Chronic obstructive pulmonary disease (COPD)- a chronic environmentally mediated inflammatory disease of the respiratory system with a predominant lesion of the distal respiratory tract and pulmonary parenchyma with the development of emphysema, manifested by partially reversible bronchial obstruction, characterized by the progression and growing symptoms of chronic respiratory failure.

Epidemiology

COPD is a common disease. According to WHO (1996), the prevalence of COPD among men is 9.34: 1000, among women - 7.33: 1000. Persons over 40 prevail. COPD as a cause of death ranks 4th in the world in the age group over 45.

Etiology and pathogenesis

COPD, regardless of the severity, is manifested by a chronic inflammatory process with a predominant lesion of the distal respiratory tract and pulmonary parenchyma. Patients with COPD are characterized by a decrease in the maximum expiratory flow rate and a slow, gradual deterioration in the gas exchange function of the lungs, which reflects the irreversible nature of the airway obstruction.

Major risk factors(GOLD, 2006).

Genetic.

Inhalation of harmful particles:

Smoking;

Industrial dust (organic and inorganic);

Household dust (home ecology);

Dust outside the home (ecology of the environment);

Lung growth and development.

Oxidative stress.

Respiratory infections.

Socioeconomic nutritional status.

Comorbid conditions.

Chronic inflammation in COPD is a key element in disease progression. The main components of the pathogenesis of chronic inflammation are oxidative stress, proteolytic tissue destruction, immune deficiency, and colonization of microorganisms. The main stages of the pathogenesis of COPD are presented in table 32-1.

Table 32-1

COPD pathogenesis scheme

Note.

This whole complex of inflammatory mechanisms leads to the formation of two main processes characteristic of COPD: impaired bronchial patency and the development of emphysema.

Conventionally, the main mechanisms of the pathogenesis of COPD can be divided into five components, mutually complementing each other (Table 32-2).

Table 32-2

The main pathogenetic mechanisms of the hoble

Note. Pulmonology: National Guide / Ed. A.G. Chuchalin, 2009.

Factors provoking an exacerbation of the disease:

bronchopulmonary infection;

increased exposure to exogenous damaging factors;

COPD classification.

The correspondence of the main clinical signs to the FVD indicators at different stages of COPD are presented in Table 32-3.

Table 32-3

Compliance of the main clinical signs with the FVD indicators

Note. Pulmonology: National Guide / ed. A.G. Chuchalin, 2009.

For the diagnosis of COPD, the following indicators are of greatest importance:

FEV 1 - forced expiratory volume in the first second,

FVC - forced vital capacity

FEV 1 / FZhEL - Tiffno index

To study the reversibility of obstruction, spirometry is performed with any bronchodilator. If the obstruction is irreversible, the FEV 1 index increases by no more than 10%.

COPD (chronic obstructive pulmonary disease) is a disease that develops as a result of an inflammatory reaction to the action of certain environmental stimuli, with damage to the distal bronchi and the development of emphysema, and which is manifested by a progressive decrease in the air flow rate in the lungs, an increase, as well as damage to other organs.

COPD is the second leading chronic noncommunicable disease and the fourth leading cause of death, and the rate is growing steadily. Due to the fact that this disease is inevitably progressive, it occupies one of the first places among the causes of disability, as it leads to a violation of the main function of our body - the function of breathing.

The problem of COPD is truly global. In 1998, an initiative group of scientists created the "Global Initiative for Chronic Obstructive Lung Disease - GOLD". The main tasks of GOLD are the wide dissemination of information about this disease, systematization of experience, explanation of the causes and corresponding prevention measures. The main message that doctors want to convey to humanity: COPD can be prevented and treated by this postulate is even included in the modern working definition of COPD.

Causes of COPD

COPD develops with a combination of predisposing factors and provoking environmental agents.

Predisposing factors

1. Hereditary predisposition. It has already been proven that congenital deficiency of certain enzymes predisposes to the development of COPD. This explains the family history of this disease, as well as the fact that not all smokers, even with long experience, get sick.
2. Gender and age. Men over 40 suffer more from COPD, but this can be explained by aging of the body and the duration of smoking experience. Data are given that now the incidence rate among men and women is almost equal. The reason for this may be the spread of smoking among women, as well as the increased sensitivity of the female body to secondhand smoke.
3. Any negative impacts that affect the development of the child's respiratory system in the prenatal period and early childhood, increase the risk of COPD in the future. In itself, physical underdevelopment is also accompanied by a decrease in lung volume.
4. Infections. Frequent respiratory infections during childhood, as well as increased susceptibility to them at an older age.
5. Bronchial hyperreactivity. Although bronchial hyperreactivity is the main mechanism of development, this factor is also considered a risk factor for COPD.

Provoking factors

COPD pathogenesis

Exposure to tobacco smoke and other irritants leads to chronic inflammation in the walls of the bronchi in susceptible individuals. The key is damage to their distal parts (that is, located closer to the pulmonary parenchyma and alveoli).

As a result of inflammation, there is a violation of the normal secretion and discharge of mucus, blockage of small bronchi, infection easily joins, inflammation spreads to the submucosal and muscle layers, muscle cells die and are replaced by connective tissue (bronchial remodeling process). At the same time, the destruction of the parenchyma of the lung tissue, the bridges between the alveoli occurs - emphysema develops, that is, the hyper-airiness of the lung tissue. The lungs seem to be inflated with air, their elasticity decreases.

On exhalation, small bronchi do not expand well - air hardly leaves the emphysematous tissue. Normal gas exchange is impaired, as the volume of inspiration also decreases. As a result, the main symptom of all patients with COPD arises - shortness of breath, especially aggravated by movement, walking.

The consequence of respiratory failure is chronic hypoxia. The whole organism suffers from this. Prolonged hypoxia leads to a narrowing of the lumen of the pulmonary vessels - it occurs, which leads to the expansion of the right heart (cor pulmonale) and the addition of heart failure.

Why is COPD isolated as a separate nosology?

The awareness of this term is so low that most of the patients already suffering from this disease do not know that they have COPD. Even if such a diagnosis is presented in the medical documentation, in everyday life of both patients and doctors, "emphysema", which was habitual earlier, still prevail.

The main components in the development of COPD are indeed chronic inflammation and emphysema of the lungs. So why, then, is COPD a separate diagnosis?

In the name of this nosology, we see the main pathological process - chronic obstruction, that is, narrowing of the airway lumen. But the process of obstruction is present in other diseases as well.

The difference between COPD and bronchial asthma is that in COPD, obstruction is almost or completely irreversible. This is confirmed by spirometric measurements using bronchodilators. In bronchial asthma, after the use of bronchodilators, there is an improvement in FEV1 and PSV indicators by more than 15%. This obstruction is interpreted as reversible. In COPD, these numbers do not change significantly.

Chronic bronchitis may precede or accompany COPD, but it is an independent disease with clearly defined criteria (prolonged cough and), and the term itself assumes damage to the bronchi only. With COPD, all structural elements of the lungs are affected - bronchi, alveoli, vessels, pleura. Chronic bronchitis is not always accompanied by obstructive disorders. On the other hand, increased sputum production is not always observed in COPD. That is, in other words, there may be chronic bronchitis without COPD, and COPD does not quite fall under the definition of bronchitis.

Chronic obstructive pulmonary disease

Thus, COPD is now a separate diagnosis, has its own criteria, and in no way replaces other diagnoses.

Diagnostic criteria for COPD

COPD can be suspected if there is a combination of all or several of the symptoms, if they occur in people over 40:

A reliable confirmation of COPD is a spirometric indicator of the ratio of the forced expiratory volume in 1 s to the forced vital capacity of the lungs (FEV1 / FVC), carried out 10-15 minutes after the use of bronchodilators (beta-sympathomimetics salbutamol, beroteka or 35-40 minutes after short-acting anticholinergics –Ipratropium bromide). The value of this indicator<0,7 подтверждает ограничение скорости воздушного потока и в сочетании с подтвержденными факторами риска является достоверным критерием диагноза ХОБЛ.

