Clinical guidelines for COPD gold. COPD - national recommendations

The goals of COPD treatment can be divided into 4 main groups:
Elimination of symptoms and improvement of quality of life;
Reducing future risks, etc.; prevention of exacerbations;
Slowing down the progression of the disease;
Reduced mortality.
Treatment of COPD includes pharmacological and non-pharmacological approaches. Pharmacologic treatments include bronchodilators, combinations of ICS and long-acting bronchodilators (LABAs), phosphodiesterase-4 inhibitors, theophylline, and influenza and pneumococcal vaccinations.
Non-pharmacological treatments include smoking cessation, pulmonary rehabilitation, oxygen therapy, respiratory support and surgery.
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. Smoking cessation is the most effective intervention and has a major impact on the progression of COPD. The usual advice from a doctor leads to smoking cessation in 7.4% of patients (2.5% more than in controls), and as a result of a 3-10-minute consultation, the smoking cessation rate reaches about 12%. With more time and more complex interventions that include skills training, problem-solving training, and psychosocial support, smoking cessation rates can reach 20-30%.
In the absence of contraindications, it is recommended to prescribe pharmacological agents for the treatment of tobacco addiction.

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

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

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

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

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

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

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

Choosing an inhaler.

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

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

Treatment tactics for stable COPD.

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

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

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

3.2 Surgical treatment.

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

3.3 Other treatments.

Long-term oxygen therapy.

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

Long-term home ventilation.

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

5
1 Federal State Budgetary Educational Institution of Higher Education USMU of the Ministry of Health of Russia, Ekaterinburg
2 Federal State Budgetary Educational Institution of Higher Education NSMU of the Ministry of Health of Russia, Novosibirsk
3 Federal State Budgetary Educational Institution of Higher Education South Ural State Medical University of the Ministry of Health of Russia, Chelyabinsk
4 Federal State Budgetary Educational Institution of Higher Education TSMU of the Ministry of Health of Russia, Vladivostok
5 Federal State Budgetary Educational Institution of Higher Education NSMU of the Ministry of Health of Russia, Novosibirsk, Russia

Currently, chronic obstructive pulmonary disease (COPD) is a global problem, which is associated with the widespread prevalence of the disease and high mortality. The main cause of death in patients with COPD is progression of the underlying disease. In 2016–2017 Several large, authoritative events were held at which the therapeutic options for treating patients with COPD were discussed, taking into account phenotypes, the need to prevent exacerbations, as well as the characteristics of inhalation therapy.
Despite the priority role of inhaled long-acting bronchodilators in the treatment of patients with COPD, the authors’ goal was to draw the reader’s attention to therapy with fixed combinations of inhaled glucocorticosteroids (ICS)/long-acting β2-agonists (LABA), emphasizing the priority of extrafine inhalation form aerosol for COPD, and combinations of ICS/LABAs in combination with long-acting anticholinergics (LAAs). An analysis of recommendations and clinical observations on the treatment of this nosology, as well as studies aimed at studying the effectiveness and safety of the triple combination of ICS/LABA/LAMA compared with the effectiveness and safety of other options for regular treatment of COPD.

Keywords: COPD, inhalation therapy, recommendations, inhaled glucocorticosteroids, long-acting β 2 -agonists, extra-fine aerosols.

For quotation: Leshchenko I.V., Kudelya L.M., Ignatova G.L., Nevzorova V.A., Shpagina L.A. Resolution of the expert council “The place of anti-inflammatory therapy for COPD in real clinical practice” dated April 8, 2017, Novosibirsk // RMZh. 2017. No. 18. pp. 1322-1324

Resolution of the Board of Experts “Place of anti-inflammatory therapy in COPD in real clinical practice” dated April 8th, 2017, Novosibirsk

Leshchenko I.V. 1, Kudelya L.M. 2, Ignatova G.L. 3, Nevzorova V.A. 4, Shpagina L.A. 2

