Angina

Chronic obstructive pulmonary disease: causes, mechanism of development. Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a primarily chronic inflammatory disease with predominant damage to the distal respiratory tract and lung parenchyma, the formation of emphysema, impaired bronchial obstruction with the development of partially or completely irreversible bronchial obstruction caused by an inflammatory reaction.

EPIDEMIOLOGY

COPD is a very common disease. According to official statistics, there are approximately 1 million patients with COPD in the Russian Federation, however, judging by epidemiological studies, their number may exceed 11 million people. The prevalence of COPD in the general population is 9.34 per 1000 in men and 7.33 per 1000 in women (WHO data). Among the patients, people over 40 years predominate.

CLASSIFICATION

The classification of COPD is based on the severity of the disease (Table 21-1).

Table 21-1. Classification of COPD*

. Stage	. Characteristic
I. Mild course	FEV 1/FVC ‹ 70% FEV 1 > 80% of expected values
II. Moderately severe course	FEV 1/FVC ‹ 70% 50% ‹ FEV 1 ‹ 80% predicted Chronic symptoms (cough, sputum production) present but not always
III. Heavy current	FEV 1/FVC ‹ 70% 30% ‹ FEV1 ‹ 50% of expected values Chronic symptoms (cough, sputum production) present but not always
IV. Extremely severe course	FEV 1/FVC ‹ 70% FEV 1 ‹ 30% of predicted values or FEV 1 ‹ 50% of predicted values in combination with chronic respiratory or right ventricular failure

Note. * All FEV 1 values in the COPD classification refer to post-bronchodilation. In the classification presented in the Global COPD Initiative (GOLD - G local Strategy for Chronic O bstructive L ung D isease), stage 0 is identified, but in domestic practice it is considered as a high-risk group (pre-illness state, which is not always realized in COPD).

ETIOLOGY

The most important risk factor for the development of COPD is active and, to a lesser extent, passive smoking: tobacco smoke has a direct damaging effect on lung tissue and the ability to cause inflammatory changes. In 10% of cases, COPD may be caused by other external factors: exposure to occupational hazards and industrial pollutants, atmospheric and home air pollution. Frequent severe respiratory diseases in early childhood and low birth weight predispose to the development of COPD throughout life. Of the genetic factors, the development of COPD can be facilitated by α 1 -antitrypsin deficiency (*107400, gene mutations P.I., AAT, 14q32.1, ℜ) and α 2 -macroglobulin deficiency. (*103950, 12p13.3-p12.3, ℜ).

PATHOGENESIS

At the first stage of the development of the disease, the main pathogenetic significance is the violation of mucociliary clearance, leading to stagnation of mucus in the lumen of the bronchi and promoting their colonization by microorganisms. A chronic inflammatory process develops with infiltration of the bronchi and alveoli by neutrophils, macrophages and lymphocytes. Activated inflammatory cells release a large number of inflammatory mediators (myeloperoxidase, neutrophil elastase, metalloproteinases, IL, TNF-α, etc.) that can damage the structure of the lungs and maintain inflammation. As a result, the balance of the proteolysis-antiproteolysis and oxidant-antioxidant systems is disrupted in the respiratory tract. Oxidative stress develops, accompanied by the release of a large number of free radicals, which, along with neutrophil proteases in the absence of their local inhibitors, lead to the destruction of the elastic stroma of the alveoli. Ultimately, two processes characteristic of COPD develop: impaired bronchial obstruction and centrilobular or panlobular emphysema.

Impaired bronchial obstruction consists of reversible (spasm of smooth muscles, swelling of the mucous membrane, hypersecretion of mucus) and irreversible (peribronchial fibrosis, emphysema with changes in respiratory biomechanics and the formation of expiratory bronchial collapse) components.

The development of emphysema is accompanied by a reduction of the vascular network, resulting in pronounced ventilation-perfusion disturbances. Conditions are created for an increase in pressure in the pulmonary artery basin - pulmonary hypertension develops, followed by the formation of a pulmonary heart.

CLINICAL PICTURE AND DIAGNOSTICS

COPD should be suspected in all patients with chronic productive cough lasting more than 3 months per year for 2 years or more and/or shortness of breath in the presence of risk factors. For smoking patients, it is advisable to calculate the smoking index (“pack/years”): the number of cigarettes smoked per day × smoking experience (years)/20. The smoking index of 10 pack/years is a significant risk factor for the development of COPD.

Cough is the earliest symptom, appearing by the age of 40-50 years of life; it can be daily or intermittent, most often occurring in the daytime.

Sputum, as a rule, is released in small quantities (rarely more than 50 ml/day) in the morning and is mucous in nature. Purulent sputum and an increase in its quantity are signs of exacerbation of the disease. The appearance of blood in the sputum gives reason to suspect another cause of cough (lung cancer, tuberculosis or bronchiectasis), although streaks of blood in the sputum are also possible in a COPD patient with a persistent cough.

Dyspnea is a cardinal sign of COPD and is often the main reason for visiting a doctor. Dyspnea that occurs during exercise usually appears 10 years later than cough, and as the disease progresses and lung function is impaired, it becomes more pronounced.

The results of an objective examination of the patient depend on the severity of bronchial obstruction and emphysema, the presence of complications such as respiratory failure and cor pulmonale. In typical cases, a boxy percussion sound, drooping of the lower borders of the lungs, hard or weakened vesicular breathing, and dry wheezing, which intensifies with forced exhalation, are detected. Central cyanosis usually appears in the presence of hypoxemia; acrocyanosis - in heart failure. Extrapulmonary manifestations of COPD include weight loss; the result of hypoxia and hypercapnia can be headache in the morning, drowsiness during the day and insomnia at night.

