Guidelines for the prevention and treatment of bronchial asthma (definition, diagnosis, treatment and management plan of bronchial asthma), Asthma Group of the Chinese Medical Association, Respiratory Diseases Branch
Bronchial asthma (asthma for short) is one of the common chronic respiratory diseases, and its prevalence has been increasing globally year by year in recent years. Many studies have shown that standardized diagnosis and treatment, especially long-term management, play an important role in improving the control of asthma and improving the quality of life of patients. This “guideline” is based on the “Bronchial Asthma Prevention and Treatment Guidelines” revised in 2003 in China, with reference to the 2006 edition of the Global Initiative for Asthma Prevention and Treatment (GINA), and revised in light of the results of evidence-based medical research at home and abroad in recent years, to provide a guiding document for the prevention and treatment of asthma in China. Wang Haifeng, Department of Pulmonary Diseases, The First Affiliated Hospital of Henan College of Traditional Chinese Medicine
I. Definition
Asthma is a chronic inflammatory disease of the airways involving multiple cells including inflammatory and structural cells of the airways (such as eosinophils, mast cells, T lymphocytes, neutrophils, smooth muscle cells, airway epithelial cells, etc.) and cellular components (cellular elements). This chronic inflammation leads to airway hyperresponsiveness, usually with widespread and variable reversible airflow limitation, and causes recurrent episodes of wheezing, shortness of breath, chest tightness, or cough, often exacerbated by attacks at night and/or early in the morning, which may resolve spontaneously or with treatment in most patients.
The risk factors for the development of asthma include both host factors (genetic factors) and environmental factors.
Diagnosis
(A) Diagnostic criteria
1. Recurrent attacks of wheezing, shortness of breath, chest tightness or cough are mostly associated with exposure to allergens, cold air, physical and chemical stimuli, as well as viral upper respiratory tract infections and exercise.
2.Dispersive or diffuse, expiratory phase dominated croup can be heard in both lungs during the attack, with prolonged expiratory phase.
3.The above symptoms and signs may be relieved by treatment or may resolve on their own.
4.Except wheezing, shortness of breath, chest tightness and cough caused by other diseases.
5.In case of atypical clinical manifestations (such as no obvious wheezing or signs), at least 1 of the following tests should be positive: (1) positive bronchial excitation test or exercise excitation test; (2) positive bronchial diastolic test with FEV1 increase ≥12 % and absolute FEV1 increase ≥200 ml; (3) peak expiratory flow (PEF) intra-day (or 2 weeks) variability ≥20 %.
Those who meet 1 to 4 or 4 or 5 can be diagnosed as asthma.
(II) Staging
According to the clinical manifestations asthma can be divided into acute exacerbation, chronic persistent and clinical remission. The chronic persistent phase refers to the symptoms (wheezing, shortness of breath, chest tightness, cough, etc.) appearing at different frequencies and/or to different degrees every week; the clinical remission phase refers to the disappearance of symptoms and signs with or without treatment, and the return of lung function to the level before the acute exacerbation, which is maintained for more than 3 months.
(iii) Grading
1.Grading of disease severity: It is mainly used to judge the severity before treatment or at the time of initial treatment, and has its application value more in clinical research.
2.Grading of control level: This grading method is more easily grasped by clinicians and helps to guide clinical treatment to achieve better asthma control. Grading of control level.
3.Grading in acute asthma attack: acute asthma attack refers to the sudden onset of wheezing, shortness of breath, cough and chest tightness, or a sharp aggravation of the original symptoms, often with dyspnea, characterized by reduced expiratory flow, often triggered by exposure to allergens, irritants or respiratory tract infections. The degree of severity varies, and the exacerbation can occur within hours or days, or occasionally within minutes, so the condition should be properly evaluated in order to provide timely and effective emergency treatment. The severity of an acute asthma attack is graded.
(iv) Related diagnostic tests
Pulmonary function measurements are useful in confirming the diagnosis of asthma and are an important basis for assessing the degree of asthma control. For patients with asthma symptoms but normal lung function, measurement of airway responsiveness and PEF intra-day variability can help confirm the diagnosis of asthma. Eosinophil or neutrophil counts in sputum can assess airway inflammation associated with asthma. Exhaled breath components such as NO partial pressure (FeNO) can also be used as a noninvasive marker of airway inflammation in the setting of asthma. Sputum eosinophil and FeNo tests are useful in selecting the best asthma treatment regimen. Allergen skin test or serum specific IgE assay can be used to confirm the allergic status of asthmatic patients to help understand the risk factors contributing to the onset and exacerbation of individual asthma, and also to help determine the specific immunotherapy regimen.
