Idiopathic fibrosing alveolitis - Diagnosis

Laboratory data

1. General blood analysis - the number of erythrocytes and hemoglobin levels are usually normal, however, with the development of severe respiratory failure, erythrocytosis appears and the hemoglobin level increases. In 25% of patients, a mild degree of normochromic anemia is possible. The number of leukocytes is normal or moderately increased, with an acute course of the disease, a shift in the leukocyte formula to the left is observed. An increase in ESR is characteristic, most pronounced with high activity of the inflammatory process.
2. General urine analysis shows no significant changes. With the development of decompensated pulmonary heart disease, moderate proteinuria and microhematuria are detected.
3. Biochemical blood test - an increase in the content of seromucoid, haptoglobin, a2- and y-globulins in the blood is noted (these indicators reflect the activity of the pathological process). Also characteristic is an increase in the level of LDH, the source of which are alveolar macrophages and alveolocytes of type 2. LDH levels correlate with the activity of the pathological process in the lungs.

An important marker of the activity of idiopathic fibrosing alveolitis is an increase in the level of surfactant glycoproteins A and D in the blood serum, which is due to a sharp increase in the permeability of the alveolar-capillary membrane.

With the development of decompensated pulmonary heart disease, a moderate increase in the blood levels of bilirubin, alanine aminotransferase, and gamma-glutamyl transpeptidase is possible.

4. Immunological blood test - characteristically a decrease in the number of T-suppressor lymphocytes and an increase in T-helpers, an increase in the general level of immunoglobulins and cryoglobulins, increased titers of rheumatoid and antinuclear factors, possible appearance of antipulmonary antibodies, circulating immune complexes. The indicated changes reflect the intensity of autoimmune processes and inflammation of the pulmonary interstitium.

In recent years, great importance has been attached to the determination of mucin antigens in the blood, which reflect both the intensity of inflammation in the pulmonary interstitium and the severity of autoimmune processes. Mucins are surface glycoproteins that provide "gluing", unification of epithelial cells (including alveolocytes) and the formation of a monolayer. The level of mucins in the blood reflects hyperplasia and hypertrophy of type 2 alveolocytes and their increased mucin-forming function. In addition, mucins can be produced by goblet cells of the bronchial epithelium and secretory cells of the glands of the submucosal layer. Mucins are markers of the activity of the pathological process and the severity of autoimmune reactions. Mucin antigens SSEA-1, KL-6, 3EG5 are detected in the blood serum in idiopathic fibrosing alveolitis.

5. A study of bronchial lavage fluid (obtained during bronchial lavage) shows a significantly increased number of neutrophils, eosinophils, lymphocytes, alveolar macrophages, increased activity of proclitic enzymes elastase and collagenase (in the late stages of idiopathic fibrosing alveolitis, a decrease in proteolysis activity is possible), and the content of immune complexes and IgG is significantly increased.

Neutrophil-eosinophil association and pronounced lymphocytosis are characteristic of active alveolitis. Pronounced eosinophilia of bronchial lavage fluid is observed in patients with an unfavorable prognosis and poor response to glucocorticoid treatment. Smoking affects the cytological composition of bronchial lavage fluid: smokers have a significantly higher number of alveolar macrophages, neutrophils, and eosinophils compared to non-smoking patients.

Of great importance is the determination of lipids and some proteins in the bronchial lavage fluid, reflecting the synthesis and functioning of surfactant. The following changes have been established:

• the overall level of phospholipids decreases (the lower their level, the worse the prognosis);
• the fractional composition of total phospholipids changes (the ratio of phosphatidylglycol to phosphatidylinositol decreases);
• the content of protein surfactant-A decreases (this sign correlates with the activity of alveolitis).

The activity of the inflammatory process in idiopathic fibrosing alveolitis is also evidenced by the high concentration of the following components in the bronchial lavage fluid:

• mucin antigens KL-6 - secretion products of alveolar cells type 2;
• procollagen-3 peptidase (secreted by fibroblasts);
• elastase (produced by neutrophil cells);
• histamine and tryptase (released during mast cell degranulation);
• angiotensin-converting enzyme (produced by endothelial cells);
• fibronectin and vitronectin - components of the extracellular matrix.

