Respir J . 2009; 34: 648-654).

Exercise tolerance was assessed using a 6-minute walk test (TLC).

Statistical data processing was performed using the STATGRAPHICS 5.1 Plus for Windows software package. For the analysis of dependencies used logistic regression analysis. The adequacy of the model was considered statistically significant at p <0.05.

Using the apparatus of multivariate regression analysis, we determined the factors affecting the frequency of exacerbations of COPD in obese patients. As prognostically significant indicators, the following set of indicators was identified: venous blood adiponectin level (μg / ml), body mass index (kg / cm ² ), venous blood leptin level (ng / ml), venous blood melatonin level (pg / ml) , the level of thyroid-stimulating hormone of venous blood (μMU / ml), the result of the CAT test for assessing the quality of life of patients with COPD (points), the result of the test with 6-minute walking (m). In addition, using a multivariate regression analysis, a model for predicting exacerbations of COPD in obese patients was obtained.

In the table. Figure 1 shows the parameters of a model that describes the likelihood of exacerbating COPD in patients with obesity within 1 year of observation.

The regression model has the form:

ExCOPD = -0.644931-0.0242142 ДИ ADIPONECTIN + 0.139113 ⋅ IMT + 0.0115153 ⋅ LEPTIN-0.0307489 ⋅ MELATONIN-0.341487 ⋅ TTG + 0.0865162 ⋅ CAT-0.00575381 ⋅ TSHX,

Where

ExCOPD - probability index of COPD exacerbation during 1 year of observation (c.u.),

ADIPONECTIN - the level of adiponectin of venous blood (μg / ml),

BMI - body mass index (kg / cm ² ),

LEPTIN - venous blood leptin level (ng / ml),

MELATONIN - venous blood melatonin level (pg / ml),

TSH - the level of thyroid-stimulating hormone of venous blood (μMU / ml),

CAT - the result of the CAT test for assessing the quality of life of patients with COPD (points),

TSHH - test result with a 6-minute walk (m).

ExCOPD less than 5 indicates a low risk of exacerbations, which is understood as the number of exacerbations per year less than 2,

ExCOPD = 5 or more - a high risk of exacerbations, the number of exacerbations per year 2 or more times.

Studies have shown that the developed model is statistically significant at a 99.99% confidence level.

Example 1

Patient J., 57 years old, with a diagnosis of COPD (GOLD 2) without exacerbation and obesity of the first degree, data from a comprehensive clinical, instrumental and laboratory examination: the level of venipheral blood adiponectin was 10.24 μg / ml, body mass index - 31 kg / cm ² , the level of venous blood leptin is 36.38 ng / ml, the level of venous blood melatonin is 8.55 pg / ml, the level of thyroid-stimulating hormone of venous blood is 4.48 μIU / ml, the test result for assessing the degree of influence of COPD on the quality of life of patients (CAT) is 19 points, the test result with a 6-minute walk of 325 m.

The number of exacerbations of COPD, calculated using our prognostic model, over the next year amounted to:

ExCOPD = -0.644931-0.0242142⋅10.24 + 0.139113⋅31 + 0.0115153⋅36.38-0.0307489⋅8.55-0.341487⋅4.48 + 0.0865162⋅19 -0.00575381⋅325 = 1.953999901.

That is, ExCOPD <5 (low risk of exacerbations).

Observation of the patient during the year revealed 1 exacerbation of COPD. Thus, the forecast made by us was realized.

Example 2

Patient B., 70 years old, with a diagnosis of COPD (GOLD 2) without exacerbation and obesity of the II degree, data from a comprehensive clinical, instrumental and laboratory examination: the level of venipheral blood adiponectin was 4.13 μg / ml, body mass index - 38 kg / cm ² , venous blood leptin level of 58.01 ng / ml, venous blood melatonin level of 3.36 pg / ml, venous blood thyroid stimulating hormone level of 1.25 μIU / ml, the result of a test to assess the degree of COPD influence on patients' QOL (CAT) - 30 points, the test result with a 6-minute walk of 300 m.

The number of COPD exacerbations calculated using our prognostic model over the coming year was: ExCOPD = -0.644931-0.0242142⋅4.13 + 0.139113⋅38 + 0.0115153 * 58.01-0.0307489 ,33.36-0.341487⋅1.25 + 0.0865162⋅30-0.00575381⋅300 = 5.5484137.

That is, ExCOPD> 5 (high risk of exacerbations).

Observation of the patient during the year revealed 4 exacerbations of COPD.

Thus, the forecast made by us was realized.

The developed method for predicting exacerbations of COPD allows predicting the frequency of exacerbations of the disease (high risk, low risk) in obese patients over the next year of observation.

Claims (3)

A method for predicting exacerbations of chronic obstructive pulmonary disease (COPD) over the coming year in patients with concomitant obesity, including calculating body mass index (BMI), conducting a 6-minute walk test (TLC) and a test to assess the degree of influence of COPD on patients' quality of life - COPD Assessment Test (CAT), characterized in that it additionally determines the levels of thyroid stimulating hormone (TSH), leptin, adiponectin, melatonin, based on the obtained data, the probability index of COPD exacerbation is calculated within 1 year of observation (E xCOPD) by the formula: ExCOPD = -0.644931-0.0242142⋅ADIPO + 0.139113⋅IMT + 0.0115153⋅LEPTIN-0.0307489⋅MELATONIN-0.341487⋅TTG + 0.0865162⋅CAT-0.00575381⋅ТШХ, and with an ExCOPD value of less than 5, a low risk of developing exacerbations of COPD with an exacerbation of up to 2 times a year is predicted, with an ExCOPD value of 5 or more, a high risk of exacerbations with an exacerbation of 2 or more times a year is predicted.