The remaining spirometry indicators - peak expiratory flow rate, as well as the measurement of FEV1 without a test with bronchodilators can be performed as a screening examination, but do not confirm the diagnosis of COPD.

Other methods prescribed for COPD, in addition to the usual clinical minimum, include chest x-ray, pulse oximetry (determination of blood oxygen saturation), blood gas analysis (hypoxemia, hypercapnia), bronchoscopy, chest CT, sputum examination.

COPD classification

There are several classifications of COPD by stages, severity, clinical options.

Stage classification takes into account the severity of symptoms and spirometry data:

• Stage 0. Risk group. Exposure to adverse factors (smoking). There are no complaints, the lung function is not impaired.
• Stage 1. Mild course of COPD.
• Stage 2. Moderate COPD.
• Stage 3. Heavy course.
• Stage 4. Extremely severe course.

In the latest GOLD report (2011), it was proposed to exclude the classification by stages, it remains classification by severity based on FEV1 indicators:

In patients with FEV1 / FVC<0,70:

• GOLD 1: Light FEV1 ≥80% of due
• GOLD 2: Moderate 50% ≤ FEV1< 80%.
• GOLD 3: Heavy 30% ≤ FEV1< 50%.
• GOLD 4: Extremely Severe FEV1<30%.

It should be noted that the severity of symptoms does not always correlate with the degree of bronchial obstruction. Patients with mild obstruction may be disturbed by a rather pronounced shortness of breath, and, conversely, patients with GOLD 3 and GOLD 4 may feel rather satisfactory for a long time. To assess the severity of shortness of breath in patients, special questionnaires are used, the severity of symptoms is determined in points. It is also necessary in assessing the course of the disease to be guided by the frequency of exacerbations and the risk of complications.

Therefore, in this report, it is proposed, based on the analysis of subjective symptoms, spirometry data and the risk of exacerbations, to divide patients into clinical groups - A, B, C, D.

Practitioners also distinguish clinical forms of COPD:

1. Emphysematous variant of COPD. Of the complaints in such patients, dyspnea predominates. Coughs are less common, and there may be no sputum. Hypoxemia, pulmonary hypertension come late. Such patients, as a rule, have a low body weight, the skin color is pink-gray. They are called "pink puffers".
2. Bronchitic option. Such patients complain mainly of cough with sputum, shortness of breath worries less, they quickly develop cor pulmonale with a corresponding picture of heart failure - blueness, edema. Such patients are called "blue edema".

The division into emphysematous and bronchitic variants is rather arbitrary, mixed forms are more often observed.

During the course of the disease, a stable phase and an exacerbation phase are distinguished.

Exacerbation of COPD

An exacerbation of COPD is an acutely developing condition when the symptoms of the disease go beyond its normal course. There is an increase in shortness of breath, cough and deterioration of the general condition of the patient. The usual therapy, which he used earlier, does not relieve these symptoms to the usual state, a change in the dose or treatment regimen is required. Hospitalization is usually required for an exacerbation of COPD.

Diagnosis of exacerbations is based solely on complaints, anamnesis, clinical manifestations, and can also be confirmed by additional studies (spirometry, complete blood count, microscopy and bacteriological examination of sputum, pulse oximetry).

The causes of exacerbation are most often respiratory viral and bacterial infections, less often other factors (exposure to harmful factors in the ambient air). A common event in a patient with COPD is an event that significantly decreases lung function, and it may take a long time to return to baseline or stabilize at more severe disease.

The more often exacerbations occur, the worse the prognosis of the disease and the higher the risk of complications.

Complications of COPD

Due to the fact that patients with COPD exist in a state of constant hypoxia, they often develop the following complications:

COPD treatment

Basic principles of treatment and prevention for COPD:

1. To give up smoking. At first glance, this is a simple, but the most difficult moment to implement.
2. Pharmacotherapy. Early initiation of basic drug treatment can significantly improve the patient's quality of life, reduce the risk of exacerbations and increase life expectancy.
3. The drug therapy regimen should be selected individually, taking into account the severity of the course, the patient's adherence to long-term treatment, the availability and cost of drugs for each individual patient.
4. Vaccinations against influenza and pneumococcal infections should be offered to patients with COPD.
5. The positive effect of physical rehabilitation (training) has been proven. This method is under development, as long as there are no effective therapeutic programs. The easiest way that can be offered to the patient is to walk for 20 minutes daily.
6. In the case of a severe course of the disease with severe respiratory failure, prolonged oxygen inhalation as a means of palliative care can improve the patient's condition and prolong life.

To give up smoking

It has been proven that smoking cessation has a significant impact on the course and prognosis of COPD. Despite the fact that chronic inflammation is considered irreversible, smoking cessation slows its progression, especially in the early stages of the disease.

Tobacco addiction is a serious problem that requires a lot of time and effort not only for the patient himself, but also for doctors and relatives. A special long-term study with a group of smokers was carried out, in which various measures were proposed to combat this addiction (conversations, beliefs, practical advice, psychological support, visual agitation). With such an investment of attention and time, it was possible to achieve smoking cessation in 25% of patients. Moreover, the longer and more often the conversations are held, the more likely they will be effective.

Anti-tobacco programs are becoming national goals. It became necessary not only to promote a healthy lifestyle, but also to legally punish smoking in public places. This will help limit the harm from at least secondhand smoke. Tobacco smoke is especially harmful for pregnant women (both active and passive smoking) and children.

In some patients, tobacco addiction is akin to drug addiction, and conducting interviews in this case will not be enough.

In addition to agitation, there are also medicinal ways to combat smoking. These are nicotine replacement pills, sprays, chewing gums, skin patches. The effectiveness of some antidepressants (bupropion, nortriptyline) in the formation of long-term smoking cessation has also been proven.

Pharmacotherapy for COPD

COPD drug therapy aims to treat symptoms, prevent flare-ups, and slow the progression of chronic inflammation. It is impossible to completely stop or cure the destructive processes in the lungs with existing drugs.

The main drugs used to treat COPD are:

Bronchodilators

Bronchodilators used to treat COPD relax the smooth muscles of the bronchi, thereby expanding their lumen and facilitating the passage of air during exhalation. All bronchodilators have been proven to increase exercise tolerance.

Bronchodilator drugs include:

1. Short-acting beta stimulants ( salbutamol, fenoterol).
2. Long-acting beta stimulants ( salmoterol, formoterol).
3. Short-acting anticholinergics ( ipratropium bromide - atrovent).
4. Long-acting anticholinergics ( tiotropium bromide - spiriva).
5. Xanthines ( euphylline, theophylline).

Almost all existing bronchodilators are used in inhalation form, which is a preferred method over oral administration. There are different types of inhalers (metered-dose aerosol, powder inhalers, inhalation-activated inhalers, liquid forms for nebulizer inhalation). In severe patients, as well as in patients with intellectual disabilities, inhalation is best done through a nebulizer.

This group of drugs is the main one in the treatment of COPD, it is used at all stages of the disease as monotherapy or (more often) in combination with other drugs. For continuous therapy, the use of long-acting bronchodilators is preferable. If it is necessary to prescribe short-acting bronchodilators, preference is given to combinations fenoterol and ipratropium bromide (berodual).

Xanthines (aminophylline, theophylline) are used in the form of tablets and injections, have many side effects, and are not recommended for long-term treatment.

Glucocorticosteroid hormones (GCS)

GCS are a powerful anti-inflammatory agent. They are used in patients with severe and extremely severe degrees, and are also prescribed in short courses for exacerbations in the moderate stage.

The best form of application is inhaled corticosteroids ( beclomethasone, fluticasone, budesonide). The use of such forms of GCS minimizes the risk of systemic side effects of this group of drugs, which inevitably occur when they are taken orally.

Monotherapy with GCS is not recommended for patients with COPD, they are more often prescribed in combination with long-acting beta-agonists. The main combination drugs: formoterol + budesonide (symbicort), salmoterol + fluticasone (seretide).