6. Sputum analysis - no significant changes. When chronic bronchitis is added, the number of neutrophilic leukocytes is increased.

Instrumental research

Chest X-ray is the most important diagnostic method for idiopathic fibrosing alveolitis. Bilateral changes are detected, mainly in the lower parts of the lungs.

M. M. Ilkovich (1998) identifies three variants of radiological changes in idiopathic fibrosing alveolitis:

• predominant damage to the interstitial tissue of the lungs (mural variant);
• predominant damage to the alveoli (desquamative variant);
• X-ray picture corresponding to "honeycomb lung".

The variant with predominant damage to the interstitial tissue is characterized at the initial stages of the disease by decreased lung transparency of the "ground glass" type, some decrease in the volume of the lower lobes of the lungs, decreased root structure, reticular deformation of the pulmonary pattern, peribronchial-perivascular cuff-like changes. As IFA progresses, against the background of coarse stringiness and restructuring of the pulmonary pattern, rounded cystic enlightenment with a diameter of 0.5-2 cm ("honeycomb lung") appears. In the late stages of idiopathic fibrosing alveolitis, tracheomegaly and tracheal deviation to the right are possible.

The variant with predominant damage to the alveoli (desquamative variant) is characterized by bilateral infiltrative darkening of varying severity and extent.

When pulmonary hypertension develops, the main branches of the pulmonary artery become dilated.

Johnson et al. (1997) consider the following radiographic signs to be the most characteristic of idiopathic fibrosing alveolitis:

• delineated nodular-linear opacities (51%);
• changes of the “honeycomb lung” type (15%);
• changes of the "frosted glass" type (5%).

Computed tomography of the lungs is a highly informative method for diagnosing lung damage in idiopathic fibrosing alveolitis and allows for the detection of changes in the pulmonary interstitium at a stage of the disease when conventional chest radiography does not detect them.

The most characteristic signs of idiopathic fibrosing alveolitis on computed tomography of the lungs are:

• uneven thickening of the interalveolar and interlobular septa (a pattern of lung reticulation, most pronounced in the subpleural and basal parts of the lungs);
• decreased transparency of the lung fields according to the “ground glass” type (this sign is revealed with minimal thickening of the alveolar walls, interstitium or partial filling of the alveoli with cells, fluid, detritus);
• signs of “honeycomb lung” (detected in 90% of cases) in the form of air cells ranging in size from 2 to 20 mm in diameter (detected significantly earlier than with chest X-rays).

Angiopulmonography - allows to judge the state of pulmonary blood flow in patients with idiopathic fibrosing alveolitis. It reveals expansion of the central branches of the pulmonary artery, narrowing and unclear contours on the periphery, slowing of the arterial phase of blood flow, the presence of areas of rapid arteriovenous shunting, accelerated contrasting of the venous bed.

Scintigraphic examination of the lungs with radioactive Ga - the method allows us to judge the activity of alveolitis, since this isotope is concentrated in tissues altered by inflammation. Gallium binds to transferrin receptors, which are expressed only on the membranes of active alveolar macrophages and therefore a more intensive accumulation of gallium is observed in active alveolitis. The coefficient of accumulation of the isotope depends on the severity of alveolitis and does not depend on its prevalence.

Positron tomography scanning of the lungs after inhalation of diethylene triamine pentaacetate labeled with technetium-99 C-Tc-DTPA) - allows to evaluate the permeability of the alveolar-capillary membrane and to identify diffuse alveolar damage. In the case of a pronounced active inflammatory process, the half-life of the isotope (T1/2) is significantly reduced.

Bronchoscopy does not play a significant role in the diagnosis of idiopathic fibrosing alveolitis. Bronchoscopy may reveal a picture of moderate catarrhal bronchitis.