In patients with moderate and severe disease, two clinical forms of COPD are distinguished - emphysematous and bronchitis, although this division is quite arbitrary and in practice mixed variants with a predominance of one of the forms are more often observed.

In the emphysematous form, the clinical picture is dominated by progressive shortness of breath during exercise and loss of body weight. Cough and sputum production are mild or absent, and hypoxemia, pulmonary hypertension, and right ventricular failure develop in later stages. Patients of this type are called “pink puffers” because there is no cyanosis with severe shortness of breath.

In the bronchitis form, a productive cough predominates, and severe hypoxia, pulmonary hypertension and cor pulmonale develop early. Shortness of breath is relatively mild. Patients of this type are called “blue puffers” because of the marked cyanosis combined with signs of right ventricular failure, including edema.

The main phases of the course of COPD are distinguished: stable and exacerbation (deterioration of the patient’s condition, manifested by an increase in symptoms and functional disorders, occurring suddenly or gradually and lasting at least 5 days).

. Complications: acute or chronic respiratory failure, pulmonary hypertension, cor pulmonale, secondary polycythemia, heart failure, pneumonia, spontaneous pneumothorax, pneumomediastinum.

INSTRUMENTAL RESEARCH

STUDY OF EXTERNAL RESPIRATORY FUNCTION

The study of respiratory function is the most important step in the diagnosis of COPD. It is necessary for making a diagnosis, determining the severity of the disease, selecting individual therapy, assessing its effectiveness, clarifying the prognosis of the disease and conducting an examination of work ability.

The most important spirographic indicators for diagnosing COPD are FEV1, forced vital capacity (FVC) and the FEV1/FVC ratio (Tiffno index). The latter in COPD, regardless of the stage of the disease, is always below 70%, even when FEV 1 remains more than 80% of the proper value. Obstruction is considered chronic if it is recorded at least 3 times within one year, despite therapy.

A test with a bronchodilator is carried out during the initial examination to determine the maximum possible FEV 1 value for a given patient (a prognostic indicator), as well as to exclude bronchial asthma. In addition, the FEV 1 value in the bronchodilator test reflects the severity of the disease (see Table 21-1). Inhaled β-adrenergic agonists (salbutamol 400 mcg or fenoterol 400 mcg), m-cholinergic blockers (ipratropium bromide 80 mcg), or combination drugs (fenoterol 50 mcg + ipratropium bromide 20 mcg) are used. When using β-adrenomimetics, the reaction is assessed 20-30 minutes after inhalation, m-anticholinergics and combination drugs - after 40-45 minutes. The test is considered positive when FEV 1 increases by more than 15% (or by more than 200 ml), which indicates the reversibility of bronchial obstruction.

Peak flowmetry (determination of PSV) is the simplest and fastest method for assessing bronchial patency, which, however, has low sensitivity and specificity. Peak flowmetry can be used to assess the effectiveness of therapy; it is also indicated for differential diagnosis with bronchial asthma [the latter is characterized by high (more than 20%) variability of indicators]. In addition, peak flowmetry is used as a screening method to identify a group at risk of developing COPD and to establish the negative impact of various pollutants.

X-RAY OF THE CHEST ORGANS

A primary X-ray examination is carried out to exclude other diseases (lung cancer, tuberculosis, etc.) accompanied by clinical symptoms similar to COPD. If a diagnosis of COPD is established, chest radiography is necessary during an exacerbation of the disease - to exclude pneumonia, spontaneous pneumothorax, pleural effusion, etc.

COMPUTED TOMOGRAPHY OF THE CHEST ORGANS

CT allows you to identify the specific anatomical type of emphysema: panacinar, centroacinar or paraseptal, as well as diagnose bronchiectasis and clearly establish their localization.

BRONCHOSCOPY

The study includes examination of the bronchial mucosa, sampling of bronchial contents for subsequent studies (microbiological, cytological). If necessary, it is possible to perform a biopsy of the bronchial mucosa and bronchoalveolar lavage, followed by determination of the cellular and microbiological composition in order to clarify the nature of the inflammation. Bronchoscopy helps in the differential diagnosis of COPD and other diseases, primarily bronchial cancer.

ELECTROCARDIOGRAPHY

An ECG can reveal signs of overload or hypertrophy of the right heart, conduction disturbances along the right branch of the His bundle (often observed in COPD).

ECHOCARDIOGRAPHY

EchoCG helps to identify and evaluate signs of pulmonary hypertension, dysfunction of the right (and, if there are changes, the left) parts of the heart.

EXERCISE TEST

It is carried out in cases where the severity of shortness of breath does not correspond to the degree of reduction in AVF 1, to monitor the effectiveness of the therapy and select patients for rehabilitation programs. Preference is given to performing a step test (6-minute walk test).

LABORATORY RESEARCH

Clinical blood test: with exacerbation of the disease, neutrophilic leukocytosis with a shift to the left and an increase in ESR are detected; as hypoxemia develops, polycythaemic syndrome is formed (increased red blood cell count, high hemoglobin concentration, low ESR, increased hematocrit by more than 47% in women and 52% in men).

A study of the gas composition of arterial blood is carried out to confirm the presence of respiratory failure and determine its degree. The study is indicated when shortness of breath increases, FEV 1 values decrease to less than 50% of the predicted value, or in the presence of clinical signs of respiratory or right ventricular failure. Pulse oximetry can be used as a routine alternative method, but if arterial blood oxygen saturation (S a O 2) decreases to less than 94%, a blood gas study is indicated.