III. Introduction of commonly used drugs
The drugs used to treat asthma can be divided into control drugs and relief drugs. (1) Control medications: These are medications that require long-term daily use. These drugs mainly maintain clinical control of asthma through anti-inflammatory effects, which include inhaled glucocorticoids (referred to as hormones) systemic hormones, leukotriene modulators, long-acting β2-agonists (LABA, which must be combined with inhaled hormones), extended-release theophylline, sodium cromoglycate, anti-IgE antibodies and other drugs that help to reduce the dose of systemic hormones, etc.; (2) Palliative drugs: are drugs that are used on an as-needed basis. These drugs relieve asthma symptoms by rapidly relieving bronchospasm, and include fast-acting inhaled β2-agonists, systemic hormones, inhaled anticholinergic drugs, short-acting theophylline and short-acting oral β2-agonists.
(i) Hormones
Hormone is the most effective drug to control airway inflammation. The routes of administration include inhalation, oral and intravenous application. Inhalation is the preferred route.
1.Inhalation administration: Inhaled hormones have strong local anti-inflammatory effects; administered through the inhalation process, the drug acts directly on the respiratory tract and requires a small dose. Most of the drugs entering the blood through the digestive and respiratory tracts are inactivated by the liver, so there are fewer systemic adverse reactions. The results of the study prove that inhaled hormones can effectively reduce asthma symptoms, improve quality of life, improve lung function, reduce airway hyperresponsiveness, control airway inflammation, reduce the frequency and severity of asthma attacks, and reduce morbidity and mortality. When different inhalation devices are used, they may produce different therapeutic effects. Most adults with asthma have good control of their asthma with small doses of inhaled hormones. Excessive increases in inhaled hormone doses have less benefit and more adverse effects on asthma control. Because smoking can reduce the effectiveness of hormones, patients who smoke must quit smoking and be given higher doses of inhaled hormones. There is a very clear relationship between the dose of inhaled hormone and the prevention of severe acute asthma attacks, so high doses of inhaled hormone over a long period of time are beneficial in patients with severe asthma. Local adverse effects of inhaled hormones in the oropharynx include hoarseness, pharyngeal discomfort, and Candida infection. The above-mentioned adverse effects can be reduced by rinsing the oropharynx with water promptly after inhalation, choosing dry powder inhalers or adding a nebulizer. The magnitude of systemic adverse reactions to inhaled hormones is related to the drug dose, bioavailability of the drug, absorption in the intestinal tract, hepatic first-pass metabolism rate and half-life of systemically absorbed drugs. Among the marketed inhaled hormones, fluticasone propionate and budesonide have fewer systemic adverse reactions. There is evidence that adult asthmatics who inhale low to moderate doses of hormones daily do not experience significant systemic adverse effects. Possible systemic adverse effects following long-term high doses of inhaled hormones include skin petechiae, suppression of adrenal function, and decreased bone mineral density. There has been research evidence that inhaled hormones may be associated with the development of cataracts and glaucoma, but there is no evidence from prospective studies of a clear association with the development of posterior subcapsular cataracts. There is no evidence that inhaled hormones can increase the incidence of pulmonary infections (including tuberculosis), so patients with asthma with active tuberculosis may be given inhaled hormone therapy in conjunction with anti-tuberculosis treatment.
Aerosol administration: There are 4 types of inhaled hormones commonly used in clinical practice, see Table 4. including beclomethasone dipropionate, budesonide, and fluticasone propionate. In general, the use of dry powder inhalation devices is more convenient than ordinary quantitative aerosols, and the amount of drug inhaled into the lower respiratory tract is higher.
Solution administration: Budesonide solution is nebulized and inhaled through a jet device powered by compressed air, which does not require high inspiratory cooperation from patients and has a faster onset of action, and is suitable for the treatment of mild to moderate asthma during acute attacks.
Inhaled hormone is the drug of choice for long-term treatment of asthma. Internationally recommended daily dose of inhaled hormone. The dose of inhaled hormone required by asthma patients in China is smaller than the dose recommended in Table 4.
