Despite the rapid development of medicine and pharmacy, chronic obstructive pulmonary disease remains an unresolved problem in modern health care.

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

According to WHO forecasts, by 2030 in the structure of mortality worldwide, COPD will take the third place. At the moment, at least 70 million inhabitants of 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.

History of the issue

Even half a century ago, significant differences were noted in the clinic and pathological anatomy in patients with bronchial obstruction. Then, in COPD, the classification looked conditional, more precisely, it was represented by only two types. The patients were divided into two groups: if the bronchitic component predominated in the clinic, then this type in COPD figuratively sounded like "blue edema" (type B), and type A was called "pink puffers" - a symbolism of the prevalence of emphysema. Figurative comparisons have survived in 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 restriction according to spirometry indicators. But such a breakdown did not take into account the severity of the clinic at a given time, the rate of deterioration in spirometry data, the risk of exacerbations, intercurrent pathology and, as a result, could not allow managing the prevention of the disease and its therapy.

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

An objective determination of the severity of the course, the type of disease are necessary for the choice of rational and adequate treatment, as well as the prevention of the disease in susceptible individuals and the progression of the disease. The following parameters are used to identify these characteristics:

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

V modern classification term " stages of COPD"Is replaced by" degrees ", but operating with the concept of staging 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 conducting spirometry, several parameters are determined, but 2 are important for making a decision: 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. Results are compared with age, weight, height, race. The severity of the flow is determined on the basis of FEV1 - this parameter forms the basis of the GOLD classification. Threshold criteria are defined for ease of use of the classification.

The lower the FEV1 score, the higher the risk of exacerbation, hospitalization, and death. In the second degree, the obstruction becomes irreversible. During an exacerbation of the disease, respiratory symptoms worsen, requiring a change in treatment. The frequency of exacerbations is different for each patient.

Clinicians noted in the course of their observations that the results of spirometry do not reflect the severity of shortness of breath, a decrease in resistance to physical activity and, as a consequence, the quality of life. After treatment of an exacerbation, when the patient notes a significant improvement in well-being, the FEV1 index may practically not change.

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

• amyotrophy;
• cachexia;
• decrease in body weight.

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 according to specially developed scales. The questionnaires (tests) are easy to execute and do not take much time. Testing is usually done before and after treatment. With their help, the severity of symptoms is assessed, general state, the quality of life.

The severity of symptoms

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

Mrc
0	I feel shortness of breath only with significant physical. load
1	I feel short of breath when accelerating, walking on a level surface, or when climbing a hill
2	Due to the fact that I feel short of breath, walking on a flat surface, I begin to walk more slowly compared to people of the same age, and if I walk the usual step on a flat surface, I feel how breathing stops
3	When I cover a distance of about 100 m, I feel that I am suffocating, or after a few minutes of a calm step
4	I cannot leave my house due to shortness of breath or suffocate when dressing / undressing

SAT
Example: I have 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		Persistent cough
I don't feel 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 compression in my chest	0 1 2 3 4 5		I feel a very strong constriction in my chest.
When I climb stairs one flight or go up, I feel short of breath.	0 1 2 3 4 5		When I go up or go up stairs one flight, I feel very short of breath
I calmly do housework	0 1 2 3 4 5		I find it very difficult to do housework
I feel confident leaving home despite my lung disease	0 1 2 3 4 5		Can't leave home with confidence due to lung disease
I have a restful and fulfilling 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 am deprived of energy
TOTAL POINT
0 — 10		Influence is negligible
11 — 20		Moderate
21 — 30		Strong
31 — 40		Very strong

Test results: CAT≥10 or MRC≥2 scale indicate significant severity of symptoms and are critical values. To assess the severity of clinical manifestations, one scale should be used, preferably CAT, since it allows the most complete assessment of the state of health. Unfortunately, Russian doctors rarely use questionnaires.

Risks and groups of COPD

When developing a risk classification for COPD, based on conditions and indicators collected from large-scale clinical research(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.

At various degrees the severity of the prognosis of the frequency of exacerbations was calculated based on the previous medical history. Risks table:

There are 3 ways to assess the risks of exacerbation:

1. Population - according to the classification of the severity of COPD based on spirometry data: at grade 3 and 4, a high risk is determined.
2. Individual history data: if in the last year there are 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. Evaluate symptoms on the CAT scale, or dyspnea on the MRC scale.
2. Look to which side of the square the result belongs to: to the left - "less symptoms", "less shortness of breath", or to the right - "more symptoms", "more shortness of breath."
3. Evaluate which side of the square (top or bottom) the result of the risks of exacerbations according to spirometry belongs to. Levels 1 and 2 indicate low risk, while levels 3 and 4 indicate high risk.
4. Indicate how many exacerbations the patient had in the last year: if 0 and 1, then the risk is low, if 2 or more, it is high.
5. Define a group.

Initial data: 19 p. according to the CAT questionnaire, according to the parameters of spirometry FEV1 - 56%, three exacerbations over the past year. The patient belongs to the category of "more symptoms" and it is necessary to define him in group B or D. According to spirometry - "low risk", but since Last year he had three exacerbations - this indicates a "high risk", therefore this patient belongs to group D. This is a group of high risk of 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"	V "Low risk" "More symptoms"	WITH "High risk" "Fewer symptoms"	D "High risk" "More symptoms"
Exacerbation rate per year	0-1	0-1	≥1-2	≥2
Hospitalizations	No	No	Yes	Yes
SAT	<10	≥10	<10	≥10
Mrc	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 provides for rational and individualized treatment. The disease progresses most easily in patients from group A: the prognosis is favorable in all respects.

COPD phenotypes

Phenotypes in COPD are a combination of clinical, diagnostic, pathomorphological signs that have formed in the process of individual development of the disease.

Phenotype identification allows for maximum optimization of the treatment regimen.

Indicators	Emphysematous type of COPD	Bronchitic type of COPD
Disease manifestation	With shortness of breath in persons from 30-40 years old	With a productive cough in people over 50
Body type	Skinny	Tendency to gain weight
Cyanosis	Not typical	Expressed strongly
Dyspnea	Significantly expressed, constant	Moderate, intermittent (aggravated during an 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
Changes in chest volume	Is increasing	Does not change
Wheezing in the lungs	No	Yes
Weakened breathing	Yes	No
Chest x-ray data	Increased airiness, small heart size, bullous changes	The heart is like a "stretched sac", strengthening of the pattern of the lungs in the root areas
Lung capacity	Increasing	Does not change
Polycythemia	Insignificant	Strongly expressed
Pulmonary hypertension at rest	Insignificant	Moderate
Lung elasticity	Significantly reduced	Normal
Pulmonary heart	Terminal stage	Developing rapidly
Pat. anatomy	Panacinar emphysema	Bronchitis, sometimes centriacinar emphysema

The assessment of biochemical parameters is carried out in the stage of exacerbation by indicators of 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 the phenotype by the level of deviation of enzymes of the antioxidant blood system":

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

The mixed phenotype of COPD - BA in modern pulmonology does not have clear criteria for classification, diagnosis and is the subject of a thorough and 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 they talk about the COPD phenotype with frequent exacerbations. Typing, determining the degree of COPD, various types of classifications and their numerous modifications set themselves important goals: to correctly diagnose, adequately treat and slow down the process.

Differentiating the differences between patients with this disease is extremely important, since both the number of exacerbations, and 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.

The classification of COPD (chronic obstructive pulmonary disease) is broad and includes a description of the most common stages of development of the disease and the variants in which it occurs. And although not all patients progress to COPD follows the same scenario and not all can distinguish 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 COPD Initiative" (in English the name sounds "Global Initiative for chronic Obstructive Lung Disease" and abbreviated to GOLD). According to her, there are four main stages, each of which is determined mainly by FEV - that is, by the volume of forced expiration in the first second:

• COPD 1 degree does not differ in special symptoms. The lumen of the bronchi is narrowed quite a bit, the air flow is also not very noticeably limited. The patient does not experience difficulties in everyday life, he experiences shortness of breath only during vigorous physical activity, and a wet cough only occasionally, most likely at night. At this stage, only a few go to the doctor, usually because of other diseases.
• COPD grade 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 release of phlegm - sometimes purulent. The patient notices that he has become less hardy, and begins to suffer from recurring respiratory diseases - from simple SARS to bronchitis and pneumonia. If the reason for going to the doctor is not suspicion of COPD, then sooner or later the patient still gets to him due to concomitant infections.
• COPD grade 3 is described as a severe stage - if the patient has enough strength, he can apply for disability and confidently wait for a certificate to be issued to him. Shortness of breath appears even with minor physical exertion - right up to climbing a flight of stairs. The patient is dizzy, darkens in the eyes. The cough appears more often, at least twice a month, becomes paroxysmal and is accompanied by chest pains. At the same time, the appearance changes - the chest expands, the veins on the neck swell, the skin changes tint either to bluish or pinkish. Body weight either decreases sharply or decreases sharply.
• Stage 4 COPD means that you can forget about any work capacity - the air flow entering the patient's lungs does not exceed thirty percent of the required volume. Any physical effort - up to changing clothes or hygiene procedures - causes shortness of breath, wheezing in the chest, dizziness. Breathing in itself is heavy, harsh. The patient has to constantly use an oxygen cylinder. In the worst cases, hospitalization is required.

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

• cough - one corresponds to the statement "no cough", five "constantly";
• sputum - one is “there is no sputum”, five is “sputum leaves 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 at the slightest exertion";
• everyday activity - from "no restrictions" to "very limited";
• leaving the house - from “confidently out of necessity” to “not even out of necessity”;
• sleep - from "good sleep" to "insomnia";
• energy - from "full of energy" to "no strength at all."

The result is determined by the calculation of points. If there are less than ten of them, the disease has almost no effect on the patient's life. Less than twenty, but more than ten - has a moderate impact. Less than thirty - has a strong impact. More than thirty - has a huge impact on life.

Also, objective indicators of the patient's condition are taken into account, which can be recorded with the help of devices. The main ones among them 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 light - up to eighty and ninety in the presence of symptoms;
• in the course of moderate severity - up to sixty and eighty;
• in severe cases - less than forty and about seventy-five.

After GOLD 2011, COPD no longer has stages. There are only grades of severity that indicate how much air enters the lungs. And the general conclusion about the patient's condition looks not as "is at a certain stage of COPD," but as "is in a certain risk group for exacerbations, adverse consequences and death due to COPD." There are four of them.

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

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

COPD phenotypes

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, which relapses for 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 disease detection is fifty or older.
• Features of the patient's appearance. The patient is distinguished by a pronounced bluish skin color, the chest is barrel-shaped, body weight usually grows due to increased appetite and may approach the border of obesity.
• The main symptom is cough, paroxysmal, with the release of copious purulent sputum.
• Infections are common because the bronchi are unable to filter out the pathogen.
• Pulmonary deformity of the heart muscle is common.

