Clinical guidelines: Chronic obstructive pulmonary disease. Degrees and phenotypes of COPD: differences, features of diagnosis, treatment Gold COPD in Russian what has changed

Despite the rapid development of medicine and pharmacy, chronic obstructive pulmonary disease remains an unsolved problem of modern healthcare.

The term COPD is the product of many years of work by experts in the field of diseases of the human respiratory system. Previously, diseases such as chronic obstructive bronchitis, simple chronic bronchitis and emphysema were considered in isolation.

According to WHO forecasts, by 2030 COPD will take third place in the structure of mortality worldwide. At the moment, at least 70 million people on the planet suffer from this disease. Until the proper level of measures to reduce active and passive smoking is achieved, the population will be at significant risk of this disease.

Background

Half a century ago, significant differences were noted in the clinical picture and pathological anatomy of patients with bronchial obstruction. Then, for COPD, the classification looked arbitrary; more precisely, it was represented by only two types. Patients were divided into two groups: if the bronchitis component predominated in the clinic, then this type of COPD figuratively sounded like “blue swelling” (type B), and type A was called “pink puffers” - a symbol of the predominance of emphysema. Figurative comparisons have remained in the everyday life of doctors to this day, but the classification of COPD has undergone many changes.

Later, in order to rationalize preventive measures and therapy, a classification of COPD by severity was introduced, which was determined by the degree of airflow limitation based on spirometry. But such a breakdown did not take into account the severity of the clinic at a given time, the rate of deterioration of spirometric data, the risk of exacerbations, intercurrent pathology and, as a result, could not allow for managing the prevention of the disease and its therapy.

In 2011, experts from the global strategy for the treatment and prevention of COPD (Global Initiative for Chronic Obstructive Lung Disease, GOLD) integrated assessment of the course of this disease with an individual approach to each patient. Now the risk and frequency of exacerbations of the disease, the severity of the course and the influence of concomitant pathology are taken into account.

An objective determination of the severity of the disease and the type of disease are necessary to select rational and adequate treatment, as well as to prevent the disease in predisposed individuals and the progression of the disease. To identify these characteristics, the following parameters are used:

• degree of bronchial obstruction;
• severity of clinical manifestations;
• risk of exacerbations.

In the modern classification, the term “stages of COPD” has been replaced by “degrees,” but using the concept of stages in medical practice is not considered a mistake.

Severity

Bronchial obstruction is a mandatory criterion for the diagnosis of COPD. To assess its degree, 2 methods are used: spirometry and peak flowmetry. When performing spirometry, several parameters are determined, but 2 are important for decision making: FEV1/FVC and FEV1.

The best indicator for the degree of obstruction is FEV1, and the integrating indicator is FEV1/FVC.

The study is carried out after inhalation of a bronchodilator drug. The results are compared with age, body weight, height, and race. The severity of the disease is determined based on FEV1 - this parameter is the basis of the GOLD classification. To make the classification easier to use, threshold criteria have been defined.

The lower the FEV1 value, the higher the risk of exacerbation rates, hospitalization, and death. In the second degree, the obstruction becomes irreversible. During an exacerbation of the disease, respiratory symptoms worsen, requiring changes in treatment. The frequency of exacerbations varies for each patient.

Clinicians noted during their observations that spirometry results do not reflect the severity of shortness of breath, decreased resistance to physical activity and, as a consequence, quality of life. After treatment of an exacerbation, when the patient notices a significant improvement in well-being, the FEV1 indicator may remain virtually unchanged.

This phenomenon is explained by the fact that the severity of the disease and the severity of symptoms in each individual patient are determined not only by the degree of obstruction, but also by some other factors that reflect systemic disorders in COPD:

• amyotrophy;
• cachexia;
• weight loss.

Therefore, GOLD experts proposed a combined classification of COPD, including, in addition to FEV1, an assessment of the risk of exacerbations of the disease, the severity of symptoms using specially developed scales. Questionnaires (tests) are easy to perform and do not require much time. Testing is usually performed before and after treatment. With their help, the severity of symptoms, general condition, and quality of life are assessed.

Symptom severity

For COPD typing, specially developed, valid questionnaire methods are used: MRC - “Medical Research Council Scale”; CAT, COPD Assessment Test, developed by the global initiative GOLD - COPD Assessment Test. Please mark the score from 0 to 4 that applies to you:

M.R.C.
0	I feel shortness of breath only during significant physical activity. load
1	I feel short of breath when accelerating, walking on level ground, or when ascending a hill
2	Because I feel short of breath when walking on a flat surface, I begin to walk slower compared to people of the same age, and if I walk at my usual pace on a flat surface, I feel my breathing stop.
3	When I cover a distance of about 100 m, I feel like I’m out of breath, or after a few minutes of calm walking
4	I can't leave my house because I feel short of breath or out of breath when getting dressed/undressed.

SAT
Example: I am in a good mood	0 1 2 3 4 5		I am in a bad mood	Points
I don't cough at all	0 1 2 3 4 5		Cough is constant
I don't feel any phlegm in my lungs at all.	0 1 2 3 4 5		I feel like my lungs are filled with phlegm
I don't feel any pressure in my chest	0 1 2 3 4 5		I feel very strong pressure in my chest
When I go up one flight of stairs or go up, I feel short of breath	0 1 2 3 4 5		When I walk up or climb one flight of stairs, I feel very short of breath
I do my housework calmly	0 1 2 3 4 5		I find it very difficult to do housework
I feel confident leaving the house despite my lung disease	0 1 2 3 4 5		Unable to confidently leave home due to lung disease
I have a restful and restful sleep	0 1 2 3 4 5		I can't sleep well because of my lung disease
I'm quite energetic	0 1 2 3 4 5		I'm out of energy
TOTAL SCORE
0 — 10		The impact is negligible
11 — 20		Moderate
21 — 30		Strong
31 — 40		Very strong

Test results: CAT≥10 or MRC≥2 scale values ​​indicate significant severity of symptoms and are critical values. To assess the strength of clinical manifestations, one scale should be used, preferably CAT, because it allows you to most fully assess your health status. Unfortunately, Russian doctors rarely resort to questionnaires.

Risks and groups of COPD

When developing the risk classification for COPD, we were based on conditions and indicators collected in large-scale clinical studies (TORCH, UPLIFT, ECLIPSE):

• a decrease in spirometric parameters is associated with the risk of death of the patient and the recurrence of exacerbations;
• hospital stay caused by an exacerbation is associated with poor prognosis and a high risk of death.

For different degrees of severity, the prognosis of the frequency of exacerbations was calculated based on the previous medical history. Table "Risks":

There are 3 ways to assess the risk of exacerbation:

1. Population - according to the classification of the severity of COPD based on spirometry data: with grades 3 and 4, high risk is determined.
2. Personal history data: if in the past year there have been 2 or more exacerbations, then the risk of subsequent ones is considered high.
3. The patient's medical history at the time of hospitalization, which was caused by an exacerbation in the previous year.

Step-by-step rules for using the integral assessment method:

1. Assess symptoms using the CAT scale or dyspnea using the MRC scale.
2. See which side of the square the result belongs to: the left side - “less symptoms”, “less shortness of breath”, or the right side - “more symptoms”, “more shortness of breath”.
3. Assess which side of the square (upper or lower) the result of exacerbation risks according to spirometry belongs to. Levels 1 and 2 indicate low, and levels 3 and 4 indicate high risk.
4. Indicate how many exacerbations the patient had in the past year: if 0 and 1, then the risk is low, if 2 or more, then the risk is high.
5. Define a group.

Initial data: 19 b. according to the CAT questionnaire, according to spirometry parameters FEV1 - 56%, three exacerbations over the past year. The patient belongs to the “more symptoms” category and must be assigned to group B or D. According to spirometry, he is “low risk”, but since he had three exacerbations over the last year, this indicates a “high risk”, therefore this patient is considered to group D. This is a high-risk group for hospitalizations, exacerbations and death.

Based on the above criteria, patients with COPD are divided into four groups according to the risk of exacerbations, hospitalizations and death.

Criteria	Groups
	A "low risk" "fewer symptoms"	IN "low risk" "more symptoms"	WITH "high risk" "fewer symptoms"	D "high risk" "more symptoms"
Frequency of exacerbations per year	0-1	0-1	≥1-2	≥2
Hospitalizations	No	No	Yes	Yes
SAT	<10	≥10	<10	≥10
M.R.C.	0-1	≥2	0-1	≥2
GOLD class	1 or 2	1 or 2	3 or 4	3 or 4

The result of this grouping is rational and individualized treatment. The disease is most mild in patients from group A: the prognosis is favorable in all respects.

Phenotypes of COPD

Phenotypes in COPD are a set of clinical, diagnostic, pathomorphological signs formed during the individual development of the disease.

Identification of the phenotype allows for maximum optimization of the treatment regimen.

Indicators	Emphysematous type of COPD	Bronchitic type COPD
Manifestation of the disease	With shortness of breath in persons from 30-40 years of age	With productive cough in people over 50 years of age
Body type	Thin	Tendency to gain weight
Cyanosis	Not typical	Strongly expressed
Dyspnea	Significantly expressed, constant	Moderate, inconsistent (increased during exacerbation)
Sputum	Slight, slimy	Large volume, purulent
Cough	Comes after shortness of breath, dry	Appears before shortness of breath, productive
Respiratory failure	Last stages	Constant with progression
Change in chest volume	Increases	Does not change
Wheezing in the lungs	No	Yes
Decreased breathing	Yes	No
Chest X-ray findings	Increased airiness, small heart size, bullous changes	The heart is like a “stretched bag”, the pattern of the lungs is enhanced in the hilar areas
Lung capacity	Increasing	Does not change
Polycythemia	Minor	Strongly expressed
Pulmonary hypertension at rest	Minor	Moderate
Lung elasticity	Significantly reduced	Normal
Pulmonary heart	Terminal stage	Developing quickly
Pat. anatomy	Panacinar emphysema	Bronchitis, sometimes centriacinar emphysema

Assessment of biochemical parameters is carried out in the acute stage according to the state of the antioxidant system of the blood and is assessed by the activity of erythrocyte enzymes: catalase and superoxide dismutase.

Table “Determination of phenotype by the level of deviation of enzymes of the antioxidant system of the blood”:

A pressing issue in respiratory medicine is the problem of the combination of COPD and bronchial asthma (BA). The manifestation of the insidiousness of obstructive pulmonary diseases in the ability to mix the clinical picture of two diseases leads to economic losses, significant difficulties in treatment, prevention of exacerbations and prevention of mortality.

The mixed phenotype of COPD - asthma in modern pulmonology does not have clear criteria for classification and diagnosis and is the subject of careful comprehensive study. But some differences make it possible to suspect this type of disease in a patient.

If the disease exacerbates more than 2 times a year, then we speak of the COPD phenotype with frequent exacerbations. Typing, determining the degree of COPD, various types of classifications and their numerous modifications set important goals: to correctly diagnose, adequately treat and slow down the process.

It is extremely important to differentiate between patients with this disease, since the number of exacerbations, the rate of progression or death, and the response to treatment are individual indicators. Experts do not stop there and continue to look for ways to improve the classification of COPD.

Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease (Version January 2017, European Respiratory Journal of Medicine)

Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease 2017 (report) European Respiratory Medical Journal. Published January 30, 2017 Copyright 2017 by the European Respiratory Society. annotation This summary of the Global Strategy for the Diagnosis, Management and Prevention of COPD (GOLD) 2017 report focuses on the revised and new parts of the document. The most significant changes include: i) COPD assessment has been improved to separate spirometric assessment from symptom assessment. The ABCD group is now offered solely for the patient's symptoms and exacerbation history; ii) for each of groups A-D, an escalation strategy for pharmacological treatment is proposed; iii) introduces the concept of de-escalation of therapy into the treatment evaluation framework; IV) non-pharmacological therapies are comprehensively presented; c) the significance of comorbid conditions in the management of COPD is considered. Content Introduction Definition and factors influencing the development and progression of COPD Key points Definition and pathogenesis Diagnostics and Initial Assessment Key Points Diagnostics Symptoms Dyspnea Cough Sputum production Wheezing and chest tightness Additional characteristics of severe disease Disease history Physical examination Spirometry Expert Questions Severity classification of airflow limitation assessment Symptom assessment Choosing an exacerbation risk assessment Blood eosinophilia count Revised Comprehensive Assessment of COPD Example Alpha-1 antitrypsin deficiency Additional Research Combined rating scales Differential diagnoses Other Considerations Prevention and maintenance therapy Key points To give up smoking Nicotine replacement products Pharmacological agent Smoking cessation programs Vaccinations Influenza and Pneumococcal vaccines Pharmacological therapy for stable COPD Review of medicines Bronchodilators Beta2-agonists, Antimuscarinics Methylxanthines Combined bronchodilator therapy Anti-inflammatory drugs ICS withdrawal Triple inhalation therapy Oral glucocorticoids Phosphodiesterase-4 inhibitors Antibiotics Mucolytics (mucokinetics, mucoregulators) and antioxidants (N-acetylcysteine, carbocysteine) Other drugs with anti-inflammatory potential associated with inhalation therapy Alpha-1 antitrypsin enhancement therapy Antitussives Vasodilators Pulmonary rehabilitation Education Self management Comprehensive care programs Support, Palliative, End of Life, and Hospice Care End of Life and Hospice Care Other treatments Oxygen Therapy and Respiratory Support Oxygen therapy Fan support Interventional therapy Surgical Interventions Lung reduction surgery Bullectomy Lung transplantation Bronchoscopic interventions to reduce airiness in severe emphysema Management of stable COPD Key points Identifying and reducing exposure to risk factors Treatment of stable COPD Drug treatment pharmacological treatment algorithms Group A Group B Group C Group D Non-pharmacological treatment Education and self-management end of life and palliative care Nutritional support Vaccination Oxygen therapy Respiratory Support Non-invasive ventilation Invasive ventilation Hospital discharges and follow-up Preventing exacerbations COPD and related diseases (comorbidity) Key points Cardiovascular diseases Heart failure Cardiac ischemia arrhythmias Peripheral vascular disease, hypertension Osteoporosis Anxiety and depression COPD and lung cancer Metabolic syndrome and diabetes mellitus, Gastroesophageal Reflux Bronchiectasis Obstructive Sleep Apnea Introduction This summary of the Global Strategy for the Diagnosis, Management and Prevention of COPD (GOLD) 2017 report is based on scientific publications up to October 2016. Levels of evidence are assigned to evidence-based recommendations where appropriate. Categories used to assess the level of evidence presented in Table S1 in the Supplementary Appendix. Definition and factors influencing the development and progression of COPD Definition and factors influencing the development and progression of COPD

Key points COPD is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation, which due to airway and/or alveolar abnormalities is usually caused by significant exposure to harmful particles or gases. Dyspnea, cough and/or sputum production are the most common symptoms; symptoms are usually underreported by patients Tobacco smoking is the main risk for COPD, but environmental exposures such as exposure to biomass fuels and air pollution may contribute. In addition to exposure, host factors (genetic abnormalities, abnormal pulmonary development and accelerated aging) predispose people to developing COPD. COPD may be punctuated by acute worsening of respiratory symptoms, called exacerbations In most patients, COPD is associated with significant comorbid chronic diseases, which lead to increased morbidity and mortality.

