Chronic obstructive bronchitis: causes and pathogenesis

Etiological factors of chronic obstructive bronchitis. This smoking (active and passive), air pollution (environmental aggression), industrial (occupational) hazards, severe congenital insufficiency of a1-antitrypsin, respiratory viral infections, bronchial hyperreactivity. There are unconditional and probable risk factors for the development of chronic obstructive bronchitis.

The most important etiologic factor is smoking. However, it should be noted that smoking alone is not enough for the development of COB. It is known that COPD occurs only in 15% of long-term smokers. According to the "Dutch hypothesis", for the development of chronic obstructive bronchitis in smoking requires a genetic predisposition to damage the respiratory tract.

Risk factors for chronic obstructive bronchitis

The main risk factor for COPD in 80-90% of cases is tobacco smoking. Among "smokers" chronic obstructive pulmonary disease develops 3-9 times more often than in non-smokers. The mortality from COPD determines the age at which smoking was started, the number of cigarettes smoked and the duration of smoking. It should be noted that the problem of smoking is especially relevant for Ukraine, where the prevalence of this harmful habit is 60-70% among men and 17-25% among women.

At the same time, the effect of tobacco smoke on the lungs is important not only as one of the most important factors that disrupt the function of the mucociliary transport system, the purifying and protective function of the bronchi, but also as a factor in the occurrence of chronic inflammation of the bronchial mucosa. The prolonged irritating effect of tobacco smoke on the alveolar tissue and the surfactant system contributes to impairing the elasticity of the lung tissue and the development of emphysema.

The second risk factor for COPD is occupational hazards, in particular work in the workplace, associated with the inhalation of dust containing cadmium, silicon and some other substances.

To professional groups with an increased risk of developing chronic obstructive pulmonary disease include:

• miners;
• builders;
• workers of metallurgical enterprises;
• railwaymen;
• workers engaged in processing grain, cotton and paper production and others.

The third risk factor is repeated acute respiratory viral infections (ARVI), also contributing to the violation of the purifying and protective function of the bronchi, the dissemination of bronchial mucosa by pathogenic and opportunistic microorganisms that initiate a chronic inflammatory process in the bronchi. In patients with already developed COPD, repeated SARS accelerate the occurrence of impaired ventilation and the formation of bronchial obstructive syndrome and respiratory failure.

An essential role is also played by the hereditary predisposition to the onset of chronic obstructive pulmonary disease. At present, the only proven and well-studied genetically determined pathology leading to the onset of COPD is the deficiency of a1-antitrypsin, which leads to the development of emphysema and chronic obstructive syndrome. Nevertheless, this genetic deficit among patients with chronic obstructive bronchitis and COPD occurs in less than 1% of cases. Most likely, there are other genetic defects that have not yet been studied, which contribute to the formation of bronchial obstructive syndrome, emphysema of the lungs and the development of respiratory failure. This is indicated, in particular, by the fact that far from all smokers or having professional harms is formed COPD.

In addition to the factors listed, the membership of the male sex, the age of 40-50 years, the violation of the local and general immune system, the bronchial hyperreactivity to various irritating and damaging factors, and some others seem to be of some importance, although the role of many of these factors in the onset COPD has not yet been proven.

A list of some risk factors for developing COPD, given in the standards of the European Respiratory Society (ERS, GOLD, 2000).

Risk factors for COPD (according to ERS, GOLD, 2000)

Probability of the importance of factors	External factors	Internal factors
Installed	Smoking. Professional hazards (cadmium, silicon)	Deficiency of a1-antitrypsin
High	Contamination of ambient air (especially SO2, NJ2, 03). Other occupational hazards, poverty, low socioeconomic status. Passive smoking in childhood	Prematurity. High IgE level. Bronchial hyperreactivity. Family nature of the disease
Possible	Adenoviral infection. Vitamin C deficiency	Genetic predisposition [blood group A (II), absence of IgA]

The main pathogenetic factors of chronic obstructive bronchitis are the disruption of the function of the local bronchopulmonary defense system, the structural rearrangement of the bronchial mucosa (hypertrophy of the mucous and serous glands, the replacement of ciliated epithelium with goblet cells), the development of the classical pathogenetic triad (hypercrinia, discrinia, mucostasis) and the release of inflammatory mediators and cytokines .

In addition, the mechanisms of bronchial obstruction are included. They are divided into two groups: reversible and irreversible.