Cor pulmonale is a concomitant symptom in which the right ventricle increases 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 drawing of the lungs is enhanced.
• The diffuse capacity of the lungs - that is, the time it takes for gas molecules to enter the blood. Normally, if it decreases, then only slightly.
• Forecast. According to statistics, the bronchitic type has a higher mortality rate.

The people call the bronchitic type "blue edema" and this is a fairly accurate description - a patient with this type of COPD is usually pale blue, overweight, constantly coughing, but vigorous - shortness of breath does not strike him as much as patients with another type.

Emphysematous type:

• Cause. The cause is chronic pulmonary emphysema.
• Changes in the lungs. On fluorography, it is clearly seen that the partitions between the alveoli are destroyed and cavities filled with air are formed - bullae. With spirometry, hyperventilation is recorded - oxygen enters the lungs, but is not absorbed into the blood.
• The classic age of disease detection 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 on 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.
• Pulmonary deformity is rare, the lack of oxygen is not so pronounced.
• X-ray. The picture shows bullae and deformities of the heart.
• Diffusion capacity - obviously greatly reduced.
• Forecast. According to statistics, this type has a longer life expectancy.

The people call the emphysematous type "pink puffer" and this is also quite accurate: a patient with this type of hodl is usually thin, with an unnaturally pink skin color, constantly suffocates and prefers not to leave the house once again.

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

• With frequent exacerbations. It is placed 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. It occurs in a third of cases - with all the symptoms of COPD, the patient feels relief if he uses drugs to combat asthma. He also has asthmatic attacks.
• Early on. It is characterized by rapid progress and is due to a genetic predisposition.
• At a young age. COPD is a disease of the elderly, but it can also occur in younger people. In this case, it is, as a rule, many times more dangerous and has a high mortality rate.

Associated diseases

With COPD, the patient has a great chance to suffer not only from the obstruction itself, but also from the diseases that accompany it. Among them:

• Cardiovascular disease, from coronary artery disease to heart failure. They occur in almost half of the cases and can be explained very simply: with a lack of oxygen in the body, the cardiovascular system undergoes heavy loads: the heart moves faster, blood flows faster through the veins, and the lumen of the vessels narrows. After some time, the patient begins to notice chest pains, a beating pulse, headaches and increased shortness of breath. A third of patients with COPD who are accompanied by cardiovascular disease die from them.
• Osteoporosis. It occurs in a third of cases. Not fatal, but very unpleasant and also provoked by a lack of oxygen. Its main symptom is brittle bones. As a result, the patient's spine is bent, posture deteriorates, back and limbs hurt, night cramps in the legs and general weakness are observed. Decreases endurance, mobility of the fingers. Any fracture heals for a very long time 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. It occurs in almost half of patients. Often its dangers remain underestimated, while 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 remains constantly 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 pleasure that the patient could get out of life.
• Infections. Occurs in seventy percent of patients and causes death in a third of cases. This is explained by the fact that the lungs affected by COPD are very vulnerable to any pathogen, and it is difficult to remove inflammation in them. Moreover, any increase in sputum production is a decrease in airflow 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 deprivation and may even die from respiratory failure.
• Cancer. It is common and causes death in one in five cases. It is explained, like infection, by the vulnerability of the lungs.

In men, COPD is often accompanied by impotence, and in older people it becomes the cause of cataracts.

Diagnosis and disability

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

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

As a result, when the examination according to the plan has passed, the patient receives a diagnosis, which sounds, for example, like this: "chronic obstructive pulmonary disease of the bronchitic type, II degree of impaired bronchial patency with severe symptoms, frequent exacerbations, aggravated by osteoporosis."

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

And although COPD is not cured, the patient must do everything in his power to maintain his health at a certain level - and then both the quality and the length of his life will increase. The main thing is to remain optimistic in the process and not neglect the advice of doctors.

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

3.1 Conservative treatment.

To give up smoking.

Smoking cessation is recommended for all patients with COPD.

Comments. Quitting smoking is the most effective intervention that has a major impact on the progression of COPD. The usual doctor's advice leads to smoking cessation in 7.4% of patients (2.5% more than in the control), and as a result of a 3-10-minute consultation, the smoking cessation rate reaches about 12%. For more time and more complex interventions, including skill training, problem solving training and psychosocial support, smoking cessation rates can reach 20-30%.
In the absence of contraindications to support smoking cessation efforts, it is recommended to prescribe a pharmacological agent for the treatment of tobacco dependence.

Comments. Pharmacotherapy effectively supports smoking cessation efforts. First-line drugs for the treatment of tobacco dependence include varenicline, extended-release bupropion, and nicotine substitutes.
The combination of medical advice, support groups, skills training and nicotine replacement therapy results in 35% of smoking cessation after 1 year, while 22% remain nonsmokers 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
DBBA	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 of DDAC / DDBA	Glycopyrronium bromide / indacaterol Tiotropium bromide / olodaterol Umeclidinium bromide / vilanterol Aclidinium bromide / formoterol
Fixed combinations of IGCS / LABA	Beclomethasone / formoterol budesonide / formoterol fluticasone / salmeterol fluticasone furoate / vilanterol
Phosphodiesterase-4 inhibitors	Roflumilast
Other	Theophylline

Note. CDBA - short-acting β2-agonists, CDAH - short-acting anticholinergics, LABA - long-acting β2-agonists, DDAC - long-acting anticholinergics.
When prescribing pharmacotherapy, it is recommended to aim to achieve symptom control and reduce future risks - etc. exacerbations of COPD and mortality (Appendix D5).

Comments. The decision to continue or end treatment is recommended based on the reduction of future risks (exacerbations). This is because it is not known how the 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 conclusive evidence that any particular pharmacotherapy slows disease progression (as measured by the mean rate of decline in trough FEV1) or decreases mortality, although preliminary data have been published indicating such effects.
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.
Short-acting bronchodilators are recommended for all patients with COPD for use as needed.
Strength of recommendation A (level of evidence - 1).
Comments. The use of short-acting bronchodilators on demand is also possible in patients receiving DBD treatment. At the same time, the regular use of high doses of short-acting bronchodilators (including through a nebulizer) in patients receiving DDBD is not justified, and should be used only in the most difficult cases. In such situations, it is necessary to comprehensively assess the need for the use of DDBD and the patient's ability to properly inhale.
β2 agonists.
For the treatment of COPD, the following long-acting β2-agonists (LABA) are recommended: formoterol, salmeterol, indacaterol, olodaterol (Appendix D6).
Strength of recommendation A (level of evidence - 1).
Comments. In terms of the effect on FEV1 and dyspnea, indacaterol and olodaterol are at least as good as formoterol, salmeterol and tiotropium bromide. In terms of influence on the risk of moderate / severe exacerbations, LABA (indacaterol, salmeterol) is inferior to tiotropium bromide.
When treating patients with COPD with concomitant cardiovascular diseases, it is recommended to assess the risk of cardiovascular complications before prescribing LABA.

Comments. The activation of β-adrenergic receptors of the heart under the action of β2-agonists can presumably cause ischemia, heart failure, arrhythmias, and also increase the risk of sudden death. However, in controlled clinical trials in patients with COPD, no data have been obtained on an increase in the frequency of arrhythmias, cardiovascular or general mortality when using β2-agonists.
In the treatment of COPD, unlike AD, LABA can be used as monotherapy (without ICS).
Anticholinergic drugs.
For the treatment of COPD, it is recommended to use the following long-acting anticholinergics (DDAC): 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 DDACs. Tiotropium bromide increases lung function, relieves symptoms, improves quality of life, and reduces the risk of exacerbations of COPD.
Aclidinium bromide and glycopyrronium bromide improve lung function, quality of life, and reduce the need for emergency medications. In studies up to 1 year, aclidinium bromide, glycopyrronium bromide, and umeclidinium bromide reduced the risk of exacerbations of COPD, but long-term studies longer 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) are relatively rare with their use.
In patients with COPD and concomitant cardiovascular diseases, the use of DDAC is recommended.
Strength of recommendation A (level of evidence - 1).
Comments. A suspicion was expressed that short-acting anticholinergics (CDAHs) cause cardiac AEs; with regard to DALs, no reports of an increase in the frequency of cardiac AEs have been received. In the 4-year UPLIFT study, patients treated with tiotropium bromide had significantly fewer cardiovascular events and had less overall mortality than the placebo group. In the TIOSPIR study (median treatment duration 2.3 years), tiotropium bromide in a liquid inhaler proved to be highly safe, with no difference from tiotropium bromide in a 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 relief of symptoms.
Strength of recommendation A (level of evidence - 1).
Comments. For example, the combination of CDAH with CDBA or LABA improves FEV1 to a greater extent than any of the monocomponents. CBAA or LABA can be given in combination with DDAC if DDAC monotherapy does not provide sufficient symptom relief.
For the treatment of COPD, the use of fixed combinations of DDAC / 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 have shown an advantage over placebo and their monocomponents in terms of their effect on minimal FEV1, shortness of breath and quality of life, while not inferior to them in terms of safety. When compared with tiotropium bromide, all DDAC / LABA combinations have shown superior effects on pulmonary function and quality of life. In terms of the effect on dyspnea, an advantage was not demonstrated for the combination of umeclidinium bromide / vilanterol, and in terms of the effect on LGI, only tiotropium bromide / olodaterol was significantly superior to tiotropium bromide monotherapy.
At the same time, the combinations of LADA / LABA have not yet demonstrated advantages over monotherapy with tiotropium bromide in terms of the effect on the risk of moderate / severe exacerbations of COPD.
Inhaled glucocorticosteroids and their combinations with β2-adrenergic agonists.
It is recommended to prescribe ICS only in addition to the ongoing therapy of DDBD in patients with COPD with a history of asthma and blood eosinophilia (the content of eosinophils in the blood without exacerbation is more than 300 cells in 1 μl).
Strength of recommendation B (level of evidence - 1).
Comments. In BA, 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 ICS treatment cannot be predicted based on the response to treatment with oral corticosteroids, the results of a bronchodilator test, or the presence of bronchial hyperreactivity.
Patients with COPD and frequent exacerbations (2 or more moderate exacerbations within 1 year, or at least 1 severe exacerbation requiring hospitalization) are also recommended to prescribe ICS in addition to DDBD.
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 (LADA / LABA / ICS) therapy. Triple therapy has been studied in studies where the addition of an ICS / LABA combination to tiotropium bromide treatment resulted in improved lung function, quality of life and an additional decrease in the frequency of exacerbations, especially severe ones. However, triple therapy warrants further study in longer studies.
For patients with COPD with a high risk of exacerbations and without blood eosinophilia, it is recommended to prescribe DDAC or ICS / LABA with the same degree of evidence.
Strength of recommendation A (level of evidence - 1).
Comments. The main expected effect of prescribing ICS in patients with COPD is a decrease in the risk of exacerbations. In this respect, ICS / LABA are not superior to DDA monotherapy (tiotropium bromide). Recent studies show that ICS / LABA combinations have an advantage over bronchodilators in terms of the effect on the risk of exacerbations only in patients with blood eosinophilia.
The use of ICS is not recommended for patients with COPD with preserved lung function and no recurrent exacerbations in the anamnesis.
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 in COPD is not recommended as part of initial therapy.
Strength of recommendation B (level of evidence - 1).
Comments. Adverse effects of ICS include oral candidiasis 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 with the use of not only fluticasone, but also other ICS. The initiation of ICS treatment was accompanied by an increased risk of diabetes mellitus in patients with respiratory pathology.
Roflumilast.
Roflumilast suppresses the inflammatory response associated with COPD by inhibiting the enzyme phosphodiesterase-4 and increasing the intracellular content of 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 relieving 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 additionally increases FEV1 by 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 disturbances 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 a high dose of oral corticosteroids (equal to ≥30 mg of oral prednisolone per day) improves lung function in the short term, there are no data on the benefits of long-term use of oral corticosteroids in low or medium and high doses with a significant increase in the risk of AE. However, this fact does not interfere with the appointment with exacerbations of the course of oral corticosteroids.
Oral corticosteroids cause a number of serious undesirable effects; one of the most important for COPD is steroid myopathy, the symptoms of which are muscle weakness, decreased physical activity, and respiratory failure in patients with extremely severe COPD.
Theophylline.
Controversy remains regarding the exact mechanism of action of theophylline, but this drug has both bronchodilatory and anti-inflammatory activity. Theophylline significantly improves pulmonary function in COPD and possibly improves respiratory muscle function, but increases the risk of AE. There is evidence that low doses of theophylline (100 mg 2 r / day) statistically significantly reduce the frequency of exacerbations of COPD.
Theophylline is recommended for the treatment of COPD as an adjunctive therapy in patients with severe symptoms.

