National recommendations for the treatment of COPD. COPD - national recommendations

1
Russian Respiratory Society
Federal clinical
recommendations for diagnosis and
treatment
chronic obstructive disease
lungs
2014

2
Team of authors
Chuchalin Alexander Grigorievich Director of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA
Russia, Chairman of the Board of the Russian Respiratory Society, chief freelance specialist pulmonologist
Ministry of Health of the Russian Federation, academician of the Russian Academy of Medical Sciences, professor, doctor of medical sciences.
Aisanov Zaurbek Ramazanovich
Head of the Department of Clinical Physiology and Clinical Research, Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Professor, Doctor of Medical Sciences.
Avdeev Sergey Nikolaevich
Deputy Director for Scientific Work, Head of the Clinical Department of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Professor, Doctor of Medical Sciences.
Belevsky Andrey
Stanislavovich
Professor of the Department of Pulmonology, State Budgetary Educational Institution of Higher Professional Education
RNRMU named after N.I. Pirogova, head of the rehabilitation laboratory
FSBI "Research Institute of Pulmonology" FMBA of Russia
, professor, doctor of medical sciences
Leshchenko Igor Viktorovich
Professor of the Department of Phthisiology and Pulmonology of the State Budgetary Educational Institution of Higher Professional Education of the USMU, chief freelance pulmonologist of the Ministry of Health
Sverdlovsk region and the Health Department of Yekaterinburg, scientific director of the clinic “Medical Association “New Hospital”, professor, doctor of medical sciences, honored doctor of Russia,
Meshcheryakova Natalya Nikolaevna
Associate Professor of the Department of Pulmonology, State Budgetary Educational Institution of Higher Professional Education, Russian National Research Medical University named after N.I. Pirogova, leading researcher at the rehabilitation laboratory
FSBI "Research Institute of Pulmonology" FMBA of Russia, Ph.D.
Ovcharenko Svetlana Ivanovna
Professor, Department of Faculty Therapy No. 1, Faculty of Medicine, State Budgetary Educational Institution of Higher Professional Education First
MSMU im. THEM. Sechenova, professor, doctor of medical sciences,
Honored Doctor of the Russian Federation
Shmelev Evgeniy Ivanovich
Head of the Department of Differential Diagnosis of Tuberculosis, Central Research Institute of Infectious Diseases of the Russian Academy of Medical Sciences, Doctor of Medical Sciences. Sciences, Professor, Doctor of Medical Sciences, Honored Scientist of the Russian Federation.

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TABLE OF CONTENTS
1.
Methodology
4
2.
COPD Definition and Epidemiology
6
3.
Clinical picture of COPD
8
4.
Diagnostic principles
11
5.
Functional tests in diagnostics and monitoring
14
COPD course
6.
Differential diagnosis of COPD
18
7.
Modern classification of COPD. Comprehensive
20
assessment of severity.
8.
Therapy for stable COPD
24
9.
Exacerbation of COPD
29
10.
Treatment for exacerbation of COPD
31
11.
COPD and related diseases
34
12.
Rehabilitation and patient education
36

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1. Methodology
Methods used to collect/select evidence:
search in electronic databases.
Description of methods used to collect/select evidence: the evidence base for recommendations is the publications included in
Cochrane Library, EMBASE and MEDLINE databases. The search depth was 5 years.
Methods used to assess the quality and strength of evidence:

Expert consensus;

Assessment of significance in accordance with the rating scheme (see Table 1).
Table 1. Rating scheme for assessing the strength of recommendations.
Levels
evidence
Description
1++
High quality meta-analyses, systematic reviews of randomized controlled trials (RCTs) or
RCT with very low risk of bias
1+
Qualitatively conducted meta-analyses, systematic, or
RCTs with low risk of bias
1-
Meta-analyses, systematic, or RCTs with a high risk of bias
2++
High-quality systematic reviews of case-control or cohort studies.
High-quality reviews of case-control or cohort studies with very low risk of confounding effects or bias and moderate probability of causality
2+
Well-conducted case-control or cohort studies with moderate risk of confounding effects or bias and moderate probability of causality
2-
Case-control or cohort studies with a high risk of confounding effects or bias and a moderate probability of causality
3
Non-analytical studies (eg case reports, case series)
4
Expert opinion
Methods used to analyze evidence:

Reviews of published meta-analyses;

Systematic reviews with evidence tables.
Description of methods used to analyze evidence:
When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The outcome of the study influences the level of evidence assigned to the publication, which in turn influences the strength of the resulting recommendations.

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Methodological examination is based on several key questions that focus on those features of the study design that have a significant impact on the validity of the results and conclusions. These key questions may vary depending on the types of studies and questionnaires used to standardize the publication assessment process. The recommendations used the MERGE questionnaire developed by
New South Wales Department of Health. This questionnaire is designed for detailed assessment and adaptation according to requirements
Russian Respiratory Society (RRO) in order to maintain an optimal balance between methodological rigor and the possibility of practical application.
The assessment process, of course, can also be affected by a subjective factor.
To minimize potential bias, each study was assessed independently, i.e. at least two independent members of the working group.
Any differences in assessments were discussed by the whole group as a whole.
If it was impossible to reach consensus, an independent expert was involved.
Evidence tables:
Evidence tables were completed by members of the working group.
Methods used to formulate recommendations:
Expert consensus.
Table 2. Rating scheme for assessing the strength of recommendations
Force
Description
A
At least one meta-analysis, systematic review or RCT rated 1++, directly applicable to the target population and demonstrating robustness of the results, or a body of evidence including results from studies rated 1+, directly applicable to the target population and demonstrating overall robustness results
IN
A body of evidence that includes results from studies rated 2++ that are directly applicable to the target population and demonstrate general robustness of the results, or evidence extrapolated from studies rated 1++ or 1+
WITH
A body of evidence that includes findings from studies rated 2+, directly applicable to the target population, and demonstrating overall robustness of the findings; or extrapolated evidence from studies rated 2++
D
Level 3 or 4 evidence; or extrapolated evidence from studies rated 2+
Good Practice Points (GPPs):
Recommended good practice is based on the clinical experience of the guideline working group members.
Economic analysis:

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No cost analysis was performed and pharmacoeconomics publications were not reviewed.
Recommendation validation method:

External expert assessment;

Internal expert assessment.
Description of the method for validating recommendations:
These draft recommendations were reviewed by independent experts who were asked to comment primarily on the extent to which the interpretation of the evidence underlying the recommendations is understandable.
Comments were received from primary care physicians and local therapists regarding the clarity of the recommendations and their assessment of the importance of the recommendations as a working tool in daily practice.
A preliminary version was also sent to a non-medical reviewer for comments from patient perspectives.
The comments received from the experts were carefully systematized and discussed by the chairman and members of the working group. Each point was discussed and the resulting changes to the recommendations were recorded. If changes were not made, then the reasons for refusing to make changes were recorded.
Consultation and expert assessment:
A preliminary version was posted for wide discussion on the website
RPO to ensure that persons not participating in the congress have the opportunity to participate in the discussion and improvement of the recommendations.
The draft guidelines were also peer-reviewed by independent experts, who were asked to comment primarily on the clarity and accuracy of the interpretation of the evidence base underlying the recommendations.
Working group:
For final revision and quality control, the recommendations were re-analyzed by members of the working group, who concluded that all comments and comments from experts were taken into account, and the risk of systematic errors in the development of recommendations was minimized.
Basic recommendations:
Strength of recommendations (A – D), levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) and good practice points (GPPs) are given in the text. recommendations.
2. Definition of COPD and epidemiology
Definition
COPD is a preventable and treatable disease
characterized by persistent air speed limitation
flow, which is usually progressive and associated with severe chronic
inflammatory response of the lungs to the action of pathogenic particles or gases.
In some patients, exacerbations and concomitant diseases may affect
overall severity of COPD (GOLD 2014).
Traditionally, COPD combines chronic bronchitis and emphysema
Chronic bronchitis is usually defined clinically as the presence of a cough producing sputum for at least 3 months over the next 2 years.

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Emphysema is defined morphologically as the presence of persistent dilation of the airways distal to the terminal bronchioles, associated with destruction of the alveolar walls, not associated with fibrosis.
In patients with COPD, both conditions are most often present, and in some cases it is quite difficult to clinically distinguish between them in the early stages of the disease.
The concept of COPD does not include bronchial asthma and other diseases associated with poorly reversible bronchial obstruction (cystic fibrosis, bronchiectasis, bronchiolitis obliterans).
Epidemiology
Prevalence
COPD is currently a global problem. In some countries around the world, the prevalence of COPD is very high (over 20% in Chile), in others it is lower (about 6% in Mexico). The reasons for this variability are differences in people's lifestyles, behavior and exposure to a variety of damaging agents.
One of the Global Studies (BOLD Project) provided a unique opportunity to estimate the prevalence of COPD using standardized questionnaires and pulmonary function tests in populations of adults over 40 years of age in both developed and developing countries. Prevalence
COPD stage II and higher (GOLD 2008), according to the BOLD study, among people over 40 years old was 10.1±4.8%; including for men – 11.8±7.9% and for women – 8.5±5.8%. According to an epidemiological study on the prevalence of COPD in the Samara region (residents 30 years of age and older), the prevalence of COPD in the total sample was 14.5% (men - 18.7%, women - 11.2%). According to the results of another Russian study conducted in the Irkutsk region, the prevalence of COPD in people over 18 years of age among the urban population was 3.1%, among the rural

6,6 %.
The prevalence of COPD increased with age: in the age group from 50 to
69 years old, 10.1% of men in the city and 22.6% suffered from the disease

in the countryside. Almost every second man over 70 years of age living in rural areas was diagnosed with COPD.
Mortality
According to WHO, COPD is currently the 4th leading cause of death in the world. About 2.75 million people die from COPD every year, which is
4.8% of all causes of death. In Europe, mortality from COPD varies significantly, from
0.20 per 100,000 population in Greece, Sweden, Iceland and Norway, up to 80 per 100,000 in Ukraine and Romania.
In the period from 1990 to 2000. mortality from cardiovascular diseases in general and from stroke decreased by 19.9% ​​and 6.9%, respectively, while mortality from COPD increased by 25.5%. A particularly pronounced increase in mortality from
COPD occurs among women.
Predictors of mortality in patients with COPD are factors such as the severity of bronchial obstruction, nutritional status (body mass index), physical endurance according to the 6-minute walk test and severity of shortness of breath, frequency and severity of exacerbations, pulmonary hypertension.
The main causes of death in patients with COPD are respiratory failure (RF), lung cancer, cardiovascular diseases and tumors of other localizations.
Socio-economic significance of COPD
In developed countries, the total economic costs associated with COPD in the structure of pulmonary diseases occupy 2nd place after lung cancer and 1st place

8 in terms of direct costs, exceeding the direct costs of bronchial asthma by 1.9 times.
The economic costs per patient associated with COPD are three times higher than for a patient with bronchial asthma. The few reports on direct medical costs for COPD indicate that more than 80% of costs are spent on inpatient care and less than 20% on outpatient care. It was found that 73% of costs are for 10% of patients with severe disease. The greatest economic damage comes from treating exacerbations of COPD. In Russia, the economic burden of COPD, taking into account indirect costs, including absenteeism (absenteeism) and presenteeism (less effective work due to poor health), amounts to 24.1 billion rubles.
3. Clinical picture of COPD
Under conditions of exposure to risk factors (smoking, both active and passive, exogenous pollutants, bioorganic fuel, etc.), COPD usually develops slowly and progresses gradually. The peculiarity of the clinical picture is that for a long time the disease proceeds without pronounced clinical manifestations (3, 4; D).
The first signs with which patients consult a doctor are a cough, often with sputum production, and/or shortness of breath. These symptoms are most pronounced in the morning. During cold seasons, “frequent colds” occur.
This is the clinical picture of the onset of the disease,
which the doctor regards as a manifestation of smoker’s bronchitis, and the diagnosis of COPD at this stage is practically not made.
Chronic cough, usually the first symptom of COPD, is often underestimated by patients, as it is considered an expected consequence of smoking and/or exposure to adverse environmental factors. Typically, patients produce a small amount of viscous sputum. An increase in cough and sputum production occurs most often in the winter months, during infectious exacerbations.
Dyspnea is the most important symptom of COPD (4; D). It is often the reason for seeking medical help and the main reason limiting the patient’s work activity. The health impact of breathlessness is assessed using the British Medical Council questionnaire.
(MRC). Initially, shortness of breath occurs with relatively high levels of physical activity, such as running on level ground or walking up stairs. As the disease progresses, shortness of breath intensifies and can limit even daily activity, and later occurs at rest, forcing the patient to stay at home (Table 3). In addition, the assessment of dyspnea using the MRC scale is a sensitive tool for predicting the survival of patients with COPD.
Table 3. Dyspnea rating according to the Medical Research Council Scale (MRC)
Dyspnea Scale.
Degree Severity
Description
0 no
I feel short of breath only during intense physical activity
1 light
I get out of breath when walking quickly on level ground or climbing a gentle hill
2 medium
Shortness of breath causes me to walk on level ground slower than people of the same age, or I stop breathing when I walk on level ground at my normal pace

9 3 heavy
I get out of breath after walking about 100 m, or after walking for a few minutes on level ground
4 very heavy
I am too short of breath to leave the house or feel out of breath when getting dressed or undressed
When describing the clinical picture of COPD, it is necessary to take into account the features characteristic of this particular disease: its subclinical onset, the absence of specific symptoms, and the steady progression of the disease.
The severity of symptoms varies depending on the phase of the disease (stable course or exacerbation). A condition in which the severity of symptoms does not change significantly over weeks or even months should be considered stable, and in this case, disease progression can only be detected with long-term (6-12 months) follow-up of the patient.
Exacerbations of the disease have a significant impact on the clinical picture - periodically occurring deterioration of the condition (lasting at least 2-3 days), accompanied by an increase in the intensity of symptoms and functional disorders. During an exacerbation, there is an increase in the severity of hyperinflation and the so-called. air traps in combination with a reduced expiratory flow, which leads to increased shortness of breath, which is usually accompanied by the appearance or intensification of distant wheezing, a feeling of constriction in the chest, and a decrease in exercise tolerance.
In addition, the cough intensity increases, changes
(increases or sharply decreases) the amount of sputum, the nature of its separation, color and viscosity. At the same time, indicators of external respiration function and blood gases deteriorate: speed indicators (FEV) decrease
1
etc.), hypoxemia and even hypercapnia may occur.
The course of COPD is an alternation of a stable phase and exacerbation of the disease, but it varies from person to person. However, progression of COPD is common, especially if the patient continues to be exposed to inhaled pathogenic particles or gases.
The clinical picture of the disease also seriously depends on the phenotype of the disease, and vice versa, the phenotype determines the characteristics of the clinical manifestations
COPD For many years, there has been a division of patients into emphysematous and bronchitis phenotypes.
Bronchitic type is characterized by a predominance of signs of bronchitis
(cough, sputum production). Emphysema in this case is less pronounced. In the emphysematous type, on the contrary, emphysema is the leading pathological manifestation, shortness of breath prevails over cough. However, in clinical practice it is very rarely possible to distinguish the emphysematous or bronchitis phenotype of COPD in the so-called. “pure” form (it would be more correct to talk about a predominantly bronchitis or predominantly emphysematous phenotype of the disease).
The features of the phenotypes are presented in more detail in Table 4.

