Obliterating bronchiolitis: causes, symptoms, diagnosis, treatment

Obliterating bronchiolitis is a disease from the group of "small respiratory tract diseases", in which bronchioles are affected - respiratory tracts with a diameter of less than 2-3 mm, which do not have a cartilaginous base and mucous glands.

There are terminal and respiratory bronchioles. Terminal (membranous) bronchioles belong to the air-breathing airways, their wall contains smooth muscle cells. Terminal bronchioles are divided into respiratory bronchioles 1, 2, 3 order.

Respiratory bronchioles of the third order branch into alveolar courses, which branch from 1 to 4 times and end with alveolar sacs. Three generations of respiratory bronchioles, alveolar courses and alveolar sacs form the respiratory department, in which gas exchange occurs between air and blood.

The wall of respiratory bronchioles contains ciliated epithelial cells and alveolocytes and does not have smooth muscle cells. The number of ciliate cells decreases with branching of respiratory bronchioles and the number of non-exfoliated cubic cells increases.

Respiratory bronchioles belong to the transitional respiratory tract, i.e. Take part in air and gas exchange.

The area of the small airway section is 53-186 cm ³, which is many times larger than the area of the trachea (3-4 cm ³ ) and large bronchi (4-10 cm ³ ). The share of small respiratory tract accounts for only 20% of the total respiratory resistance. That is why the damage to bronchioles in the early stages of the disease may not be accompanied by a marked symptomatology. A bright clinical picture appears with a far-gone defeat of small airways.

Causes and pathogenesis of obliterating bronchiolitis

The main causes of the disease are:

• transplantation of the heart-lung complex, bone marrow;
• viral infections (respiratory syncytial virus, HIV, adenovirus, cytomegalovirus, etc.);
• Mycoplasma infection;
• inhalation of toxic substances (sulfur dioxide, nitrogen, chlorine, phosgene, ammonia, chloropicrin, etc.);
• diffuse connective tissue diseases (rheumatoid arthritis, systemic lupus erythematosus, Sjogren's syndrome);
• taking certain medicines (D-penicillamine, preparations of gold, sulfasalazine);
• inflammatory bowel disease;
• radiation therapy;
• IgA-nephropathy;
• Stephen-Johnson syndrome (a form of acute multiforme exudative erythema, characterized by extremely severe course).

The forms that developed after lung transplantation are most well studied. In most cases, the cause of obliterating bronchiolitis can be determined. If the cause is unknown, talk about the idiopathic form of the disease.

With obliterating bronchiolitis, bronchioles develop inflammation and further severe fibrosis.

The main pathogenetic factors are:

• excess production of cytokines, among which an important role is played by gamma-interferon and interleukin 1-0; with obliterating bronchiolitis, the gene expression of these cytokines is increased. Interleukin 1-beta regulates the growth of lymphocytes, their differentiation and cytotoxicity, and gamma interferon induces the expression of antigens of the class II HLA system on epithelial cells of bronchioles and regulates the production of immunoglobulins;
• increased expression of antigens of class II HLA-system on bronchiolar epithelial cells (this mechanism is important mainly for autoimmune, medicinal post-transplantation forms of the disease);
• activation of cytotoxic T-lymphocytes;
• high activity of platelet-derived growth factor, which stimulates the proliferation of fibroblasts;
• increased secretion of epithelial cells of bronchioles of fibronectin, which is a chemoapractant for fibroblasts;
• a significant increase in the activity of integrins that perform the function of adhesion of fibroblasts, endothelial cells to fibronectin, fibrinogen. Cell adhesion to fibronectin occurs with the help of alpha-5-beta-1-integrin, to fibrinogen - with the help of alpha-5-beta-3-integrin. These processes stimulate fibrosis in bronchioles.

The main pathomorphological manifestations of the disease are:

• bronchiolar or peribronioolar inflammatory infiltrate of varying density;
• development of bronchioloectasis with stasis of secretion, accumulation of macrophages, mucous plugs;
• partial or complete obliteration of bronchioles with a rough cicatrical connective tissue;

With obliterating bronchiolitis, terminal bronchioles are usually affected. Respiratory bronchioles, alveolar courses, alveolar sacs and alveoli are not involved in the inflammatory process. In addition to small airways, large bronchi are also involved in the inflammatory process, they often display cylindrical bronchioloectasises, mucous plugs, purulent exudate, chronic inflammatory infiltration.

