idiopathic pulmonary fibrosis in the elderly
Introduction
Introduction to idiopathic pulmonary fibrosis in the elderly Idiopathic pulmonary fibrosis refers to unexplained, limited to interstitial fibrosis. In the past, Hamman-Rich syndrome, cryptogenic fibrosingal velocitis (CFA) and other disease names have been used. IPF and CFA represent the same An inflammatory disease of chronic diffuse lung parenchyma of unknown cause. IPF can occur at any age, but is mainly for people over the age of 50. It is a disease that mainly affects the elderly. The incidence rate of men and women is similar. The reason for its research over the years has not been clearly concluded. The disease is currently considered to be an autoimmune disease. basic knowledge The proportion of sickness: 0.0051% Susceptible people: the elderly Mode of infection: non-infectious Complications: hemoptysis spontaneous pneumothorax emphysema pulmonary hypertension respiratory failure pulmonary encephalopathy
Cause
The cause of idiopathic pulmonary fibrosis in the elderly
(1) Causes of the disease
As mentioned above, there are 180 diseases that cause pulmonary fibrosis, and only 1/3 can identify the cause, and most of them do not know the cause.
(two) pathogenesis
Whether it is idiopathic or occult, the direct pathogenic factors of this disease are still unclear, but because of the family of pulmonary fibrosis, the presence of genetic factors or congenital susceptibility factors is worth studying, and the virus Whether infection or certain drugs are related to the pathogenesis of this disease, it is still necessary to investigate and study clinical epidemiology to be clear. Because some patients have autoantibodies, there are immune complexes on the alveolar capillary wall, which may be autoimmune. disease.
The pathogenesis of IPF can be summarized as the main links of alveolitis, lung parenchymal injury and repair (or fibrosis). Clinical basic research and molecular biology in the past 10 years have further understanding of the chronic inflammatory process of this disease. .
Alveolitis
A series of studies have shown that IgG may act as a conditioning factor and may also act as part of an immune complex on the surface of alveolar macrophages (AM), causing AM to activate, followed by a series of inflammatory damages, activated AM. Can produce a large number of fibronectin (FN), FN is a chemokine of monocytes and neutrophils, these cells from the endovascular extravasation into the lesion, promote alveolitis, in alveolar macrophage-derived growth factor The combination of (AMDGF) and activated platelet-derived growth factor (PDGF) promotes fibroblast (F6) replication, proliferation and secretion of collagen, and FN decreases or disappears in the late stage, so FN increases to the early stage of idiopathic pulmonary fibrosis.
The number of neutrophils (PMN) in alveolar lavage (BAL) fluid in patients with IPF was significantly higher than normal. Crystal et al first proposed neutrophil alveolitis. The study found that PMN has the function of releasing free oxygen and strong protease. And has a damaging effect on lung parenchyma in the pathogenesis of IPF.
The study also found that patients with increased PMN ratio in BAL fluid of IPF were mostly in advanced progression, but the PMN ratio in BAL fluid was not increased in patients with early disease.
Some authors have reported that lymphocytes can be as high as 32% (normally about 10%) in BAL fluid in patients with early IPF, and only 6% in patients with IPF in the late course of the disease, while 23% in PMN, lymphocytosis in BAL It is closely related to the inflammation formed by lymphocytic infiltration in the alveolar septum in lung tissue specimens. On the contrary, it is negatively correlated with pulmonary fibrosis and honeycomb formation. Therefore, some authors believe that lymphocyte aggregation may cause damage to the lungs before pulmonary fibrosis is formed. The role of the organization, studies have shown that T lymphocytes can mediate cytotoxicity and directly destroy the lung parenchyma. Some scholars have suggested another explanation. Lymphocytes may also play an anti-fibrosis effect, as the fibrosis progresses in BAL fluid. The number of lymphocytes is close to normal. Scholars studied 30 cases of IPF. The lymphocytes and PMN in BAL fluid increased. The results showed that 20/30 cases showed stable clinical index improvement, 10/30 cases deteriorated, and 10 cases showed relative restrictive lung. Functional (VC, TLC, and DLCO) changes, eosinophils and lymphocytes in BAL fluid and clinical index statistical analysis showed that lymphocyte elevation or eosinophilia was beneficial The clinical condition is improved and the prognosis is better, because the increase of eosinophils means entering the stage of pulmonary fibrosis.