Group I - reversible mechanisms of bronchial obstruction:

• bronchospasm; it is caused by the excitation of m-cholinergic receptors and receptors of the non-adrenergic, non-cholinergic nervous system;
• inflammatory edema, infiltration of the mucosa and submucosa of the bronchi;
• Obturation of the respiratory tract with mucus due to a violation of its coughing. As the disease progresses, this mechanism becomes more pronounced, as the ciliated epithelium of the bronchi transforms into a mucus (ie, goblet cells). The number of goblet cells within 5-10 years of illness increases 10 times. Gradually, the rate of daily accumulation of mucus in the bronchial tree exceeds the rate of its removal.

Group II - irreversible mechanisms of bronchial obstruction (these mechanisms are based on morphological disorders):

• stenosis, deformation and obliteration of the bronchus lumen;
• fibroblastic changes in the wall of the bronchi;
• expiratory collapse of small bronchi due to declining production of surfactant and gradually developing emphysema;
• expiratory prolapse of the membrane part of the trachea and major bronchi in their lumen.

Insidiousness of obslrukugivnyh lung diseases lies in the fact that in the absence of systematic treatment unnoticed for the patient and the doctor reversible mechanisms are replaced by irreversible and the disease in 12-15 years out of control.

Pathomorphology of chronic obstructive bronchitis

In the major bronchi, there are characteristic changes:

• increased submucosal glands;
• hyperplasia of goblet cells;
• predominance in the mucous membrane of mononuclear cells and netrophils;
• atrophic changes in the cartilage of the disease progression.

Small bronchi and bronchioles undergo also characteristic morphological changes:

• appearance and increase in the number of goblet cells;
• increase in the amount of mucus in the lumen of the bronchi;
• inflammation, increased muscle mass, fibrosis, obliteration, narrowing of the lumen.

Formation of COPD

At the initial stage of the disease, the impact of the described factors, some of which can be attributed to etiological (smoking, industrial and household dust, infections, etc.), bronchial mucosa, interstitial tissue and alveoli leads to the formation of a chronic inflammatory process that captures all of the listed structures. In this case, the activation of all cellular elements of neutrophils, macrophages, mast cells, platelets, etc. Occurs.

The main role in the onset of inflammation is given to neutrophils, whose concentration in the area of chronic stimulation of bronchial mucosa increases severalfold. Penetrating into the intercellular space, neutrophils release cytokines, prostaglandins, leukotrienes and other proinflammatory substances that contribute to the formation of chronic inflammation of the bronchial mucosa, hyperplasia of goblet cells, including in places not characteristic for their localization, i.e. In the distal (small) bronchi. In other words, the described processes lead to the formation of a universal response of the body - inflammation to chronic irritation of the bronchial mucosa.

Thus, at the initial stages of the development of the disease, its pathogenetic mechanisms resemble the mechanisms of the formation of chronic non-obstructive bronchitis. The main difference is that with COPD:

1. inflammation captures bronchi of different calibres, including the smallest bronchioles, and
2. the activity of inflammation is significantly higher than in chronic non-obstructive bronchitis.

Formation of emphysema

The formation of emphysema is a key issue in the onset of COPD and the progression of respiratory failure characteristic of this disease. Of decisive importance in this process is, as is well known, the destruction of elastic fibers of the lung tissue, which develops mainly as a result of the pathogenic action of neutrophils, accumulating in large quantities in the intercellular space.

Against the background of prolonged irritating effect of tobacco smoke and other, volatile pollutants, seeding with mucous viruses and / or microbes, the content of neutrophils in the distal parts of the respiratory system is increased by 10 times. At the same time, the release by neutrophils of proteases (elastase) and free oxygen radicals, which have a strong damaging (destructive) effect on all molecular components of tissues and cytopathogenic action, sharply increases. This rapidly depletes the local antiprotease and antioxidant potential, which leads to destruction of the structural elements of the alveoli and the formation of emphysema of the lung. In addition, various components of tobacco smoke inactivate the alpha 1-antiprotease inhibitor, further reducing the antiprotease potential of the tissues.

The main cause of the destruction of the elastic framework of lung tissue is a pronounced imbalance in the "protease-antiprotease" and "oxidant-antioxidant" systems, caused by the pathogenic functioning of neutrophils accumulating in large numbers in the distal parts of the lungs.