1 Ural State Medical University, Yekaterinburg, Russia
2 Novosibirsk State Medical University, Russia
3 South-Ural State Medical University, Chelyabinsk, Russia
4 Pacific State Medical University, Vladivistok, Russia

Currently, chronic obstructive pulmonary disease (COPD) represents a global problem, which is associated with the prevalence of the disease and high mortality. The main cause of the death of patients with COPD is the progression of the disease. In 2016-2017 years there were a number of major authoritative meetings, where the therapeutic options of the treatment of patients with COPD were discussed, taking into account the phenotypes, the need of prevention of exacerbations, as well as the features of inhalation therapy. Despite the fact that the inhaled long-acting bronchodilators take the first place in the treatment of COPD patients, the aim of the authors was to draw the reader's attention to the therapy with fixed combinations of inhaled glucocorticosteroids (ICS) / long-acting β 2 -agonists (LABA), emphasizing the priority of the extra-fine particle aerosols in COPD, and a combination of ICS / LABA together with long-acting anticholinergics (LAMA). Recommendations and clinical observations of the treatment of this nosology are given , as well as results of comparative studies of efficacy and safety of the triple combination ICS / LABA / LAMA versus other COPD therapies presented.

Key words: COPD, inhalation therapy, recommendations, inhaled glucocorticosteroids, long-acting β 2 -agonists, extra-fine-particles aerosols.
For citation: Leshchenko I.V., Kudelya L.M., Ignatova G.L. et al. Resolution of the Board of Experts “Place of anti-inflammatory therapy in COPD in real clinical practice” dated April 8th, 2017, Novosibirsk // RMJ. 2017. No. 18. P. 1322–1324.

The resolution of the expert council “The place of anti-inflammatory therapy for COPD in real clinical practice” dated April 8, 2017, Novosibirsk was presented

Research transparency. The authors received no grants, honoraria, or sponsorship for the preparation of this article. The authors are solely responsible for submitting the final version of the manuscript for publication.
Declaration of financial and other relationships. The authors took part in the development of the concept, design of the work and in writing the manual.
copies. The final version of the manuscript was approved by all authors.

In 2017, another revision of the “Global Strategy for the Diagnosis, Treatment and Prevention of COPD” was published, containing significant changes both in the stratification of patients and in the scheme for choosing therapy.
Currently COPD is global problem, which is associated with widespread prevalence and high mortality.
In a published cross-sectional population-based epidemiological study conducted in 12 regions of Russia (as part of the GARD program) and including 7164 people ( average age 43.4 years), the prevalence of COPD among people with respiratory symptoms was 21.8%, and in the general population – 15.3%.
According to WHO, today COPD is the 3rd leading cause of death in the world; about 2.8 million people die from COPD every year, accounting for 4.8% of all causes of death. About 10–15% of all COPD cases are occupational COPD, which increases the social significance of the disease.
The main cause of death in patients with COPD is progression of the underlying disease. About 50–80% of COPD patients die from respiratory causes associated with progressive respiratory failure, pneumonia, or from severe cardiovascular pathology or malignant neoplasms.
In 2016–2017 Several large, authoritative events were held at which the therapeutic options for treating patients with COPD were discussed, taking into account phenotypes, the need to prevent exacerbations, as well as the characteristics of inhalation therapy.