2. Lung injury Inflammation of diffuse lung parenchyma causes extensive lung injury to play an important role in the pathogenesis of IPF. Toxic oxides may be the most important causative substances currently confirmed. Activated AM cells and granulocytes release more than normal 7~ 13 times, these oxygen free radicals are strong damage substances in lung parenchyma, especially epithelial cells; proteoglycan may be neutrophil-derived collagenase and other lysozymes can also directly destroy lung tissue; cell adhesion factors (adhesion molecules) Or the role of intergrins, in recent years, an important advance in cell biology research reveals that inflammatory cells (lymphocytes and granulocytes) from the blood circulation into the inflammatory disease area, and damage target cells, adhesion factors play an important role .
There are also genetic factors involved in the pathogenesis, and 2 to 4 of the same family members have occasional reports.
In recent years, immunohistochemical studies have been performed on lung tissue in patients with a variety of monoclonal and polyclonal antibodies. It has been found that T cells and their various subpopulations increase in the alveolar septum, interstitial, lymphoid follicle and fibrotic lesions. CD8+ is about 1.5 times that of CD4+, and CD4+ causes lung tissue damage.
3. Repair and fibrosis
At the same time as lung injury, complex repair processes are also underway, including stromal cell proliferation, increased matrix component production, abnormal collagen metabolism, and continuous development of pulmonary fibrosis, ending with honeycomb lung.
Collagen metabolism is abnormal, collagen is the most important component of lung matrix, accounting for 60%-65% of non-cellular part, collagen in IPF stromal tissue accounts for about 70%, total lung collagen content is not obvious, but collagen type I and III The synthesis and degradation of the type protein were not normal. The content of collagen type III increased in the early stage of the disease, and the ratio of type I to type III increased as the disease progressed.
Increased fibroblasts and enhanced function. The lung specimens of IPF patients show a significant increase in the number of fibroblasts, and the function also changes. The abnormal proliferation of fibroblasts in the lung leads to the synthesis of type I collagen and the degradation of type III collagen, which is the key link in the pathogenesis of IPF. .
The incidence of IPF is very complicated, and many important links have not yet been elucidated. A lot of in-depth research work is still needed. However, under the stimulation of certain persistent antigenic substances, intrapulmonary lymphocytes accumulate immunoglobulin production, in some Under the action of cytokines such as -interferon, and immune complexes together activate AM, activated AM chemotactic leukocytes form alveolitis, causing extensive damage to connective tissue and epithelium, endothelial cells, and releasing factor-producing factors in AM. Under the action, fibroblasts are abnormally proliferated and activated, collagen metabolism is abnormal, some components that inhibit fibroblast proliferation cannot be antagonized, F6 (fibroblasts) continue to replicate, fibrosis progresses, accompanied by smooth muscle cell proliferation, pulmonary vascular involvement And, the normal alveolar function unit is blocked to form a large scar tissue and is transformed into a honeycomb lung.
Pathology: The pathological features of IPF evolved from alveolitis to interstitial fibrosis.
4. Gross specimen inspection
Chronic lung volume shrinks, the lungs have lost normal sponge-like structure, the lung volume becomes small and hard as rubber, the lung surface is rough, and cysts of different sizes protrude from the lung surface, and the cut surface is covered with gray-white nodules and dark red consolidation. Can be fused into large pieces, and the honeycomb is widely distributed.
5. Microscopic examination
In the early alveolar space, there are serous proteins and exfoliated epithelial cells, mainly type II alveolar cells and a small number of macrophage mononuclear cells. The alveolar wall is diffusely thickened due to vasodilation, exudation and cell infiltration, and progresses with the disease. The cellular components in the alveolar cavity are gradually reduced, the exudate is mechanized, and a large number of proliferating fibroblasts, collagen fibers and smooth muscle cells appear in the alveolar wall. The number of advanced alveoli is significantly reduced, and the alveolar spaces and bronchioles with irregular or residual fissures are blocked. Expanded to form a honeycomb lung.
However, it must be pointed out that in the whole lung, the lesions are dotted, and lesions at different stages can occur in different parts. In addition, about 10% of patients with IPF may develop lung cancer, which is worth noting.
