Introduction to asthma

Description: Bronchial asthma (asthma) is a chronic airway inflammation involving a variety of cells, especially mast cells, eosinophils and T lymphocytes. In susceptible individuals, this inflammation can cause recurrent wheezing. Symptoms such as shortness of breath, chest tightness and/or cough occur mostly at night and/or in the early hours of the morning, and the airway is more reactive toward multiple stimuli. However, the symptoms can be relieved by themselves or by treatment. In the past ten years, the prevalence and mortality of asthma in the United States, Britain, Australia, New Zealand and other countries have increased. About 100 million asthma patients in the world have become a major chronic disease that seriously threatens public health. The prevalence of asthma in China is about 1%, and children can reach 3%. It is estimated that there are more than 10 million asthma patients in the country. Etiology: The etiology of this disease is more complicated, and most of them are considered to be a polygenic genetic disease, which is affected by both genetic and environmental factors. (1) Genetic factors The relationship between asthma and heredity has received increasing attention. According to family data, most of the early studies considered that asthma is a monogenic genetic disease. Some scholars believe that it is an autosomal dominant inheritance disease, and it is also considered to be autosomal recessive inheritance. At present, asthma is considered to be a polygenic genetic disease with a heritability of about 70% to 80%. Polygenic genetic diseases are caused by multiple pairs of pathogenic genes on different chromosomes. There is no obvious difference between these genes. Each has a weak effect on phenotype, but it has an additive effect. The incidence is affected by the environment. The influence of factors is large. Therefore, bronchial asthma is composed of several genetic factors that have a small but cumulative effect, and the genetic risk determines the risk of an individual's illness as susceptibility. The possibility that genetic factors and environmental factors work together to determine whether an individual is susceptible to asthma is called susceptibility. The degree of heritability can measure the role of genetic factors in its pathogenesis. The higher the heritability, the greater the role of genetic factors in its pathogenesis. The higher the heritability, the greater the role of genetic factors in the pathogenesis. Many survey data show that the prevalence of relatives of asthma patients is higher than the prevalence of the population, and the closer the relationship, the higher the prevalence rate; in a family, the more patients, the higher the prevalence of relatives; patients The more serious the condition, the higher the prevalence of relatives. Wang Mingang et al investigated the prevalence of asthma in children with grade I and II in asthma, and compared with the control group, the prevalence of asthma in class I relatives in the asthma group was 8.2%, and the prevalence of class II relatives was 2.9%. The prevalence is significantly higher than the latter. The prevalence of asthma in the control group's I and II relatives was 0.9% and 0.4%, respectively, and the prevalence was lower than that of the asthmatic group I and II relatives. An important feature of asthma is the presence of airway hyperresponsiveness. Studies in humans and animals have shown that some genetic factors control the response of the airways to environmental stimuli. Zhang Xiaodong et al used tissue inhalation method to measure the airway responsiveness of 40 parents of asthmatic children and 34 normal children. Most of the parents of asthma had different degrees of airway responsiveness, and PC20 averaged 11.6 mg/ml, while normal children. The PC20 of both parents is greater than 32mg/ml, indicating that there is a basis for airway hyperresponsiveness in the family of asthma patients, so the inheritance of airway hyperresponsiveness plays an important role in the inheritance of asthma. At present, the genes related to asthma are not completely clear, but studies have shown that there may be asthma specific genes, IgE regulatory genes and specific immune response genes. Autosomal 11q12q13 contains an asthma gene that controls the reactivity of IgE. In recent years, foreign studies on serum total IgE genetics suggest that the gene that regulates total IgE is located on chromosome 5; the specific immune response is not the IgE regulatory gene. Controlled by the immune response gene, the immune response gene has a high recognition capacity of the antigen molecule, and it is confirmed in the mouse experiment that the immune response gene is located in the MHC region on chromosome 17. Studies have shown that there are also immune response genes in the DR site of the HLA region on human chromosome 6, which controls the immune response to a specific antigen. Therefore, the interaction between IgE regulatory genes and immune response genes is involved in the pathogenesis of asthma. In addition, different sensitive states of cellular receptors in the nervous system and respiratory system, and the congenital deficiency of certain enzymes may also be affected by genetic factors. In short, the relationship between asthma and heredity needs to be further studied to facilitate early diagnosis, early prevention and treatment. (B) the stimulating factors The formation of asthma and repeated onset, often the result of a combination of many complex factors. 