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1 Federal State Budgetary Educational Institution of Russian National Research Medical University named after. N.I. Pirogov Ministry of Health of Russia, Moscow
2 Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA of Russia, Moscow
3 Federal State Budgetary Educational Institution of Higher Education USMU of the Ministry of Health of Russia, Ekaterinburg
4 Federal State Autonomous Educational Institution of Higher Education First Moscow State Medical University named after. I. M. Sechenov Ministry of Health of Russia (Sechenov University), Moscow
5 Federal State Budgetary Institution "CNIIT", Moscow

For quotation: Chuchalin A.G., Aisanov Z.R., Avdeev S.N., Leshchenko I.V., Ovcharenko S.I., Shmelev E.I. Federal clinical guidelines for the diagnosis and treatment of chronic obstructive pulmonary disease // RMZh. 2014. No. 5. P. 331

1. Methodology

1. Methodology
Methods used to collect/select evidence:
. search in electronic databases.
Description of methods used to collect/select evidence:
. The evidence base for the recommendations is publications included in the Cochrane Library, EMBASE and MEDLINE databases. The search depth was 5 years.
Methods used to assess the quality and strength of evidence:
. expert consensus;
. assessment of significance in accordance with the rating scheme (Table 1).
Methods used to analyze evidence:
. reviews of published meta-analyses;
. systematic reviews with evidence tables.
Description of the methods used to analyze the evidence.
When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The outcome of the study influences the level of evidence assigned to the publication, which in turn influences the strength of the resulting recommendations.
Methodological examination is based on several key questions that focus on those features of the study design that have a significant impact on the validity of the results and conclusions. These key questions may vary depending on the types of studies and questionnaires used to standardize the publication assessment process. The recommendations used the MERGE questionnaire developed by the New South Wales Department of Health. This questionnaire is intended to be assessed in detail and adapted to meet the requirements of the Russian Respiratory Society in order to maintain an optimal balance between methodological rigor and practical applicability.
The assessment process, of course, can also be affected by a subjective factor. To minimize potential bias, each study was assessed independently, i.e. by at least two independent members of the working group. Any differences in assessments were discussed by the whole group as a whole. If it was impossible to reach consensus, an independent expert was involved.
Evidence tables:
. evidence tables were completed by members of the working group.
Methods used to formulate recommendations:
. expert consensus.
Basic recommendations:
The strength of recommendations (A-D), levels of evidence (1++, 1+, 1-, 2++, 2+, 2-, 3, 4) and indicators of good practice (good practice points) are given when presenting the text of the recommendations (Table. 1 and 2).

2. Definition of chronic obstructive pulmonary disease (COPD) and epidemiology
Definition:
COPD is a disease characterized by impaired ventilation function of an obstructive type, partially reversible, which usually progresses and is associated with an increased chronic inflammatory response of the lungs to the action of pathogenic particles or gases. In some patients, exacerbations and comorbidities may influence the overall severity of COPD.
Traditionally, COPD combines chronic bronchitis and emphysema.
Chronic bronchitis is usually defined clinically as the presence of a cough producing sputum for at least 3 months. over the next 2 years. Emphysema is defined morphologically as the presence of persistent dilation of the airways distal to the terminal bronchioles, associated with destruction of the alveolar walls, not associated with fibrosis. In patients with COPD, both conditions are most often present and it is quite difficult to clinically distinguish between them.
The concept of COPD does not include bronchial asthma (BA) and other diseases associated with poorly reversible bronchial obstruction (cystic fibrosis, bronchiectasis, bronchiolitis obliterans).

Epidemiology
Prevalence
COPD is currently a global problem. In some countries around the world, the prevalence of COPD is very high (over 20% in Chile), in others it is lower (about 6% in Mexico). The reasons for this variability are differences in people's lifestyles, behavior and exposure to a variety of damaging agents.
One global study (the BOLD project) provided a unique opportunity to estimate the prevalence of COPD using standardized questionnaires and pulmonary function tests in populations of adults over 40 years of age in both developed and developing countries. The prevalence of COPD stage II and higher (GOLD 2008), according to the BOLD study, among people over 40 years of age was 10.1±4.8%, including for men - 11.8±7.9% and for women - 8.5±5.8%. According to an epidemiological study on the prevalence of COPD in the Samara region (residents 30 years and older), the prevalence of COPD in the overall sample was 14.5% (among men - 18.7%, among women - 11.2%). According to the results of another Russian study conducted in the Irkutsk region, the prevalence of COPD in people over 18 years of age among the urban population was 3.1%, among the rural population - 6.6%. The prevalence of COPD increased with age: in the age group from 50 to 69 years, 10.1% of men in the city and 22.6% in rural areas suffered from the disease. Almost every second man over 70 years of age living in rural areas was diagnosed with COPD.

Mortality
According to WHO, COPD is currently the 4th leading cause of death in the world. About 2.75 million people die from COPD each year, accounting for 4.8% of all causes of death. In Europe, mortality from COPD varies significantly: from 0.2 per 100 thousand population in Greece, Sweden, Iceland and Norway to 80 per 100 thousand in Ukraine and Romania.
Between 1990 and 2000, mortality from overall cardiovascular disease (CVD) and stroke decreased by 19.9% ​​and 6.9%, respectively, while mortality from COPD increased by 25.5%. A particularly pronounced increase in mortality from COPD is observed among women.
Predictors of mortality in patients with COPD include factors such as the severity of bronchial obstruction, nutritional status (body mass index (BMI)), physical endurance according to the 6-minute walk test and severity of shortness of breath, frequency and severity of exacerbations, and pulmonary hypertension.
The main causes of death in patients with COPD are respiratory failure (RF), lung cancer, CVD and tumors of other localizations.
Socio-economic significance of COPD
In developed countries, the total economic costs associated with COPD in the structure of pulmonary diseases occupy 2nd place after lung cancer and 1st place in direct costs, exceeding the direct costs of asthma by 1.9 times. Economic costs per patient associated with COPD are 3 times higher than for a patient with asthma. The few reports on direct medical costs for COPD indicate that more than 80% of financial resources are spent on inpatient care and less than 20% on outpatient care. It was found that 73% of costs are for 10% of patients with severe disease. The greatest economic damage comes from treating exacerbations of COPD. In Russia, the economic burden of COPD, taking into account indirect costs, including absenteeism (absenteeism) and presenteeism (less effective work due to poor health), amounts to 24.1 billion rubles.

3. Clinical picture of COPD
Under conditions of exposure to risk factors (smoking, both active and passive, exogenous pollutants, bioorganic fuel, etc.), COPD usually develops slowly and progresses gradually. The peculiarity of the clinical picture is that for a long time the disease proceeds without pronounced clinical manifestations (3, 4; D).
The first signs with which patients consult a doctor are a cough, often with sputum production, and/or shortness of breath. These symptoms are most pronounced in the morning. During cold seasons, “frequent colds” occur. This is the clinical picture of the onset of the disease.
Chronic cough, usually the first symptom of COPD, is often underestimated by patients and doctors, because it is considered an expected consequence of smoking and/or exposure to adverse environmental factors. Typically, patients produce a small amount of viscous sputum. An increase in cough and sputum production occurs most often in the winter months, during infectious exacerbations.
Dyspnea is the most important symptom of COPD (4; D). It is often the reason for seeking medical help and the main reason limiting the patient’s work activity. The health impact of breathlessness is assessed using the British Medical Research Council (mMRC) questionnaire. Initially, shortness of breath occurs with relatively high levels of physical activity, such as running on level ground or walking up stairs. As the disease progresses, shortness of breath intensifies and can limit even daily activity, and later occurs at rest, forcing the patient to stay at home (Table 3). In addition, assessment of dyspnea using the mMRC scale is a sensitive tool for predicting survival in patients with COPD.
When describing the clinical picture of COPD, it is necessary to take into account the features characteristic of this disease: its subclinical onset, the absence of specific symptoms, and the steady progression of the disease.
The severity of symptoms varies depending on the phase of the disease (stable course or exacerbation). A condition in which the severity of symptoms does not change significantly over weeks or even months should be considered stable, and in this case, the progression of the disease can be detected only with long-term (6-12 months) dynamic observation of the patient.
Exacerbations of the disease have a particular impact on the clinical picture - periodically occurring deterioration of the condition (lasting at least 2-3 days), accompanied by an increase in the intensity of symptoms and functional disorders. During an exacerbation, there is an increase in the severity of hyperinflation and so-called “air traps” in combination with a reduced expiratory flow, which leads to increased shortness of breath, which is usually accompanied by the appearance or intensification of distant wheezing, a feeling of constriction in the chest, and a decrease in exercise tolerance. In addition, the intensity of the cough increases, the amount of sputum, the nature of its separation, color and viscosity change (increase or sharply decrease). At the same time, indicators of external respiration function (FER) and blood gases deteriorate: speed indicators decrease (forced expiratory volume in 1 s (FEV1), etc.), hypoxemia and even hypercapnia may occur. Exacerbations can begin gradually, gradually, or can be characterized by a rapid deterioration of the patient’s condition with the development of acute respiratory failure, and less often, right ventricular failure.
The course of COPD is an alternation of a stable phase and exacerbation of the disease, but it varies from person to person. However, progression of COPD is common, especially if the patient continues to be exposed to inhaled pathogenic particles or gases. The clinical picture of the disease also seriously depends on the phenotype of the disease, and vice versa, the phenotype determines the characteristics of the clinical manifestations of COPD. For many years, there has been a division of patients into emphysematous and bronchitis phenotypes.
The bronchitis type is characterized by a predominance of signs of bronchitis (cough, sputum production). Emphysema in this case is less pronounced. In the emphysematous type, on the contrary, emphysema is the leading pathological manifestation, shortness of breath prevails over cough. However, in clinical practice it is very rarely possible to isolate the emphysematous or bronchitis phenotype of COPD in the so-called “pure” form (it would be more correct to speak of a predominantly bronchitis or predominantly emphysematous phenotype of the disease). The features of the phenotypes are presented in more detail in Table 4.
If it is impossible to distinguish the predominance of one phenotype or another, one should speak of a mixed phenotype. In clinical settings, patients with a mixed type of disease are more common.
In addition to the above, other phenotypes of the disease are currently identified. First of all, this applies to the so-called overlap phenotype (a combination of COPD and asthma). It is necessary to carefully differentiate between patients with COPD and asthma. But despite the significant differences in chronic inflammation in these diseases, in some patients COPD and asthma can be present simultaneously. This phenotype can develop in smoking patients suffering from asthma. Along with this, as a result of large-scale studies, it has been shown that about 20-30% of patients with COPD may have reversible bronchial obstruction, and eosinophils appear in the cellular composition during inflammation. Some of these patients can also be attributed to the “COPD + BA” phenotype. Such patients respond well to corticosteroid therapy.
Another phenotype that has been talked about recently is patients with frequent exacerbations (2 or more exacerbations per year or 1 or more exacerbations leading to hospitalization). The importance of this phenotype is determined by the fact that the patient emerges from an exacerbation with reduced functional indicators of the lungs, and the frequency of exacerbations directly affects the life expectancy of patients; an individual approach to treatment is required. The identification of numerous other phenotypes requires further clarification. Several recent studies have drawn attention to differences in the clinical presentation of COPD between men and women. As it turned out, women are characterized by more pronounced hyperreactivity of the respiratory tract, they note more pronounced shortness of breath at the same levels of bronchial obstruction as in men, etc. With the same functional indicators, oxygenation occurs better in women than in men. However, women are more likely to develop exacerbations, they show less effect of physical training in rehabilitation programs, and they rate their quality of life (QoL) lower according to standard questionnaires.
It is well known that patients with COPD have numerous extrapulmonary manifestations of the disease due to the systemic effect of chronic inflammation characteristic of COPD. This primarily concerns dysfunction of peripheral skeletal muscles, which makes a significant contribution to reduced exercise tolerance. Chronic persistent inflammation plays an important role in damage to the vascular endothelium and the development of atherosclerosis in patients with COPD, which in turn contributes to the growth of CVD (arterial hypertension (AH), coronary heart disease (CHD), acute myocardial infarction (AMI), heart failure (HF) ) in patients with COPD and increases the risk of mortality. Changes in nutritional status are clearly evident. In turn, reduced nutritional status can serve as an independent risk factor for the death of patients. Systemic inflammation also contributes to the development of osteoporosis. Patients suffering from COPD have more pronounced signs of osteoporosis compared to the same age groups of people who do not have COPD. Recently, attention has been drawn to the fact that in addition to polycythemia, anemia occurs in 10-20% of cases in patients with COPD. Its cause is not fully understood, but there is reason to believe that it is the result of the systemic effect of chronic inflammation in COPD.
Neuropsychiatric disorders, manifested by memory loss, depression, the appearance of “fears” and sleep disturbances, have a significant impact on the clinical picture of the disease.
Patients with COPD are characterized by the frequent development of concomitant diseases that occur in older patients regardless of the presence of COPD, but with its presence - with a higher probability (coronary artery disease, hypertension, atherosclerosis of the lower extremity vessels, etc.). Other comorbidities (diabetes mellitus (DM), gastroesophageal reflux disease, prostate adenoma, arthritis) may co-exist with COPD because they are part of the aging process and also have a significant impact on the clinical picture of a patient suffering from COPD.
During the natural development of COPD, the clinical picture may change taking into account the emerging complications of the disease: pneumonia, pneumothorax, acute DN (AP), pulmonary embolism (PE), bronchiectasis, pulmonary hemorrhage, development of cor pulmonale and its decompensation with severe circulatory failure.
To summarize the description of the clinical picture, it should be emphasized that the severity of the clinical manifestations of the disease depends on many of the above factors. All this, along with the intensity of exposure to risk factors and the rate of progression of the disease, creates the appearance of the patient at different periods of his life.