Prevention
Elderly patients with idiopathic pulmonary fibrosis prevention
The prevention of this disease should focus on the prevention and treatment of secondary pulmonary fibrosis of known etiology, such as rheumatoid arthritis in connective tissue diseases, scleroderma, Sjogren's syndrome, systemic lupus erythematosus, etc. Onset, prevention of complications, ie pulmonary fibrosis, drug-induced pulmonary fibrosis, immediate withdrawal and appropriate treatment due to allergies, prognosis is good, prognosis is poor due to cytotoxicity, but once diagnosed as drug Pulmonary fibrosis should be discontinued immediately and treated with corticosteroids. Due to the inhalation of organic dust or toxic gases, pulmonary fibrosis can be caused. Health education should be carried out for those engaged in relevant occupations, labor protection should be done to minimize harmful gases or organic dust. Inhalation, if there are clinical symptoms, stop contact and apply corticosteroid treatment, the condition and X-ray shadow have improved significantly.
Complication
Elderly patients with idiopathic pulmonary fibrosis complications Complications hemoptysis spontaneous pneumothorax emphysema pulmonary hypertension respiratory failure pulmonary encephalopathy
The complications of this group of diseases are more serious, including pulmonary infection, hemoptysis, spontaneous pneumothorax, emphysema, pulmonary pulmonary hypertension, chronic pulmonary heart disease, respiratory failure and pulmonary encephalopathy.
Symptom
Symptoms of idiopathic pulmonary fibrosis in the elderly Common symptoms Difficulty breathing, sitting breathing, loss of appetite, respiratory failure, dry cough, labor, dyspnea, joint pain, right heart failure, purulent sputum
Although IPF can be found in all ages, it is on average over 50 years old.
Symptom
Progressive aggravation of dyspnea is the most important symptom, accounting for 84% to 100%. The rate of progression of dyspnea often varies from person to person, and generally enters respiratory insufficiency, affecting activities for more than 1 to 3 years.
Another common symptom is irritating dry cough, often more serious, accompanied by pulmonary infection, fever, cough, sputum, etc., often accompanied by fatigue, fear of eating, weight loss, etc., sometimes joint pain.
2. Signs
The symmetry of the thoracic cavity is reduced on both sides, the chest is flat, and the diaphragm is lifted. Most patients can hear continuous, high-pitched pop sounds (Velcro voice), clubbing, early toe, and hypoxia and cyanosis in the late stage. The improvement of oxygen deficiency by oxygen therapy is not obvious. The patient has the characteristics of comfort and difficulty in breathing when sitting on the side or supine position, which is obviously different from the hypoxia caused by chronic obstructive pulmonary disease.
Because the symptoms and signs of IPF are not characteristic, in the diagnosis of this disease, the differential diagnosis of other pulmonary interstitial is important, but it is more difficult, detailed inquiry of medical history is very important, such as occupational history, whether or not engaged in related occupations, such as History of exposure to asbestos, life history, such as history of allergic poultry, leading to a history of exogenous allergic alveolitis, such as the clinical features of the disease such as prominent dyspnea, clubbing, Velcro, etc., and imaging, Pulmonary function test abnormalities can be initially diagnosed, and TBLB and BAL examinations are performed under the condition of the disease, and most patients can be diagnosed.
Some scholars believe that the maximum likelihood diagnosis can be made according to the following four items:
1 progressively aggravate the clinical symptoms of dyspnea;
2X chest radiographs have typical IPF lung diffuse shadows, plus high-resolution CT confirmed more valuable;
3 with restrictive ventilatory dysfunction, especially the decline of diffuse function is valuable, its value often drops by 30% to 50%;
4 No other cause of illness was found.
Examine
Examination of idiopathic pulmonary fibrosis in the elderly
Hematological examination: increased erythrocyte sedimentation rate, increased immunoglobulin, no differential significance, but the examination of various immune indicators of collagen vascular disease is conducive to its diagnosis and differential diagnosis.
1. Chest X-ray film changes
Early IPF patients can show the blurring of the double lung fields, such as the increased density of ground glass-like lesions, suggesting the pathological basis of alveolar invasive lesions, showing the X-ray features of alveolitis. As the disease progresses, linear cord-like texture appears in the lung field. Such as the fine mesh, called the mesh shadow, in the late stage, there are thick lines and coarse netting. When the alveolar atresia, the bronchial compensatory expansion into a saclike shape, surrounded by a large number of fibrous connective tissue, the honeycomb lung appears on the chest.
Most of them have no mediastinum, lymph nodes in the hilar area, and the pleura is not invaded, but pneumothorax often occurs due to rupture of the lung.