In severe cases, as well as during an exacerbation, systemic GCS can be prescribed - prednisone, dexamethasone, kenalog... Long-term therapy with these drugs is fraught with the development of severe side effects (erosive and ulcerative lesions of the gastrointestinal tract, Itsenko-Cushing's syndrome, steroid diabetes, osteoporosis, and others).

Bronchodilators and corticosteroids (and more often a combination of them) are the main most affordable drugs that are prescribed for COPD. The doctor selects the treatment regimen, doses and combinations individually for each patient. In the choice of treatment, not only the recommended GOLD regimens for different clinical groups matter, but also the patient's social status, the cost of drugs and its availability for a particular patient, the ability to learn, and motivation.

Other drugs used for COPD

Mucolytics (sputum-thinning agents) are prescribed for viscous, difficult-to-cough up sputum.

Phosphodiesterase-4 inhibitor roflumilast (Daxas) Is a relatively new drug. It has a prolonged anti-inflammatory effect and is a kind of alternative to GCS. It is used in tablets of 500 mg once a day in patients with severe and extremely severe COPD. Its high efficiency has been proven, but its use is limited due to the high cost of the drug, as well as a rather high percentage of side effects (nausea, vomiting, diarrhea, headache).

There are studies that the drug fenspiride (Erespal) has an anti-inflammatory effect, similar to GCS, and can also be recommended for such patients.

From physiotherapeutic methods of treatment, the method of intrapulmonary percussion ventilation of the lungs is becoming widespread: a special device generates small volumes of air that are supplied to the lungs with rapid jerks. From such pneumomassage, the collapsed bronchi are straightened and ventilation of the lungs is improved.

Treating an exacerbation of COPD

The goal of treating exacerbations is to stop the current exacerbation as much as possible and prevent them from occurring in the future. Depending on the severity, the treatment of exacerbations can be carried out on an outpatient basis or in a hospital.

The main principles for the treatment of exacerbations:

• It is necessary to correctly assess the severity of the patient's condition, exclude complications that can be disguised as exacerbations of COPD, and promptly send for hospitalization in life-threatening situations.
• With an exacerbation of the disease, the use of short-acting bronchodilators is preferable to long-acting. Doses and frequency of administration tend to be higher than usual. It is advisable to use spacers or nebulizers, especially in critically ill patients.
• In case of insufficient effect of bronchodilators, intravenous administration of aminophylline is added.
• If monotherapy was previously used, a combination of beta-stimulants with anticholinergics (also short-acting) is used.
• In the presence of symptoms of bacterial inflammation (the first sign of which is the appearance of purulent sputum), broad-spectrum antibiotics are prescribed.
• Connection of intravenous or oral glucocorticosteroids. An alternative to the systemic use of corticosteroids is inhalation of pulmicort through a nebulizer 2 mg twice a day after inhalations of berodual.
• Dosed oxygen therapy when treating patients in a hospital through nasal catheters or a Venturi mask. The oxygen content in the inhaled mixture is 24-28%.
• Other measures are maintenance of water balance, anticoagulants, treatment of concomitant diseases.

Caring for patients with severe COPD

As already mentioned, COPD is a steadily progressive disease and inevitably leads to the development of respiratory failure. The speed of this process depends on many things: the patient's refusal to smoke, adherence to treatment, the patient's material capabilities, his memory abilities, and the availability of medical care. Starting with a moderate degree of COPD, patients are referred to MSEC to receive a disability group.

With an extremely severe degree of respiratory failure, the patient cannot even carry out the usual household load, sometimes he cannot even take a few steps. Such patients need constant outside care. Inhalation for seriously ill patients is carried out only with the help of a nebulizer. The condition is greatly facilitated by long-term low-flow oxygen therapy (more than 15 hours a day).

For these purposes, special portable oxygen concentrators have been developed. They do not require refueling with pure oxygen, but concentrate oxygen directly from the air. Oxygen therapy increases the life expectancy of these patients.

Prevention of COPD

COPD is a preventable disease. It is important that the level of prevention of COPD very little depends on the doctors. The main measures should be taken either by the person himself (quitting smoking) or by the state (anti-tobacco laws, improving the environment, promoting and promoting a healthy lifestyle). It has been proven that the prevention of COPD is economically beneficial by reducing the incidence and disability of the working-age population.

Video: COPD in the Healthy Living Program

Video: what is COPD and how to detect it in time

CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) -

primary chronic inflammatory lung disease with a predominant lesion of the distal airways and parenchyma, the formation of emphysema, impaired bronchial patency with the development of incompletely reversible or irreversible bronchial obstruction caused by a pathological inflammatory reaction. The disease develops in predisposed individuals and manifests itself as cough, sputum production and increasing shortness of breath, has a steadily progressive nature with an outcome in chronic respiratory failure and cor pulmonale.

COPD is a common disease.

According to the WHO, the prevalence of COPD among men is 9.34: 1000, among women - 7.33: 1000. Persons over 40 prevail.

In Russia, there are about 1 million patients with COPD (official data from the Ministry of Health of the Russian Federation), but in reality their number may exceed 11 million (data from epidemiological studies).

ClassificationCOPD is classified according to the severity (stage) of the disease. There are 4 stages of COPD.

According to international recommendations [Global Initiative for Chronic Obstructive Lung Disease (GOLD), 2003], the defining and unifying feature of all stages of COPD is a decrease in the ratio of FEV ^ FVC< 70 %, характеризующее ограничение экспираторного воз­душного потока. Разделяющим признаком, позволяющим оценить степень тяжести (стадию) ХОБЛ - легкое (I стадия), среднетяжелое (II стадия), тя­желое (IIIstage) and extremely severe (stage IV) course, - the value of the FEV indicator (determined after the appointment of bronchodilators) is used.

Stage I:mild course of COPD. FEV / FZHEL< 70 %. На этой стадии больной может не замечать, что функция легких у него нарушена. Обструктивные нарушения выражены незначительно - fEV value,\u003e 80% of the proper values. Usually, but not always, COPD presents with chronic cough and sputum production. Therefore, only in 25% of cases the disease is diagnosed in a timely manner (data from the European Respiratory Society), i.e. at this stage of development of COPD.

Stage II:moderate course of COPD. OFV, / FZHEL< 70 %. This is the stage at which patients seek medical attention due to shortness of breath or exacerbation of the disease, characterized by an increase in obstructive disorders (50%< ОФВ 1 < 80 % от должных величин). Отмечается усиление симптомов заболевания и одышки, появляющейся при физической нагрузке.

Stage III:severe course of COPD. FEV / FVC< 70 %. Characterized by a further increase in airflow restriction (30 % < ОФВ, < 50 % от должных величин), нарастанием одышки, частыми обострениями.

Stage IV:extremely severe course of COPD. FEV / FZHEL< 70%. At this stage, the quality of life deteriorates markedly, and exacerbations can be life threatening. The disease takes on a disabling course. It is characterized by extremely severe bronchial obstruction (FEV,< 30 % от должных величин или ОФВ, < 50 % от должных величин при наличии дыхательной недостаточности). На этой стадии возможно раз­витие легочного сердца.

Etiology.The main risk factors for developing COPD are:

1) smoking (both active and passive);

2) exposure to occupational hazards (dust, chemical pollutants, acid and alkali vapors) and industrial pollutants (S0 2, K0 2, black smoke, etc.);

3) atmospheric and domestic (smoke from cooking and fossil fuels) air pollution;

4) hereditary predisposition (most often a deficiency of a g anti-

trypsin);

5) respiratory diseases in early childhood, low weight

bodies at birth.

Epidemiological studies confirm that heavy cigarette smoking is the most important risk factor for COPD. Only 10% of COPD cases are associated exclusively with other risk factors.

Each of these factors can act independently or in combination with each other.

Pathogenesis.Exposure to tobacco smoke and toxic gases has an irritating effect on the irritative receptors of the vagus nerve located in the epithelium of the bronchi, which leads to the activation of cholinergic mechanisms of the autonomic nervous system, which are realized by bronchospastic reactions.