Comments. The effect of theophylline on pulmonary function and symptoms in COPD is less pronounced than for LABA formoterol and salmeterol.
The exact duration of action of theophylline, including modern slow-release drugs, is unknown in COPD.
When prescribing theophylline, it is recommended to control 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. Pharmacokinetics of theophylline is characterized by interindividual differences and a tendency to drug interactions. Theophylline has a narrow therapeutic concentration range and is capable of causing toxicity. The most common AEs include stomach irritation, nausea, vomiting, diarrhea, increased urine output, signs of central nervous system stimulation (headache, nervousness, anxiety, agitation), and cardiac arrhythmias.
Antibacterial drugs.
The appointment of macrolides (azithromycin) in the long-term therapy regimen is recommended for patients with COPD with bronchiectasis and frequent purulent exacerbations.
Strength of recommendation C (evidence level 2).
Comments. A recent meta-analysis showed that long-term treatment with macrolides (erythromycin, clarithromycin and azithromycin) in 6 studies lasting from 3 to 12 months resulted in a 37% reduction in the incidence of COPD exacerbations compared with placebo. In addition, the number of hospitalizations decreased by 21%. The widespread use of macrolides is limited by the risk of growth of bacterial resistance to them and side effects (hearing loss, cardiotoxicity).
Mucoactive drugs.
This group includes several substances with different mechanisms of action. The routine use of mucolytics for COPD has been studied in several studies with conflicting results.
The appointment of N-acetylcysteine ​​and carbocysteine ​​is recommended for patients with COPD with bronchitic phenotype and frequent exacerbations, especially if ICS therapy is not carried out.
Strength of recommendation C (level of evidence 3).
Comments. N-acetycysteine ​​and carbocisteine ​​may have antioxidant properties and may reduce exacerbations, but they do not improve lung function and quality of life in COPD patients.

Choosing an inhaler.

It is recommended to educate patients with COPD on the correct use of inhalers at the beginning of treatment and then monitor their use at subsequent visits.

Comments. A significant proportion of patients make mistakes when using inhalers. With a metered-dose powder inhaler (PMI), no coordination is required between pushing the button and inhaling, but sufficient inspiratory effort is needed to generate sufficient inspiratory flow. When using a metered-dose aerosol inhaler (MDI), it is not required to create a high inspiratory flow, but the patient must be able to coordinate the activation of the inhaler with the start of inspiration.
It is recommended to use spacers when prescribing AIM 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 PIM (including 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 correct inhaler are described in Appendix D7.

Management of stable COPD.

All patients with COPD are advised to implement non-drug measures, prescribe a short-acting bronchodilator for use as needed, vaccinate against influenza and pneumococcal infections, and treat concomitant diseases.

Comments. Non-drug interventions include smoking cessation, training in inhalation techniques and basic self-control, influenza and pneumococcal vaccination, inducement of physical activity, assessment of the need for long-term oxygen therapy (VCT) and non-invasive ventilation (NVL).
All patients with COPD are recommended to prescribe DDBD - a combination of DDAC / LABA or one of these drugs in monotherapy regimen (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 LADA / LABA immediately after the diagnosis of COPD.
Strength of recommendation A (level of evidence - 1).
Comments. Most patients with COPD go to the doctor with severe symptoms - shortness of breath and decreased exercise tolerance. Prescribing a combination of DDAC / LABA allows, due to maximum bronchodilation, to relieve shortness of breath, increase exercise tolerance and improve the quality of life of patients.
Initial monotherapy with a single long-acting bronchodilator (LADA 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 DDAC is a more pronounced effect on the risk of exacerbations.
If symptoms persist (dyspnea and reduced exercise tolerance) against the background of monotherapy with LBD alone, it is recommended to intensify bronchodilator therapy - transfer to a combination of LADA / LABA (Appendix B).

Prescribing a combination of LADA / LABA 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 LADA / 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 COPD patients with FEV1 25–60% of normal and no high eosinophilia.
If repeated exacerbations in a patient with COPD and asthma or with blood eosinophilia occur during therapy with LABD alone, then the patient is recommended to prescribe 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 (without exacerbation) of 300 cells in 1 μl.
If repeated exacerbations in patients with COPD with asthma or eosinophilia occur during therapy with a combination of DDAC / LABA, then the patient is recommended to add ICS (Appendix B).
Strength of recommendation A (level of evidence 2).
Comments. The patient may come to triple therapy even with insufficient effectiveness of ICS / LABA therapy, when DDAC is added to the treatment.
The triple therapy of LADA / LABA / ICS currently can be carried out in two ways: 1) using a fixed combination of LADA / LABA and a separate inhaler of ICS; 2) using a fixed combination of LABA / ICS and a separate inhaler, DDAH. The choice between these methods depends on the initial therapy, compliance with different inhalers and the availability of drugs.
If repeated exacerbations occur during therapy with a combination of LADA / LABA in a patient without asthma and eosinophilia or relapse of exacerbations on triple therapy (LADA / LABA / ICS), it is recommended to clarify the COPD phenotype and prescribe phenotype-specific therapy (roflumilast, N-acetylcysteine, azdithromycin and t ; - Appendix B).
Strength of recommendation B (level of evidence 3).
It is not recommended to reduce the volume of bronchodilatory therapy (in the absence of AE), even in the case of maximum relief of symptoms.
Strength of recommendation A (evidence level –2).
Comments. This is due to the fact that COPD is a progressive disease, therefore, complete normalization of the functional parameters of the lungs is impossible.
In patients with COPD without recurrent exacerbations and with preserved lung function (FEV1 50% of the due), complete abolition of ICS is recommended, provided that DDBD is prescribed.
Strength of recommendation B (evidence level –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 canceled without increasing the risk of exacerbations.
In FEV1 patients< 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.

Lung reduction surgery is recommended for patients with COPD with upper lobe emphysema and low exercise tolerance.
Strength of recommendation C (level of evidence 3).
Comments. Lung volume reduction surgery is performed by removing part of the lung to reduce hyperinflation and achieve more efficient pumping of the respiratory muscles. At present, less invasive methods can also be used to reduce the volume of the lungs - 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, D - dyspnea (dyspnea), 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 performance in carefully selected COPD patients.

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 (CDF). The main sign of CDI is the development of hypoxemia, etc. a decrease in the oxygen content in arterial blood (PaO2).
VCT today is one of the few therapies that can reduce mortality in patients with COPD. Hypoxemia not only shortens the life of patients with COPD, but also has other significant adverse consequences: a deterioration in the quality of life, the development of polycythemia, an increased risk of cardiac arrhythmias during sleep, the development and progression of pulmonary hypertension. VCT can reduce or eliminate all of these negative effects of hypoxemia.
VCT is recommended for patients with COPD with CDF (see Appendix D8 for indications).
Strength of recommendation A (evidence level –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 justified method of CDF therapy. Unlike a number of emergency conditions (pneumonia, pulmonary edema, trauma), the use of oxygen in patients with chronic hypoxemia should be constant, long-term and, as a rule, carried out at home, therefore this form of therapy is called VCT.
The gas exchange parameters, on which the indications for VCT are based, are recommended to be assessed only during the stable condition of patients, etc. 3-4 weeks after exacerbation of COPD.
Strength of recommendation C (level of evidence 3).
Comments. This is the time required for the restoration of gas exchange and oxygen transport after the ONE period. 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 borderline values.
When prescribing oxygen therapy, it is recommended to strive to achieve the values ​​of PaO2 60 mm and SaO2 90%.
Strength of recommendation C (level of evidence 3).
VCT is not recommended in patients with COPD who continue to smoke; not receiving 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).
For most patients with COPD, VCT is recommended for at least 15 hours a day with maximum breaks between sessions, not exceeding 2 hours in a row, with a flow of xylogen of 1-2 l / min.
Strength of recommendation B (level of evidence 2).

Long-term home ventilation of the lungs.

Hypercapnia (td; an increase in the partial tension of carbon dioxide in arterial blood - PaCO2 ≥ 45 mm) is a marker of a decrease in ventilation reserve in terminal stages of pulmonary disease and also serves as a negative prognostic factor for patients with COPD. Nocturnal hypercapnia changes the sensitivity of the respiratory center to CO2, leading to higher levels of PaCO2 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 breathing apparatus further aggravates hypercapnia in patients with COPD, thus a “vicious circle” develops, which can only be broken by respiratory support (ventilation).
In patients with COPD with a stable course of CDF, who do not need 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 of the lungs (DPVL).
The use of DPWL in patients with COPD is accompanied by a number of positive pathophysiological effects, the main of which are an improvement in gas exchange indicators - an increase in PaO2 and a decrease in PaCO2, an improvement in respiratory muscle function, an increase in exercise tolerance, an improvement in sleep quality, and a decrease in PHI. Recent studies have shown that with adequately selected parameters of non-invasive ventilation (NVV), a significant improvement in the survival rate of patients with COPD complicated by hypercapnic CDF is possible.
DLSP is recommended for patients with COPD who meet the following criteria:
- The presence of CDF symptoms: weakness, shortness of breath, morning headaches;
- The presence of one of the following indicators: PaCO2 55 mm, PaCO2 50-54 mm and episodes of night 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).