4. Diagnostic principles
To correctly diagnose COPD, it is necessary first of all to rely on the key (basic) provisions arising from the definition of the disease. A diagnosis of COPD should be considered in all patients when cough, sputum production, or shortness of breath is present and risk factors for COPD are identified. In real life, in the early stages of the disease, a smoker does not consider himself sick, because he evaluates cough as a normal condition if his work activity has not yet been impaired. Even the appearance of shortness of breath that occurs during physical activity is regarded by him as a result of old age or detraining.
The key anamnestic factor that helps establish the diagnosis of COPD is the establishment of the fact of inhalation exposure to pathogenic agents, primarily tobacco smoke, on the respiratory system. When assessing smoking status, the index of the person smoking (pack-years) is always indicated. When collecting anamnesis, great attention should also be paid to identifying episodes of passive smoking. This applies to all age groups, including exposure to tobacco smoke on the fetus in the prenatal period as a result of smoking by the pregnant woman herself or those around her. Occupational inhalation exposures, along with smoking, are considered to be factors leading to the onset of COPD. This applies to various forms of air pollution in the workplace, including gases and aerosols, as well as exposure to smoke from fossil fuels.
Thus, the diagnosis of COPD should include the following areas:
- identification of risk factors;
- objectification of obstruction symptoms;
- monitoring of respiratory function of the lungs.
It follows that the diagnosis of COPD is based on the analysis of a number of stages:
- creating a verbal portrait of the patient based on information gleaned from a conversation with him (careful collection of anamnesis);
- objective (physical) examination;
- results of laboratory and instrumental research. The diagnosis of COPD should always be confirmed by spirometry. Post-bronchodilation FEV1/forced vital capacity (FVC) values<70% - обязательный признак ХОБЛ, который существует на всех стадиях заболевания.
Due to the fact that COPD does not have specific manifestations and the criterion for diagnosis is the spirometric indicator, the disease can remain undiagnosed for a long time. The problem of underdiagnosis is also due to the fact that many people suffering from COPD do not feel sick due to the absence of shortness of breath at a certain stage of the disease and do not come to the attention of the doctor. It follows that in the vast majority of cases, the diagnosis of COPD is carried out at the disabling stages of the disease.
A detailed conversation with each smoking patient will contribute to the early detection of the disease, since with active questioning and the absence of complaints, it is possible to identify signs characteristic of the development of chronic inflammation in the bronchial tree, primarily cough.
During a conversation with the patient, you can use a questionnaire to diagnose COPD* (Table 5).
In the process of the formation of irreversible changes in the bronchial tree and lung parenchyma, shortness of breath appears (in a conversation with the patient, it is necessary to assess its severity, connection with physical activity, etc.).
In the early stages of the disease (if for some reason the patient still comes to the attention of the doctor at this time), the examination does not reveal any abnormalities characteristic of COPD, however, the absence of clinical symptoms does not exclude its presence. With the increase of emphysema and the irreversible component of bronchial obstruction, exhalation can occur through tightly closed or folded lips, which indicates a pronounced expiratory collapse of the small bronchi and slows down the flow rate of exhaled air, which alleviates the condition of patients. Other signs of hyperinflation may be a barrel-shaped chest, horizontal direction of the ribs, and decreased cardiac dullness.
The inclusion of the Scalenae and Sternocleidomastoideus muscles in the act of breathing is an indicator of further aggravation of the violation of respiratory mechanics and increased load on the respiratory apparatus. Another sign may be a paradoxical movement of the anterior wall of the abdominal cavity - its retraction during inhalation, which indicates fatigue of the diaphragm. Flattening of the diaphragm leads to retraction of the lower ribs during inspiration (Hoover sign) and widening of the kyphosternal angle. When the respiratory muscles become fatigued, hypercapnia often occurs, which requires appropriate assessment.
During a physical examination of patients, it is possible to objectify the presence of bronchial obstruction by listening to dry wheezing, and during percussion, a boxy percussion sound confirms the presence of hyperinflation.
Among the laboratory diagnostic methods, mandatory tests include a clinical blood test and cytological examination of sputum. In cases of severe emphysema and a young patient, α1-antitrypsin should be determined. During exacerbation of the disease, neutrophilic leukocytosis with a band shift and an increase in ESR are most common. The presence of leukocytosis serves as an additional argument in favor of an infectious factor as a cause of exacerbation of COPD. Both anemia (the result of a general inflammatory syndrome) and polycythemia can be detected. Polycythaemic syndrome (increased red blood cell count, high hemoglobin level -
>16 g/dl in women and >18 g/dl in men, increased hematocrit >47% in women and >52% in men) may indicate the existence of severe and prolonged hypoxemia.
Cytological examination of sputum provides information about the nature of the inflammatory process and the degree of its severity. The detection of atypical cells increases the suspicion of cancer and requires the use of additional examination methods.
It is advisable to carry out cultural microbiological examination of sputum in case of uncontrolled progression of the infectious process and use it to select rational antibiotic therapy. For the same purpose, a bacteriological study of bronchial contents obtained during bronchoscopy is carried out.
Chest radiography should be performed in all patients with a suspected diagnosis of COPD. This method is not a sensitive tool for making a diagnosis, but it makes it possible to exclude other diseases accompanied by similar clinical symptoms (tumor, tuberculosis, congestive heart failure, etc.), and during an exacerbation, to identify pneumonia, pleural effusion, spontaneous pneumothorax, etc. In addition, the following radiological signs of bronchial obstruction can be identified: flattening of the dome and limitation of the mobility of the diaphragm during breathing movements, changes in the anteroposterior size of the thoracic cavity, expansion of the retrosternal space, vertical position of the heart.
Bronchoscopic examination serves as an additional method for diagnosing COPD to exclude other diseases and conditions that occur with similar symptoms.
Electrocardiography and echocardiography are performed to exclude cardiac origin of respiratory symptoms and identify signs of hypertrophy of the right heart.
All patients suspected of having COPD should undergo spirometry.

5. Functional diagnostic tests
monitoring the course of COPD
Spirometry is the main method for diagnosing and documenting changes in pulmonary function in COPD. The classification of COPD according to the severity of obstructive ventilation disorders is based on spirometry indicators. It allows you to exclude other diseases with similar symptoms.
Spirometry is the preferred initial test to assess the presence and severity of airway obstruction.

Methodology
. There are various recommendations for the use of spirometry as a method for diagnosing and determining the severity of obstructive pulmonary diseases.
. The study of pulmonary function using forced spirometry can be considered complete if 3 technically acceptable breathing maneuvers are obtained. At the same time, the results must be reproducible: the maximum and subsequent FVC indicators, as well as the maximum and subsequent FEV1 indicators, should differ by no more than 150 ml. In cases where the FVC value does not exceed 1000 ml, the maximum permissible difference in both FVC and FEV1 should not exceed 100 ml.
. If reproducible results are not obtained after 3 attempts, breathing maneuvers must be continued up to 8 attempts. More breathing maneuvers may result in patient fatigue and, in rare cases, decreased FEV1 or FVC.
. If the indicators drop by more than 20% from the initial value as a result of repeated forced maneuvers, further testing should be stopped in the interests of patient safety, and the dynamics of the indicators should be reflected in the report. The report must present graphical results and numerical values ​​of at least the 3 best attempts.
. The results of technically acceptable attempts that do not meet the reproducibility criterion may be used to write a conclusion indicating that they are not reproducible.
Spirometric manifestations of COPD
When performing spirometry, COPD is manifested by expiratory airflow limitation due to increased airway resistance (Fig. 1).
The obstructive type of ventilation disorders is characterized by a decrease in the ratio of FEV1/FVC indicators<0,7.
There is depression in the expiratory part of the flow-volume curve, and its descending limb takes on a concave shape. Disturbance in the linearity of the lower half of the flow-volume curve is a characteristic feature of obstructive ventilation disorders, even when the FEV1/FVC ratio is >0.7. The severity of changes depends on the severity of obstructive disorders.
As bronchial obstruction progresses, there is a further decrease in expiratory flow, an increase in “air traps” and hyperinflation of the lungs, which leads to a decrease in FVC indicators. To exclude mixed obstructive-restrictive disorders, it is necessary to measure total lung capacity (TLC) using body plethysmography.
To assess the severity of emphysema, TLC and diffusion DSL should be examined.

Reversibility test (bronchodilator test)
If signs of bronchial obstruction are recorded during the initial spirometric study, then it is advisable to perform a reversibility test (bronchodilator test) in order to determine the degree of reversibility of obstruction under the influence of bronchodilators.
To study the reversibility of obstruction, tests are carried out with inhaled bronchodilators, their effect on FEV1 is assessed. Other indicators of the flow-volume curve, which are mainly derived and calculated from FVC, are not recommended for use.

Methodology
. When conducting the test, it is recommended to use short-acting bronchodilators in the maximum single dose:
- for β2-agonists - salbutamol 400 mcg;
- for anticholinergic drugs - ipratropium bromide 160 mcg.
. In some cases, it is possible to use a combination of anticholinergic drugs and short-acting β2-agonists at the indicated doses. Metered-dose aerosol inhalers must be used with a spacer.
. A repeat spirometric study must be performed after 15 minutes. after inhalation
β2-agonists or after 30-45 min. after inhalation of anticholinergic drugs or their combination with
β2-agonists.

Criteria for a positive answer
A bronchodilator test is considered positive if, after inhalation of a bronchodilator, the bronchodilation coefficient (CBD) reaches or exceeds 12%, and the absolute increase is 200 ml or more:
CBD = (FEV1 post (ml) - FEV1 raw (ml)/FEV1 raw (ml)) x 100%

Absolute increase (ml) = FEV1 after (ml) - FEV1 out. (ml),
where FEV1 ref. - the value of the spirometric indicator before inhalation of the bronchodilator, FEV1 after - the value of the indicator after inhalation of the bronchodilator.

To conclude a positive bronchodilator test, both criteria must be achieved.
When assessing a bronchodilator test, it is important to take into account adverse reactions from the cardiovascular system: tachycardia, arrhythmia, increased blood pressure, as well as the appearance of symptoms such as agitation or tremor.
Technical variability in spirometry results can be minimized with regular calibration of equipment, careful patient instruction, and advanced training of personnel.

Proper values
The proper values ​​depend on anthropometric parameters, mainly height, gender, age, race. However, individual variations in the norm should also be taken into account. Thus, in people with initial indicators above the average level, with the development of pulmonary pathology, these indicators will decrease relative to the initial ones, but may still remain within the population norm.
Monitoring (serial studies)
Monitoring spirometric parameters (FEV1 and FVC) reliably reflects the dynamics of changes in pulmonary function during long-term observation, but the likelihood of technical and biological variability of the results must be taken into account.
In healthy individuals, changes in FVC and FEV1 are considered clinically significant if, with repeated studies within 1 day, the difference exceeds 5%, over several weeks - 12%.
An increased rate of decline in pulmonary function (more than 40 ml/year) is not a mandatory sign of COPD. In addition, it cannot be confirmed individually, since the permissible level of variability in FEV1 within one study significantly exceeds this value and is 150 ml.
Peak expiratory flow (PEF) monitoring
PEF is used to exclude increased diurnal variability that is more characteristic of asthma and response to drug therapy.
The best indicator is recorded after 3 attempts to perform a forced maneuver with a pause not exceeding 2 s after inhalation. The maneuver is performed while sitting or standing. More measurements are performed if the difference between the 2 maximum PEF values ​​exceeds 40 l/min.
PEF is used to assess airflow variability across multiple measurements taken over at least 2 weeks. Increased variability can be recorded with double measurements within 1 day. More frequent measurements improve the score. An increase in measurement accuracy in this case is achieved especially in patients with reduced compliance.
PEF variability is best calculated as the difference between the maximum and minimum values ​​as a percentage of the average or maximum daily PEF.
The upper limit of normal values ​​for variability from the maximum value is about 20% when 4 or more measurements are taken within 1 day. However, it may be lower when using double measurements.
The variability of PEF may be increased in diseases with which the differential diagnosis of asthma is most often carried out. Therefore, in clinical practice there is a lower level of specificity for increased PEF variability than in population studies.
PEF values ​​should be interpreted taking into account the clinical situation. The PEF study is only applicable for monitoring patients with an established diagnosis of COPD.

6. Differential diagnosis of COPD
The main task of differential diagnosis of COPD is to exclude diseases with similar symptoms. Despite the very definite differences between asthma and COPD in the mechanisms of development, clinical manifestations and principles of prevention and treatment, these 2 diseases have some common features. In addition, a combination of these diseases in one person is possible.
Differential diagnosis of BA and COPD is based on the integration of basic clinical data, results of functional and laboratory tests. Features of inflammation in COPD and asthma are presented in Figure 2.
The leading starting points for the differential diagnosis of these diseases are given in Table 6.
At certain stages of the development of COPD, especially at the first meeting with the patient, there is a need to differentiate it from a number of diseases with similar symptoms. Their main distinguishing features are given in Table 7.
Differential diagnosis at different stages of COPD development has its own characteristics. In mild cases of COPD, the main thing is to identify differences from other diseases associated with factors of environmental aggression, occurring subclinically or with minor symptoms. First of all, this concerns various variants of chronic bronchitis. Difficulty arises when making a differential diagnosis in patients with severe COPD. It is determined not only by the severity of the patients’ condition, the severity of irreversible changes, but also by a large set of concomitant diseases (coronary heart disease, hypertension, metabolic diseases, etc.).

