alveolar proteinosis
Introduction
Introduction to alveolar proteinosis Pulmonary alveolar proteinosis (PAP) is a rare disease of unknown cause. It is characterized by the deposition of insoluble phospholipid-rich protein in the alveoli. The clinical symptoms are mainly shortness of breath, cough and cough, and the chest X-ray shows diffuse lung infiltration shadows of both lungs. Pathological examination characterized by a protein-like substance in the alveoli filled with periodic acid-stained Schiff (PAS) staining, first reported by Rosen in 1958. Alveolar proteinosis can be classified as primary, secondary, and congenital depending on the cause. basic knowledge The proportion of sickness: 0.00001% Susceptible people: no special people Mode of infection: non-infectious Complications: respiratory failure
Cause
Causes of alveolar proteinosis
Decreased immune function (20%):
The so-called low immune function is a pathological feature. Generally speaking, human immunity is the ability of our body to resist invasion in the face of external invasion. For example, when ubiquitous bacteria and stubborn viruses attack you, the resistance of your body directly determines whether you will get sick.
Alcohol abuse (10%):
Drinking exceeds the standard for moderate drinking or general social drinking. Heavy drinking is often determined by exceeding a certain amount of daily drinking (eg 3 standard cups per day) or per drinking (eg 5 standard cups at a time, at least once a week).
Genetic (10%):
Genetics generally refers to the phenomenon that the traits of the parent are expressed in the next generation, but genetically refers to the phenomenon that the genetic material is passed from the upper generation to the offspring.
Microbial infection (20%):
Microbial infection refers to infection with bacteria, mold, trichomoniasis, mycoplasma, and the like.
A large amount of dust inhalation (20%):
A large amount of dust inhalation refers to the inhalation of dust such as aluminum or silica.
(1) Causes of the disease
Although the triggering factor is still unclear, it basically agrees that the pathogenesis is caused by lipid metabolism disorder, that is, the metabolism of alveolar surfactant is abnormal due to the action of external factors in the body. So far, more alveolar macrophages have been studied. Cell viability, animal experiments show that the activity of macrophages after phagocytosis of dust is significantly reduced, and the macrophage particles in the patient's lavage fluid can reduce the normal cell viability, and the alveolar macrophage viability after bronchoalveolar lavage treatment. It can be raised, and the study found no increase in type II cell-producing protein and no abnormality in systemic lipid metabolism. Therefore, it is generally believed that this disease is associated with decreased clearance ability.
(two) pathogenesis
1. The pathogenesis of alveolar proteinosis is not fully understood, and there are several hypotheses :
(1) Surfactant clearance disorder: It was found by electron microscopy that alveolar protein deposits and whole lung lavage were structurally similar to lamellar surfactants secreted by type II alveolar epithelial cells, suggesting alveolar protein deposition. May be associated with alveolar surfactant metabolism disorders, most of the evidence currently suggests that alveolar protein deposits may be due to alveolar surfactant clearance disorders, rather than excessive production, normal alveolar surfactant (SP) production With clearing is a complex dynamic process, alveolar type II epithelial cells not only synthesize and secrete alveolar surfactants, but also participate in the clearance of alveolar surfactants along with alveolar macrophages, when certain factors such as infection, drugs, etc. The function of alveolar type II cells is altered, resulting in a decrease in the clearance of alveolar surfactants, which leads to the deposition of surfactants in the alveoli. Recent studies have also found that surfactant protein A (SP-A) can not only Regulation of surfactant secretion and regulation of alveolar type II epithelial cells Alveolar macrophages on pulmonary surfactant reuptake, their role in the pathogenesis of PAP unclear.
(2) Alveolar macrophage function defects: Many scholars have found that alveolar macrophages in patients with alveolar proteinosis have low chemotactic activity, phagocytic function and decreased phagolysosome activity, and Gonzalez et al. report normal human alveoli. When macrophages are co-cultured with alveolar lavage fluid in patients with alveolar proteinosis, normal human alveolar macrophages lose their phagocytic capacity, suggesting that alveolar macrophages are present in the alveolar lavage fluid of patients with alveolar proteinosis. Factors, recent studies suggest that alveolar macrophage dysfunction may be associated with granulocyte macrophage colony-stimulating factor (GM-CSF) deficiency or with GM-CSF/IL-3/IL-5 receptor beta chain defects.
(3) secondary to other diseases: clinically some diseases, especially hematological malignancies, can occur alveolar proteinosis, such as myeloid leukemia, lymphoma, Fanconi anemia and IgG-type immunoglobulin disease, although the literature reports the malignancy of the blood system The average incidence of secondary pulmonary alveolar proteinosis in tumors is about 5.3%, but the incidence of secondary myeloid leukemia patients can be as high as 10%, unlike primary alveolar proteinosis, secondary alveolar protein deposition The disease is often focal, and the symptoms are mild, usually without bronchoalveolar lavage.