Treatment

Currently, the main drugs used in the treatment of COPD are long-acting anticholinergics (LAAs) and long-acting β2-agonists (LABAs), recently introduced fixed combinations of LABAs/LABAs, fixed combinations of inhaled glucocorticosteroids (ICS)/LABAs and ICS/LABAs in combined with DDAH.
Although inflammation is excluded from the definition of the new GOLD-2017 edition, the pathophysiology of the disease still corresponds to the inflammatory model of COPD development, in which a large role is given to inflammation of small organs. respiratory tract. Peculiarity inflammatory process in COPD it consists mainly of damage to the small airways, leading to their remodeling, parenchymal destruction and obstruction. The severity of inflammation, determined by the level of inflammatory biomarkers (neutrophils, macrophages, CD-4, CD-8 cells), and occlusion of small bronchi correlate with a decrease in forced expiratory volume in 1 second. In this regard, the use of an extra-fine inhalation form of an iGCS/LABA aerosol, as well as a combination of an iGCS/LABA with a LABA in patients with COPD becomes especially relevant.
Comparative analysis published data, presented at the annual congress of the American Thoracic Society in San Francisco on May 18, 2016, showed that the use of extra-fine fixed combinations containing inhaled corticosteroids in patients with COPD naturally leads to a significant reduction in the frequency of exacerbations, improvement clinical manifestations and quality of life of patients compared with the effects of LABA use (on average by 25–30%). This confirms the importance of using ICS-containing combinations in the prevention of exacerbations of COPD and the additional advantages of extra-fine drugs that provide better delivery active ingredients V distal sections respiratory tract.
The FLAME study demonstrated the superiority of a specific fixed-dose combination of LABA/LAMA over a specific fixed-dose combination of ICS/LABA in reducing the number of exacerbations. It is worth noting that this study had limitations, because the vast majority of patients had a history of rare exacerbations and only 20% had 2 or more exacerbations in the previous year. When conducting an additional analysis of the frequency of exacerbations in patients who had more than one exacerbation in history, the combination of LABA/LABA did not show superiority compared to the combination of ICS/LABA.
To date, there is no evidence that replacing LABA/LABA with ICS/LABA will prevent exacerbations. If the combination of ICS/LABA is not effective in reducing symptoms and exacerbations, the addition of a LABA is required.
Currently, a number of clinical studies of the fixed combination of ICS/LABA/LAMA are being conducted, aimed at studying the effectiveness and safety of the triple combination compared to other options for regular treatment of COPD. There is evidence of the benefit of triple therapy compared with ICS/LABA therapy. Studies are being conducted to compare the effects of the combination of ICS/LABA/LAMA and the combination of LABA/LAMA in preventing exacerbations of COPD.
Regarding the risk of pneumonia associated with the use of inhaled corticosteroids, the European Medicines Agency indicates that the reduction in the incidence of exacerbations of COPD outweighs the risk of an increase in the incidence of pneumonia associated with the use of inhaled corticosteroids, and the increased risk of pneumonia does not lead to an increased risk of death in patients.
Thus, clinical studies and actual clinical practice show that in a number of patients, a fixed combination of ICS/LABA or a triple combination of ICS/LABA/LABA provide significant advantages over other treatment regimens.
Patients in this category have the following indications:
2 or more exacerbations per year or 1 exacerbation requiring hospitalization during LAMA or LABA/LAMA therapy;
history of bronchial asthma, manifesting before the age of 40 years;
eosinophilia of sputum or blood outside of exacerbation (there is no consensus on this biomarker). According to GOLD 2017 experts, prospective studies are required to evaluate eosinophilia as a predictor of response to ICS therapy to determine cutoff values ​​and their value in clinical practice. Until now, the mechanism that enhances the response to ICS therapy in patients with COPD and blood eosinophilia remains unclear.
As clinical practice shows, if therapy with a combination of corticosteroids/LABAs brings clear benefits to the patient (improvement of pulmonary function, alleviation of symptoms or reduction in the frequency of exacerbations), then its discontinuation is not advisable. Moreover, if a patient with COPD achieves a clinical effect (no exacerbations and severe symptoms) against a background of high daily dose iGCS, then in the future, after 3 months, it is advisable to gradually reduce the daily dose of iGCS from high to medium or low in combination with a LABA or against the background of triple therapy with iGCS/LABA/LAMA.
To reduce the risk of pneumonia and improve the effectiveness of therapy, it is advisable to use extra-fine inhaled corticosteroids containing combinations that have an anti-inflammatory effect directly in the small airways.