Key Points boxes as they were in original GOLD (http://www.atsjournals.org/doi/pdf/10.1164/rccm.201204-0596PP).] COPD is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or Dyspnea, cough and/or sputum production are the most frequent symptoms; symptoms are commonly under-reported by Tobacco smoking is the main risk exposure for COPD, but environmental exposures like biomass fuel exposure and air pollution may contribute. Besides exposures, host factors (genetic abnormalities, abnormal lung development and accelerated aging) predispose individuals to develop COPD may be punctuated by acute worsening of respiratory symptoms, called exacerbations. In most patients, COPD is associated with significant concomitant chronic diseases, which increase morbidity and

Definition and pathogenesis COPD is a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation, which due to airway and/or alveolar abnormalities is usually caused by significant exposure to harmful particles or gases. The chronic airflow limitation that characterizes COPD is caused by a mixture of minor airway diseases (eg, obstructive bronchiolitis) and parenchymal destruction (emphysema), the relative contribution of which varies from person to person. Chronic inflammation leads to structural changes in the small bronchi, narrowing and destruction of the lung parenchyma. Loss of the small airways may contribute to airflow limitation and mucociliary dysfunction, a characteristic feature of the disease. Chronic respiratory symptoms may precede the development of airflow limitation and are associated with acute respiratory events. Chronic respiratory symptoms may exist in people with normal spirometry, and a significant number of smokers without respiratory dysfunction have structural signs of lung disease, manifested by the presence of emphysema, airways, wall thickening and gas-filled alveoli. Factors influencing disease development and progression Although cigarette smoking is the most well-studied risk factor for COPD, epidemiological studies have shown that nonsmokers may also develop chronic airflow limitation. Compared to smokers with COPD, never-smokers with chronic airflow limitation have fewer symptoms, lung disease, and a reduced burden of systemic inflammation. Never smokers with chronic airflow limitation do not have an increased risk of developing lung cancer or cardiovascular comorbidities; however, they have an increased risk of developing pneumonia and mortality from respiratory failure. Processes that occur during pregnancy, childbirth and radiation exposure in childhood and adolescence affect lung growth. Reduced maximum achieved lung function (as measured by spirometry) may identify individuals at increased risk of COPD. Factors in early life are called “childhood minus factors” and are as important as heavy smoking in predicting lung function in adulthood. A study of three different longitudinal cohorts found that approximately 50% of patients had COPD due to an accelerated decline in FEV; in the remaining 50%, advanced COPD is caused by abnormal growth and development of the lungs. Cigarette smokers have a higher prevalence of respiratory symptoms and impaired pulmonary function, an increased annual rate of decline in FEV, and greater COPD mortality than nonsmokers. Other types of tobacco (eg, pipe, cigars, hookah) and marijuana are also risk factors for COPD. Passive exposure to tobacco smoke, also known as environmental tobacco smoke (ETS), may also contribute to respiratory symptoms and COPD by increasing the overall burden on the lungs by inhaling particles and gases. Smoking during pregnancy may pose a risk to the fetus by affecting lung growth and development in the uterus, and possibly stimulating the immune system. Occupational hazards, including organic and inorganic dusts, chemicals and fumes, are underestimated risk factors for the development of COPD. Wood, animal manure, crop residues and coal, usually burned on fires or poorly functioning stoves, can lead to air pollution. Pollution from cooking and heating with biomass in poorly ventilated areas is a risk factor for COPD. Asthma may be a risk for developing chronic airflow limitation and COPD. Airway hyperresponsiveness can exist without clinical diagnosis of asthma and is an independent predictor of COPD and respiratory mortality in population populations, and may indicate the risk of excessive decline in lung function in mild COPD. A history of severe childhood respiratory infection is associated with decreased lung function and increased respiratory symptoms in adulthood. HIV infection accelerates the onset of smoking-related emphysema and COPD; tuberculosis has also been identified as a risk for COPD, as well as a potential comorbidity. Diagnosis and initial assessment

Key points COPD should be considered in any patient with a history of shortness of breath, chronic cough or sputum production, and/or exposure to risk factors. Spirometry is mandatory for diagnosis; after bronchodilator FEV1/FVC<0.70 подтверждает наличие стойкое ограничение воздушного потока. The goals of evaluating COPD are to determine the degree of airflow limitation, the impact of the disease on the patient's health status, and the risk of future events (eg, exacerbations, hospitalization, or death) to guide treatment decisions. Comorbid chronic diseases often occur in patients with COPD and should be treated because they can independently influence mortality and hospitalization.

Diagnosis COPD should be considered in any patient with shortness of breath, chronic cough or sputum production and/or a history of exposure to risk factors for disease development (Figure 1 and Table 1). Spirometry is necessary to make a diagnosis in this clinical context; after bronchodilator FEV1/FVC<0.70 подтверждает наличие стойких ограничений воздушного потока и определяет наличие ХОБЛ у пациентов с соответствующими симптомами и предрасполагающими рисками. Rice. 1. Pathways to the diagnosis of COPD Figure 1. Pathways to the diagnosis of COPD Figure 1. Pathways to the diagnosis of COPD
Table 1. Key indicators to confirm the diagnosis of COPD

Assess the diagnosis of COPD and perform spirometry if any of these indicators occur in a person over 40 years of age. These indicators are not diagnostic in themselves, but the presence of several key indicators increases the likelihood of a diagnosis of COPD. Spirometry is mandatory to establish the diagnosis of COPD.

What is shortness of breath: progresses over time. Intensifies with exercise. Long-lasting, continuous.

Chronic cough: May be temporary and may be non-productive. Intermittent wheezing.

Chronic sputum production: any type.

Recurrent lower respiratory tract infections

Collection of risk factors: Host factors (such as genetic factors, congenital/developmental anomalies, etc.). Tobacco smoke. Smoke from home cooking and heating fuels. Presence of dust, fumes, fumes, gases and other chemicals.

Family history of COPD and/or childhood factors: eg, low birth weight, childhood respiratory infections.

Consider COPD, and perform spirometry, if any of these indicators are present in an individual over age 40. These indicators are not diagnostic themselves, but the presence of multiple key indicators increases the probability of a diagnosis of COPD. Spirometry is required to establish a diagnosis of COPD.
Dyspnea that is:	Progressive over time. Characteristically worse with exercise. Persistent.
Chronic cough:	May be intermittent and may be unproductive. Recurrent wheeze.
Chronic sputum production:	With any pattern.
Recurrent lower respiratory tract infections
History of risk factors:	Host factors (such as genetic factors, congenital/developmental abnormalities etc.). Tobacco smoke.Smoke from home cooking and heating fuels. Occupational dusts, vapors, fumes, gases and other chemicals.
Family history of COPD and/or childhood factors:	For example low birthweight, childhood respiratory infections.

Symptoms Chronic and progressive shortness of breath is the most characteristic symptom of COPD. Dyspnea. Dyspnea is one of the main causes of disability and anxiety in COPD. The terms used to describe shortness of breath vary individually and across cultures. Cough. Chronic cough is often the first symptom of COPD and is often underestimated by the patient, regarded as a consequence and/or environmental exposure to smoking. Sputum production. Regular sputum production > 3 months 2 years - consecutively is the classic definition of chronic bronchitis; an arbitrary definition that does not reflect the full range of sputum reported in COPD. Patients who produce large volumes of sputum may have latent bronchiectasis. Wheezing and tightness in the chest. Wheezing and chest tightness can vary from days to days. Additional signs of severe illness. Fatigue, weight loss and anorexia are often observed in patients with more severe forms of COPD. Disease history A detailed medical history of any patient who has or is suspected of having COPD should include: Exposure to risk factors such as smoking and environmental or occupational exposure. medical history, including asthma, allergies, sinusitis, or nasal polyps; respiratory tract infections in childhood; other chronic respiratory and non-respiratory diseases. Family history of COPD or other chronic respiratory disease. Pattern of symptom development: age of onset, pattern of symptoms, more frequent or prolonged “winter colds,” and social deprivation. History of exacerbations or previous hospitalizations for respiratory diseases. The presence of concomitant diseases, such as heart disease, osteoporosis, musculoskeletal system, and malignant neoplasms. The impact of the disease on the patient's life, including limitation of activity, loss of work and economic impact, and feelings of depression or anxiety. Social and family support for the patient. Opportunities to reduce risk factors, especially smoking. Physical examination Although important for assessing overall health, physical examination is rarely helpful in diagnosing COPD. Physical signs of airflow limitation/hyperventilation are usually not detected until significantly impaired lung function appears. Spirometry Spirometry is the most reproducible and objective measurement of airflow limitation. This is a non-invasive and affordable test. Good quality spirometry is possible in any medical setting; All health care workers who care for patients with COPD should have access to spirometry. After bronchodilator, fixed FEV1/FVC ratio<0.70 является критерием спирометрического ограничения воздушного потока. Этот критерий является простым и независимым от референтных значений и используется в многочисленные клинические испытания. Однако, это может привести к более частому диагностики ХОБЛ в пожилом возрасте, и менее частым диагнозом у взрослых <45 лет, особенно при легком течении заболевания, по сравнению с отсечкой, основанная на точке отсчета по нижней границе нормы (lower limit of normal (LLN) значения ОФВ1/ФЖЕЛ. Ряд ограничений возникает при использовании LLN в качестве диагностического критерия для спирометрических обструкции: 1) LLN значения зависят от выбора эталонных значений, после бронходилататора ОФВ1, 2) нет таких пролонгированных исследований, которые проверяют с помощью LLN, и 3) исследования с использованием LLN в популяциях, где курение не является основной причиной ХОБЛ отсутствуют. Определение нормальной спирометрией определено новый подходом Global Lung Initiative (GLI) глобальной инициативе легких (ГЛИ)., Используя GLI уравнений, Z-значения были рассчитаны для ОФВ1, ФЖЕЛ и ОФВ1/ФЖЕЛ и по сравнению с фиксированным соотношением данных. Полученные данные свидетельствуют, что среди взрослых с GLI – определенными спирометрия, использование фиксированного коэффициента может неправильно отбирать лиц, имеющих респираторные нарушения. Эти результаты ждут дополнительные исследования в других исследованиях. Риск неправильной диагностики и лечения с использованием фиксированного коэффициента в качестве диагностического критерия, ограничен поскольку спирометрия-это только один параметр, используемый для установления клинического диагноза ХОБЛ. Золотой стандарт с использованием фиксированного коэффициента LLN является диагностически простым и согласованным что являются важнейшим для занятого клинициста. Оценивать степень обратимости ограничения воздушного потока (например, измерение ОФВ1 до и после бронходилататора или глюкокортикостероиды), чтобы сделать терапевтические решения не рекомендуется так как это не помощь в диагностике ХОБЛ, а дифференцировать ХОБЛ от астмы, или предсказать долгосрочный ответ на лечение. У бессимптомных лиц без воздействия табака или других вредных раздражителей, скрининг спирометрии не показан. Однако у пациентов с симптомами и/или факторами риска (например, >20 pack-years or recurrent chest infections), reliable diagnostic results for COPD are relatively high and spirometry should be considered. The GOLD guidelines advocate performing spirometry in patients with symptoms and/or risk factors, but not routine screening of spirometry in asymptomatic individuals without COPD risk factors. Grade The goals of COPD assessment for treatment selection are: 1) to determine the degree of airflow limitation; 2) determine its impact on the patient and health status; 3) determining the risk of future events (eg, exacerbations, hospitalizations, or death). To achieve these goals, the assessment of COPD must consider separately the following aspects of the disease: Presence and severity of spirometric abnormalities Current status and severity of symptoms History/future risk of exacerbations Presence of comorbidities Classification of severity of airflow limitation Spirometry should be performed after an adequate dose of at least one short-acting inhaled bronchodilators to minimize variability. The role of spirometry in the diagnosis, evaluation and follow-up of COPD is summarized in Table 2. Diagnostics Assess severity of airflow obstruction (for prognosis) Follow-up Therapeutic decisions Pharmacological in selected circumstances (inconsistency between spirometry and symptom level Consideration of alternative diagnosis when symptoms are disproportionate to level of airflow obstruction Non-pharmacological (i.e. interventional procedures) Determination of rate of decline table 2. The role of spirometry Table 2. Role of spirometry

Diagnosis Assessment of severity of airflow obstruction (for prognosis) Follow-up assessment Therapeutic Pharmacological in selected circumstances (e.g., discrepancy between spirometry and level of symptoms). Consider alternative diagnoses when symptoms are disproportionate to degree of airflow Non-pharmacological (e.g., interventional procedures). Identification of rapid

Symptom assessment COPD was previously regarded as a disease largely characterized by shortness of breath. Simple dyspnoea questionnaires such as the Modified British Medical Research Council (mMRC) Questionnaire are considered sufficient to assess symptoms. However, patients with COPD tolerate shortness of breath well. For this reason, a comprehensive assessment of symptoms is recommended. The most comprehensive disease-specific and health questionnaires include the Chronic Respiratory Questionnaire (CRQ)53 and St. George's Respiratory Questionnaire (SGRQ). There are 2 too complex to be used in clinical practice, but with fewer measures, such as the COPD Assessment Test (CATTM) that are suitable. Selecting SGRQ score thresholds< 25 не редкость у пациентов с ХОБЛ и оценки ≥ 25 очень редко у здоровых людей. Эквивалентные точки для CATTM составляет 10. Порог mMRC ≥ 2 используется для разделения “меньше одышка” от “более одышка”. Оценка риска обострений Лучшим предиктором частых обострений (определяется как ≥ 2 обострений в год) – это история ранее случившихся событий. Госпитализации в связи с обострением ХОБЛ имеет плохой прогноз и повышенный риск смерти. Уровень эозинофилов крови. Пост анализ двух клинических испытаний у больных с обострением ХОБЛ история показала, что высокое количество эозинофилов в крови может предсказать, увеличение частоты обострения у больных, получавших бета агонисты длительного действия (ДДБА) (LABA) (без ингаляционных кортикостероидов, ИКС inhaled corticosteroid, ICS). Лечебный эффект от ИС/ЛАБА против ЛАБА на обострения была выше у пациентов с более высоких эозинофилов в крови. Эти данные свидетельствуют о том, что эозинофилы в крови являются 1) биомаркера риска обострения у пациентов с наличием в анамнезе обострений и 2) может предсказать последствия применения ИКС на предотвращение обострения. Перспективные испытания, необходимые для проверки подсчета эозинофилов крови для прогнозирования влияния ИКС, определять пороговую величину крови эозинофилов, которая предсказывает риск обострения и прояснить значения снижения эозинофилов в крови, которые могут быть использованы в клинической практике. Assessment of concomitant chronic diseases (comorbidity) Patients with COPD often have important comorbid chronic diseases, while COPD is an important component of multimorbidity, especially in old age. The ABCD GOLD Report 2011 Revised COPD Composite Score Tool was a big step forward from the simple spirometry scoring system of the GOLD Reports because it included long-term patient outcomes and emphasized the importance of exacerbation prevention in the management of COPD. However, there are important restrictions. ABCD scores do not perform any better than spirometric scores for predicting mortality or other important health outcomes. In addition, the results of group “D” were modified by two parameters: pulmonary function and/or history of exacerbation, which caused confusion. To address these issues, the 2017 GOLD Report provides a refinement of the ABCD score that separates the spirometric scores in the “ABCD” groups. According to some treatment recommendations, especially pharmacological treatments, ABCD groups are derived solely from the patient's symptoms and history of their exacerbation. However, spirometry, in conjunction with the patient's symptoms and history of exacerbation, remains vital for diagnosis, prognosis and consideration of other important therapeutic approaches, especially non-pharmacological therapy. This new assessment approach is shown in Figure 2.
Rice. 2. ABCD Tool Assessment Tool Figure 2. The refined ABCD assessment tool The assessment scheme outlines that patients should undergo spirometry to determine the severity of airflow limitation (ie, spirometric grade). They should also complete an assessment of either dyspnea using the mMRC questionnaire or symptoms using the CATTM. Finally, their history of exacerbations (including previous hospitalizations) should be recorded. The number provides information about the severity of airflow limitation (spirometric grades 1 to 4), and the letter (groups A-D) provides information about symptom burden and risk of exacerbation. FEV1 is a very important parameter at the population level in predicting important clinical outcomes such as mortality and hospitalization or transition to non-pharmacological treatments such as lung resection or lung transplantation. However, at the individual patient level, FEV1 loses precision and therefore cannot be used in isolation to identify all therapeutic options. In addition, in some cases, such as hospitalization or emergency presentation to a clinic or emergency room, determining the patient's condition based on symptoms and history of exacerbation, independent of the value of spirometry, allows physicians to develop a treatment plan based on the revised ABCD scheme. This approach recognizes the limitations of FEV1 in guiding treatment decisions for individual patient management and emphasizes the importance of patient symptoms and exacerbation risk in guiding COPD therapy. Separating airflow limitation from clinical parameters makes it clearer what is assessed and ranked. This should facilitate more precise parameter-based treatment recommendations that are based on a patient's symptoms at any point in time. Example. Let's consider two patients - patients with FEV1<30% прогнозов, баллы CAT 18 и без обострений в прошлом году, а другой с тремя обострений в течение года. Оба были помечены GOLD D в схеме классификации. Однако, с новой предложенной схеме, пациент с 3 обострений в течение года будет маркироваться GOLD 4 класс, группа D. B ндивидуальные решения по фармакотерапевтических подходe будет использовать рекомендации, основанные на оценке АВСD лечить пациента основной проблемой в это время, т. е. персистирующие обострения. Другой пациент, который не имел обострений, будет классифицироваться как GOLD класс 4, группы В. У таких больных, помимо медикаментозного лечения и реабилитации - резекцмя лёгкого, трансплантация легких или буллэктомия bullectomy могут быть важные терапевтические рекомендации с учетом тяжести симптом и уровня снижения спирометрии.. Альфа-1-антитрипсина дефицит Всемирная организация здравоохранения рекомендует всем пациентам с диагнозом ХОБЛ один раз скрининг на Альфа-1-антитрипсина дефицит. Низкая концентрация (< 20% нормальном) свидетельствует о недостаточности гомозиготной. Члены семьи должны обследоваться и совместно с пациентом в специализированных центры за консультацией и управления. Дополнительные исследования Для того, чтобы исключить другие сопутствующие заболевания, способствующие респираторных симптомов или в случаях, когда пациенты не отвечают на лечение, как и ожидалось, дополнительные испытания могут быть необходимы. Грудной визуализации (рентгенография грудной клетки, КТ грудной клетки); оценка легочных объемов и/или диффузионной способностью, оксиметрии и газов артериальной крови измерение и тестирование и оценку физической активности следует выполнить. Составные(комбинированные) шкалы. The BODE (Body mass index, Obstruction, Dyspnea, and Exercise) способ дает комплексный счет, что является лучшим предиктором последующего выживания, чем любой отдельный компонент. Простые альтернативы, которые не включают нагрузочное тестирование необходимо проверки для пригодности для рутинного клинического использования. Дифференциальный диагноз. У некоторых пациентов, особенности с астмой и ХОБЛ могут сосуществовать. Условия астма-ХОБЛ перекрестный синдром (АХПС) Asthma-COPD Overlap Syndrome (ACOS) или астма-ХОБЛ перекрест (АХП) Asthma-COPD Overlap (ACO) признает наложение этих двух распространенных заболеваний, вызывающих хроническое ограничение воздушного потока, а не ярко выраженный синдром. Большинство других возможных дифференциальных диагнозов легче отличить от ХОБЛ. Другие соображения. Некоторые пациенты без признаков ограничения воздушного потока имеют доказательства структурные болезни легких на снимках грудной клетки (эмфизема, ателектаз, утолщение стенки дыхательных путей). Такие пациенты могут сообщать обострений респираторных симптомов или даже требуют лечения респираторных препаратов на хронической основе. Являются ли эти пациенты имеют острый или хронический бронхит, стойкая форма бронхиальной астмы или более ранней презентации что станет с ХОБЛ как в настоящее время определено, остается неясным и требует дальнейшего изучения. Профилактика и поддерживающая терапия