12.10.2017

The Global Strategy for the Diagnosis, Management and Prevention of COPD (GOLD) is the document that every European practitioner dealing with COPD patients is guided by today. The prevalence of diseases occurring with symptoms of broncho-obstructive syndrome (BOS), in particular COPD, is growing every year.

At the same time, science and medicine do not stand still, methods of treating biofeedback are constantly being improved, new drugs and their combinations are being created, devices for drug delivery are improving, the evidence base for certain drugs is being replenished. That is why the authors of the GOLD strategy consider it necessary to reflect the dynamics of the success of the global fight against COPD regularly, issuing annual updates of the recommendation document. So, in February 2017, another update of the GOLD recommendations was released. What changes does the updated manual GOLD-2017 contain? Let's try to figure it out in detail.

GOLD-2017: changes compared to the 2016 version

Major changes:

Revised definition of COPD;

A new, improved principle for assessing membership in ABCD groups is presented;

A new algorithm for pharmacological treatment with the possibility of escalation and de-escalation is presented.

Definition."COPD is a common preventable and treatable disease characterized by persistent respiratory symptoms and airflow limitation resulting from airway and / or alveolar abnormalities, usually caused by significant exposure to harmful particles or gases."

Patient stratification into ABCD groups for subsequent treatment choices is based on symptom scores (using standard CAT or mMRC questionnaires) and exacerbation history. Spirometry data, together with symptoms and history of exacerbations, remain an important aspect of diagnosis, prognosis and other therapeutic approaches needed.

In addition, for the first time presented COPD pharmacotherapy algorithm- a shift towards a more personalized approach with a strategy of escalating or de-escalating therapy within a patient group.

GOLD-2017: changes in assessment

The basic principles for assessing the severity of COPD for the 2017 sample are shown in Figure 1.

OVF 1 - forced expiratory volume in 1 s;

FVC — forced vital capacity of the lungs.

Patient classification according to GOLD-2017

Group A: low risk of exacerbations, few symptoms.

Group B: low risk of exacerbations, many symptoms.

Group C: high risk of exacerbations, few symptoms.

Group D: high risk of exacerbations, many symptoms.

mMRC 0-1 point or CAT<10 баллов означает «мало симп­томов».

mMRC ≥2 points or CAT ≥10 points means “many symptoms”.

"Low risk of exacerbations": 0 or 1 exacerbation (no hospitalization) in the previous year.

"High risk of exacerbations": ≥2 exacerbations or ≥1 exacerbations leading to hospitalization in the previous year.

Major changes in the treatment algorithm

Pharmacotherapy is determined on the basis of clinical characteristics, the degree of airflow restriction is not a determining factor.

The combination of long-acting β-adrenergic agonists (BAAD) / long-acting M-anticholinergics (MCDD) has become the first choice for most patients.

The main changes in the choice of therapy are reflected in Figure 2.

Group A

All patients in group A should be prescribed bronchodilators depending on their effect on dyspnea. It can be both short-acting and long-acting drugs.

This treatment can be continued if there is a positive effect on the symptoms.

Group B

A long-acting bronchodilator should be chosen as the initial therapy.

There is no evidence that either class of long-acting bronchodilators are beneficial in reducing symptoms in this group of patients. The choice between drug classes is based on the patient's individual perception of symptom reduction.

Patients with persistent dyspnea on monotherapy are recommended to use two bronchodilators.

In patients with severe dyspnea, two bronchodilators may be considered as initial therapy.

If the addition of a second bronchodilator does not improve symptoms, monotherapy should be reverted.

Patients in group B are likely to have comorbidity, which can add symptomatology, affect prognosis, and require additional evaluation.

Group C

Initial therapy should consist of bronchodilator monotherapy. In two direct comparisons, MCDD prevented exacerbations better than dietary supplements. Thus, it is recommended to start therapy in this group with MCDD.

Patients with persistent exacerbations may benefit from the addition of a second bronchodilator or from a combination of dietary supplements / ICS. Since ICS increases the risk of pneumonia in some patients, the first choice is the combination of dietary supplements / MCDD.

- BADD / MCDD in studies were assessed by patients as more effective treatment than monopreparations. If a monobronchodilator is chosen for initial therapy, then MCDD is preferable in terms of preventing exacerbations than dietary supplements.

- BADD / MCDD are more effective in preventing exacerbations than BADD / ICS, and also have advantages in influencing other endpoints in patients of group D.

- Patients of group D have a high risk of developing pneumonia when taking ICS.

In some patients, ICS / dietary supplements may be considered the first choice. This applies to patients with a history of or signs suggestive of ACOS. A high level of blood eosinophils can also be considered as a criterion supporting the appointment of ICS, however, this issue is under discussion.

In patients with exacerbations, despite BADD / MCDD therapy, there are two alternative pathways:

- Escalation to BUDD / MHDD / IKS. Comparison of the effectiveness of prevention of exacerbations of dietary supplements / MCDD and dietary supplements / MCDD / ICS is under study.

- Switching to BUDD / IKS. However, there is no evidence that switching from dietary supplements / MCDD to dietary supplements / ICS will lead to better prevention of exacerbations. If dietary supplementation / ICS therapy did not have a positive effect on symptoms / exacerbations, MCDD may be added.

If exacerbations persist in the patient while taking dietary supplements / MCDD / ICS, the following should be considered:

- Addition of roflumilast. Decision can be made in patients with FEV1<50% от должного и хроническим бронхитом, в частности, в случае минимум одной госпитализации в связи с обострением за предшествующий год.

- Adding macrolide. The best available evidence base has azithromycin. The possibility of developing resistance should also be considered when making a decision.

- Cancellation of IKS. The lack of efficacy, the increased risk of adverse events (including pneumonia), and the evidence base demonstrating their cancellation without any harm support this recommendation.

As you can see, the new GOLD edition is quite noticeably different from the 2016 version. A large number of new studies, the accumulation of data on the effectiveness of certain therapy regimens in various "squares" of COPD gives hope that in the coming years we will be able to talk about complete control over such a disease as COPD.

GOLD-2017: Global Strategy for the Diagnosis,

Abstract translation from English. Alexandra Merkulova

Thematic issue "Pulmonology, Alergology, Rhinolaryngology" No. 2 (39), May 2017

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

Global strategy for the diagnosis, management and prevention of chronic obstructive pulmonary disease 2017 (report) European Respiratory Medical Journal. Published on 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) The COPD score has been improved to separate the spirometric score from the symptom score. ABCD groups are now offered exclusively for patient symptoms and history of exacerbations; Ii) for each of the groups from A to D, an escalation strategy for pharmacological treatment is proposed; Iii) the concept of de-escalation of therapy is introduced into the treatment evaluation scheme; Iv) non-pharmacological therapy is 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 Diagnosis and Initial Evaluation Key Points Diagnostics Symptoms Dyspnea Cough Excretion of sputum Wheezing and tightness in the chest Additional characteristics of the severe course of the disease Disease history Physical examination Spirometry Expert questions Severity Classification of Airflow Restriction Assessment Assessment of symptoms Choice of exacerbation risk assessment Counting blood eosinophilia Revised Comprehensive Assessment of COPD Example Alpha 1-antitrypsin deficiency Additional research Combined rating scales Differential diagnoses Other considerations Prevention and supportive 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 Medicines overview Bronchodilators Beta2 agonists, Antimuscarinic drugs 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 medicines with anti-inflammatory potential associated with inhalation therapy Alpha 1-Antitrypsin Boosting 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 volume reduction surgery Bullectomy Lung transplant Bronchoscopic interventions to reduce airiness in severe emphysema Management of stable COPD Key points Identifying and reducing exposure to risk factors Treatments for 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 mechanical ventilation Invasive mechanical ventilation Hospital discharge and follow-up Prevention of exacerbations COPD and comorbidities (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 compiled from scientific publications through October 2016. Evidence levels are assigned to evidence-based recommendations as appropriate. The 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 characterized by persistent respiratory symptoms and airflow restriction, which, due to airway and / or alveolar abnormalities, is usually caused by significant exposure to harmful particles or gases. Shortness of breath, cough, and / or phlegm production are the most common symptoms; symptoms are usually underreported by patients Tobacco smoking is the main risk for COPD, but environmental influences such as exposure to biomass fuels and air pollution can contribute. In addition to exposure, host factors (genetic abnormalities, abnormal lung development, and accelerated aging) predispose people to develop COPD. COPD can be interspersed with an acute worsening of respiratory symptoms called exacerbations In the majority of patients, COPD is associated with significant concomitant chronic diseases that lead to an increase in 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 characterized by persistent respiratory symptoms and airflow restriction, which, due to airway and / or alveolar abnormalities, is usually caused by significant exposure to harmful particles or gases. The chronic airflow restriction 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, constriction and destruction of the lung parenchyma. Loss of small airways can contribute to airflow restriction and mucociliary dysfunction, a characteristic feature of the disease. Chronic respiratory symptoms may precede the development of airflow restriction and are associated with acute respiratory events. Chronic respiratory symptoms can exist in people with normal spirometry and a significant number of non-respiratory smokers have structural features of lung disease, manifested by the presence of emphysema of the lungs, airways, wall thickening and gas alveoli. Factors influencing the development of the disease and progression Although cigarette smoking is the best-studied risk factor for COPD, epidemiological studies have shown that nonsmokers can also develop chronic airflow restriction. Compared to smokers with COPD, never smokers, people with chronic airflow restriction have fewer symptoms, lung disease and a lower burden of systemic inflammation. People who have never smoked with chronic airflow restriction do not have an increased risk of lung cancer, or cardiovascular comorbidities; however, they have an increased risk of pneumonia and death from respiratory failure. Processes during pregnancy, childbirth and radiation exposure during childhood and adolescence affect the growth of the lungs. Reduced maximum lung function achieved (as measured by spirometry) can identify individuals at increased risk of COPD. Factors in early life called childhood minus factors are as important as smoking abuse in predicting lung function in adulthood. A study of three different longitudinal cohorts found that approximately 50% of COPD patients are due to an accelerated decline in FEV; in the remaining 50%, developed COPD is due to abnormal growth and development of the lungs. Cigarette smokers have a higher prevalence of respiratory symptoms and impaired lung function, an increase in the annual rate of decline in FEV and COPD, and higher mortality rates than nonsmokers. Other types of tobacco (eg pipe, cigars, shisha) and marijuana are also risk factors for COPD. Environmental tobacco smoke (ETS), also known as environmental tobacco smoke (ETS), can also contribute to respiratory symptoms and COPD by increasing the overall lung burden when particles and gases are inhaled. Smoking during pregnancy can pose a threat to the fetus, 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 developing COPD. Wood, animal dung, crop residues and coal, usually burned on campfires or a poorly functioning stove, can lead to air pollution. Pollution from cooking and biomass heating in poorly ventilated areas is a risk factor for COPD. Asthma may be at risk for developing chronic airflow restriction and COPD. Airway hyperresponsiveness can exist without a clinical diagnosis of asthma and is an independent predictor of COPD and respiratory mortality in populations, and may indicate the risk of excessive decrease 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 dyspnea, chronic cough or sputum production and / or a history of risk factors. Spirometry is mandatory for diagnosis; after bronchodilator FEV1 / FVC<0.70 подтверждает наличие стойкое ограничение воздушного потока. The objectives of the COPD assessment are to determine the degree of airflow restriction, the effect of the disease on the patient's health, and the risk of future events (eg, exacerbations, hospitalizations, or death) for the choice of therapy. Chronic comorbidities often occur in patients with COPD and must be treated because they can independently affect mortality and hospitalizations.