(4) Abnormal injury of inhaled substances: Alveolar proteinosis may be related to certain physical and chemical factors and mineral dust inhalation, such as busulfan, chlorambucil, whisk and aluminum dust, etc. Animals inhaled dust particles It can also cause alveolar proteinosis. These suggest that alveolar proteinosis may be associated with certain physical and chemical factors and mineral dust inhalation, but in humans, there is no direct evidence in epidemiological studies that alveolar proteinosis is associated with these substances.
(5) Gene mutation: Alveolar surfactant-associated protein B (SP-B) gene mutation has been confirmed to be associated with congenital alveolar proteinosis (CPAP), and it has been confirmed that there are at least two mutation sites in the SP-B gene. One is that the 121st base C is replaced by the 3 base GAA, and the other is the 1st base T deleted at the 122nd position. Both gene mutations can cause SP-B deletion in the alveolar surfactant. However, the clinical manifestations of congenital alveolar proteinosis vary widely, suggesting that there may be other sites or new SP gene mutations involved.
(6) Abnormalities of GM-CSF and its receptors: In 1994, Dranoff et al found that there was protein-like deposition in the alveoli of mice that had removed granulocyte-macrophage colony-stimulating factor (GM-CSF), which was followed by many scholars. Studies have shown that patients with alveolar proteinosis have a disorder of cytokine regulation, ie, elevated IL-10 expression and decreased expression of GM-CSF and loss of GM-CSF/IL-3/IL-5 receptor beta chain. Happening.
In conclusion, the pathogenesis of alveolar proteinosis is not fully understood, and none of the above mentioned causes can fully explain all cases and further research is needed in the future.
2. Pathological manifestations
(1) Visual observation: most of the lungs are solid, diffuse yellow or gray-yellow nodules or small plaques can be seen under the pleura. The diameter of the nodules varies from a few millimeters to 2 cm. The cut surface shows a thick yellow liquid flowing out. Combined infection, the pleural surface is smooth.
(2) Light microscopy: the alveolar and bronchial lumens are filled with a non-morphological, periodic acid-rich substance that is positive for periodic acid staining (PAS). The alveolar septum is normal or the number of alveolar septa is increased, but there is no obvious fibrosis in the interval. There is no inflammation in the alveolar cavity except for the occasional discovery of macrophages.
(3) Electron microscopy: There are a large number of layered structures in the debris in the alveolar cavity, composed of coiled three layers of phospholipids, which are similar in structure to alveolar surfactants.
Prevention
Alveolar proteinosis prevention
1, to avoid infection with mycobacterial disease, Karst lung cyst pneumonia, cytomegalovirus and so on. 2, pay attention to exercise, improve immunity.
Complication
Pulmonary alveolar proteinosis complications Complications, respiratory failure
Often complicated by bacterial infections such as Nocardia, fungal genus, histoplasma, mycobacteria and cytomegalovirus, but also complicated by pulmonary infection and respiratory failure.
Symptom
Alveolar proteinosis symptoms Common symptoms Alveolitis inflammation Chest pain fatigue alveolar lavage fluid visible... Fever with cough, slightly... Difficulty breathing cyanosis dry cough
More men than women, male to female ratio of about 2.5:1, the disease can occur at any age, from infants to 70-year-olds, but middle-aged people aged 30 to 50 are common, accounting for about 80% of the total number of cases.
The clinical manifestations of this disease vary widely, and some may have no clinical symptoms. Only in the physical examination, this type accounts for about 1/3; about 1/5 of the patients have the symptoms of secondary lung infection as the first performance There are cough, fever, chest discomfort, etc.; about 1/2 of the patients have insidious onset, manifested as cough, difficulty breathing, fatigue, a few cases may have hypothermia and hemoptysis, respiratory symptoms and lung lesions have a certain range of involvement Relationship, physical examination generally no special positive findings, sometimes a small amount of sputum pronunciation can be heard at the bottom of the lungs. Although respiratory symptoms are related to the extent of lung lesions, clinical signs and chest X-ray imbalance are one of the characteristics of this disease. Patients may have cyanosis, clubbing and retinal spotted hemorrhage, and in very few cases may be associated with pulmonary heart disease.
Pulmonary alveolar proteinosis patients with a greater chance of opportunistic infection, about 15%, in addition to common pathogenic bacteria, some special pathogens such as Nocardia, fungal genus, histoplasma, mycobacteria and giant Cell virus, etc.
Examine
Examination of alveolar proteinosis
1. Blood routine: Most patients have normal hemoglobin, only a few mildly elevated, white blood cells are generally normal, and erythrocyte sedimentation rate is normal.