1. Inhaled inhalants are classified into specific and non-specific. The former such as dust mites, pollen, fungi, animal dander, etc.; non-specific inhalants such as sulfuric acid, sulfur dioxide, chloramine and the like. Specific inhalation of occupational asthma such as toluene diisocyanate, phthalic anhydride, ethylenediamine, penicillin, protease, amylase, silk, animal dander or excrement, in addition, non-specific formaldehyde, formic acid Wait. 2. The formation and onset of infection with asthma are associated with repeated respiratory infections. In asthma patients, specific IgE may be present in bacteria, viruses, mycoplasmas, etc., and asthma may be stimulated if the corresponding antigen is inhaled. After the virus is infected, the airway epithelium can be directly damaged, resulting in increased respiratory responsiveness. Some scholars believe that interferon and IL-1 produced by viral infection increase the amount of histamine released by basophils. In the early childhood, respiratory viruses (especially respiratory syncytial virus) are infected, and there are many symptoms of asthma. Asthma caused by parasites such as mites and hookworms is still visible in rural areas. 3, food due to dietary relationship caused by asthma attacks are often seen in asthma patients, especially infants and young children are easy to food allergies, but gradually decrease with age. The most common foods that cause allergies are fish, shrimps, crabs, eggs, milk, etc. 4. Climate change When the temperature, temperature, air pressure and/or air ions change, it can induce asthma, so it is more common in the cold season or autumn and winter climate change. 5, mental factors patients with emotional excitement, nervousness, anger, etc., will promote asthma attacks, it is generally believed that it is caused by cerebral cortex and vagus nerve reflex or hyperventilation. 6. Exercise: About 70% to 80% of asthma patients induce asthma after strenuous exercise, called exercise-induced asthma, or exercise-induced asthma. A typical case is 6 to 10 minutes of exercise, and bronchospasm is most pronounced within 1 to 10 minutes after stopping exercise. Many patients recover spontaneously within 30 to 60 minutes. There is an refractory period of about 1 hour after exercise, during which 40% to 50% of the patients exercise again without bronchospasm. Clinical manifestations include cough, chest tightness, shortness of breath, wheezing, auscultation audible and wheezing. Some patients have no typical asthmatic performance after exercise, but pulmonary function tests before and after exercise can detect bronchospasm. The disease is more common in adolescents. If cromolyn sodium, ketotifen or aminophylline is administered in advance, the onset can be alleviated or prevented. Related studies suggest that due to hyperventilation after strenuous exercise, the moisture and heat of the airway mucosa are lost, and the concentration of molecules in the airway epithelium temporarily appears to be too high, leading to contraction of bronchial smooth muscle. 7, asthma and drugs Some drugs can cause asthma attacks, such as propranolol and other causes of asthma caused by blocking β2-adrenergic receptors. About 2.3% to 20% of asthma patients induce asthma as a result of taking aspirin, called aspirin asthma. Patients with nasal polyps and low tolerance to aspirin are referred to as aspirin triad. Its clinical features are: taking aspirin can induce severe asthma, symptoms appear more than 2 hours after medication, and occasionally as late as 2 to 4 hours. Patients may have cross-reactions with other antipyretic analgesics and non-steroidal anti-inflammatory drugs; children with asthma are mostly before the age of 2, but most of them are middle-aged patients, mostly 30 to 40 years old; more women than men, The ratio of male to female is about 2:3; the attack has no obvious seasonality, the condition is heavier and stubborn, most of them are dependent on hormones; more than half have nasal polyps, often accompanied by perennial allergic rhinitis and/or sinusitis, nasal After polypectomy, asthma symptoms sometimes worsen or trigger; common inhalation allergens are negative in the skin test; serum total IgE is normal; patients with less allergic diseases in the family. Regarding its pathogenesis has not yet been fully elucidated, it has been suggested that the patient's bronchial epoxidase may be affected by an infectious agent (probably a virus), making the epoxidase susceptible to aspirin inhibition, that is, intolerance to aspirin. Therefore, when patients use aspirin drugs, it affects the metabolism of arachidonic acid, inhibits the synthesis of prostaglandins, deregulates PGE2/PGF2α, and increases the production of leukotrienes, resulting in strong and long-lasting contraction of bronchial smooth muscle. 