Diagnosis COPD should be considered in any patient with dyspnea, chronic cough or sputum production and / or exposure to a history of risk factors for disease development (Figure 1 and Table 1). Spirometry needs to be diagnosed in a given 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
Table 1. Key indicators for confirming the diagnosis of COPD

Specify the diagnosis of COPD and perform spirometry if any of these indicators are manifested in a person over 40 years old. These indicators are not diagnostic by themselves, but the presence of several key indicators increases the likelihood of a diagnosis of COPD. Spirometry is a must for the diagnosis of COPD.

Shortness of breath what it is: it progresses over time. It gets worse with exercise. Long-term, prolonged.

Chronic cough: May be temporary and may be unproductive. Periodic wheezing.

Chronic sputum production: any kind.

Recurrent lower respiratory tract infections

Collection of risk factors: Host factors (such as genetic factors, congenital / developmental abnormalities, etc.) Tobacco smoke Smoke from home cooking and heating fuels Dust, fumes, smoke, 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 common symptom of COPD. Dyspnoea. Shortness of breath is one of the leading causes of disability and anxiety in COPD. The terms used to describe shortness of breath vary individually and from culture to culture. Cough. Chronic cough is often the first symptom of COPD and is often underestimated by the patient as a consequence and / or environmental exposure of smoking. Excretion of sputum. Regular sputum production> 3 months 2 years in a row is the classic definition of chronic bronchitis; an arbitrary definition that does not reflect the full range of sputum is reported in COPD. Patients secreting large volumes of sputum may have occult bronchiectasis. Wheezing and tightness in the chest. Wheezing and chest tightness can vary from days to overnight. Additional signs in case of severe illness. Fatigue, weight loss, and anorexia are common in patients with more severe 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 during childhood; other chronic respiratory and non-respiratory diseases. Family history of COPD or other chronic respiratory disease. The nature of the development of the symptom: the age of onset, the nature of the symptom, more frequent or prolonged “winter colds”, and social deprivation. A history of exacerbations or previous hospitalizations with respiratory diseases. The presence of concomitant diseases such as heart disease, osteoporosis, musculoskeletal system, and malignant neoplasms. The impact of the illness on the patient's life, including reduced activity, job loss and economic consequences, and feelings of depression or anxiety. Social and family support for the patient. Possibilities for reducing risk factors, especially smoking. Physical examination While this is important for assessing overall health, physical examination rarely helps diagnose COPD. Physical signs of airflow restriction / hyperventilation are usually undetectable until significantly impaired lung function appears. Spirometry Spirometry is the most reproducible and objective measurement of airflow restriction. It is a non-invasive and affordable test. Good quality spirometry is possible in any healthcare setting; all healthcare professionals who provide care for patients with COPD should have access to spirometry. Fixed FEV1 / FVC after bronchodilator<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. GOLD guidelines suggest performing spirometry in patients with symptoms and / or risk factors, but not routine screening for spirometry in asymptomatic individuals without COPD risk factors. Grade The goals of assessing COPD for the choice of therapy are: 1) to determine the degree of airflow restriction; 2) determine its impact on the patient and health status; 3) determination of the risk of future events (for example, exacerbations, hospitalizations or death). To achieve these goals, according to the assessment of COPD, the following aspects of the disease must be considered separately: Presence and severity of spirometric abnormalities Current state and significance of symptoms History / future risks of exacerbations Presence of concomitant diseases Classification of the severity of airflow restriction Spirometry should be performed after the administration of an adequate dose of at least one short-acting inhaled bronchodilators to minimize variability. The role of spirometry in the diagnosis, assessment and follow-up of COPD is summarized in Table 2. Diagnostics Assessment of the severity of obstruction (for prognosis) Follow-up treatment Therapeutic decisions Pharmacological in individual circumstances (contradictions between spirometry and symptom level Consideration of an alternative diagnosis when symptoms are disproportionate to the level of bronchial obstruction Non-pharmacological (i.e. interventional procedures) Determination of the 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

Assessment of symptoms COPD was previously considered a disease largely characterized by shortness of breath. Simple shortness of breath questionnaires such as the Modified British Medical Research Council (mMRC) Questionnaire are considered sufficient to assess symptoms. However, shortness of breath is well tolerated in patients with COPD. For this reason, a comprehensive symptom assessment is recommended. The most comprehensive disease-specific health condition questionnaires include the Chronic Respiratory Questionnaire (CRQ) 53 and St. George's Respiratory Questionnaire (SGRQ). There are 2 that are too complex to be used in clinical practice, but with fewer indicators, such as the COPD Assessment Test (CATTM), which are appropriate. Choice of thresholds for SGRQ scores< 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 comorbid chronic diseases (comorbidity) Patients with COPD often have important concomitant chronic diseases, while COPD is an important component of multimorbid pathology, especially in old age. The revised COPD aggregate score The ABCD GOLD Report 2011 “Tool” was a big step forward from the simple spirometry scoring system compared to the earlier GOLD Reports because it included long-term patient outcomes and emphasized the importance of exacerbation prevention in COPD management. However, there are important restrictions. The ABCD score "works" no better than the spirometric score for predicting mortality or other important health outcomes. In addition, the group “D” results were modified by two parameters: lung function and / or history of exacerbation, which caused confusion. To address these issues, the 2017 GOLD Report provides a refinement of the ABCD score, which separates the spirometric score in the "ABCD" groups. In some therapeutic guidelines, especially pharmacological treatments, ABCD groups are derived solely from the patient's symptoms and history of exacerbation. However, spirometry, in combination with the patient's symptoms and history of exacerbation, remains vital for diagnosis, prognosis, and consideration of other important therapeutic approaches, especially non-drug therapy. This new assessment approach is shown in Figure 2.
Rice. 2. Assessment tool for ABCD instruments Figure 2. The refined ABCD assessment tool The assessment outline highlights that patients should undergo spirometry to determine the severity of the airflow restriction (ie, spirometric grade). They should also be assessed for either dyspnea on the mMRC questionnaire or symptoms using the CATTM. Finally, their history of exacerbations (including previous hospitalizations) should be recorded. The number provides information on the severity of the airflow restriction (spirometric ranks 1 to 4), while the letter (groups A-D) provides information on the burden of the symptom and the risk of exacerbation. FEV1 is a very important parameter at the population level in predicting important clinical outcomes such as mortality and hospitalizations or the 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 determine all therapeutic options. In addition, in some cases, for example, during hospitalization or an urgent visit to the clinic or trauma center, to determine the condition of patients based on symptoms and history of exacerbation, does not depend on the value of spirometry, allows doctors to develop a treatment plan based on the revised ABCD regimen. This approach recognizes the limitations of FEV1 in treatment decisions for individual patient management and emphasizes the importance of patient symptoms and the risk of exacerbations in guiding therapy in COPD. The separation of airflow restriction from clinical parameters makes it clearer, which is assessed and ranked. This should facilitate more accurate parameter-based treatment recommendations that are based on the patient's symptoms at any given time. Example. Consider two patients - FEV1 patients<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 Smoking cessation is key. Pharmacotherapy and nicotine prolong the replacement period for smoking abstinence . The efficacy and safety of 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 and exercise tolerance. Each drug treatment regimen should be individualized and guided by the severity of symptoms, the risk of exacerbations, side effects, concomitant diseases, drugs available and cost, and patient response, preferences and possibilities of using different drug delivery devices. The inhaler technique should be regularly evaluated. Influenza and pneumococcal vaccinations reduce the incidence of lower respiratory tract infections. Pulmonary rehabilitation improves symptoms, quality of life, 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 therapy should not be prescribed routinely, however, individual patient factors should be considered. In patients with severe chronic hypercapnia and a history of acute respiratory failure for hospitalization, prolonged non-invasive ventilation can reduce mortality and prevent re-hospitalization. In some patients with severe pulmonary emphysema refractory to optimized care, surgical and bronchoscopic interventional treatment may be beneficial. Palliative approaches are effective in managing 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. Smoking Cessation Smoking cessation affects the natural course of COPD. If effective resources and time are devoted to smoking cessation, long-term smoking cessation 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, but should be used as part of an intervention program and not as a sole intervention. Smoking cessation programs. The Five-Step Program for Cessation provides a framework for shaping health care providers to help patients quit smoking. The consultation provided by health care professionals significantly increases self-initiated smoking cessation. The combination of pharmacotherapy and behavioral support increases smoking cessation rates. Vaccinations Influenza and Pneumococcal Vaccines Influenza vaccination reduces serious illness, death, the risk of coronary heart disease, and the overall incidence of exacerbations. Vaccines containing killed or live inactivated viruses are recommended as they are more effective in elderly patients with COPD. Pneumococcal vaccinations with PCV13 and PPSV23 are recommended for all patients ≥ 65 years of age (see Table C2 in the Supplementary Appendix). Drug treatment of stable COPD Drug review Pharmacological therapy for COPD reduces the severity of symptoms, the frequency and severity of exacerbations, and improves exercise tolerance and health status. Existing medications do not alter the long-term decline in lung function. Classes of drugs used to treat COPD are presented in Table C3 of the Supplementary Appendix. The choice in each class depends on the availability and cost of the drugs and the favorable clinical response balanced in terms of side effects. Each treatment regimen should 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, decrease dynamic hyperinflation at rest and during exercise, and improve physical performance. Bronchodilators are usually prescribed on a regular basis to prevent or reduce symptoms. The toxicity is dose-dependent. Beta2-adrenergic agonists. Beta2-adrenergic agonists, including short-acting short-acting Beta2-agonists (SABA) and long-acting long-acting Beta2-agonists (LABA) Activity of agents, relax the smooth muscles of the airways. Stimulation of beta2-adrenergic receptors can produce sinus tachycardia in rest and cardiac arrhythmias in sensitive patients Excessive somatic tremor occurs in some patients treated with higher doses of beta2-adrenergic agonists Antimuscarinic drugs Ipratropium, a short-acting muscarinic antagonist, provides the benefits of a shorter-acting beta2-agonist in lung 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 great its effect on treatment aggravation for LAMA (tiotropium) versus LABA treatment. An unexpected slight increase in cardiovascular events has been 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 versus Respimat® Inhaler. Methylxanthines. Theophylline is a moderate bronchodilator in stable COPD, and improves FEV1 and dyspnea when added to salmeterol. There are limited and conflicting data regarding the effect of low doses of theophylline on the incidence of exacerbations. Toxicity is dose dependent, which is a problem as most of the effects occur at toxic doses. Combined bronchodilator therapy Combining drugs with different mechanisms and duration of action can increase the degree of bronchodilator therapy with a lower risk of side effects compared to increasing the dose of a single bronchodilator (Table 3). There are many combinations of LABA and LAMA in one single inhaler (Table S3). These combinations improved lung function compared to placebo and had a greater effect on the patient reported results compared to monotherapy. LABA / LAMA improves symptoms and health in patients with COPD, is more effective than long-acting monotherapy bronchodilators for preventing exacerbations, and reduces exacerbations to a greater extent than the ICS LABA combination. Table 3. Bronchodilators for stable COPD

