Bronchial asthma (asthma for short) is a common chronic lung disease in pediatric patients, and early diagnosis and standardized treatment are critical to the prognosis. Since its establishment in 1993, the Global Initiative for Asthma (GINA) committee has been committed to promoting asthma prevention and treatment strategies worldwide.Since its first publication in 1995, the GINA protocol has been continuously revised and updated to reflect the latest advances in this field, thus maintaining the advanced and authoritative nature of the guidelines.In May 2014, the GINA committee, based on recent research data and other The guidelines were revised again, with more updates in the definition of asthma, diagnosis, assessment, treatment and management of childhood asthma, and more diagrams and flowcharts compared to the previous version. In this article, we will interpret the updated parts of GINA 2014 edition related to childhood asthma, so that readers can understand the changes of the new edition of the guidelines in depth and thus be beneficial to the prevention and treatment of childhood asthma.
1. Definition of asthma
The GINA 2014 edition provides an important update to the definition of asthma, defining asthma as “a heterogeneous disease characterized by chronic airway inflammation; a history of respiratory symptoms of wheezing, shortness of breath, chest tightness, and cough, accompanied by variable expiratory airflow limitation, with respiratory symptoms and intensity varying over time”. The previous guidelines emphasized that “asthma is a chronic airway inflammation involving multiple cells and cellular components”, while the new guidelines emphasize that asthma is a “heterogeneous disease characterized by chronic airway inflammation”. The author understands the definition of asthma as “heterogeneous” as a reminder of the complexity and diversity of asthma disease, which is the result of individual differences and the combined influence of multiple factors, such as genetic, environmental and host factors. The new guidelines also emphasize “variable respiratory symptoms” and “variable expiratory airflow limitation” in the definition, which will be used in the diagnosis, evaluation and management of asthma in the future.
2. Asthma typing
The 2012 edition of GINA classified asthma into eosinophilic and non-eosinophilic phenotypes based on airway inflammation, but these two phenotypes are difficult to identify in clinical practice and therefore difficult to guide treatment. The new edition of the guidelines, however, suggests that in some severe asthma, phenotypes may be able to guide treatment. The following commonly used phenotypes are recommended: (1) Allergic asthma: the most easily identified asthma phenotype, usually starting in childhood with a personal or family history of allergic diseases, such as eczema, allergic rhinitis, food or drug allergy. Induced sputum examination in this group of patients before treatment often suggests eosinophilic airway inflammation. This group of patients responds better to inhaled glucocorticoid (ICS) therapy. (2) Non-allergic asthma: This refers to some asthma that occurs in adults and is not related to allergies. Induced sputum examination may have neutrophils, eosinophils, or only some inflammatory cells, and responds poorly to ICS therapy. (3) Late-onset asthma: Some adults, especially adult women, have their first asthma attack in adulthood. This group of patients has no allergic manifestations and requires high-dose ICS therapy or ICS is relatively refractory. (4) Asthma with fixed airflow limitation: Some patients with long-term asthma develop fixed airflow limitation, which may be associated with airway remodeling. (5) Asthma with obesity: some obese asthma patients with significant respiratory symptoms but little eosinophilic airway inflammation.
3.Diagnosis of asthma
The diagnosis of asthma is still a difficult issue, and the GINA 2014 edition divides the diagnosis of asthma into two parts according to age, 5 years and younger and 6 years and older.
(1) About the diagnosis of asthma in children aged 6 years and above
For the diagnosis of asthma in children aged 6 years and above, a flow chart for the initial diagnosis of asthma is given, which, in the author’s opinion, is helpful. Two points are emphasized in the diagnosis, namely “variable respiratory symptoms” and “variable expiratory airflow limitation”, which are closely integrated with the definition of asthma.
a. Symptoms should be consistent with the asthma symptom pattern, i.e., a history of variable respiratory symptoms, including changes over time and in intensity.
b. Variable expiratory airflow limitation is determined mainly by the response of pulmonary function indicators (FEV1, PEF, etc.) to bronchodilators and bronchial excitation tests. It is also proposed that daytime PEF variability >13% in children can be used as one of the indicators for the diagnosis of variable airflow limitation. A positive bronchial excitation test does not confirm the diagnosis of asthma, as it can also be seen in allergic rhinitis, cystic fibrosis, BPD, and other diseases.