2.Oral administration: It is suitable for patients with moderate asthma exacerbations, chronic persistent asthma who have inhaled high doses of inhaled hormone combination therapy that is ineffective and as sequential therapy after intravenous application of hormone therapy. Generally use hormones with short half-life (such as prednisone, prednisolone or methylprednisolone, etc.). For hormone-dependent asthma, daily or every other day early morning dose administration can be used to reduce the inhibitory effect of exogenous hormones on the hypothalamic-pituitary-adrenal axis. Long-term oral hormone administration can cause osteoporosis, hypertension, diabetes mellitus, suppression of the hypothalamic-pituitary-adrenal axis, obesity, cataracts, glaucoma, skin thinning leading to skin tags and ecchymosis, and muscle weakness. Systemic hormone therapy for asthma with tuberculosis, parasitic infections, osteoporosis, glaucoma, diabetes, severe depression or peptic ulcer should be administered with caution and closely followed. Patients with asthma on long-term or even short-term systemic hormone therapy can be infected with the deadly herpes virus and it is necessary to avoid exposure to the herpes virus in these patients. Although systemic hormones are not a frequently used method of relieving asthma symptoms, they are needed for severe acute asthma because they can prevent worsening of asthma, reduce the chance of emergency room visits or hospitalization for asthma, prevent early relapses, and reduce morbidity and mortality. Recommended dose: Prednisolone 30-50 mg/d for 5-10 d. Specific use depends on the severity of the disease, and discontinuation or dose reduction may be considered when symptoms are relieved or their lung function has reached a personal best. Dexamethasone is not recommended for long-term use because of its large inhibitory effect on the pituitary-adrenal gland.
3.Intravenous administration: In severe acute asthma attacks, hydrocortisone succinate (400-1000mg/d) or methylprednisolone (80-160mg/d) should be given intravenously in a timely manner. For those without hormone dependence, the drug can be stopped within a short period of time (3-5d); for those with hormone dependence, the duration of administration should be extended, and after controlling asthma symptoms, the drug should be changed to oral administration, and the amount of hormone should be gradually reduced.
(ii) β2-agonists
Through the action of β2-receptors on the surface of airway smooth muscle and mast cells and other cell membranes, they can relax airway smooth muscle, reduce the release of mast cell and basophil degranulation and mediators, reduce the permeability of microvessels, and increase the oscillation of airway epithelial cilia to relieve asthma symptoms. There are more such drugs, which can be divided into short-acting (action maintained for 4-6h) and long-acting (maintained for 12h) β2-agonists. The latter can be divided into fast-acting (a few minutes onset) and slow-acting (30min onset) 2, see Table 5.
1. Short-acting β2-agonists (SABA for short): commonly used drugs such as salbutamol and terbutalin.
Inhalation administration: Short-acting β2-agonists available for inhalation include aerosols, dry powders and solutions. These drugs have a strong effect on airway smooth muscle relaxation, usually within a few minutes, and the effect can be maintained for several hours, and are the drugs of choice for relieving mild to moderate acute asthma symptoms. If 100-200 μg salbutamol or 250-500 μg terbutaline is inhaled each time, repeat every 20 min if necessary. 1h after unsatisfactory efficacy should consult a doctor or go to the emergency room. These drugs should be used intermittently as needed and should not be used for a long time or in single doses, nor should they be applied in excess, as they can cause adverse reactions such as skeletal muscle tremor, hypokalemia, and cardiac rhythm disturbances. Pressure-based quantitative hand-controlled aerosol (pMDI) and dry powder inhalation device inhaled short-acting β2-agonists are not indicated for severe asthma attacks; their solutions (e.g., salbutamol, terbutaline, fenoterol and their combination formulations) are indicated for mild to severe asthma attacks via nebulizer pump inhalation.
Oral administration: such as salbutamol, terbutaline, and procarterol tablets, etc., usually take effect 15-30 min after taking the drug, and the effect is maintained for 4-6 h. For example, salbutamol 2-4 mg, terbutaline 1.25-2.5 mg, 3 times a day; procarterol 25-50 μg, 2 times a day. Although more convenient to use, adverse effects such as palpitations and skeletal muscle tremors are more pronounced than when administered by inhalation. The duration of maintenance of the asthma-relieving effect of extended-release and controlled-release dosage forms can be 8-12 h. The effect of bambuterol, the precursor drug of terbutaline, can be maintained for 24 h. The number of doses can be reduced, and it is suitable for the prevention and treatment of patients with nocturnal asthma. Long-term, single application of β2-agonists can cause downward regulation of cell membrane β2-receptors, manifesting as a clinical drug resistance phenomenon, and should therefore be avoided.
Injectable administration: Although the effect of asthma is more rapid, it is less used in China because of the high incidence of systemic adverse reactions.
Patch administration: It is a transdermal absorption dosage form. The existing products include tulobuterol, which is divided into 3 doses of 0.5mg, 1mg and 2mg. Since the crystalline storage system is used to control the release of the drug, the drug is absorbed through the skin, so it can reduce the systemic adverse reactions, only need to be applied once a day, the effect can be maintained for 24 h. Effective for the prevention of morning descent, the use of simple methods.