Under the influence of risk factors at the first stage of the development of the disease, the movement of the cilia of the ciliated epithelium of the bronchi is disrupted until they stop completely. Metaplasia of the epithelium develops with the loss of ciliated epithelial cells and an increase in the number of goblet cells. The composition of the bronchial secretion changes (its viscosity and adhesion increase), which disrupts the movement of significantly thinned cilia. There is a violation of mucociliary transport in the bronchi, which contributes to the occurrence of mucostasis, which causes blockage of small airways and further creates optimal conditions for the colonization of microorganisms.

The main consequence of the impact of etiological factors (risk factors) is the development of a specific chronic inflammation, the biomarker of which is neutrophil. Along with neutrophils, macrophages and T-lymphocytes are involved in the formation and implementation of inflammation. Under the influence of triggering factors, neutrophils circulating in the blood are concentrated in large quantities in the lungs and are the main source of free radicals, biologically active substances and enzymes. Neutrophils secrete a large amount of myeloperoxidase, neutrophil elastase, metalloproteases, which, along with interleukins and tumor necrosis factor, are the main mediators of inflammation in COPD. In conditions of a high concentration of neutrophils in the respiratory tract, the balance of the "proteolysis-antiproteolysis" and "oxidants-antioxidant anta" systems is disturbed. "Oxidative stress" develops, which in turn promotes the release of a large number of free radicals in the airways. Due to "oxidative stress" depletion of local protease inhibitors occurs, which, along with the release of a large amount of proteases by neutrophils, leads to disruption of the elastic stroma of the alveoli, involvement of the pulmonary parenchyma in the pathological process and the development of emphysema.

The whole complex of mechanisms of inflammation leads to the formation of two main processes characteristic of COPD: a violation of the bronchial

mileage and development of centrilobular, panlobular emphysema. Violation of bronchial patency in patients with COPD is formed due to reversible (smooth muscle spasm, edema of the mucous membrane and mucus hypersecretion) and irreversible (formation of expiratory collapse of small bronchi and bronchioles, peribronchial fibrosis and emphysema with changes in respiratory mechanics) components. In the early stages of COPD development, bronchial obstruction is formed mainly due to a reversible component. As the disease progresses, an irreversible component becomes the leading component in the violation of bronchial patency.

The main difference between the development of COPD and CB is that emphysema is not a complication, but a manifestation of the disease, which forms in parallel with changes in the airways.

The development of emphysema leads to a reduction in the vasculature in areas of the lung tissue that are not capable of gas exchange, resulting in pronounced ventilation-perfusion disorders. Conditions are created to increase the pressure in the pulmonary artery basin. At this stage, pulmonary hypertension forms with the further development of cor pulmonale.

Pathological changes characteristic of COPD are found in cartilaginous (more than 2 mm in diameter) and distal bronchi (less than 2 mm) of the 9-17th generation and acini, including respiratory bronchioles, alveolar passages, sacs, alveolar wall, as well as in the pulmonary arterioles, venules and capillaries. Thus, COPD is characterized by the development of a chronic inflammatory process of the respiratory tract, pulmonary parenchyma and blood vessels, in which an increased number of neutrophils, macrophages and T-lymphocytes is detected in various anatomical structures of the respiratory system.

The clinical picture.On the Ithe diagnostic search stage reveals the main symptoms of COPD: chronic cough, sputum production and / or shortness of breath. Studying the anamnesis, much attention is paid to identifying risk factors for the development of COPD (smoking and tobacco smoke, industrial dust and chemicals, smoke from home heating appliances and fumes from cooking) due to the fact that the disease begins to develop long before the onset of pronounced symptoms and lasts a long time without clear clinical symptoms. As the disease progresses, COPD is characterized by the severity of clinical manifestations and a steadily progressive course.

The severity of the main symptoms depends on the severity of the disease and the phase of the course - stable or exacerbation. A condition is considered stable when the progression of the disease can be detected with long-term follow-up of the patient (6-12 months), and the severity of symptoms does not change significantly over weeks or even months. An exacerbation is characterized by a worsening of the patient's condition, manifested by an increase in symptoms and functional disorders that arise suddenly or gradually and last at least 5 days.

At the first stage of the diagnostic search, a thorough analysis of the patient's complaints is carried out. In cases where the patient underestimates his condition and does not make complaints on his own, the doctor, when talking with the patient, should actively detect the presence of cough and sputum production.

Cough(it is necessary to establish the frequency of its occurrence and intensity) is the earliest symptom, which manifests itself by 40-50

give life. It is observed daily or is intermittent (more often observed during the day, rarely at night).

Sputum(it is necessary to find out the nature and its quantity), as a rule, it is excreted in a small amount in the morning (rarely\u003e 50 ml per day), has a slimy character. The appearance of purulent sputum and an increase in its amount are signs of an exacerbation of the disease. The appearance of blood in sputum suggests another cause of cough (lung cancer, tuberculosis, or bronchiectasis), although streaks of blood in the sputum may appear in a COPD patient as a result of persistent hacking cough.

Chronic cough and excessive sputum production in most cases long precede ventilation disorders leading to the development of shortness of breath.

Dyspnea(it is necessary to assess its severity, the relationship with physical activity) is a cardinal sign of COPD and serves as the reason why the majority of patients turn to a doctor, since it is the main factor limiting their physical activity. Quite often, the diagnosis of COPD is established at this stage of the disease. Dyspnea felt during exertion occurs on average 10 years after the cough. It is extremely rare for the onset of the disease to begin with shortness of breath. This happens in the presence of emphysema, which develops in situations when a person is in contact at work with fine (less than 5 microns) pollutants, as well as with a hereditary deficiency of wasps, -an-titrypsin, leading to the early development of panlobular emphysema.

As pulmonary function decreases, shortness of breath becomes more pronounced and can vary over a very wide range: from a feeling of lack of air during habitual physical exertion to severe respiratory failure. Patients describe shortness of breath in different ways: "increasing efforts during breathing", "heaviness", "air starvation", "shortness of breath". Dyspnea in COPD is characterized by progression (constant increase), persistence (every day), increased with physical exertion and with respiratory infections.

In addition, the patient may be disturbed by morning headache, drowsiness during the day and insomnia at night due to hypoxia and hypercapnia, which develop in the later stages of the disease.

When collecting anamnesis, attention is paid to the study of factors provoking an exacerbation of the disease (bronchopulmonary infection, increased exposure to exogenous damaging factors, inadequate physical activity, etc.), the frequency of exacerbations and hospitalizations for COPD. As the disease progresses, the intervals between exacerbations become shorter, and with increasing severity, they become almost persistent.

Clarifies the presence of concomitant diseases (pathology of the cardiovascular system, gastrointestinal tract), occurring in more than 90% of patients with COPD and affecting the severity of COPD and the nature of complex drug therapy. The efficacy and tolerability of previously prescribed therapy, the regularity of its implementation by the patient, are determined.

At the second stage of the diagnostic search, the greatest information can be obtained at the stage of detailed clinical manifestations of the disease and the development of complications. In the early stages of the disease, clinical symptoms may be absent. Pathological symptoms that can be detected as the disease progresses depend on the severity of bronchial obstruction, emphysema and the severity of pulmonary hyperin-

inflation (hyperextension of the lungs), the presence of complications such as respiratory failure and chronic cor pulmonale.