Serum protein electrophoresis is carried out if α 1 -antitrypsin deficiency is suspected (allows us to detect the absence of α 1 -globulin peak).

Cytological analysis of sputum allows one to obtain information about the nature of the inflammatory process and its severity, and to detect atypical cells (differential diagnosis with cancer). Bacteriological examination of sputum is carried out in the presence of a productive cough to identify the pathogen and assess its sensitivity to antibiotics.

DIFFERENTIAL DIAGNOSTICS

Most often, COPD must be differentiated from bronchial asthma. The main differential diagnostic feature is the reversibility of bronchial obstruction: in patients with COPD after taking a bronchodilator, the increase in FEV 1 is less than 15% (or less than 200 ml) of the initial one, while in bronchial asthma it usually exceeds 15% (or 200 ml). In approximately 10% of patients, COPD is combined with bronchial asthma. During exacerbation of COPD, it is necessary to differentiate with left ventricular failure (pulmonary edema), pulmonary embolism, upper respiratory tract obstruction, pneumothorax, and pneumonia.

TREATMENT

Treatment for COPD is aimed at preventing disease progression, increasing exercise tolerance, improving quality of life and reducing mortality.

GENERAL EVENTS

The first and most important step in the treatment program is to stop smoking. This is the only and so far the most effective method to reduce the risk of development and progression of COPD. Special programs for the treatment of tobacco addiction have been developed. In addition, preventive measures are needed to help reduce the adverse effects of atmospheric, industrial and household pollutants.

TREATMENT FOR STABLE DISEASE

DRUG THERAPY

Bronchodilators occupy a leading place in the complex therapy of patients with COPD. All categories of bronchodilators have been shown to improve exercise tolerance even in the absence of changes in FEV 1 . Preference should be given to inhalation therapy. For mild COPD, short-acting drugs are used as needed; in moderate, severe and extremely severe cases, long-term regular treatment with bronchodilators is necessary (Table 21-2). The most effective combination of bronchodilators.

Table 21-2. The choice of bronchodilators depending on the severity of COPD

Disease stage

Treatment as needed

Inhaled bronchodilators

Permanent treatment

Not shown

Regular use of short-acting m-anticholinergics (ipratropium bromide), or:

Regular use of long-acting m-anticholinergics (tiotropium bromide), or:

Regular use of long-acting β-adrenergic agonists (salmeterol, formoterol), or:

Regular use of short- or long-acting m-anticholinergic blockers + short- or long-acting inhaled β-adrenergic agonists (fenoterol, salbutamol), or:

Regular use of long-acting m-anticholinergics + long-acting theophyllines, or:

inhaled long-acting β-adrenergic agonists + long-acting theophyllines, or

regular use of short- or long-acting m-anticholinergics + short- or long-acting inhaled β-adrenergic agonists + long-acting theophyllines

. ◊ Dosages of the most common inhaled bronchodilators: ipratropium bromide - 40 mcg 4 times a day; tiotropium bromide - 18 mcg via handihaler 1 time per day; salbutamol - 100-200 mcg up to 4 times a day; fenoterol - 100-200 mcg up to 4 times a day; salmeterol - 25-50 mcg 2 times a day; formoterol - 4.5-9 mcg 2 times a day; formoterol - 12 mcg 2 times a day. When using short-acting bronchodilators, preference should be given to their freon-free form.

. ◊ In patients with severe and extremely severe COPD, bronchodilators are administered through a nebulizer. Nebulizer therapy or the use of a metered-dose aerosol with a spacer is also advisable in elderly patients and patients with mental disorders.

Inhaled GCs are prescribed in addition to bronchodilator therapy in patients with FEV 1 less than 50% of predicted (severe and extremely severe COPD) and frequent exacerbations (3 times or more in the last 3 years). The most effective combination of inhaled GCs with long-acting β-adrenergic agonists (salmeterol + fluticasone, formoterol + budesonide).

Mucolytics do not significantly affect the course of the disease and are indicated for a limited number of patients in the presence of viscous sputum. To prevent exacerbation of COPD, long-term use of acetylcysteine, which simultaneously has antioxidant activity, seems promising.

Prescribing antibiotics for prophylactic purposes in patients with COPD has low effectiveness and is not recommended.

NON-DRUG TREATMENT

Patients with chronic respiratory failure undergo constant long-term (more than 15 hours per day) low-flow oxygen therapy, which is so far the only method that can reduce mortality in extremely severe COPD.

Lung transplantation is indicated for a limited number of patients with very severe COPD. Palliative surgery is bullectomy, which can reduce the severity of shortness of breath and improve lung function.

REHABILITATION

For COPD at all stages of the disease, physical training programs are highly effective, increasing exercise tolerance and reducing shortness of breath and fatigue.

TREATMENT IN CASE OF EXCERNSATION OF THE DISEASE

All exacerbations should be considered as a factor in the progression of COPD, and therefore therapy should be more intensive. Depending on the severity of COPD and the severity of the exacerbation, treatment can be carried out both in an outpatient setting (mild exacerbation or moderate exacerbation in patients with mild COPD) and in an inpatient setting. To stop an exacerbation, along with bronchodilator therapy, antibiotics, GCs are used, and in a hospital setting - oxygen therapy and non-invasive ventilation.

DRUG THERAPY

The doses of bronchodilators are increased and the methods of their delivery are modified (preference is given to nebulizer therapy).

In case of exacerbation of COPD, accompanied by a decrease in FEV 1 less than 50% of the predicted value, GCs are prescribed orally (prednisolone 30-40 mg for 10-14 days).