7. Modern classification of COPD.
Comprehensive assessment of disease severity
The classification of COPD (Table 8) in recent years has been based on indicators of the functional state of the lungs, based on post-bronchodilator FEV1 values; it distinguishes 4 stages of the disease.
The GOLD 2011 Expert Committee abandoned the use of the term “stages” because this indicator is based only on FEV1 value and was not adequate to characterize the severity of the disease. Recent studies have shown that staging is not present in all cases of the disease. There is no evidence for the real existence of COPD stages (the transition from one stage to another with modern therapy). At the same time, FEV1 values ​​remain relevant, since they reflect the degree (from mild - stage I, respectively, to extremely severe - stage IV) of the severity of air flow limitation. They are used in a comprehensive assessment of the severity of patients with COPD.
The 2011 revision of the GOLD document proposed a new classification based on an integrated assessment of the severity of COPD patients. It takes into account not only the severity of bronchial obstruction (the degree of impairment of bronchial obstruction) according to the results of a spirometric study, but also clinical data about the patient: the number of exacerbations of COPD per year and the severity of clinical symptoms according to the results of mMRC (Table 3) and COPD Assessment Test (CAT) (Table 9).
It is known that the “gold standard” for assessing the impact of symptoms on QOL is the results of the St. George's Respiratory Questionnaire (SGRQ), its “symptoms” scale. The CAT assessment test and, more recently, the Clinical COPD Questionnaire (CCQ) have become more widely used in clinical practice.
In GOLD 2013, the assessment of symptoms was more expanded through the use of the CCQ scale, which makes it possible to objectify symptoms both for 1 day and for the last week and give them not only qualitative, but also clinical characteristics (Table 10).
The final score is calculated from the sum of points received by answering all questions and divided by 10. With its value<1 симптомы оцениваются как невыраженные, а при ≥1 - выраженные, т. е. оказывающие влияние на жизнь пациента. Вместе с тем еще окончательно не установлены значения CCQ, соответствующие выраженному влиянию симптомов на КЖ, эквивалентные значениям SGRQ. Пограничными значениями отличия выраженных от невыраженных симптомов предлагаются значения 1,0-1,5 (GOLD 2014).
The classification of COPD taking into account the recommendations of the GOLD program is presented in Table 11.
When assessing risk, it is recommended to select the highest grade based on GOLD airflow limitation or history of exacerbations.
The new 2013 edition of GOLD added a provision that if a patient had even one exacerbation in the previous year that led to hospitalization (i.e., severe exacerbation), the patient must be classified as a high-risk group.
Thus, an integral assessment of the impact of COPD on a particular patient combines symptom assessment with spirometric classification with an assessment of the risk of exacerbations.
With this in mind, the diagnosis of COPD may look like this:
“Chronic obstructive pulmonary disease...” and then the assessment follows:
- degree of severity (I-IV) of bronchial obstruction;
- severity of clinical symptoms: pronounced (CAT ≥10, mMRC ≥2, CCQ ≥1), not expressed (CAT<10, mMRC <2, CCQ <1);
- frequency of exacerbations: rare (0-1), frequent (≥2);
- COPD phenotype (if possible);
- concomitant diseases.
The role of concomitant diseases is extremely important in assessing the severity of COPD, however, even in the latest GOLD recommendation of 2013, it did not find a worthy place in the given classification.
8. Therapy for stable COPD
The main goal of treatment is to prevent the progression of the disease. Treatment goals are described in Table 12.
Main areas of treatment:
I. Non-pharmacological effects:
- reducing the influence of risk factors;
- educational programs.
Non-pharmacological methods of exposure are presented in Table 13.
In patients with severe disease (GOLD 2-4), pulmonary rehabilitation should be used as a necessary measure.

II. Drug treatment
The choice of the volume of pharmacological therapy is based on the severity of clinical symptoms, the value of post-bronchodilator FEV1 and the frequency of exacerbations of the disease (Tables 14, 15).
Schemes of pharmacological therapy for patients with COPD, compiled taking into account a comprehensive assessment of the severity of COPD (frequency of exacerbations of the disease, severity of clinical symptoms, stage of COPD, determined by the degree of bronchial obstruction), are given in Table 16.
Other treatments include oxygen therapy, respiratory support and surgery.
Oxygen therapy
It was found that long-term administration of oxygen (O2) (>15 hours/day) increases survival in patients with chronic DN and severe hypoxemia at rest (B, 2++).
Respiratory support
Noninvasive ventilation (NIV) is widely used in patients with extremely severe, stable COPD.
The combination of NIV with long-term oxygen therapy may be effective in selected patients, especially in the presence of obvious daytime hypercapnia.
Surgery
Lung Volume Reduction Surgery (LVLR)
VAOL is performed by removing part of the lung to reduce hyperinflation and achieve more efficient pumping of the respiratory muscles. Its use is carried out in patients with upper lobe emphysema and low exercise tolerance.
Lung transplantation
Lung transplantation can improve quality of life and functional outcomes in carefully selected patients with very severe COPD. The selection criteria are FEV1<25% от должной величины, РаО2 <55 мм рт. ст., РаСО2 >50 mmHg Art. when breathing room air and pulmonary hypertension (Ppa >40 mm Hg).
9. Exacerbation of COPD
Definition and meaning of exacerbations of COPD
The development of exacerbations is a characteristic feature of the course of COPD. According to the GOLD (2013) definition: “An exacerbation of COPD is an acute event characterized by a worsening of respiratory symptoms that extends beyond normal daily fluctuations and leads to a change in current therapy.”
Exacerbation of COPD is one of the most common reasons for patients seeking emergency medical care. The frequent development of exacerbations in patients with COPD leads to a long-term deterioration (up to several weeks) in respiratory function and gas exchange, more rapid progression of the disease, a significant decrease in the quality of life of patients and is associated with significant economic costs for treatment. Moreover, exacerbations of COPD lead to decompensation of concomitant chronic diseases. Severe exacerbations of COPD are the leading cause of death in patients. In the first 5 days from the onset of exacerbations, the risk of developing AMI increases by more than 2 times.
Classification of exacerbations of COPD
One of the most well-known classifications of the severity of exacerbations of COPD, proposed by the working group on the definition of exacerbations of COPD, is presented in table 17.
Steer et al. developed a new scale to assess the prognosis of patients with exacerbation of COPD hospitalized in the hospital. The 5 strongest predictors of death were identified: 1) severity of shortness of breath according to the eMRCD scale; 2) eosinopenia of peripheral blood (<0,05 клеток x109/л); 3) признаки консолидации паренхимы легких по данным рентгенографии грудной клетки; 4) ацидоз крови (pH <7,3) и 5) мерцательная аритмия. Перечисленные признаки были объединены в шкалу DECAF (по аббревиатуре первых букв в английской транскрипции) (табл. 17).
This score has demonstrated excellent discriminatory power for predicting mortality during exacerbation of COPD.
Causes of exacerbations
The most common causes of exacerbations of COPD are bacterial and viral respiratory infections and atmospheric pollutants, but the causes of approximately 20-30% of exacerbations cannot be determined.
Among bacteria during exacerbation of COPD, the most important role is played by non-typeable Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis. Studies involving patients with severe exacerbations of COPD have shown that gram-negative enterobacteriaceae and Pseudomonas aeruginosa may be more common in such patients (Table 18).
Rhinoviruses are one of the most common causes of acute respiratory viral infections and may be a significant cause of exacerbations of COPD. It has been noted that exacerbations of COPD most often develop in the autumn-winter months. An increase in the number of exacerbations of COPD may be associated with an increase in the prevalence of respiratory viral infections in the winter months and an increase in the sensitivity of the upper respiratory tract epithelium to them during the cold season.
Conditions that may resemble exacerbations and/or aggravate their course include pneumonia, pulmonary embolism, congestive heart failure, arrhythmias, pneumothorax, and pleural effusion. These conditions should be differentiated from exacerbations and, if present, appropriate treatment should be provided.
10. Therapy for exacerbation of COPD
The management tactics for COPD patients with varying degrees of exacerbation severity are presented in Table 19.
Inhaled bronchodilators
The prescription of inhaled bronchodilators is one of the main links in the treatment of exacerbation of COPD (A, 1++). Traditionally, patients with exacerbation of COPD are prescribed either fast-acting β2-agonists (salbutamol, fenoterol) or fast-acting anticholinergic drugs (ipratropium bromide). The effectiveness of β2-agonists and ipratropium bromide in exacerbation of COPD is approximately the same (B, 2++), the advantage of β2-agonists is a faster onset of action, and anticholinergic drugs have high safety and good tolerability. Today, many experts consider β2-agonist/ipratropium bromide combination therapy as the optimal strategy for the management of exacerbations of COPD (B, 2++), especially in the treatment of COPD patients with severe exacerbations.
GKS
According to clinical studies on exacerbations of COPD that required hospitalization of patients in a hospital, systemic corticosteroids reduce the time of onset of remission, improve pulmonary function (FEV1) and reduce hypoxemia (PaO2), and can also reduce the risk of early relapse and treatment failure, reduce the length of stay in hospital (A, 1+). A course of oral prednisolone therapy at a dose of 30-40 mg/day for 5-14 days is usually recommended (B, 2++). According to recent data, patients with exacerbation of COPD and blood eosinophilia >2% have the best response to systemic corticosteroids (C, 2+).
A safer alternative to systemic corticosteroids for exacerbation of COPD are inhaled, especially nebulized corticosteroids (B, 2++).
Antibacterial therapy (ABT)
Since bacteria are not the cause of all exacerbations of COPD (50%), it is important to determine the indications for prescribing ABT in the event of exacerbations. Current guidelines recommend prescribing antibiotics to patients with the most severe exacerbations of COPD, for example, with type I exacerbations according to Anthonisen classification (i.e., in the presence of increased shortness of breath, increased volume and degree of purulence of sputum) or with type II exacerbations (the presence of 2 out of 3 listed characteristics) (B, 2++). In patients with similar scenarios of exacerbations of COPD, antibiotics are most effective, since the cause of such exacerbations is a bacterial infection. Antibiotics are also recommended for patients with severe exacerbation of COPD requiring invasive or NIV (D, 3). The use of biomarkers such as C-reactive protein (CRP) helps improve diagnosis and treatment approaches for patients with exacerbation of COPD (C, 2+). An increase in CRP levels ≥15 mg/L during exacerbation of COPD is a sensitive sign of bacterial infection.
The choice of the most appropriate antibiotics for the treatment of exacerbations of COPD depends on many factors, such as the severity of COPD, risk factors for poor treatment outcome (for example, older age, low FEV1 values, previous frequent exacerbations and comorbidities of previous antibiotic therapy (D, 3)).
For mild and moderate exacerbations of COPD without risk factors, it is recommended to prescribe modern macrolides (azithromycin, clarithromycin), cephalosporins (cefixime, etc.) (Table 18). Either amoxicillin/clavulanate or a respiratory fluoroquinolone (levofloxacin or moxifloxacin) is recommended as first-line treatment for patients with severe exacerbations of COPD and risk factors (B, 2++). If there is a high risk of P. aeruginosa infection, use ciprofloxacin and other drugs with antipseudomonas activity (B, 2++).

Oxygen therapy
Hypoxemia poses a real threat to the patient’s life, therefore oxygen therapy is a priority in the treatment of ARF against the background of COPD (B, 2++). The goal of oxygen therapy is to achieve PaO2 in the range of 55-65 mm Hg. Art. and SaO2 88-92%. In case of ARF in patients with COPD, nasal cannulas or a Venturi mask are most often used to deliver O2. When administering O2 via cannulas, an O2 flow of 1–2 L/min is sufficient for most patients (D, 3). The Venturi mask is considered the more preferable method of O2 delivery, since it allows for fairly accurate values ​​of the O2 fraction in the inhaled mixture (FiO2), independent of the minute ventilation and inspiratory flow of the patient. On average, oxygen therapy with FiO2 24% increases PaO2 by 10 mm Hg. Art., and with FiO2 28% - by 20 mm Hg. Art. After initiating or changing the oxygen therapy regimen within the next 30-60 minutes. It is recommended to conduct a gas analysis of arterial blood to monitor PaCO2 and pH levels (D, 3).

NVL
NIV - providing ventilation assistance without installing artificial airways. The development of this new direction of respiratory support makes it possible to safely and effectively achieve unloading of the respiratory muscles, restoration of gas exchange and reduction of dyspnea in patients with ARF. During NIV, the relationship between the patient and the respirator is carried out using nasal or face masks (less often, helmets and mouthpieces), the patient is conscious, and, as a rule, the use of sedatives and muscle relaxants is not required. Another important advantage of NIV is the ability to quickly stop it, as well as immediately resume it if necessary. Indications and contraindications for NIV are given below.
Inclusion criteria for NIV for ARF due to COPD are:
1. Symptoms and signs of ARF:
- severe shortness of breath at rest;
- respiratory rate >24, participation of auxiliary respiratory muscles in breathing, abdominal paradox.
2. Signs of gas exchange disorders:
- PaCO2 >45 mm Hg. Art., pH<7,35;
- PaO2/FiO2<200 мм рт. ст.
Exclusion criteria for performing NIV for ARF are:
1. Stopping breathing.
2. Unstable hemodynamics (hypotension, uncontrolled arrhythmias or myocardial ischemia).
3. Inability to protect the respiratory tract (disturbances in coughing and swallowing).
4. Excessive bronchial secretion.
5. Signs of impaired consciousness (agitation or depression), the patient’s inability to cooperate with medical personnel.
Patients with acute respiratory failure who require emergency tracheal intubation and invasive respiratory support are considered unsuitable candidates for this method of respiratory support (C, 2+). NIV is the only proven method of therapy that can reduce mortality in patients with COPD with ARF (A, 1++).
Invasive respiratory support
Mechanical ventilation is indicated for COPD patients with ARF in whom drug or other conservative therapy (NVL) does not lead to further improvement (B, 2++). Indications for ventilation should take into account not only the lack of effect of conservative methods of therapy, the severity of functional indicators, but also the speed of their development and the potential reversibility of the process that caused ARF.
The absolute indications for mechanical ventilation for ARF against the background of exacerbation of COPD are:
1) respiratory arrest;
2) severe disturbances of consciousness (stupor, coma);
3) unstable hemodynamics (SBP)<70 мм рт. ст., частота сердечных сокращений <50/мин. или >160/min);
4) fatigue of the respiratory muscles.
Relative indications for mechanical ventilation for ARF against the background of exacerbation of COPD are:
1) respiratory rate >35/min;
2) arterial blood pH<7,25;
3) RaO2<45 мм рт. ст., несмотря на проведение кислородотерапии.
As a rule, when prescribing respiratory support, a comprehensive clinical and functional assessment of the patient's status is carried out. Weaning from mechanical ventilation should begin as early as possible in patients with COPD (B, 2++), since each additional day of invasive respiratory support significantly increases the risk of developing complications of mechanical ventilation, especially such as ventilator-associated pneumonia (A, 1+) .
Mobilization and removal methods
bronchial secretion
Overproduction of secretions and poor clearance from the airways can be a serious problem for many patients with severe exacerbation of COPD.
According to recent studies, therapy with mucoactive drugs (acetylcysteine, carbocysteine, erdosteine) accelerates the resolution of exacerbations of COPD and makes an additional contribution to reducing the severity of systemic inflammation (C, 2+).
With exacerbation of COPD, significant improvement can be achieved using special methods to enhance the drainage function of the respiratory tract. For example, high-frequency percussion ventilation is a method of respiratory therapy in which small volumes of air (“percussion”) are delivered to the patient at a high, controlled frequency.
(60-400 cycles/min.) and a controlled pressure level through a special open breathing circuit (phasitron). “Percussion” can be delivered through a mask, mouthpiece, endotracheal tube and tracheostomy. Another method is high-frequency vibrations (oscillations) of the chest wall, which are transmitted through the chest to the respiratory tract and the gas flow passing through it. High-frequency vibrations are created using an inflatable vest that fits tightly around the chest and is connected to an air compressor.