Inhaled bronchodilators for COPD are central to symptomatic management and are usually prescribed on a regular basis to prevent or reduce symptoms (Evidence A). Regularly and as needed, use of SABA or SAMA improves FEV1 and symptoms (Evidence A). The combination of SABA and SAMA is superior to drug monotherapy in improving FEV1 and symptoms (Evidence A). LABAs and LAMAs significantly improve lung function, shortness of breath, health status, and reduce the incidence of exacerbations (Evidence A). LAMAs have a greater effect on exacerbation reduction compared to LABAs (Evidence A) and decreased hospital admissions (Evidence B). Combination treatment with LABA and LAMA increases FEV1 and decreases symptoms compared to monotherapy (Evidence A). Combination treatment with LABA and LAMA reduces the number of exacerbations compared to monotherapy (evidence B) or ICS / LABA (evidence B). Tiotropium improves the effectiveness of pulmonary rehabilitation in improving physical performance (level of evidence B). Theophylline has little bronchodilator effect in stable COPD (evidence level 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 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 main clinically relevant endpoints 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 and reducing exacerbations in patients with exacerbations of moderate to very severe COPD (Evidence A). Regular treatment with ICS increases the risk of pneumonia, especially in those with severe illness (Evidence A). ICS / LAMA / LABA triple inhalation therapy improves lung function, symptoms and health (Evidence A) and reduces exacerbations (Evidence B) compared to ICS / LABA or LAMA monotherapy. Oral glucocorticoids Long-term use of oral glucocorticoids has many side effects (evidence level A) there is no evidence of benefit (evidence C). PDE4 inhibitors In patients with chronic bronchitis, severe to very severe COPD, and exacerbations: o PDE4 inhibitor improves lung function and reduces moderate to severe exacerbations (Evidence A). o PDE4 inhibitor improves lung function and reduces exacerbations in patients who are on a fixed dose of the LABA / ICS combination (level of evidence B). Antibiotics Long-term therapy with azithromycin and erythromycin reduces exacerbations within one year (Evidence A). Azithromycin treatment is associated with an increased incidence of bacterial resistance (evidence level 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-inflammatories Simvastatin does not prevent exacerbations in patients with COPD who are at increased risk of exacerbation and are not indicated for statin therapy (evidence A). However, observational studies suggest that statins may have a beneficial effect on some of the outcomes in COPD patients who receive them from cardiovascular and metabolic signs (Evidence C). Leukotriene modifiers have not been adequately tested in COPD patients.

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 corticosteroids ICS combined with LABA is more effective than the individual components in improving lung function and health and reducing exacerbations in patients with exacerbations of moderate to very severe COPD (Evidence A). Regular treatment with ICS increases the risk of pneumonia, especially in those with severe illness (Evidence A). ICS / LAMA / LABA triple inhalation therapy improves lung function, symptoms and health (Evidence A) and reduces exacerbations (Evidence B) compared to ICS / LABA or LAMA monotherapy. Oral glucocorticoids Long-term use of oral glucocorticoids has many side effects (Evidence A) there is no evidence of benefit (Evidence C). PDE4 inhibitors In patients with chronic bronchitis, severe to very severe COPD and exacerbations: o PDE4 inhibitor improves lung function and reduces moderate to severe exacerbations (Evidence A). o PDE4 inhibitor improves lung function and reduces exacerbations in patients who are on a fixed dose of the LABA / ICS combination (level of evidence B). Antibiotics Long-term therapy with azithromycin and erythromycin reduces exacerbations within one year (Evidence A). Azithromycin treatment is associated with an increased incidence of bacterial resistance (evidence level 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 who are at increased risk of exacerbation and are not indicated for statin therapy (evidence A). However, observational studies suggest that statins may have a beneficial effect on some of the outcomes in COPD patients who receive them from cardiovascular and metabolic signs (Evidence C). Leukotriene modifiers have not been adequately tested in COPD patients. Inhaled corticosteroids In patients with moderate to severe COPD and exacerbations, an inhaled corticosteroid (ICS) in combination with LABA is more effective than either component alone in improving lung function, health status, and reducing exacerbations. However, combination therapy does not affect survival. Application of ICS results in a high prevalence of oral candidiasis, hoarseness, blue skin, and pneumonia. Patients at increased risk of pneumonia include those who currently smoke, are> 55 years of age, 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 complex intervention based on a thorough inpatient examination followed by patient-adapted treatments (e.g. training, education, self-management, behavioral change interventions to improve physical and psychological well-being and to encourage adherence to wellness behaviors in patients with COPD). The benefits of pulmonary rehabilitation are significant (Table S5 in the Supplementary Appendix). Pulmonary rehabilitation can reduce readmissions and mortality in patients following a recent exacerbation (≤ 4 weeks prior to hospitalization). Initiating pulmonary rehabilitation before hospital discharge, however, can jeopardize survival. Pulmonary rehabilitation is an integrated patient management that involves the involvement of a range of healthcare professionals and the location, including inpatient and outpatient care, and / or at the patient's home. Education, self-government, and comprehensive care Education. Smoking cessation, proper use of inhalation devices, early detection of flare-ups, decision-making when seeking help, surgery, and consideration of preventive measures are examples of teaching topics. Self-management. Self-regulatory measures, the use of written agreed action plans when symptoms worsen can lead to a decrease in illness leading to hospitalization and all causes of hospitalizations and improved health. The health benefits of COPD self-management programs can be offset by increased mortality. Generalization in real life remains difficult. Comprehensive care programs. Comprehensive care programs improve clinical outcomes, although not mortality. However, large multicenter studies into existing well-organized health care systems do not support this. Comprehensive telemedicine interventions 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 alleviate suffering, and to improve the quality of life of patients and their families, regardless of the stage of the disease or other methods of treatment. Palliative efforts should be directed towards relieving dyspnea, pain, anxiety, depression, fatigue, and poor nutrition. End of life and hospice care The end-of-life care discussion should include patients and their families. Advance planning can reduce the anxiety of patients and their families, provide care according to their wishes, and avoid unnecessary, unnecessary and costly invasive treatments. Table S6 in the supplementary appendix summarizes the approach to palliative goals, end-of-life and hospice care Other Treatment Methods Oxygen therapy and mechanical ventilation Oxygen therapy. Long-term administration of oxygen (> 15 hours a day) to patients with chronic respiratory failure increases the survival rate of patients with severe hypoxemia. Long-term oxygen therapy does not lengthen time to death or first hospitalization, or provide sustained benefits for any of the measurable outcomes in patients with stable resting COPD or exercise of moderate arterial oxygen desaturation. Mechanical ventilation. Whether NPPV should be used chronically at home to treat patients with acute chronic respiratory failure during hospitalization remains uncertain. In retrospect, the data were inconclusive. RCTs have provided conflicting evidence on the use of NPPV at home for survival and readmission for 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 the volume of the lungs. One study confirmed that patients with COPD with upper lobe of emphysema and low postoperative exercise tolerance experienced improved survival when treated with lung volume reduction surgery (LVRS) compared with drug therapy. In patients with high post-pulmonary rehabilitation physical performance, no difference in survival was noted after LVRS, although health and exercise performance improved. LVRS has been demonstrated to result in a higher mortality rate than drug treatment in severe emphysema in patients with FEV1 ≤ 20%, and homogeneous emphysema with high-resolution computed tomography or DLCO was predicted to be ≤ 20%. Bullectomy. In selected patients with relatively intact basal lungs, bullectomy is associated with decreased dyspnea, improved lung function, and exercise tolerance. Lung transplant. In selected patients, lung transplantation has been shown to improve health and function, but not prolong survival. Bilateral lung transplants have been reported to have a 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 Pointsrisk 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 the 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 must be complemented by appropriate non-pharmacological interventions Effective management of COPD must be based on individual assessment to reduce current symptoms and future risks of exacerbations (Figure C1 in Supplementary Appendix). We offer personalization of initiation and escalation / de-escalation procedures based on the level of symptoms and the individual's risk of exacerbations. The basis for these recommendations is based in part on the evidence collected from RCTs. These guidelines are intended to support the physician's decision making. Identifying and reducing exposure to risk factors Cigarette smoking is the most common and easily identifiable risk factor for COPD; smoking cessation should be continually recommended for smokers. Reducing general personal exposure to occupational dust, fumes and gases, and indoor and outdoor harmful substances, must be addressed. Treatment for stable COPD Drug Treatment Drug treatment can reduce symptoms, the risk and severity of exacerbations, and improve health and exercise tolerance. The choice in each class depends on the availability of the drug and the patient's response and preferences (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 (Evidence A). Long-term treatment with ICS may be considered in relation to 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 exacerbated patients despite LABA / ICS or LABA / LAMA / ICS, chronic bronchitis, and severe to very severe airflow obstruction, supplementation with a PDE4 inhibitor may be considered (Evidence B). In ex-smokers with exacerbations, macrolides may be prescribed despite appropriate therapy (Evidence B). Statin therapy is not recommended for the prevention of exacerbations (Evidence A). The mucolytic antioxidant is recommended only in selected patients (level of evidence: 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 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 The proposed model for initiation and subsequent escalation and / or de-escalation of pharmacological management according to individual assessment of symptoms and risk of exacerbation is shown in Figure 3. In the past GOLD Reports, recommendations were given only for initial therapy. However, many patients with COPD are already on treatment and have persistent symptoms returning after initial therapy, or less often with resolution of some symptoms, which may subsequently require less therapy. Therefore, we now propose escalation and de-escalation strategies. Recommendations are based on available efficacy and safety data. We recognize that treatment escalation is not systematically monitored; de-escalation trials are also limited and only include ICS. Lack of direct evidence to support therapeutic recommendations for patients in groups C and D. These recommendations will be revised as additional data. Rice. 3. GOLD Grade pharmacological treatment algorithms (boxes highlighted and arrows indicate preferred treatments] Figure 3. Pharmacologic treatment algorithms by GOLD Grade Group A All patients in group A should be offered bronchodilators to relieve shortness of breath. It can be either short 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 symptom 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 bronchodilataromas may be considered. Group C Initial therapy should be the only long-acting bronchodilator. In two parallel studies, LAMA testing outperformed LABA in preventing flare-ups, so we recommend starting with LAMA in this group. Patients with persistent exacerbations may benefit from the addition of 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 the combined LABA / LAMA because: § Studies have reported patient outcomes as the primary endpoint, and the LABA / LAMA combination has shown superior results compared to a single bronchodilator. § The LABA / LAMA combination was superior to the LABA / ICS combined in preventing exacerbations and improving other patients in group D patients. § Group D patients have an increased risk of pneumonia with ICS treatment. If a bronchodilator is initially chosen, LAMA is preferred for prevention of exacerbation based on comparison with LABAs. LABA / ICS may be the first choice for initial therapy in some patients. These patients may have a history of and / or signs suggestive of asthma-COPD crushing and / or increased blood eosinophils. In patients who develop additional exacerbations on LABA / LAMA therapy, we suggest two alternative routes: § Escalation of LABA / LAMA / ICS. § LABA / ICS transition. If LABA / ICS therapy does not have a beneficial effect on the sequelae / symptoms of flare-ups, LAMA may be added. If patients with LABA / LAMA / ICS still have ongoing exacerbations, the following options may be considered: § Add roflumilast. This may be considered in FEV1 patients.<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 Individual patient assessment and risk assessments (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 complete rehabilitation program, taking into account the characteristics of the individual and comorbidities. Workout Combining sustained 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 tolerance. Upper limb exercise training increases arm strength and endurance and improves the activity ability of the upper limb. Self-government education The educational program should include smoking cessation; basic information about COPD; aspects of medical treatment (respiratory drugs and inhalation devices); strategies to minimize shortness of breath; advice on when to seek help; and possibly discussion of perspectives and questions at the end of life. End of life and palliative care Patients should be informed that they must become critically ill, they or their family members may need to decide whether intensive care is most likely 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, COPD supplementation 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. The PPSV23 is also recommended for young COPD patients with serious comorbidities, 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 mm Hg) or SaO2 at or below 88%, with or without hypercapnia confirmed twice over a three week period; or PaO2 between 7.3 kPa (55 mm Hg) and 8.0 kPa (60 mm Hg) or SaO2 at 88% if there is evidence of pulmonary hypertension, peripheral edema, suspected congestive heart failure , or polycythemia (hematocrit> 55%). NIV ventilation support is sometimes used in patients with stable very severe COPD. NIV may be considered in a select 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 optimized care, surgical and bronchoscopic types of lungs, volume reduction (eg, endobronchial unilateral valves or pulmonary rings) may be considered. In selected patients with large bullae, surgical bullectomy may be suggested. In selected patients with extremely severe COPD and without appropriate contraindications, lung transplantation may be discussed. Choosing bronchoscopic lung reduction or LVRS for the treatment of hyperinflammation in an emphysematous patient depends on a number of factors, which include: the extent and nature of pulmonary emphysema detected on VR CT; the presence of interlobar collateral ventilation is measured by fracture integrity on VR CT or physiological assessment (endoscopic balloon occlusion and flow assessment); local assessment when performing the procedure; patient and performer's preferences. An algorithm depicting various activities based on radiological and physiological characteristics is shown in Figure 4. Rice. 4. Bronchoscopic interventional and surgical treatments for COPD Figure 4. Interventional bronchoscopic and surgical treatments for COPD Criteria for referral to 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 RT. Art. or 6.6 kPa and / or Rao2<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 An exacerbation of COPD is an acute exacerbation of respiratory symptoms that leads to adjunctive therapy. Exacerbations can be caused by several factors. Respiratory tract infections are the most common causes. The goal for treating exacerbations is to minimize the negative effects of the current exacerbation and to prevent subsequent events. Short-acting inhaled beta2-agonists, with or without short-acting anticholinergics, are recommended as initial bronchodilator treatment for exacerbation. Maintenance therapy with long-acting bronchodilators should be started as soon as possible, before hospital discharge. Systemic corticosteroids improve pulmonary function (FEV1), oxygenation, and shorten recovery time and hospital stay. Antibiotics are indicated to shorten recovery time, reduce the risk of early relapse, treatment failure, and length of hospital stay. Methylxanthines are not recommended due to side effects. Non-invasive mandatory ventilation should be the first ventilation mode used to treat acute respiratory failure. After an exacerbation, appropriate measures to prevent an exacerbation should be initiated.