Antibiotics are indicated for increased shortness of breath, increased volume of sputum and its purulent nature. In most cases, antibiotics are prescribed orally. The duration of antibacterial therapy is 7-14 days. For uncomplicated exacerbation, the drug of choice is amoxicillin (alternative drugs are fluoroquinolones, amoxicillin + clavulanic acid, azithromycin, clarithromycin). For complicated exacerbations, the drugs of choice are fluoroquinolones (levofloxacin, moxifloxacin) or II-III generation cephalosporins, including those active against Pseudomonas aeruginosa. Parenteral administration of antibiotics is indicated for severe exacerbation, mechanical ventilation, and gastrointestinal disorders.

OXYGEN THERAPY AND ARTIFICIAL VENTILATION

For uncomplicated exacerbations, oxygen inhalation through nasal catheters (flow rate 1-2 l/min) or a Venturi mask (oxygen content in the inhaled mixture 24-28%) allows you to quickly achieve an adequate level of oxygenation [Pa O 2 more than 8.0 kPa (60 mmHg)]. 30-45 minutes after the start of oxygen therapy, it is necessary to examine the gas composition of arterial blood; if the level of oxygenation is unsatisfactory, the need for non-invasive mechanical ventilation (spontaneous breathing at constant positive pressure) is considered. If non-invasive ventilation is ineffective in a patient with severe exacerbation of COPD (or if it is not available), invasive ventilation is performed.

DISPANSERIZATION

In case of COPD, constant monitoring is required by a general practitioner at the place of residence (visiting at least once every 6 months with monitoring of respiratory function). To prevent exacerbations, patients with COPD are vaccinated and revaccinated with polyvalent pneumococcal and influenza vaccines. Patients over 65 years of age are eligible for booster vaccination with pneumococcal vaccine if the first dose of the vaccine was administered at least 5 years ago and they were under 65 years of age at that time.

FORECAST

The determining factors of the course and prognosis are the elimination of provoking factors (smoking, air pollutants, frequent infections), the age of the patient and the FEV 1 value after the use of bronchodilators. Unfavorable prognostic signs are malnutrition, cor pulmonale, hypercapnia and tachycardia.

Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease. characterized by persistent airflow limitation that is usually progressive and associated with an increased chronic inflammatory response of the lungs to pathogenic particles or gases. In some patients, exacerbations and comorbidities may influence 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%. The prevalence and costs of COPD are projected to increase due to increasing exposure to risk factors and increasing life expectancy of the population. In the USA there are about 14 million, in the Russian Federation it is expected that there are about 11 million patients with COPD (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. Men aged 50-52 years are more often affected. An increase in incidence is recorded among young people 20-30 years old. Among women, the predominant age of patients is 40-49 years. Disability in COPD is established approximately 10 years after diagnosis; more often, at the time of treatment, there is a 2-3 degree of severity of the disease, which indicates late appeal.

Mortality from COPD is trending upward According to the forecast, by 2030 it will become the 4th leading cause of death in the general population. The main healthcare costs - about 80% - are spent on inpatient treatment, of which the largest part - 73% - is spent on treating seriously ill patients.

Etiology

COPD occurs as a result of exposure to a complex of risk factors over a long period of 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 prevalence of smoking is up to 50% among men and up to 11% among women; among 10th grade students, 50% and 28%, respectively. According to WHO, 1/3 of the population over 15 years of age smoke. Tobacco smoke consists of 2 fractions: gaseous (formaldehyde, nitrogen oxide, urethane, vinyl chloride) and a fraction of suspended particles (benzopyrene, nicotine, nitrosonicotine, nickel, cadmium, phosphorus). The ingredients affect the entire body, but to a greater extent 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

Mechanisms	Damage
Antioxidant-producing Clara cells glutathione	Exhaustion
Type II alveolocytes, producing surfactant and indirectly influencing the composition of bronchial secretions	A decrease in the gel phase and an increase in the sol phase, which leads to a deterioration in the rheology of mucus and MCT
Factors of local immune defense: interferon, lactoferrin, lysozyme, IgA, alveolar macrophages	Exhaustion due to constant intense exposure to air pollutants
MCT: normal ratio of mucous and ciliated cells of the bronchial mucosa.	Disturbance of MCT: the number of mucous cells increases and the number of ciliated cells decreases, which leads to a deterioration in the drainage function of the bronchi, hyper-discrimination

Smoking 15 cigarettes completely paralyzes the motor ability of the cilia. AM absorb some of the insoluble particles of tobacco smoke, their number increases early - at the pre-nosological stage of the disease. The development of respiratory symptoms and COPD may also be associated with passive smoking. Smoking during pregnancy may have a negative effect on fetal growth and lung development and may 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 are the cause of COPD in 10-20%. What matters is the intensity and duration of exposure, as well as the combination with smoking. Professions with an increased risk of developing COPD: miners, workers at metallurgical enterprises, workers involved in cotton processing, paper production, etc.

Atmospheric and household pollutants

In the Russian Federation, more than 30 million tons of harmful substances from industrial emissions and about 20 million tons of emissions from motor vehicles enter the atmosphere annually, which creates a load of 400 kg per year per inhabitant. About 735 thousand people live in conditions where the maximum permissible concentration of harmful substances in the atmospheric air is 5-10 times higher. Aeropollutants of industrial smog (particulate dust particles, sulfur dioxide, carbon monoxide, polycyclic hydrocarbons) predominate in winter. Aeropollutants of photochemical smog (nitrogen oxides, ozone, aldehydes) predominate in summer. Under the influence of aeropollutants, the following changes occur: activation of AM and phagocytes with the formation of strong oxidizing agents (chlorine and hydrogen oxides) causing damage to cell membranes; formation of new proteins with new antigenic properties; inflammation (endobronchitis); hyper i-discrimination; violation of MCT; vasoconstriction and bronchoconstriction; decreased activity of beta 2-adrenergic receptors, increased 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 considerable evidence that indoor air pollution from the combustion of bioorganic fuels (wood, manure, straw, coal) is an important risk factor for the development of COPD.