Examination of the external respiratory function. Idiopathic fibrosing alveolitis is characterized by a symptom complex of disorders of the ventilation capacity of the lungs:

• increased respiratory rate;
• decrease in inspiratory volume;
• decrease in vital capacity, residual lung volume, total lung capacity;
• increase in elastic resistance of the lungs;
• decreased diffusion capacity of the lungs;
• absence of bronchial obstruction or minor changes in it.

It should be noted that spirography values may be normal in the early stages of the disease, but at the same time there may be a decrease in the values of total lung capacity, functional residual capacity and residual volume, which is detected using body plethysmography or the gas dilution method. A decrease in total lung capacity correlates with the severity of the inflammatory reaction in the lung tissue and, unfortunately, with an unfavorable prognosis.

A highly sensitive method in the early stage of ELISA is the analysis of the pressure-volume curve (by measuring the pressure in the middle third of the esophagus, which corresponds to the intrapleural pressure, and then recording the pressure and volume of the lungs over the entire range of vital capacity). This technique reveals a decrease in lung compliance and a decrease in lung volume.

Of great importance is also the determination of the diffusion capacity of the lungs, which is studied using the method of a single inhalation of test gas (carbon monoxide) with breath holding. In recent years, the method of a single inhalation of carbon monoxide without holding the breath with a gradual smooth exhalation has been used. Idiopathic fibrosing alveolitis is characterized by a decrease in the diffusion capacity of the lungs, which is due to a decrease in lung volumes, thickening of the alveolar-capillary membrane, and a decrease in the capillary network.

With pronounced progression of the pathological process in idiopathic fibrosing alveolitis, obstructive disorders can form at the level of the peripheral respiratory tract, which can manifest itself as a decrease in the forced expiratory volume in the first second.

It should be noted that the study of the functional capacity of the lungs should be carried out not only at rest, but also during physical activity, which is especially important for identifying disorders at an early stage of the disease.

Study of the gas composition of arterial blood. In the early stages of the disease, a decrease in partial oxygen tension is observed only during physical exertion, but as the disease progresses, hypoxemia is also detected at rest. In the terminal stage of idiopathic fibrosing alveolitis, hypercapnia (a sharp increase in the saturation of the blood with carbon dioxide) develops.

Open lung biopsy - this method is considered the "gold standard" for diagnosing idiopathic fibrosing alveolitis. The informativeness of the method exceeds 94%. Biopsy is performed from several areas of the lungs - with the greatest and least changes according to X-ray and computed tomography of the lungs. It is recommended to take 2-4 samples from the upper and lower lobes of the lung. Biopsy samples are subjected to morphological, bacteriological, virological, immunofluorescent, immunogastochemical and electron microscopic studies. These methods reveal changes typical for idiopathic fibrosing alveolitis.

In recent years, television-assisted lung biopsy has become increasingly widespread.

Percutaneous puncture biopsy of the lungs has also been proposed for the diagnosis of idiopathic fibrosing alveolitis; its information content is about 90%, but the number of complications (primarily pneumothorax) is about 30%.

Transbronchial lung biopsy is rarely used due to its low information content in the diagnosis of idiopathic fibrosing alveolitis, but it is important for differential diagnosis with sarcoidosis, obliterating bronchiolitis, and bronchogenic cancer.

ECG - changes characteristic of chronic pulmonary heart disease are determined (signs of right ventricular myocardial hypertrophy, deviation of the electrical axis of the heart to the right).

Diagnostic criteria for idiopathic fibrosing alveolitis

The main criteria that allow the diagnosis of idiopathic fibrosing alveolitis can be considered the following:

• progressive shortness of breath (not caused by any other disease);
• diffuse ash-gray cyanosis;
• shortening of the inhalation and exhalation phases;
• constant "gentle" crepitation heard over both lungs;
• predominantly interstitial changes in both lungs,
• bilateral infiltrative darkening of varying severity and extent, the “honeycomb lung” pattern in X-ray examination of the lungs);
• restrictive type of respiratory failure (according to spirography data);
• hypoxia without hypercapnia at rest or only during physical exertion;
• characteristic morphological picture of lung biopsies;
• the absence of a connection between the appearance of the named criteria and any reliable etiological factor.