Literature

1. Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2017. Available from: http://www.goldcopd.org
2. Fishwick D., Sen D., Barber C. et al. Occupational chronic obstructive pulmonary disease: a standard of care // Occup Med (Lond). 2015. Vol. 65(4). P. 270–282.
3. Clinical guidelines Russian Respiratory Society. Chronic obstructive pulmonary disease [Electronic resource]. 2016. URL: http://pulmonology.ru. 2016. URL: http://pulmonology.ru (in Russian)].
4. Hogg J.C. Pathophysiology of airflow limitation in chronic obstructive pulmonary disease // Lancet. 2004. Vol. 364. P. 709–721.
5. Hogg J.C., Chu F., Utokaparch S. et al. The Nature of Small-Airway Obstruction in Chronic Obstructive Pulmonary Disease // N Engl J Med. 2004. Vol. 350. P. 2645–2653.
6. Hogg J.C., Chu F.S.F., Tan W.C. et al. Survival after Lung Volume Reduction in Chronic Obstructive Pulmonary Disease. Insights from Small Airway Pathology // Am J Respir Crit Care Med. 2007. Vol. 176. P. 454–459.
7. Singh D. Comparison of extra fine beclomethasone dipropionate/formoterol fumarate versus other double combinations on reduction of moderate/severe exacerbations. Report at ATS, 05/18/2016.
8. Wedzicha J.A., Banerji D., Chapman K.R. et al. Indacaterol–Glycopyrronium versus Salmeterol–Fluticasone for COPD // N Engl J Med. 2016. Vol. 374. P. 2222–2234.
9. PRAC reviews known risk of pneumonia with inhaled corticosteroids for chronic obstructive pulmonary disease. URL: http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2016/03/news_detail_002491.jspandmid=WC0b01ac058004d5c1.
10. Festic E., Bansal V., Gupta E., Scanion P.D. Association of Inhaled Corticosteroids with Incident Pneumonia and Mortality in COPD Patients; Systematic Review and Meta-Analysis // COPD. 2016. Vol. 13. P. 312–326.
11. Kerwin E. A new alphabet for COPD care // Eur Respir J. 2016. Vol. 48. P. 972–975.

Russian Respiratory Society

chronic obstructive pulmonary disease

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

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

1. Methodology

Methods used to collect/select evidence:

search in electronic databases.

Description of methods used to collect/select evidence:

Methods used to assess the quality and strength of evidence:

Expert consensus;

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

Methods used to analyze evidence:

Systematic reviews with evidence tables.

Description of methods used to analyze evidence:

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

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

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

Evidence tables:

Evidence tables were completed by members of the working group.

Methods used to formulate recommendations:

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

Good Practice Points (GPPs):

Economic analysis:

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

External expert assessment;

Internal expert assessment.

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

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

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

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

Consultation and expert assessment:

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

Working group:

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

2. Definition of COPD and epidemiology

Definition

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

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

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

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

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

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

Epidemiology

Prevalence

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

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

Mortality

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

V Ukraine and Romania.

IN period from 1990 to 2000 mortality from cardiovascular diseases

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

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

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

Socio-economic significance of COPD

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

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

3. Clinical picture of COPD

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

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

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

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

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

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

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

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

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

The course of COPD is an alternation of a stable phase and exacerbation of the disease, but in different people it does not proceed the same way. However, progression of COPD is common, especially if the patient continues to be exposed to inhaled pathogenic particles or gases.

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

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

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

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

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

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

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

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

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

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

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

Background

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

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

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

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

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

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

Severity

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

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

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

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

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

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

• amyotrophy;
• cachexia;
• weight loss.