Key points Quitting smoking is key. Pharmacotherapy and nicotine increase the duration of smoking abstinence replacement . The effectiveness and safety of using e-cigarettes as a smoking cessation aid is uncertain. Drug treatment can reduce the severity of COPD symptoms, reduce the frequency and severity of exacerbations, and improve health status and exercise capacity. Each drug treatment regimen should be individualized and guided by severity of symptoms, risk of exacerbations, side effects, comorbidities, medications available and cost, and patient response, preferences, and availability of various drug delivery devices. Inhaler technique should be assessed regularly. Influenza and pneumococcal vaccinations reduce the incidence of lower respiratory tract infections. Pulmonary rehabilitation improves symptoms, quality of life, and physical and emotional participation in daily activities. In patients with severe chronic hypoxemia, long-term oxygen therapy improves survival. In patients with stable COPD and moderate desaturation at rest or exercise, long-term oxygen treatment should not be routinely prescribed, however, individual patient factors should be considered. In patients with severe chronic hypercapnia and a history of hospitalization for acute respiratory failure, prolonged noninvasive ventilation may reduce mortality and prevent readmission. In some patients with severe pulmonary emphysema refractory to optimized medical care, surgical and bronchoscopic interventional treatment may be beneficial. Palliative approaches are effective in controlling symptoms in advanced COPD.

Prevention and Maintenance Therapy

Key Points Smoking cessation is key. Pharmacotherapy and nicotine replacement increase long-term smoking abstinence The effectiveness and safety of e-cigarettes as a smoking cessation aid is uncertain. Pharmacologic therapy can reduce COPD symptoms, reduce the frequency and severity of exacerbations, and improve health status and exercise Each pharmacologic treatment regimen should be individualized and guided by the severity of symptoms, risk of exacerbations, side-effects, comorbidities, drug availability and cost, and the patient’s response, preference and ability to use various drug delivery Inhaler technique needs to be assessed Influenza and pneumococcal vaccinations decrease the incidence of lower respiratory tract Pulmonary rehabilitation improves symptoms, quality of life, and physical and emotional participation in everyday In patients with severe resting chronic hypoxemia, long-term oxygen therapy improves In patients with stable COPD and resting or exercise-induced moderate desaturation, long-term oxygen treatment should not be prescribed routinely, however, individual patient factors should be In patients with severe chronic hypercapnia and a history of hospitalization for acute respiratory failure, long-term non-invasive ventilation may decrease mortality and prevent re-hospitalization. In select patients with advanced emphysema refractory to optimized medical care, surgical or bronchoscopic interventional treatments may be

Palliative approaches are effective in controlling symptoms in advanced COPD. Quitting Smoking Quitting smoking affects the natural history of COPD. If effective resources and time are allocated to smoking cessation, long-term quit rates of up to 25% can be achieved. Nicotine replacement products. Nicotine replacement therapy increases long-term smoking abstinence and is more effective than placebo. E-cigarettes are increasingly used as a form of nicotine replacement therapy, although their effectiveness remains controversial. Pharmacological products. Varenicline, bupropion, and nortriptyline increase long-term smoking cessation rates, but should be used as part of an intervention program rather than as a sole intervention. Smoking cessation programs. The Five-Step Cessation Program provides a framework for health care providers to use to help patients quit smoking. Counseling provided by health professionals significantly increases spontaneous quitting rates. A combination of pharmacotherapy and behavioral support improves smoking cessation rates. Vaccinations Influenza Vaccine and Pneumococcal Vaccine Influenza vaccination reduces severe illness, death, the risk of coronary heart disease, and the overall number of exacerbations. Vaccines containing killed or live inactivated viruses are recommended as they are more effective in older patients with COPD. Pneumococcal vaccination with PCV13 and PPSV23 is recommended for all patients ≥ 65 years of age (see Table C2 in the Supplementary Appendix). Drug Treatment of Stable COPD Overview of Drugs Pharmacologic therapy for COPD reduces symptoms, the frequency and severity of exacerbations, and improves exercise capacity and health status. Current medications do not reverse long-term decline in lung function. The drug classes used to treat COPD are presented in Supplementary Appendix Table C3. Selection in each class depends on the availability and cost of drugs and favorable clinical response balanced against side effects. Each treatment regimen must be individualized as the relationship between the severity of symptoms, the degree of obstruction, and the severity of exacerbations varies between patients. Bronchodilators Bronchodilators increase FEV1, reduce dynamic hyperinflation at rest and during exercise and improve physical performance. Bronchodilators are usually prescribed on a regular basis to prevent or reduce symptoms. Toxicity is dose dependent. Beta2-adrenergic agonists. Beta2-agonists, including short-acting Beta2-agonists (SABA) and long-acting long-acting Beta2-agonists (LABA) act as agents that relax the smooth muscles of the airways. Stimulation of beta2-adrenergic receptors can produce sinus tachycardia in rest and the occurrence of cardiac arrhythmias in sensitive patients. Excessive somatic tremors occur in some patients receiving higher doses of beta2-agonists. Antimuscarinics. Ipratropium, a short-acting muscarinic antagonist, provides the benefits of a shorter-acting beta2-agonist on pulmonary function, condition health and the need for oral steroids. Long acting muscarinic antagonist (LAMA) improves symptoms and treatment of health conditions, increases the effectiveness of pulmonary rehabilitation and reduces the number of exacerbations and associated hospitalizations. Clinical trials have shown a greater effect on treatment exacerbation rates for LAMA ( tiotropium) versus LABA treatment. An unexpected small increase in cardiovascular events was reported in COPD patients regularly receiving ipratropium bromide. A large study reported no difference in mortality, cardiovascular disease, or exacerbation rates when using tiotropium as a dry powder inhaler compared with the Respimat® inhaler. Methylxanthines. Theophylline is a moderate bronchodilator in stable COPD, and improves FEV1 and dyspnea when added to salmeterol. There is limited and conflicting data regarding the effect of low doses of theophylline on exacerbation rates. Toxicity is dose dependent, which is a problem since most effects occur at toxic doses. Combination bronchodilator therapy Combining drugs with different mechanisms and duration of action can increase the degree of bronchodilator with a lower risk of side effects compared to increasing the dose of a single bronchodilator (Table 3). There are multiple combinations of LABA and LAMA in one single inhaler (Table S3). These combinations improve lung function compared to placebo and have a greater impact on patient reported outcomes compared to monotherapy. LABA/LAMA improves symptoms and health status in patients with COPD, is more effective than long-acting bronchodilator monotherapy for the prevention of exacerbations, and reduces exacerbations to a greater extent than the ICS LABA combination. Table 3. Bronchodilators for stable COPD

Inhaled bronchodilators are central to symptomatic treatment for COPD and are usually prescribed on a regular basis to prevent or reduce symptoms (Evidence Level A). Regular and as-needed use of SABA or SAMA improves FEV1 and symptoms (Evidence Level A). Combinations of SABA and SAMA are superior to drug monotherapy in improving FEV1 and symptoms (Evidence Level A). LABAs and LAMAs significantly improve lung function, dyspnea, health status, and reduce exacerbation rates (Evidence Level A). LAMAs have a greater effect on reducing exacerbations compared to LABAs (Evidence A) and reduced hospitalizations (Level of Evidence B). Combination treatment with LABA and LAMA increases FEV1 and reduces symptoms compared with monotherapy (level of evidence A). Combination treatment with LABA and LAMA reduces the number of exacerbations compared with monotherapy (Evidence B) or ICS/LABA (Evidence B). Tiotropium enhances the effectiveness of pulmonary rehabilitation in improving physical performance (Level of Evidence B). Theophylline has little bronchodilator effect in stable COPD (Evidence A), which is associated with modest symptomatic effects (Evidence B).

Table 3. Bronchodilators in stable COPD

Inhaled bronchodilators in COPD are central to symptom management and commonly given on a regular basis to prevent or reduce symptoms (Evidence A). Regular and as-needed use of SABA or SAMA improves FEV1 and symptoms (Evidence A). Combinations of SABA and SAMA are superior compared to either medication alone in improving FEV1 and symptoms (Evidence A). LABAs and LAMAs significantly improve lung function, dyspnea, health status, and reduce exacerbation rates (Evidence A). LAMAs have a greater effect on exacerbation reduction compared with LABAs (Evidence A) and decrease in hospitalizations (Evidence B). Combination treatment with a LABA and LAMA increases FEV 1 and reduces symptoms compared to monotherapy (Evidence A). Combination treatment with a LABA and LAMA reduces exacerbations compared to monotherapy (Evidence B) or ICS/LABA (Evidence B). Tiotropium improves the effectiveness of pulmonary rehabilitation in increasing exercise performance (Evidence B). Theophylline exerts a small bronchodilator effect in stable COPD (Evidence A) that is associated with modest symptomatic benefits (Evidence B).

Anti-inflammatory agents Exacerbations are the primary clinically relevant endpoint used to assess the effectiveness of anti-inflammatory drugs (Table 4). Table 4. Anti-inflammatory therapy in stable COPD

Inhaled corticosteroids ICS combined with LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations of moderate to very severe COPD (Evidence Level A). Regular treatment with ICS increases the risk of developing pneumonia, especially in those with severe disease (Evidence Level A). Triple inhaled therapy ICS/LAMA/LABA improves lung function, symptoms and health status (Evidence Level A) and reduces exacerbations (Evidence Level B) compared with ICS/LABA or LAMA monotherapy. Oral glucocorticoids Long-term use of oral glucocorticoids has many side effects (Evidence A) and no evidence of benefit (Evidence C). PDE4 inhibitors In patients with chronic bronchitis, severe and very severe COPD and exacerbations: o A PDE4 inhibitor improves lung function and reduces moderate to severe exacerbations (Evidence Level A). o A PDE4 inhibitor improves lung function and reduces exacerbations in patients who are on a fixed dose LABA/ICS combination (Evidence Level B). Antibiotics Long-term therapy with azithromycin and erythromycin reduces exacerbations within one year (Evidence Level A). Azithromycin treatment is associated with an increased incidence of bacterial resistance (Evidence A) and hearing impairment (Evidence B). Mucolytics/antioxidants Regular use of ACETYLCYSTEINE and carbocysteine ​​reduces the risk of exacerbations in certain populations (Evidence B). Other anti-inflammatory drugs Simvastatin does not prevent exacerbations in patients with COPD at increased risk of exacerbation and without an indication for statin therapy (Evidence A). However, observational studies suggest that statins may have a beneficial effect on some outcomes in patients with COPD who receive them for cardiovascular and metabolic measures (Evidence Level C). Leukotriene modifiers have not been adequately tested in patients with COPD.

Table 4. Anti-inflammatory therapy in stable COPD

Inhaled corticosteroids

An ICS combined with a LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to very severe COPD ( Evidence A). Regular treatment with ICS increases the risk of pneumonia especially in those with severe disease ( Evidence A). Triple inhaled therapy of ICS/LAMA/LABA improves lung function, symptoms and health status ( Evidence A) and reduces exacerbations ( Evidence B) compared to ICS/LABA or LAMA monotherapy.

Oral glucocorticoids

Long-term use of oral glucocorticoids has numerous side effects ( Evidence A) with no evidence of benefits ( Evidence C).

PDE4 inhibitors

In patients with chronic bronchitis, severe to very severe COPD and a history of exacerbations: A PDE4 inhibitor improves lung function and reduces moderate and severe exacerbations ( Evidence A). A PDE4 inhibitor improves lung function and decreases exacerbations in patients who are on fixed-dose LABA/ICS combinations ( Evidence B).

Antibiotics

Long-term azithromycin and erythromycin therapy reduces exacerbations over one year ( Evidence A). Treatment with azithromycin is associated with an increased incidence of bacterial resistance ( Evidence A) and hearing test impairment ( Evidence B).

Mucolytics/antioxidants

Regular use of NAC and carbocysteine ​​reduces the risk of exacerbations in select populations ( Evidence B).

Other anti-inflammatory agents

Simvastatin does not prevent exacerbations in COPD patients at increased risk of exacerbations and without indications for statin therapy ( Evidence A). However, observational studies suggest that statins may have positive effects on some outcomes in patients with COPD who receive them for cardiovascular and metabolic indications ( Evidence C). Leukotriene modifiers have not been tested adequately in COPD patients.