Infections

Increased susceptibility to infections can provoke exacerbations of COPD, but their effect on the development of COPD has not yet been proven. A severe respiratory infection in childhood can lead to decreased lung function and contribute to the risk of COPD later in life. 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 parts and alveoli are predominantly affected. Viruses cause degenerative-dystrophic damage and desquamation of the bronchial epithelium, disruption of trophism and local immune mechanisms, and promote colonization of the lower respiratory tract, which is normally sterile, by microbial flora. Viruses and their individual components persist for a long time in epithelial cells and AM, have 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. In this case, AMs are replaced by neutrophils that secrete proteases. The persistence of bacteria and repeated exacerbations lead to the depletion of antiprotease protection, creating conditions for the destruction of the elastic framework of the alveoli and the formation of centrilobular emphysema.

Socioeconomic status

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

Internal risk factors

Genetic.

The best 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 achievable lung function may increase the risk of developing COPD. Disruption of fetal maturation processes, low birth weight, harmful effects on the child's body, and lung diseases in childhood predispose to the development of COPD. Infections of the lower respiratory tract in childhood impair lung growth and lead to a decrease in lung volumes.

Hereditary hypersensitivity and hyperresponsiveness of the respiratory tract.

Bronchial hyperreactivity accounts for 15% of population risk factors.

Gender and age.

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

Other factors

The influence of concomitant diseases on the development of COPD has been established. Of particular importance are bronchial asthma and pulmonary tuberculosis.

Thus, a variety of risk factors are involved in the development of COPD. Characteristic is the combination of risk factors in various combinations, which determines the variety of clinical manifestations and the existence of different 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 and belongs to the category of “heavy smokers” - smoker index (SI) 240.

Pathogenesis

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

The physiological role of inflammation is to limit the action of various pathogenic substances that enter the internal environment. In COPD, the inflammatory reaction is formed under the influence of long-term exposure to risk factors and is in the nature of a pathologically enhanced - abnormal inflammatory process in the respiratory tract 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.

All cellular elements of the respiratory tract are involved in the chronic inflammatory process, which interact with each other through the formation of cytokines.

Neutrophils Neutrophils play a key role in the implementation of inflammation. Under the influence of smoking, the structure and ability of cells to deform changes, 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 parts of the 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 towards other cells, including neutrophils, attracting them to the inflammation 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.

Macrophages accumulate in places of alveolar destruction . Activated macrophages release proinflammatory 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 observed in all pulmonary structures. It is assumed that the allocation CD8+ perforin, granzyme-B and TNF-a cause cytolysis and apoptosis of alveolar epithelial cells and stimulate inflammation.

Eosinophils The role of eosinophils in inflammation in COPD has not been clarified. An increase in the content in the respiratory tract is observed in some cases during 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 contained in the inhaled air and formed 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 pro-oxidants that can form free radicals. The main initiator of oxidative stress is tobacco smoke. The source 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 is detected - hydrogen peroxide, 8-isoprostane in exhaled air condensate, sputum and systemic circulation. 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. Changes in the structure of proteins lead to disruption of the immune response, contractile properties of bronchial smooth muscle, 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, consisting of non-enzymatic systems (vitamin E, beta-carotene, vitamin C, uric acid, bilirubin) and antioxidant enzymes, each of which neutralizes a specific form of ROS:. The main antioxidant enzymes are: superoxide dismutase, catalase, glutathione peroxidases, glutathione-S-transferase, etc. In patients with lung diseases, a decrease in the level of endogenous antioxidants is observed with the development of an imbalance in the oxidant-antioxidant system and increased 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 the 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 the blood serum, protein oxidation, a decrease in edema and inflammation in the lung tissue. It has been suggested that Prx6 is a major protective factor against oxidative stress and may be the most active natural antioxidant known 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 produced in inflammatory and epithelial cells increases (neutrophil elastase, cathepsin G, proteinase-3, metalloproteinases, cathepsins), which leads to depletion of the plasma antiprotease potential in the capillary network of the alveoli, an imbalance between proteas that break down the components of the connective tissue. tissue, and antiproteinases (alpha-1-antitrypsin, secretory inhibitor of leukoproteinases, tissue inhibitors of metalloproteinases). Oxidants have an inhibitory effect on protease inhibitors. This leads to irreversible structural changes. Elastase destroys the elastin of the alveolar walls, promoting the development of emphysema and reducing the elastic resistance of the lungs, destroys the bronchial epithelium and causes metaplasia of 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. There are three known forms of NOS: endothelial (eNOS), neuronal (nNOS) and inducible (iNOS). NO molecules can be formed nonenzymatically during the reduction of nitrites and nitrates during acidification of the environment and undergo reverse ionization. The influence of NO secreted 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 immunity of the respiratory tract. In smokers, a decrease in NO formation in the respiratory tract may be due to inhibition of endogenous synthesis against the background of an excess supply of NO with tobacco smoke via a 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 detected. Excessive formation of NO and its metabolites - nitroxide anion, perosinitrite 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 structures of the respiratory tract create conditions for the colonization of the respiratory tract by viruses and bacteria. Viruses stimulate the processes of inflammation, tissue proteolysis and destruction of alveoli, disrupt the mechanisms of local immunity, and promote the attachment of bacterial flora. Adhesion of pneumotropic bacteria to bronchial mucus mucin, epithelial cells, and extracellular matrix occurs through adhesion receptors with the participation of bacterial invasiveness factors. The density of adhesion receptors increases during the repair of tissue structures, which accompanies inflammation. The insufficiency of local immunity factors such as secretory IgA, lysozyme and lactoferin in bronchial mucus, which is formed under the influence of risk factors for COPD, contributes to the colonization of microorganisms in all parts of the respiratory tract. The persistence of microorganisms stimulates the inflammatory process, increases the migration and activation of neutrophils, changes the activity of adrenergic receptors, and further suppresses local immunity. Against the background of immunodeficiency, fungal flora attaches. An imbalance between the microflora and the protective mechanisms of the respiratory tract leads to exacerbation of COPD with increased symptoms of local and systemic inflammation. Thus, persistent infection in the respiratory tract, stimulating the activation of inflammatory effector cells, is a mechanism that maintains inflammation in COPD.