8. Menstruation, Pregnancy and Asthma Many women with asthma have aggravation of asthma 3 to 4 days before the menstrual period, which may be related to the sudden decline of progesterone in the premenstrual period. If some patients are required to have a monthly dose and the amount of menstruation is small, progesterone may be injected in a timely manner, sometimes preventing severe premenstrual asthma. Pregnancy has no regular effect on asthma. There are asthma symptoms improvement and worsening, but most of the conditions have not changed significantly. The effect of pregnancy on asthma is mainly manifested in mechanical effects and changes in hormones associated with asthma. In the third trimester of pregnancy, as the uterus increases, the position of the diaphragm increases, resulting in different amounts of residual gas, expiratory volume, and functional residual capacity. The degree of decline, and there is an increase in ventilation and oxygen consumption. If asthma is treated properly, it will not have adverse consequences for pregnancy and childbirth. (A) allergic bronchial asthma is associated with allergic reactions, has been recognized as the main type I allergic reaction. Most patients are atopic, often accompanied by other allergic diseases. When the allergen enters the body to stimulate the body, it can synthesize high titer-specific IgE and bind to the surface of mast cells and basophils. Affinity Fcε receptor (FcεR1); also binds to certain B cells, macrophages, monocytes, eosinophils, NK cells, and low-affinity Fcε receptors (FcεR2) on the surface of platelets. However, the affinity of FcεR2 to IgE is about 10-100 times lower than that of FcεR1. If the allergen re-enters the body, it can cross-link with IgE bound to FcεR, synthesize and release a variety of active mediators, resulting in bronchial smooth muscle contraction, increased mucus secretion, increased vascular permeability and inflammatory cell infiltration. Moreover, inflammatory cells can release a variety of media under the action of the medium, which makes the airway inflammation worse. According to the time of asthma after allergen inhalation, it can be divided into immediate asthma response (IAR), delayed-onset asthma response (LAR) and bipolar asthma response (DAR). IAR reacts almost immediately while inhaling allergens, peaks in 15 to 30 minutes, and gradually returns to normal in about 2 hours. LAR is delayed, about 6 hours, and lasts for several days. Some patients with severe asthma are closely related to delayed type of response. The clinical symptoms are severe, the lung function is impaired and persistent, and it is often necessary to inhale glucocorticoid drugs and other treatments to recover. In recent years, the clinical importance of LAR has attracted people's attention. The mechanism of LAR is more complicated, not only related to IgE-mediated degranulation of mast cells, but mainly due to airway inflammation, which may involve re-granulation of mast cells and leukotrienes (LT), prostaglandins (PG), thromboxane. Release of delayed media such as (TX). Studies have shown that mast cell degranulation is not unique to immune mechanisms, non-immune stimuli such as exercise, cold air, inhaled sulfur dioxide, etc. can activate mast cells to release particles. It is believed that asthma is a chronic inflammatory disease involving multiple inflammatory cell interactions, many mediators and cytokines involved, LAR is the result of airway inflammation, mast cells are primary effector cells, and eosinophils Cells, neutrophils, monocytes, lymphocytes and platelets are secondary effector systems, which in turn release a large number of inflammatory mediators, activate airway target organs, cause bronchial smooth muscle spasm, microvascular leakage, mucosal edema, The nervous response to mucus hypersecretion is excitatory, and the patient's airway responsiveness is significantly increased. Clinically, general bronchodilators are not easy to relieve, and the use of corticosteroids and sodium cromolyn inhalation can prevent the occurrence of LAR. The relationship between bronchial asthma and type III allergies is now controversial. Traditionally, exogenous asthma is a type I allergy, manifested as IAR; and endogenous asthma is a type III allergy (Arthus phenomenon), which is expressed as LAR. However, some studies have shown that the vast majority of LAR is secondary to IAR, and LAR has a significant dependence on IAR. Therefore, not all LARs are type III allergies. (B) airway inflammation Airway inflammation is an important advance in the field of asthma pathogenesis research in recent years. Airway inflammation in patients with bronchial asthma is involved in a variety of cells, especially mast cells, eosinophils and T lymphocytes, and there are more than 50 inflammatory mediators and more than 25 cytokines interacting with an airway chronic non-special Heterologous inflammation. Airway inflammation is an important determinant of airway reversible obstruction and non-specific bronchial hyperresponsiveness in asthmatic patients. The airway inflammatory response process in asthma has three phases, namely, IgE activation and FcεR initiation, inflammatory mediators and cytokine release, and expression of adhesion molecules that promote leukocyte transmembrane movement. When the allergen enters the body, the B cells recognize and activate the antigen. The activation pathways are: T, B cell recognition antigens, different epitopes, respectively, activation; B cells