11. COPD and related diseases
COPD, along with hypertension, coronary artery disease and diabetes, constitute the leading group of chronic diseases - they account for more than 30% of all other human pathologies. COPD is often combined with these diseases, which can significantly worsen the prognosis of patients.
The most common comorbidities in COPD are presented in Table 20.
In patients with COPD, the risk of death increases with the number of concomitant diseases and does not depend on the FEV1 value (Fig. 3).
All causes of death in patients with COPD are shown in Table 21.
According to large population studies, the risk of death from CVD in patients with COPD is increased by 2-3 times compared with patients of the same age groups and without COPD and accounts for approximately 50% of the total number of deaths.
Cardiovascular pathology is the main pathology that accompanies COPD. This is probably the group of most common and most serious diseases coexisting with COPD. Among them, we should highlight coronary artery disease, chronic heart failure, atrial fibrillation, and hypertension, which, apparently, is the most common concomitant of COPD.
Often, the treatment of such patients becomes controversial: drugs (angiotensin-converting enzyme inhibitors, β-blockers) used for ischemic heart disease and/or hypertension can worsen the course of COPD (risk of cough, shortness of breath, appearance or worsening of bronchial obstruction), and drugs prescribed for for COPD (bronchodilators, corticosteroids), can negatively affect the course of cardiovascular pathology (risk of developing cardiac arrhythmia, increased blood pressure). However, treatment of CVD in patients with COPD should be carried out in accordance with standard recommendations, since there is no evidence that they should be treated differently in the presence of COPD. If it is necessary to prescribe β-blockers to patients with COPD with concomitant cardiovascular pathology, preference should be given to selective β-blockers.
Osteoporosis and depression are important comorbidities that are often underdiagnosed. However, they are associated with decreased health status and poor prognosis. Prescribing repeated courses of systemic corticosteroids for exacerbations should be avoided, since their use significantly increases the risk of developing osteoporosis and fractures.
In recent years, cases of a combination of metabolic syndrome and diabetes in patients with COPD have become more frequent. Diabetes has a significant impact on the course of COPD and worsens the prognosis of the disease. In patients with COPD in combination with type 2 diabetes, DN is more pronounced, exacerbations are more common, a more severe course of coronary heart disease, the presence of chronic HF and hypertension are noted, pulmonary hypertension increases with less severity of hyperinflation.
In patients with mild COPD, the most common cause of death is lung cancer. In patients with severe COPD, reduced lung function significantly limits the possibility of surgical intervention for lung cancer.

12. Rehabilitation and patient education
One of the recommended additional methods of treatment for patients with COPD, starting from stage II of the disease, is pulmonary rehabilitation. Its effectiveness has been proven in improving exercise tolerance (A, 1++), daily activity, reducing the perception of shortness of breath (A, 1++), the severity of anxiety and depression (A, 1+), reducing the number and duration of hospitalizations (A, 1 ++), recovery time after discharge from hospital and, in general, an increase in quality of life (A, 1++) and survival (B, 2++).
Pulmonary rehabilitation is a comprehensive program of interventions based on patient-centered therapy and includes, in addition to physical training, educational and psychosocial programs designed to improve the physical and emotional well-being of patients and ensure long-term adherence to health behaviors.
According to the 2013 ERS/ATS recommendations, rehabilitation should continue for
6-12 weeks (at least 12 lessons, 2 times/week, lasting 30 minutes or more) and include the following components:
1) physical training;
2) correction of nutritional status;
3) patient education;
4) psychosocial support.
This program can be conducted in either an outpatient or inpatient setting.
The main component of pulmonary rehabilitation is physical training, which can increase the effectiveness of long-acting bronchodilators (B, 2++). An integrated approach to their implementation is especially important, combining exercises for strength and endurance: walking, training the muscles of the upper and lower extremities with the help of expanders, dumbbells, step machines, and exercises on a bicycle ergometer. During these trainings, various groups of joints are also involved in the work, and fine motor skills of the hand are developed.
All exercises should be combined with breathing exercises aimed at developing the correct breathing pattern, which brings additional benefits (C, 2+). In addition, breathing exercises should include the use of special simulators (Threshold PEP, IMT), which differentially involve the inspiratory and expiratory respiratory muscles.
Correction of nutritional status should be aimed at maintaining muscle strength through adequate protein and vitamins in the diet.
In addition to physical rehabilitation, much attention should be paid to measures aimed at changing the behavior of patients, by teaching them the skills to independently recognize changes in the course of the disease and methods for their correction.

*Chronic Airways Diseases, A Guide for Primary Care Physicians, 2005.

The classification of COPD (chronic obstructive pulmonary disease) is broad and includes a description of the most common stages of the disease and the variants in which it occurs. And although not all patients progress with COPD according to the same scenario and not everyone can identify a certain type, the classification always remains relevant: most patients fit into it.

COPD stages

The first classification (spirographic classification of COPD), which determined the stages of COPD and their criteria, was proposed back in 1997 by a group of scientists united in a committee called the “World Initiative for COPD” (in English the name is “Global Initiative for chronic Obstructive Lung Disease” and abbreviated as GOLD). According to it, there are four main stages, each of which is determined primarily by FEV - that is, the volume of forced expiration in the first second:

• COPD stage 1 does not have any special symptoms. The lumen of the bronchi is narrowed quite a bit, and the air flow is also not too noticeably limited. The patient does not experience difficulties in everyday life, shortness of breath is experienced only during active physical activity, and a wet cough occurs only occasionally, most likely at night. At this stage, only a few people go to the doctor, usually because of other diseases.
• COPD degree 2 becomes more pronounced. Shortness of breath begins immediately when trying to engage in physical activity, a cough appears in the morning, accompanied by a noticeable discharge of sputum - sometimes purulent. The patient notices that he has become less resilient and begins to suffer from recurring respiratory diseases - from simple ARVI to bronchitis and pneumonia. If the reason for visiting a doctor is not suspicion of COPD, then sooner or later the patient will still see him due to concomitant infections.
• COPD degree 3 is described as a severe stage - if the patient has enough strength, he can apply for disability and confidently wait until he is given a certificate. Shortness of breath appears even with minor physical exertion - even climbing a flight of stairs. The patient feels dizzy and his vision becomes dark. The cough appears more often, at least twice a month, becomes paroxysmal and is accompanied by chest pain. At the same time, the appearance changes - the chest expands, veins swell in the neck, the skin changes color to either bluish or pinkish. Body weight either decreases or decreases sharply.
• Stage 4 COPD means that you can forget about any ability to work - the air flow entering the patient’s lungs does not exceed thirty percent of the required volume. Any physical effort - including changing clothes or hygiene procedures - causes shortness of breath, wheezing in the chest, and dizziness. The breathing itself is heavy and forced. The patient has to constantly use an oxygen cylinder. In the worst cases, hospitalization is required.

However, in 2011, GOLD concluded that such criteria are too vague, and making a diagnosis solely on the basis of spirometry (which is used to determine expiratory volume) is incorrect. Moreover, not all patients developed the disease sequentially, from mild to severe stages - in many cases, determining the stage of COPD was impossible. The CAT questionnaire has been developed, which is filled out by the patient himself and allows you to determine the condition more fully. In it, the patient needs to determine on a scale from one to five how severe his symptoms are:

• cough – one corresponds to the statement “no cough”, five “constantly”;
• sputum – one means “no sputum”, five means “sputum comes out constantly”;
• feeling of tightness in the chest – “no” and “very strong”, respectively;
• shortness of breath - from “no shortness of breath at all” to “shortness of breath with the slightest exertion”;
• household activities – from “without restrictions” to “severely limited”;
• leaving the house – from “confidently when necessary” to “not even when necessary”;
• sleep – from “good sleep” to “insomnia”;
• energy – from “full of energy” to “no energy at all.”

The result is determined by counting points. If there are less than ten, the disease has almost no effect on the patient’s life. Less than twenty, but more than ten – has a moderate effect. Less than thirty – has a strong influence. Over thirty has a huge impact on life.

Objective indicators of the patient’s condition, which can be recorded using instruments, are also taken into account. The main ones are oxygen tension and hemoglobin saturation. In a healthy person, the first value does not fall below eighty, and the second does not fall below ninety. In patients, depending on the severity of the condition, the numbers vary:

• with relatively mild – up to eighty and ninety in the presence of symptoms;
• during moderate severity - up to sixty and eighty;
• in severe cases - less than forty and about seventy-five.

After 2011, according to GOLD, COPD no longer has stages. There are only degrees of severity, which indicate how much air enters the lungs. And the general conclusion about the patient’s condition does not look like “he is at a certain stage of COPD,” but like “he is at a certain risk group for exacerbations, adverse consequences and death due to COPD.” There are four of them in total.

• Group A – low risk, few symptoms. The patient belongs to the group if he has had no more than one exacerbation in a year, he scored less than ten points on the CAT, and shortness of breath occurs only during exercise.
• Group B – low risk, many symptoms. The patient belongs to the group if there has been no more than one exacerbation, but shortness of breath occurs frequently, and the CAT score is more than ten points.
• Group C – high risk, few symptoms. The patient belongs to the group if he has had more than one exacerbation in a year, shortness of breath occurs during exertion, and the CAT score is less than ten.
• Group D – high risk, many symptoms. More than one exacerbation, shortness of breath occurs at the slightest physical exertion, and CAT scores more than ten.

The classification, although it was made in such a way as to take into account the condition of a particular patient as much as possible, still did not include two important indicators that affect the patient’s life and are indicated in the diagnosis. These are COPD phenotypes and associated diseases.

Phenotypes of COPD

In chronic obstructive pulmonary disease, there are two main phenotypes that determine how the patient looks and how the disease progresses.

Bronchitic type:

• Cause. It is caused by chronic bronchitis, relapses of which occur over at least two years.
• Changes in the lungs. Fluorography shows that the walls of the bronchi are thickened. Spirometry shows that the air flow is weakened and only partially enters the lungs.
• The classic age of detection of the disease is fifty and older.
• Features of the patient's appearance. The patient has a pronounced bluish skin color, a barrel-shaped chest, body weight usually increases due to increased appetite and may approach the border of obesity.
• The main symptom is a cough, paroxysmal, with the discharge of copious purulent sputum.
• Infections are common, since the bronchi are not able to filter out the pathogen.
• Deformation of the heart muscle according to the “pulmonary heart” type is common.

Cor pulmonale is a concomitant symptom in which the right ventricle enlarges and the heart rate accelerates - in this way the body tries to compensate for the lack of oxygen in the blood:

• X-ray. It can be seen that the heart is deformed and enlarged, and the pattern of the lungs is enhanced.
• The diffusion capacity of the lungs is the time required for gas molecules to enter the blood. Normally, if it decreases, it is not much.
• Forecast. According to statistics, the bronchitis type has a higher mortality rate.

The bronchitis type is popularly called “blue edema” and this is a fairly accurate description - a patient with this type of COPD is usually blue-pale, overweight, constantly coughs, but is alert - shortness of breath does not affect him as much as patients with the other type.

Emphysematous type:

• Cause. The cause is chronic pulmonary emphysema.
• Changes in the lungs. Fluorography clearly shows that the partitions between the alveoli are destroyed and air-filled cavities - bullae - are formed. Spirometry detects hyperventilation - oxygen enters the lungs, but is not absorbed into the blood.
• The classic age of detection of the disease is sixty and older.
• Features of the patient's appearance. The patient has a pink skin color, the chest is also barrel-shaped, veins swell in the neck, body weight decreases due to decreased appetite and may approach the border of dangerous values.
• The main symptom is shortness of breath, which can occur even at rest.
• Infections are rare, because the lungs still cope with filtration.
• Deformation of the “cor pulmonale” type is rare; the lack of oxygen is not so pronounced.
• X-ray. The image shows bullae and deformation of the heart.
• Diffusion capacity is obviously greatly reduced.
• Forecast. According to statistics, this type has a longer life expectancy.

Popularly, the emphysematous type is called the “pink puffer” and this is also quite accurate: a patient with this type of hodl is usually thin, with an unnaturally pink skin color, is constantly out of breath and prefers not to leave the house again.

