Who can talk about the pathophysiology of bronchial asthma?

Bronchial asthma is the most common chronic respiratory disease in childhood. Asthma is a chronic airway inflammation, which involves many kinds of cells, especially mast cells, eosinophils and T lymphocytes, causing airway hyperresponsiveness and leading to reversible airway obstructive diseases. The clinical manifestations are repeated wheezing, dyspnea, chest tightness or cough. In recent years, the incidence of asthma is on the rise. There are 654.38 billion asthma patients in the world, and the incidence rate in some developed countries is as high as 20% ~ 30%. In the United States, about 10% ~ 15% of boys and 7% ~ 10% of girls have had asthma attacks. The total prevalence of asthma in children in China is 0.9%- 1. 1%, and it is 2% ~ 5% in the south. It is estimated that the actual incidence rate is much higher than this, and there is an obvious upward trend in recent years. 70%-80% of children's asthma occurs before the age of 5, and 50% of children's asthma occurs before the age of 3, and the youngest is 3 months. The prevalence rate of boys in childhood is twice that of girls, but there is no gender difference in adolescence. 【 Pathogenesis 】 The pathogenesis of asthma is extremely complicated, which is not completely clear, and is closely related to immune, nervous, mental and endocrine factors and genetic background. (1) Allergy is the most definite risk factor for asthma. Asthma patients are accompanied by chronic airway inflammation with hyperIGE, mast cells, eosinophils and T lymphocytes infiltration, suggesting that immune response is of great significance in the pathogenesis of asthma. Recent studies show that the immunological pathogenesis of atopy and asthma is: the maturation of type I dendritic cells (DCl) is damaged, and the secretion of 1L- 12 is insufficient, which prevents TH0 from differentiating into TH 1 cell; CDII promotes THO cells to develop into TH2 under the induction of IL-4, which leads to the functional imbalance of TH1(decreased IFN-γ secretion)/TH2 (increased IL-4 secretion). TH2 cells promote D cells to produce a large amount of IgE (including antigen-specific IgE) and secrete inflammatory cytokines (including adhesion molecules), and stimulate other cells (such as epithelial cells, endothelial cells, basophils, mast cells and eosinophils) to produce a series of inflammatory mediators (such as leukotrienes, endothelin, prostaglandin and thromboxane A2), and finally induce rapid allergic reaction (1gE increase) and chronic airway inflammation. There are many factors that affect the differentiation and maturation of DC, including the nature, dosage, contact routes and times of antigen or allergen, DC itself and its microenvironment (various cytokines). Neonatal period is the key period that affects the development of DC. Hyperfunction of neonatal physiological cells D 1. At this time, exposure to allergens will strengthen the TH2 cell advantage induced by DCII, which is conducive to the formation of atopy and increase the probability of asthma. On the contrary, newborn microorganisms and their proteins (such as BCG) induce DCI to secrete IL- 12, which can resist the function of TH2 cells and reduce the formation of atopy and the occurrence of asthma in the future. (2) Neurological, mental and endocrine factors The function of β -adrenergic receptor in children with asthma is low, and the airway nerve tension is increased, or the α -adrenergic nerve reactivity is increased, resulting in airway hyperresponsiveness. Non-adrenergic and non-cholinergic (NANC) nerves are the main innervation for relaxing airway smooth muscle. NACN nerve dysfunction in asthmatic children further aggravates airway hyperresponsiveness. Epithelial exfoliation and nerve endings exposure caused by airway inflammation may be the cause of autonomic nerve dysfunction. Some children's asthma attacks are related to emotions, and the reasons are unknown. More commonly, severe asthma attacks can affect the mood of children and their families. About two-thirds of children with asthma disappear completely in adolescence, and their symptoms get worse during menstruation, pregnancy and hyperthyroidism, all of which suggest that the onset of asthma may be related to endocrine dysfunction, and the specific mechanism is unknown. (III) Genetic background Asthma has obvious genetic