endocytosis, treatment of antigens and binding to major histocompatibility complexes ( MHC II), this complex is recognized by Th and releases IL-4, IL-5 to further promote B cell activation. The activated B cells produce corresponding specific IgE antibodies, which are then cross-linked with mast cells, eosinophils, etc., and then produce and release inflammatory mediators under the action of allergens. It is known that mast cells, eosinophils, neutrophils, epithelial cells, macrophages, and endothelial cells all have the ability to produce inflammatory mediators, which can be divided into rapid release mediators (such as histamine) according to the sequence of media production. There are three types of secondary producing media (PG, LT, PAF, etc.) and particle-derived mediators (such as heparin). Mast cells are the primary primary effector cells of airway inflammation. After mast cell activation, histamine, eosinophil chemotactic factor (ECF-A), neutrophil chemotactic factor (NCF-A), LT can be released. Such as media. Alveolar macrophages may also play an important role in the initiation of asthma inflammation, which can release mediators such as TX, PG and platelet active factor (PAF) upon activation. ECF-A chemotaxis of eosinophils and induces release of major base protein (MBP), eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), eosinophil neurotoxin ( EDN), PAF, LTC4, etc., MBP, EPO can cause airway epithelial cells to fall off, expose sensory nerve endings, resulting in airway hyperresponsiveness. MBP and EPO can also activate mast cell release media. NCF-A can neutrophil chemotaxis and release LT, PAF, PGS, oxygen free radicals and lysosomal enzymes, etc., aggravating the inflammatory response. LTC4 and LTD4 are extremely strong bronchoconstrictors and promote increased mucus secretion and increased vascular permeability. LTB4 can oxidize, aggregate and secrete mediators of neutrophils and eosinophils. PGD2, PGF2, PGF2α, PGI2 and TX are all powerful airway contractions. PAF can contract bronchial tubes and chemotaxis, activate inflammatory cells such as eosinophils, and induce microvascular oozing. It is one of the important mediators of asthma inflammation. In recent years, endothelin (ET5) produced in airway epithelial cells and vascular endothelial cells has been found to be an important mediator of airway contraction and reconstruction. ET1 is the strongest bronchial smooth muscle contraction agent known to date, and its contractile strength is LTD4 and nerve. The kinin is 100 times more potent than acetylcholine, and ET also has the effect of promoting the secretion of submucosal glands and promoting the proliferation of smooth muscle and fibroblasts. The pre-inflammatory cytokine TNFα can stimulate the secretion of ET1 by airway smooth muscle cells, which not only aggravates the contraction of smooth muscle, but also enhances the contractile reactivity of airway smooth muscle, and can lead to airway remodeling caused by abnormal proliferation of airway cells, which may become chronic. An important cause of refractory asthma. Adhesion molecules (AMs) are a class of glycoproteins that mediate cell-to-cell adhesion. A large number of studies have confirmed that adhesion molecules play an important role in the pathogenesis of asthma. Molecular mediated adhesion of leukocytes to endothelial cells and trans-endothelial transfer to the site of inflammation. In short, the inflammatory response of asthma is caused by a variety of inflammatory cells, inflammatory mediators and cytokines, and the relationship is very complicated and needs to be further explored. (3) Airway hyperresponsive airway reactivity refers to the contractile response of the airway to various chemical, physical or drug stimuli. Airway hyperresponsiveness (AHR) refers to an excessive airway contraction response of a non-antigenic stimulator of the airway that does not normally cause or only causes a mild response. Airway hyperresponsiveness is one of the important features of asthma. AHR often has a family tendency and is influenced by genetic factors, but the role of external factors is more important. Airway inflammation is currently considered to be one of the most important mechanisms leading to airway hyperresponsiveness. When the airway is affected by allergens or other stimuli, AHR is caused by the involvement of various inflammatory cells, inflammatory mediators and cytokines, damage to the airway epithelium and intraepithelial nerves. It is believed that the autocrine and paracrine secretion of endothelin in airway stromal cells, as well as the interaction of cytokines, especially TNFα, with endothelin play an important role in the formation of AHR. In addition, AHR is associated with hypofunction of β-adrenergic receptors, increased cholinergic neuronal excitability, and defects in the inhibition of non-adrenergic non-cholinergic (NANC) nerves. Stimulation of physical and chemical factors such as viral respiratory infections, SO2, cold air, dry air, hypotonic and hypertonic solutions can increase airway reactivity. The degree of airway hyperresponsiveness is closely related to airway inflammation, but the two are not equivalent. AHR is currently recognized as a common pathophysiological feature of bronchial asthma patients, but not all BHR