Alveolar pulmonary proteinosis

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

Alveolar proteinosis of the lungs is the accumulation of surfactant in the alveoli. The cause of alveolar proteinosis of the lungs is almost always unknown. It manifests itself as dyspnea, malaise and fatigue. Diagnosis of alveolar proteinosis of the lungs is based on the results of the study of washing waters of bronchoalveolar lavage, although there are characteristic radiographic and laboratory changes. Bronchoalveolar lavage is also used in treatment. The prognosis, subject to treatment, is generally favorable.

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

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

[ 5 ], [ 6 ], [ 7 ]

Causes of alveolar proteinosis of the lungs

The cause and pathogenesis of alveolar proteinosis of the lungs have not been definitively established. The following assumptions about the etiology are put forward: viral infection, genetic metabolic disorders, occupational hazards (plastics production, etc.).

Pulmonary alveolar proteinosis is most often idiopathic and occurs in apparently healthy men and women aged 30 to 50 years. Rare secondary forms occur in patients with acute silicosis; in Pneumocystis jiroveci (formerly P. carinii) infection; in hematological malignancies or immunosuppression; and in individuals with significant inhalational exposure to aluminum, titanium, cement, or cellulose dust. Rare congenital forms causing neonatal respiratory failure also occur. There are no data on the similarities or differences in the pathophysiological mechanisms of idiopathic and secondary cases. Impaired surfactant production by alveolar macrophages due to abnormal granulocyte-macrophage colony-stimulating factor (GM-CSF) activity is thought to contribute to the disease and may be associated with decreased or suppressed function of the mononuclear cell GM-CSF/IL-13/IL-5 receptor common beta chain (which is seen in some children but not in adults with the disease). Anti-GM-CSF antibodies have also been found in most patients. Toxic lung injury is suspected but not proven in secondary inhalational alveolar proteinosis.

Histological examination reveals filling of the alveoli with acellular, PAS-positive lipoprotein surfactant. Alveolar and interstitial cells remain normal. The posterobasal segments of the lung are most frequently affected. The pleura and mediastinum are usually spared.

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

• predominantly lesion of the basal and posterior parts of the lungs; lesion of the anterior segments is rare; the pleura and mediastinum are intact;
• the presence of light grayish-whitish tubercles in the form of grains on the surface;
• the presence of large amounts of protein-lipid substances in the alveoli and bronchioles;
• hyperplasia and hypertrophy of alveolar cells type II.

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

Symptoms of alveolar proteinosis of the lungs

The leading symptoms of alveolar proteinosis of the lungs are gradually increasing dyspnea and cough. Dyspnea initially bothers mainly during physical exertion, and then at rest. The cough is unproductive or accompanied by the discharge of a small amount of yellowish sputum, hemoptysis is very rare. Patients also complain of sweating, weight loss, general weakness, decreased performance, chest pain (a rare symptom). Body temperature often rises (usually up to 38°C), most often due to the addition of a non-bacterial superinfection (for example, Nocardia, Aspergillus, Gyptococcus). In the absence of a secondary infection, persistent fever is not typical.

When examining patients, attention is drawn to dyspnea, predominantly of the inspiratory type. As the disease progresses and respiratory failure intensifies, cyanosis, the symptom of "drumsticks" and "watch glasses" (Hippocratic fingers) appear.

Physical examination of the lungs reveals a shortened percussion sound, predominantly over the lower parts of the lungs. Auscultation reveals weakened vesicular breathing, gentle crepitation over the affected areas of the lungs, and, less frequently, fine bubbling rales.

When examining the cardiovascular system, tachycardia and muffled heart sounds are detected. Chronic pulmonary heart disease develops when the disease persists for a long time. Examination of the abdominal organs does not reveal any significant changes.

Diagnosis of alveolar proteinosis of the lungs

Diagnosis requires examination of bronchoalveolar lavage fluid, possibly in combination with transbronchial biopsy. Fluids are usually milky or turbid, are PAS-positive, and show surfactant-laden macrophages, increased T-lymphocytes, and high levels of surfactant apoprotein-A. Thoracoscopic or open lung biopsy is performed when bronchoscopy is contraindicated or when bronchoalveolar lavage fluid examination is uninformative. High-resolution CT (HRCT), pulmonary function tests, arterial blood gases, and standard laboratory tests are usually performed before treatment.

HRCT reveals ground-glass opacity, thickening of intralobular structures, and interlobular septa of typical polygonal shape. These changes are not specific and can also be found in patients with lipoid pneumonia, bronchoalveolar cancer, and pneumonia caused by Pneumocystis jiroveci.

Pulmonary function tests reveal a slow decline in the diffusing capacity for carbon monoxide (DLCO), often out of proportion to the decline in vital capacity, residual volume, functional residual volume, and total lung capacity.

Laboratory findings include polycythemia, hypergammaglobulinemia, increased serum LDH activity, and increased serum surfactant proteins A and D. All of these findings are suggestive but not specific. Arterial blood gas studies may show hypoxemia with moderate to mild exercise or at rest if the disease is more advanced.