If a patient has a combination of symptoms of both types, they speak of a mixed phenotype of COPD - it occurs quite often in a wide variety of variations. Also in recent years, scientists have identified several subtypes:

• With frequent exacerbations. Diagnosed if the patient is sent to the hospital with exacerbations at least four times a year. Occurs in stages C and D.
• With bronchial asthma. Occurs in a third of cases - with all symptoms of COPD, the patient experiences relief if he uses drugs to combat asthma. He also experiences asthmatic attacks.
• With an early start. It is characterized by rapid progress and is explained by genetic predisposition.
• At a young age. COPD is a disease of older people, but can also affect young people. In this case, it is usually many times more dangerous and has a high mortality rate.

Concomitant diseases

With COPD, the patient has a high chance of suffering not only from the obstruction itself, but also from the diseases that accompany it. Among them:

• Cardiovascular diseases, from coronary heart disease to heart failure. They occur in almost half of the cases and are explained very simply: with a lack of oxygen in the body, the cardiovascular system experiences great stress: the heart moves faster, blood flows faster through the veins, and the lumen of blood vessels narrows. After some time, the patient begins to notice chest pain, a racing pulse, headaches and increased shortness of breath. A third of patients whose COPD is accompanied by cardiovascular diseases die from them.
• Osteoporosis. Occurs in a third of cases. Not fatal, but very unpleasant and also caused by a lack of oxygen. Its main symptom is brittle bones. As a result, the patient's spine is bent, his posture deteriorates, his back and limbs hurt, night cramps in the legs and general weakness are observed. Endurance and finger mobility decrease. Any fracture takes a very long time to heal and can be fatal. Often there are problems with the gastrointestinal tract - constipation and diarrhea, which are caused by the pressure of the curved spine on the internal organs.
• Depression. Occurs in almost half of patients. Often its dangers remain underestimated, and the patient meanwhile suffers from low tone, lack of energy and motivation, suicidal thoughts, increased anxiety, feelings of loneliness and learning problems. Everything is seen in a gloomy light, the mood constantly remains depressed. The reason is both the lack of oxygen and the impact that COPD has on the patient’s entire life. Depression is not fatal, but it is difficult to treat and significantly reduces the enjoyment that the patient could get from life.
• Infections. They occur in seventy percent of patients and cause death in a third of cases. This is explained by the fact that lungs affected by COPD are very vulnerable to any pathogen, and it is difficult to relieve inflammation in them. Moreover, any increase in sputum production means a decrease in air flow and the risk of developing respiratory failure.
• Sleep apnea syndrome. With apnea, the patient stops breathing at night for more than ten seconds. As a result, he suffers from constant oxygen starvation and may even die from respiratory failure.
• Cancer. It occurs frequently and causes death in one case out of five. It is explained, like infections, by the vulnerability of the lungs.

In men, COPD is often accompanied by impotence, and in older people it causes cataracts.

Diagnosis and disability

The formulation of the diagnosis of COPD implies a whole formula that doctors follow:

1. name of the disease – chronic lung disease;
2. COPD phenotype – mixed, bronchitis, emphysematous;
3. severity of bronchial obstruction – from mild to extremely severe;
4. severity of COPD symptoms – determined by CAT;
5. frequency of exacerbations – more than two frequent, less rare;
6. accompanying illnesses.

As a result, when the examination has been completed as planned, the patient receives a diagnosis that sounds, for example, like this: “chronic obstructive pulmonary disease of the bronchitis type, II degree of bronchial obstruction with severe symptoms, frequent exacerbations, aggravated by osteoporosis.”

Based on the results of the examination, a treatment plan is drawn up and the patient can claim disability - the more severe the COPD, the more likely it is that the first group will be diagnosed.

And although COPD has no cure, the patient must do everything in his power to maintain his health at a certain level - and then both the quality and length of his life will increase. The main thing is to remain optimistic during the process and not to neglect the advice of doctors.

Russian Respiratory Society

chronic obstructive pulmonary disease

Chuchalin Alexander Grigorievich	Director of the Federal State Budgetary Institution "Research Institute of Pulmonology" FMBA
	Russia, Chairman of the Board of the Russian
	Respiratory Society, Chief
	freelance specialist pulmonologist
	Ministry of Health of the Russian Federation, academician of the Russian Academy of Medical Sciences, professor,
Aisanov Zaurbek Ramazanovich	Head of the Department of Clinical Physiology
	and clinical studies of the Federal State Budgetary Institution "Research Institute
Avdeev Sergey Nikolaevich	Deputy Director for Research,
	Head of the Clinical Department of the Federal State Budgetary Institution "Research Institute
	pulmonology" FMBA of Russia, professor, doctor of medical sciences.
Belevsky Andrey	Professor of the Department of Pulmonology, State Budgetary Educational Institution of Higher Professional Education
Stanislavovich	RNRMU named after N.I. Pirogova, head
	rehabilitation laboratory of the Federal State Budgetary Institution "Research Institute
	Pulmonology" FMBA of Russia , professor, doctor of medical sciences
Leshchenko Igor Viktorovich	Professor of the Department of Phthisiology and
	pulmonology GBOU VPO USMU, chief
	freelance specialist pulmonologist of the Ministry of Health
	Sverdlovsk Region and Administration
	health care of Yekaterinburg, scientific
	Head of the Medical Clinic
	association "New Hospital", professor,
	Doctor of Medical Sciences, Honored Doctor of Russia,
Meshcheryakova Natalya Nikolaevna	Associate Professor, Department of Pulmonology, State Budgetary Educational Institution of Higher Professional Education, Russian National Research Medical University
	named after N.I. Pirogova, leading researcher
	rehabilitation laboratory of the Federal State Budgetary Institution "Research Institute
	Pulmonology" FMBA of Russia, Ph.D.
Ovcharenko Svetlana Ivanovna	Professor of the Department of Faculty Therapy No.
	1st Faculty of Medicine, State Budgetary Educational Institution of Higher Professional Education First
	MSMU im. THEM. Sechenova, professor, doctor of medical sciences,
	Honored Doctor of the Russian Federation
Shmelev Evgeniy Ivanovich	Head of the Department of Differential
	diagnostics of tuberculosis Central Research Institute of the Russian Academy of Medical Sciences, doctor
	honey. Sciences, Professor, Doctor of Medical Sciences, Honored
	scientist of the Russian Federation.

	Methodology
	COPD Definition and Epidemiology
	Clinical picture of COPD
	Diagnostic principles
	Functional tests in diagnostics and monitoring
	COPD course
	Differential diagnosis of COPD
	Modern classification of COPD. Comprehensive
	assessment of severity.
	Therapy for stable COPD
	Exacerbation of COPD
	Treatment for exacerbation of COPD
	COPD and related diseases
	Rehabilitation and patient education

1. Methodology

Methods used to collect/select evidence:

search in electronic databases.

Description of methods used to collect/select evidence:

Methods used to assess the quality and strength of evidence:

Expert consensus;

					Description
	evidence
			High quality meta-analyses, systematic reviews
			randomized controlled trials (RCTs) or
			RCT with very low risk of bias
			Qualitatively conducted meta-analyses, systematic, or
			RCTs with low risk of bias
			Meta-analyses, systematic, or high-risk RCTs
			systematic errors
			High quality	systematic reviews		research
			case-control		cohort	research.
			High-quality reviews of case-control studies or
			cohort studies with very low risk of effects
			confounding or systematic errors and average probability
			causal relationship
			Well-conducted case-control studies or
			cohort studies with moderate risk of confounding effects
			or systematic errors and the average probability of causality
			relationships
			Case-control or cohort studies with
			high risk of mixing effects or systematic
			errors and average probability of causal relationship
			Non-analytical studies (e.g. case reports,
			case series)
			Expert opinion

Methods used to analyze evidence:

Systematic reviews with evidence tables.

Description of methods used to analyze evidence:

When selecting publications as potential sources of evidence, the methodology used in each study is examined to ensure its validity. The outcome of the study influences the level of evidence assigned to the publication, which in turn influences the strength of the resulting recommendations.

Methodological examination is based on several key questions that focus on those features of the study design that have a significant impact on the validity of the results and conclusions. These key questions may vary depending on the types of studies and questionnaires used to standardize the publication assessment process. The recommendations used the MERGE questionnaire developed by the New South Wales Department of Health. This questionnaire is designed to be assessed in detail and adapted to meet the requirements of the Russian Respiratory Society (RRS) in order to maintain an optimal balance between methodological rigor and practical applicability.

The assessment process, of course, can also be affected by a subjective factor. To minimize potential bias, each study was assessed independently, i.e. at least two independent members of the working group. Any differences in assessments were discussed by the whole group as a whole. If it was impossible to reach consensus, an independent expert was involved.

Evidence tables:

Evidence tables were completed by members of the working group.

Methods used to formulate recommendations:

	Description
	At least one meta-analysis, systematic review or RCT,
	demonstrating sustainability of results
	A body of evidence including the results of studies assessed
	overall sustainability of results
	extrapolated evidence from studies rated 1++
	A body of evidence including the results of studies assessed
	overall sustainability of results;
	extrapolated evidence from studies rated 2++
	Level 3 or 4 evidence;
	extrapolated evidence from studies rated 2+

Good Practice Points (GPPs):

Economic analysis:

No cost analysis was performed and pharmacoeconomics publications were not reviewed.

External expert assessment;

Internal expert assessment.

These draft recommendations were reviewed by independent experts who were asked to comment primarily on the extent to which the interpretation of the evidence underlying the recommendations is understandable.

Comments were received from primary care physicians and local therapists regarding the clarity of the recommendations and their assessment of the importance of the recommendations as a working tool in daily practice.

A preliminary version was also sent to a non-medical reviewer for comments from patient perspectives.

The comments received from the experts were carefully systematized and discussed by the chairman and members of the working group. Each point was discussed and the resulting changes to the recommendations were recorded. If changes were not made, then the reasons for refusing to make changes were recorded.

Consultation and expert assessment:

The preliminary version was posted for wide discussion on the RPO website so that persons not participating in the congress had the opportunity to participate in the discussion and improvement of the recommendations.

Working group:

For final revision and quality control, the recommendations were re-analyzed by members of the working group, who concluded that all comments and comments from experts were taken into account, and the risk of systematic errors in the development of recommendations was minimized.

2. Definition of COPD and epidemiology

Definition

COPD is a preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with a significant chronic inflammatory response of the lungs to pathogenic particles or gases. In some patients, exacerbations and comorbidities may influence the overall severity of COPD (GOLD 2014).

Traditionally, COPD combines chronic bronchitis and emphysema. Chronic bronchitis is usually defined clinically as the presence of a cough with

sputum production for at least 3 months over the next 2 years.

Emphysema is defined morphologically as the presence of persistent dilation of the airways distal to the terminal bronchioles, associated with destruction of the alveolar walls, not associated with fibrosis.

In patients with COPD, both conditions are most often present, and in some cases it is quite difficult to clinically distinguish between them in the early stages of the disease.

The concept of COPD does not include bronchial asthma and other diseases associated with poorly reversible bronchial obstruction (cystic fibrosis, bronchiectasis, bronchiolitis obliterans).

Epidemiology

Prevalence

COPD is currently a global problem. In some countries around the world, the prevalence of COPD is very high (over 20% in Chile), in others it is lower (about 6% in Mexico). The reasons for this variability are differences in people's lifestyles, behavior and exposure to a variety of damaging agents.

One of the Global Studies (BOLD Project) provided a unique opportunity to estimate the prevalence of COPD using standardized questionnaires and pulmonary function tests in populations of adults over 40 years of age in both developed and developing countries. The prevalence of COPD stage II and higher (GOLD 2008), according to the BOLD study, among people over 40 years of age was 10.1 ± 4.8%; including for men – 11.8±7.9% and for women – 8.5±5.8%. According to an epidemiological study on the prevalence of COPD in the Samara region (residents 30 years of age and older), the prevalence of COPD in the total sample was 14.5% (men - 18.7%, women - 11.2%). According to the results of another Russian study conducted in the Irkutsk region, the prevalence of COPD in people over 18 years of age among the urban population was 3.1%, among the rural population 6.6%. The prevalence of COPD increased with age: in the age group from 50 to 69 years, 10.1% of men in the city and 22.6% in rural areas suffered from the disease. Almost every second man over 70 years of age living in rural areas was diagnosed with COPD.

Mortality

According to WHO, COPD is currently the 4th leading cause of death in the world. About 2.75 million people die from COPD each year, accounting for 4.8% of all causes of death. In Europe, mortality from COPD varies significantly: from 0.20 per 100,000 population in Greece, Sweden, Iceland and Norway, to 80 per 100,000

V Ukraine and Romania.

IN period from 1990 to 2000 mortality from cardiovascular diseases

V overall and from stroke decreased by 19.9% ​​and 6.9%, respectively, while mortality from COPD increased by 25.5%. A particularly pronounced increase in mortality from COPD is observed among women.

Predictors of mortality in patients with COPD are factors such as the severity of bronchial obstruction, nutritional status (body mass index), physical endurance according to the 6-minute walk test and severity of shortness of breath, frequency and severity of exacerbations, pulmonary hypertension.

The main causes of death in patients with COPD are respiratory failure (RF), lung cancer, cardiovascular diseases and tumors of other localizations.

Socio-economic significance of COPD

IN In developed countries, the total economic costs associated with COPD in the structure of pulmonary diseases occupy 2nd place after lung cancer and 1st place

in terms of direct costs, exceeding the direct costs of bronchial asthma by 1.9 times. The economic costs per patient associated with COPD are three times higher than for a patient with bronchial asthma. The few reports on direct medical costs for COPD indicate that more than 80% of costs are spent on inpatient care and less than 20% on outpatient care. It was found that 73% of costs are for 10% of patients with severe disease. The greatest economic damage comes from treating exacerbations of COPD. In Russia, the economic burden of COPD, taking into account indirect costs, including absenteeism (absenteeism) and presenteeism (less effective work due to poor health), amounts to 24.1 billion rubles.

3. Clinical picture of COPD

Under conditions of exposure to risk factors (smoking, both active and passive, exogenous pollutants, bioorganic fuel, etc.), COPD usually develops slowly and progresses gradually. The peculiarity of the clinical picture is that for a long time the disease proceeds without pronounced clinical manifestations (3, 4; D).