2. LABA: These β2-agonists have a long side chain in the molecular structure, and the effect of diastolic bronchial smooth muscle can be maintained for more than 12h. At present, there are 2 types of inhaled LABA in clinical use in China. Salmeterol: administered by aerosol or disc device, the effect starts 30min after administration, and the effect of asthma can be maintained for more than 12h. The recommended dose is 50μg, 2 inhalations per day. Formoterol: administered by inhalation device, with onset of action 3~5min after administration, and the asthmatic effect is maintained for more than 8~12h. Asthma effect has a certain dose dependence, the recommended dose is 4.5-9μg, 2 inhalations per day. Inhaled LABA is suitable for the prevention and treatment of asthma (especially nocturnal asthma and exercise-induced asthma). Formoterol can be used on an as-needed basis for the treatment of acute asthma attacks due to its rapid onset of action.
In recent years, a combination of inhaled hormone and LABA has been recommended for the treatment of asthma. The two have synergistic anti-inflammatory and asthma-calming effects, which are equivalent to (or better than) those achieved with doubled doses of inhaled hormones, and may increase patient compliance and reduce adverse effects associated with higher doses of inhaled hormones, especially for the long-term treatment of patients with moderate to severe persistent asthma. Long-term use of LABA alone is not recommended and should be used in combination with inhaled hormones under medical supervision.
(iii) Leukotriene modulators
They include cysteinyl leukotriene receptor antagonists and 5-lipoxygenase inhibitors. Apart from inhaled hormones, they are the only long-acting control agents that can be applied alone, and can be used as alternative treatment drugs for mild asthma and combined treatment drugs for moderate to severe asthma. Currently, cysteinyl leukotriene receptor antagonists are mainly used in China to inhibit the asthmogenic and inflammatory effects of cysteinyl leukotrienes released from mast cells and eosinophils by antagonizing leukotriene receptors on the surface of airway smooth muscle and other cells, producing mild bronchodilation and reducing allergens, exercise and sulfur dioxide (SO2)-induced bronchospasm, and having some degree of anti-inflammatory effects . It can reduce asthma symptoms, improve lung function, and reduce the deterioration of asthma. However, it is not as effective as inhaled hormones and cannot replace them. As one of the drugs in combination therapy, it can reduce the daily dose of inhaled hormone in patients with moderate to severe asthma and improve the clinical efficacy of inhaled hormone therapy. The efficacy of combining this product with inhaled hormone is slightly less than that of combining inhaled LABA with inhaled hormone. However, this product is convenient to take. It is especially suitable for the treatment of patients with aspirin asthma, exercising asthma and asthma with allergic rhinitis. This product is relatively safe to use. Although Churg-Strauss syndrome has been reported in patients treated with these drugs, the causal relationship with leukotriene modulators has not been established and may be related to a reduction in the dose of systemic hormones. 5-Lipoxygenase inhibitor zileuton may cause liver damage and liver function needs to be monitored. It is usually administered orally. The leukotriene receptor antagonist zalutostat 20 mg twice daily, montelukast 10 mg once daily, and isatinostat 10 mg twice daily.
(iv) Theophylline
It has the effect of diastolic bronchial smooth muscle, and has the effect of cardiac, diuretic, dilating coronary artery, excitation of respiratory center and respiratory muscle. Some research data show that low concentration theophylline has anti-inflammatory and immunomodulatory effects. As a symptom reliever, although theophylline is still used intravenously in the treatment of severe asthma in clinical practice, short-acting theophylline for asthma exacerbation or worsening is controversial because it has no advantage in diastolic bronchial, compared with rapid beta2-agonists used in adequate doses, but it may improve respiratory drive. Short-acting theophylline is not recommended for patients already on long-term extended-release theophylline, except when that patient has a low serum theophylline concentration or when serum theophylline concentration monitoring is available.
Oral administration: Includes aminophylline and controlled (extended) release theophylline. For mild to moderate asthma attacks and maintenance therapy. The general dose is 6-10mg/kg/day, and the oral controlled (extended) release theophylline has a stable blood concentration around the clock, and the asthma calming effect can be maintained for 12-24h, especially for the control of asthma symptoms at night. Combined application of theophylline, hormone and anticholinergic drugs has synergistic effect. However, when this product is combined with β2-agonist, it is easy to have increased heart rate and arrhythmia, so it should be used with caution and the dose should be reduced appropriately.