Inhaled corticosteroid ICS combined with LABA is more effective than the individual components in improving lung function and health status and reducing exacerbations in patients with exacerbations of moderate to very severe COPD (Evidence Level A). Regular treatment with ICS increases the risk of developing pneumonia, especially in those with severe disease (Evidence Level A). Triple inhaled therapy ICS/LAMA/LABA improves lung function, symptoms and health status (Evidence Level A) and reduces exacerbations (Evidence Level B) compared with ICS/LABA or LAMA monotherapy. Oral glucocorticoids Long-term use of oral glucocorticoids has many side effects (Evidence A) and no evidence of benefit (Evidence C). PDE4 inhibitors In patients with chronic bronchitis, severe and very severe COPD and exacerbations: o A PDE4 inhibitor improves lung function and reduces moderate and severe exacerbations (Evidence Level A). o A PDE4 inhibitor improves lung function and reduces exacerbations in patients who are on a fixed dose LABA/ICS combination (Evidence Level B). Antibiotics Long-term therapy with azithromycin and erythromycin reduces exacerbations within one year (Evidence Level A). Azithromycin treatment is associated with an increased incidence of bacterial resistance (Evidence A) and hearing impairment (Evidence B). Mucolytics/antioxidants Regular use of ACETYLCYSTEINE and carbocysteine ​​reduces the risk of exacerbations in certain populations (Evidence B). Other anti-inflammatory drugs Simvastatin does not prevent exacerbations in patients with COPD at increased risk of exacerbation and without an indication for statin therapy (Evidence A). However, observational studies suggest that statins may have a beneficial effect on some outcomes in patients with COPD who receive them for cardiovascular and metabolic measures (Evidence Level C). Leukotriene modifiers have not been adequately tested in patients with COPD. Inhaled Corticosteroids In patients with moderate to severe COPD and exacerbations, inhaled corticosteroids (ICS) in combination with LABA are more effective than either component alone in improving lung function, health status, and reducing exacerbations. However, combination therapy does not affect survival. The use of ICS results in a high incidence of oral thrush, hoarseness, bluish skin and pneumonia. Patients at increased risk of pneumonia include those who are current smokers, aged >55 years, have a history of previous exacerbations or pneumonia, Body Mass Index (BMI)<25 кг/м2, низкий MRC класс одышка и/или резкого ограничения потока воздуха. Результаты РКИ не дали однозначных результатов относительно риска снижения плотности костной ткани и переломы при лечении ICS. Обсервационные исследования предполагают, что лечение ICS может быть связан с повышенным риском диабета/плохого контроля сахарного диабета, катаракты и микобактериальные инфекций в том числе туберкулеза. Выводы по ICS. Исследования вывода обеспечивают противоречивые результаты, касающиеся последствий влияния на легочной функции, симптомов и обострений. Тройной ингаляционная терапия Сочетание LABA плюс LAMA плюс ICS (тройная терапия triple therapy) может улучшить функцию легких пациента и отдаленные результаты. и снизить риск обострения. Однако, ни одному РКИ не удалось продемонстрировать какую-либо выгоду из добавления ICS к LABA плюс LAMA на обострения.Больше доказательства необходимы, чтобы сравнить преимущества тройной терапии (LABA/LAMA/ICS) to LABA/LAMA. Пероральные глюкокортикоиды Пероральные глюкокортикоиды не играют никакой роли в хронической ежедневной лечение при ХОБЛ из-за отсутствия выгоды в сравнении с высокая частота системных осложнений. Фосфодиэстеразы-4 ингибиторы Roflumilast снижает среднетяжелых и тяжелых обострений лечение на фоне лечения системными кортикостероидами у пациентов с хроническим бронхитом, тяжелым и очень тяжелым ХОБЛ, а также с историей обострений. Фосфодиэстеразы-4 (PDE4) ингибиторы имеют больше побочных эффектов, чем ингаляционные лекарства для ХОБЛ. Наиболее часто встречаются диарея, тошнота, снижение аппетита, потеря веса, боли в животе, нарушения сна и головная боль. Roflumilast следует избегать у пациентов с повышенной массой тела и применять с осторожностью у пациентов с депрессией. Антибиотики Азитромицин (250 мг/сут или 500 мг три раза в неделю) или эритромицина (500 мг два раза в день) в течение одного года снижает риск обострений у пациентов, склонных к обострениям.160-162 использовать Азитромицин показал снижение частоты обострений только у бывших курильщиков и было связано с увеличением заболеваемости бактериальной резистентности и нарушением слуха. Пульс моксифлоксацин терапии у пациентов с хроническим бронхитом и частыми обострениями не уменьшал частоты обострений. Муколитики (mucokinetics, mucoregulators) и антио ICS ксиданты (N – ацетилцистеин, карбоцистеин) Регулярное применение муколитических средств, таких как карбоцистеин и N-ацетилцистеин может уменьшать обострений и скромно улучшения состояния здоровья у больных, не получавших ICS. Другие лекарства с противовоспалительным потенциалом Хотя рандомизированные клинические исследования предполагают, что immunoregulators уменьшают тяжесть и частоту обострений, долгосрочные последствия такой терапии неизвестны. Nedocromil и лейкотриена модификаторы не были должным образом проверены при ХОБЛ. Нет никаких доказательств пользу, и некоторые доказательства вреда, после лечения анти-ФНО- Альфа антитела (инфликсимаб) при умеренной до тяжелой ХОБЛ. Симвастатин не предотвращает обострений у пациентов с ХОБЛ, которые не имели метаболических или сердечно-сосудистых показаний к терапии статинами. Ассоциацию между пользой статинов и улучшения результатов сообщили в обсервационном исследовании пациентов с ХОБЛ, которые получали их от сердечно-сосудистых и метаболических признаков. Нет никаких доказательств, что дополнительный прием витамина D уменьшает обострений в неотобранных пациентов. Вопросы, связанные с ингаляционным способом введения Обсервационные исследования выявили значимую связь между недостаточным использование ингалятора и контроль симптомом при ХОБЛ. Причины недостаточного использования ингалятор включают в себя пожилой возраст, использование нескольких устройств, и отсутствие предшествующего образования по технике ингаляции. Обучение улучшает технику ингаляции в некоторых, но не всех пациентов, особенно когда “учить-поддерживать”“teach-back”, реализуемого подхода. Другие Фармакологические методы лечения ХОБЛ представлены в таблице S4 в дополнительном приложении. Альфа-1-антитрипсина аугментации терапии. Обсервационные исследования предполагают снижение прогрессирования спирометрическое при Альфа-дефицит 1 антитрипсина у пациентов, получавших аугментации терапии в сравнении с не-леченных больных. Исследования с использованием чувствительных параметры прогрессирования эмфиземы определяется КТ подтверждают эффект на сохранении легочной ткани по сравнению с плацебо. Противокашлевые средства. Роль противокашлевые средства у пациентов с ХОБЛ являются неубедительными. Вазодилататоры. Имеющиеся исследования показывают ухудшение газообмена с небольшим улучшением при физических нагрузках или состояния здоровья у больных ХОБЛ. Rehabilitation, education, self-government Pulmonary Rehabilitation Pulmonary rehabilitation is a comprehensive intervention based on a thorough inpatient assessment followed by patient-adapted treatment methods (eg, training, education, self-management, behavioral change interventions to improve physical and psychological well-being and encourage adherence to health-promoting behaviors in patients with COPD). The benefits of pulmonary rehabilitation are significant (Table S5 in the Supplementary Appendix). Pulmonary rehabilitation may reduce readmissions and mortality in patients following a recent exacerbation (≤ 4 weeks before hospitalization). Initiating pulmonary rehabilitation before hospital discharge, however, may compromise survival. Pulmonary rehabilitation is integrated patient management that involves a range of health care professionals and settings, including inpatient, outpatient, and/or home care. Education, self-management, and comprehensive care Education. Smoking cessation, proper use of inhalation devices, early detection of exacerbations, decision-making when seeking help, surgical interventions, and consideration of preventative measures are examples of teaching topics. Self-management. Self-regulatory measures, the use of written agreed plans for dealing with worsening symptoms, can lead to a reduction in illness leading to hospitalization and all causes of hospitalization and improvement in health status. The health benefits of COPD self-management programs may be offset by increased mortality. Generalization in real life remains difficult. Comprehensive care programs. Integrated care programs improve clinical outcomes, although not mortality. However, a large multicenter study in an existing well-organized medical care system does not confirm this. Comprehensive telemedicine arrangements provide no significant benefits. Support, Palliative, End of Life, and Hospice Care Symptom control and palliative care The goal of palliative care is to prevent and relieve suffering and improve the quality of life of patients and their families, regardless of the stage of the disease or other treatments. Palliative efforts should be aimed at relieving dyspnea, pain, anxiety, depression, fatigue, and poor nutrition. End of Life and Hospice Care End of life care discussions should include patients and their families. Advance planning can reduce anxiety for patients and their families, ensure care is consistent with their wishes, and avoid unnecessary, unnecessary, and costly invasive treatments. Table S6 in the Supplementary Appendix provides approaches to palliative, end-of-life, and hospice care. Other Treatment Methods Oxygen therapy and mechanical ventilation Oxygen therapy. Long-term administration of oxygen (>15 hours per day) to patients with chronic respiratory failure improves survival in patients with severe hypoxemia. Long-term oxygen therapy does not prolong time to death or first hospitalization or provide sustained benefits for any of the measured outcomes in patients with stable COPD at rest or exercise with moderate arterial oxygen desaturation. Ventilation Whether NPPV should be used chronically at home to treat patients with acute chronic respiratory failure during hospitalization remains uncertain. Retrospective studies found inconclusive data. RCTs have provided conflicting evidence on the use of home NPPV on survival and readmission in chronic hypercapnic COPD. In patients with both COPD and obstructive sleep apnea, continuous positive airway pressure improves survival and avoids hospitalization (Table S7 in the Supplementary Appendix). Interventional Therapy Surgical Interventions Operations to reduce lung volume. One study confirmed that COPD patients with upper lobe emphysema and poor postoperative exercise tolerance experienced improved survival when treated with lung volume reduction surgery (LVRS), compared with medical treatment. In patients with high post-pulmonary rehabilitation physical performance, no difference in survival was noted after LVRS, although health status and exercise performance improved. LVRS has been demonstrated to result in a higher mortality rate than medical treatment for severe emphysema in patients ≤ FEV1 20%, and homogeneous emphysema with high-resolution computed tomography or DLCO has been shown to be ≤ 20% predicted. Bullectomy. In selected patients with relatively intact underlying lungs, bullectomy is associated with decreased dyspnea, improved lung function, and exercise capacity. Lung transplantation. In selected patients, lung transplantation has been indicated to improve health and function but not to prolong survival. Bilateral lung transplants have been reported to have a longer lifespan than single lung transplants in patients with COPD, especially<60 лет. Бронхоскопических вмешательств для уменьшения гиперинфляции при тяжелой Эмфиземе Менее инвазивные подходы бронхоскопических к сокращению легких были разработаны. Проспективных исследований показали, что использование бронхиальных стентов не эффективно при при использовании герметика легкого вызвавшего значительную заболеваемость и смертность. В РКИ размещения эндобронхиального клапана показали статистически значимое улучшение ОФВ1 и 6-минутной ходьбы по сравнению с контрольной терапией в течение 6 месяцев после интервенции, но масштабы наблюдаемых улучшений не было клинически значимыми. Впоследствии, эффективность же эндобронхиального клапана была изучена у пациентов с гетерогенными,217 или гетерогенных и гомогенных эмфиземой со смешанными результатами. Два многоцентровых исследованиях изучался нитиноловой спиралью имплантируется в легких по сравнению с обычным лечением сообщили об увеличении в 6 минутах ходьбы при лечение спиралью по сравнению с контролем и небольшие улучшение ОФВ1 и качества жизни по by St George’s Respiratory Questionnaire. Дополнительные сведения необходимы, чтобы определить оптимальное количество пациентов для получения конкретного метода объем бронхоскопических легких и сравнивать продолжительность улучшения в функциональных или физиологических показателей в LVRS относительно побочных эффектов. Ключевые моменты для интервенционной терапии при стабильной ХОБЛ представлены в таблице S8 в дополнительном приложении. Management of stable COPD ManagementofStableCOPD

Key Points Risk The management strategy for stable COPD should be based on individualized symptom assessment and future of

All individuals who smoke should be supported to quit.

The main treatment goals are reduction of symptoms and future risk of exacerbations.

Management strategies are not limited to pharmacologic treatments, and should be complemented by appropriate non-pharmacologic interventions.

Key Points Management strategy for stable COPD should be based on an assessment of individual symptoms and risk of future exacerbations. All people who smoke should be supported to quit. The main goal of treatment is to reduce symptoms and the risk of future exacerbations. Management strategies are not limited to drug treatment, and should be complemented by appropriate non-pharmacological interventions. Effective management of COPD should be based on individual assessment with the goal of reducing current symptoms and future risks of exacerbations (Figure C1 in the Supplementary Appendix). We offer personalized initiation and escalation/de-escalation procedures based on the individual's symptom level and risk of exacerbation. The basis for these recommendations is based in part on evidence collected in RCTs. These guidelines are intended to support physician decision making. Identifying and Reducing Risk Factors Cigarette smoking is the most common and easily identifiable risk factor for COPD; Smoking cessation should be constantly recommended for smokers. Reducing overall personal exposure to occupational dusts, fumes and gases, as well as indoor and outdoor hazardous substances, must be addressed. Treatment of stable COPD Drug Treatment Drug treatment can reduce symptoms, reduce the risk and severity of exacerbations, and improve health and exercise capacity. The choice in each class depends on the availability of the drug and the patient's response and preference (Table 5 - Table 5. Key points for the use of bronchodilators Table 5. Key points for the use of bronchodilators

LABAs and LAMAs are preferred over short-acting agents except for patients with only occasional dyspnea ( Evidence A). Patients may be started on single long-acting bronchodilator therapy or dual long-acting bronchodilator therapy. In patients with persistent dyspnea on one bronchodilator treatment should be escalated to two ( Evidence A). Inhaled bronchodilators are recommended over oral bronchodilators ( Evidence A). Theophylline is not recommended unless other long-term treatment bronchodilators are unavailable or unaffordable ( Evidence B).

Table 6. Key Points for Using Anti-Inflammatory Agents

Long-term monotherapy with ICS is not recommended (level of evidence A). Long-term treatment with ICS may be considered in conjunction with LABAs for patients with a history of exacerbations despite appropriate treatment with long-acting bronchodilators (Evidence Level A). Long-term therapy with oral corticosteroids is not recommended (level of evidence A). In patients with exacerbations despite LABA/ICS or LABA/LAMA/ICS, chronic bronchitis and severe to very severe airflow obstruction, addition of a PDE4 inhibitor may be considered (Level of Evidence B). In former smokers with exacerbations despite appropriate therapy, macrolides may be prescribed (Evidence B). Statin therapy is not recommended for the prevention of exacerbations (Evidence Level A). Antioxidant mucolytics are recommended only in selected patients (Evidence Level A).

Table 6. Key points for the use of anti-inflammatory agents

Long-term monotherapy with ICS is not recommended ( Evidence A). Long-term treatment with ICS may be considered in association with LABAs for patients with a history of exacerbations despite appropriate treatment with long-acting bronchodilators ( Evidence A). Long-term therapy with oral corticosteroids is not recommended ( Evidence A). In patients with exacerbations despite LABA/ICS or LABA/LAMA/ICS, chronic bronchitis and severe to very severe airflow obstruction, the addition of a PDE4 inhibitor can be considered ( Evidence B). In former smokers with exacerbations despite appropriate therapy, macrolides can be considered ( Evidence B). Statin therapy is not recommended for prevention of exacerbations ( Evidence A). Antioxidant mucolytics are recommended only in selected patients ( Evidence A).

Table 7. Key points for the use of other pharmacological treatments Table 7. Key points for the use of other pharmacologic treatments

Patients with severe hereditary alpha-1 antitrypsin deficiency and established emphysema may be candidates for alpha-1 antitrypsin augmentation therapy ( Evidence B). Antitussives cannot be recommended ( Evidence C). Drugs approved for primary pulmonary hypertension are not recommended for patients with pulmonary hypertension secondary to COPD ( Evidence B). Low-dose long acting oral and parenteral opioids may be considered for treating dyspnea in COPD patients with severe disease ( Evidence B).