The first signs with which patients consult a doctor are a cough, often with sputum production, and/or shortness of breath. These symptoms are most pronounced in the morning. During cold seasons, “frequent colds” occur. This is the clinical picture of the onset of the disease, which the doctor regards as a manifestation of smoker’s bronchitis, and the diagnosis of COPD at this stage is practically not made.

Chronic cough, usually the first symptom of COPD, is often underestimated by patients, as it is considered an expected consequence of smoking and/or exposure to adverse environmental factors. Typically, patients produce a small amount of viscous sputum. An increase in cough and sputum production occurs most often in the winter months, during infectious exacerbations.

Dyspnea is the most important symptom of COPD (4; D). It is often the reason for seeking medical help and the main reason limiting the patient’s work activity. The health impact of breathlessness is assessed using the British Medical Council (MRC) questionnaire. Initially, shortness of breath occurs with relatively high levels of physical activity, such as running on level ground or walking up stairs. As the disease progresses, shortness of breath intensifies and can limit even daily activity, and later occurs at rest, forcing the patient to stay at home (Table 3). In addition, the assessment of dyspnea using the MRC scale is a sensitive tool for predicting the survival of patients with COPD.

Table 3. Dyspnea score using the Medical Research Council Scale (MRC) Dyspnea Scale.

			Description
			I only feel short of breath during intense physical activity.
			load
			I get out of breath when I walk quickly on level ground or
			walking up a gentle hill
			Shortness of breath makes me walk slower on level ground,
			than people of the same age, or stops at me
			breathing when I walk on level ground in the usual
			tempo for me

When describing the clinical picture of COPD, it is necessary to take into account the features characteristic of this particular disease: its subclinical onset, the absence of specific symptoms, and the steady progression of the disease.

The severity of symptoms varies depending on the phase of the disease (stable course or exacerbation). A condition in which the severity of symptoms does not change significantly over weeks or even months should be considered stable, and in this case, disease progression can only be detected with long-term (6-12 months) follow-up of the patient.

Exacerbations of the disease have a significant impact on the clinical picture - periodically occurring deterioration of the condition (lasting at least 2-3 days), accompanied by an increase in the intensity of symptoms and functional disorders. During an exacerbation, there is an increase in the severity of hyperinflation and the so-called. air traps in combination with a reduced expiratory flow, which leads to increased shortness of breath, which is usually accompanied by the appearance or intensification of distant wheezing, a feeling of constriction in the chest, and a decrease in exercise tolerance. In addition, the intensity of the cough increases, the amount of sputum, the nature of its separation, color and viscosity changes (increases or sharply decreases). At the same time, indicators of the function of external respiration and blood gases deteriorate: speed indicators (FEV1, etc.) decrease, hypoxemia and even hypercapnia may occur.

The course of COPD is an alternation of a stable phase and exacerbation of the disease, but it varies from person to person. However, progression of COPD is common, especially if the patient continues to be exposed to inhaled pathogenic particles or gases.

The clinical picture of the disease also seriously depends on the phenotype of the disease, and vice versa, the phenotype determines the characteristics of the clinical manifestations of COPD. For many years, there has been a division of patients into emphysematous and bronchitis phenotypes.

The bronchitis type is characterized by a predominance of signs of bronchitis (cough, sputum production). Emphysema in this case is less pronounced. In the emphysematous type, on the contrary, emphysema is the leading pathological manifestation, shortness of breath prevails over cough. However, in clinical practice it is very rarely possible to distinguish the emphysematous or bronchitis phenotype of COPD in the so-called. “pure” form (it would be more correct to talk about a predominantly bronchitis or predominantly emphysematous phenotype of the disease). The features of the phenotypes are presented in more detail in Table 4.

Table 4. Clinical and laboratory features of the two main phenotypes of COPD.

Peculiarities	external	Reduced nutrition			Increased nutrition
		Pink complexion			Diffuse cyanosis
		Extremities are cold			Limbs are warm
Predominant symptom
		Scanty – often mucous			Abundant – often mucous-
Bronchial infection
Pulmonary heart
		terminal stage
Radiography		Hyperinflation,			Gain	pulmonary
chest		bullous	changes,			increase
		"vertical" heart			heart size
Hematocrit, %
PaO2
PaCO2
Diffusion						small
ability					decline

If it is impossible to distinguish the predominance of one phenotype or another, one should speak of a mixed phenotype. In clinical settings, patients with a mixed type of disease are more common.

In addition to the above, other phenotypes of the disease are currently identified. First of all, this applies to the so-called overlap phenotype (a combination of COPD and asthma). Although it is necessary to carefully differentiate between patients with COPD and asthma and the significant difference in chronic inflammation in these diseases, in some patients COPD and asthma may be present simultaneously. This phenotype can develop in smoking patients suffering from bronchial asthma. Along with this, as a result of large-scale studies it has been shown that about 20–30% of patients with COPD may have reversible bronchial obstruction, and eosinophils appear in the cellular composition during inflammation. Some of these patients can also be attributed to the “COPD + BA” phenotype. Such patients respond well to corticosteroid therapy.

Another phenotype that has been reported recently is that of patients with frequent exacerbations (2 or more exacerbations per year, or 1 or more exacerbations leading to hospitalization). The importance of this phenotype is determined by the fact that the patient emerges from an exacerbation with reduced functional indicators of the lungs, and the frequency of exacerbations directly affects the life expectancy of patients and requires an individual approach to treatment. The identification of numerous other phenotypes requires further clarification. Several recent studies have drawn attention to differences in the clinical presentation of COPD between men and women. As it turned out, women are characterized by more pronounced hyperreactivity of the respiratory tract, they report more pronounced shortness of breath at the same levels of bronchial obstruction as in men, etc. With the same functional indicators, oxygenation occurs better in women than in men. However, women are more likely to develop exacerbations, they show less effect of physical training in rehabilitation programs, and they rate their quality of life lower according to standard questionnaires.

It is well known that patients with COPD have numerous extrapulmonary manifestations of the disease due to the systemic effect of chronic

Chronic obstructive pulmonary disease (COPD) is a generally preventable and curable disease characterized by persistent airflow limitation that is usually progressive and associated with an increased chronic inflammatory response of the airways and lungs in response to exposure to harmful particles and gases. Exacerbations and concomitant diseases contribute to a more severe course of the disease.

This definition of the disease has been preserved in the document of the international organization, which calls itself the Global Initiative for Chronic Obstructive Lung Disease (GOLD) and constantly monitors this problem, and also presents its annual documents to doctors. The latest update GOLD-2016 has decreased in volume and has a number of additions, which we will discuss in this article. In Russia, most of the GOLD provisions have been approved and implemented in national clinical guidelines.

Epidemiology

COPD is a significant public health problem and will remain so as long as the proportion of the population who smokes remains high. A separate problem is COPD in non-smokers, when the development of the disease is associated with industrial pollution, unfavorable working conditions in both urban and rural areas, contact with fumes, metals, coal, other industrial dusts, chemical fumes, etc. All this leads to consideration of COPD as an occupational disease. According to the Central Research Institute for Organization and Informatization of Health Care of the Ministry of Health in the Russian Federation, the incidence of COPD from 2005 to 2012 increased from 525.6 to 668.4 per 100 thousand population, i.e. the growth dynamics was more than 27%.

The website of the World Health Organization presents the structure of causes of death over the past 12 years (2010-2012), in which COPD and lower respiratory tract infections share 3-4 place, and in total actually come out on top. However, when dividing countries by income level, this position changes. In low-income countries, the population does not survive to the end stages of COPD and dies from lower respiratory tract infections, conditions associated with HIV infection, and diarrhea. COPD is not among the top ten causes of death in these countries. In countries with high per capita income, COPD and lower respiratory tract infections share 5-6 places, and the leaders are coronary heart disease and stroke. With income above average, COPD came in third place in the causes of death, and below average - in 4th place. In 2015, a systematic analysis of 123 publications was conducted on the prevalence of COPD among the population aged 30 years and older in the world from 1990 to 2010. During this period, the prevalence of COPD increased from 10.7% to 11.7% (or from 227.3 million to 297 million patients with COPD). The increase in the rate was greatest among Americans, and the smallest in Southeast Asia. Among urban residents, the prevalence of COPD increased from 13.2% to 13.6%, and among rural residents - from 8.8% to 9.7%. Among men, COPD was almost 2 times more common than among women - 14.3% and 7.6%, respectively. For the Republic of Tatarstan, COPD is also a pressing problem. At the end of 2014, 73,838 patients with COPD were registered in Tatarstan, the mortality rate was 21.2 per 100 thousand population, and the mortality rate was 1.25%.

The unfavorable dynamics of the epidemiology of COPD has been noted despite great progress in the clinical pharmacology of bronchodilators and anti-inflammatory drugs. Along with improving quality and selectivity of action, new drugs are becoming more and more expensive, significantly increasing the economic and social burden of COPD for the healthcare system (according to expert estimates of the Quality of Life Public Foundation, the economic burden of COPD for the Russian Federation in 2013 prices was estimated at more than 24 billion rub., while almost 2 times exceeding the economic burden of bronchial asthma).

The assessment of epidemiological data on COPD is complicated by a number of objective reasons. First of all, until recently, in ICD-10 codes, this nosology was in the same column as bronchiectasis. In the updated version of the classification, this position has been eliminated, but it should become legislatively enshrined and consistent with statistics from the Ministry of Health of the Russian Federation, Roszdravnadzor, Rospotrebnadzor and Rosstat. So far this position has not been implemented, which has a negative impact on forecasting the volume of medical care and budgeting of compulsory health insurance funds.

Clinic and diagnostics

COPD is a preventable condition because its causes are well known. First of all, smoking. In the latest edition of GOLD, along with smoking, occupational dusts and chemical exposures, indoor air pollution from cooking and heating (especially among women in developing countries) are considered risk factors for COPD.

The second problem is that the criterion for the final diagnosis of COPD is the presence of forced expiratory spirometry data after a test with a short-acting bronchodilator. A procedure that is understandable and provided with a wide range of equipment, spirometry has not yet received the proper distribution and availability in the world. But even if the method is available, it is important to control the quality of recording and interpretation of curves. It should be noted that according to the latest GOLD revision, spirometry is required to make a definitive diagnosis of COPD, whereas previously it was used to confirm the diagnosis of COPD.

The comparison of symptoms, complaints and spirometry in the diagnosis of COPD is the subject of research and additions to guidelines. On the one hand, a recently published study of the prevalence of broncho-obstructive syndrome in northwestern Russia showed that the prognostic value of symptoms does not exceed 11%.

At the same time, it is extremely important to focus doctors, especially internists, general practitioners and family medicine doctors, on the presence of characteristic symptoms of COPD in order to promptly identify these patients and carry out their correct further routing. The latest edition of GOLD notes that “cough and sputum production are associated with increased mortality in patients with mild to moderate COPD,” and the assessment of COPD is based on severity of symptoms, risk of future exacerbations, severity of spirometric abnormalities, and identification of comorbidities.

The regulations on the interpretation of spirometry in COPD are being improved from year to year. The absolute value of the FEV1/FVC ratio may lead to overdiagnosis of COPD in older people because the normal aging process results in decreased lung volumes and flows, and may also lead to underdiagnosis of COPD in people under 45 years of age. GOLD experts noted that the concept of determining the degree of impairment based only on FEV 1 is not accurate enough, but there is no alternative system. The most severe degree of spirometric impairment GOLD 4 does not include a reference to the presence of respiratory failure. In this regard, the modern balanced position for assessing patients with COPD, both from the point of view of clinical assessment and according to spirometric criteria, best meets the requirements of real clinical practice. Treatment decisions are recommended to be made based on the impact of the disease on the patient's condition (symptoms and limitation of physical activity) and the risk of future progression of the disease (especially the frequency of exacerbations).

It should be noted that an acute test with short-acting bronchodilators (salbutamol, fenoterol, fenoterol/ipratropium bromide) is recommended both through metered-dose aerosol inhalers (MDIs) and during nebulization of these drugs. The values ​​of FEV 1 and FEV 1 /FVC after a bronchodilator are decisive for diagnosing COPD and assessing the degree of spirometric impairment. At the same time, it is recognized that the bronchodilator test has lost its leading position both in the differential diagnosis of bronchial asthma and COPD, and in predicting the effectiveness of the subsequent use of long-acting bronchodilators.

Since 2011, it has been recommended to divide all patients with COPD into ABCD groups based on three coordinates - spirometric gradations according to GOLD (1-4), the frequency of exacerbations (or one hospitalization) during the last year and answers to standardized questionnaires (CAT, mMRC or CCQ) . A corresponding table has been created, which is also presented in the GOLD revision 2016. Unfortunately, the use of questionnaires remains a priority in those medical centers where active epidemiological and clinical research is carried out, while in general clinical practice in public health care settings, the assessment of patients with COPD using the CAT, mMRC or CCQ is the exception rather than the rule for a variety of reasons .

Russian federal recommendations for the diagnosis and treatment of COPD reflect all the criteria proposed by GOLD, but it is not yet necessary to include them in medical documentation when describing COPD. According to domestic recommendations, the diagnosis of COPD is as follows:

“Chronic obstructive pulmonary disease...” and then the assessment follows:

• degree of severity (I-IV) of bronchial obstruction;
• severity of clinical symptoms: pronounced (CAT ≥ 10, mMRC ≥ 2, CCQ ≥ 1), not expressed (CAT< 10, mMRC < 2, CCQ < 1);
• exacerbation frequencies: rare (0-1), frequent (≥ 2);
• COPD phenotype (if possible);
• concomitant diseases.

When conducting research and comparing foreign publications on COPD before 2011 and later, it should be understood that the division of COPD according to spirometric criteria 1-4 and into ABCD groups is not identical. The most unfavorable variant of COPD - GOLD 4 does not fully correspond to type D, since the latter may include both patients with signs of GOLD 4 and with a large number of exacerbations during the last year.

Treatment of COPD is one of the most dynamic areas of guidelines and recommendations. The treatment approach begins with eliminating the damaging agent - stopping smoking, changing hazardous work, improving indoor ventilation, etc.