Examining the patient, assess his appearance, behavior, the reaction of the respiratory system to a conversation, movement around the office. The lips are collected with a "tube", the forced position of the body indicates a severe COPD. The color of the skin is assessed: central gray cyanosis is usually a manifestation of hypoxemia; revealed at the same time, acrocyanosis is usually a consequence of heart failure. Examining the chest, pay attention to its shape - deformed, "barrel-shaped", inactive when breathing, paradoxical retraction (retraction) of the lower intercostal spaces on inspiration (Hoover's sign) and participation in the act of breathing of the auxiliary muscles of the chest, abdominal press, significant expansion of the chest cells in the lower sections are all signs of severe COPD. With percussion of the chest, a boxed percussion sound and lowered lower borders of the lungs (signs of emphysema) are determined. The auscultatory picture of the lungs depends on the predominance of emphysema or bronchial obstruction. So, with emphysema, breathing is weakened vesicular, and in patients with severe bronchial obstruction, as a rule, it is hard, and the main auscultatory symptom is dry, mainly wheezing, aggravated by forced exhalation, imitation of cough, in the supine position.

With irreversible bronchial obstruction, signs of respiratory failure predominate, pulmonary hypertension increases, and chronic cor pulmonale is formed. It is difficult to identify signs of a compensated cor pulmonale during physical examination, heart sounds are difficult to listen to, but it is possible to identify an accent of the II tone over the pulmonary artery. It is possible to detect pulsation in the epigastric region due to the right ventricle. As the disease progresses, diffuse cyanosis is determined. In the future, a decompensated cor pulmonale is formed: the liver enlarges, pastiness appears, and then swelling of the legs and feet.

In patients with moderate and severe course of the disease, two clinical forms of COPD are distinguished - emphysematous (panacinar emphysema, "pink puffy") and bronchitic (centroacinar emphysema, "blue puffy"). Their main differences are shown in table. 5. However, in practice, the most common form of the disease is mixed.

The sensitivity of physical (objective) methods of examining patients in diagnosing COPD and determining the degree of its severity is low. They provide guidelines for the further direction of diagnostic research using instrumental and laboratory methods.

Stage III of the diagnostic search is the defining stage in the diagnosis of COPD.

FVD studyserves as the most important method in the diagnosis of COPD and differentiation from chronic bronchitis. Its implementation is necessary for all patients with chronic cough and sputum production, a history of risk factors even in the absence of shortness of breath in order to detect COPD in the early stages of the disease. This study is carried out not only to make a diagnosis, but also to determine the severity of the disease, select individual therapy, assess its effectiveness, clarify the prognosis of the course of the disease and when assessing the ability to work.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by persistent airflow limitation, which usually progresses and is associated with an increased chronic inflammatory response of the lungs to pathogenic particles or gases... In some patients, exacerbations and comorbidities may affect the overall severity of COPD.

Epidemiology

According to the results of mass special studies of the population of large cities, the share of COPD among other lung diseases is 90%. According to forecasts, the prevalence of COPD and the damage from it will increase, due to the increasing impact of risk factors and an increase in the life expectancy of the population. In the United States, there are about 14 million, in the Russian Federation, about 11 million patients with COPD are expected, (according to statistics - less than 1 million). The prevalence of COPD in the Russian Federation is about 10%, rural residents are 2 times more likely to get sick, more often men aged 50-52. An increase in the incidence rate is registered in young people aged 20-30. Among women, the prevailing age of patients is 40-49 years. Disability with COPD is established approximately 10 years after the diagnosis is made, more often at the time of treatment there is a 2-3 degree of severity of the disease, which indicates a late appeal.

COPD mortality tends to rise, according to the forecast, by 2030 it will come out on the 4th place among the causes of death in the general population. The main health care costs - about 80%, are spent on inpatient treatment, of which most - 73% - on the treatment of severe patients.

Etiology

COPD occurs as a result of exposure to a complex of risk factors for a long time

Factors influencing the development and progression of COPD

External risk factors

Smoking tobacco

Among other risk factors for COPD, tobacco smoking accounts for 39%. The smoking prevalence is up to 50% among men and up to 11% among women; among students in grade 10 50% and 28%, respectively. According to the WHO, 1/3 of the population over 15 years old smoke. Tobacco smoke consists of 2 fractions: gaseous (formaldehyde, nitrogen oxide, urethane, vinyl chloride) and suspended particles (benzopyrene, nicotine, nitrosonicotine, nickel, cadmium, phosphorus). The ingredients affect the entire body, but to a greater extent on the bronchopulmonary system, where the biotransformation of tobacco smoke products occurs. Secondary products also have a toxic effect. First of all, highly differentiated cells of the bronchial mucosa and the endothelium of small vessels are damaged.

Mechanisms involved in the biotransformation of tobacco smoke and their damage

Smoking 15 cigarettes completely paralyzes the motor ability of the cilia. AMs absorb part of the insoluble particles of tobacco smoke, their number increases early - at the prenosological stage of the disease. The development of respiratory symptoms and COPD may also be associated with secondhand smoke. Smoking during pregnancy can adversely affect fetal growth and lung development, and possibly have a primary antigenic effect on the immune system.

Professional pollutants (dust and chemicals)

Occupational hazards such as organic and inorganic dusts, chemical agents and fumes account for 10-20% of COPD. What matters is the intensity and duration of exposure, the combination with smoking. Occupations with an increased risk of developing COPD: miners, workers in metallurgical enterprises, workers employed in cotton processing, papermaking, etc.

Atmospheric and domestic pollutants

In the Russian Federation, more than 30 million tons of harmful substances from industrial emissions, about 20 million tons of emissions from vehicles, enter the atmosphere annually, which creates a load on one inhabitant of 400 kg per year. About 735 thousand people live in conditions of exceeding the maximum permissible concentration of harmful substances in the air by 5-10 times. Air pollutants of industrial smog (particulate dust, sulfur dioxide, carbon monoxide, polycyclic hydrocarbons) prevail in winter. Aeropollutants of photochemical smog (nitrogen oxides, ozone, aldehydes) prevail in summer. Under the influence of air pollutants, the following shifts occur: activation of AM and phagocytes with the formation of strong oxidants (chlorine and hydrogen oxides), which cause damage to cell membranes; the formation of new proteins with new antigenic properties; inflammation (endobronchitis); hyper i-discrimination; violation of MCT; vasoconstriction and bronchoconstriction; a decrease in the activity of beta 2-adrenergic receptors, an increase in the activity of cholinergic receptors; stimulation of the formation of substances with vasoactive and procoagulant effects (leukotrienes, thromboxanes); collagen destruction. Under conditions of oxidative stress, the antioxidant system (ceruloglobulin, superoxide dismutase, tocopherols) is depleted. There is a significant body of evidence that indoor air pollution from bio-organic fuels (wood, manure, straw, coal) is an important risk factor for COPD.

Infections

An increased susceptibility to infections can provoke exacerbations of COPD, but their effect on the development of COPD has not yet been proven. A severe childhood respiratory infection can lead to decreased lung function and contribute to the risk of COPD later. Respiratory infectious agents are pneumotropic. In patients with COPD, there is persistence of viruses in the respiratory tract, often in associations (influenza viruses, parainfluenza, adenoviruses, rhinosyncytial viruses, etc.). In COPD, the distal portions and alveoli are predominantly affected. Viruses cause degenerative-dystrophic damage and desquamation of the bronchial epithelium, disruption of trophism and local immune mechanisms, contribute to the colonization of the microbial flora of the lower respiratory tract, which is normally sterile. Viruses and their individual components persist for a long time in epithelial and AM cells, possess proteolytic activity and can cause destruction of alveoli and interalveolar septa. Viruses contribute to bronchial hyperreactivity.

Bacteria (pneumococcus, influenza bacillus, moraxella) cause sensitization and chronic inflammation. At the same time, AM is replaced by neutrophils secreting proteases. Bacterial persistence and repeated exacerbations lead to the depletion of antiprotease protection, conditions are created for the destruction of the elastic frame of the alveoli and the formation of centrilobular emphysema.

Socio-economic status

There is evidence that the risk of developing COPD depends on socioeconomic status.

Internal risk factors

Genetic.

The most documented genetic risk factor is severe hereditary deficiency of alpha-1-antitrypsin, the main inhibitor of serine proteinases in the systemic circulation. Other genes are also associated with impaired lung function: the gene encoding matrix proteinase 12, the alpha-nicotine-acetylcholine receptor gene, the cystic fibrosis gene, genetically determined defects in the antioxidant defense system, cytochrome P 450, etc.

