The prevalence and severity of bronchial asthma (asthma for short) has increased in industrialized countries over the past 20 years. Approximately 300 million people are currently affected, and this number is expected to increase to 400 million by 2025. In the United States, asthma is one of the most common chronic diseases in children. The increased prevalence of asthma is associated with increased individual atopic sensitivity and the increased onset of other allergic diseases such as rhinitis. The perception of a disease can directly influence how it is treated. In the past, bronchospasm was seen as a hallmark of asthma, so treatment focused on relieving bronchospasm. The herb ephedra was used for asthma and allergies about 5000 years ago and was later found to contain the muscle relaxant ephedrine. isoprenaline was used for asthma in the 1940s to activate beta-adrenergic receptors. Later, short-acting β2 agonists (SABA) and long-acting β2 agonists (LABA) were also used to treat bronchospasm. These treatments are very effective for short-term relief of asthma and for making the patient breathe more comfortably and easily. It is now believed that the nature of asthma is a chronic inflammatory disease of the airways and that inflammation is the main pathological change in asthma. Localized chronic persistent inflammatory responses occurring in the central airways lead to irreversible airway remodeling and dysfunction. A complex inflammatory response also occurs in the nasal and sinus and small airways. Clinically, the inflammatory response in the small airways can lead to asthma exacerbations, nocturnal asthma, and significant worsening of exercise-induced asthma. These findings have led to further development of the asthma treatment paradigm, which has begun to target airway inflammation, as well as combination therapy. Short-term formal anti-inflammatory therapy, while able to suppress airway inflammation, is difficult to clear completely. A systemic approach and long-term, even lifelong, maintenance therapy with continuous evaluation, monitoring and adjustment is needed to achieve asthma control, and there is no other way to do so. For many years, the GINA (Global Initiative for the Prevention and Treatment of Bronchial Asthma) guidelines have recommended escalating therapy for chronic persistent asthma, implementing a continuous cycle of long-term asthma management treatment based on the patient’s level of asthma control. The process of adjustment involves many specific components, including initial therapy, step-down therapy, escalation therapy, and treatment of acute exacerbations. In clinical practice, it is also necessary to correctly understand and flexibly apply the guidance of the GINA guidelines according to the specific conditions of the patient and in combination with local medical conditions, to carefully and meticulously start with each case, to gradually accumulate treatment experience, and to find the best time and the best way to adjust the treatment. The initial treatment of asthma is an important part of the overall asthma treatment, and its success or failure is crucial for the next step of treatment, for patients to build confidence in overcoming the disease, to establish trust in their doctors, and to be able to adhere to long-term maintenance treatment. For most newly diagnosed but untreated patients and those who have been on intermittent treatment or have stopped treatment for a long time, initial treatment should start with Tier 2, which is a low to moderate dose of inhaled glucocorticoids (ICS) or leukotriene modifiers alone. In contrast, for patients with significant symptoms, it is recommended to start treatment with Tier 3, which is low-dose ICS plus LABA or other controller medications. In our country, asthma patients often come to the clinic because of significant symptoms, and most of them belong to moderate to severe asthma, and initial treatment needs to start from Tier 3. It should be noted that most experts believe that anti-leukotriene agents alone are less effective than ICS and that a combination with ICS is advisable. Theophylline is weak in both anti-inflammatory and asthma-calming effects and is generally used only as a second-line agent. The overall efficacy of these drugs in combination with ICS is less than that of ICS plus LABA, therefore, it is recommended that initial treatment of most asthmatic patients should begin with ICS/LABA combination therapy when available. For most asthma controller medications, the onset of efficacy and improvement in symptoms can be seen within days, but it takes 3 to 4 months to achieve full efficacy. For patients with more severe disease or those who have been untreated or inadequately treated for a long time, it can take longer to achieve a satisfactory outcome. If complete asthma control persists for 3 months or more, a step-down regimen may be used, and the goal of step-down therapy should be to reduce therapeutic medications while continuing to maintain asthma control. How to choose the best time for step-down treatment? At present, the clinical practice mainly relies on asthma symptoms and lung function and other indicators to determine. There are two main types of step-down therapy: ICS alone and ICS plus other drugs in combination. With complete asthma control, patients on ICS alone can be treated with a 50% dose reduction every 3 months. When the reduction to the lowest dose still maintains asthma control (e.g., budesonide at only 200 μg daily), the dose can be changed from twice daily to once daily administration. If a combination regimen of ICS plus LABA and other controller medications is used, after 3 months of achieving and maintaining asthma control, the dose is first reduced from ICS by 50% every 3 months until the lowest dose of ICS is achieved before other controller medications such as LABA are discontinued and ICS therapy is continued. After 1 year of maintenance of the lowest dose of ICS therapy, if asthma control is maintained without recurrence, discontinuation of the drug for observation may be considered. Step-down from combination therapy also includes a direct transition to ICS alone or a change from combination therapy given twice daily to once daily. For some patients with asthma, the latter two step-down therapies have the potential to result in poor asthma control.