Pathomorphology

Pathomorphological changes characteristic of COPD are found in all pulmonary 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 viscosity increases. Metaplasia of goblet and mucous cells develops, hypersecretion of mucus, which leads to damage to mucociliary clearance.

Structural changes in the respiratory tract increase as the disease progresses. The consequence of inflammation of the bronchi is bronchial remodeling, which is characterized by:

Thickening of the submucosal and adventitial layer due to edema, deposition of collagen and protein glycans;

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

Increased bronchial microvascular network;

Hypertrophy and hyperplasia of the muscles in the bronchi.

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

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

In the peripheral respiratory tract (small bronchi and bronchioles with a diameter of less than 2 mm), hypertrophy of muscle fibers, 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 dysfunction of external respiration.

In the lung parenchyma (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, and in advanced cases it affects the entire lung. Panacinar Emphysema is characteristic of alpha-1 antitrypsin deficiency. The lower lobes are affected, destruction covers the alveolar ducts, sacs and respiratory bronchioles.

Changes in the pulmonary vessels form in the early stages of COPD. Thickening of the vascular wall is detected. Characteristic is endothelial dysfunction in the branches of the pulmonary artery, which leads to the formation of pulmonary arterial hypertension. An increase in pressure in the pulmonary artery is facilitated by a reduction in the capillary bed due to pulmonary emphysema.

Pathophysiology

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

Air Molasses Speed Limit

Airflow limitation is the major pathophysiological mechanism in COPD. It is based on both reversible and irreversible components.

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

Reversible mechanisms of obstruction: accumulation of inflammatory cells, mucus and plasma exudate in the bronchi, contraction of smooth muscles of the 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 loss of elastic traction of the lungs ( static LGI) or due to insufficient expiratory time in conditions of severe limitation of expiratory air flow ( dynamic LGI).

A reflection of pulmonary hypertension is an increase in residual lung volume (RLV), functional residual capacity (FRC), and total lung capacity (TLC). An increase in dynamic hyperinflation occurs when performing physical activity, since this increases breathing speed, exhalation is shortened, and most of the lung volume is retained at the level of the alveoli.

The pathogenesis of COPD determines the development of a rather dangerous lung disease, fraught with serious complications. The disease is a pressing problem due to its prevalence and the risk of human disability. Many scientific centers around the world are studying the disease and methods of combating it.

WHO has developed a number of criteria to help assess the severity of the disease. The established pathogenesis of COPD helps to correctly use these criteria and develop a scheme for treatment, prevention and rehabilitation of patients.

Essence of the disease

Chronic obstructive pulmonary disease (COPD) is a disease that causes an irreversible reduction in air flow in the respiratory canals. The change in flow is constantly shifting towards its limitation, and is caused by an inflammatory reaction of the lung tissue to the effects of various particles and gas. The pathology first occurs in the bronchial mucosa, where, in response to pathogenic influences, the secretion of enzymes changes: mucus production increases, and the separation of bronchial secretions is disrupted. Infection is added to this process, which leads to a series of reflexive reactions that ultimately lead to destructive phenomena in the bronchi, bronchioles and alveoli.

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Etiology of the disease

The etiology and pathogenesis of COPD are based on the mechanism of mutual influence of genetic factors and factors caused by environmental influences.

The question of the etiology of the disease is still at the stage of controversy and discussion among scientists.

Reasons that do not raise doubts about reliability include internal parameters - lack of alpha-antitrypsin; external influences - smoking and harmful substances used in professional activities (cadmium, silicon, etc.).

With a high degree of probability, the etiology of COPD is due to the following reasons: internal - birth pathology, in particular prematurity, bronchial hyperreactivity, heredity, increased levels of lgE; external - harmful impurities in the air, lifestyle and diet, passive smoking, especially in childhood.

Smoking is recognized as the main provoking factor in the development of the disease, and the proportion of COPD patients who smoke reaches 80% of all registered cases of the disease. Shortness of breath caused by this disease appears in smokers at about 40 years of age, which is almost 15 years earlier than in non-smokers.

The second most common cause of COPD is an occupational factor caused by inhalation of dust containing silicon and cadmium.

In this regard, the mining industry is considered the most hazardous industry, and the professions included in the maximum risk group are miners, concrete workers, metallurgists, and railway workers; workers involved in the processing of pulp, grain and cotton.

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Pathogenesis of the disease

The pathogenesis of COPD is based on the following characteristic processes, such as the inflammatory response, proteinase and antiproteinase imbalance, and oxidative stress.