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 hospitalization Antibiotics, when indicated, shorten recovery time, reduce the risk of early relapse, treatment failure, and hospitalization

Exacerbations are important events in the management of COPD as they negatively affect health status, hospitalization and readmission rates, and disease progression. Exacerbations of COPD are a combination of events usually associated with increased airway inflammation, increased mucus production, and the formation of gas traps. Dyspnea increases and is the main symptom of an exacerbation. Other symptoms include increased phlegm, pus, and volume, along with increased coughing and wheezing. As concomitant diseases 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 only with short-acting bronchodilators, SABDs) Moderate (treated with SABDs plus antibiotics and / or oral corticosteroids) or Severe (patient requires hospitalization or an emergency room visit). Severe exacerbations can be associated with acute respiratory failure. Exacerbations are mainly caused by respiratory viral infections, although bacterial infections and environmental factors can also initiate and / or exacerbate these events. Exacerbations can be associated with increased secretion of sputum and, if purulent, the bacteria causing this can 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 COPD patients. Exacerbations are associated with increased sputum or blood eosinophils may be more susceptible to systemic steroids although more prospective data are needed.243 Symptoms usually last 7 to 10 days during an exacerbation, 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 are prone to frequent exacerbations (defined as ≥ 2 exacerbations per year) and have poorer health and mortality than those with less frequent exacerbations. Other factors associated with an increased risk of exacerbations and / or severity of exacerbations include an increase in the pulmonary artery to aortic cross-sectional ratio (i.e., a 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 of treatment in order 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 on an outpatient or inpatient basis. More than 80% of exacerbations occur on an outpatient basis with bronchodilators, corticosteroids, and antibiotics. Indications for hospitalization for exacerbation of COPD are presented in table S10 in the supplementary appendix. When patients with acute exacerbation of COPD are referred to an emergency room, they should be given supplemental oxygen and evaluated to determine whether the exacerbation is life-threatening and warrants consideration for non-invasive ventilation, intensive care, and respiratory block hospitalization. The long-term prognosis after hospitalization for exacerbation of COPD is low; 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 exacerbations of COPD, clinical severity of the exacerbation index, and the need for long-term oxygen therapy at discharge. Patients with a higher prevalence and severity of respiratory symptoms, worse quality of life, worse lung function, decreased physical performance, lower lung density, and thickening of the bronchial wall on CT have an increased risk of mortality after 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 C). Systemic corticosteroids improve pulmonary function (FEV1), oxygenation and shorten recovery time and hospital stay. The duration of therapy should not be more than 5-7 days (Evidence level A). Antibiotics, when indicated, can shorten recovery time, reduce the risk of early relapse, treatment failure, and length of hospital stay. 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 Non-invasive mechanical ventilation) should be the first ventilation mode used in patients with COPD with acute respiratory failure who have no absolute contraindications, since it improves gas exchange, reduces the work of breathing and the need for intubation, reduces the duration of hospitalization and improves survival (Evidence 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 morethan 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).

Medication Treatment The most commonly used classes of drugs 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 are no significant differences in FEV1 when using metered-dose inhalers (MDIs) (with or without an inhalation device) or nebulizers to deliver the agent, although the latter may be an easier delivery route 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 hospitalization times. The recommended dose is 40 mg of prednisone per day for 5 days. therapy with oral prednisolone is equally effective for intravenous administration. glucocorticoids may be less effective for treating exacerbations in patients with lower blood eosinophil levels. Antibiotics The use of antibiotics for exacerbations remains controversial. evidence supports the use of antibiotics in patients with exacerbations and increased purulent sputum. One review reported that antibiotics reduced the risk of term mortality by 77%, treatment failure by 53%, and sputum purulence by 44%. Procalcitonin-targeted antibiotic treatment can reduce antibiotic exposure and side effects with the same clinical efficacy. A study in patients with exacerbations requiring mechanical ventilation (invasive or non-invasive) reported an increase in mortality and an increase in mean nosocomial pneumonia when the antibiotic was not given. Antibiotics should be given to patients with acute exacerbations who have three cardinal symptoms: increased dyspnea, sputum volume, and sputum purulence; there are two cardinal symptoms if an increase in sputum purulence is one of two symptoms; or require mechanical ventilation (invasive or non-invasive). The recommended duration of antibiotic therapy is 5-7 days. The choice of antibiotic should be based on the local pattern of bacterial resistance. The usual initial empiric treatment is aminopenicillin with clavulanic acid, macrolides, or tetracycline. In patients with frequent exacerbations, severe airflow restrictions, and / or exacerbations requiring mechanical ventilation, culture from sputum or other materials from the lungs is performed to detect 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 must be monitored to ensure satisfactory oxygenation without carbon dioxide retention and / or worsening acidosis. Mechanical ventilation. Some patients require hospitalization in an intensive care unit. Admission of patients with severe exacerbations to moderate levels 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 ventilation regimen for the management of acute respiratory failure in patients hospitalized for acute exacerbations of COPD. NIV has been studied in randomized clinical trials to show a success rate of 80-85%. Mortality and intubation rates decrease with NIV. Invasive mechanical ventilation. Indications for invasive mechanical ventilation during an exacerbation include failure to respond to initial NIV administration. In patients who did not respond to non-invasive ventilation as initial therapy and receive invasive ventilation as subsequent resuscitation therapy, morbidity, length of hospital stay, and increased mortality. Hospital discharge and follow-up Lack of spirometric assessment and arterial blood gas analysis have been 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 concomitant diseases, including anxiety and depression. The set of measures upon discharge from the hospital and includes education, optimization of drug treatment, control and correction of inhaler technique, assessment and optimal management of concomitant diseases, early rehabilitation, telemonitoring and constant patient contact were investigated. There is sufficient evidence that they affect readmission rates, short-term urgency, or cost-effectiveness. Early observation during the 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 comorbidities

