Bronchial asthma (broncahialasthma), referred to as asthma, is the most common chronic respiratory disease of childhood. It is now classified as an immune disease. It is a chronic immune inflammatory disease manifested in the respiratory airways. Definition of asthma: It is a chronic inflammation of the airways involving multiple cells, especially mast cells, eosinophils and T lymphocytes, causing airway hyperreactivity and resulting in reversible airway obstructive disease. The clinical manifestations are recurrent episodes of wheezing, dyspnea, chest tightness or cough. The incidence of asthma has been on the rise in recent years, with 100 million asthma patients worldwide, and the incidence in some developed countries is as high as 20% to 30%. In the United States, about 10%-15% of boys and 7%-10% of girls have had asthma attacks. The total prevalence of childhood asthma in China is 0.9%-1.1%, and 2%-5% in the southern region, and the actual prevalence is estimated to be much higher, with a significant upward trend in recent years. Seventy percent to 80% of children with asthma develop before the age of 5 years, and 50% of children with asthma develop before the age of 3 years, with the youngest being 3 months old. The prevalence of asthma is twice as high in boys as in girls during childhood, with no gender differences by adolescence. The pathogenesis of asthma is extremely complex and not fully understood, and is closely related to immune, neurological, psychiatric, endocrine factors and genetic background. (i) Immune factors Atopy is the most definite risk factor for the development of asthma, and the presence of chronic airway inflammation with hyper-IgEemia, mast cells, eosinophils and T-lymphocytes in asthmatic patients suggests the importance of the immune response in the development of asthma. Recent studies suggest that the immunological pathogenesis of atopy and asthma is characterized by impaired maturation of type I dendritic cells (DCl) and insufficient secretion of 1L-12, which prevents differentiation of TH0 to TH1 cells; CDII promotes the development of THO cells to TH2 under IL-4 induction, leading to a decrease in TH1 (secretion of IFN-γ TH2 cells promote D cells to produce large amounts of IgE (including antigen-specific IgE) and secrete inflammatory cytokines (including adhesion molecules) to stimulate other cells (e.g., epithelial cells, endothelial cells, basophils, mast cells, and eosinophils) to produce a range of inflammatory mediators (e.g., leukotrienes, endothelin, prostaglandin, and thromboxane A2), ultimately inducing tachyphylaxis (increased 1gE) metaplasia and chronic airway inflammation. Many factors influence the maturation of DC differentiation, including the nature of the antigen or allergen, the dose, the route and frequency of exposure, and the DC itself and its microenvironment (various cytokines). The neonatal period is a critical period affecting DC development. There is physiological ding1 mouth cell hyperfunction in neonates, and exposure to allergens at this time will enhance DCII-induced TH2 cell dominance, favoring atopic formation and increasing the chances of asthma. Conversely, induction of IL-12 secretion by DCI with microorganisms and their proteins (e.g. BCG vaccine) during the neonatal period will resist TH2 cell function and reduce atopic formation and later asthma occurrence. (ii) Neurological, psychiatric and endocrine factors Airway hyperresponsiveness occurs in children with asthma due to hypo-adrenergic receptor function and hyper-vagal tone or concomitantly with increased alpha-adrenergic neuroresponsiveness. Non-adrenergic non-cholinergic (NANC) nerves are the main innervated nerves that relax airway smooth muscle, and NACN nerve dysfunction in children with asthma further exacerbates airway hyperresponsiveness. Epithelial detachment and exposure of nerve endings due to airway inflammation may contribute to the phytonadic dysfunction. Some children have asthma attacks related to emotions, the cause of which is unknown. More commonly, severe asthma attacks affect the child and his or her family emotionally. The complete disappearance of asthma symptoms during adolescence in about 2/3 of children and the worsening of symptoms during menstruation, pregnancy and hyperthyroidism suggest that the onset of asthma may be related to endocrine dysfunction, but the exact mechanism is unknown. (iii) Genetic background Asthma has a clear genetic predisposition, and children and their family members with allergic diseases and atopic constitution are significantly higher than the normal population. Asthma is a polygenic genetic disease, and many genes (disease-related genes) associated with the development of asthma have been identified, such as IgE, IL-4, IL-13, TCR and other gene polymorphisms. However, the incidence of asthma has increased significantly in the last 30 years, which cannot be explained solely by genetic variants, and environmental factors may be more prominent in the change. (iv) Triggering factors 1. Respiratory tract infections Data suggest that respiratory tract viral infections are an important cause of asthma attacks, especially respiratory syncytial virus, rhinovirus and parainfluenza virus. However, in terms of global incidence, the areas with high incidence of asthma are developed countries with good sanitary conditions and fewer respiratory viral infections. Therefore, the hygeianhypothesis of asthma development has been proposed, which states that newborns or infants with less exposure to infectious agents and those with access to allergens (e.g., dust mites, animal fur, etc.) are more likely to develop allergic diseases and asthma later in life. Conversely, newborns or infants with frequent viral respiratory infections have a significantly lower chance of developing allergic diseases and asthma later in life, and even if asthma occurs, its symptoms are milder. According to the ‘hygiene doctrine’, respiratory viral infections are only a trigger, not a cause, of acute asthma attacks. These children with asthma caused by respiratory viral infections are actually atopic individuals. 2. Other triggers Non-specific irritants (e.g. dust, smoke, chemical gases, paint, cold air), climate change, strenuous exercise, food (eggs, peanuts, fish and shrimp, etc.) and drugs (e.g. aspirin, etc.) may all be triggers for acute asthma attacks. In summary, the pathogenesis of asthma may be as follows: exposure to allergens early in life promotes the development of persistent dominant TH2 cell function in individuals with an atopic genetic background, resulting in an atopic physique that produces airway hyperresponsiveness and asthma attacks under the stimulation of triggers including respiratory tract infections and various allergens. Pathology and pathophysiology (a) Pathology The lung tissue of children who die of asthma is emphysematous and the large and small airways are filled with mucus plugs. The mucus plug consists of mucus, serum proteins, inflammatory cells and cellular debris. Microscopy shows detachment of bronchial and capillary bronchial epithelial cells, infiltration of eosinophils and monocytes in the walls, vasodilatation and microvascular leakage, thickening of the basement membrane, hypertrophy of smooth muscle, and hyperplasia of cupped cells and submucosal glands. (B) Pathophysiology Airflow obstruction is the core of the pathophysiological changes in asthma. Bronchospasm, inflammatory swelling of the tube wall, mucus plug formation and airway remodeling are all causes of airway obstruction in children. Acute bronchospasm is caused by the release of IgE-dependent mediators (type 1 metaplasia), including histamine, prostaglandins and leukotrienes from mast cells. Pulmonary function is manifested by a transient one-second forceful expiratory volume (FEV1) decrease early in the disease. 2.Late onset asthma Inflammatory exudation of the small airway wall occurs 6 to 24 hours after antigen stimulation and mucosal edema, narrowing the lumen, which may be without bronchospasm, or bronchospasm may be caused by inflammatory factors stimulating neuromediators or direct stimulation of exposed vegetative nerves. Pulmonary function shows a persistent decrease in FEVl 4 to 6 hours after the attack. Either IgE (tachyphylaxis) or inflammation-induced (late-onset asthma) bronchospasm is called airway hyperresponsiveness. 3.Mucus plug formation Mainly occurs in late-stage asthma, mucus secretion increases and mucus plugs are formed. In severe cases, mucus plugs extensively obstruct fine bronchioles, causing severe respiratory distress and even respiratory failure. 4.Airway remodeling Due to chronic and repeated inflammatory damage, the airway wall becomes thickened and the airway inner diameter irreversibly narrowed. Pulmonary function is progressively declining, and various treatments are not effective at this time. Clinical manifestations (a) Typical manifestations The cough and wheezing are paroxysmal, and are heavier at night and in the early morning. The attacks may be preceded by runny nose, sneezing and chest tightness, with dyspnea and prolonged expiratory phase accompanied by wheezing sounds. In severe cases, there is telangiectatic breathing, fear and anxiety, profuse sweating, and a blue and gray face. Physical examination reveals barrel-shaped chest, trismus, and lungs full of croup. In severe cases, the croup may disappear due to extensive airway obstruction. The coarse wet rales in the lungs may appear and disappear after a violent cough or change in position, suggesting that the production of wet rales is due to secretions located in the trachea. Some children have a history of allergy and a family history of allergy. According to the severity of symptoms, they can be divided into intermittent attacks, mild, moderate and severe attacks. 1.Intermittent attacks Less than one attack per week, each lasting from a few hours to a few days, less than two asthma attacks per month at night, with normal lung function during the intervals. 2.Severe exacerbation Existence of dyspnea at rest, telangiectatic breathing, profuse sweating, irritability, trismus, diffuse and loud croup in the lungs, significantly increased heart rate, PEF improvement <60% with F2-agonists, effect lasting <2 hours. Blood gas analysis shows PaO2: <8kPa, PaCO2: >6kPa, SaO2: Q90%. pH decreased. 3. Moderate attack The symptoms are milder than severe attack, with dyspnea after a little activity and a preference for sitting, and the PEF improves 60% to 80% after using β2-agonist. Blood gas analysis shows PaO2: 8-10.5kPa, PaCO2: ≤6kPa, SaO2: 91%-95%. 4.Mild attack Respiratory distress during walking, lying down, quiet, no trismus and tachycardia, PEF improved by 60%-80% after using β2-agonist. Blood gas analysis shows PaO2: normal (usually no need to check), PaCO2: <6kPa, SaO2: >95%. (B) Cough variant asthma (coughvariantasthma) Children with asthma may not have wheezing symptoms, but only have recurrent and chronic cough, which is called cough variant asthma. The cough is often attacked at night and early in the morning and can be aggravated by exercise. Some children eventually develop typical asthma. (a) Pulmonary function tests: FEV1/FVC ratio and peak expiratory flow rate (PEFR) are used to determine whether there is airflow obstruction. If the FEVl/FVC is normal, an excitation test can be applied: a 15% decrease in FEVl or 20% decrease in PEF at 5-15 minutes in the standard 6-minute exercise excitation test can confirm the diagnosis of asthma. Histamine or ethylene choline excitation test can also be used. (b) Chest X-ray The chest X-ray in the acute phase is normal or interstitial, and there may be emphysema or pulmonary atelectasis. Chest X-ray can also exclude other diseases of the lung, such as pneumonia, tuberculosis, tracheobronchial foreign bodies and congenital malformations. (iii) Allergen testing Intradermal testing of various allergens can identify suspected allergens. The sensitivity and specificity of allergen skin tests are yet to be further observed. Serum allergen-specific IgE assay has some value, but serum total IgE assay does not have diagnostic significance. Diagnosis and differential diagnosis (a) Diagnosis Diagnosis is based on clinical manifestations, family history, response to treatment, evidence of airflow obstruction, and similar manifestations due to other diseases can be excluded. 1998, the National Pediatric Asthma Prevention and Control Collaborative Group revised the routine of childhood asthma prevention and control, and the diagnostic criteria of childhood asthma are as follows. 1. Infantile asthma ① Age <3 years, with ≥3 wheezing episodes; ② Exhalation phase croup is heard in both lungs during the attack, with prolonged exhalation phase; ③ Atopic physique, such as allergic eczema, allergic rhinitis, etc.; ④ Parents have a history of allergy such as asthma; ⑤ Excluding other diseases causing wheezing. Anyone with ①, ② and ⑤ can confirm the diagnosis. If there are 2 episodes of wheezing with ② and ⑤, it is suspected asthma or wheezing bronchitis; if ③ and/or ④ are present, therapeutic diagnosis can be given. 2.Children's asthma ① Age ≥ 3 years, wheezing is recurrent (or can be traced to some allergens or irritants); ② expiratory phase croup is heard in both lungs during the attack, and the expiratory phase is prolonged; ③ bronchodilators have obvious efficacy; ④ except other diseases causing wheezing, chest tightness and cough. Bronchodilator test should be performed in suspicious cases: ① β2 agonist aerosol inhalation; ② 0.1% epinephrine 0.01ml/kg subcutaneous injection, after 15 minutes, wheezing is obviously relieved, lung croup is obviously reduced, FEVl rises >15%, and positive bronchodilator test can be used for asthma diagnosis. 3. Cough variant asthma ① persistent or recurrent cough attacks >1 month, and effective antibiotic treatment is ineffective; ② bronchodilators can relieve cough attacks (basic diagnostic condition); ③ history of allergy or allergic family history; ④ airways are hyperreactive, and bronchial excitation test is positive; ⑤ except other diseases causing chronic cough. (ii) Differential diagnosis It should be differentiated from other wheezing and chronic cough diseases, including gastroesophageal reflux, primary ciliary dyskinesia syndrome, congenital heart disease, foreign body aspiration, and various conditions that can cause compressive obstruction of the lower airways. Treatment The goal of asthma treatment is to minimize the symptoms of asthma attacks, reduce the number of attacks, prevent irreversible airway obstruction, maintain normal or near-normal lung function, and ensure and encourage children to participate in normal school and physical activities. The principles of treatment are long-term, continuous, standardized and individualized. Treatment during the flare-up period focuses on anti-inflammation and asthma to provide rapid symptom relief; long-term anti-inflammation, avoidance of triggers and self-care should be maintained during the remission period. In terms of drug use, drug side effects should be minimized, with anti-inflammatory drugs as the mainstay, and β2 agonists used sparingly or not as much as possible. (A) Drugs for asthma 1. glucocorticoids Based on the understanding that asthma is an airway inflammation, glucocorticoids are the drugs of choice for the treatment of asthma. Its anti-inflammatory mechanism is to inhibit the synthesis of TH2-like cytokines and the migration of inflammatory cells to the airway mucosa, induce apoptosis of eosinophils, and block the release of inflammatory factors such as leukotrienes, prostaglandins, thromboxanes and endothelin. (1) Inhalation medication: once the diagnosis of asthma is confirmed, glucocorticoid inhalation agents should be used, the commonly used inhalation agents are beclomethasone dipropionate (domethasonedipropionate), budesonide (promethazine), the dose of 300~600ug per day for severe children, divided into three inhalations. For children under 3 years of age, the daily dose can be increased to 600-800ug with the aid of aerosol cans. 200-400gg for moderate children (400-600ug with aerosol cans), 200-300ug for mild children (200-400ug with aerosol cans), and 100-200ug for intermittent patients (200ug with aerosol cans). Inhalation treatment should be continued for at least 6 months, and the efficacy should be evaluated every 1-3 months. After 3 months of continuous asthma control, the treatment can be downgraded. If asthma recurs, treatment should be escalated immediately. Long-term treatment at minimal but effective doses that vary with disease is the stepwise treatment regimen for asthma. Local adverse effects of glucocorticoid inhalation therapy are Candida infection of the oropharynx, hoarseness, and upper respiratory tract discomfort. The use of a storage fog canister and mouth wash with water after inhalation can reduce local adverse reactions and drug absorption. (2) Oral medication Prednisone should be given for a short course (1-7 days) in acute cases, 1-2mg/kg per day, divided into 2-3 times. The long-term use of oral glucocorticoids for the treatment of asthma in children is generally not recommended. (3) Intravenous medication In severe asthma attacks, hydrocortisone succinate or hydrocortisone should be given intravenously at 5-10mg/kg each time, or methylprednisolone at 2-6mg/kg per day in 2-3 infusions. The dose can be increased if necessary. Generally, intravenous glucocorticosteroids are used for 1-7 days, and the intravenous medication will be stopped after the symptoms are relieved. If glucocorticosteroids are needed continuously, they can be changed to oral prednisone. 2.Bronchodilators It takes 2-4 days for glucocorticoids to control asthma. Bronchodilators can rapidly control bronchospasm and relieve airway hyperresponsiveness. Short-acting & receptor agonist action time is 4-6 hours, there are hydroxymethyl isobutyrin (salbutamol, salbutamol, albuterol), tert-butyl asthma (terbutaline, asthma Kang speed), phenylpropanol asthma (fonoter01) and so on. The long-acting turn agonists with an action time of 8-12 hours include Meperidine and Salbutamol (salmater01), while the longest action time is 24 hours for Banbuter01. Long-term use of & receptor agonists can lead to down-regulation of p2 receptor function and reduced effect, and even aggravate airway inflammation and airway hyperresponsiveness. Therefore, long-term regular drug use is not advocated, but rather intermittent use or not used if possible. Theophylline drugs inhibit phosphodiesterase and have a bronchodilating effect and have the effect of regulating THl/I and H2 cytokines. Theophylline extended-release agents Shuflumet and eugenol are used for chronic and nocturnal exacerbations with a duration of action of 12 hours. Other bronchodilators include cholinergic drugs such as ipratropine, potassium channel activators (such as kamakrine), calcium antagonists (such as nifedipine), etc. 3.Immunosuppressants Methotrexate (methotrexate) cyclosporin A (cyclosporinA) are used for those who are sensitive to glucocorticoids. 4.Other drugs Disodium cromoglycate, a mast cell membrane stabilizer, inhibits the release of histamine, leukotrienes and prostaglandins from mast cells and reduces airway inflammation. The dosage is 4 mg per dose, 2-4 times daily. Other drugs include leukotriene receptor antagonists (Encore) and anti-allergic agents. (ii) Treatment of persistent asthma Keep the child quiet, use hydrated chloral enema if necessary, give oxygen, replenish fluids and correct acidosis. Intravenous methylprednisolone can control airway inflammation within 2-3 days. Intravenous aminophylline, beta agonist aspiration or intravenous administration may also be used to relieve bronchospasm. In case of severe persistent dyspnea (no improvement even after inhalation of 40% oxygen cyanosis, PaCO2≥8.6kPa (≥65mmHg), mechanical respiration should be performed. (iii) Prevention of recurrence: 1. removal of triggers; 2. specific immunotherapy; 3. education and management of asthma. Avoid contact with allergens, actively treat and remove infectious foci, and remove all kinds of triggering factors (smoking, respiratory tract infection and climate change, etc.). Long-term correct use of glucocorticoid aerosol therapy is the key to relapse prevention. Its dosage should be individualized and a stepwise treatment protocol should be used. Specific immunotherapy (desensitization therapy) involves repeated intradermal injections of skin test-positive allergens in small doses to achieve immune tolerance. The effect of desensitization therapy is yet to be further observed. Education and management of asthma 1. Asthma homes, clubs, associations, BA control club groups. 2.Strengthen the doctor-patient contact and cooperate with the implementation of the medical plan. 3.Teaching BA prevention and control knowledge: news media, information, mastering the disease pattern, rational use of medication (inhalation treatment guidance). 4.Patiently explain the condition, psychotherapy. 5.Emphasize avoidance of allergen exposure, self-monitoring of lung function (PEF meter). 6.Rational daily life regime, physical exercise (swimming, gymnastics). Prognosis The prognosis of children’s asthma is better than that of adults, the death rate is about 2-4/100,000, about 70%-80% of the symptoms no longer recur after growing older, but there may still be varying degrees of airway inflammation and hyperresponsiveness, 30%-60% of children can be completely cured.