Alveolar Proteinosis of the Lung

Alveolar proteinosis of the lungs is a disease of the lungs of unknown etiology, characterized by the accumulation of a protein-lipid substance in the alveoli and moderately progressive dyspnea.

Alveolar proteinosis of the lungs is the accumulation of surfactant in the alveoli. The cause of alveolar lung proteinase is almost always unknown. It is manifested by shortness of breath, malaise and fatigue. Diagnosis of alveolar pulmonary proteinosis is based on the results of a study of washing water of bronchoalveolar lavage, although there are characteristic radiographic and laboratory changes. The treatment also uses bronchoalveolar lavage. The prognosis, provided that the treatment is carried out, is generally favorable.

[1], [2], [3], [4],

Alveolar proteinosis of the lungs was first described in 1958. It occurs mainly at the age of 30-50 years, more often in men.

[5], [6], [7]

Causes of alveolar lung proteinase

The cause and pathogenesis of alveolar lung proteinase have not been fully established. The following assumptions about etiology are suggested: viral infection, genetic metabolic disorders, occupational hazards (plastics production, etc.).

Alveolar proteinosis of the lung is most often idiopathic and occurs in practically healthy men and women aged 30 to 50 years. Rare secondary forms occur in patients with acute silicosis; infection caused by Pneumocystis jiroveci (formerly called P. Carinii); in hematologic malignant diseases or immunosuppression, as well as in persons exposed to significant inhalation exposure of aluminum, titanium, cement or cellulose dust. Also there are rare congenital forms that cause neonatal respiratory failure. Information about the similarity or difference of the pathophysiological mechanisms of idiopathic and secondary cases is absent. Disrupted surfactant production by alveolar macrophages due to the pathological effect of granulocyte and macrophage colony stimulating factor (GM-CSF) is thought to contribute to the development of the disease and is possibly associated with a reduced or completely suppressed function of the common beta-chain of the GM-CSF / IL- 13 / IL-5 mononuclear cells (which is found in some children, but not in adults with this disease). Antibodies to GM-CSF were also found in most patients. Toxic lung damage is suspected, but not proven with secondary inhalation alveolar proteinosis.

Histological examination reveals the filling of alveoli with an acellular Schick-positive lipoprotein surfactant. Alveolar and interstitial cells remain normal. The posterior basal segments of the lung are most often affected. Pleura and mediastinum are usually not affected.

The pathomorphological picture of alveolar proteinosis is characterized by the following features:

• primary lesion of the basal and posterior parts of the lungs; defeat of anterior segments is rare; the pleura and mediastinum are intact;
• presence on the surface of the lungs of grayish-whitish tubercles in the form of grains;
• presence in the alveoli and bronchioles of large quantities of protein-lipid substance;
• hyperplasia and hypertrophy of type II alveolocytes.

[8], [9], [10], [11], [12], [13], [14]

Symptoms of alveolar proteinosis of the lungs

Leading symptoms of alveolar proteinosis of the lungs are gradually increasing dyspnoea and cough. Dyspnoea initially worries primarily with physical exertion, and then at rest. Cough is unproductive or accompanied by the departure of a small amount of phlegm yellowish, very rarely hemoptysis. Patients also complain of perspiration, weight loss, general weakness, decreased performance, pain in the chest (a rare symptom). Often the body temperature rises (usually up to 38 ° C), most often due to the addition of non-bacterial superinfection (for example, Nocardia, Aspergillus, Gyptococcus). In the absence of secondary infection, persistent fever is not characteristic.

When examining patients, dyspnoea primarily inspiratory type attracts attention. As diseases progressed and respiratory insufficiency increased, cyanosis appeared, a symptom of "drumsticks" and "watch glasses" (Hippocrates fingers).

In the physical examination of the lungs, a shortening of percussion sound is determined predominantly over the lower parts of the lungs. Auscultation reveals weakening of vesicular breathing, gentle crepitation over the affected parts of the lungs, less often - small bubbling rales.

When examining the cardiovascular system, tachycardia, muffled heart tones are determined. If the disease lasts for a long time, a chronic pulmonary heart develops. Studies of the abdominal cavity do not reveal any significant changes.

Diagnosis of alveolar lung proteinase

To establish the diagnosis, a study of the washing water obtained during bronchoalveolar lavage, possibly in combination with transbronchial biopsy, is required. Flushing waters are usually milky or cloudy, characterized by their SHIC-positive staining and the presence of macrophages overloaded with surfactant, an increase in the number of T lymphocytes and the presence of a surfactant in high concentrations of apoprotein-A. Thoracoscopic or open biopsy of the lung is performed in the presence of contraindications to bronchoscopy or in the noninformativity of the study of washing water of bronchoalveolar lavage. Before the start of treatment, CT high resolution (CTWR), pulmonary function tests, arterial blood gases and standard laboratory tests are usually performed.

When HRCT reveals changes in the type of frosted glass, thickening of the intralobular structures and interlobular septa of a typical polygonal shape. These changes are not specific and can also be detected in patients with lipoid pneumonia, broncho-alveolar cancer and pneumonia caused by Pneumocystis jiroveci.

Lung function tests show a slow decrease in diffusion capacity for carbon monoxide (DLCO), often not corresponding to the decrease in vital capacity of lungs, residual volume, functional residual volume and total lung capacity.

Changes in laboratory studies include polycythemia, hypergammaglobulinemia, increased serum LDH activity and an increase in serum surfactant proteins A and D. All these changes are suspicious, but not specific. Investigation of arterial blood gases can demonstrate hypoxemia with moderate or mild physical exertion or at rest, if the disease is more pronounced.