patients are bronchial asthma, such as long-term smoking, exposure to ozone, viral upper respiratory tract infection, chronic obstructive pulmonary disease (COPD), allergic rhinitis, BHR can also occur in patients with bronchiectasis, tropical pulmonary eosinophilia, and allergic alveolitis, so the clinical significance of BHR should be fully understood. (4) Neurological factors The autonomic innervation of the bronchi is complex. In addition to the previously known cholinergic and adrenergic nerves, there is also a non-adrenergic non-cholinergic (NANC) nervous system. Bronchial asthma is associated with hypofunction of beta adrenergic receptors and hyperkinetic vagal tone, and may have increased reactivity with alpha-adrenergic nerves. NANC inhibits the nervous system as the main nervous system that produces airway smooth muscle relaxation. Its neurotransmitters have not been fully elucidated. It may be vasoactive intestinal peptide (VIP) and/or peptide histidine methionine, while airway smooth muscle. Shrinkage may be associated with impaired functioning of the system. The NANC excitatory nervous system is an unmyelinated sensory nervous system whose neurotransmitter is substance P, which is present in the C-type afferent fibers that are chemically sensitive to airway vagus nerves. When the airway epithelium is damaged, C-fiber afferent nerve endings are exposed, stimulated by inflammatory mediators, causing local axonal reflexes, reverse conduction along the afferent nerve lateral cord, and releasing sensory neuropeptides, such as substance P, neurokinin, Calcitonin gene-related peptide results in bronchial smooth muscle contraction, enhanced vascular permeability, and increased mucus secretion. Recent studies have shown that nitric oxide (NO) is the main neurotransmitter of human NANC, and endogenous NO has a dual effect on the airway. On the one hand, it can relax airway smooth muscle and kill pathogenic microorganisms, in airway smooth muscle tension. Regulation and pulmonary immune defense play an important role; on the other hand, local large amount of NO production can aggravate airway tissue damage and induce AHR. The effect may vary depending on local tissue concentration and target site, and may regulate airway NO production. Good for asthma treatment. The basic pathological changes of the airways are mast cells, pulmonary macrophages, citrate granulocytes, lymphocytes and neutrophil infiltration. Airway mucosal tissue edema, increased microvascular permeability, bronchial endocrine retention, bronchial smooth muscle spasm, ciliated epithelial detachment, basement membrane exposure, goblet cell proliferation and increased bronchial secretion, etc., called chronic exfoliation Eosinophilic bronchitis. The above changes can vary with the degree of airway inflammation. If the asthma is recurrent for a long time, it can enter the irreversible stenosis stage of the airway, mainly manifested as thickening of the bronchial smooth muscle, airway reconstruction under the airway epithelial cells, and support of the surrounding lung tissue to the airway. The effect disappears. In the early stage of the disease, due to the reversibility of pathology, organic changes are rarely found anatomically. As the disease progresses, pathological changes gradually become apparent. The lungs can be seen with enlarged lung swelling and emphysema. The lungs are soft, loose and elastic. The bronchi and bronchioles contain viscous sputum and mucus plugs. The bronchial wall is thickened, the mucosal congestion and swelling are formed, and the atelectasis can be found locally in the mucus embolism. Symptoms: typical bronchial asthma, there are aura symptoms such as sneezing, runny nose, cough, chest tightness, etc. before the attack, if not treated in time, asthma may occur due to increased bronchial obstruction, severe cases may be forced to take a seat or sit-up breath , dry cough or a lot of white foam sputum, and even purple sputum. However, it can usually be relieved by itself or by treatment with self-administered or anti-asthmatic drugs. Some patients may relapse after a few hours of remission, and even lead to persistent asthma. In addition, atypical manifestations of asthma also exist clinically. Such as cough variant asthma, patients with no obvious incentives for cough for more than 2 months, frequent attacks at night and in the morning, exercise, cold air and other induced aggravation, airway reactivity determination of high reactivity, antibiotics or antitussive, expectorant Ineffective treatment, effective with bronchial spasmolytic agents or corticosteroids, but need to rule out other diseases that cause cough. According to the presence or absence of allergens and age of onset, it is clinically divided into exogenous asthma and endogenous asthma. Exogenous asthma often occurs in childhood and adolescents, and there is a history of family allergies, which is type I allergic reaction. Endogenous asthma has no known allergens. It has no obvious seasonality in adults, and has a history of allergies. It may be caused by infection in the body. Regardless of the type of asthma, mild symptoms can gradually resolve spontaneously, without any symptoms or abnormal signs during the remission period. Diagnosis: (1) Diagnostic criteria Read more...