Intravenous administration: Aminophylline is added to glucose solution and injected slowly intravenously (injection rate should not exceed 0.25mg?kg-1?min-1) or intravenously by drip, for patients with acute asthma attack who have not used theophylline drugs in the last 24h. Because of the narrow “therapeutic window” of theophylline and the large individual differences in theophylline metabolism, it can cause arrhythmia, blood pressure drop, and even death, so the blood concentration should be monitored and adjusted in time if possible. The concentration and titration rate should be adjusted in time. There are many factors affecting theophylline metabolism, such as febrile diseases, pregnancy, anti-tuberculosis treatment can reduce the blood concentration of theophylline; while liver disorders, congestive heart failure, and the combination of metformin or quinolones, macrolides and other drugs can affect theophylline metabolism and slow down its excretion, increasing the toxic effects of theophylline, which should attract the attention of clinicians. This should be taken seriously by the clinician and the dose should be adjusted as appropriate. The effect of doxorubicin is the same as that of aminophylline, but the adverse effects are milder. The effect of dihydroxypropyl theophylline is weaker and has fewer adverse reactions.
(E) Anticholinergic drugs
Inhaled anticholinergic drugs such as ipratropium bromide, oxytropium bromide and tiotropium bromide can block the postganglionic vagus nerve efferent branch, which can diastole the bronchi by decreasing the vagal tone. The effect of bronchodilator is weaker than that of β2-agonist and the onset of action is slower, but the long-term application is less likely to produce drug resistance, and the efficacy for the elderly is no less than that for the young.
The product is available in aerosol and nebulized solution forms. The common dose of ipratropium bromide aerosol by pMDI inhalation is 20-40μg, 3-4 times a day; the common dose of ipratropium bromide solution by nebulizer pump inhalation is 50-125μg, 3-4 times a day. It is a new long-acting anticholinergic drug with selective inhibitory effect on M1 and M3 receptors, and only needs to be administered by inhalation once a day. It has synergistic and complementary effects in combination with β2-agonists. It is suitable for elderly asthmatic patients with a history of smoking, but should be used with caution in women in early pregnancy and in patients with glaucoma or prostatic hypertrophy. Although ipratropium bromide has been used in some patients with asthma due to intolerance of β2-agonists, there is no evidence to date that it is significantly effective in the long-term management of asthma.
(vi) Anti-IgE therapy
Anti-IgE monoclonal antibody (omalizumab) can be used in asthma patients with elevated serum IgE levels. Currently it is mainly used in patients with severe asthma whose symptoms are not controlled after combined treatment with inhaled glucocorticoids and LABA. No significant adverse effects of anti-IgE therapy have been found in treatment studies of asthma patients aged 11 to 50 years, but because the clinical use of this drug is still short, its long-term efficacy and safety need further observation. The high price also limits its clinical application.
(vii) Allergen-specific immunotherapy (SIT)
It can reduce asthma symptoms and airway hyperresponsiveness by subcutaneous administration of common inhaled allergen extracts (e.g., dust mite, cat hair, ragweed, etc.) and is indicated for patients with asthma in which allergens are clearly identified but difficult to avoid. Its long-term efficacy and safety remain to be further studied and evaluated. The standardization of allergen preparation also needs to be enhanced. The application of this therapy in asthma patients should be strictly under the guidance of a physician. Sublingual administration of allergen immunotherapy has been tried, and SIT should be considered in cases where strict environmental isolation and pharmacological interventions (including inhaled hormones) are not effective. There are no studies comparing the difference in efficacy between this and pharmacological interventions. There is no evidence at this time to support the value of immunotherapy with compound allergens.
(viii) Other drugs for asthma
1) Antihistamines: Oral second-generation antihistamines (H1 receptor antagonists) such as ketotifen, loratadine, acepromazole, azelastine, and terfenadine have anti-allergic effects and have a weaker role in asthma treatment. They can be used in the treatment of patients with asthma with allergic rhinitis. The main adverse effect of these drugs is drowsiness. Astemizole and terfenadine can cause serious cardiovascular adverse reactions and should be used with caution.
2. Other oral anti-allergic drugs: such as tranilast and repirinast can be used in the treatment of mild to moderate asthma. The main adverse effect is drowsiness.
3. Drugs that may reduce the dose of oral glucocorticoids: including oral immunomodulators (methotrexate, cyclosporine, gold preparations, etc.), certain macrolide antibiotics and intravenous immunoglobulins. The efficacy of these drugs has yet to be further studied.
4. Chinese herbal medicine: the use of evidence-based treatment can help the treatment of asthma in chronic remission. It is necessary to carry out a multicenter randomized double-blind clinical study on Chinese medicines or formulas with more definite clinical efficacy.
IV. Treatment
Asthma is a chronic disease that has a significant impact on patients, their families and society. Airway inflammation is a common feature of almost all types of asthma and underlies the clinical symptoms and airway hyperresponsiveness. Airway inflammation is present in all periods of asthma. Although there is no cure for asthma, standardized treatment focused on suppressing inflammation can control the clinical symptoms of asthma. An international study has shown asthma control rates approaching 80% with fixed-dose escalation and maintenance treatment with fluticasone/salmeterol. Although the cost of controlling asthma may seem high from the patient’s and society’s point of view, the cost of incorrectly treating asthma can be even higher.
(i) Determination of long-term treatment regimen
The treatment of asthma should be based on the severity of the patient’s condition and the appropriate treatment regimen should be selected according to his or her level of control category. The choice of asthma medication should take into account both the efficacy of the medication and its safety, as well as the actual situation of the patient, such as economic income and local medical resources. An asthma control plan should be developed for each initial patient, with regular follow-up and monitoring to improve patient compliance and timely revision of the treatment plan according to changes in the patient’s condition. The long-term treatment plan for asthma patients is divided into 5 levels.
Patients with primary asthma who have not been treated in the past can choose the level 2 treatment plan, and patients with asthma who have obvious symptoms should choose the level 3 treatment plan directly. Different asthma control medications are available in the treatment regimens from level 2 to level 5. And in each level, relief medications should be used as needed to provide rapid relief of asthma symptoms. When combined therapy with a single inhalation device containing formoterol and budesonide is used, it can be applied as a control and relief medication.
If asthma control is not achieved with this tiered regimen, the regimen should be escalated until asthma control is achieved. When asthma is controlled and maintained for at least 3 months, the regimen may be considered for downgrading. Suggested reduction regimens: (1) reduce the inhaled hormone dose by 50% for patients on moderate to high dose inhaled hormones alone; (2) switch to once daily dosing for patients on low dose hormones alone; (3) reduce the inhaled hormone dose by approximately 50% for patients on combined inhaled hormones and LABA and still continue to use the LABA combination therapy. When low-dose combination therapy is reached, there is an option to change to once-daily combination therapy or to discontinue LABA and treat with inhaled hormone alone. If the patient achieves asthma control with the lowest dose of control medication for 1 year and no more asthma symptoms occur, discontinuation of medication may be considered. The above dose reduction regimen is subject to further validation. Usually, patients return 2 to 4 weeks after the initial diagnosis and are followed up every 1 to 3 months thereafter. Asthma attacks should be seen promptly when they occur, and return visits should be made within 2 weeks to 1 month after the asthma attack.
For asthma patients in poor areas or low economic income in China, depending on the severity of their disease, the recommended medications for long-term asthma control are.
(1) inhaled low-dose hormones; (2) oral extended-release theophylline; (3) inhaled hormones combined with oral extended-release theophylline; and (4) oral hormones and extended-release theophylline. The efficacy and safety of these treatment options need further clinical studies, especially to monitor the possible systemic adverse effects caused by long-term oral hormone administration.
(ii) Management of acute exacerbations
The treatment of an acute asthma attack depends on the severity of the attack and the response to treatment. The aim of treatment is to relieve symptoms, airflow limitation and hypoxemia as soon as possible, and also to develop a long-term treatment plan to prevent further acute attacks.
Patients with high risk factors for asthma-related mortality need to be given high priority and these patients should be seen at the earliest possible time by a health care provider. Patients at high risk include (1) a history of near-fatal asthma with tracheal intubation and mechanical ventilation; (2) hospitalization or emergency room visits for asthma in the past 1 year; (3) current or recently discontinued use of oral hormones; (4) not currently using inhaled hormones; and (5) over-reliance on rapid-acting β2-agonists, particularly with more than 1 salbutamol ( or equivalent) more than 1 dose per month; (6) psychological disorders or psychosocial problems, including sedation use; (6) history of noncompliance with asthma treatment plans.
Mild and some moderate acute exacerbations can be treated in the home or in the community. Treatment at home or in the community is primarily with repeated inhalation of a rapid-acting β2-agonist, with 2 to 4 sprays every 20 min in the first hour. Subsequently, depending on the response to treatment, mild acute attacks can be adjusted to 2-4 sprays every 3-4 h, and moderate acute attacks to 6-10 sprays every 1 to 2 h. If the response to inhaled β2-agonists is good (significant relief of dyspnea, PEF >80% of expected value or personal best, and efficacy maintained for 3 to 4 h), no other medication is usually required. If the response to therapy is incomplete, especially in acute attacks occurring on the basis of controlled therapy, oral hormones (prednisolone 0.5-1 mg/kg or equivalent doses of other hormones) should be administered as early as possible, and hospital visits should be made if necessary.