Lung growth and development

Lung growth depends on various influences on the fetus during pregnancy and childbirth, as well as on the body during childhood and adolescence. Reduced maximum attainable lung function can increase the risk of developing COPD. Violation of fetal maturation processes, low birth weight, harmful effects on the child's body, lung diseases in childhood predispose to the development of COPD. Infections of the lower respiratory tract in childhood impair lung growth, leading to a decrease in lung volume.

Hereditary hypersensitivity and hyperresponsiveness of the airways.

Bronchial hyperreactivity is 15% among population risk factors.

Gender and age.

The prevalence of COPD, according to recent studies, is the same among men and among women, which is associated with tobacco smoking. There are fewer women smokers than men, but females are more sensitive to the damaging effects of tobacco smoke. It has been established that the prevalence of COPD is higher among smokers than among nonsmokers, the number of patients in the age group over 40 is increasing, in men more than in women.

Other factors

The influence of concomitant diseases on the formation of COPD was established. Bronchial asthma and pulmonary tuberculosis are of particular importance.

Thus, a variety of risk factors are involved in the development of COPD. The combination of risk factors in various combinations is characteristic, which determines the variety of clinical manifestations and the existence of various phenotypes of the disease.

To carry out the diagnostic process in the clinical case of patient A, let us pay attention to the fact that the patient is an older man, belongs to the category of "hard smokers" - smoker index (IC) 240.

Pathogenesis

Airway inflammation in patients with COPD is a key pathogenic mechanism of COPD .

The physiological role of inflammation is to limit the action of various pathogenic substances that have entered the internal environment. In COPD, the inflammatory reaction is formed under the influence of long-term exposure to risk factors, it has the character of a pathologically enhanced - abnormal inflammatory process in the airways in response to long-term irritating factors. All cellular elements and structures of the respiratory tract are involved in the inflammatory process. bronchi

Cellular elements and inflammatory mediators.

The chronic inflammatory process involves all cellular elements of the respiratory tract, which interact with each other through the formation of cytokines.

Neutrophils The key role in the implementation of inflammation belongs to neutrophils. Under the influence of smoking, the structure and ability of cells to deform change, which makes it difficult for them to pass through the pulmonary capillaries, which have a smaller diameter compared to the diameter of neutrophils. There is an accumulation of neutrophils in the distal lungs. An increase in the expression of adhesion molecules by the vascular endothelium promotes the attachment of neutrophils to the vascular wall and their subsequent migration under the influence of various chemoattractants (IL-8, LT B4, PAF, C5, etc.) into the intercellular space. Neutrophils secrete pro-inflammatory mediators (PAF, LT B4, etc.), which have chemotactic properties in relation to other cells, including neutrophils, attracting them to the inflammatory zone, vasoactive prostaglandins (PGE2, PGF2a). Neutrophils secrete proteases (elastin), oxygen radicals, cationic proteins, beta-glucuronidase, which cause tissue damage - destruction of the lung parenchyma, chronic hypersecretion of mucus by the bronchial glands.

Macrophagesaccumulate in places of destruction of the alveoli . Activated macrophages secrete pro-inflammatory mediators (TNF-alpha, interleukin 8, leukotriene B4), which promote the migration of neutrophils into the lower respiratory tract.

T-lymphocytes Increased presence of cytotoxic CD8+ lymphocytes is noted in all pulmonary structures. It is assumed that the selection CD8+ perforin, granzyme-B, and TNF-a cause cytolysis and apoptosis of alveolar epithelial cells and stimulate inflammation.

EosinophilsThe role of eosinophils in inflammation in COPD has not been clarified. An increase in the content in the airways in a number of cases is noted with exacerbation of COPD.

Epithelial cells of the bronchial mucosa secrete pro-inflammatory mediators (eicosanoids, cytokines, adhesion molecules).

Oxidative stress.

The respiratory tract is exposed to oxidants in the inhaled air that are produced endogenously in response to various stimuli. One of the factors involved in the development of the inflammatory process in the airways in COPD is oxidative stress with the formation of reactive oxygen species (ROS), which include free radicals and prooxidants that can form free radicals. The main initiator of oxidative stress is tobacco smoke. The sources of oxidants are activated inflammatory cells, primarily neutrophils and alveolar macrophages. In patients with COPD, an increase in the concentration of biological markers of oxidative stress, hydrogen peroxide, 8-isoprostane, in the condensate of exhaled air, sputum and systemic circulation is found. Oxygen radicals damage the lung parenchyma, bronchi and pulmonary vessels. The synthesis of collagen, elastin, surfactant decreases, the structures of other components of the extracellular matrix are disrupted, such as hyaluronan... A change in the structure of proteins leads to a violation of the immune response, contractile properties of bronchial smooth muscles, stimulation of the production of bronchial secretions, activation of mast cells, increased vascular permeability, inactivation of protease inhibitors, activation of TNF-alpha, IL 8 and other pro-inflammatory proteins. All this is accompanied by increased inflammation.

The regulator that limits the accumulation of highly toxic free radicals is the antioxidant system, which consists of non-enzymatic systems (vitamin E, beta-carotene, vitamin C, uric acid, bilirubin) and antioxidant enzymes, each of which neutralizes a certain form of ROS: The main antioxidant enzymes are: superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase, etc. Patients with lung diseases experience a decrease in the level of endogenous antioxidants with the development of an imbalance in the oxidant-antioxidant system and an increase in lipid peroxidation. Recently, a family of antioxidant proteins-peroxiredoxins has been studied, of which a special role in the lungs belongs to the secretory water-soluble protein peroxyperidoxin 6 - (Prx6). It is synthesized in the trachea and bronchi by Clara cells and goblet cells and secreted into mucus. The share of Prx6 in the total antioxidant protection in the bronchi is 70%. In an experimental model of acute inflammation and damage to bronchial epithelium, it was shown that overexpression of Prx6 in goblet cells is accompanied by a decrease in the oxidative process: a decrease in markers of lipid peroxidation in blood serum, protein oxidation, and a decrease in edema and inflammation in the lung tissue. It has been suggested that Prx6 is one of the main protective factors that counteracts oxidative stress and may be the most active known natural antioxidant in the treatment of various respiratory diseases.

Imbalance of the proteinase-antiproteinase system.

Excessive accumulation of neutrophils in the respiratory tract is accompanied by high protease activity. In COPD, the level of several types of proteases that are formed in inflammatory and epithelial cells (neutrophil elastase, cathepsin G, proteinase-3, metalloproteinases, cathepsins) increases, which leads to depletion of the plasma antiprotease potential in the capillary network of the alveoli, imbalance between the proteins that break down components tissue, and antiproteinases (alpha-1-antitrypsin, secretory inhibitor of leukoproteinases, tissue inhibitors of metalloproteinases). Oxidants have a depressing effect on protease inhibitors. This leads to irreversible structural changes. Elastase destroys the elastin of the alveolar walls, contributing to the development of emphysema and a decrease in the elastic resistance of the lungs, destroys the epithelium of the bronchi and causes metaplasia of the goblet cells.

The role of nitric oxide and its metabolites in the pathogenesis of COPD.

Recently, the role of nitric oxide (NO) and its metabolites in the pathogenesis of COPD has been studied. NO is synthesized from arginine with the participation of NO synthases (NOS) and calcium ions. Three forms of NOS are known: endothelial (eNOS), neuronal (nNOS), and inducible (i NOS). NO molecules can be formed in a non-enzymatic way during the reduction of nitrites and nitrates during acidification of the medium and undergo reverse ionization. The effect of NO released by endothelial cells has a vasodilating effect at the level of small arteries, neutralizes the bronchoconstrictor effect of acetylcholine, and prevents thrombus formation. Macrophage NO has a stimulating effect on the ciliated epithelium and local airway immunity. In smokers, a decrease in the formation of NO in the respiratory tract may be due to inhibition of endogenous synthesis against the background of excess intake of NO with tobacco smoke by the feedback mechanism. It is known that the inflammatory process is accompanied by an increase in the synthesis of i NOS and the formation of NO. In patients with exacerbation of COPD, an increase in NO metabolites in the blood and exhaled air was found. Excessive formation of NO and its metabolites - nitroxyl anion, perosynitrite is considered as one of the mechanisms of oxidative stress involved in the implementation of inflammation in COPD.