In addition, a shift in the ratio of damage and repair processes is important, which are regulated, as is known, by a large number of proinflammatory and anti-inflammatory mediators. Violation of the balance of these processes also contributes to the destruction of the elastic framework of lung tissue.

Finally, the violation of mucociliary clearance, hypercrinia and mucus discretation create conditions for colonization by microflora, which further activates neutrophils, macrophages, and lymphocytes, which also enhances the destructive potential of cellular inflammation cells.

All described elements of chronic inflammation lead to destruction of the alveolar walls and interalveolar septa, increased pulmonary airiness and the formation of emphysema.

Since inflammation affects primarily terminal and respiratory bronchioles in COPD, the destruction of the alveoli and the increase in the airiness of the lung tissue often have a focal character, localizing mainly in the central parts of the acinus, which are surrounded by a macroscopically small change in the pulmonary parenchyma. This centroacinar form of emphysema is typical for patients with bronchial type of chronic obstructive bronchitis. In other cases, a panacinar form of emphysema is formed, characteristic of patients with emphysematous type of chronic obstructive bronchitis.

Bronchoobstructive syndrome

Bronchoobstructive syndrome, which is a characteristic and indispensable sign of chronic obstructive bronchitis and COPD, is formed, as is known, due to the reversible and irreversible components of bronchial obstruction. At the initial stages of the development of the disease, the reversible component of bronchial obstruction predominates, which is caused by three basic mechanisms:

• inflammatory edema of the bronchial mucosa;
• hypersecretion of mucus;
• spasm of smooth muscles of small bronchi.

In patients with COPD, especially in the phase of exacerbation of the disease, a pronounced narrowing of the lumen of small bronchi and bronchioles with a diameter less than 2 mm is revealed up to the occlusion of individual peripheral airways by mucous plugs. There is also a hypertrophy of the smooth muscles of the small bronchi and their propensity to spasmodic contraction, which further reduces the total lumen of the airways and promotes an increase in the total bronchial resistance.

The causes and mechanisms of bronchospasm in chronic obstructive bronchitis, bronchial asthma or other airway disease are different. However, it should be borne in mind that bacterial and viral bacterial infection in itself and the chronic inflammatory process in the bronchi are usually accompanied by a decrease in sensitivity and loss of beta2-adrenergic receptors, the stimulation of which is known to be accompanied by a bronchodilator effect.

In addition, in patients with COPD, an increase in the tone of the wandering pepper is observed. The tendency to bronchospasm is more characteristic of patients with bronchial asthma. Nevertheless, in patients with chronic obstructive bronchitis, the hyperreactivity of small bronchi also has some significance in the pathogenesis of bronchial obstructive syndrome, although the term "asthmatic" bronchitis or bronchitis with the "asthmatic component", widely used in the past, is currently not recommended.

Further progression of the disease leads to an increasing predominance of the irreversible component of bronchial obstruction, which is determined by the emerging emphysema and structural changes in the airways, primarily peribronchial fibrosis.

The most important cause of irreversible bronchial obstruction in patients with chronic obstructive bronchitis and pulmonary emphysema is the early expiratory closure of the bronchi, or the expiratory collapse of the small bronchi. This is primarily due to a decrease in the support function of the pulmonary parenchyma, which has lost its elasticity, and bronchioles for small airways. The latter, as it were, are immersed in the lung tissue, and the alveoli closely adhere to their walls, the elastic response of which normally keeps these airways open during the entire inhalation and exhalation. Therefore, a decrease in the elasticity of lung tissue in patients with pulmonary emphysema leads to a collapse (collapse) of small bronchi in the middle or even at the beginning of exhalation, when the volume of the lungs decreases and the elastic response of the lung tissue decreases rapidly.

In addition, the insufficiency of bronchoalveolar surfactant is important, the synthesis of which is significantly reduced in patients with COPD who abuse smoking. Lack of surfactant leads, as you know, to an increase in the surface tension of the alveolar tissue and even greater "instability" of the small airways.

Finally, peribronchial fibrosis, which develops in COPD patients as a result of chronic inflammation, and other structural changes in the airway pathways (densification of the walls and deformation of the bronchi) are also of great importance in the development and progression of bronchial obstructive syndrome, but their role in the formation of an irreversible obstruction component is less than the role of emphysema.