Some moderate and all severe acute attacks should be treated in the emergency room or hospital. In addition to oxygen therapy, a rapid-acting β2-agonist should be repeated, either administered through a pressure-dosing aerosol reservoir or through a jet nebulization device. Continuous nebulized dosing is recommended for initial treatment, followed by intermittent dosing (every 4 h) as needed. There is no evidence to support the routine intravenous use of β2 agonists. Better bronchodilatory effects are achieved with the combination of β2-agonists and anticholinergic agents (e.g. ipratropium bromide). The bronchodilatory effect of theophylline is weaker than that of SABA and should be used with caution due to greater adverse effects. Theophylline blood levels should be monitored as much as possible in patients taking theophylline extended-release preparations intravenously. Systemic hormones should be used as early as possible in acute attacks of moderate to severe asthma, especially in patients with incomplete response to initial treatment with rapid-acting β2-agonists or whose efficacy cannot be maintained, and in patients who still have acute attacks on the basis of oral hormones. Oral hormones are comparable in efficacy to intravenous administration and have fewer side effects. Recommended Use: Prednisolone 30-50 mg or equivalent other hormone, given as a single daily dose. In severe acute attacks or when oral hormones are not tolerated, intravenous injections or drips, such as methylprednisolone 80-160 mg or hydrocortisone 400-1000 mg given in divided doses, may be used. Dexamethasone is generally not recommended because of its long half-life and strong inhibitory effect on adrenal cortical function. Sequential therapy with intravenous and oral administration has the potential to reduce hormone dosage and adverse effects, such as intravenous hormones for 2-3 d followed by oral hormones for 3-5 d. The routine use of magnesium preparations is not recommended for severe acute exacerbations (FEV1 25%-30%) or for those who do not respond well to initial therapy. The process of in-hospital treatment of acute asthma exacerbations is shown in Figure 2.
Severe and critical acute asthma attacks without improvement in clinical symptoms and pulmonary function or even continued deterioration after the above drug therapy should be promptly treated with mechanical ventilation, the indications of which include: altered consciousness, respiratory muscle fatigue, PaCO2 ≥ 45 mmHg (1 mmHg = 0.133 kPa), etc. Non-invasive mechanical ventilation via nasal (face) mask can be used first, and if there is no effect, early mechanical ventilation by tracheal intubation can be performed. Mechanical ventilation for acute asthma exacerbation requires high inspiratory pressure and can be treated with appropriate levels of positive end-expiratory pressure (PEEP). If excessive peak and plateau airway pressures are required to maintain normal ventilation volume, a permissive hypercapnic ventilation strategy may be tried to reduce ventilator-associated lung injury.
Those with significant symptomatic improvement on initial treatment and PEF or FEV1 % of expected value recovered to or above 60% of personal best may go home to continue treatment, those with PEF or FEV1 of 40% to 60% should return to home or community under supervision to continue treatment, those with PEF or FEV1 <25% before treatment or <40% after treatment should be admitted to hospital. At discharge or at recent follow-up, a detailed action plan should be developed for the patient, auditing the patient for proper use of medications, inhalation devices, and peak flow meters, finding triggers for acute exacerbations and developing measures to avoid exposure, and adjusting controlled treatment regimens. Severe acute asthma exacerbations imply failure of asthma management, and these patients should be given close monitoring, long-term follow-up, and long-term asthma education.
Most acute asthma attacks are not caused by bacterial infection and the indications for the use of antimicrobial drugs should be strictly controlled unless there is evidence of bacterial infection or it is a severe or critical acute asthma attack.
V. Asthma management
Although asthma is not yet curable, asthma control can usually be achieved through effective asthma management. The goals of successful asthma management are to (1) achieve and maintain symptom control; (2) maintain normal activity, including exercise capacity; (3) maintain lung function levels as close to normal as possible; (4) prevent acute exacerbations of asthma; (5) avoid adverse effects due to asthma medication; and (6) prevent death due to asthma.
Establishing a partnership between doctor and patient is the primary measure to achieve effective asthma management. The goal is to guide patients to self-manage, reach consensus on treatment goals, and develop an individualized written management plan that includes self-monitoring, periodic assessment of treatment regimens and asthma control levels, and timely adjustment of therapy for control levels to achieve and maintain asthma control if symptoms and/or PEF suggest changes in asthma control levels. Of these, asthma education for the patient is the most essential component.
Asthma education must be an integral part of all mutually supportive relationships between physicians and patients. Continuing education for hospitals, communities, specialists, general practitioners, and other medical staff is needed to improve communication skills with patients and educate patients and families through training in asthma management. The goals of patient education are to increase understanding, enhance skills, increase satisfaction, increase self-confidence, increase adherence and self-management skills, and improve health reduce health care resource use.
1, education content: (1) through long-term standardized treatment can effectively control asthma; (2) avoid triggers, triggering factors methods; (3) the nature of asthma, pathogenesis; (4) long-term asthma treatment methods; (5) drug inhalation devices and use; (6) self-monitoring: how to measure, record, and explain the contents of asthma diary: symptom scores, application of drugs, PEF, asthma control test ( ACT) changes; (7) asthma aura, asthma attack signs and corresponding self-treatment methods, how and when to seek medical attention; (8) knowledge of asthma control drugs; (9) how to determine the level of control and choose treatment based on self-monitoring results; (10) the role of psychological factors in the development of asthma.
2. Education methods: (1) initial education: the most important basic and initiation education, individualized education at the beginning of the doctor-patient partnership, which should first provide information about the patient’s diagnosis, understand the patient’s expectations and achievable level of asthma treatment, and educate at least the contents of (1) to (6) above, schedule follow-up appointments and provide educational materials; (2) follow-up education and evaluation: a long-term management method. Follow-up visits should be conducted to answer patient questions and assess initial efficacy. Regular evaluation, correction of inhalation techniques and monitoring techniques, evaluation of written management plans, understanding the degree of implementation, and repeated provision of updated educational materials; (3) centralized education: regular asthma schools, study classes, clubs, and fellowships for large classes and centralized question and answer sessions; (4) self-study education: through reading newspapers, magazines, articles, watching TV programs, and listening to the radio; (5) internet education: through the China Asthma Alliance Network (www.chinaasthma.net), Global Asthma Prevention and Control Initiative Network GINA (www.ginasthma.org), or interactive multimedia technology to disseminate prevention and control information; (6) Mutual learning: holding patient experience exchange meetings on asthma prevention and control; (7) Targeted education: cooperating with community health units to carry out community, patient and public education in a planned manner (8) mobilize all levels of society to promote and popularize asthma prevention and control.
Asthma education is a long-term, continuous process that requires frequent education, repeated reinforcement, constant updating, and persistence.
(i) Identify and reduce risk factor exposure.
Although pharmacological interventions applied to patients with diagnosed asthma are very effective in controlling symptoms and improving quality of life, exposure to risk factors should be avoided or reduced as much as possible to prevent asthma onset and exacerbation of symptoms.
Many risk factors can cause acute exacerbations of asthma and are referred to as “triggers,” including allergens, viral infections, pollutants, tobacco smoke, and medications. Reducing a patient’s exposure to risk factors can improve asthma control and reduce the need for therapeutic medications. Early identification of occupational allergens and prevention of further exposure are important components of occupational asthma management.
(ii) Assessment, treatment and monitoring
The goal of asthma treatment is to achieve and maintain asthma control. Most patients or family members are able to achieve this goal through pharmacologic intervention strategies developed in collaboration with the physician and patient. Patient initiation of therapy and adjustment is based on the patient’s level of asthma control and includes a continuous cycle of assessing asthma control, treating to achieve control, and monitoring to maintain control, as shown in Figure 3.
Some clinically validated asthma control assessment tools such as the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), and Asthma Treatment Assessment Questionnaire (ATAQ) can also be used to assess the level of asthma control. The ACT has been validated in multiple centers in China and is easy to learn, easy to use, and suitable for the Chinese context, and is based on a composite of five questions about asthma symptoms and quality of life, with 25 being control, 20-24 being partial control, and 19 or less being no control, and does not require patients to have their lung function checked. These questionnaires are not only used in clinical studies, but also in clinical work to assess the level of asthma control of patients and to maintain asthma control through long-term continuous testing. They are particularly suitable for promotion in primary care as a supplement to lung function, both for physicians and for patients to self-assess asthma control, which can be completed by patients at home or in the hospital, before or during visits to the clinic. These questionnaires help to improve the assessment of asthma control and improve two-way communication between physicians and patients, providing objective indicators that can be used repeatedly for long-term monitoring.
It is important to use methods of assessing asthma control during long-term asthma management treatment, with continuous monitoring providing repeatable objective indicators to adjust treatment and determine the minimum level of treatment needed to maintain asthma control in order to maintain asthma control and reduce healthcare costs.