In post-transplantation obliterating bronchiolitis, pulmonary vascular lesions are characteristic.

Symptoms of obliterating bronchiolitis

The main clinical manifestations of obliterating bronchiolitis are:

1. Progressive dyspnea is a cardinal symptom of the disease. At first, shortness of breath worries mainly after physical exertion, but in the future it quickly grows and becomes constant.
2. Low-yield cough is a common symptom of the disease.
3. With auscultation of the lungs at various stages of the disease, dry wheezing sounds are heard, sometimes a characteristic inspiratory "peep", especially in the lower parts of the lungs, however, as the disease progresses, vesicular breathing becomes more and more weakened and dry wheezing disappears.
4. The pathological process often involves large bronchi, in which colonization of bacterial (most often Pseudomonas aeruginosa), fungal (Aspergillus fumigatus) flora can occur, with high body temperature, productive cough, and possible formation of bronchiectasis.
5. In the late stages of the disease, diffuse warm cyanosis develops, "puffing" the breathing, a pronounced tension of the auxiliary respiratory muscles.

The onset of the obliterating bronchiolitis can be acute (after inhalation of hydrochloric acid or sulfur dioxide, after viral infections), delayed, i.e. After a light interval (after inhalation of nitric oxide) and a gradual, almost invisible - in diffuse connective tissue diseases and after lung transplantation.

Diagnosis of obliterating bronchiolitis

Instrumental research

Radiography of the lungs

When X-ray examination, there may be increased transparency of the lungs (hyper-air), less often - a weakly expressed dissemination in the focal-mesh type. However, these changes are observed only in 50% of patients.

High-resolution computed tomography

Normally unchanged bronchioles on a computer tomogram are not visible, since their wall thickness is no more than 0.2 mm, which is less than the resolving power of the method. With obliterating bronchiolitis, the bronchioles become visible due to the inflammatory and fibrous thickening of the walls.

Typical diagnostic signs on computer tomograms are:

• small branched blackouts or centrolobular nodules (due to peribronchial thickening);
• bronchiectasis, revealed on exhalation in 70% of patients;
• mosaic oligemia "spotty" character due to hypoventilation and "air trap" (bronchioles obliteration prevents complete evacuation of air). Obliteration of bronchioles is accompanied by a secondary vasoconstriction against a background of local hypoxia. Mosaic oligemia is manifested by the fact that the lung parenchyma region corresponding to unchanged bronchioles becomes more dense on exhalation, and the affected areas are super-transparent.

Functional tests

Examination of the function of external respiration reveals violations according to the obstructive type:

• decreased maximum ventilation of the lungs;
• reduction in FVC and FEV1, as well as in the Tiffno index (FEV / ZHEL).

An increase in the concentration of nitric oxide in the exhaled air is also considered characteristic.

Investigation of blood gas composition

The most characteristic are hypoxemia and hypocapnia, less often hypercapnia is detected.

Bronchoscopy, lung biopsy

Bronchoscopy is of little informative, since the pathological process is localized distal to the bronchi, in bronchioles and is not widely available for inspection. Transbronchial or open lung biopsy reveals characteristic inflammatory and fibroplastic changes in bronchioles.

Clinical classification

The International Society for Heart and Lung Transplantation (1993) proposes to determine the baseline level of FEV1 as the mean of the two largest previous measurements to determine the degree of obliterating bronchiolitis, and then compare the present value of FEV1 with the baseline.

• 0 degree: FEV1 more than 80% of the initial level.
• I degree: FEV1 - 66-79% of the initial level.
• II degree: FEV1 - 51-65% of the initial level.
• III degree: FEV1 less than 50% of the baseline.

In addition, it is necessary to evaluate the histological pattern for revealing signs of obliterating bronchiolitis.

• Type A - there are no signs of obliterating bronchiolitis (or a biopsy was not performed).
• Type B-morphological signs of obliterating bronchiolitis.

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