[15], [16]

Laboratory Diagnosis of Alveolar Proteinosis of the Lung

1. General blood test. Essential changes are not revealed. Perhaps a moderate decrease in the amount of hemoglobin and erythrocytes, an increase in ESR. When joining superinfection of the lower respiratory tract appears leukocytosis.
2. General analysis of urine. As a rule, there are no pathological changes.
3. Blood chemistry. Perhaps a slight decrease in albumin levels, an increase in the content of gamma globulins, an increase in the level of total lactate dehydrogenase (a characteristic feature).
4. Immunological research. The content of B- and T-lymphocytes and immunoglobulins, as a rule, is normal. Circulating immune complexes are not detected.
5. Determination of the gas composition of blood. In most patients, arterial hypoxemia is observed even at rest. With a short duration of the disease and mild its form, hypoxemia is determined after physical exertion.
6. Investigation of the lavage fluid of the bronchi. A characteristic feature is an increase in the protein content in the lavage fluid by a factor of 10-50 compared with the norm. A great diagnostic value is the positive reaction of bronchial flushing fluid with immunoperoxidase. In patients with secondary lung proteinase, this reaction is negative. An important diagnostic feature is also the very low content of alveolar macrophages, in which eosinophilic granular inclusions are determined. In the sediment of the lavage liquid, the "eosinophilic grains" are located freely, outside the connection with the cells.
7. Sputum analysis. In sputum, a large number of SHC-positive substances is detected.

Instrumental diagnosis of alveolar proteinosis of the lungs

1. X-ray examination of the lungs. X-ray signs of alveolar proteinosis are:
   • bilateral fine-focal darkening, located mainly in the lower and middle sections and tending to merge;
   • symmetrical or asymmetric darkening in the area of the roots of the lungs (the pattern of infiltration in the form of a "butterfly", similar to the picture when swelling of the lungs);
   • interstitial fibrotic changes (may be detected in the final stages of the disease);
   • absence of changes from the intrathoracic lymph nodes, pleura, heart.
2. Research of ventilating function of the lungs. The development of respiratory insufficiency is of a restrictive type, which is manifested by a progressive decrease in GEL. The signs of bronchial obstruction, as a rule, are not revealed.
3. ECG. It is possible to decrease the amplitude of the T wave mainly in the left thoracic leads, as a reflection of myocardial dystrophy, which develops as a result of arterial hypoxemia.
4. Study of lung tissue biopsy. A biopsy of the lung tissue (perebrohialnaya, open, thoracoscopic) is performed in order to verify the diagnosis. In the alveoli, the protein-lipid exudate is determined by a histochemical Schick reaction (PAS reaction). This technique reveals glycogen, glycolipids, neutral mucoproteins, glycoproteins, sialomucoproteins. When stained with Schiff's reagent, protein-lipid substances give a purple or purple-red color. There is also a reaction with immunoperoxidase: it is positive for primary alveolar proteinosis and negative for secondary forms of the disease.

Electron microscopic examination of biogeochemistry of pulmonary tissue in alveoli and alveolar macrophages reveals surfaktang in the form of plates.

In the differential diagnosis of primary and secondary alveolar proteinosis (in leukemia, pneumocystis infection), the nature of the location of Schick-positive substances should be taken into account. In primary alveolar proteinosis, SHC-positive substances are stained uniformly in the alveoli, while in the secondary alveolar, they are stained (granularly).

Program of examination for alveolar lung proteinase

1. Common blood tests, urine tests.
2. Sputum analysis for the content of CHC-positive substances.
3. Biochemical blood test: determination of blood content of total protein, protein 1 fraction, total LDH.
4. Radiography of the lungs in three projections.
5. Spirography.
6. ECG.
7. The study of bronchial flushing water (determination of the protein content, the number of alveolar macrophages, the setting of the SHIC response, and also the reaction with immunoperoxidase)
8. Investigation of lung biopsy specimens (detection of protein-lipid exudate in alveoli, reaction with immunoperoxidase and Schick reaction).

Treatment of alveolar proteinosis of the lungs

Treatment of alveolar proteinosis of the lungs is not required, not having manifestations of the disease or with a slight degree of their severity. Therapeutic bronchoalveolar lavage is performed by patients suffering from severe shortness of breath, under general anesthesia and against the background of artificial ventilation of the lungs through a double-lumen intubation tube. One lung is washed up to 15 times; The volume of sodium chloride solution is from 1 to 2 liters, at this time another lung is ventilated. Then a similar procedure is carried out on the other side. The lung transplantation is inadvisable, as the disease recurs in the transplant.

Systemic glucocorticoids do not have a therapeutic effect and may increase the risk of secondary infection. The role of GM-CSF (with intravenous or subcutaneous injection) in the treatment of the disease requires clarification. Open studies showed a clinical recovery, observed in 57% of patients included in them.

What prognosis does alveolar pulmonary proteinosis have?

The prognosis of alveolar proteinosis is considered relatively favorable. Alveolar proteinosis of the lungs proceeds for a long time, characterized by a slowly progressing course. Spontaneous recovery is possible in 25% of patients. In the remaining patients, there may be a significant improvement when using bronchial pulmonary lavage as the main treatment method. In an unfavorable course, death can result from severe respiratory failure or a decompensated pulmonary heart.

Without treatment, alveolar proteinosis of the lung passes on its own in 10% of patients. The only procedure for bronchoalveolar lavage is curative in 40% of patients; other patients require lavage once every 6-12 months for many years. The five-year survival rate is approximately 80%; the most common cause of death is respiratory failure, typically developing during the first year after diagnosis. Secondary lung infections caused by bacteria Mycobacteria, Nocardia) and other organisms of Aspergillus, Cryptococcus and other opportunistic fungi), sometimes develop due to a decrease in the function of macrophages; these infections require treatment.