Asthma is the most common chronic disease in childhood, which can lead to the inability of children to attend school normally, frequent emergency medical treatment and even hospitalization. The prevalence of asthma in children in China has increased significantly in the last decade or so, and a survey in 2002 found that the prevalence of asthma among urban children aged 0-14 years in China was 0.5%-3.4%.
Asthma is characterized by chronic airway inflammation and airway hyperresponsiveness to a variety of allergens and other stimuli, resulting in reversible airflow limitation. Typical symptoms are paroxysmal wheezing, chest tightness and cough. However, in children younger than 5 years of age, the clinical manifestations of asthma are variable and non-specific; in addition, cough and wheezing are common in childhood infections, so asthma diagnosis should be made with caution especially in children younger than 3 years of age. In children with recurrent wheezing, if the parents have a history of asthma or eczema and have their own atopic constitution, such as a history of food allergy, allergic rhinitis and allergic dermatitis, bronchial asthma should be considered and experimental treatment or pulmonary function tests are feasible.
Asthma medication mainly targets airway inflammation to reduce airway hyperresponsiveness, while relieving airway constriction and improving asthma symptoms. Asthma treatment in children is different from that in adults because children are in the process of growth and development and have a different level of coordination and cooperation in response to medication and use of inhalation devices. The goal of asthma control is to achieve good asthma control, maintain normal lung function, and to minimize the impact on the child’s growth and development. In standardized treatment, asthma medications are divided into control medications and relief medications. Because asthma is a chronic inflammation of the airways associated with exposure to allergens, inhaled glucocorticosteroid (ICS) is the most effective of the control medications. For pediatric asthma patients of all ages, ICS is the first-line treatment. The condition can be classified as asthma controlled, partially controlled and uncontrolled by clinical symptoms and use of relieving medications (see Table 1).
Table 1. Classification of asthma control in children aged 5 years and younger
Clinical characteristics
Controlled
Partially controlled (any week with any of the following manifestations)
Uncontrolled (any 1 week presentation)
Partially controlled with ≥3 manifestations
Daytime symptoms (paroxysmal wheezing, cough, dyspnea)
None (less than 2 times/week)
Greater than 2 times/week
Greater than 2 times/week
Activity limitation
None
Any one time
Any time
Nocturnal symptoms/waking up
None
Any time
Any time
Need emergency treatment/relief medication
No more than 2 days/week
More than 2 days/week
More than 2 days/week
Choice of inhalation device
Because of the differences in coordination between children of different ages, it is important to select the appropriate inhalation device for the patient’s treatment. Different devices should be selected for inhalation therapy in children of different ages (see Table 2). A Metered Dose Inhaler (MDI) with a Spacer is the most convenient and easy to learn way to facilitate the deposition of the drug in the lungs and reduce the side effects caused by the deposition of ICS in the oropharynx, and it is inexpensive. During acute attacks, MDI+ canisters or inhalation of relieving medications through a nebulizer device can also be used. The inhalation efficiency of the nebulizer device is equivalent to that of the MDI with a nebulizer canister, with the disadvantage that the dose of the nebulized inhalation medication is less accurate and more expensive, and the device requires regular maintenance.
Table 2. Selection of inhalation devices for children of different ages
Age
Preferred device
Other optional devices
Less than 4 years old
Mask-type nebulizer
Mask-type nebulizer
Age
Mouthpiece nebulizer
Mask-type nebulizer, mouthpiece-type or mask-type nebulizer
Older than 6 years
Dry powder inhaler, or MDI, or
or MDI + Mouthpiece Nebulizer
Mouthpiece nebulizer
Dose selection and regimen optimization for inhaled glucocorticoids
Lower doses of ICS are used in children with asthma compared to adults, as shown in Tables 3 and 4. Once the child has inhaled ICS using an appropriate inhalation device, the child’s response to treatment needs to be monitored. After clinical control of asthma is achieved, ICS should be reduced to the lowest dose necessary to maintain asthma control in order to reduce ICS-related side effects.