Pharmacotherapy algorithms A proposed model for initiation and then subsequent escalation and/or de-escalation of pharmacologic management according to individual assessment of symptoms and risk of exacerbation is shown in Figure 3. In the past GOLD Reports, recommendations were made only for initial therapy. However, many patients with COPD are already on treatment and experience a return of persistent symptoms after initial therapy, or less commonly with resolution of some symptoms that may subsequently require less therapy. That's why we now offer escalation and de-escalation strategies. Recommendations are based on available efficacy and safety data. We acknowledge that treatment escalation has not been systematically tested; de-escalation tests are also limited and only include ICS. There is no direct evidence to support therapeutic recommendations for patients in groups C and D. These recommendations will be reviewed as additional evidence. Rice. 3. Pharmacological treatment algorithms GOLD Grade (highlighted boxes and arrows indicate preferred treatment routes] Figure 3. Pharmacologic treatment algorithms by GOLD Grade Group A All Group A patients should be offered bronchodilators to reduce shortness of breath. These can be either short-acting or long-acting bronchodilators based on patient preference. Bronchodilators should be continued if symptomatic benefit is noted. Group B Initial therapy should be a long-acting bronchodilator. Long-acting bronchodilators are superior to short-acting bronchodilators that are taken intermittently. There is no evidence to recommend one class of long-acting bronchodilators over another for symptomatic relief; the choice should depend on the individual patient's response. For patients with persistent dyspnea on monotherapy, the use of two bronchodilators is recommended. For patients with severe dyspnea, initial therapy with bronchodilation may be considered. Group C Initial therapy should be a single long-acting bronchodilator. In two parallel studies, LAMA testing was superior to LABA in preventing exacerbations, so we recommend starting with LAMA in this group. Patients with persistent exacerbations may benefit from adding a second long-acting bronchodilator (LABA/LAMA), or using a combination of long-acting beta2-agonists and inhaled corticosteroids (LABA/ICS). As ICS increases the risk of pneumonia, our primary choice is LABA/LAMA. Group D We recommend starting with a LABA/LAMA combination because: § In studies reporting patient outcomes as the primary endpoint, the LABA/LAMA combination showed superior results compared with a single bronchodilator. § LABA/LAMA combination was superior to LABA/ICS combination in preventing exacerbations and improving other patients' results obtained in group D patients. § Group D patients have an increased risk of pneumonia when treated with ICS. If one bronchodilator is initially chosen, LAMA is preferred for exacerbation prevention based on comparison with LABAs. LABA/ICS may be the first choice for initial therapy in some patients. These patients may have a history and/or features suggestive of asthma-COPD overlap and/or elevated blood eosinophils. In patients who develop additional exacerbations on LABA/LAMA therapy, we offer two alternative routes: § LABA/LAMA/ICS escalation. § LABA/ICS transition. If LABA/ICS therapy does not have a positive effect on the sequelae/symptoms of exacerbations, LAMA may be added. If patients with LABA/LAMA/ICS continue to have exacerbations, the following options may be considered: § Add roflumilast. This may be considered in patients with FEV1<50%, прогнозирует и хроническим бронхитом, особенно если они испытали как минимум одну госпитализации по поводу обострения в предыдущем году. § Добавить макролид у бывших курильщиков. Возможность развития устойчивых микроорганизмов должны быть учтены при принятии решений. § Остановка ICS. Эта рекомендация подтверждается данными, что показывает повышенный риск побочных эффектов (в т. ч. пневмония) и отсутствие значительного ущерба от отмены ICS. Non-pharmacological treatment Education and Self-Management Assessing the individual patient and assessing risks (eg, exacerbations, patient needs, preferences, and personal goals) should help design personalized self-management. Pulmonary rehabilitation programs Patients with a high level of symptoms and risk of exacerbations (groups B, C and D) should participate in a full rehabilitation program, taking into account the characteristics of the individual and comorbidities. Training Combining constant load or interval training with strength training provides better results than either method. Adding strength training to aerobic training is effective in increasing endurance, but does not improve health or exercise capacity. Upper limb exercise training increases arm strength and endurance and improves the ability to perform upper limb activities. Self-government education The educational program should include smoking cessation; basic information about COPD; aspects of medical treatment (respiratory medications and inhalation devices); strategies to minimize shortness of breath; advice on when to seek help; and perhaps discussing perspectives and end-of-life questions. End of life and palliative care Patients should be informed that if they become seriously ill, they or their family members may need to decide whether a course of intensive care is likely to be pursued to achieve their personal treatment goals. Simple, structured conversations about these possible scenarios should be discussed while patients are stable. Nutritional support For malnourished patients with COPD nutritional supplements is recommended. Vaccination Influenza vaccination is recommended for all patients with COPD. Pneumococcal vaccination with PCV13 and PPSV23 is recommended for all patients >65 years of age. PPSV23 also recommends for younger COPD patients with significant underlying medical conditions, including chronic heart and lung disease. Oxygen Therapy Long-term oxygen therapy is indicated for stable patients who have: PaO2 at or below 7.3 kPa (55 mmHg) or SaO2 at or below 88%, with or without hypercapnia confirmed twice within a three-week period; or PaO2 between 7.3 kPa (55 mmHg) and 8.0 kPa (60 mmHg) or SaO2 at 88%, in the presence of signs of pulmonary hypertension, peripheral edema, suspected congestive heart failure , or polycythemia (hematocrit > 55%). NIV ventilatory support is sometimes used in patients with stable, very severe COPD. NIV may be considered in a selected group of patients, especially those with severe daytime hypercapnia and recent hospitalizations, despite conflicting evidence regarding its effectiveness. In patients with COPD and obstructive sleep apnea, continuous positive airway pressure is indicated. Interventional Bronchoscopy and Surgery In selected patients with heterogeneous or homogeneous emphysema and significant hyperinflammation refractory to optimization of medical care, surgical and bronchoscopic types of lung volume reduction (eg, endobronchial one-way valves or pulmonary rings) may be considered. In selected patients with large bullae, surgical bullectomy may be offered. In selected patients with extremely severe COPD and no relevant contraindications, lung transplantation may be considered. Choosing bronchoscopic pulmonary reduction or LVRS to treat hyperinflammation in an emphysematous patient depends on a number of factors, which include: the extent and nature of pulmonary emphysema detected on HR CT; the presence of interlobar collateral ventilation is measured by fracture integrity on HR CT or physiological assessment (endoscopic balloon occlusion and flow assessment); local assessment when performing the procedure; patient and performer preferences. An algorithm depicting various activities based on radiological and physiological features is shown in Figure 4. Rice. 4. Bronchoscopic interventional and surgical methods for the treatment of COPD Figure 4. Interventional bronchoscopic and surgical treatments for COPD Criteria for referral for lung transplantation include COPD with progressive disease, not suitable for endoscopic or surgical lung volume reduction, have a score of 5 to 6, Pco2 > 50 mm Hg. Art. or 6.6 kPa and/or Pao2<60 мм РТ. ст. или 8 кПа, а ОФВ1 <25% по прогнозам. Рекомендуемые критерии включения включать одно из следующего: индекс BODE index>7, FEV1<15-20%, прогнозирует, три или более тяжелых обострений в предыдущем году, одно тяжелое обострение с острой гиперкапнической дыхательной недостаточности или умеренной до тяжелой легочной гипертензии. Ключевые моменты для использования Не-Фармакологического лечения приведены в таблице S9 в дополнительном приложении. Мониторинг и последующее наблюдение Регулярное медицинское наблюдение за пациентами ХОБЛ имеет важное значение. Симптомов, обострений и объективные оценки ограничения воздушного потока должны быть проверены, чтобы определить, когда необходимо изменения тактики ведения и выявления каких-либо осложнений и/или сопутствующих заболеваний, которые могут развиваться. Для того, чтобы скорректировать терапию соответствующим образом, так как болезнь прогрессирует, каждое последующее посещение должно включать в себя обсуждение актуального терапевтического режима. Симптомы, которые указывают на ухудшение или развитие другого, сопутствующие заболевания должны быть обследованы и пролечены. Tactics for exacerbations

Key points Exacerbation of COPD is an acute exacerbation of respiratory symptoms that leads to additional therapy. Exacerbations can be caused by several factors. The most common causes are respiratory tract infections. The goal for treating exacerbations is to minimize the negative effects of the current exacerbation and prevent subsequent events. Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are recommended as initial bronchodilators for the treatment of exacerbations. Maintenance therapy with long-acting bronchodilators should be started as soon as possible before hospital discharge. Systemic corticosteroids improve pulmonary function (FEV1), oxygenation, and reduce recovery time and length of hospitalization. Antibiotics, when indicated, shorten recovery time, reduce the risk of early relapses, treatment failure, and length of hospitalization. Methylxanthines are not recommended due to side effects. Non-invasive mandatory ventilation should be the first mode of ventilation used to treat acute respiratory failure. After an exacerbation, appropriate measures to prevent exacerbation should begin

Management of Exacerbations

Key Points An exacerbation of COPD is an acute worsening of respiratory symptoms that results in additional Exacerbations can be precipitated by several factors. The most common causes are respiratory tract Methylxanthines are not recommended due to side Non-invasive mechanical ventilation should be the first mode of ventilation used to treat acute respiratory Following an exacerbation, appropriate measures for exacerbation prevention should be initiated. The goal for treatment of exacerbations is to minimize the negative impact of the current exacerbation and to prevent subsequent Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are recommended as the initial bronchodilators to treat an acute Maintenance therapy with long-acting bronchodilators should be initiated as soon as possible before hospital Systemic corticosteroids improve lung function (FEV1), oxygenation and shorten recovery time and hospitalizationAntibiotics, when indicated, shorten recovery time, reduce the risk of early relapse, treatment failure, and hospitalization

Exacerbations are important events in the management of COPD because they negatively impact health status, hospitalization and readmission rates, and disease progression. Exacerbations of COPD are a collection of events usually associated with increased inflammation of the airways, increased mucus production and the formation of gas traps. Increased shortness of breath is the main symptom of exacerbation. Other symptoms include increased sputum, pus, and volume, along with increased coughing and wheezing. As comorbidities are common in patients with COPD, exacerbations must be differentiated from acute coronary syndrome, worsening congestive heart failure, pulmonary embolism, and pneumonia. Exacerbations of COPD are classified as: Mild (treated with short-acting bronchodilators, SABDs only), Moderate (treated with SABDs plus antibiotics and/or oral corticosteroids) or Severe (patient requires hospitalization or emergency room visit). Severe exacerbations may be associated with acute respiratory failure. Exacerbations are primarily caused by respiratory viral infections, although bacterial infections and environmental factors may also initiate and/or intensify these events. Exacerbations may be associated with increased sputum production and, if purulent, the causative bacteria may be found in the sputum. Some evidence supports the concept that eosinophils are elevated in the airways, lungs, and blood in a significant proportion of patients with COPD. Exacerbations are associated with increased sputum or blood eosinophils may be more responsive to systemic steroids although more prospective data are needed.243 Symptoms typically last 7 to 10 days during the exacerbation period, but some events may last longer. Within 8 weeks, 20% of patients had not recovered to their pre-exacerbation state. Exacerbations of COPD increase sensitivity to additional events. Patients with COPD who experience frequent exacerbations (defined as ≥ 2 exacerbations per year) have poorer health outcomes and mortality than patients with less frequent exacerbations. Other factors associated with increased risk of exacerbations and/or severity of exacerbations include an increased pulmonary artery to aortic cross-sectional size ratio (ie, ratio >1), a greater percentage of emphysema or airway wall thickness measured by chest CT, and the presence of chronic bronchitis . Treatment Options Setting (selection) Treatment (therapy) The goals of exacerbation treatment are to minimize the negative consequences of the current exacerbation, and to prevent the development of subsequent events. Depending on the severity of the exacerbation and/or the severity of the underlying disease, the exacerbation can be carried out in an outpatient or inpatient setting. More than 80% of exacerbations are carried out in an outpatient setting with bronchodilators, corticosteroids and antibiotics. Indications for hospitalization for exacerbation of COPD are presented in Table S10 in the Supplementary Appendix. When patients with exacerbation of COPD present to the emergency room, they should be given supplemental oxygen and assessed to determine whether the exacerbation is life-threatening and requires consideration for noninvasive ventilation, intensive care, and respiratory unit admission. Long-term prognosis after hospitalization for exacerbation of COPD is poor; The five-year mortality rate is about 50%. Factors associated with poor outcome include older age, low body mass index, comorbidities (eg, cardiovascular disease or lung cancer), previous hospitalizations for COPD exacerbations, clinical severity of the exacerbation index, and the need for long-term oxygen therapy at discharge. Patients with higher prevalence and severity of respiratory symptoms, poorer quality of life, worse lung function, decreased physical performance, lower lung density, and bronchial wall thickening on CT have an increased risk of mortality after an acute exacerbation. Key points for managing all exacerbations are summarized in Table 8. Table 8. Key Points for Managing Exacerbations

Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are recommended as initial bronchodilators for the treatment of exacerbations (Evidence Level C). Systemic corticosteroids improve pulmonary function (FEV1), oxygenation, and reduce recovery time and length of hospitalization. The duration of therapy should not exceed 5-7 days (level of evidence A). Antibiotics, when indicated, can shorten recovery time, reduce the risk of early relapse, treatment failure, and length of hospitalization. The duration of therapy should be 5-7 days (level of evidence B). Methylxanthines are not recommended due to increased side effect profiles (Evidence B). NIV ( Noninvasive mechanical ventilation Noninvasive mechanical ventilation should be the first mode of ventilation used in COPD patients with acute respiratory failure who have no absolute contraindications because it improves gas exchange, reduces work of breathing and the need for intubation, reduces length of hospitalization, and improves survival (Evidence Level A).

Table 8. Key points for the management of exacerbations

Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are recommended as the initial bronchodilators to treat an acute exacerbation (Evidence C).

Systemic corticosteroids improve lung function (FEV1), oxygenation and shorten recovery time and hospitalization duration. Duration of therapy should not be more than 5-7 days (Evidence A).

Antibiotics, when indicated, can shorten recovery time, reduce the risk of earlyrelapse, treatment failure, and hospitalization duration. Duration of therapy should be 5-7 days (Evidence B).

Methylxanthines are not recommended due to increased side effect profiles (Evidence B).

NIV( Noninvasive mechanical ventilation) should be the first mode of ventilation used in COPD patients with acute respiratory failure who have no absolute contraindication because it improves gas exchange, reduces work of breathing and the need for intubation, decreaseshospitalization duration and improves survival (Evidence A).

Drug Treatment The most commonly used classes of medications for exacerbations of COPD are bronchodilators, corticosteroids, and antibiotics. Bronchodilators. Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are the initial bronchodilators recommended for the treatment of acute exacerbations. There is no significant difference in FEV1 when using metered dose inhalers (MDIs) (with or without an inhalation device) or nebulizers for agent delivery, although the latter may be a simpler route of delivery in debilitated patients. Intravenous methylxanthines are not recommended due to side effects. Glucocorticoids. Systemic corticosteroids during exacerbations of COPD reduce recovery time and improve FEV1. They also improve oxygenation, the risk of early relapse, treatment failure, 267 and length of hospital stay. The recommended dose is 40 mg of prednisolone per day for 5 days. therapy with oral prednisolone is equally effective when given intravenously. glucocorticoids may be less effective in treating exacerbations in patients with lower blood eosinophil levels. Antibiotics. The use of antibiotics during exacerbations remains controversial. Evidence supports the use of antibiotics in patients with exacerbations and increased sputum purulence. One review reported that antibiotics reduced the risk of mortality by 77%, treatment failure by 53%, and sputum purulence by 44%. Procalcitonin-targeted antibiotic treatment may reduce antibiotic exposure and side effects with the same clinical efficacy. A study in patients with exacerbations requiring mechanical ventilation (invasive or noninvasive) reported an increase in mortality and an increase in mean nosocomial pneumonia when an antibiotic was not given. Antibiotics should be prescribed to patients with acute exacerbations who have three cardinal symptoms: increased dyspnea, sputum volume, and sputum purulence; there are two cardinal symptoms if increased purulence of sputum is one of the two symptoms; or require mechanical ventilation (invasive or non-invasive). The recommended duration of antibacterial therapy is 5-7 days. The choice of antibiotic should be based on the local pattern of bacterial resistance. Usually the initial empirical treatment is aminopenicillin with clavulanic acid, macrolides or tetracycline. In patients with frequent exacerbations, severe airflow limitation, and/or exacerbations requiring mechanical ventilation, cultures of sputum or other lung materials are performed to identify the presence of resistant pathogens. The route of administration depends on the patient's ability to eat and the pharmacokinetics of the antibiotics. Respiratory Support Oxygen therapy. Supplemental oxygen should be titrated to improve hypoxemia with a target saturation of 88-92%. Once oxygen is started, blood gases should be checked to ensure satisfactory oxygenation without carbon dioxide retention and/or worsening acidosis. Ventilation Some patients require admission to the intensive care unit. Reception of patients with severe exacerbations to moderate level or special respiratory therapy units may be appropriate if there are adequate staff skills and equipment to manage acute respiratory failure. Non-invasive mechanical ventilation. Niv is preferred over invasive ventilation as the initial mode of ventilation for the treatment of acute respiratory failure in patients hospitalized for acute exacerbations of COPD. NIV has been studied in randomized clinical trials showing a success rate of 80-85%. Mortality and intubation rates are reduced with NIV. Invasive mechanical ventilation. Indications for invasive mechanical ventilation during an exacerbation include failure to respond to initial NIV administration. Patients who do not respond to noninvasive ventilation as initial therapy and receive invasive ventilation as subsequent resuscitation therapy have increased morbidity, length of hospitalization, and increased mortality. Hospital Discharges and Follow-Up Failure to evaluate spirometry and arterial blood gas analysis were associated with readmission and mortality. Mortality is associated with the patient's age, the presence of severe respiratory failure, the need for respiratory support, and comorbidities, including anxiety and depression. A set of interventions at hospital discharge and includes education, optimization of drug treatment, monitoring and correction of inhaler technique, assessment and optimal management of concomitant diseases, early rehabilitation, telemonitoring and constant patient contact were studied. There is sufficient evidence that they affect readmission rates, short-term urgency, or cost-effectiveness. Early follow-up during follow-up<30 дней) после выписки следует проводить, когда это возможно и было связано с менее обострения, связанные с повторными госпитализации. Раннее наблюдение позволяет оценить терапию и возможность вносить изменения в терапии. Пациенты, не получающие раннее наблюдение показали рост 90-дневной смертности. Дополнительное наблюдение в течении трех месяцев рекомендуется чтобы обеспечить возврат в стабильное состояние и оценку симптомов пациента, функции легких (с помощью спирографии), и при возможности оценки прогноза через несколько шкал, таких как BODE. Оценку наличия и ведения сопутствующих заболеваний, также должны быть приняты (Таблица S11 в дополнительном приложении). Профилактика обострений После обострения, меры по недопущению дальнейшего обострения должна быть начата (табл. S12 в дополнительном приложении). COPD and related diseases

Key Points COPD often coexists with other diseases (comorbidities) that may significantly impact patient outcome. The presence of comorbidities should not alter COPD treatment and comorbidities should be treated per usual standards regardless of the presence of COPD. When COPD is part of a multi-morbidity care plan, attention should be directed to ensure simplicity of treatment and minimize polypharmacy .

