Pediatric pulmonary alveolar proteinosis

　　One: Etiology

　　The etiology is unclear; some believe that the disease is a non-specific allergic reaction to inhaled chemical irritants; others believe it is related to immune deficiency in the body; the disease is often accompanied by various fungal and bacterial infections; the disease is occasionally familial, suggesting a genetic factor; some believe that the disease is similar to desquamative interstitial pneumonia, which may be different manifestations of the same disease, but desquamative interstitial pneumonia is effective in treating with corticosteroids, while this disease is not. A small part of congenital PAP is related to a deficiency of surfactant protein B. There are reports that in 4 cases of PAP infants, there is a defect in the expression of the beta subunit of the granulocyte-macrophage colony stimulating factor (GM-CSF) receptor. In older children, the bronchoalveolar lavage fluid contains SP-A, B, and C, but these proteins have significant structural changes, thereby altering the function and metabolism of surfactant substances.

　　Second, pathogenesis.

　　Possible pathogenic mechanisms include:

　　1. Excessive generation of normal or abnormal substances in the alveoli (including phospholipids and lamellar bodies).

　　2. Abnormal clearance function of alveoli for phospholipoproteins.

　　3. Imbalance in the generation and clearance of alveolar phospholipids.

　　4. Impaired ability of alveolar macrophages to degrade lamellar bodies.

　　5. Overgrowth and destruction of alveolar type II cells. The patient's bronchoalveolar lavage fluid shows an increase in immunoglobulins, and alveolar sedimentation is a reaction to infection or environmental toxic substances. Animal experiments suggest that alveolar protein deposition is related to excessive secretion of surfactant substances by type II alveolar epithelial cells and reduced clearance ability of alveolar macrophages for this lipoprotein-like substance. Some children may have thymus and lymphoid hypoplasia or immunoglobulin deficiency, often accompanied by various fungal and bacterial infections; associated with genetic factors; some congenital PAP is related to the lack of surfactant protein B (surfactant protein B).

　　It is mainly respiratory failure and infection. Respiratory failure is a severe impairment of pulmonary ventilation and (or) gas exchange due to various causes, resulting in ineffective gas exchange, leading to hypoxemia accompanied (or not accompanied) by carbon dioxide retention, thereby causing a series of physiological and metabolic disorders. Under sea-level atmospheric pressure, breathing indoor air at rest, and excluding conditions such as intracardiac anatomical shunts and primary decrease in cardiac output, the partial pressure of oxygen in arterial blood (PaO2) is below 8 kPa (60 mmHg), or accompanied by a partial pressure of carbon dioxide (PaCO2) higher than 6.65 kPa (50 mmHg), it is considered respiratory failure (shortened as ARF). It is a state of dysfunction rather than a disease, which can be caused by pulmonary diseases or complications of various diseases.

　　The onset can be acute or chronic, with intolerance to exercise being the most common initial symptom. If not diagnosed, it may present with progressive dyspnea and cough, accompanied by fever, weakness, weight loss, chest pain, hemoptysis, and decreased appetite. Respiratory symptoms in infants and young children are often hidden, often presenting with growth and development delay, with vomiting and diarrhea as the initial symptoms. Secondary infection may cause sputum to become yellow and purulent. As the condition progresses, cyanosis and severe dyspnea may occur, with very few signs, only a few scattered moist rales or pleural friction sounds, and sometimes clubbing of the fingers and toes.

　　Pay attention to the prevention of recurrent infections. Due to unknown reasons, especially congenital PAP, there is no effective preventive method. The clinical course of PAP is highly variable, it can be naturally relieved, or it may die of pneumonia or respiratory failure. PAP patients can be divided into three types: stable type, progressive type, and natural remission type, among which the natural remission cases are less than 10%. The survival rates of PAP patients at 2 years, 5 years, and 10 years are 79%, 75%, and 68%, respectively. PAP patients are prone to complications such as infections, especially opportunistic pathogen infections (such as nocardia) infections, indicating the host's immune dysfunction.