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 associated with other diseases (comorbidity) that can have a significant impact on the prognosis. Some of these occur independently of COPD, while others may be causally related to common risk factors, or one condition increases the risk or severity of others. The management of a patient with COPD should include the identification and treatment of his comorbidities, the most common in COPD are given below. Cardiovascular disease 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 on mechanical ventilation, 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 injury in patients with concomitant coronary artery disease who have exacerbations of COPD. Patients who exhibit 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 previously been described as potentially pro-arrhythmic agents; however, the available data suggest a generally acceptable safety profile for long-acting beta2-agonists, anticholinergics (and inhaled corticosteroids). Peripheral artery disease In a large cohort of patients with COPD of all severities, 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 reported poorer functional ability and 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 adjusting the steroid dose, age, pack-years of smoking, smoking, and exacerbations. An association between inhaled corticosteroids and fractures has been found in pharmaco-epidemiological studies. Systemic corticosteroids significantly increase the risk of osteoporosis. Anxiety and depression Anxiety and depression are both associated with a poor prognosis. COPD and lung cancer The link between emphysema and lung cancer is stronger than between airflow restriction and lung cancer. Older age and long smoking history increases the risk. 2 low-dose chest computed tomography (LDCT) studies have shown improved survival in 55-74 year olds, smokers, or those who have quit smoking within the previous 15 years with a history of smoking not less than 30 package - years. LDCTs are now recommended in the US for patients meeting these demographic requirements; 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 affect the prognosis. The prevalence of metabolic syndrome is over 30%. Gastroesophageal reflux Gastroesophageal reflux is an independent risk factor for exacerbations and associated with worse health conditions. Bronchiectasis Bronchiectasis is associated with longer OSA exacerbations and increased mortality. Obstructive Sleep Apnea(Obstructive Sleep Apnea OSA) Patients with “overlap syndrome” (COPD and OSA) have a worse prognosis compared to COPD or OSA. Apnea events in patients with OSA and COPD have deeper hypoxemia and cardiac arrhythmias and are more likely to develop daytime pulmonary hypertension than patients with isolated OSA or COPD alone. Evidence level description Additional Appendices Table C1: Evidence level description Table C2: Vaccination with stable COPD Table S3: Commonly used support drugs for COPD Table S4: Other Pharmacological therapies Table S5: Pulmonary rehabilitation, self-management and comprehensive care for COPD Table C6: Palliative care at the end of life and hospice care for COPD Table S7: Oxygen therapy and mechanical ventilation for stable COPD Table S8: Interventional Therapy for Stable COPD Figure S1: Treatment Goals for Stable COPD Table S9: Key Points for Using Non-Pharmacological Treatment Table S10 Potential Indications for Hospitalization Table S11: Discharge Criteria and Recommendations for Follow-up does not reduce the 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

Evidence category	Sources of evidence	Definitions
A	Randomized controlled trials (RCTs) RCTs Most of the evidence is high quality without any significant limitations or bias	Endpoint evidence of well-designed RCTs that provide consistent findings in a population for which recommendations are not critical Requires high quality evidence ;; 2 clinical trials with a significant number of subjects, or one high quality RCT with a significant number of patients without any bias
V	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, posthospital or subgroup analyzes of RCTs, or meta-analyzes of RCTs Also applies when there are multiple RCTs, or important limitations are evident (methodological weaknesses, small numbers, short duration, sample in a population that differs from target population and recommendations, or results are somewhat conflicting
C	Non-randomized studies Observational studies	Evidence from uncontrolled or nonrandomized studies or from Observational studies
D	Consensus judgment panels	The consensus decision panel is considered to be of value, but the clinical literature on this issue is inadequate. Consensus panel is based on clinical experience or knowledge that does not meet the above criteria

Tab 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 consistentfindings 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 metaanalyses of RCTs. Limited body of Evidence also pertains when few RCTs exist, or important limitations are evident (methodologic 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 uncontrolledor non-randomized trials or from Observational studies observational studies.
D	Panel consensus judgment Provision of guidance is deemed 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 V). 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 (EvidenceV). ln the general population of adults ;; 65 years the 13-valent conjugated pneumococcal vaccine (PCV13) reduces bacteremia and serious invasive pneumococcal disease (Evidence V).

Table C3. Commonly Used COPD Support Drugs Tab S3. Commonly used maintenance medications in COPD
(version 2011.)
Table S4. Other pharmacological treatments Table S4. Other pharmacologic treatments

Alpha-1 antitrypsin augmentation therapy

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

Antitussives

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

Vasodilators

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

tableS5... Pulmonary rehabilitation, self-management and comprehensive care for COPD

Pulmonary rehabilitation Pulmonary rehabilitation improves shortness of breath, health status and exercise tolerance in stable patients ( Evidence level A). Pulmonary rehabilitation reduces hospital admissions in patients with recent exacerbations (: 5-4 weeks before admission) (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 and reduces the number of hospitalizations and visits to emergency departments ( proof B). Programslntegrated care lntegrated care and telemedicine has no benefit at the moment (Level of Evidence: B)

Tab 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) ( EvidenceV).

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 ( EvidenceV).

lntegrated careprograms

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

tableS6. End-of-life palliative care and hospice care for COPD Tab 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 (EvidenceV). 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 use of oxygen improves the survival rate of patients with severe chronic arterial hypoxemia at rest ( evidence A). In patients with stable COPD and moderate at rest or physically-induced arterial desaturation, the administration of long-term oxygen oxygen therapy does not lengthen the time to death or first hospitalization or provide sustained benefits in health, lung function, and 6 minutes of walking ( evidence A). Oxygenation at rest while 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 recent hospitalization, especially in those with severe persistent daytime hypercapnia (PaCO2 ;; 52 mm Hg.) ( evidence B).

Tab S7. Oxygen therapy and ventilatory support in stable COPD

Oxygentherapy

The long-term administration of oxygen increases survival 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 traveling does not exclude the development of severe hypoxemia when 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) ( EvidenceV).

Table S8. Surgical therapy for stable COPD

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

Tab S8. lnterventional 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).

Вronchoscopic 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 ( EvidenceV); Lung coils ( EvidenceV).

Rice.S1... Goals of treatment for stable COPD
Figure S1. Goals for treatment of stable COPD
tableS9... Key points for using non-pharmacological treatments

Education, self-government and pulmonary rehabilitation Education enhances patient knowledge, but there is no evidence that education itself changes patient behavior. Education in self-government with the support of a case manager with or without a written action plan is recommended for the prevention of exacerbations of complications such as hospitalization ( proof B). Rehabilitation is indicated for all patients with appropriate symptoms and / or a high risk of exacerbation and is the most effective intervention to improve physical performance and health (Level of Evidence: A). Physical activity is a strong predictor (predictor) of mortality ( Evidence level A). Patients should be encouraged to increase their level of physical activity. Vaccination Influenza vaccination is recommended for all patients with COPD ( Evidence level A). Pneumococcal vaccination: in PCV13 and PPSV23 is recommended for all patients> 65 years of age and in younger patients with serious comorbidities, including chronic heart disease or lung disease (level Evidence B). Nutrition Consideration is given to taking nutritional supplements in malnourished patients with COPD ( level of evidence B). End of life and palliative care All clinicians in the management of COPD patients should be made aware of the effectiveness of palliative approaches for symptom control ( level of evidenceD). End-of-life care should include discussions with patients and their families about their views on resuscitation and directive preferences ( level of evidenceD). Hypoxemia treatment In patients with severe hypoxemia at rest, prolonged oxygen therapy has been shown to reduce mortality ( level of evidence, A). In patients with a stable course of COPD and moderate desaturation at rest or during exercise, the appointment of long-term oxygen therapy does not lengthen the time to death or first hospitalization or provide a sustained improvement in quality of life, lung function, and within 6 minutes of walking ( evidence A). Resting oxygenation at sea level does not preclude the development of severe hypoxemia when traveling by air ( level of evidence C). Hypercapnia treatment Nlv should be the first ventilation mode used in COPD patients with acute respiratory failure, as it improves gas exchange, reduces the need for intubation, reduces hospital stay and improves survival ( Evidence level A). In patients with severe chronic hypercapnia and a history of hospitalization with acute respiratory failure, prolonged non-invasive ventilation may be considered ( proof B). Surgical bronchoscopy and surgery Surgery to reduce lung volume, improves respiratory function, exercise tolerance and quality of life in selected patients with the upper lobe of pulmonary emphysema and survival in the subgroup with upper pulmonary emphysema and low rehabilitation of physical performance ( Evidence level A). In selected patients with severe emphysema, bronchoscopic interventions, reduce end-expiratory lung volume and increase exercise tolerance, quality of life and lung 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 of 7 to 10, not candidates for operative lung volume reduction) lung transplantation may be considered for referral with at least one of the following: (1) History of hospitalizations for 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).

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

Education,self-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 ( EvidenceV). 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 ( EvidenceV).

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 ( EvidenceV).

lntervention 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 ( EvidenceV) or lung coils ( EvidenceV). ln selected patients with a large bulla surgical bullectomy may be considered (Evidence C). ln patients with very severe COPD (progressive disease, in 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 exacerbationassociated 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 assessing hospitalization * * 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. Аcute 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

Complete analysis of all clinical and laboratory data. Check supportive care and understanding. Revise the inhalation technique. Provide an understanding of the withdrawal of acute medications (steroids and / or antibiotics). Evaluate the need for continuing any oxygen therapy. Provide a treatment plan for comorbid conditions and follow-up. Ensure the implementation of activities: at the beginning of the subsequent<4 недель, и в конце последующих < 12 недель, как указано. All clinical or complementary methods of abnormalities should be identified. 1-4 weeks follow-up Assess coping skills in his / her usual environment. Review and understanding of the treatment regimen. Reassessment of inhalation techniques. Document the ability to be physically active and able to live in daily life. Determine comorbidity status 12-16 weeks follow-up Assess self-care skills in his / her usual environment. Review of the understanding of the treatment regimen. Reassessment of inhalation techniques. Assess the need for long-term oxygen therapy. Document the ability to be physically active and activities in daily life. Spirometry measurement: FVD1. Document symptoms: CAT or mMRC. Determine the comorbidity status.

Table S11. Discharge criteria and recommendations for follow-up

Full review of all clinical and laboratory Check maintenance therapy and Reassess inhaler Ensureunderstanding of withdrawal of acute medications (steroids and / or antibiotics). Аssess 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 Evaluateability to cope in his / her usual Reviewand understanding treatment Reassessmentof inhaler Reassess need for long-term Document symptoms: CAT or Determinestatus 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 Determinestatus of

Table S12. Activities that reduce the incidence of exacerbations of COPD Tab S12. lnterventions that reduce the frequency of COPD exacerbations

lntervention class	lntervention
Вronchodilators	LАвАs LAMАsLАвА + LAMА
Corticosteroid-containing regimens	LABA + lCSLAbA + LAMA + lCS
Anti-inflammatory (non-steroid)	Roflumilast
Anti-infectives	VaccinesLong term macrolides
Mucoregulators	N-acetylcysteine ​​Carbocysteine
Various others	Smoking cessation RehabilitationLung volume reduction