The role of infection in the pathogenesis of COPD

Long-term exposure to risk factors and damage to the respiratory tract structures create conditions for the colonization of the respiratory tract by viruses and bacteria. Viruses stimulate the processes of inflammation, tissue proteolysis and destruction of the alveoli, disrupt the mechanisms of local immunity, and facilitate the attachment of bacterial flora. The adhesion of pneumotropic bacteria to mucin of bronchial mucus, epithelial cells, and extracellular matrix occurs through adhesion receptors with the participation of bacterial invasive factors. The density of adhesion receptors increases during the repair of tissue structures that accompanies inflammation. Lack of local immunity factors e secretory IgA, lysozyme and lactoferin of bronchial mucus, formed under the influence of COPD risk factors, contributes to the colonization of all parts of the respiratory tract by microorganisms. The persistence of microorganisms stimulates the inflammatory process, increases the migration and activation of neutrophils, alters the activity of adrenergic receptors, and further suppresses local immunity. Against the background of immunodeficiency, the fungal flora is attached. An imbalance between the microflora and the protective mechanisms of the respiratory tract leads to an exacerbation of COPD with increased symptoms of local and systemic inflammation. Thus, persistent airway infection by stimulating the activation of inflammatory effector cells is a mechanism supporting inflammation in COPD.

Pathomorphology

Pathomorphological changes characteristic of COPD are found in all lung structures. These changes are characterized by chronic inflammation, damage and repair of the epithelium.

Under the influence of risk factors, the properties of bronchial mucus are disrupted, and the viscosity increases. Metaplasia of goblet and mucous cells develops, mucus hypersecretion, which leads to damage to mucociliary clearance.

The restructuring of the airways increases as the disease progresses. The consequence of bronchial inflammation is bronchial remodelingcharacterized by:

Thickening of the submucosal and adventitious layer due to edema, deposition of collagen and proteinlycans;

An increase in the number and size of mucous and goblet cells;

An increase in the bronchial microvascular network;

Hypertrophy and hyperplasia of the muscles in the bronchi.

Structural changes occur in the central, peripheral airways, pulmonary parenchyma, and pulmonary vessels.

In the central airways (trachea, bronchi and bronchioles more than 2 mm in diameter), there is hypertrophy of the mucous glands and goblet cells, a decrease in ciliated cells and villi, squamous cell metaplasia, an increase in the mass of smooth muscles and connective tissue, degeneration of cartilaginous tissue, signs of sclerosis of the bronchial wall are found in 1/3 of patients. Clinically, the defeat of the large airways is characterized by cough and sputum production.

In the peripheral airways (small bronchi and bronchioles less than 2 mm in diameter), muscle fiber hypertrophy, epithelial metaplasia, regeneration with an increase in collagen content and scarring occur. Changes in the small airways in COPD lead to their narrowing, a decrease in the number of terminal bronchioles and an increase in resistance. These processes are accompanied by progressive disturbances in the function of external respiration.

In the parenchyma of the lungs (respiratory bronchioles, alveoli, pulmonary capillaries), destruction of the walls of the alveoli develops with the formation centrilobular emphysema, dilatation and destruction of respiratory bronchioles. More often, centrilobular emphysema is localized in the upper sections, in advanced cases it captures the entire lung. Panacinar emphysema is characteristic of alpha-1-antitrypsin deficiency. The lower lobes are affected, destruction covers the alveolar passages, sacs and respiratory bronchioles.

Changes in the pulmonary vessels form in the early stages of COPD. A thickening of the vascular wall is found. Dysfunction of the endothelium in the branches of the pulmonary artery is characteristic, which leads to the formation of pulmonary arterial hypertension. The increase in pressure in the pulmonary artery is facilitated by the reduction of the capillary bed due to pulmonary emphysema.

Pathophysiology

The processes underlying COPD lead to the formation of typical pathophysiological disorders and symptoms.

Limiting the speed of molasses

Limiting the velocity of molasses is the main pathophysiological mechanism in COPD. It is based on both reversible and irreversible components.

Irreversible obstruction mechanisms:fibrosis and narrowing of the bronchi (remodeling), loss of alveolar attachments and destruction of alveolar support for the lumen of small airways and elastic traction due to destruction of the parenchyma.

Reversible obstruction mechanisms: accumulation of inflammatory cells, mucus and plasma exudate in the bronchi, contraction of smooth muscles of peripheral and central bronchi, dynamic hyperinflation during exercise .

Pulmonary hyperinflation (LGI) - increased airiness of the lungs.

LGI is based on air trap, which occurs due to incomplete emptying of the alveoli during exhalation due to the loss of elastic traction of the lungs ( static LGI) or due to insufficient expiratory time in conditions of pronounced restriction of expiratory air flow ( dynamic LGI).

Reflection of LGI is an increase in the residual volume of the lungs (OBL), functional residual capacity (FRC), and total lung capacity (OEL). An increase in dynamic hyperinflation occurs during exercise, since breathing becomes more frequent, exhalation is shortened, and most of the lung volume is retained at the level of the alveoli.

The pathogenetic basis of COPD is:

¾ chronic inflammatory process of the respiratory tract, pulmonary parenchyma and blood vessels, including the phases of exudative, productive and sclerotic processes;

¾ oxidative stress;

¾ imbalance in the proteolysis system.

The concept of a systemic inflammatory response in COPD is relatively new. In the early stages of the disease, the inflammatory process in the respiratory tract, provoked by tobacco smoke, industrial pollutants, can be reversible. However, over time, airway inflammation takes on a chronic persistent course. The main localization of inflammation in COPD is the small airways, but active inflammation is also present in the large bronchi, and in the pulmonary parenchyma, and in the pulmonary vessels. In COPD, a frequent finding is an increase in the level of inflammatory markers in the peripheral blood: C-reactive protein, fibrinogen, leukocytes, proinflammatory cytokines IL-1β, IL-6, IL-8, tumor necrosis factor TNFα (1,2). The relationship between local and systemic inflammation is carried out:

1.the release of stress-induced cytokines and free radicals from the bronchopulmonary system into the systemic circulation;

2. activation of peripheral blood leukocytes;

3. Stimulation of bone marrow and liver with pro-inflammatory mediators released by inflammatory cells.

Stimulation of these organs results in even greater production of leukocytes, platelets, CRP, and fibrinogen. However, the exact mechanisms of systemic inflammation in COPD are not well understood.

The severity of the inflammatory response in patients with COPD increases as the disease progresses and FEV 1 decreases.

Oxidative stress develops with a powerful release of neutrophils, followed by the release of an exorbitant amount of free oxygen radicals into the airways, which have a damaging effect on all structural components of the lungs. Subsequently, this leads to irreversible changes in the pulmonary parenchyma, airways and blood vessels of the lungs. A change in the structure of tissues, protein components, caused by oxidants, leads to a violation of the immune response, contractile properties of smooth muscles of the bronchi, the function of β-adrenergic receptors, stimulation of the production of bronchial secretions, activation of mast cells, increased permeability of pulmonary vessels, inactivation of α 1 -proteinase inhibitor and secretory leukoprotease inhibitor.