(2) Diagnosis of asthma in children aged 5 years and younger
The diagnosis of asthma in children under 5 years of age is still difficult, and it is a difficult point in the diagnosis of childhood asthma. The new edition of the guideline includes the diagnosis and management of asthma in children under 5 years of age as a separate section, which is the first update of the “Diagnosis and management of asthma in children 5 years of age and younger” first introduced in the 2009 edition, with emphasis on the differentiation and diagnosis of asthma in children and viral-induced wheezing, so as to develop long-term management plans. Since wheezing is the most common respiratory symptom in children under 5 years of age, and is somewhat heterogeneous and mostly associated with viral infections, it remains difficult to distinguish wheezing after viral infections from first or recurrent asthma attacks. Based on the 2009 edition, the new edition of the guideline proposes a symptom pattern that supports the diagnosis of asthma, which is not simultaneous but changes over time and remains to be observed dynamically. The diagnosis of virus-induced wheezing is preferred for those with symptoms (cough, wheezing, heavy breathing sounds) for less than 10 d after viral infection, with 2-3 episodes in 1 year and no symptoms between episodes. In contrast, those with symptoms >10 d, >3 episodes and/or nocturnal exacerbations in 1 year, symptoms after exercise or laughing between episodes, and an atopic physique or family history of asthma were more inclined to the diagnosis of asthma. On the basis of this symptom pattern, the diagnosis can be further clarified based on the response to anti-asthma treatment. The previous guidelines had less description of pulmonary function tests in children under 5 years of age. The new version of the guidelines specifically states that for children aged 4 to 5 years, pulmonary function tests can be completed under the guidance of an experienced technician to determine airflow limitation, emphasizing the importance of pulmonary function tests in the diagnosis of asthma in children. In addition, for children aged 1 to 5 years, exhaled breath nitric oxide (FeNO) testing under feasible tidal breathing and studies have shown that preschool children with recurrent wheezing and cough symptoms can predict school-age asthma if FeNO increases persist for more than 4 weeks after upper respiratory tract infection.
(3) On differential diagnosis
The differential diagnosis was subdivided again into age groups of 0 to 5 years, 6 to 11 years, and 12 years and above. For the differential diagnosis of asthma in children aged 0-5 years, chronic sinusitis (which was attributed to coexisting diseases) was no longer mentioned, but tracheal tenderness and vascular ring were explicitly proposed, mainly because their incidence was on the rise, so special clinical attention was needed, and if necessary, relevant tests could be improved to differentiate them. The differential diagnosis of asthma in children aged 6 to 11 years was first proposed to include chronic upper airway cough syndrome, foreign body aspiration, bronchiectasis, primary ciliary dyskinesia, congenital heart disease, bronchopulmonary dysplasia and cystic fibrosis.
4.Asthma assessment
(1) About asthma control assessment
Unlike previous editions, the GINA 2014 edition describes asthma assessment in detail as a separate chapter, arguing that asthma assessment should include three aspects of asthma control, treatment problems and coexisting diseases, focusing on the assessment of asthma control. Asthma control was first redefined to include the two main aspects of asthma control: symptom control and future risk of poor prognosis (previously, only the former was emphasized). The new version of the guideline emphasizes a comprehensive assessment of asthma, rather than just focusing on symptom control, and places more emphasis on the assessment of future risk, fully reflecting the importance of adverse prognostic risk assessment in the management of asthma.
The GINA 2014 edition still assesses asthma symptom control in four areas: daytime symptoms, nocturnal stifling, relief medication use, and activity limitation. The difference is that while pulmonary function (FEV1, PEF) used to be an important indicator to assess the level of asthma control in children aged 6 years and older, the new GINA guidelines no longer use pulmonary function parameters to assess the level of asthma symptom control, but include them in the future risk assessment, considering pulmonary function (FEV1) as a good indicator to assess future risk. The author believes that the main reason for this is that lung function does not exactly match the symptoms of asthma, especially in children, who may show normal lung function during two acute exacerbations. Also although lung function decreases in some patients, symptoms can be well controlled if they do not exercise in daily life. In the future risk assessment, detailed listings are provided for the risk of acute exacerbation, the risk of developing fixed airflow limitation, and the risk of drug side effects, respectively, as an aid to clinician interpretation. The assessment of asthma in children under 5 years of age was also divided into two areas: symptom control assessment and future risk assessment for adverse prognosis. For symptom control assessment, both daytime asthma symptoms and relief medication use were adjusted from 2 times/week to 1 time/week, which more strictly defines symptom control. In terms of future risk assessment, the risk of a “worsening” season was emphasized, unlike in children aged 6 years and older, mainly because asthma attacks in children under 5 years of age are mostly associated with viral infections.