COPD is often combined with other diseases (comorbidity), which can have a significant impact on the prognosis. Some occur independently of COPD, while others may be causally related to common risk factors, or one disease increases the risk or severity of others. Management of a patient with COPD should include identification and treatment of his concomitant diseases, the most common in COPD are listed below. Cardiovascular diseases Heart failure The prevalence of systolic or diastolic heart failure in patients with COPD ranges from 20 to 70%. Undiagnosed heart failure may mimic or accompany exacerbations of COPD; in 40% of patients with COPD who are mechanically ventilated because hypercapnic respiratory failure indicates left ventricular dysfunction. Treatment with ß1-blockers improves survival in chronic heart failure and is recommended. Selective ß1 – blockers should be used. Cardiac ischemia There is an increased risk of myocardial damage in patients with concomitant coronary artery disease who have exacerbations of COPD. Patients who demonstrate abnormal cardiac troponins have an increased risk of adverse outcomes, including short-term (30 days) and long-term mortality. Arrhythmias Cardiac arrhythmias are common in COPD and vice versa. Atrial fibrillation is common and is directly related to FEV1. Bronchodilators have been previously described as potentially pro-arrhythmic agents; however, available data suggest a generally acceptable safety profile for long-acting beta2-agonists, anticholinergics (and inhaled corticosteroids). Peripheral vascular disease In a large cohort of patients with COPD of all severity levels, 8.8% were diagnosed with peripheral artery disease (PAD), which was higher than in the non-COPD control group (1.8%). In COPD patients with PAD have been reported to have worse functional capacity and poorer health status than those without PAD. Hypertension Arterial hypertension is the most common comorbidity in COPD and may have implications for prognosis. Osteoporosis Osteoporosis is most often associated with emphysema, decreased body mass index and low fat mass. Low bone mineral density and fractures are common in patients with COPD even after adjustment for steroid dosage, age, pack-years of smoking, smoking history, and exacerbations. An association between inhaled corticosteroids and fractures has been found in pharmacoepidemiological studies. Systemic corticosteroids significantly increase the risk of osteoporosis. Anxiety and depression Anxiety and depression are both associated with poor prognosis. COPD and lung cancer The link between emphysema and lung cancer is stronger than that between airflow restriction and lung cancer. Old age and long history of smoking increases the risk. 2 low-dose chest computed tomography (LDCT) studies showed improved survival in individuals aged 55–74 years who were smokers or those who had quit smoking within the previous 15 years with a history of smoking at least 30 package – years. LDCT is now recommended in the US for patients meeting these demographics; however, this is not a worldwide practice. Metabolic syndrome and diabetes mellitus Metabolic syndrome and diabetes mellitus are more common in COPD and the latter is likely to influence prognosis. The prevalence of metabolic syndrome is more than 30%. Gastroesophageal reflux Gastroesophageal reflux is an independent risk factor for exacerbations and is associated with poorer health status. Bronchiectasis Bronchiectasis is associated with longer duration of OSA exacerbations and increased mortality. Obstructive Sleep Apnea(Obstructive Sleep Apnea OSA) Patients with “overlap syndrome” (COPD and OSA) have a worse prognosis than COPD or OSA. Apnea events in patients with OSA and COPD have more profound hypoxemia and cardiac arrhythmias and are more likely to develop daytime pulmonary hypertension than in patients with isolated OSA or COPD alone. Description of levels of evidence Supplementary Appendices Table C1: Description of levels of evidence Table C2: Vaccination in stable COPD Table S3: Commonly Used Support Medications for COPD Table S4: Other Pharmacological Treatments Table S5: Pulmonary Rehabilitation, Self-Management, and Integrated Care for COPD Table S6: End-of-Life Palliative and Hospice Care for COPD Table S7: Oxygen Therapy and Ventilation for Stable COPD COPD Table S8: Interventional Therapies for Stable COPD Figure S1: Treatment Goals for Stable COPD Table S9: Key Points for Using Non-Pharmacological Treatments Table S10 Potential Indications for Admission Table S11: Discharge Criteria and Recommendations for Follow-up Table S12: Interventions to Reduce frequency of exacerbations of COPD Additional Files

• Supplementary Appendix

Tables and figures Files in this Data Supplement: Supplementary Appendix – Table S1: Description of levels of evidence Table S2: Vaccination for stable COPD Table S3: Commonly used maintenance medications in COPD Table S4: Other pharmacologic treatments Table S5: Pulmonary rehabilitation, self-management and integrative care in COPD Table S6: Palliative care, end of life and hospice care in COPD Table S7: Oxygen therapy and ventilatory support in stable COPD Table S8: Interventional therapy in stable COPD Figure S1: Goals for treatment of stable COPD Table S9: Key points for the use of non- pharmacologic treatments Table S10: Potential indications for hospitalization assessment Table S11: Discharge criteria and recommendations for follow-up Table S12: Interventions that reduce the frequency of COPD exacerbations Table S1. Description of levels of evidence

Category of evidence	Sources of evidence	Definitions
A	Randomized controlled trials (RCTs) RCTs Most evidence of high quality without any significant limitations or bias	Evidence for endpoints of well-designed RCTs that provide consistent conclusions in the population for which recommendations are made without important limitations Requires high quality evidence;; 2 clinical trials involving a significant number of subjects, or one high-quality RCT involving a significant number of patients without any bias
IN	Randomized controlled trials (RCTs) RCTs with important limitations Limited body of evidence	Evidence from randomized clinical trials that include only a limited number of patients, post-hospital or subgroup analyzes of RCTs or meta-analyses of RCTs Also applies when there are multiple RCTs, or important limitations are apparent (methodological shortcomings, small numbers, short duration, samples in a population that differs from target population and recommendations, or results are somewhat inconsistent
C	Non-randomized studies Observational studies	Evidence from uncontrolled or non-randomized studies or from observational studies
D	Panel Judgment Consensus	The decision panel is considered by consensus to provide valuable guidance but the clinical literature on the subject is insufficient. Panel consensus is based on clinical experience or knowledge that does not meet the above criteria

Table S1. Description of levels of evidence

Evidence Sources of evidence Definition category
A	Randomized controlled Evidence is from endpoints of well- trials (RCTs) designed RCTs that provide consistent findings in the population for which the Rich body of high quality recommendation is made without any evidence without any important limitations. significant limitation or bias Requires high quality evidence from ;; 2 clinical trials involving a substantial number of subjects, or a single high quality RCT involving substantial numbers of patients without any bias.
V	Randomized controlled Evidence is from RCTs that include only a trials (RCTs) with important limited number of patients, post hoc or limitations subgroup analyzes of RCTs or meta-analyses of RCTs. Limited body of Evidence Also pertains when few RCTs exist, or important limitations are evident (methodological flaws, small numbers, short duration, undertaken in a population that differs from the target population of the recommendation, or the results are somewhat inconsistent).
C	Non-randomized trials Evidence is from outcomes of uncontrolled or non-randomized trials or from Observational studies observational studies.
D	Panel consensus judgment Provision of guidance is considered valuable
	but clinical literature addressing the subject
	is insufficient.
	Panel consensus is based on clinical
	experience or knowledge that does not
	meet the above stated criteria.

Table S2. Vaccination for stable COPD Table S2. Vaccination for stable COPD

lnfluenza vaccination reduces serious illness and death in COPD patients (Evidence IN). The 23-valent pneumococcal polysaccharide vaccine (PPSV23) reduces the incidence of community-acquired pneumonia in COPD patients aged< 65 years with an FEV1< 40% predicted and in those with comorbidities (EvidenceIN). ln the general population of adults;; 65 years the 13-valent conjugated pneumococcal vaccine (PCV13) reduces bacteremia and serious invasive pneumococcal disease (Evidence IN).

Table C3. Commonly used support medications for COPD Table S3. Commonly used maintenance medications in COPD
(version 2011)
Table S4. Other Pharmacological Treatments Table S4. Other pharmacological treatments

Alpha-1 antitrypsin augmentation therapy

lntravenous augmentation therapy may slow the progression of emphysema ( EvidenceIN).

Antitussives

There is no evidence of benefit of antitussives in patients with COPD ( EvidenceC).

Vasodilators

Vasodilators do not improve outcomes and may worsen oxygenation ( EvidenceIN).

TableS5. Pulmonary rehabilitation, self-management and comprehensive care for COPD

Pulmonary rehabilitation Pulmonary rehabilitation improves dyspnea, health status, and exercise capacity in stable patients ( Level of evidence A). Pulmonary rehabilitation reduces hospitalizations in patients with a recent exacerbation (:5 4 weeks before hospitalization) (level of evidence B)). Education and self-government Education by itself is not effective ( level of evidence C). Self-management with communication with a doctor improves health status and reduces hospitalizations and emergency department visits ( proof B). Programslntegrated care lntegrated care and telemedicine have no benefit at this time (Level of Evidence B).

Table S5. Pulmonary rehabilitation, self-management and integrative care in COPD

Pulmonary rehabilitation

Pulmonary rehabilitation improves dyspnea, health status and exercise tolerance in stable patients ( EvidenceA). Pulmonary rehabilitation reduces hospitalizations in patients with recent exacerbation (:5 4 weeks from prior hospitalization) ( EvidenceIN).

Education and self-management

Education alone is not effective ( EvidenceC). Self-management intervention with communication with a health care professional improves health status and decreases hospitalizations and emergency department visits ( EvidenceIN).

lntegrated careprograms

lntegrated care and telehealth have no benefit at this time ( EvidenceIN).

TableS6. Palliative care at the end of life and hospice care for COPD Table S6. Palliative care, end of life and hospice care in COPD

Opiates, neuromuscular electrical stimulation (NMES), oxygen and fans blowing air onto the face can relieve breathlessness (Evidence C). ln malnourished patients, nutritional supplementation may improve respiratory muscle strength and overall health status (EvidenceIN). Fatigue can be improved by self-management education, pulmonary rehabilitation, nutritional support and mind-body interventions (Evidence B).

TableS7. Oxygen therapy and mechanical ventilation in stable COPD

Oxygen therapy Long-term oxygen supplementation improves survival in patients with severe chronic arterial hypoxemia at rest ( evidence A). In patients with stable COPD and moderate resting or exercise-induced arterial desaturation, administration of continuous oxygen therapy does not prolong time to death or first hospitalization or provide sustained benefits in health status, pulmonary function, and 6-minute walking distance ( evidence A). Oxygenation at rest at sea level does not exclude the development of severe hypoxemia when traveling by air ( level of evidence C). mechanical ventilation NPPV may improve hospitalization survival in selected patients after a recent hospitalization, especially in those with severe persistent daytime hypercapnia (PaCO2 ;; 52 mm Hg) ( evidence B).

Table S7. Oxygen therapy and ventilatory support in stable COPD

Oxygentherapy

The long-term administration of oxygen survival increases in patients with severe chronic resting arterial hypoxemia ( EvidenceA). ln patients with stable COPD and moderate resting or exercise-induced arterial desaturation, prescription of long-term oxygen does not lengthen time to death or first hospitalization or provide sustained benefit in health status, lung function and 6-minute walk distance ( EvidenceA). Resting oxygenation at sea level does not exclude the development of severe hypoxemia when traveling by air ( EvidenceC).

Ventilatory support

NPPV may improve hospitalization-free survival in selected patients after recent hospitalization, particularly in those with pronounced daytime persistent hypercapnia (PaCO2 ;; 52 mmHg) ( EvidenceIN).

Table S8. Surgical therapy for stable COPD

Surgeries to reduce lung capacity Light volume reduction surgery improves survival in patients with severe upper lobe emphysema and low post-rehabilitation exercise capacity (level of evidence A). Bullectomy In some patients, bullectomy is associated with decreased shortness of breath, improved lung function, and improved exercise capacity ( level of evidence C). Transplantation In properly selected patients with very severe COPD, lung transplantation improves quality of life and functional capacity ( level of evidence C). Bronchoscopic interventions In selected patients with severe emphysema, bronchoscopic interventions reduce end-tidal lung volume and improve exercise capacity, health status, and lung function at 6–12 months after treatment. Endobronchial valves ( level of evidence B); lung rings ( level of evidence B).

Table S8. Interventional therapy in stable COPD

Lung volumereduction surgery

Lung volume reduction surgery improves survival in severe emphysema patients with upper-lobe emphysema and low post-rehabilitation exercise capacity ( EvidenceA).

Bullectomy

ln selected patients bullectomy is associated with decreased dyspnea, improved lung function and exercise tolerance ( EvidenceC).

Transplantation

ln appropriately selected patients with very severe COPD, lung transplantation improves quality of life and functional capacity ( EvidenceC).

Bronchoscopic interventions

ln select patients with advanced emphysema, bronchoscopic interventions reduce end- expiratory lung volume and improve exercise tolerance, health status and lung function at 6-12 months following Endobronchial valves ( EvidenceIN); Lung coils ( EvidenceIN).

Rice.S1. Treatment goals for stable COPD
Figure S1. Goals for treatment of stable COPD
TableS9. Key Points for Using Non-Pharmacological Treatments

Education, self-management and pulmonary rehabilitation Education increases patient knowledge, but there is no evidence that education itself changes patient behavior. Education in self-management with the support of a case manager with or without a written action plan is recommended to prevent exacerbations of complications such as hospitalization ( proof B). Rehabilitation is indicated for all patients with relevant symptoms and/or high risk of exacerbation and is the most effective intervention to improve physical performance and health status (level of evidence A). Physical activity is a strong predictor of mortality ( level of evidence A). Patients should be encouraged to increase their level of physical activity. Vaccination Influenza vaccination is recommended for all patients with COPD ( level of evidence A). Pneumococcal vaccination: PCV13 and PPSV23 is recommended for all patients >65 years of age and in younger patients with serious underlying medical conditions, including chronic heart disease or lung disease (level evidence B). Nutrition Nutritional supplementation is being considered in malnourished patients with COPD ( Level of evidence B). End of life and palliative care All physicians caring for patients with COPD should be aware of the effectiveness of palliative approaches to control symptoms ( level of evidenceD). End of life care should include discussions with patients and their families about their views on resuscitation and policy preferences ( level of evidenceD). Treatment of hypoxemia In patients with severe resting hypoxemia, long-term oxygen therapy has been shown to reduce mortality ( level of evidence, A). In patients with stable COPD and moderate desaturation at rest or with exercise, administration of long-term oxygen therapy does not prolong time to death or first hospitalization or provide sustained improvements in quality of life, pulmonary function, and 6-minute walking distance ( evidence A). Oxygenation at rest at sea level does not exclude the development of severe hypoxemia during air travel ( level of evidence C). Treatment of hypercapnia Nlv should be the first mode of ventilation used in COPD patients with acute respiratory failure because it improves gas exchange, reduces the need for intubation, reduces length of hospitalization and improves survival ( level of evidence A). In patients with severe chronic hypercapnia and a history of hospitalization with acute respiratory failure, prolonged noninvasive ventilation may be considered ( proof B). Surgical bronchoscopy and surgery Surgery to reduce lung volume improves pulmonary function, exercise tolerance and quality of life in individual patients with upper lobe emphysema and survival in a subgroup with upper lobe emphysema and low rehabilitation physical performance ( level of evidence A). In selected patients with severe emphysema, bronchoscopic interventions reduce end-expiratory lung volume and improve exercise capacity, quality of life, and pulmonary function for 6-12 months after endobronchial valve treatment ( evidence B) or pulmonary rings ( proof B). In selected patients with large bullae, surgical bullectomy may be considered ( evidence C). In patients with severe COPD (progressive disease, on an ODE scale with a score of 7 to 10, and not candidates for surgical lung debulking), lung transplantation may be considered for referral with at least one of the following: (1) A history of hospitalizations for an exacerbation associated with acute hypercapnia (Pco 2> 50 mm Hg); (2) pulmonary hypertension and/or cor pulmonale despite oxygen therapy; or (3) FEV1<20% и < 20% или равномерное распределение эмфиземы легких (level of evidence C).