2. Chest CT
Because CT has no organizational overlap and high resolution, CT has also been applied to the diagnosis of IPF in recent years, especially high-resolution CT (HRCT), which is superior to chest X-ray and conventional CT. HRCT can be found on chest X-ray. There is no abnormal manifestation of interstitial fibrosis in the lungs, and it is helpful to analyze the morphology, distribution and severity of the lesions. HRCT should be used for selective scanning, generally for 3 levels, ie aortic arch level, tracheal bifurcation and 1 cm above the iliac crest. The level can represent the lesions in the three lung fields to reduce the radiation dose. The HRCT examination shows irregular linear changes, accompanied by cystic small air cavities, which reflect inflammation when patchy alveolar exudative blurred shadows appear. The activity of the lesion, pleural thickening between the lobes is also a common sign of IPF. Because CT can clearly show the mediastinum and pleura, it can provide a basis for differential diagnosis with some interstitial diseases that are easy to invade. CT can be seen small. In the middle nodules and net nodules, sometimes large-scale high-density lesions can be seen, which can be seen by distorting or expanding the bronchial images containing gas, and late appearance of honeycomb lungs, which can be seen in the vicinity of large fibrosis. Emphysema, increase the air content showed local pulmonary vascular Movies sparse, irregular pleural thickening, particularly in the lungs showed diffuse distribution significantly.
3. Pulmonary function test
General routine ventilation function measurement can be found in relation to restrictive ventilation dysfunction, and some airway obstruction is helpful in identifying the airway obstructive disease. IPF pulmonary function testing is characterized by restrictive ventilation disorder.
Diagnosis
Diagnosis and differential diagnosis of idiopathic pulmonary fibrosis in the elderly
diagnosis
There are more than 130 kinds of interstitial lung diseases, most of which are diffuse damage of the lungs. Some diseases are combined with clinical, laboratory examination, and the chest X-ray features are easy to diagnose, such as pulmonary sarcoidosis, acute exogenous allergic alveolitis, Silicaosis, etc., one-third of the diseases can not be diagnosed by multiple examinations, especially in the late stage of various interstitial diseases, clinical symptoms and X-ray findings similar to pulmonary interstitial fibrosis, requiring lung biopsy.
Differential diagnosis
1. Connective tissue disease causes secondary pulmonary fibrosis
Such as scleroderma, rheumatoid arthritis, systemic lupus erythematosus, mixed connective tissue disease, Sjogren's syndrome, etc., clinical symptoms of secondary pulmonary interstitial fibrosis, X-ray and lung function and IPF complete Similarly, the difference is that the cause is different. After the connective tissue disease itself is controlled, fibrosis stops developing and is in a stable state. All kinds of connective tissue diseases have damages of various organs outside the lungs and present different positive biochemicals. Antibody response.
2. Occlusive bronchiolitis with organizing pneumonia (Boop)
The typical symptoms of Boop are subacute dyspnea, cough, fever, etc. The incidence is slow, and most of the lungs hear tearing sounds. Few fingers are rare. There are two types of blood chest radiographs: one is a diffuse reticular shadow on the base of the two lungs or a small nodular interstitial shadow, and there is no honeycomb lung, the lung volume is normal; the other is multiple lung patchy The shadow is infiltrated and can also be distributed in large leaves. The frosted glassy shadow has the characteristics of migration in some patients. The diagnosis requires lung biopsy. The pathological features are alveolar, granular granulation tissue in alveolar duct, and alveolar wall Chronic inflammatory infiltration, mainly monocytes, can have low to moderate fiber, but still retain alveolar structure, the clinical symptoms of the disease can range from mild self-limiting to severe dyspnea and even respiratory failure, X-ray shadow from mild Short-term shadow to lung interstitial changes, antibiotic treatment is ineffective, corticosteroids are ideal.
3. Alveolar proteinosis
A fever-free alveolar proteinosis, clinically coughing and progressively worsening dyspnea, and finally death from respiratory failure, characterized by coughing a large amount of foamy sputum, up to hundreds of milliliters per day, and sputum and lung biopsy can be identified.
4. Pulmonary sarcoidosis
In stage III of sarcoidosis, some patients may have pulmonary fibrosis, but the clinical symptoms are mild, no progressive severe dyspnea, no clubbing, good clinical prognosis, fiberoptic biopsy, X-ray features can help diagnose And differential diagnosis.
5. Drug-induced pulmonary fibrosis
Such as blood pressure lowering drugs, anti-cancer drugs, anti-arrhythmia drugs can lead to pulmonary fibrosis, its clinical symptoms are mild, pulmonary fibrosis stops developing after stopping the drug, but bleomycin-induced pulmonary fibrosis, the condition can continue to deteriorate, Prednisone is effective and can be relapsed.