[ 15 ], [ 16 ]

Laboratory diagnostics of alveolar proteinosis of the lungs

1. Complete blood count. No significant changes are detected. A moderate decrease in hemoglobin and erythrocytes, an increase in ESR are possible. Leukocytosis appears when superinfection of the lower respiratory tract occurs.
2. General urine analysis. As a rule, there are no pathological changes.
3. Biochemical blood test. A slight decrease in albumin levels, an increase in gamma globulin levels, and an increase in the level of total lactate dehydrogenase (a characteristic sign) are possible.
4. Immunological studies. The content of B- and T-lymphocytes and immunoglobulins is usually normal. Circulating immune complexes are not detected.
5. Determination of blood gas composition. Most patients have arterial hypoxemia even at rest. With a short duration of the disease and its mild form, hypoxemia is determined after physical exertion.
6. Study of bronchial lavage fluid. A characteristic sign is an increase in the protein content in the lavage fluid by 10-50 times compared to the norm. A positive reaction of the bronchial lavage fluid with immunoperoxidase is of great diagnostic importance. In patients with secondary pulmonary proteinosis, this reaction is negative. An important diagnostic sign is also a very low content of alveolar macrophages, in which eosinophilic granular inclusions are determined. In the sediment of the lavage fluid, "eosinophilic grains" are located freely, without connection with cells.
7. Sputum analysis. A large number of PAS-positive substances are determined in the sputum.

Instrumental diagnostics of alveolar proteinosis of the lungs

1. X-ray examination of the lungs. X-ray signs of alveolar proteinosis are:
   • bilateral small focal darkening, located mainly in the lower and middle sections and tending to merge;
   • symmetrical or asymmetrical darkening in the area of the roots of the lungs (a “butterfly” pattern of infiltration, similar to the pattern seen in pulmonary edema);
   • interstitial fibrous changes (may be detected in the final stages of the disease);
   • no changes in the intrathoracic lymph nodes, pleura, or heart.
2. Study of the ventilation function of the lungs. The development of respiratory failure of the restrictive type is typical, which is manifested by a progressive decrease in the vital capacity. Signs of bronchial obstruction are usually not detected.
3. ECG. A decrease in the amplitude of the T wave is possible, mainly in the left chest leads, as a reflection of myocardial dystrophy developing as a result of arterial hypoxemia.
4. Examination of lung tissue biopsy. Lung tissue biopsy (transbronchial, open, thoracoscopic) is performed to verify the diagnosis. Protein-lipid exudate is determined in the alveoli using the histochemical PAS reaction. This method reveals glycogen, glycolipids, neutral mucoproteins, glycoproteins, sialomucoproteins. When stained with Schiff reagent, protein-lipid substances give a purple or lilac-red color. A reaction with immunoperoxidase is also performed: it is positive in primary alveolar proteinosis and negative in secondary forms of the disease.

Electron microscopic examination of lung tissue biochemistry reveals surfactant in the form of plates in the alveoli and alveolar macrophages.

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

Examination program for alveolar proteinosis of the lungs

1. General blood and urine tests.
2. Analysis of sputum for the content of PAS-positive substances.
3. Biochemical blood test: determination of the content of total protein, protein fractions, and total LDH in the blood.
4. X-ray of the lungs in three projections.
5. Spirometry.
6. ECG.
7. Study of bronchial lavage waters (determination of protein content, number of alveolar macrophages, setting up the PAS reaction, as well as the reaction with immunoperoxidase)
8. Examination of lung tissue biopsies (detection of protein-lipid exudate in the alveoli, performing a reaction with immunoperoxidase and the PAS reaction).

Treatment of alveolar proteinosis of the lungs

Treatment of alveolar proteinosis of the lungs is not required if there are no symptoms of the disease or if they are minor. Therapeutic bronchoalveolar lavage is performed in patients suffering from severe dyspnea, under general anesthesia and against the background of artificial ventilation of the lungs through a double-lumen endotracheal tube. One lung is washed up to 15 times; the volume of sodium chloride solution is from 1 to 2 liters, while the other lung is ventilated. Then a similar procedure is performed on the other side. Lung transplantation is inappropriate, since the disease recurs in the graft.

Systemic glucocorticoids have no therapeutic effect and may increase the risk of secondary infection. The role of GM-CSF (intravenous or subcutaneous) in the treatment of the disease requires clarification. Open studies have demonstrated clinical recovery in 57% of patients included in them.

What is the prognosis for pulmonary alveolar proteinosis?

The prognosis of alveolar proteinosis is considered relatively favorable. Alveolar proteinosis of the lungs is a long-term disease, characterized by a slowly progressive course. Spontaneous recovery is possible in 25% of patients. The remaining patients may experience significant improvement when using bronchiolung lavage as the main treatment method. In an unfavorable course, death may occur from severe respiratory failure or decompensated pulmonary heart disease.

Without treatment, pulmonary alveolar proteinosis resolves spontaneously in 10% of patients. A single bronchoalveolar lavage procedure is curative in 40% of patients; other patients require lavage every 6 to 12 months for many years. Five-year survival is approximately 80%; the most common cause of death is respiratory failure, typically occurring within the first year of diagnosis. Secondary pulmonary infections with Mycobacteria, Nocardia) and other organisms (Aspergillus, Cryptococcus, and other opportunistic fungi) sometimes occur as a result of decreased macrophage function; these infections require treatment.