It is important that smoking cessation is recommended by all health care providers. A compromise by one doctor in the chain of contacts of a COPD patient can have irreversible consequences - the patient will remain a smoker and thereby worsen the prognosis of his life. Currently, medicinal methods for quitting smoking have been developed - nicotine replacement and blocking dopamine receptors (depriving the patient of the “pleasure of smoking”). In any case, the decisive role is played by the strong-willed decision of the patient himself, the support of loved ones and reasoned recommendations of a medical professional.

It has been proven that patients with COPD should lead as physically active a lifestyle as possible, and special fitness programs have been developed. Physical activity is also recommended for the rehabilitation of patients after exacerbations. The doctor should be aware of the possibility of developing depression in patients with severe COPD. GOLD experts regard depression as a risk factor for the ineffectiveness of rehabilitation programs. To prevent infectious exacerbations of COPD, seasonal influenza vaccination is recommended, and after 65 years, pneumococcal vaccination.

Therapy

Treatment of COPD is determined by periods of illness - stable course and exacerbation of COPD.

The physician must clearly understand the tasks of managing a patient with stable COPD. It should relieve symptoms (shortness of breath and cough), improve exercise tolerance (the patient should be able to at least care for himself). It is necessary to reduce the risk to which a patient with COPD is exposed: to slow down the progression of the disease as much as possible, to prevent and promptly treat exacerbations, to reduce the likelihood of death, to influence the quality of life of patients and the frequency of relapses of the disease. Preference should be given to long-acting inhaled bronchodilators (compared to short-acting inhaled agents and oral drugs). However, it is necessary to take into account that the combination of ipratropium bromide with fenoterol (Table, drug 1 and 2) in the form of a MDI and a solution for nebulizer therapy has been successfully used in clinical practice for more than 30 years and is included in domestic standards of therapy and clinical recommendations.

Olodaterol was added to the latest revision of the GOLD document. Previously, this list included formoterol (Table, drug 3), tiotropium bromide, aclidinium bromide, glycopyrronium bromide, indacaterol. Among them are drugs with beta2-adrenomimetic (LABA) and M3-anticholinergic (MABA) effects. Each of them has shown its effectiveness and safety in large randomized studies, but the latest generation of drugs are fixed combinations of long-acting bronchodilators with different mechanisms of bronchodilation (indacaterol/glycopyrronium, olodaterol/tiotropium bromide, vilanterol/umeclidinium bromide).

The combination of long-acting drugs on an ongoing basis and short-acting drugs on an as-needed basis is allowed by GOLD experts if drugs of one type are insufficient to control the patient’s condition.

At the same time, the latest current List of vital and essential drugs for medical use (VED) for 2016 includes only three selective beta2-adrenergic agonists in mono form, including salbutamol (Table, drug 5) and formoterol (Table , drug 3) and three anticholinergic drugs, including ipratropium bromide (Table, drug 7 and 8).

When selecting a bronchodilator, it is extremely important to prescribe a drug delivery device that is understandable and convenient for the patient, and he will not make mistakes when using it. Almost every new drug has a newer and more advanced delivery system (especially dry powder inhalers). And each of these inhalation devices has its own strengths and weaknesses.

The administration of oral bronchodilators should be the exception to the rule; their use (including theophylline) is accompanied by a higher incidence of adverse drug reactions without the benefit of a bronchodilator effect.

A test with short-acting bronchodilators has long been considered a compelling argument for prescribing or not prescribing regular bronchodilator therapy. The latest edition of GOLD noted the limited prognostic value of this test, and the effect of long-acting drugs over the course of a year does not depend on the result of this test.

Over the past three decades, physicians' attitudes toward the use of inhaled glucocorticosteroids (ICS) have changed. At first there was extreme caution, then the use of inhaled corticosteroids was practiced in all patients with FEV1 less than 50% of the expected values, and now their use is limited to certain phenotypes of COPD. If in the treatment of bronchial asthma, inhaled corticosteroids form the basis of basic anti-inflammatory therapy, then in COPD their prescription requires strong justification. According to the modern concept, inhaled corticosteroids are recommended for stages 3-4 or for types C and D according to GOLD. But even at these stages and types, in the emphysematous phenotype of COPD with rare exacerbations, the effectiveness of inhaled corticosteroids is not high.

The latest edition of GOLD noted that discontinuation of inhaled corticosteroids in patients with COPD at low risk of exacerbations can be safe, but they should definitely retain long-acting bronchodilators as basic therapy. The combination of inhaled corticosteroids/LABAs for a single dose did not show significant differences in effectiveness compared with a double dose. In this regard, the use of inhaled corticosteroids is justified in cases of combination of bronchial asthma and COPD (a phenotype with the overlap of two diseases), in patients with frequent exacerbations and FEV1 less than 50% of predicted. One of the criteria for the effectiveness of inhaled corticosteroids is an increase in the number of eosinophils in the sputum of a COPD patient. A factor that causes reasonable caution when using inhaled corticosteroids for COPD is the increased incidence of pneumonia associated with an increase in the dose of the inhaled steroid. On the other hand, the presence of severe emphysema indicates little prospects for prescribing corticosteroids due to the irreversibility of the disorders and the minimal inflammatory component.

All these considerations do not in any way detract from the advisability of using fixed combinations of corticosteroids/LABAs for COPD with indications. Long-term monotherapy with inhaled corticosteroids for COPD is not recommended, since it is less effective than the combination of inhaled corticosteroids/LABAs and is associated with an increased risk of developing infectious complications (purulent bronchitis, pneumonia, tuberculosis) and even an increase in bone fractures. Fixed combinations such as salmeterol + fluticasone (Table, drug 4) and formoterol + budesonide have not only a large evidence base in randomized clinical trials, but also confirmation in real clinical practice when treating patients with COPD stages 3-4 according to GOLD.

Systemic glucocorticosteroids (sGCS) are not recommended for stable COPD, since their long-term use causes serious adverse drug reactions, sometimes comparable in severity to the underlying disease, and short courses outside of exacerbation do not have a significant effect. The physician must understand that prescribing sICS on an ongoing basis is a therapy of desperation, an admission that all other safer treatment options have been exhausted. The same applies to the use of parenteral depot steroids.

For patients with severe COPD with frequent exacerbations, with a bronchitis phenotype of the disease, in whom the use of LABAs, LAMAs and their combinations does not provide the required effect, phosphodiesterase-4 inhibitors are used, among which only roflumilast is used in the clinic (once a day orally).

Exacerbation of COPD is a key negative event in the course of this chronic disease, which negatively affects the prognosis in proportion to the number of repeated exacerbations during the year and the severity of their course. Exacerbation of COPD is an acute condition characterized by a worsening of a patient's respiratory symptoms beyond normal daily fluctuations and resulting in a change in therapy. The importance of COPD in worsening the condition of patients should not be overestimated. Such acute conditions as pneumonia, pneumothorax, pleurisy, thromboembolism and the like in a patient with chronic shortness of breath should be excluded when the doctor suspects an exacerbation of COPD.

When assessing a patient with signs of exacerbation of COPD, it is important to determine the main direction of therapy - antibiotics for infectious exacerbation of COPD and bronchodilators/anti-inflammatory drugs for increasing broncho-obstructive syndrome without indications for antibiotics.

The most common cause of exacerbation of COPD is a viral infection of the upper respiratory tract, trachea and bronchi. An exacerbation is recognized both by an increase in respiratory symptoms (shortness of breath, cough, amount and purulence of sputum) and by an increased need for the use of short-acting bronchodilators. However, the causes of exacerbation may also be the resumption of smoking (or other pollution of inhaled air, including industrial pollution), or violations in the regularity of continuous inhalation therapy.

When treating an exacerbation of COPD, the main task is to minimize the impact of this exacerbation on the subsequent condition of the patient, which requires rapid diagnosis and adequate therapy. Depending on the severity, it is important to determine the possibility of treatment in an outpatient setting or in a hospital setting (or even in an intensive care unit). Particular attention should be paid to patients who have had exacerbations in previous years. Currently, patients with frequent exacerbations are considered a persistent phenotype, among them the risk of subsequent exacerbations and worsening prognosis is higher.

During the initial examination, it is necessary to assess the saturation and state of blood gases and, in case of hypoxemia, immediately begin low-flow oxygen therapy. For extremely severe COPD, non-invasive and invasive ventilation is used.

Universal first aid drugs are short-acting bronchodilators - beta2-adrenergic agonists (salbutamol (Table, drug 5), fenoterol (Table, drug 5)) or their combinations with anticholinergics (ipratropium bromide (Table, drug 7 and 8)) . In the acute period, it is recommended to use medications through any MDI, including with a spacer. The use of drug solutions in the acute period through delivery through nebulizers of any type (compressor, ultrasonic, mesh nebulizers) is more appropriate. The dose and frequency of use are determined by the patient’s condition and objective data.

If the patient's condition allows, then prednisolone is prescribed orally at a dose of 40 mg per day for 5 days. Oral corticosteroids in the treatment of exacerbations of COPD lead to improvements in symptoms, pulmonary function, reduce the likelihood of treatment failure for exacerbations, and reduce the length of hospitalization during exacerbations. Systemic corticosteroids used to treat exacerbations of COPD may reduce the incidence of hospitalization due to recurrent exacerbations over the next 30 days. Intravenous administration is indicated only in the intensive care unit, and only until the patient can take the drug orally.

After a short course of sGCS (or without it), in case of moderate exacerbation, nebulization of iGCS is recommended - up to 4000 mcg per day of budesonide (when using a budesonide suspension, an ultrasonic nebulizer cannot be used, since the active substance in the suspension is destroyed, and it is not advisable to inhale the suspension through a membrane (mesh) nebulizer, since there is a serious possibility of clogging the miniature holes of the nebulizer membrane with the suspension, which will lead, on the one hand, to a shortfall in the therapeutic dose, and on the other, to a malfunction of the nebulizer membrane and the need to replace it). An alternative may be a budesonide solution (Table, drug 9), developed and produced in Russia, which is compatible with any type of nebulizer, which is convenient for both inpatient and outpatient use.

Indications for the use of antibiotics in COPD are increased shortness of breath and cough with purulent sputum. The purulence of sputum is a key criterion for prescribing antibacterial agents. GOLD experts recommend aminopenicillins (including beta-lactmase inhibitors), new macrolides and tetracyclines (in Russia there is a high level of resistance of respiratory pathogens to them). If there is a high risk or obvious seeding of Pseudomonas aeruginosa from the sputum of a COPD patient, treatment is focused on this pathogen (ciprofloxacin, levofloxacin, antipseudomonas beta-lactams). In other cases, antibiotics are not indicated.

The 6th chapter of the latest edition of GOLD is devoted to concomitant diseases in COPD. The most common and important comorbidities are coronary artery disease, heart failure, atrial fibrillation and hypertension. Treatment of cardiovascular diseases in COPD does not differ from their treatment in patients without COPD. It is especially noted that among beta1 blockers, only cardioselective drugs should be used.

Osteoporosis also often co-occurs with COPD, and treatment of COPD (systemic and inhaled steroids) may contribute to decreased bone density. This makes the diagnosis and treatment of osteoporosis in COPD an important component in patient management.

Anxiety and depression worsen the prognosis of COPD and complicate the rehabilitation of patients. They are more common in younger patients with COPD, in women, with a pronounced decrease in FEV1, and with severe cough syndrome. The treatment of these conditions also does not have any special features for COPD. Physical activity and fitness programs can play a positive role in the rehabilitation of patients with anxiety and depression in COPD.

Lung cancer is common in patients with COPD and is the most common cause of death in patients with mild COPD. Respiratory tract infections are common in COPD and cause exacerbations. Inhaled steroids used for severe COPD increase the likelihood of developing pneumonia. Repeated infectious exacerbations of COPD and concomitant infections with COPD increase the risk of developing antibiotic resistance in this group of patients due to the prescription of repeated courses of antibiotics.

Treatment of metabolic syndrome and diabetes mellitus in COPD is carried out in accordance with existing recommendations for the treatment of these diseases. A factor that increases the incidence of this type of comorbidity is the use of sGCs.

Conclusion

The work of doctors to preserve patients in the contingents of additional drug provision is extremely important. Citizens’ refusal of this initiative in favor of monetization of benefits leads to a reduction in potential costs for medicines for patients who remain committed to the benefit. The connection between drug supply levels and clinical diagnosis (COPD or bronchial asthma) contributes to both distortion of statistical data and unreasonable costs in the existing drug supply system.

In a number of regions of Russia, there is a “staff shortage” in pulmonologists and allergists, which is a significant unfavorable factor in relation to the possibility of providing qualified medical care to patients with obstructive bronchopulmonary diseases. In a number of regions of Russia there is a general reduction in bed capacity. At the same time, existing “pulmonology beds” are also being repurposed to provide medical care in other therapeutic areas. Along with this, the reduction in bed capacity in the “pulmonology” profile is often not accompanied by an adequate proportional provision of outpatient and inpatient care.

An analysis of actual clinical practice in Russia indicates insufficient adherence of doctors in their prescriptions to accepted standards for the management of COPD. The transition of patients to self-sufficiency in medications leads to decreased adherence to treatment and irregular use of medications. One of the ways to increase adherence to therapy is schools of asthma and COPD, the work of which is not organized on a regular basis in all regions of the Russian Federation.

Thus, COPD is a very common disease in the world and the Russian Federation, which creates a significant burden on the healthcare system and the country’s economy. Diagnosis and treatment of COPD are constantly improving, and the main factors that support the high prevalence of COPD in the population of people in the second half of life are the continuing number of people who have smoked for 10 years or more and harmful occupational factors. A significant alarming aspect is the lack of downward dynamics in mortality, despite the emergence of ever new drugs and delivery vehicles. The solution to the problem may consist in increasing the availability of medicines for patients, which should be maximally facilitated by the state import substitution program, timely diagnosis and increasing patient adherence to prescribed therapy.

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A. A. Vizel 1,Doctor of Medical Sciences, Professor
I. Yu. Vizel, Candidate of Medical Sciences

GBOU VPO KSMU Ministry of Health of the Russian Federation, Kazan

* The drug is not registered in the Russian Federation.

** For state and municipal needs, the priority of supplying patients with domestic drugs and limiting the admission of purchases of drugs originating from foreign countries are determined by Decree of the Government of the Russian Federation of November 30, 2015 No. 1289.