tendency, and the incidence of allergic diseases and atopic constitution of children and their family members is significantly higher than that of normal people. Asthma is a polygenic disease. At present, many genes related to asthma (disease-related genes) have been found, such as IgE, IL-4, IL- 13, TCR and other gene polymorphisms. However, the incidence of asthma has increased significantly in the past 30 years, which cannot be explained by genetic variation alone, and the change of environmental factors may be more prominent. (4) Inducing factors 1. Respiratory infection data show that respiratory virus infection is an important cause of asthma attack, especially respiratory syncytial virus, rhinovirus and parainfluenza virus. But as far as the global incidence is concerned, the areas with high incidence of asthma are all developed countries with good sanitary conditions and less respiratory virus infection. Therefore, some people put forward the' hygiene theory' of asthma, that is, newborns or babies are less exposed to infectious agents and have the opportunity to contact allergens (such as dust mites and animal fur). ), it is easy to get allergic diseases and asthma in the future. On the contrary, newborns or babies often suffer from viral respiratory infections, and the chances of suffering from allergic diseases and asthma in the future are significantly reduced. Even if asthma occurs, its symptoms are very mild. According to the viewpoint of "hygiene theory", respiratory virus infection is only the cause of acute asthma attack, not the cause. These children with asthma caused by respiratory virus infection are actually atopic individuals. 2. Other nonspecific stimuli (such as dust, smoke, chemical gas, paint, cold air), climate change, strenuous exercise, food (eggs, peanuts, fish and shrimp, etc.). ) and drugs (such as aspirin, etc. ) may be the cause of acute asthma attack. To sum up, the pathogenesis of asthma may be: exposure to allergens in early life promotes the continuous development of TH2 cell function of individuals with atopic genetic background, forms a specific constitution, and produces airway hyperresponsiveness under the stimulation of incentives including respiratory tract infection and various allergens, resulting in asthma attack (Figure 9-5) [Pathology and pathophysiology] (1). The lung tissue of children who died of pathological asthma showed emphysema, and the large and small airways were filled with mucus plugs. Mucous suppository consists of mucus, serum protein, inflammatory cells and cell fragments. Microscopically, bronchial epithelial cells shed, eosinophils and monocytes infiltrated in the wall, blood vessels dilated and microvascular leaked, basement membrane thickened, smooth muscle proliferated and hypertrophy, goblet cells and submucosal glands proliferated. (2) Pathophysiological airflow obstruction is the core of pathophysiological changes of asthma. Bronchial spasm, inflammatory swelling of the tube wall, mucus embolism formation and airway remodeling are all causes of airway obstruction in children. 1, acute bronchospasm of acute asthma is caused by the release of IgE-dependent mediators (1 allergic reaction), including histamine, prostaglandin and leukotrienes released by mast cells. Lung function is characterized by a transient one-second forced expiratory volume (FEV 1) decrease in the early stage of the disease. 2. After 6-24 hours of delayed asthma antigen stimulation, inflammatory exudation and mucosal edema appeared in the small airway wall, which narrowed the lumen without bronchospasm, or caused by inflammatory factors stimulating nerve media or directly stimulating exposed autonomic nerves. 4 ~ 6 hours after the attack, the pulmonary function showed that FEVl decreased continuously. Both IgE (i.e. primary asthma) and inflammation-induced bronchospasm (delayed asthma) are called airway hyperresponsiveness. 3. The formation of mucus plug mainly occurs in delayed asthma, and mucus secretion increases, forming mucus plug. In severe cases, mucus plug widely blocks bronchioles, causing severe dyspnea and even respiratory failure. 4, airway remodeling Due to chronic and repeated inflammatory injuries, airway wall hyperplasia and thickening, airway inner diameter irreversible stenosis. Lung function gradually declines, and at this time, all kinds of treatment methods are difficult to work.