(2) Assessment of asthma severity
The new guidelines clearly state that the assessment of asthma severity is based on the level of control therapy that is effective in controlling asthma symptoms and acute exacerbations in asthma patients who have been on regular control therapy for several months. The “intermittent, mildly persistent, moderately persistent, and severe persistent” assessment methods previously proposed by the GINA guidelines are no longer mentioned, primarily because they are not effective in guiding treatment. Although GINA 2012 has proposed a classification based on the level of control therapy, it only classifies mild asthma and severe asthma. The new GINA guidelines classify asthma severity based on level of control therapy for children 6 years and older as follows: (1) mild asthma: asthma that is well controlled with level 1 or 2 therapy; (2) moderate asthma: asthma that is well controlled with level 3 therapy; (3) severe asthma: asthma that requires level 4 or 5 (3) Severe asthma: asthma that requires level 4 or 5 treatment. There are many ways to describe the severity of asthma, including the severity of asthma symptoms, the severity of airflow limitation, or the severity of acute exacerbations, which are closer to the concept of the degree of asthma control than the severity of the disease itself. Patients with asthma can have frequent exacerbations, and if it is only because they are not using medications regularly, or have persistent allergen exposure that can be quickly relieved and controlled with ICS therapy, then it can only be said that the asthma is not under control, not severe asthma. Therefore, before diagnosing severe asthma, care must be taken to differentiate it from uncontrolled asthma by excluding the following: (1) inappropriate inhalation techniques; (2) poor medication compliance; (3) inappropriate diagnosis of asthma with differential diagnostic symptoms; (4) coexisting or concomitant diseases such as sinusitis, gastroesophageal reflux, obesity, obstructive sleep apnea; and (5) persistent allergen exposure. Refractory asthma is also a subtype of asthma, and the new version of the guidelines classify it as severe asthma. The author believes that its occurrence is mainly related to environmental allergy, poor compliance, special physical conditions, concomitant diseases, and diagnostic errors.
5.Management program for asthma
The long-term management plan of asthma is crucial to the effectiveness and prognosis of asthma treatment. Based on the cycle of “assessment of asthma control → treatment to achieve control → monitoring to maintain control” in the previous edition, the GINA 2014 edition further refines it into a cycle of “asthma control-based management (1) With regard to asthma control medications, the GINA 2014 edition has further refined the management cycle into “asthma control-based cyclic management”, i.e. “assessment → adjustment of treatment → monitoring of treatment response”, which again emphasizes that the goal of long-term management is to control symptoms and reduce future risks, and it is integrated throughout the cycle of asthma management.
(1) About asthma control medication
As in previous guidelines, inhalation therapy remains the basis of asthma treatment in children. inhalation devices should be selected individually according to age and other conditions, and attention should be paid to the technical approach to inhalation to reduce adverse effects and increase effective drug deposition in the lungs. iCS is the drug of choice for controlling asthma symptoms and reducing future risk. The low, medium and high doses of different ICS in children of different ages have also been adjusted, subdividing children over 5 years of age into two sections, 6-11 years and 12 years and older; the low dose of ciclesonide (160 μg) has been added for children under 5 years of age. ICS side effects are a major concern for clinicians, and the new guideline first emphasizes that uncontrolled or severe asthma can also affect the growth and adult height of children, so one should not The new guidelines first emphasize that uncontrolled or severe asthma can also affect the growth and adult height of children, so the therapeutic effects should not be overlooked in favor of side effects. It is generally accepted that 100-200 μg of ICS per day does not affect growth in children. However, a recent study showed that the 1.2 cm height lag caused by 400 μg daily budesonide treatment did not recover in adulthood, especially in those who started using ICS within 10 years of age. Inhaled long-acting β2 agonists (LABA) still need to be used in combination with ICS, mainly in asthma patients with poorly controlled moderate doses, and the ICS dose needs to be chosen according to the condition rather than a fixed dose combination. The use of leukotriene receptor antagonists may improve clinical symptoms in patients with asthma, but they are not as effective as low-dose ICS and the combination is not as effective as increasing the ICS dose. The new guidelines provide more detailed descriptions of anti-IgE therapy (omalizumab), such as indications for use in children aged 6 years and older with asthma. Because of the high toxicity of theophylline, the new guidelines do not recommend its use for the control of asthma in children, except for those who cannot use ICS.