Of course, using combination therapy for as long as possible will help maintain more stable asthma control. It is generally accepted that once asthma is out of control, escalation therapy should be administered immediately. If the patient fails to achieve asthma control with the current regular therapy, escalation therapy should be instituted. Classically, escalation therapy is a step up in treatment level. However, in clinical workup, the patient should be asked about the cause of symptoms, such as a history of significant allergen exposure, weather changes, and other triggers, and the triggers should be removed and fast-acting β2 agonist therapy should be given for observation; if the patient’s condition is stable after such treatment, the control medication can be left unincreased. However, if the patient does not return to the original level after 1 to 2 days of repeated use, additional control medication is required. If the patient continues to have symptoms despite regular use of the control medication, this is also an indication that the medication is inadequate and treatment needs to be escalated as soon as possible. Patients with more financial difficulties may choose a short course of oral low-dose prednisone or methylprednisolone for 5 to 6 days, which may also provide similar results. It is important to note in particular that airway inflammation can spread systemically through the circulation and flow of inflammatory mediators. The effects of asthma are not limited to the lower respiratory tract, but are associated with rhinitis, atopic dermatitis, inflammatory bowel disease, cardiovascular disease, and sleep and cognitive disorders, and the strong epidemiologic, etiologic, and immunologic links with rhinitis in particular illustrate the systemic nature of asthma. If asthma is a systemic disease, then treatment should focus on systemic pathologic changes, which requires targeting common mediators or pathogenic mechanisms that are present only during the active phase of the disease, or both. Among the currently available therapeutic approaches, allergen-specific immunotherapy is a systemic, disease-specific intervention. In children, early application of allergen-specific immunotherapy has been shown to interfere with the natural course of allergic disease and prevent the progression of asthma and airway hyperresponsiveness. Leukotriene receptor antagonists improve the symptoms of asthma, rhinitis and other systemic diseases associated with asthma. Other treatments include receptor blocking molecules and synthetic inhibitors associated with arachidonic acid inflammation. Thus, the treatment of asthma should not only treat inflammation of the central and small airways, but also the causative systemic inflammatory response, concomitant rhinitis, and other comorbidities, and it is critical to identify common disease-specific targets for systemic therapy. Clinical trials are urgently needed to assess the efficacy of new therapeutic approaches in improving lung function and broader systemic pathological changes. New treatment strategies need to be evaluated in clinical trials that are based on both traditional primary treatment endpoints and include systemic treatment effects. In conclusion, a good asthma treatment regimen should be consistent with the severity of asthma and with the current level of asthma control, with the ultimate goal of achieving optimal asthma control with the least amount of medication and at the lowest cost. The treatment of asthma is a dynamic and changing one and the first consideration should be the stability, invariance and continuity of treatment. Secondly, treatment should be adapted to the level of asthma control and reflect the existence of variability in asthma.