The inflammatory process of a chronic nature extends to most areas of the respiratory system, parenchyma and pulmonary vessels. The chronic course of inflammation leads to the gradual destruction of lung tissue and irreversible pathologies. The remaining two processes of pathogenesis are also caused by the development of an inflammatory reaction in conjunction with the influence of external and internal factors.

As a result of inflammatory reactions, there is a significant increase in the concentration of so-called inflammatory cells: neutrophils, macrophages and T-lymphocytes, causing a pathogenic imbalance. Thus, neutrophils increase the secretion of proteinases of various types. Macrophages secrete tumor necrosis factor, leukotriene, and T-lymphocytes promote cytolysis of alveolar epithelial cells.

The most significant role in the development of COPD is played by tumor necrosis factor and interleukin, which actively destroy the lung structure and increase neutrophilic inflammation.

During inflammation, oxidants are actively formed that can destroy proteins, fats, and nucleic acids that cause cell death.

As a result of oxidative stress, proteinase imbalance increases. Under its influence, obstruction of the bronchi of a reversible nature is detected.

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Pathological physiology

The pathogenesis of COPD develops in the direction of the appearance of such pathological disorders as excessive mucus production, impaired cilia function, bronchial obstruction, destruction of parenchyma and emphysema, impaired gas exchange, pulmonary hypertension, the occurrence of “pulmonary heart”, systemic pathologies.

In the process of disease progression, the following basic elements of pathological physiology should be noted:

Restriction of air flow, obstructions to flow. Pathogenesis processes lead to bronchial obstruction, which creates obstacles to the flow during exhalation; the resulting hyperinflation leads to a decrease in the volume of inhaled air, shortness of breath and premature fatigue, which, in turn, disrupts the contractile functions of the respiratory muscles.
Anomaly of gas exchange: hypoxemia and hypercapnia develop, carbon dioxide accumulates and oxygen transport deteriorates.
Excessive mucus production: leads to a characteristic cough with phlegm.
Pulmonary hypertension: caused by spasm of small pulmonary arteries and develops in the later stages of COPD; the progression of pulmonary hypertension leads to atrophy of the right cardiac ventricle and the appearance of “pulmonary heart”.
Exacerbation of respiratory manifestations: provoked by the addition of a viral or bacterial infection, exposure to external factors (harmful air components); the inflammatory reaction intensifies, air flow decreases even more due to increased hyperinflation and the emergence of new sources of resistance to flow movement; ventilation imbalance can lead to complicated hypoxia; exacerbation of respiratory manifestations of COPD can also be caused by heart failure and pneumonia.
Systemic disorders: respiratory rhythm disturbances and hyperinflation affect the functioning of the cardiovascular system and metabolism in the body, which leads to the onset of other diseases (ischemia, diabetes, depression, etc.), a significant decrease in muscle tone and cachexia.

Epidemiology

Etiology

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

Factors influencing the development and progression of COPD

External risk factors

Smoking tobacco

Mechanisms involved in the biotransformation of tobacco smoke and their damage

Mechanisms	Damage
Antioxidant-producing Clara cells glutathione	Exhaustion
Type II alveolocytes, producing surfactant and indirectly influencing the composition of bronchial secretions	A decrease in the gel phase and an increase in the sol phase, which leads to a deterioration in the rheology of mucus and MCT
Factors of local immune defense: interferon, lactoferrin, lysozyme, IgA, alveolar macrophages	Exhaustion due to constant intense exposure to air pollutants
MCT: normal ratio of mucous and ciliated cells of the bronchial mucosa.	Disturbance of MCT: the number of mucous cells increases and the number of ciliated cells decreases, which leads to a deterioration in the drainage function of the bronchi, hyper-discrimination

Professional pollutants (dust and chemicals)

Atmospheric and household pollutants

Infections

Socioeconomic status

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

Internal risk factors

Genetic.

Lung growth and development

Hereditary hypersensitivity and hyperresponsiveness of the respiratory tract.

Bronchial hyperreactivity accounts for 15% of population risk factors.

Gender and age.

Other factors

The influence of concomitant diseases on the development of COPD has been established. Of particular importance are bronchial asthma and pulmonary tuberculosis.

Pathogenesis

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

Cellular elements and inflammatory mediators.

All cellular elements of the respiratory tract are involved in the chronic inflammatory process, which interact with each other through the formation of cytokines.

Eosinophils The role of eosinophils in inflammation in COPD has not been clarified. An increase in the content in the respiratory tract is observed in some cases during exacerbation of COPD.

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

Oxidative stress.

Imbalance of the proteinase-antiproteinase system.

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

The role of infection in the pathogenesis of COPD

Pathomorphology

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

Structural changes in the respiratory tract increase as the disease progresses. The consequence of inflammation of the bronchi is bronchial remodeling, which is characterized by:

Thickening of the submucosal and adventitial layer due to edema, deposition of collagen and protein glycans;

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

Increased bronchial microvascular network;

Hypertrophy and hyperplasia of the muscles in the bronchi.

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

Pathophysiology

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

Air Molasses Speed Limit

Airflow limitation is the major pathophysiological mechanism in COPD. It is based on both reversible and irreversible components.

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

The pathogenetic basis of COPD is:

¾ chronic inflammatory process of the respiratory tract, pulmonary parenchyma and blood vessels, including 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 and industrial pollutants, can be reversible. However, over time, inflammation of the airways 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, in the pulmonary parenchyma, and in the pulmonary vessels. In COPD, a common 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 by:

1. 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 the bone marrow and liver by proinflammatory mediators released by inflammatory cells.