(2) Stepped treatment regimen for asthma in children aged 6 years and older
In the previous stepped treatment regimens, the initial treatment selection, escalation and step-down treatment were centered on symptom control. The new version of the guideline list gives evidence-based opinions on initial treatment selection for adolescents, while pointing out that escalation and downgrading of treatment regimens should be centered on symptom control and reduction of future risks, with more emphasis on the assessment including the risk of acute exacerbation, the risk of fixed airflow limitation and the risk of drug side effects to guide the selection of treatment regimens. Tier 1 treatment remains inhaled rapid-acting beta2 agonists (SABA) on an as-needed basis, but the new guideline considers low-dose ICS as an option, especially when there is a risk of acute exacerbation, because this group of patients may also have chronic airway inflammation, but there is a lack of research on this. For the first time, the guideline specifies that low-dose ICS/formoterol can be used directly as a control and relief agent for adolescents in Tier 3 and Tier 4 treatment, and is preferable to regular ICS/LABA or high-dose ICS in patients with risk factors for asthma; however, in children 6 to 11 years of age, increasing the dose of ICS with SABA as needed is preferred. The new guidelines classify them into three types according to the duration of escalation maintenance, namely: (1) continuous escalation: escalation therapy is maintained for at least 2 to 3 months, and then re-evaluated, and if ineffective, downgraded to the pre-escalation level and considered with additional therapies; (2) short-term escalation: generally 1 to 2 weeks, mainly for the onset of viral infection or allergy season; (3) daily dose adjustment: mainly for the use of budesonide/formoterol or di Beclomethasone propionate/formoterol as a control and relief drug, when it needs to be applied temporarily as a relief drug, the dose can be increased according to the symptoms and needs to be restored to the maintenance dose after the symptoms are relieved. The overall principles of step-down therapy are: (1) If asthma symptoms are well controlled and lung function has been stable for 3 months or more, then step-down therapy is considered. If risk factors for acute exacerbation or fixed airflow limitation are present, no step-down therapy is allowed without close supervision. (2) Select the appropriate time (absence of respiratory infection, etc.). (3) All levels of treatment used are experimental. (4) Reducing the ICS dose by 25 to 50% every 3 months is safe and feasible for most patients. For discontinuation, the new version of the guideline considers discontinuation of the control drug if it has been asymptomatic for the past 6 to 12 months and there are no risk factors.
(3) Regarding the management of acute asthma attacks in children aged 6 years and older
The new version of the guideline considers that the treatment and management of acute asthma attacks should be a continuum that includes early self-management, management in primary care, and management in emergency medical facilities. The new guideline emphasizes that children aged 6 years and above with severe asthma exacerbations can be treated with intravenous glucocorticoids on top of the original treatment, and intravenous magnesium sulfate can be considered; and for those who fail to use systemic glucocorticoids in time within the first hour, the application of high-dose ICS can reduce the hospitalization rate. In addition, the new guidelines clearly state that intravenous aminophylline or theophylline should not be used for the treatment of acute asthma exacerbations, mainly because of their greater side effects and their inferiority to SABA. reassessment after treatment is shortened from 1 to 2 h to 1 h, emphasizing the importance of repeated evaluation and timely management. In addition, food allergy is listed as one of the risk factors for asthma-related death, so effective allergen avoidance for clearly diagnosed food allergy can reduce acute exacerbations and asthma-related death.
(4) About asthma management in children aged 5 years and younger
The new edition of the guidelines gives a stepped treatment plan based on symptom pattern, risk of acute exacerbation, risk of side effects, and response to treatment, which is more finely divided into four levels than the 2009 edition, and suggests indications for each level of treatment. Based on the GINA 2012 edition, the new guideline gives clear principles regarding the treatment of viral-induced wheeze, i.e., although viral-induced wheeze is infrequent, regular control therapy is needed if the attacks are severe. For those with a suspected diagnosis of asthma and requiring frequent relief with SABA [>1 episode/(6-8 weeks)], diagnostic treatment may be indicated. The overall goal of stepwise therapy is symptom control and reduction of future risk. The choice of specific control therapy medications has changed little from the previous edition of the guidelines. In the new version of the guidelines, the assessment of the severity of an acute asthma attack is more stringent than in the 2009 version, with oxygen saturation >0.95 defined as mild and <0.92 defined as severe. In addition, for acute asthma attacks in children aged 2 years and older, especially those with symptoms lasting <6 h, magnesium sulfate inhalation therapy may be an alternative to conventional inhaled SABA and ipratropium bromide; intravenous magnesium sulfate may also be tried.