Differential diagnosis

Most often, idiopathic fibrosing alveolitis must be differentiated from the following diseases.

1. Fibrosing alveolitis syndrome in diffuse connective tissue diseases. The signs that distinguish this syndrome from idiopathic fibrosing alveolitis are:
   • the presence of pronounced systemic manifestations (damage to the skin, kidneys, muscles, joints, nervous system); the clinical features of these manifestations are characteristic of certain nosological forms of diffuse connective tissue diseases;
   • frequent presence of polyserositis syndrome (especially in systemic lupus erythematosus);
   • articular syndrome;
   • determination of autoantibodies in the blood that are specific to certain nosological forms of diffuse connective tissue diseases (antinuclear antibodies in systemic lupus erythematosus, rheumatoid factor in rheumatoid arthritis, etc.);
   • absence of steadily progressing shortness of breath.
2. Sarcoidosis of the lungs differs from idiopathic fibrosing alveolitis in the following characteristic features:
   • systemic nature of the lesion (most often the hilar lymph nodes, lungs, skin, joints are affected, less often the liver, spleen, heart, nervous and endocrine systems);
   • the presence of Löfgren's syndrome (a combination of lymphadenopathy, erythema nodosum, polyarthritis);
   • positive Kveim reaction (see " Sarcoidosis ");
   • increased levels of angiotensin-converting enzyme in the blood;
   • absence of severe progressive respiratory failure of the restrictive type (in some patients, its moderate manifestations are possible);
   • relatively benign and asymptomatic course;
   • the presence of specific sarcoid tubercles on the bronchial mucosa (detected during bronchoscopy);
   • detection of characteristic epithelioid cell granulomas in lung tissue biopsies obtained during transbronchial biopsy.
3. Disseminated pulmonary tuberculosis. Unlike idiopathic fibrosing alveolitis, disseminated pulmonary tuberculosis is characterized by:
   • anamnestic data (contact with a patient with tuberculosis, previous tuberculosis of the lungs or other organs);
   • recurrent fibrinous or exudative pleurisy;
   • frequent tuberculosis of other organs and systems (kidneys, spine, etc.);
   • characteristic radiological changes (multiple symmetrical small focal shadows throughout all lung fields measuring 1-2 mm with a zone of perifocal inflammation, sometimes the formation of cavities);
   • positive tuberculin tests;
   • detection of tuberculosis bacteria in sputum and bronchial washings.
4. Exogenous allergic alveolitis. A characteristic feature of exogenous allergic alveolitis is a clear connection between the development of the disease and a known etiologic factor.
5. Pneumoconiosis. The most important features that distinguish pneumoconiosis from idiopathic fibrosing alveolitis are:
   • connection between the development of the disease and work in a dusty production facility;
   • predominant localization of radiological changes in the mid-lateral pulmonary fields and a tendency for small focal shadows to merge into medium and large ones;
   • detection of silicotic granulomas in lung tissue biopsies.
6. Idiopathic hemosiderosis of the lungs. The main distinguishing feature of hemosiderosis of the lungs is a combination of hemoptysis, anemia, and restrictive respiratory failure.

Survey program

1. Complete blood count.
2. Immunological studies: determination of the content of B- and T-lymphocytes, subpopulations of T-lymphocytes, immunoglobulins, circulating immune complexes.
3. Biochemical blood test: determination of total protein, protein fractions, haptoglobin, seromucoid, bilirubin, alanine and aspartate aminotransferases, urea, creatinine.
4. ECG.
5. Chest X-ray (computerized tomography of the lungs is preferred).
6. Determination of blood gas composition.
7. Spirometry.
8. Study of bronchial lavage fluid: determination of cellular composition, lipids and surfactant proteins, proteolytic enzymes, mucin antigens.
9. Open lung biopsy.

Examples of diagnosis formulation

1. Idiopathic fibrosing alveolitis, acute course, stage II respiratory failure.
2. Idiopathic fibrosing alveolitis, chronic course, slowly progressive variant, stage II respiratory failure, chronic compensated pulmonary heart disease.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ]