Persistent asthma state

　　1. Causes of Onset

　　1. Genetic Factors

　　Asthma is a disease with complex traits, showing a polygenic inheritance tendency. Its characteristics include ①incomplete penetrance, ②genetic heterogeneity, ③polygenic inheritance, and ④synergistic effects. These lead to the presence of genetic linkage in one population, but not in another different population. The Collaborative Study on Asthma Genetics (CSGA) studied 140 pedigrees from three races, using 360 short tandem repeat polymorphisms on autosomes for whole genome scanning. The candidate asthma genes were roughly located at 5p15; 5q23-31; 6p21-23; 11q13; 12q14-24.2; 13q21.3; 14q11.2-13; 17p11.1q11.2; 19q13.4; 21q21 and 2q33. The chromosomal regions identified by genetics may contain asthma susceptibility genes, which are roughly divided into three categories: ①genetic polymorphism of HLA-Ⅱ class molecules determining susceptibility to allergic diseases (such as 6p21-23); ②high diversity and specificity of T cell receptors (TcR) and IgE (such as 14q11.2); ③cytokine genes and drug-related genes determining IgE regulation and the development of characteristic airway inflammation in asthma (such as 11q13, 5q31-33). The 5q31-33 region contains multiple candidate genes related to asthma pathogenesis, including cytokine clusters (IL-3, IL-4, IL-9, IL-13, GM-CSF), β2 adrenergic receptor, lymphocyte glucocorticoid receptor (GRL), and leukotriene C4 synthase (LTC4S). These genes are important for IgE regulation and the inflammatory progression of asthma, and therefore, 5q31-33 is also known as the 'cytokine gene cluster'.

　　None of the identified chromosomal regions showed evidence of linkage with more than one racial population, indicating that specific asthma susceptibility genes have only relative importance, and also indicates that environmental factors or regulatory genes may exist differences in disease expression among different races. It also suggests that asthma and atopy have different molecular genetic bases. These genetic chromosomal regions are very large, averaging more than 20Mb of DNA and thousands of genes. And at present, due to the limitation of the amount of specimens, many results cannot be repeated. It can be seen that there is still a lot of work to be done in searching for and identifying asthma-related genes.

　　2. Allergens

　　The most important trigger factor for asthma may be the inhalation of allergens.

　　(1) Indoor allergens: Dust mites are the most common and harmful indoor allergens, and are an important trigger factor for asthma worldwide. There are four common types: house dust mites, dust mites, dust mites, and multi-haired mites. More than 90% of mites exist in house dust, with house dust mites being the most common mites in persistently moist climates. The main antigens are DerpI and DerpⅡ, and the main components are cysteine proteases or tyrosine proteases. Pets such as cats, dogs, and birds kept at home release allergens in their fur, saliva, urine, and feces. Cats are the most important sensitizers among these animals, and their main allergen component feldl exists in the fur and sebaceous secretions of cats, which is a major risk factor for acute asthma attacks. Cockroaches are common indoor allergens in Asian countries; the common cockroaches related to asthma are American cockroaches, German cockroaches, oriental cockroaches, and black-banded cockroaches, among which the black-banded cockroach is the most common in China. Fungi are also allergens present in indoor air, especially in dark, damp, and poorly ventilated places, commonly including penicillium, aspergillus, fusarium, branch孢子菌, and Candida. Among them, Alternaria has been confirmed as a risk factor for asthma. Common outdoor allergens: Pollen and grass powder are the most common outdoor allergens that trigger asthma attacks. Angiosperm plants (tree pollen) often cause spring asthma, while grass and weed pollen from monocotyledonous plants often cause autumn asthma. In the eastern region of China, mugwort pollen is mainly present; in the northern region, mainly artemisia.

　　(2) Occupational allergens: Common allergens that can cause occupational asthma include grain powder, flour, wood, feed, tea, coffee beans, silkworms, pigeons, mushrooms, antibiotics (penicillin, cephalosporins), isocyanates, phthalates, rosin, reactive dyes, persulfates, ethylenediamine, etc.

　　(3) Drugs and food additives: Aspirin and some non-steroidal anti-inflammatory drugs are the main allergens causing drug-induced asthma. Food additives such as salicylates, preservatives, and dyes can also cause acute asthma attacks. Royal jelly liquid is widely used in China and Southeast Asia as a health food. It has been confirmed that royal jelly can cause acute asthma attacks in some patients, which is an IgE-mediated allergic reaction.

　　3. Triggers

　　(1) Air pollution: Air pollution (SO2, NOx) can cause bronchoconstriction, transient increased airway reactivity, and enhance the response to allergens.

　　(2) Smoking: Cigarette smoke (including passive smoking) is the main source of indoor triggers and is an important asthma trigger, especially for children with asthma whose parents smoke, who often have asthma attacks caused by smoking.

　　(3) Respiratory virus infection: There is a close relationship between respiratory virus infection and asthma attacks. Infants' bronchial virus infection, as a triggering cause of asthma, is particularly of concern. Common respiratory viruses include respiratory syncytial virus (RSV), adenovirus, rhinovirus, influenza virus, parainfluenza virus, coronavirus, and some enteroviruses. Rhinovirus and influenza virus are the main viruses associated with adult asthma; respiratory syncytial virus, parainfluenza virus, adenovirus, and rhinovirus are closely related to asthma attacks in children. Respiratory syncytial virus is the main pathogen in the first year after birth, accounting for 44% of infectious asthma in children under 2 years of age and more than 10% in asthma in older children. Some reports have shown that nearly 100% of asthma or bronchiolitis patients infected with RSV have IgE attached to their epithelial cells. Children hospitalized due to acute RSV infection have a 42% chance of developing asthma 10 years later.

　　(4) Perinatal fetal environment: The thymus of a fetus at 9 weeks of gestation can produce T lymphocytes, and B lymphocytes have been produced in various organs of the fetus from the 19th to 20th week. Since the placenta mainly produces helper type Ⅱ T cell (Th2) cytokines throughout pregnancy, Th2 responses are dominant in the lung microenvironment. If the mother has a specific体质 and is exposed to a large amount of allergens (such as lactoglobulin in milk, ovalbumin in eggs, or DerpI in mites) during pregnancy or is repeatedly infected with respiratory viruses, especially respiratory syncytial virus, it may exacerbate her Th2-mediated allergic reactions, thereby increasing the possibility of allergic reactions and asthma after birth.

　　In addition, the amount of polyunsaturated fatty acids ingested in the late stage of pregnancy will affect the production of prostaglandin E, which may be related to the变态reaction regulation by Th2 cells. Smoking during pregnancy is definitely harmful to the lung function of the fetus and the susceptibility to wheezing in the future.

　　(5) Others: Severe exercise, changes in climate, and various non-specific stimuli such as: inhaling cold air, droplets of distilled water vapor, etc. In addition, psychological factors can also trigger asthma.

　　2. Pathogenesis

　　There are many reasons for the formation of persistent asthma, and the mechanism is also relatively complex. The reasons why asthma patients develop severe asthma are often multifaceted. As clinical doctors, it is important to be aware that in order to effectively control the condition, in addition to timely diagnosis and treatment of severe asthma, it is very important to find the causes of each patient developing severe asthma and to exclude them. The main causes that have been basically clarified include the following points:

　　5. Persistent presence of allergens or other asthma-inducing factors

　　Asthma is caused by bronchial mucosal receptors developing rapid and late-phase reactions after specific stimulation, leading to bronchospasm, airway inflammation, and airway hyperreactivity, causing narrowing of the respiratory tract. If patients continue to inhale or come into contact with allergens or other asthma-inducing factors (including respiratory infections), it can lead to persistent spasms of bronchial smooth muscle and progressive worsening of airway inflammation, desquamation and injury of epithelial cells, causing mucosal congestion and edema, excessive secretion of mucus, and even the formation of mucus plugs. In addition, with extreme spasm of the airway smooth muscle, it can severely block the respiratory tract, causing persistent asthma and difficulty in relief.

　　4. Improper use of β2-agonists and/or insufficient anti-infection treatment

　　It has been confirmed that asthma is an airway inflammatory disease, and therefore anti-inflammatory drugs have been recommended as the first-line treatment for asthma. However, in clinical practice, many asthma patients have long been treated primarily with bronchodilators, with insufficient anti-infection treatment or inappropriate use of anti-infection drugs, leading to ineffective control of airway allergic inflammation, making airway inflammation increasingly severe, airway hyperreactivity exacerbated, and asthma symptoms worsening. Moreover, the long-term blind and excessive use of β2-agonists can cause down-regulation of β2 receptors, leading to desensitization. In this situation, sudden discontinuation of medication can cause a significant increase in airway reactivity, thus triggering severe asthma attacks.

　　3. Dehydration, electrolyte imbalance, and acidosis

　　During asthma attacks, patients sweat a lot and breathe through their mouths, causing an increased loss of moisture in the respiratory tract; oxygen therapy fails to adequately humidify and warm; drugs such as aminophylline, which are strong heart and diuretics, increase urine output relatively; in addition, factors such as respiratory difficulty and less drinking water. Therefore, patients with asthma attacks often have varying degrees of dehydration. This leads to tissue dehydration, thickening of sputum, the formation of mucus plugs that cannot be coughed out, widespread obstruction of small and medium-sized airways, exacerbation of respiratory difficulty, leading to ventilatory dysfunction, hypoxemia, and hypercapnia. At the same time, due to hypoxia and reduced intake of food, the production of acidic metabolic products in the body increases, which may lead to metabolic acidosis. In the case of acidosis, the responsiveness of the airways to many bronchodilators decreases, further exacerbating asthma symptoms.

　　4, Sudden discontinuation of hormones

　　The 'rebound phenomenon' may occur in some patients due to the ineffectiveness of general asthma drugs or due to inappropriate treatment by doctors, long-term repeated use of corticosteroids, causing the body to produce dependence or tolerance. Once for some reason such as drug shortage, surgery, pregnancy, gastrointestinal bleeding, diabetes, or treatment failure, the sudden discontinuation of corticosteroids can cause asthma to be uncontrolled and exacerbated.

　　5, Excessive emotional tension

　　On one hand, the worry and fear of the patient about the illness can exacerbate bronchospasm and dyspnea through the cortex and autonomic nerve reflex; on the other hand, insomnia day and night can exhaust the patient's physical strength; in addition, the mental and emotional state of the attending physician and the family can also affect the patient, promoting further deterioration of asthma.

　　6, The influence of physical and chemical factors and factors

　　Some reports have found that some physical and chemical factors such as temperature, humidity, atmospheric pressure, air ions, etc., can have varying degrees of impact on some asthmatic patients, but the mechanism is not clear so far. Some people believe that climatic factors can affect the nervous system, pH value of endocrine body fluids, potassium and calcium balance, and immune mechanism of the human body. An excess of positive ions in the air can also cause changes in potassium and calcium in the blood, leading to bronchial smooth muscle contraction.

　　7, Severe complications or accompanying symptoms

　　Complications such as pneumothorax, mediastinal emphysema, or accompanying cardiac asthma attack, renal failure, pulmonary embolism, or intravascular thrombosis can all worsen asthma symptoms.

　　Persistent asthma status can lead to chronic obstructive pulmonary disease, emphysema, pulmonary heart disease, heart failure, respiratory failure, and circulatory failure, mucus plug obstruction, and other complications, which are relatively common. The lung function of most asthmatic patients deteriorates gradually over a few days, but the acute exacerbation of asthma in a few patients evolves rapidly, with respiratory and circulatory failure crisis appearing within minutes to several hours. Lactic acidosis may occur.

　　The clinical manifestations of patients with persistent asthma status are:

　　1, The patient cannot lie flat, is anxious and restless, sweating profusely, speaking incoherently, breathing > 30 times/min, the chest is full, the range of motion decreases, accessory respiratory muscles are working (sternocleidomastoid muscle contraction, tricuspid sign), heart rate > 120 times/min, often with a paradoxical pulse (> 25 mmHg), and adults may have PEF below 60% of their best value or 45 mmHg, blood pH decreases, X-ray shows overinflation of the lungs, pneumothorax or mediastinal emphysema, and electrocardiogram may show pulmonary P wave, right axis deviation, sinus tachycardia. In more severe cases, there may be drowsiness or confusion, and paradoxical motion of the chest and abdomen (diaphragmatic fatigue), wheezing may change from obvious to disappeared.

　　2, The lung function of most asthmatic patients deteriorates gradually over a few days, but the acute exacerbation of asthma in a few patients evolves rapidly, with respiratory and circulatory failure crisis appearing within minutes to several hours. Therefore, some people divide asthma with acute respiratory failure into two categories: acute severe asthma and acute asphyxiating asthma.

　　First-level prevention

　　Most patients (especially children) have allergic asthma. The fetal immune response is a Th2 dominant response. In the later stages of pregnancy, certain factors such as excessive exposure to allergens by the mother, viral infections, etc., can enhance the Th2 response and worsen the imbalance between Th1/Th2, especially for mothers with allergic constitution, so it should be avoided as much as possible. In addition, there is sufficient evidence to support that smoking by the mother can increase the probability of wheezing and asthma in infants after birth, while breastfeeding for 4 to 6 months after birth can reduce the incidence of allergic diseases in infants, so the mother should avoid smoking during pregnancy. These are all important links in preventing the occurrence of asthma. As for the influence of maternal diet on the fetus, more observations are still needed.

　　Second-level prevention

　　1. Avoid allergens

　　Especially for patients with specific体质, eliminate or try to avoid contact with factors that induce asthma. Such as house dust mites, pollen, animal fur, allergenic foods, drugs, etc., for occupational asthma patients, they should leave the occupational environment.

　　As mentioned before, whether respiratory viruses are allergens for asthma is still controversial, but they are closely related to the occurrence and development of asthma, especially respiratory syncytial virus in children and rhinovirus in adults. Avoiding respiratory virus infection is also an important preventive measure for asthma.

　　2. Prevention and treatment of allergic rhinitis

　　The relationship between allergic rhinitis and asthma is very close. Some people have followed up on patients with simple allergic rhinitis for nearly 20 years and found that nearly 17% of them have developed asthma, which is much higher than the control group (5%); studies also show that 20% to 25% of patients with simple allergic rhinitis have airway hyperreactivity (histamine or amantadine stimulation), so it is believed that these patients may belong to 'subclinical asthma'. Asthma patients with allergic rhinitis account for about 28% to 50%. Recent data show that if such patients can actively control allergic rhinitis (such as oral non-sedative H1 receptor blockers, nasal inhalation of corticosteroids) on the basis of bronchial inhalation of corticosteroids, it can significantly reduce the frequency of asthma attacks and alleviate symptoms, so active treatment of allergic rhinitis is valuable for preventing the occurrence of asthma and reducing its attacks.

　　3. Third-level prevention

　　1. Early diagnosis and early treatment

　　For patients with mild or atypical symptoms (such as simple cough, paroxysmal chest tightness, or chest tightness after exercise), an early diagnosis should be made. Studies have shown that for patients diagnosed with bronchial asthma, the earlier they use airway anti-infection treatment (inhaled corticosteroids), the less damage to their lung function in the future (including the recovery of lung function and the growth of lung function in children with age), so for the vast majority of patients (except for a few in the 'intermittent' period), once diagnosed, anti-infection treatment should be carried out. With the standardization of specific immunotherapy, it may become an effective measure for the third-level prevention of allergic asthma patients.

　　2. Do a good job in the education and management of asthma patients

　　Asthma is a chronic disease, and there is currently no cure. However, by taking effective prevention and treatment measures, it is completely possible to promote the normal life, work, and study of patients. Strengthening the education and management of patients is very important. First, educate patients to understand the nature, triggers, signs of attacks, types of medication, and methods, especially emphasizing the preventive and therapeutic treatment of long-term anti-inflammatory. Second, educate patients to learn to use peak flow meters to monitor their own condition so that they can take medication in time when the condition changes.

　　China has gained good experience in implementing the global asthma prevention and treatment strategy, especially in establishing 'Asthma Home', 'Asthma Club', which has strengthened the cooperation between doctors and patients, significantly reducing the frequency of asthma attacks, emergency rates, hospitalization rates, and medical expenses. In the future, it is necessary to further promote it throughout the country.

　　Persistent asthma can be diagnosed through laboratory blood tests, routine X-ray examination:X-ray manifestations include overinflation of the lungs, pneumothorax, or mediastinal emphysema, and the electrocardiogram may show pulmonary P wave, right axis deviation, and sinus tachycardia.

　　1. What foods are good for the body in the persistent state of asthma

　　1. Correct malnutrition, trace the allergen. Avoid eating suspected allergenic foods. Quality and quantity of protein, vitamins, and high carbohydrate diet can be adopted, but the fat supply should be appropriate.

　　2. For obese patients, the fat supply should be low to achieve the purpose of removing phlegm and dampness and appropriate weight loss. Obese patients have an upward shift of the diaphragm and a decrease in diaphragmatic mobility, which can worsen asthma.

　　3. To alleviate the difficulty of chewing and swallowing caused by respiratory distress, soft rice or semi-liquid (not containing hard, tough foods) diet can be used, which is conducive to digestion and absorption and can prevent food reflux.

　　4. Avoid eating gas-producing foods (such as sweet potatoes, chives, soybeans, bread, etc.), and use more alkaline foods.

　　5. According to the needs of the disease, increase the intake of liquids in various forms (such as drinks, soups, etc.) to prevent and correct dehydration, which is particularly important for fever patients.

　　2. What foods should not be eaten in the persistent state of asthma

　　Avoid eating spicy foods. For example, fish such as hairtail, yellow croaker, clam, clam, carp, silver carp, crab, shrimp, etc. in aquatic products; livestock and poultry such as pork head meat, chicken head, lamb, dog meat, donkey meat, horse meat, etc.; vegetables such as chives, celery, bamboo shoots, eggplant in autumn, etc.; condiments such as scallion, garlic, chili, wine, sweet rice wine, etc., can all be considered as 'spicy foods'.

　　1. Treatment

　　1. Asthma

　　General comprehensive treatment for persistent state

　　(1) Oxygen therapy: There is often varying degrees of hypoxemia in the persistent state of asthma, so oxygen inhalation should be given in principle. The oxygen flow rate is 1-3L/min, and the oxygen concentration is generally not more than 40%. In addition, to avoid airway dryness, the inhaled oxygen should be as warm and moist as possible.

　　(2) β-receptor agonists: It is not advisable for patients with severe asthma to be administered orally or directly through a metered-dose inhaler (MDI) because at this time, patients are unable to take a deep breath, hold their breath, or coordinate the synchronization of medication administration with breathing. The available modes of administration include:

　　① Continuous nebulization inhalation: β2 receptor agonists are inhaled through nebulization using high-flow oxygen (or compressed air) as the power source. Generally, adults inhale 1 to 2ml of salmeterol or terbutaline nebulization solution, half for children under 12 years old, and repeat every 20 minutes within the first hour. High-end and mid-range ventilators are generally equipped with devices for nebulization inhalation, so nebulization inhalation can also be administered through the管道 connected to the ventilator for critically ill patients with tracheal intubation.

　　② Using a spacer with MDI: β2 receptor agonists are administered at a dose of 2 sprays, and they can be repeated every 20 minutes within the first hour if necessary.

　　③ Intravenous or subcutaneous administration: Salmeterol 0.5mg (or terbutaline 0.25mg) is administered subcutaneously, and then 1mg of salmeterol is added to 100ml of fluid for slow intravenous infusion (about 2 to 8 μg per minute). Young patients without cardiovascular disease can be administered 0.3ml of 1:1000 epinephrine subcutaneously, and a repeat injection can be given once after 1 hour. Note: Caution should be exercised when using β-receptor agonists intravenously or subcutaneously in elderly patients, patients with severe hypertension, arrhythmias, or in adults with a heart rate exceeding 140 beats/min.

　　Once a patient is diagnosed with severe asthma, corticosteroids should be administered intravenously in a timely and adequate manner in conjunction with bronchodilators. Commonly used hydrocortisone succinate is 200 to 400mg daily, diluted and administered intravenously, or methylprednisolone 100 to 300mg daily, or dexamethasone 5 to 10mg intravenously, which can be repeated every 6 hours. Gradually reduce the dose after the condition is controlled and improved.

　　(3) Intravenous administration of aminophylline: The initial dose of aminophylline is 0.25g added to 100ml of glucose solution for intravenous infusion or injection, followed by a continuous intravenous infusion at a rate of 0.5 to 0.8 mg/(kg·h). It is recommended that the total daily dose of aminophylline for adults not exceed 1g. For the elderly, children, patients with liver and kidney dysfunction, hyperthyroidism, or those taking cimetidine, quinolones, or macrolide antibiotics, etc., the blood concentration of aminophylline should be monitored.

　　(4) Anticholinergic drugs: Inhaled anticholinergic drugs, such as ipratropium bromide, can block the postganglionic vagus nerve efferent branches, dilate the bronchi by reducing vagal tone, and their bronchodilatory effect is weaker than that of β2 receptor agonists, and their onset is also slower, but adverse reactions are rare. They can be inhaled together with β2 receptor agonists to enhance and maintain the bronchodilatory effect. They are particularly suitable for patients with nocturnal asthma and excessive sputum. They can be administered using a metered-dose inhaler (MDI), 2 to 3 sprays per time, 3 times a day, or 3 to 4 ml of a solution of 100 to 150 μg/ml added to a nebulizer for continuous nebulization and inhalation.

　　(5) Correction of dehydration: Asthmatic patients in a state of exacerbation often have varying degrees of dehydration due to insufficient water intake, excessive breathing, and sweating, which makes the airway secretions thick, sputum difficult to be expectorated, and affects ventilation. Therefore, fluid replacement helps correct dehydration, dilute sputum, and prevent the formation of mucus plugs. According to the heart and dehydration conditions, generally, 2000 to 3000 ml of intravenous fluid is administered daily.

　　(6) Active correction of acid-base imbalance and electrolyte disturbance: During asthma exacerbation, metabolic acidosis is prone to occur due to reasons such as hypoxia, excessive consumption, and insufficient intake, which can prevent many bronchodilators from fully exerting their effects in an acidic environment, so it is very important to correct acidosis in a timely manner. It is recommended to adjust the pH

　　(7) Prevention and treatment of factors that trigger attacks and complications or associated symptoms: such as timely withdrawal from allergenic environments; for patients with asthma exacerbation caused by infection, active and targeted anti-infection treatment should be carried out, including the use of antibiotics, but the use of antibiotics should not be excessive, unless there is evidence that the patient has bacterial lung infection, otherwise routine use of antibiotics is not advocated. In addition, prevention and treatment of severe asthma complications or associated symptoms should also be carried out, including arrhythmia, intracranial hypertension, cerebral edema, gastrointestinal bleeding, etc.

　　2. Mechanical ventilation treatment for asthma exacerbation

　　The absolute indication for mechanical ventilation in asthmatic patients is sudden cardiac and respiratory arrest, shallow breathing accompanied by loss of consciousness or coma. The general indication is the presence of the aforementioned clinical manifestations, especially progressive increase in PaCO2 with acidosis. Patients with PaCO2 > 45 mmHg and any of the following conditions may consider mechanical ventilation: ① Those who have had respiratory arrest due to severe asthma attacks and have been intubated previously; ② Those with a history of asthma exacerbation, who have developed severe asthma exacerbation again under the use of corticosteroids.

　　(1) Non-invasive positive pressure ventilation (NIPPV): Due to the complications associated with tracheal intubation and the significant increase in airway resistance, severe asthmatics should apply nasal or oral (nasal) face masks for mechanical ventilation as soon as possible. The most ideal approach is to first use a simple breathing bag for artificial assisted respiration with higher oxygen concentration following the patient's breathing, and then switch to ventilator-assisted ventilation after the patient adapts and acidosis is relieved, which is safer. Currently, CPAP combined with pressure support ventilation (PSV), also known as bi-level positive airway pressure (BiPAP), is advocated. The method is: the initial CPAP level is 0, and PSV is 10 cmH2O. After the patient gradually adapts, adjust CPAP to 5 cmH2O, and then gradually increase PSV to achieve maximum tidal volume (VT) ≥ 7 ml/kg, respiratory rate

　　(2) Tracheal intubation for mechanical ventilation: If active treatment is ineffective and the patient develops extreme respiratory muscle fatigue, hypotension, arrhythmia, and abnormal consciousness, artificial airway should be established. We recommend orotracheal intubation for the following reasons: orotracheal intubation is relatively easy and quick, and sedatives can be administered if necessary before operation; orotracheal intubation has a relatively larger caliber, which is beneficial for reducing resistance and facilitating sputum aspiration; in addition, the time for asthma intubation to start the machine is generally short, and there is no need for long-term oral care.

　　To avoid overinflation of the lungs and even cause barotrauma, it is currently generally advocated to use a ventilation strategy with low ventilation, low frequency, and permissible hypercapnia (PHC). Although various literature has not clarified the highest safe PaCO2 and the lowest safe pH range, many reports indicate that a PaCO2 of 80-100mmHg and a pH value of 7.15 are safer than lung injury caused by excessive ventilation pressure. Some scholars also believe that the main focus of attention during PHC should be the pH value, rather than the level of PaCO2. The initial setting mode of the ventilator should be volume control ventilation (VCV), and the parameters can be set as: tidal volume 8-10ml/kg, frequency 10-15 times/min, minute ventilation ≤115ml/kg (8-10L), end-expiratory positive pressure (PEEP) = 0cmH2O, inspiratory-to-expiratory ratio 1:3. By adjusting the inspiratory airflow rate, or using the auto-flow mode, it is possible to maintain a relatively appropriate minute ventilation volume while keeping the inspiratory end plateau as low as possible.

　　(3) Application of sedatives and muscle relaxants: When critically ill asthma patients are using tracheal intubation or tracheotomy for mechanical ventilation, attention should be paid to the application of sedatives and muscle relaxants. Sedatives can give patients a sense of comfort, prevent human-machine conflict, reduce oxygen consumption and the production of carbon dioxide. Commonly used sedatives include diazepam (Valium), midazolam (Midazolam), and propofol (Isoflurane), etc. The commonly used dose of diazepam (Valium) is 10mg intravenous injection; compared with diazepam (Valium), midazolam is a rapid and relatively short-acting benzodiazepine, with less pain and vascular stimulation at the injection site, and can produce a more comfortable hypnotic effect than diazepam, while also producing a significant anti-anxiety effect. The time to reach the central peak effect of midazolam is 2-4 minutes, and its elimination half-life is about 2 hours, and it is usually administered by continuous infusion, with a loading dose of 0.025-0.05mg/kg initially injected intravenously, followed by maintenance at 1.0-2.0μg/(kg·min). Caution should be exercised when using diazepam (Valium) and midazolam in patients with low blood pressure. Propofol (Isoflurane) has a rapid onset, a smooth process, few adverse reactions, and easily adjustable sedative levels. In addition, the drug has a certain bronchodilatory effect. The method of use is continuous infusion at approximately 50μg/(kg·min), which can be adjusted according to the patient's sedative state. Sometimes, even though sedatives have been used, human-machine conflict has not been resolved, causing high airway pressure, even a decrease in PaO2. In this case, muscle relaxants should be applied, but muscle relaxants should not be used for too long, especially in critically ill asthma patients receiving high-dose corticosteroid therapy, to avoid the syndrome of steroidal myorelaxants, which may cause difficulties in ventilator withdrawal.

　　(4) Regarding the withdrawal of mechanical ventilation: Once the airway resistance begins to decrease and PaCO2 returns to normal, sedatives and muscle relaxants have been withdrawn, and symptoms have significantly improved, it should be considered to withdraw the ventilator.

　　3. Unconventional treatment for persistent asthma

　　(1) Intravenous magnesium sulfate infusion: The mechanism of action is not yet clear, and it may be related to the relaxation of bronchial smooth muscle caused by reducing intracellular calcium concentration and its sedative effect. Common methods include:

　　① Intravenous injection: Add 5ml of 25% magnesium sulfate to 40ml of glucose solution for intravenous injection, which takes about 20 minutes to administer.

　　② Intravenous infusion: Add 10ml of 25% magnesium sulfate to 250ml of 5% glucose solution, at a drop rate of 30 to 40 drops/min. When using this drug, attention should be paid to the occurrence of hypotension and bradycardia.

　　(2) Inhalation of helium-oxygen mixture: Helium has a lower density, which can reduce eddies caused by narrowing of small airways and increased secretions on the mucosal surface during asthma, thereby reducing airway resistance, reducing respiratory work, oxygen consumption, and carbon dioxide production; in addition, helium can enhance the diffusion of CO2, thereby increasing the amount of CO2 exhaled per unit time. Multiple studies have reported that in patients with asthma with tracheal intubation or non-tracheal intubation and respiratory failure with hypercapnia, the PaCO2 significantly decreases and pH increases within 20 minutes of inhaling helium-oxygen mixture (helium concentration of 60% to 80%). Close monitoring of oxygen concentration is required during the treatment process.

　　4. Monitoring of asthma status

　　Severe asthma can cause respiratory failure. If not corrected in time, it can also lead to the failure of important organs such as the heart, brain, liver, and kidneys, thereby endangering life. In addition, when performing mechanical ventilation through intubation, one should also be alert to the occurrence of mechanical ventilation-related lung injury. Therefore, in places where conditions permit, the Respiratory Intensive Care Unit (RICU) is the best place for rescue, which concentrates experienced specialist medical staff and related rescue and monitoring equipment. Continuous and close physiological and pathological monitoring should be carried out at the bedside of severe asthma patients, including timely observation of changes in the condition, the function of important organs such as the heart and lungs, and changes in respiratory力学 parameters, etc., and necessary strengthening treatment measures should be taken at any time to ensure and support the patient's life to the maximum extent and quality.

　　II. Prognosis

　　For patients with good physical condition before asthma attack, the prognosis is good, while for patients with pulmonary heart disease, severe lung infection, toxic myocarditis, and severe complications, the prognosis is poor. To reduce serious complications due to delayed treatment, it is recommended that tracheal intubation and mechanical ventilation be performed as soon as possible when medical conditions permit, especially when the patient shows signs of respiratory muscle fatigue and it is estimated that PaCO2 begins to exceed the patient's baseline PaCO2 value. This is to avoid missing the best rescue opportunity.