Table S9. Key points for the use of non-pharmacologic treatments

Educationself-management and pulmonary rehabilitation

Education improves patient’s knowledge but there is no evidence that education alone changes patient Education in self-management with the support of a case manager with or without a written action plan is recommended for prevention of exacerbation complications such as hospitalization ( EvidenceIN). Rehabilitation is indicated in all patients with relevant symptoms and/or a high risk for exacerbation and is the most effective intervention to improve exercise capacity and health status ( EvidenceA). Physical activity is a strong predictor of mortality ( EvidenceA). Patients should be encouraged to increase the level of physical

Vaccination

lnfluenza vaccination is recommended for all patients with COPD ( Evidence A). Pneumococcal vaccination: the PCV13 and PPSV23 are recommended for all patients > 65 years of age, and in younger patients with significant comorbidities including chronic heart or lung disease ( EvidenceIN).

Nutrition

Consider nutritional supplementation in malnourished patients with COPD ( Evidence B).

End of life and palliative care

All clinicians managing patients with COPD should be aware of the effectiveness of palliative approaches to control symptoms ( EvidenceD). End of life care should include discussions with patients and their families about their views on resuscitation and advance directive preferences ( EvidenceD).

Treatment of hypoxemia

ln patients with severe resting hypoxemia long-term oxygen therapy is indicated as it has been shown to reduce mortality ( EvidenceA). ln patients with stable COPD and resting or exercise-induced moderate desaturation, prescription of long-term oxygen does not lengthen time to death or first hospitalization or provide sustained benefit in quality of life, lung function and 6-minute walk distance ( EvidenceA). Resting oxygenation at sea level does not exclude the development of severe hypoxemia when traveling by air ( EvidenceC).

Treatment of hypercapnia

NlV should be the first mode of ventilation used in COPD patients with acute respiratory failure because it improves gas exchange, reduces the need for intubation, decreases hospitalization duration and improves survival ( EvidenceA). ln patients with severe chronic hypercapnia and a history of hospitalization for acute respiratory failure, long term non-invasive ventilation may be considered ( EvidenceIN).

intervention bronchoscopyand surgery

Lung volume reduction surgery improves lung function, exercise capacity and quality of life in selected patients with upper-lobe emphysema and survival in a subset with upper lobe emphysema and low post rehabilitation exercise performance ( EvidenceA). ln select patients with advanced emphysema, bronchoscopic interventions reduces end-expiratory lung volume and improves exercise tolerance, quality of life and lung function at 6-12 months following treatment endobronchial valves ( EvidenceIN) or lung coils ( EvidenceIN). ln selected patients with a large bulla surgical bullectomy may be considered (Evidence C). ln patients with very severe COPD (progressive disease, ODE score of 7 to 10, and not candidate for lung volume reduction) lung transplantation may be considered for referral with at least one of the following: (1) history of hospitalization for exacerbation associated with acute hypercapnia (Pco2 > 50 mm Hg); (2) pulmonary hypertension and/or cor pulmonale, despite oxygen therapy; or (3) FEV1< 20% and either DLCO < 20% or homogenous distribution of emphysema (EvidenceC).

Table S10. Potential indications for hospitalization evaluation* *Local resources should be considered. Table S10. Potential indications for hospitalization assessment*

Severe symptoms such as sudden worsening of resting dyspnea, high respiratory rate, decreased oxygen saturation, confusion, drowsiness. Acute respiratory failure. Onset of new physical signs (e.g., cyanosis, peripheral edema). Failure of an exacerbation to respond to initial medical management. Presence of serious comorbidities (e.g., heart failure, newly occurring arrhythmias, etc.). lnsufficient home support.

*Local resources need to be considered. Table S11. Discharge criteria and recommendations for follow-up

Full analysis of all clinical and laboratory data. Check supportive care and understanding. Review the inhalation technique. Provide understanding of acute drug withdrawal (steroids and/or antibiotics). Assess the need to continue any oxygen therapy. Provide a plan for treatment of comorbidities and follow-up. Ensure implementation of measures: at the beginning of subsequent<4 недель, и в конце последующих < 12 недель, как указано. All clinical or additional method abnormalities must be identified. 1-4 week follow-up Assess ability to cope in his/her usual environment. Review and understand the treatment regimen. Re-evaluation of inhalation methods. Document the ability to engage in physical activity and activities of daily living. Determine comorbidity status 12-16 week follow-up Assess self-care skills in his/her usual environment. Review of understanding the treatment regimen. Re-evaluation of inhalation methods. Assess the need for long-term oxygen therapy. Document capacity for physical activity and activities of daily living. Spirometry measurement: FVD1. Document symptoms: CAT or mMRC. Determine comorbidity status.

Table S11. Discharge criteria and recommendations for follow-up

Full review of all clinical and laboratory Check maintenance therapy and Reassess inhaler Ensure understanding of withdrawal of acute medications (steroids and/or antibiotics). Assess need for continuing any oxygen Provide management plan for comorbidities and follow-up. Ensurefollow-up arrangements: early follow-up< 4 weeks, and late follow-up < 12 weeks as Аll clinical or investigational abnormalities have been 1-4 weeks follow-up Evaluability to cope in his/her usual Reviewand understanding treatment Reassessmentof inhaler Reassess need for long-term Document symptoms:CAT or Determine status of 12-16 weeks follow-up Evaluate ability to cope in his/her usual Reviewunderstanding treatment Reassessmentof inhaler Reassessneed for long-term Document the capacity to do physical activity and activities of daily Measure spirometry: FEV1. Document symptoms:CAT or Determine status of

Table S12. Activities that reduce the frequency of exacerbations of COPD Table S12. interventions that reduce the frequency of COPD exacerbations

Intervention class	intervention
Bronchodilators	LAVAs LAMAsLAVA + LAMA
Corticosteroid-containing regimens	LAVA + lCSLAVA + LAMA + lCS
Anti-inflammatory (non-steroid)	Roflumilast
Anti-infectives	VaccinesLong term macrolides
Mucoregulators	N-acetylcysteine ​​Carbocysteine
Various others	Smoking cessation Rehabilitation Lung volume reduction

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

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 “is at a certain stage of COPD,” but rather “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.

The goals of COPD treatment can be divided into 4 main groups:
Elimination of symptoms and improvement of quality of life;
Reducing future risks, etc.; prevention of exacerbations;
Slowing down the progression of the disease;
Reduced mortality.
Treatment of COPD includes pharmacological and non-pharmacological approaches. Pharmacologic treatments include bronchodilators, combinations of ICS and long-acting bronchodilators (LABAs), phosphodiesterase-4 inhibitors, theophylline, and influenza and pneumococcal vaccinations.
Nonpharmacologic options include smoking cessation, pulmonary rehabilitation, oxygen therapy, respiratory support, and surgery.
Treatment of exacerbations of COPD is discussed separately.

3.1 Conservative treatment.

To give up smoking.

Smoking cessation is recommended for all patients with COPD.

Comments. Smoking cessation is the most effective intervention and has a major impact on the progression of COPD. The usual advice from a doctor leads to smoking cessation in 7.4% of patients (2.5% more than in controls), and as a result of a 3-10-minute consultation, the smoking cessation rate reaches about 12%. With more time and more complex interventions that include skills training, problem-solving training, and psychosocial support, smoking cessation rates can reach 20-30%.
In the absence of contraindications, pharmacological treatments for tobacco dependence are recommended to support smoking cessation efforts.

Comments. Pharmacotherapy effectively supports smoking cessation efforts. First-line drugs for the treatment of tobacco dependence include varenicline, extended-release bupropion, and nicotine replacement drugs.
A combination of medical advice, support group, skills training and nicotine replacement therapy leads to cessation of smoking in 35% of cases after 1 year, while 22% remain non-smokers after 5 years.
Principles of pharmacotherapy for stable COPD.
Pharmacological classes of drugs used in the treatment of COPD are presented in Table. 5.
Table 5. Pharmacological classes of drugs used in the treatment of COPD.

Pharmacological class	Drugs
KDBA	Salbutamol Fenoterol
DDBA	Vilanterol Indacaterol Salmeterol Olodaterol Formoterol
KDAH	Ipratropium bromide
DDAH	Aclidinium bromide Glycopyrronium bromide Tiotropium bromide Umeclidinium bromide
ICS	Beclomethasone Budesonide Mometasone Fluticasone Fluticasone furoate Cyclesonide
Fixed combinations LADAH/LABA	Glycopyrronium bromide/indacaterol Tiotropium bromide/olodaterol Umeclidinium bromide/vilanterol Aclidinium bromide/formoterol
Fixed combinations of ICS/LABA	Beclomethasone/formoterol Budesonide/formoterol Fluticasone/salmeterol Fluticasone furoate/vilanterol
Phosphodiesterase-4 inhibitors	Roflumilast
Other	Theophylline

Note. SABA - short-acting β2-agonists, CDAC - short-acting anticholinergics, LABA - long-acting β2-agonists, LAAC - long-acting anticholinergics.
When prescribing pharmacotherapy, it is recommended to set the goal of achieving symptom control and reducing future risks, etc.; exacerbations of COPD and mortality (Appendix G5).

Comments. The decision to continue or terminate treatment is recommended to be made based on reducing future risks (exacerbations). This is because it is not known how a drug's ability to improve lung function or reduce symptoms correlates with its ability to reduce the risk of exacerbations of COPD. To date, there is no convincing evidence that any specific pharmacotherapy slows disease progression (as assessed by the mean rate of decline in trough FEV1) or reduces mortality, although preliminary data suggesting such effects have been published.
Bronchodilators.
Bronchodilators include β2-agonists and anticholinergic drugs, including short-acting (duration of effect 3-6 hours) and long-acting (duration of effect 12-24 hours) drugs.
It is recommended that all patients with COPD be prescribed a short-acting bronchodilator for use as needed.
Strength of recommendation: A (level of evidence: 1).
Comments. The use of short-acting bronchodilators as needed is also possible in patients receiving treatment with LABD. At the same time, the regular use of high doses of short-acting bronchodilators (including through a nebulizer) in patients receiving LABD is not justified and should be used only in the most difficult cases. In such situations, it is necessary to fully evaluate the need for the use of LABD and the patient's ability to perform inhalations correctly.
β2-agonists.
For the treatment of COPD, the following long-acting β2-agonists (LABAs) are recommended: formoterol, salmeterol, indacaterol, olodaterol (Appendix G6).
Strength of recommendation: A (level of evidence: 1).
Comments. In terms of their effect on FEV1 and shortness of breath, indacaterol and olodaterol are at least as good as formoterol, salmeterol and tiotropium bromide. In terms of their effect on the risk of moderate/severe exacerbations, LABAs (indacaterol, salmeterol) are inferior to tiotropium bromide.
When treating patients with COPD with concomitant cardiovascular diseases, it is recommended to assess the risk of developing cardiovascular complications before prescribing a LABA.

Comments. Activation of cardiac β-adrenergic receptors by β2-agonists can presumably cause ischemia, heart failure, arrhythmias, and also increase the risk of sudden death. However, in controlled clinical studies in patients with COPD, there was no evidence of an increase in the incidence of arrhythmias, cardiovascular or overall mortality with the use of β2-agonists.
In the treatment of COPD, unlike asthma, LABAs can be used as monotherapy (without ICS).
Anticholinergic drugs.
For the treatment of COPD, it is recommended to use the following long-acting anticholinergics (LAAs): tiotropium bromide, aclidinium bromide, glycopyrronium bromide, umeclidinium bromide (Appendix D6).
Strength of recommendation: A (level of evidence: 1).
Comments. Tiotropium bromide has the largest evidence base among the DDACs. Tiotropium bromide increases pulmonary function, relieves symptoms, improves quality of life, and reduces the risk of exacerbations of COPD.
Aclidinium bromide and glycopyrronium bromide improve pulmonary function, quality of life and reduce the need for rescue medications. In studies of up to 1 year, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide reduced the risk of exacerbations of COPD, but long-term studies of more than 1 year similar to those of tiotropium bromide have not been conducted to date.
Inhaled anticholinergics are generally well tolerated, and adverse events (AEs) with their use are relatively rare.
In patients with COPD and concomitant cardiovascular diseases, the use of LAMA is recommended.
Strength of recommendation: A (level of evidence: 1).
Comments. While short-acting anticholinergics (SAAs) have been suspected of causing cardiac AEs, there have been no reports of an increased incidence of cardiac AEs with SAAs. In the 4-year UPLIFT study, patients treated with tiotropium bromide had significantly fewer cardiovascular events and overall mortality than those in the placebo group. In the TIOSPIR trial (median treatment duration 2.3 years), tiotropium bromide liquid inhaler was found to be highly safe, with no difference compared with tiotropium bromide dry powder inhaler in terms of mortality, serious cardiac AEs, and exacerbations of COPD.
Combinations of bronchodilators.
It is recommended to combine bronchodilators with different mechanisms of action in order to achieve greater bronchodilation and relieve symptoms.
Strength of recommendation: A (level of evidence: 1).
Comments. For example, the combination of CDAC with a SABA or LABA improves FEV1 to a greater extent than either single component. A SABA or LABA may be given in combination with a LAMA if LAMA monotherapy does not provide sufficient symptom relief.
For the treatment of COPD, the use of fixed combinations of LAMA/LABA is recommended: glycopyrronium bromide/indacaterol, tiotropium bromide/olodaterol, umeclidinium bromide/vilanterol, aclidinium bromide/formoterol.
Strength of recommendation: A (level of evidence: 1).
Comments. These combinations showed an advantage over placebo and their monocomponents in terms of their effect on minimum FEV1, shortness of breath and quality of life, without being inferior to them in terms of safety. When compared with tiotropium bromide, all LAMA/LABA combinations showed superior effects on pulmonary function and quality of life. In terms of the effect on dyspnea, no benefit was demonstrated for the combination of umeclidinium bromide/vilanterol, and in terms of the effect on PHI, only tiotropium bromide/olodaterol was significantly superior to tiotropium bromide monotherapy.
At the same time, LAMA/LABA combinations have not yet demonstrated any advantages over tiotropium bromide monotherapy in terms of their effect on the risk of moderate/severe exacerbations of COPD.
Inhaled glucocorticosteroids and their combinations with β2-adrenergic agonists.
ICS is recommended to be prescribed only in addition to ongoing LABD therapy in patients with COPD with a history of asthma and with blood eosinophilia (the content of eosinophils in the blood outside of an exacerbation is more than 300 cells in 1 μl).
Level of strength of recommendation B (level of evidence – 1).
Comments. In asthma, the therapeutic and undesirable effects of ICS depend on the dose used, however, in COPD there is no such dose dependence, and in long-term studies only medium and high doses of ICS were used. The response of patients with COPD to treatment with inhaled corticosteroids cannot be predicted based on the response to treatment with oral corticosteroids, the results of a bronchodilation test, or the presence of bronchial hyperresponsiveness.
In patients with COPD and frequent exacerbations (2 or more moderate exacerbations within 1 year or at least 1 severe exacerbation requiring hospitalization), ICS is also recommended in addition to LABD.
Level of strength of recommendation B (level of evidence – 1).
Comments. Long-term (6 months) treatment with ICS and ICS/LABA combinations reduces the frequency of exacerbations of COPD and improves the quality of life of patients.
ICS can be used as part of either double (LABA/ICS) or triple (LAMA/LABA/ICS) therapy. Triple therapy has been studied in studies where the addition of an ICS/LABA combination to tiotropium bromide treatment resulted in improvements in pulmonary function, quality of life, and an additional reduction in the incidence of exacerbations, especially severe exacerbations. However, triple therapy requires further study in longer studies.
In patients with COPD at high risk of exacerbations and without blood eosinophilia, it is recommended to prescribe LAMA or ICS/LABA with the same level of evidence.
Strength of recommendation: A (level of evidence: 1).
Comments. The main expected effect of prescribing ICS to patients with COPD is a reduction in the risk of exacerbations. In this regard, ICS/LABAs are not superior to LAMA (tiotropium bromide) monotherapy. Recent studies show that ICS/LABA combinations have an advantage over bronchodilators in terms of their effect on the risk of exacerbations only in patients with blood eosinophilia.
Patients with COPD with preserved pulmonary function and no history of repeated exacerbations are not recommended to use ICS.
Level of strength of recommendation B (level of evidence – 1).
Comments. Therapy with ICS and ICS/LABA combinations does not affect the rate of decline in FEV1 and mortality in COPD.
Given the risk of serious adverse effects, ICS is not recommended for initial therapy in COPD.
Level of strength of recommendation B (level of evidence – 1).
Comments. Adverse effects of ICS include oral thrush and hoarseness. There is evidence of an increased risk of pneumonia, osteoporosis and fractures with the use of ICS and ICS/LABA combinations. The risk of pneumonia in patients with COPD increases when using not only fluticasone, but also other ICS. Initiation of ICS treatment was accompanied by an increased risk of developing diabetes mellitus in patients with respiratory pathology.
Roflumilast.
Roflumilast suppresses the inflammatory response associated with COPD by inhibiting the enzyme phosphodiesterase-4 and increasing intracellular cyclic adenosine monophosphate.
Roflumilast is recommended for patients with COPD with FEV1< 50% от должного, с хроническим бронхитом и частыми обострениями, несмотря на применение ДДБД для уменьшения частоты среднетяжелых и тяжелых обострений .
Strength of recommendation: A (level of evidence: 1).
Roflumilast is not recommended for use to relieve symptoms of COPD.
Strength of recommendation: A (level of evidence: 1).
Comments. Roflumilast is not a bronchodilator, although during long-term treatment in patients receiving salmeterol or tiotropium bromide, roflumilast increases FEV1 by an additional 50–80 mL.
The effect of roflumilast on quality of life and symptoms is weak. The drug causes significant undesirable effects, typical of which are gastrointestinal disorders and headache, as well as weight loss.
Oral glucocorticosteroids.
It is recommended to avoid long-term treatment with oral corticosteroids in patients with COPD, since such treatment may worsen their long-term prognosis.

