Pulmonary alveolar proteinosis is a pulmonary pathology associated with hyperproduction of surfactant and filling of the alveolar cavity with excess protein-lipid mass. In the case of pulmonary alveolar proteinosis, dyspnea is steadily progressing, an unproductive cough occurs, subfebrile fever may occur, weight loss, sweating, fatigue, respiratory failure may develop. Diagnostics is based on the data of radiography and computed tomography of the lungs, respiratory function, lung biopsy, laboratory tests. Therapy consists in carrying out therapeutic bronchoalveolar lavage.
ICD 10
J84.0 Alveolar and parietal-alveolar disorders
Meaning
Pulmonary alveolar proteinosis is an interstitial lung disease accompanied by changes in lung tissue due to deposition of a protein-lipid substrate on the inner surface of the alveoli. The prevalence of pathology is low – 0.2 cases per 1 million population. In most cases, the disease manifests at the age of 30-50 years, although it can occur in children and elderly patients. Among the patients, there is a clear predominance of males – the ratio of men and women is 5:1. Pulmonary alveolar proteinosis can be primary (idiopathic) and secondary (develop against the background of existing pathology), congenital or acquired. In the course of pulmonology, acute and chronic forms of pulmonary alveolar proteinosis are differentiated.
Causes
Various forms of pulmonary alveolar proteinosis have their own determining factors. Congenital pulmonary alveolar proteinosis is caused by gene mutations leading to pathology of pulmonary metabolism, in particular, impaired synthesis of surfactant type B or C proteins, abnormalities of the GM-CSF receptor. The most common idiopathic pulmonary alveolar proteinosis develops in the presence of autoantibodies to GM-CSF, causing damage to its structure and a decrease in functional activity. Rare forms of secondary alveolar proteinosis are associated with deficiency and functional insufficiency of alveolar macrophages. The cause of this condition may be chronic viral or bacterial infections (especially caused by pneumocysts, mycobacteria, fungi), smoking, occupational hazards (prolonged inhalation of pollutants in the production of heavy metals, silicon, aluminum, plastics), hemoblastosis, decreased immunity.
Pathogenesis
The protein-lipid substance accumulating in the lungs consists of surfactant phospholipids, “foamy” alveolar macrophages (loaded with lipid granules), eosinophilic grains, immunoglobulins and proteins of the alveolar fluid. The pulmonary surfactant (antiatelectatic factor), 90% represented by the lipid fraction, as well as proteins and a small number of polysaccharides, is secreted by the epithelial cells of the pulmonary sacs – type II alveolocytes. Covering the inner surface of the alveoli in the form of a thin film, it regulates the surface tension at the air-liquid interface, preventing the alveoli from falling off during breathing. Surfactant promotes the diffusion and assimilation of oxygen, regulates water metabolism in the lungs, has a bactericidal and immunomodulatory effect. Surfactant catabolism is provided by a full cycle of recirculation in alveolocytes, as well as its phagocytosis by alveolar macrophages. The key factor in the regulation of this process is the granulocyte-macrophage colony stimulating factor (GM-CSF).
The mechanism of development of pulmonary alveolar proteinosis is associated with the hyperproduction of the altered surfactant, its incomplete absorption by alveolar macrophages, and the insufficiency of GM-CSF. The capture of a large amount of surfactant by alveolar macrophages leads to their degenerative changes and dysfunction, which contributes to the further progressive accumulation of excess protein-lipid substance inside the alveoli.
Symptoms
There are 3 stages in the clinical development of pulmonary alveolar proteinosis. In the initial stage I, there are no pronounced functional disorders and clinical manifestations, pathology is detected during a planned X-ray examination. Stage II is characterized by the occurrence of respiratory insufficiency of the I degree, increased radiological changes on the part of the lungs. The next stage, stage III, is manifested by a detailed clinical picture, progression of respiratory failure to degree II, the addition of secondary infection and bronchitis. In the terminal stage, the formation of a pulmonary heart is possible.
The leading symptoms defining the clinic of alveolar proteinosis are increasing shortness of breath and cough. At first, shortness of breath appears only against the background of physical exertion, then it begins to bother at rest. The nature of the cough is unproductive with the release of scanty sputum, first – mucous, then – purulent. Hemoptysis with pulmonary alveolar proteinosis occurs rarely. In the acute period, there is a subfebrile temperature, malaise, sweating, weight loss, fatigue, sometimes chest pain. With a prolonged course, cyanosis may be noted as a manifestation of respiratory insufficiency, a symptom of “Hippocratic fingers”.