An imbalance of proteases and antiproteases also contributes to irreversible changes in lung tissue in patients with COPD. Disruption of the balance of proteases and antiproteases in COPD can occur due to the overproduction of proteases and suppression of the activity of antiproteases. The sources of proteases in the lungs are the direct participants in inflammation - macrophages and neutrophils, and to some extent - the bronchial epithelium. The most studied protease is neutrophilic elastase (NE), which is involved in the natural degradation of proteins of the extracellular matrix of the lung parenchyma - elastin, collagen, fibronectin, laminin, proteoglycans. NE is a powerful inducer of mucus secretion and mucosal hyperplasia. It is also an active component of infectious defense, participating in the breakdown of the protein structures of the bacterial wall. The release of NE from neutrophils into the extracellular space occurs under the influence of various substances: cytokines (TNFα, IL8), lipopolysaccharides, fragments of the bacterial wall.

The group of antiproteases that resist the destructive action of proteases includes alpha-one antitrypsin (AAT), α 2 - macroglobulin, cystatins, secretory inhibitors of leukoproteinase and tissue inhibitors. Loss of the ability of AAT to neutralize excessive amounts of NE leads to damage to the elastic frame of the lungs and the development of emphysema. There are two main types of emphysema that can form within the acinus:

1.centriacinar, accompanied by the expansion and destruction of the respiratory bronchioles;

2. panatsinarny, leads to the destruction of the entire acinus.

Centriacinar emphysema is most common in COPD and is more common in the upper lungs. Panacinar emphysema is more common in patients with alpha-1-antitrypsin deficiency and is localized in the lower lungs. In the early stages of the disease, these changes are microscopic and can be detected by random histological examinations. Later, with the progression of the disease, they can develop into macroscopic lesions with the formation of bullae (from 1 to 5 cm in diameter).

Thus, inflammation, oxidative stress and imbalance in the proteolysis system are important in the development of COPD (Fig. 1)

Fig. 1. COPD pathogenesis

There is a certain stage in the manifestation of clinical and morphological symptoms: the disease begins with mucus hypersecretion followed by impaired function of the ciliated epithelium, bronchial obstruction develops, which leads to the formation of emphysema, impaired gas exchange, respiratory failure, pulmonary hypertension and the development of cor pulmonale.

The given data show that, in terms of etiopathogenesis, morphology, COPD is the result of chronic bronchitis and pulmonary emphysema with progressive irreversible broncho-obstructive syndrome.

12. Clinical picture.The clinical picture of COPD is characterized by the same type of clinical manifestations - cough and shortness of breath, despite the heterogeneity of the diseases that make up it. The degree of their severity depends on the stage of the disease, the rate of progression of the disease and the predominant level of damage to the bronchial tree. The rate of progression and severity of COPD symptoms depends on the intensity of exposure to etiological factors and their summation. Thus, the standards of the American Thoracic Society emphasize that the appearance of the first clinical symptoms in patients with COPD is usually preceded by smoking at least 20 cigarettes a day for 20 or more years. The first signs with which patients usually see a doctor are coughing and shortness of breath, sometimes accompanied by wheezing with sputum production. These symptoms are more pronounced in the morning. The earliest symptom that appears by the age of 40-50 is cough. By the same time, in cold seasons, episodes of respiratory infection begin to appear, which are not initially associated with one disease. Dyspnea felt during exertion occurs on average 10 years after the onset of cough. However, in some cases, the onset of the disease from shortness of breath is possible. Sputum is secreted in small quantities (rarely more than 60 ml / day) in the morning, has a slimy character. Exacerbations of an infectious nature are manifested by the aggravation of all signs of the disease, the appearance of purulent sputum and an increase in its amount. It should be emphasized that bronchopulmonary infection, although frequent, is not the only reason for the development of exacerbation. Along with this, exacerbations of the disease are possible, associated with an increased effect of exogenous damaging factors or with inadequate physical activity. In these cases, signs of an infectious lesion of the respiratory system are minimal. As COPD progresses, the intervals between flare-ups become shorter. Shortness of breath can vary over a wide range, from feeling short of breath during normal physical activity to severe respiratory failure.

13. Objective research... The results of an objective study of patients with COPD depend on the severity of bronchial obstruction and emphysema. As the disease progresses, wheezing is added to the cough, which is most noticeable with a rapid expiration. Dry rales of different timbers are often revealed during auscultation. As bronchial obstruction and pulmonary emphysema progresses, the anteroposterior chest size increases. With severe emphysema, the patient's appearance changes, a barrel-shaped chest appears (increase in the anteroposterior direction). Due to the expansion of the chest and the upward displacement of the clavicles, the neck seems short and thickened, the supraclavicular fossae are protruding (filled with the expanded tops of the lungs). With percussion of the chest, a boxed percussion sound is noted. In cases of severe emphysema, the absolute dullness of the heart may not be completely determined. The edges of the lungs are displaced downward, their mobility during breathing is limited. As a result, from under the edge of the costal arch, a soft, painless edge of the liver can protrude at its normal size. The mobility of the diaphragm is limited, the auscultatory picture changes: weakened breathing appears, the severity of wheezing decreases, exhalation is lengthened.

The sensitivity of objective methods for determining the severity of COPD is low. Among the classic signs are wheezing exhalation and prolonged expiratory time (more than 5 seconds), which indicate bronchial obstruction. However, the results of physical examination do not fully reflect the severity of the disease, and the absence of clinical symptoms does not exclude the presence of COPD in the patient. Other signs, such as discoordination of respiratory movements, central cyanosis, also do not characterize the degree of airway obstruction. With mild COPD, respiratory pathology is usually not detected. In patients with moderate disease, when examining the respiratory system, dry wheezing or slightly weakened breathing (a sign of emphysema) may be heard, but these symptoms may not be able to determine the severity of airway obstruction. With the loss of a reversible component of obstruction, persistent signs of respiratory failure dominate, pulmonary hypertension increases, and chronic cor pulmonale is formed. It is difficult to identify signs of compensated cor pulmonale during physical examination. As the disease progresses, first transient and then constant hypoxia and hypercapnia are observed, blood viscosity often increases, which is due to secondary polycythemia. Decompensated cor pulmonale develops. Patients with severe COPD are characterized by worsening shortness of breath, diffuse cyanosis, and weight loss.

There are two clinical forms of the disease - emphysematous and bronchitis.

Emphysematous form(type) COPD is associated primarily with panacinar emphysema. Such patients are figuratively called "pink puffers", because to overcome the premature expiratory collapse of the bronchi, exhalation is performed through the lips folded into a tube and is accompanied by a kind of puffing. In the clinical picture, dyspnea at rest prevails due to a decrease in the diffusion surface of the lungs. Such patients are usually thin, their cough is often dry or with a small amount of thick and viscous sputum. The complexion is pink because adequate blood oxygenation is maintained by increasing ventilation as much as possible. The ventilation limit is reached at rest, and patients do not tolerate physical activity very well. Pulmonary hypertension is moderate, because reduction of the arterial bed caused by atrophy of interalveolar septa does not reach significant values. Cor pulmonale is compensated for a long time. Thus, the emphysematous type of COPD is characterized by the predominant development of respiratory failure.

Bronchitic form(type) is observed with centriacinar emphysema. Continuous hypersecretion causes an increase in resistance during inspiration and expiration, which contributes to a significant violation of ventilation. In turn, a sharp decrease in ventilation leads to a significant decrease in the O 2 content in the alveoli, a subsequent violation of the perfusion-diffusion ratios and blood shunting. This is what determines the characteristic blue tint of diffuse cyanosis in patients of this category. Such patients are obese, the clinical picture is dominated by cough with profuse sputum production. Diffuse pneumosclerosis and obliteration of blood vessels lead to the rapid development of cor pulmonale and its decompensation. This is facilitated by persistent pulmonary hypertension, significant hypoxemia, erythrocytosis and constant intoxication due to a pronounced inflammatory process in the bronchi.

Allocation of two forms has prognostic value. So, with the emphysematous type in the later stages, there is a decompensation of the cor pulmonale in comparison with the bronchitic variant of COPD. In clinical settings, patients with a mixed type of disease are more common.

Thus, COPD is characterized by a slow, gradual onset, the development and progression of the disease occurs under the influence of risk factors. The first signs of COPD are coughing and shortness of breath, other signs join later as the disease progresses.