　　1. Examination

　　1. Sputum examination

　　Firstly, fix the sputum specimen, use hematoxylin and eosin, PAS staining, and visible PAS positive protein granules containing needle-like crystalline layered bodies. However, due to the fact that children's sputum is often swallowed into the digestive tract and cannot be collected, and the sputum is contaminated by oral secretions, mixed with desquamated cells and other proteins, its diagnostic value is not great. Some people also use the thick sputum block discharged after lung lavage, add 0.1 equivalent sodium hydroxide drop by drop, shake, and see its upper layer turn pink. Based on this substance, perform spectral analysis, which is the same as the spectrum of phenol sulfonphthalein. Phenol sulfonphthalein has a great affinity for proteins in an acidic environment.

　　2. Blood tests

　　Under the condition of no liver disease, serum lactate dehydrogenase (LDH) is often elevated, and LDH returns to normal when recovering health. Blood routine examination shows that about half of the cases have lymphopenia, and serum IgA is reduced.

　　Second, auxiliary examination

　　1. X-ray manifestations:

　　The typical X-ray chest film shows fine, diffuse feather-like infiltrative shadows around the hilum, spreading from the hilum to the lung periphery,呈 butterfly-like, slightly resembling pulmonary edema; or it may appear as soft, low-density nodular shadows,呈 butterfly distribution, sometimes showing infiltrative lesions in the lower lobes of both lungs, or some patients initially present with nodular density deepening shadows, which begin to separate from each other, from the lower lobes infiltrating to the entire lobe consolidation, between the lesions there is compensatory emphysema or the formation of small translucent areas, the mediastinum is significantly widened, the X-ray is like pulmonary edema, but without K-B lines.

　　2. Chest CT examination:

　　Especially high-resolution CT has great diagnostic value for PAP, the affected lung tissue often shows a ground-glass change, interlobar and intralobular pleura thickening and irregularity.

　　3. Pulmonary function testing:

　　It shows restrictive ventilatory dysfunction, decreased vital capacity, diffusion dysfunction, and arterial blood gas shows reduced oxygen saturation and chronic alkalosis.

　　4. Bronchoalveolar lavage fluid (BALF) examination:

　　The typical bronchoalveolar lavage fluid is milky or thick, pale yellow liquid, under light microscopy, there are a large number of irregularly shaped, unevenly sized eosinophilic granular lipoprotein-like substances between inflammatory cells, PAS staining is positive. Under electron microscopy, the filling material in the alveoli is composed of a large number of cells of different sizes, surface active substance particles, and other protein-like substances. Under a 30,000 times microscope, these surface active substance particles can be seen as a characteristic concentric circular layered structure.

　　Nourishing the lungs, the basic principle in diet is to prevent dryness and protect yin, and to nourish yin and moisten the lungs.

　　1. Eat more sesame seeds, walnuts, fresh lotus root, pears, honey, silver ear, mung beans, etc., to achieve the purpose of nourishing yin, moistening the lungs, and nourishing the blood;

　　2. Eat fresh fruits and vegetables regularly, such as pears, grapes, jujubes, pomegranates, sugarcane, persimmons, radishes, etc., which can supplement a wealth of vitamins. Eat less scallions, ginger, cassia bark, star anise, chili, etc.

　　3. Reduce the intake of spicy foods, reduce the intake of hot foods such as fatty meat, animal oil, smoked food, fried food, etc.

　　I. Treatment

　　There is no effective treatment, and adrenal cortical hormones are ineffective. Protamine sulfate nebulizer inhalation or intermittent positive pressure breathing machine inhalation have been tried. In recent years, bronchoalveolar lavage has been performed, which is the only treatment method proven effective to date. Using saline containing 10g of acetylcysteine and 7500U of heparin per liter for lung lavage to clear the alveolar substances has been effective. Simple saline lavage can achieve the same effect. Bronchoalveolar lavage, through BAIL, removes the surface active substances deposited in the alveoli, thereby improving pulmonary ventilation and gas exchange function. In many cases, it can only temporarily alleviate symptoms and needs to be performed regularly and repeatedly. Other treatment methods being studied include GM-CSF replacement therapy, lung transplantation, and bone marrow transplantation.

　　II. Prognosis

　　The prognosis is generally poor. If diagnosed in time and conditions allow for bronchoalveolar lavage, the condition of some children may improve. This disease progresses slowly in adults, with about 30% to 40% able to recover to health. However, when children are affected by this disease, the course of the disease can range from a few days to several months in younger children, and several years in older children, usually dying within one year due to respiratory failure with a mortality rate as high as 75%. The prognosis in adults is slightly better, with death due to respiratory failure, with an average survival age of 7 months.