Diagnostics
During physical examination, weakened vesicular respiration and slight crepitation are heard above the lower parts of the lungs, a shortening of the percussion sound is detected. Blood changes are nonspecific – polycythemia, gamma-globulinemia, increased LDH activity, high cholesterol, Ca, serum surfactant proteins A and D. The presence of CHIC+ substances is determined in the sputum. Analysis of the gas composition of blood with pronounced alveolar proteinosis indicates arterial hypoxemia; with a mild course, it is observed only after physical exertion.
Radiography and CT of the lungs visualize bilateral disseminated fine-focal shadows in the basal and basal segments, prone to fusion, decreased transparency (the phenomenon of “frosted glass”). At the terminal stage, interstitial dystrophic and fibrous changes are noted. Spirometry reveals a restrictive type of respiratory failure, a decrease in blood pressure. Analysis of bronchial flushing waters reveals their turbid hue, increased protein content, CHIC-positive staining, high level of T-lymphocytes, a decrease in the number of alveolar macrophages. Open, thoracoscopic or transbronchial lung biopsy with histology of biopsies confirms the presence of protein-lipid exudate in the alveoli and surfactant plates in alveolar macrophages.
Pulmonary alveolar proteinosis is differentiated from other disseminated processes in the lungs (tuberculosis, sarcoidosis, radiation lung lesions, fibrosing alveolitis, bronchoalveolar cancer, Goodpasture syndrome, leiomyomatosis, collagenosis, rheumatoid vasculitis), secondary proteinosis developed against the background of hematological pathology (leukemia, lymphoma).
Treatment
In the absence or insignificance of manifestations, treatment of alveolar proteinosis may not be carried out. In the case of a pronounced clinical picture, a therapeutic bronchoalveolar lavage with saline solution and medications (heparin, trypsin, streptase, acetylcysteine) helps to improve the general condition and ensure prolonged remission. The use of systemic corticosteroids and immunosuppressants does not have a therapeutic effect, but may increase the risk of secondary infections. Antibiotic therapy is indicated only in the presence of bacterial complications.
Bronchoalveolar lavage is performed under general anesthesia and ventilation. The lungs are washed alternately, up to 15 times each. With further rapid accumulation of protein-lipid complexes in the alveoli, repeated therapeutic procedures are required after 6-12-24 months. After bronchoalveolar lavage procedures, there is an improvement in clinical and functional indicators, positive dynamics of the X-ray picture. Lung transplantation is not advisable, since pulmonary alveolar proteinosis recurs in the transplanted organ.
Prognosis and prevention
The course of pulmonary alveolar proteinosis is relatively favorable. The disease progresses slowly, spontaneous remissions and recoveries are possible, the 5-year survival rate is 80%. Inadequate therapy, the addition of secondary superinfection significantly worsen the prognosis. The fatal outcome in alveolar proteinosis is associated with the development of severe respiratory failure and decompensation of the pulmonary heart. Prevention consists in the exclusion of smoking, exposure to provoking professional and household factors. During remission, patients with pulmonary alveolar proteinosis are observed by a pulmonologist.
Literature
- Pulmonary Alveolar Proteinosis Syndrome. Kelly A, McCarthy C. Semin Respir Crit Care Med. 2020 Apr;41(2):288-298. link
- Pulmonary Alveolar Proteinosis Syndrome. Suzuki T, Trapnell BC. Clin Chest Med. 2016 Sep;37(3):431-40. link
- Alveolar proteinosis syndrome: pathogenesis, diagnosis, and management. Huizar I, Kavuru MS. Curr Opin Pulm Med. 2009 Sep;15(5):491-8. link
- Pulmonary alveolar proteinosis: time to shift? Papiris SA, Tsirigotis P, Kolilekas L, Papadaki G, Papaioannou AI, Triantafillidou C, Papaporfyriou A, Karakatsani A, Kagouridis K, Griese M, Manali ED. Expert Rev Respir Med. 2015 Jun;9(3):337-49 link
- Pulmonary alveolar proteinosis. Wang T, Lazar CA, Fishbein MC, Lynch JP 3rd. Semin Respir Crit Care Med. 2012 Oct;33(5):498-508.
