| disease | Pulmonary Alveolar Proteinosis |
| alias | Pulmonary Alveolar Proteinosis |
Pulmonary alveolar proteinosis refers to the diffuse deposition of protein in the alveoli of unknown cause, first reported by Rose in 1958. To date, approximately 400–500 cases have been reported in the literature, with the first domestic case reported in 1965. Clinically, it is characterized by progressive dyspnea, and bronchoalveolar lavage serves as the primary diagnostic and therapeutic method. The prognosis varies widely, ranging from spontaneous recovery to death within one or two years after diagnosis.
bubble_chart Epidemiology
The male-to-female ratio is 2–3:1, and it can occur at any age, with the majority of cases occurring between 20 and 50 years old. The onset is insidious, with the main symptom being progressive dyspnea. About one-third of cases present with low-grade fever, and most have a cough, with sputum appearing as milky-white foam; sometimes, clumps, gelatinous masses, or casts are coughed up. Physical examination may reveal weakened respiratory movements, grade I dullness on percussion, prominent pathological bronchial breath sounds in the lungs, and occasionally moist rales. Severe cases may exhibit clubbing of fingers, cyanosis, and manifestations of pulmonary stirred pulse hypertension.
Radiographic findings show diffuse alveolar infiltrates around the hilar regions, appearing butterfly-shaped, with bilateral symmetry not always exact, closely resembling pulmonary edema.
The disease cause is unknown and is speculated to be related to several factors, such as the inhalation of large amounts of dust (aluminum, silica, etc.), decreased immune function (especially in infants and young children), genetic factors, alcoholism, microbial infections, etc. Regarding infections, it is sometimes difficult to determine whether they are the primary disease cause or secondary to pulmonary alveolar proteinosis. For example, infections such as cytomegalovirus, Pneumocystis carinii, and Histoplasma have been found to be associated with high protein deposition in the alveoli.
Although the initiating factors remain unclear, it is generally agreed that the disease process results from lipid metabolism disorders. That is, abnormal metabolism of alveolar surfactant is caused by internal and external factors in the body. So far, research has focused more on the activity of alveolar macrophages. Animal experiments have shown that macrophage activity significantly decreases after ingesting dust, and the granules within macrophages in patients' lavage fluid can reduce the activity of normal cells. After bronchoalveolar lavage treatment, the activity of alveolar macrophages can increase. However, studies have not found an increase in protein production by type II cells, nor any abnormalities in systemic lipid metabolism. Therefore, it is currently generally believed that this disease is related to a decline in clearance capacity.bubble_chart Pathological Changes
Gross examination reveals that the lungs may become significantly hardened with increased weight. Lung excess changes coexist with compensatory lung qi swelling. Under light microscopy, the alveolar structure is essentially normal, with alveoli filled with fine granular, structureless PAS-positive proteinaceous material. Type II pneumocytes show hyperplasia and hypertrophy, with increased lamellar bodies in the cytoplasm arranged concentrically. The number and size of macrophages are also markedly increased. Pulmonary interstitial fibrosis may be present, and some authors have reported the detection of proteinaceous material in the supraclavicular lymph nodes.
bubble_chart Clinical Manifestations
The male-to-female ratio is 2-3:1, and it can occur at any age, with the majority of cases occurring between 20 and 50 years old. The onset is insidious, with the main symptom being progressive dyspnea. Approximately one-third of cases present with low-grade fever, and most have a cough with milky white frothy sputum, sometimes expectorating lumps, gelatinous masses, or casts. Physical examination may reveal weakened respiratory movements, grade I dullness on percussion, obvious pathological bronchial breath sounds in the lungs, and occasionally moist rales. Severe cases may present with clubbing of fingers, cyanosis, and manifestations of pulmonary hypertension.
Radiographic findings show diffuse alveolar infiltrates around the hilar regions, appearing butterfly-shaped, with bilateral symmetry not always perfect, closely resembling pulmonary edema.The diagnosis should be suspected when chest X-ray shows centripetal alveolar infiltrates without signs of heart failure. Bronchoalveolar lavage revealing turbid, milky, or yellow fluid with abundant acellular eosinophilic bodies in the sediment confirms the diagnosis. Combining bronchoscopic lung biopsy further solidifies the diagnosis. Currently, open lung biopsy is rarely necessary. Some reports suggest that measuring surfactant protein A in sputum serves as a simple auxiliary diagnostic method.
bubble_chart Treatment Measures
No effective drugs have been discovered yet. Currently, the widely adopted and effective method is bronchoalveolar lavage, preferably performed under general anesthesia for whole lung lavage if conditions permit. Alternatively, lobar or segmental lavage can be conducted via fiberoptic bronchoscopy, with similar efficacy. However, patients often find the bronchoscopic method less tolerable, and large-volume lavage is not feasible.
Pediatric patients have a poor prognosis, often dying within a few years. In adults, there are cases of self-healing in the philtrum, but some patients experience relapse after recovery. Approximately half of the patients show gradual progression or die within 5 to 10 years due to complications such as infection or respiratory failure.