Comments. Although high-dose oral corticosteroids (equal to ≥30 mg oral prednisolone per day) improve pulmonary function in the short term, there is no data on the benefit of long-term use of oral corticosteroids in low or medium-to-high doses with a significant increase in the risk of AEs. However, this fact does not prevent the prescription of a course of oral corticosteroids during exacerbations.
Oral corticosteroids cause a number of serious undesirable effects; One of the most important in relation to COPD is steroid myopathy, the symptoms of which are muscle weakness, decreased physical activity and respiratory failure in patients with extremely severe COPD.
Theophylline.
There remains controversy regarding the exact mechanism of action of theophylline, but the drug has both bronchodilation and anti-inflammatory activity. Theophylline significantly improves pulmonary function in COPD and possibly improves respiratory muscle function, but it also increases the risk of AEs. There is evidence that low doses of theophylline (100 mg 2 times / day) statistically significantly reduce the frequency of exacerbations of COPD.
Theophylline is recommended for the treatment of COPD as adjunctive therapy in patients with severe symptoms.

Comments. The effect of theophylline on pulmonary function and symptoms in COPD is less pronounced than that of the LABAs formoterol and salmeterol.
The exact duration of action of theophylline, including modern slow-release formulations, in COPD is unknown.
When prescribing theophylline, it is recommended to monitor its concentration in the blood and adjust the dose of the drug depending on the results obtained.
Strength of recommendation: C (level of evidence: 3).
Comments. The pharmacokinetics of theophylline is characterized by interindividual differences and a tendency for drug interactions. Theophylline has a narrow therapeutic concentration range and can lead to toxicity. The most common AEs include gastric irritation, nausea, vomiting, diarrhea, increased diuresis, signs of central nervous system stimulation (headache, nervousness, anxiety, agitation) and cardiac arrhythmias.
Antibacterial drugs.
The administration of macrolides (azithromycin) in long-term therapy is recommended for patients with COPD with bronchiectasis and frequent purulent exacerbations.
Strength of recommendation: C (level of evidence: 2).
Comments. A recent meta-analysis showed that long-term treatment with macrolides (erythromycin, clarithromycin and azithromycin) in 6 studies lasting 3 to 12 months resulted in a 37% reduction in the incidence of exacerbations of COPD compared with placebo. There was an additional 21% reduction in hospitalizations. The widespread use of macrolides is limited by the risk of increasing bacterial resistance to them and side effects (hearing loss, cardiotoxicity).
Mucoactive drugs.
This group includes several substances with different mechanisms of action. The regular use of mucolytics in COPD has been studied in several studies, with conflicting results.
The administration of N-acetylcysteine ​​and carbocysteine ​​is recommended for patients with COPD with a bronchitis phenotype and frequent exacerbations, especially if ICS therapy is not performed.
Strength of recommendation: C (level of evidence: 3).
Comments. N-acetycysteine ​​and carbocysteine ​​may exhibit antioxidant properties and may reduce the number of exacerbations, but they do not improve pulmonary function or quality of life in patients with COPD.

Choosing an inhaler.

It is recommended that patients with COPD be taught the correct use of inhalers at the start of treatment and then monitor their use at subsequent visits.

Comments. A significant proportion of patients make mistakes when using inhalers. When using a metered-dose inhaler (MDI), coordination between button press and inhalation is not required, but sufficient inspiratory force is required to generate sufficient inspiratory flow. When using a metered dose aerosol inhaler (MDI), high inspiratory flow is not required, but the patient must be able to coordinate activation of the inhaler with the initiation of inspiration.
It is recommended to use spacers when prescribing MDIs to eliminate coordination problems and reduce drug deposition in the upper respiratory tract.
Strength of recommendation: A (level of evidence: 3).
In patients with severe COPD, it is recommended to give preference to a MDI (including with a spacer) or a liquid inhaler.
Strength of recommendation: A (level of evidence: 3).
Comments. This recommendation is due to the fact that in patients with severe COPD, when using DPI, the inspiratory flow is not always sufficient.
The basic principles for choosing the right inhaler are described in Appendix G7.

Treatment tactics for stable COPD.

All patients with COPD are recommended to implement non-pharmacological measures, prescribe a short-acting bronchodilator for use as needed, vaccination against influenza and pneumococcal infection, and treatment of concomitant diseases.

Comments. Non-pharmacological measures include smoking cessation, training in inhalation techniques and basic self-control, vaccination against influenza and pneumococcal disease, encouragement of physical activity, assessment of the need for long-term oxygen therapy (COT) and non-invasive ventilation (NIV).
All patients with COPD are recommended to be prescribed a LABA - a combination of LAMA/LABA or one of these drugs in monotherapy (Appendix B).
Strength of recommendation: A (level of evidence: 1).
If the patient has severe symptoms (mMRC ≥2 or CAT≥10), it is recommended to prescribe a combination of LAMA/LABA immediately after the diagnosis of COPD is made.
Strength of recommendation: A (level of evidence: 1).
Comments. Most patients with COPD consult a doctor with severe symptoms - shortness of breath and decreased exercise tolerance. The administration of a LAMA/LABA combination allows, due to maximum bronchodilation, to relieve shortness of breath, increase exercise tolerance and improve the quality of life of patients.
Initial monotherapy with one long-acting bronchodilator (LABA or LABA) is recommended for patients with mild symptoms (mMRC< 2 или САТ.
Strength of recommendation: A (level of evidence: 1).
Comments. The advantage of LAMA is that it has a more pronounced effect on the risk of exacerbations.
If symptoms persist (shortness of breath and reduced exercise tolerance) during monotherapy with a single LABA, it is recommended to intensify bronchodilator therapy - transfer to a LAMA/LABA combination (Appendix B).

Prescribing a LAMA/LABA combination instead of monotherapy is also recommended for repeated exacerbations (2 or more moderate exacerbations within 1 year or at least 1 severe exacerbation requiring hospitalization) in patients without indications of asthma and without blood eosinophilia (Appendix B).
Strength of recommendation: A (level of evidence: 2).
Comments. The combination of LAMA/LABA glycopyrronium bromide/indacaterol in the FLAME study reduced the risk of moderate/severe exacerbations of COPD more effectively than the combination of ICS/LABA (fluticasone/salmeterol) in patients with COPD with an FEV1 of 25–60% predicted and the absence of high blood eosinophilia.
If repeated exacerbations in a patient with COPD and asthma or with blood eosinophilia occur during therapy with a single LABA, then the patient is recommended to be prescribed a LABA/ICS (Appendix B).
Strength of recommendation: A (level of evidence: 2).
Comments. The criterion for blood eosinophilia is the content of eosinophils in the blood (out of exacerbation) of 300 cells in 1 μl.
If repeated exacerbations in patients with COPD with asthma or eosinophilia occur during therapy with a LAMA/LABA combination, then the patient is recommended to add ICS (Appendix B).
Strength of recommendation: A (level of evidence: 2).
Comments. The patient may also resort to triple therapy if ICS/LABA therapy is insufficiently effective, when LAMA is added to the treatment.
Triple therapy with LAMA/LABA/ICS can currently be carried out in two ways: 1) using a fixed combination of LAMA/LABA and a separate ICS inhaler; 2) using a fixed LABA/ICS combination and a separate LAMA inhaler. The choice between these methods depends on the initial therapy, compliance with various inhalers and availability of drugs.
If repeated exacerbations occur on therapy with a LAMA/LABA combination in a patient without asthma and eosinophilia or relapse of exacerbations on triple therapy (LAMA/LABA/ICS), it is recommended to clarify the COPD phenotype and prescribe phenotype-specific therapy (roflumilast, N-acetylcysteine, azithromycin, etc. ; – Appendix B) .
Strength of recommendation: B (level of evidence: 3).
It is not recommended to reduce the volume of bronchodilator therapy (in the absence of AEs) even in the case of maximum symptom relief.
Strength of recommendation level A (level of evidence – 2).
Comments. This is due to the fact that COPD is a progressive disease, so complete normalization of lung function parameters is impossible.
In patients with COPD without repeated exacerbations and with preserved pulmonary function (FEV1 50% of predicted), complete withdrawal of ICS is recommended, subject to the prescription of a LABD.
Strength of recommendation level B (level of evidence – 2).
Comments. If, in the opinion of the doctor, the patient does not need to continue treatment with ICS, or AEs have arisen from such therapy, then ICS can be discontinued without increasing the risk of exacerbations.
In patients with FEV1< 50% от должного, получающих тройную терапию, рекомендуется постепенная отмена ИГКС со ступенчатым уменьшением его дозы в течение 3 месяцев .
Strength of recommendation: A (level of evidence – 3).
Comments. FEV1 value< 50% ранее считалось фактором риска частых обострений ХОБЛ и рассматривалось как показание к назначению комбинации ИГКС/ДДБА. В настоящее время такой подход не рекомендуется, поскольку он приводит к нежелательным эффектам и неоправданным затратам , хотя в реальной практике ИГКС и комбинации ИГКС/ДДБА назначаются неоправданно часто.

3.2 Surgical treatment.

In COPD patients with upper lobe emphysema and low exercise tolerance, lung volume reduction surgery is recommended.
Strength of recommendation: C (level of evidence: 3).
Comments. Lung reduction surgery is performed by removing part of the lung to reduce hyperinflation and achieve more efficient pumping of the respiratory muscles. Currently, to reduce lung volume, it is possible to use less invasive methods - occlusion of segmental bronchi using valves, special glue, etc.;
Lung transplantation is recommended for a number of patients with very severe COPD in the presence of the following indications: BODE index ≥ 7 points (BODE – B – body mass index, O – obstruction (obstruction), D – dyspnea (shortness of breath), E – exercise tolerance (exercise tolerance), FEV1< 15% от должных, ≥ 3 обострений в предшествующий год, 1 обострение с развитием острой гиперкапнической дыхательной недостаточности (ОДН), среднетяжелая-тяжелая легочная гипертензия (среднее давление в легочной артерии ≥35 мм) .
Strength of recommendation: C (level of evidence: 3).
Comments. Lung transplantation can improve quality of life and functional outcomes in carefully selected patients with COPD.

3.3 Other treatments.

Long-term oxygen therapy.

One of the most severe complications of COPD, developing in its late (terminal) stages, is chronic respiratory failure (CRF). The main sign of CDN is the development of hypoxemia, etc.; decrease in oxygen content in arterial blood (PaO2).
VCT today is one of the few methods of therapy that can reduce the mortality of patients with COPD. Hypoxemia not only shortens the life of patients with COPD, but also has other significant adverse consequences: deterioration in quality of life, development of polycythemia, increased risk of cardiac arrhythmias during sleep, development and progression of pulmonary hypertension. VCT can reduce or eliminate all these negative effects of hypoxemia.
Patients with COPD and chronic respiratory failure are recommended to undergo VCT (for indications, see Appendix G8).
Strength of recommendation level A (level of evidence – 1).
Comments. It should be emphasized that the presence of clinical signs of cor pulmonale suggests an earlier appointment of VCT.
Correction of hypoxemia with oxygen is the most pathophysiologically based method of treating chronic renal failure. Unlike a number of emergency conditions (pneumonia, pulmonary edema, trauma), the use of oxygen in patients with chronic hypoxemia must be constant, long-term and, as a rule, carried out at home, which is why this form of therapy is called VCT.
Gas exchange parameters, on which the indications for DCT are based, are recommended to be assessed only when patients are in a stable condition, etc.; 3-4 weeks after an exacerbation of COPD.
Strength of recommendation: C (level of evidence: 3).
Comments. This is exactly the time required to restore gas exchange and oxygen transport after a period of ARF. Before prescribing VCT to patients with COPD, it is recommended to make sure that the possibilities of drug therapy have been exhausted and the maximum possible therapy does not lead to an increase in PaO2 above the limit values.
When prescribing oxygen therapy, it is recommended to strive to achieve PaO2 values ​​of 60 mm and SaO2 90%.
Strength of recommendation: C (level of evidence: 3).
VCT is not recommended for patients with COPD who continue to smoke; those who do not receive adequate drug therapy aimed at controlling the course of COPD (bronchodilators, ICS); insufficiently motivated for this type of therapy.
Strength of recommendation: C (level of evidence: 3).
Most patients with COPD are recommended to undergo VCT for at least 15 hours a day with maximum breaks between sessions not exceeding 2 hours in a row, with an oxygen flow of 1-2 l/min.
Strength of recommendation: B (level of evidence: 2).

Long-term home ventilation.

Hypercapnia (td; increased partial tension of carbon dioxide in arterial blood - PaCO2 ≥ 45 mm) is a marker of decreased ventilation reserve in the terminal stages of pulmonary diseases and also serves as a negative prognostic factor for patients with COPD. Nocturnal hypercapnia alters the sensitivity of the respiratory center to CO2, leading to higher PaCO2 levels during the day, which has negative consequences for the function of the heart, brain and respiratory muscles. Dysfunction of the respiratory muscles in combination with a high resistive, elastic and threshold load on the respiratory apparatus further aggravates hypercapnia in patients with COPD, thus developing a “vicious circle” that can only be broken by respiratory support (ventilation).
In patients with COPD with a stable course of CDN who do not require intensive care, it is possible to carry out long-term respiratory support on an ongoing basis at home - the so-called long-term home ventilation (LHV).
The use of DDVL in patients with COPD is accompanied by a number of positive pathophysiological effects, the main of which are improved gas exchange parameters - increased PaO2 and decreased PaCO2, improved respiratory muscle function, increased exercise tolerance, improved sleep quality, and decreased pulmonary hypertension. Recent studies have demonstrated that, with adequately selected parameters of non-invasive ventilation (NIV), a significant improvement in survival of patients with COPD complicated by hypercapnic chronic respiratory failure is possible.
DDVL is recommended for patients with COPD who meet the following criteria:
- Presence of symptoms of CDN: weakness, shortness of breath, morning headaches;
- Presence of one of the following indicators: PaCO2 55 mm, PaCO2 50-54 mm and episodes of nocturnal desaturations (SaO2< 88% в течение более 5 мин во время O2-терапии 2 л/мин), PaCO2 50-54 мм и частые госпитализации вследствие развития повторных обострений (2 и более госпитализаций за 12 мес).
Strength of recommendation: A (level of evidence: 1).