Stimulation of these organs leads to even greater production of white blood cells, 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 with the subsequent release into the airways of an excessively large number of free oxygen radicals, which have a damaging effect on all structural components of the lungs. Subsequently, this leads to irreversible changes in the pulmonary parenchyma, respiratory tract and pulmonary vessels. Changes in the structure of tissues and protein components caused by oxidants lead to disruption of the immune response, contractile properties of bronchial smooth muscles, 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.

Serious disorders caused by oxidative stress contribute to the progression of COPD, frequent exacerbations, and increased respiratory failure.

An imbalance of proteases and antiproteases also contributes to irreversible changes in lung tissue in patients with COPD. An imbalance of proteases and antiproteases in COPD can occur due to 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 neutrophil 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 hyperplasia of mucous glands. It is also an active component of infectious defense, participating in the breakdown of 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 leukoproteinase inhibitors and tissue inhibitors. Loss of the ability of AAT to neutralize excess amounts of NE leads to damage to the elastic framework 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 expansion and destruction of respiratory bronchioles;

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

Centriacinar emphysema is most characteristic of COPD and often forms in the upper parts of the 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, as the disease progresses, 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. Pathogenesis of COPD

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

The data presented show that, according to etiopathogenesis and morphology, COPD is the result of chronic bronchitis and 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 it up. The degree of their severity depends on the stage of the disease, the rate of disease progression and the predominant level of damage to the bronchial tree. The rate of progression and severity of COPD symptoms depends on the intensity of the impact of 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 per day for 20 years or more. The first signs with which patients usually consult a doctor are cough and shortness of breath, sometimes accompanied by wheezing and sputum production. These symptoms are more pronounced in the morning. The earliest symptom, appearing by the age of 40-50, is cough. By this time, during cold seasons, episodes of respiratory infection begin to occur, which at first are not associated with one disease. Shortness of breath felt during physical activity occurs on average 10 years after the onset of cough. However, in some cases the disease may begin with shortness of breath. Sputum is released in small quantities (rarely more than 60 ml/day) in the morning and is mucous in nature. Exacerbations of an infectious nature are manifested by a worsening of all signs of the disease, the appearance of purulent sputum and an increase in its quantity. It should be emphasized that bronchopulmonary infection, although common, is not the only cause of exacerbation. Along with this, exacerbations of the disease are possible due to increased exposure to exogenous damaging factors or inadequate physical activity. In these cases, signs of infection of the respiratory system are minimal. As COPD progresses, the intervals between exacerbations become shorter. Shortness of breath can vary widely: from a feeling of shortness 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, the cough is accompanied by wheezing, which is most noticeable with rapid exhalation. Auscultation often reveals dry rales of different timbres. As bronchial obstruction and emphysema progress, the anterior-posterior size of the chest increases. With severe emphysema, the patient’s appearance changes, a barrel-shaped chest appears (enlargement in the anteroposterior direction). Due to the expansion of the chest and upward displacement of the clavicles, the neck appears short and thick, the supraclavicular fossae are protruded (filled with expanded apices of the lungs). When percussing the chest, a boxy 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 shifted downwards, their mobility during breathing is limited. As a result, a soft, painless edge of the liver may protrude from under the edge of the costal arch, although its size is normal. The mobility of the diaphragm is limited, the auscultatory picture changes: weakened breathing appears, the severity of wheezing decreases, and exhalation lengthens.

The sensitivity of objective methods for determining the severity of COPD is low. Classic signs include wheezing and prolonged expiratory time (more than 5 seconds), which indicate bronchial obstruction. However, the results of an objective 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 incoordination of respiratory movements, central cyanosis, also do not characterize the degree of airway obstruction. In mild COPD, respiratory pathology is usually not detected. In patients with moderate disease, when examining the respiratory system, dry wheezing may be heard or slightly weakened breathing may be noted (a sign of emphysema), but it may be impossible to determine the severity of airway obstruction from these symptoms. With the loss of the reversible component of obstruction, persistent signs of respiratory failure dominate, pulmonary hypertension increases, and chronic cor pulmonale forms. It is difficult to identify signs of compensated cor pulmonale during physical examination. As the disease progresses, first transient and then permanent hypoxia and hypercapnia are observed, and blood viscosity often increases, which is caused by secondary polycythemia. A decompensated cor pulmonale develops. Patients with severe COPD are characterized by worsening shortness of breath, diffuse cyanosis, and loss of body weight.

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”, since in order to overcome the premature expiratory collapse of the bronchi, exhalation is made through pursed lips and is accompanied by a kind of puffing. The clinical picture is dominated by shortness of breath at rest 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... Sufficient blood oxygenation is maintained by increasing ventilation as much as possible. The limit of ventilation is reached at rest, and patients tolerate physical activity very poorly. Pulmonary hypertension is moderate, because the reduction of the arterial bed caused by atrophy of the interalveolar septa does not reach significant values. Cor pulmonale has been compensated for a long time. Thus, the emphysematous type of COPD is characterized by the predominant development of respiratory failure.

Bronchitic form(type) observed in centriacinar emphysema. Constant hypersecretion causes an increase in resistance during inhalation and exhalation, which contributes to a significant impairment of ventilation. In turn, a sharp decrease in ventilation leads to a significant decrease in the O 2 content in the alveoli, subsequent disruption of perfusion-diffusion relationships and blood shunting. This causes the characteristic blue tint of diffuse cyanosis in patients in this category. Such patients are obese, and the clinical picture is dominated by cough with copious 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.

The identification of two forms has prognostic significance. Thus, with the emphysematous type, decompensation of the cor pulmonale occurs in later stages compared to the bronchitis 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 cough and shortness of breath; other signs appear later as the disease progresses.