2. Blood biochemical examination: serum lactate dehydrogenase (LDH) is significantly elevated in most patients, and its specific isozyme has no obvious abnormality. It is generally considered that elevated serum LDH is related to the degree of disease and activity, and its elevation is high. The mechanism may be related to the increase of alveolar macrophages and alveolar type II epithelial cell death. A few patients may also have elevated serum globulin, but no specificity. In recent years, some scholars have found alveolar surfactant activity in serum of patients with alveolar proteinosis. Substance-associated protein A (SP-A) and alveolar surfactant-associated protein D (SP-D) were significantly higher than normal, but SP-A was in idiopathic pulmonary interstitial fibrosis (IPF), pneumonia, tuberculosis and Patients with panbronchiolitis also have varying degrees of elevation, and SP-D is only elevated in patients with pulmonary interstitial fibrosis complicated by IPF, PAP, and connective tissue, so serum SP is performed in patients who cannot undergo bronchoscopy. -A and SP-D examinations may have certain diagnostic and differential diagnostic implications.
3. Sputum examination: Although as early as the 1960s, some scholars found that PAS staining was positive in patients with PAP, but other sputum diseases such as chronic bronchitis, bronchiectasis, pneumonia and lung cancer patients may also appear. Positive, plus PAP patients have very few coughs, so the use of sputum in PAP patients is greatly limited. In recent years, some scholars have reported that SP-A concentrations in PAP patients are about 400 times higher than the control group. The control group included chronic bronchitis, bronchial asthma, emphysema, IPF, pneumonia and lung cancer patients, suggesting that SP-A examination has a certain significance in the differential diagnosis of the lung, but further research is needed.
4. Arterial blood gas analysis: The arterial oxygen partial pressure and oxygen saturation are reduced, and arterial carbon dioxide is also reduced by compensatory hyperventilation. Martin et al reported that the intrapulmonary shunt measured by PAP patients when inhaled pure oxygen can be as high as 20%. 8.9% higher than other diffuse pulmonary interstitial fibrosis patients.
5. X-ray performance: conventional chest X-ray film shows diffuse fine feathery or nodular infiltrates in both lungs, blurred borders, and visible bronchial aeration. These lesions tend to have higher density in the hilar region. Peripheral density is low, similar to cardiogenic pulmonary edema, lesions generally do not occur calcification, and no pleural lesions or hilar and mediastinal lymphadenopathy.
6. Chest CT examination: especially high-resolution CT (HRCT) can be frosted glass and / or reticular and patchy shadows, can be symmetrical or asymmetrical, sometimes visible bronchial aeration, lesions and surrounding lung tissue often There are obvious boundaries and irregular boundaries, resulting in a more characteristic "map-like" change, and the interlobular septa and interlobular septa of the lesion are often thickened.
7. Pulmonary function test: mild restrictive ventilatory dysfunction, showing a decrease in vital capacity and functional residual capacity, but the most significant decrease in lung diffusing function may be due to the filling of protein-like substances in the alveolar space.
8. Fiberoptic bronchoscopy lung biopsy and open lung biopsy: pathological examination revealed a large number of amorphous and granular eosinophilic deposition in the alveolar cavity, PAS staining positive, Austar blue staining and mucin card red staining negative, Mild reactive thickening and reactive hyperplasia of alveolar type II epithelial cells were observed in the alveolar septum, but the pathologically negative did not completely rule out the disease due to the small tissue of the lung biopsy.
9. Bronchoalveolar lavage fluid examination: The typical bronchoalveolar lavage fluid is milky or mud-like. The solubility of alveolar protein deposits is very low. Generally, it can be precipitated for about 20 minutes, and the cell sorting of bronchoalveolar lavage fluid It is not helpful for the diagnosis of PAP. BALF can be mainly macrophages or lymphocytes. The CD4/CD8 ratio can be increased or decreased. The biochemical examination of BALF such as SP-A and SP-D can be significantly increased. After the BAL solution was added to formalin for centrifugation, it was embedded in paraffin and examined by pathological examination. Unique histological changes were observed: in the background of diffuse eosinophils, large, cell-free eosinophilic cells were observed. Body; PAS staining positive, while Alcian blue staining and mucin card red staining negative.
Diagnosis
Diagnosis and diagnosis of alveolar proteinosis
Diagnosis requires synergistic clinical manifestations, radiological signs and histopathology and / or alveolar lavage fluid cytology can be diagnosed, the diagnosis is based on: 1 clinical manifestations of activity after shortness of breath, occasional cough, progressive progressive symptoms, no infection And the basis of blood diseases; 2 chest X-ray can be expressed as diffuse nodules, patchy shadow or large solid shadow, HRCT can be seen "map-like" or "paving stone" characteristic changes; 3 fiber bronchi Pathological examination of the biopsy showed that the alveolar cavity was filled with PAS-positive coarse granular material, and a large number of amorphous fragments were observed in the alveolar lavage fluid, often accompanied by PAS-positive macrophages.
Differential diagnosis: 1 idiopathic pulmonary interstitial fibrosis; 2 alveolar carcinoma; 3 miliary tuberculosis; 4 lung diseases such as viral pneumonia, mycoplasma pneumonia and chlamydia pneumonia.
Chest X-ray findings of PAP should be differentiated from pulmonary edema, pneumonia, pulmonary mycosis, sarcoidosis, pulmonary connective tissue disease, silicosis, Pneumocystis carinii pneumonia and IPF.