In general, a significant predominance of the irreversible component of bronchial obstruction in patients with COPD, usually means the onset of the final stage of the disease, characterized by rapid progression of respiratory and pulmonary heart disease.

Respiratory failure

Slow progressing of respiratory failure is the third mandatory sign of COPD. Chronic respiratory failure according to the obstructive type, ultimately, leads to severe disturbances in gas exchange and is the main reason for the decrease in physical activity tolerance, performance and death in COPD patients.

Recall that from a practical point of view, there are two main forms of respiratory failure:

Parenchymal (hypoxemic), developing mainly as a result of sharp ventilation-perfusion ratios in the lungs and an increase in intrapulmonary right-left cord blood shunting, which leads to arterial hypoxemia (PaO2 <80 mmHg).

The ventricular (hypercapnic) form of respiratory failure, which occurs as a result of primary impairment of effective pulmonary ventilation (alveolar hypoventilation), which is accompanied by both a reduction in the excretion of CO2 from the body (hypercapnia) and a violation of oxygenation of the blood (hypoxemia).

For patients with COPD at a certain stage of the disease, the most common combination of arterial hypoxemia and hypercapnia, i.e. Mixed form of respiratory failure. There are several main mechanisms that determine the violation of gas exchange and ventilation in patients with COPD:

1. Disturbance of bronchial patency resulting from edema of bronchial mucosa, bronchospasm, hypersecretion of mucus and expiratory collapse of small bronchi in patients with concomitant emphysema of the lungs. Obstruction of the respiratory tract leads to the emergence of gipovoptiliruemyh or non-ventilated areas, as a result of which the blood flowing through them, is not sufficiently oxygenated, as a result, decreases PaO2, i.e. Develops arterial hypoxemia. Thus, bronchoobstructive syndrome, in itself, significantly hampers alveolar ventilation, which is further exacerbated by the development of micro-teloctasis in places of critical constriction of the bronchi.
2. Reduction of the total area of the functioning alveolar-capillary membrane in patients with severe pulmonary emphysema. At the same time, as a result of destruction of the interalveolar septa, the volume of the alveoli increases, and their total surface significantly decreases.
3. Reduction of ventilation as a result of a decrease in the reserve volume of inspiration, characteristic for patients with emphysema due to a change in configuration, an increase in the volume of the chest and an increase in its rigidity.
4. Pronounced fatigue of the respiratory muscles, primarily the diaphragm, which develops as a result of a significant increase in the load on the respiratory muscles in patients with bronchial obstructive syndrome and pulmonary emphysema.
5. Reduction of the function of the diaphragm as a result of its flattening, characteristic for patients with emphysema of the lungs,
6. Disturbance of diffusion of gases at the level of the alveolar-capillary membrane due to its thickening, disturbance of microcirculation and desolation of peripheral vessels.

As a result of the implementation of some of these mechanisms, ventilation-perfusion ratios in the lungs are violated, resulting in the flow of insufficiently oxygenated blood from the lungs, which is accompanied by a decrease in PaO2. Indeed, the destruction of the airways leads to the emergence of hypoventilated or non-ventilated areas, as a result of which the blood flowing through them is not sufficiently oxygenated. As a result, PaO2 decreases and arterial hypoxemia develops.

Further progression of structural and functional changes in the lungs leads to a decrease in the effectiveness of pulmonary ventilation (for example, as a result of disruption of the function of the respiratory muscles), which is accompanied by an increase in ventilation, the form of respiratory failure with the development of hypercapnia (an increase in PaCO2 greater than 45 mmHg).

Mixed form of respiratory failure is especially pronounced in the period of exacerbation of the disease, when, on the one hand, bronchial patency is severely disrupted, and on the other, the weakness (fatigue) of the respiratory muscles (diaphragm) increases, due to a sharp increase in the load on them.

Recall that the severity of respiratory failure is usually estimated by the oxygen tension (PaO2) and carbon dioxide (PaCO2) in the arterial blood.

Evaluation of the severity of respiratory failure (the voltage of gases in the arterial blood is expressed in mm Hg)

Degree of Nam	Parenchymal DNA	Ventilation DN
Moderate	Pa0 2 > 70	PaCO 2 <50
Moderate Gravity	Pa0 2 = 70-50	PaCO 2 = 50-70
Heavy	Pa0 2 <50	PaCO 2 > 70 Hypercapnia coma

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]