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

Symptom severity

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

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

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

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

Risks and groups of COPD

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

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

At various degrees severity, the prediction of the frequency of exacerbations was calculated based on the previous medical history. Table "Risks":

There are 3 ways to assess the risk of exacerbation:

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

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

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

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

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

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

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

Phenotypes of COPD

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

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

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

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

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

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

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

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

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

12.10.2017

The Global Strategy for the Diagnosis, Management and Prevention of COPD (GOLD) is a document that every practicing physician in Europe who deals with patients with COPD is guided by today. The prevalence of diseases associated with 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 being improved, and 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 success in the global fight against COPD regularly, releasing annual updates of the recommendation document. So, in February 2017, another update of the GOLD recommendations was released. What changes does the updated GOLD‑2017 manual contain? Let's try to figure it out in detail.

GOLD-2017: changes compared to the 2016 version

Main changes:

Revised definition of COPD;

A new, improved principle for assessing ABCD group membership 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 abnormalities of the airways and/or alveoli, usually caused by significant exposure to noxious particles or gases.”

Stratification of patients into ABCD groups for subsequent treatment selection is based on symptom assessment (using standard CAT or mMRC questionnaires) and history of exacerbations. Spirometry data, together with symptoms and history of exacerbations, remain an important aspect of diagnosis, prognosis, and decisions about other necessary therapeutic approaches.

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

GOLD‑2017: changes in assessment

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

EF 1 – volume of forced expiration in 1 s;

FVC – forced vital capacity.

Classification of patients 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 (without hospitalization) in the previous year.

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

Major changes in the treatment algorithm

Pharmacotherapy is determined based on clinical characteristics; the degree of airflow limitation is not a determining factor.

The combination of long-acting beta-agonists (LAAs)/long-acting anticholinergics (LAMAs) 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 based on their effect on dyspnea. These can be both short-acting and long-acting drugs.

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

Group B

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

There is no evidence that one class or another of long-acting bronchodilators is superior in reducing symptoms in this group of patients. The choice between drug classes is made based on the patient's individual perception of symptom relief.

For patients with persistent shortness of breath who are on monotherapy, the use of two bronchodilators is recommended.

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

If adding a second bronchodilator does not improve symptoms, return to monotherapy.

Group B patients are likely to have comorbidities that may add to symptoms, affect prognosis, and require additional testing.

Group C

Initial therapy should consist of bronchodilator monotherapy. In two head-to-head comparisons, MCDD was better at preventing exacerbations than LABA. Thus, it is recommended to initiate therapy in this group with MCDD.

Patients with persistent exacerbations may benefit from adding a second bronchodilator or taking a SABA/ICS combination. Because ICS increase the risk of pneumonia in some patients, the first choice is a combination of dietary supplements and MCDDs.

– BADD/MCDD in studies were assessed by patients as a more effective treatment than single drugs. If a monobronchodilator is chosen for initial therapy, then MCDD is preferable in terms of preventing exacerbations than LABA.

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

– Group D patients have a high risk of developing pneumonia when taking ICS.

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

In patients with exacerbations despite therapy with dietary supplements/MCDD, there are two alternative routes:

– Escalation to BADD/MHDD/ICS. A comparison of the effectiveness of preventing exacerbations of LABA/MCDD and LABA/MCDD/ICS is under investigation.

– Switching to BADD/ICS. However, there is no evidence that switching from a dietary supplement/MCDD to a dietary supplement/ICS will result in better prevention of exacerbations. If LABA/ICS therapy has not had a positive effect on symptoms/exacerbations, MCDD may be added.

If a patient continues to have exacerbations while taking a dietary supplement/MCDD/ICS, the following should be considered:

– Addition of roflumilast. Decision may 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.

– Addition of macrolide. Azithromycin has the best existing evidence base. The possibility of resistance development should also be considered when making decisions.

– Cancellation of ICS. Lack of effectiveness, increased risk of adverse events (including pneumonia), and the evidence base demonstrating their withdrawal without harm support this recommendation.

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

GOLD‑2017: Global Strategy for the Diagnosis,

Abstract translation from English. Alexandra Merkulova

Thematic issue “Pulmonology, Allergology, Rhinolaryngology” No. 2 (39), May 2017

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