ICS treatment in patients over 5 years of age
In children over 5 years of age, maintenance therapy with ICS to control asthma symptoms may reduce the number of acute asthma exacerbations and hospitalizations, improve lung function and airway hyperresponsiveness, and thus protect lung function and improve quality of life. Clinical studies have shown that small doses of ICS (e.g., budesonide 100-200 μg/day) can rapidly achieve symptom control and improve lung function. In most children with mild asthma, early treatment with low-dose ICS improves symptoms and avoids the need to add other medications. Some patients require 400 μg of budesonide daily, and only a few patients require high-dose ICS. symptoms and lung function improve quickly in most patients after 1-2 weeks of ICS use, and for better improvement of airway hyperresponsiveness, ICS use is needed for several months. However, acute asthma attacks can occur several weeks to months after discontinuation of ICS.
Table 3. Estimated equivalent daily inhaled glucocorticoid doses in children older than 5 years with asthma
Drug
Low daily dose (μg)
Moderate daily dose (μg)
High daily dose (μg)
Beclomethasone propionate
Budesonide
Budesonide nebulizer
Fluticasone propionate
Mometasone furoate
Triamcinolone acetonide
Flunisolide
Ciclesonide
ICS treatment in patients 5 years and younger
ICS is considered effective in the treatment of asthma in children aged 5 years and younger, although there is a lack of adequate clinical studies on the dose-efficacy relationship. ICS improves lung function, relieves symptoms, increases the number of symptom-free days, reduces other medications and systemic glucocorticoids (CS), and reduces the number of acute exacerbations. Its effectiveness depends on the choice of inhalation device and whether the child can use the device correctly. There is no evidence that ICS can alter the course of asthma. For intermittent virus-induced wheezing, the role of intermittent systemic use or inhaled ICS is controversial. Continued use of low-dose ICS does not prevent the onset of early transient wheezing. Symptoms can recur after two years of ICS use and discontinuation of the drug.
Initial treatment should be low-dose ICS for 3 months. If asthma is not controlled after 3 months of treatment with the correct inhalation technique, the best option is to double the dose of ICS or to add a leukotriene modulator to the low-dose ICS. If doubling the ICS dose still does not completely control asthma symptoms, treatment goals and feasibility should be discussed with the child’s family, and the child’s medication inhalation pattern and compliance should be carefully evaluated again, environmental allergen control should be enhanced, and the correct diagnosis of asthma should be evaluated again. Treatment may include further increases in the dose of ICS or the addition of leukotriene modulators, theophylline, or oral glucocorticoids (OCS) for several weeks until asthma symptoms improve.
In children younger than 5 years, the need for continued treatment needs to be evaluated periodically (every 3-6 months). Children with seasonal asthma should be reviewed regularly after discontinuation of ICS therapy, every 3-6 weeks, and ICS therapy should be resumed if symptoms reappear. For wheezing episodes of 3 consecutive seasons, ICS should be initiated for symptom control.
Table 4. daily inhaled low-dose glucocorticosteroid doses in patients with asthma aged 5 years and younger
Drug
Low daily dose (μg)
Beclomethasone propionate
Budesonide MDI+ Mist reservoir
Budesonide nebulization
Fluticasone propionate
Mometasone furoate
No study yet
Triamcinolone acetonide
No study yet
Ciclesonide
No studies available
Related Adverse Effects
Most parents of children with long-term ICS use are concerned about the safety of glucocorticoids. In fact, small doses of ICS do not cause serious adverse effects.
Growth inhibition, with long-term use of high doses of ICS, may result in slow growth and delayed puberty by about age 10, but ultimately does not affect adult height. Effects on growth rate are often temporary in the first year after CS inhalation, and children 4-10 years of age are more sensitive than adolescent patients. Small doses of ICS have not been found to affect growth and development in children. In fact, uncontrolled asthma and recurrent acute exacerbations can also affect the development of children and their height in adulthood.
Skeletal effects, mainly in the form of osteoporosis and fractures, are seen in children with high systemic CS use. ICS may reduce bone deposition in boys at puberty; however, there is no evidence that ICS increases the risk of fracture. Appropriate use of ICS reduces systemic use of CS and has a much lesser effect on bone.
No significant effects on the hypothalamic-pituitary-adrenal axis were found with inhalation of budesonide less than 200 μg/day and equivalent doses of other ICS. Changes in the hypothalamic-pituitary-adrenal axis can be detected using sensitive methods when large amounts of ICS are used; however, no ICS-related adrenal crises have been detected in clinical trials. Adrenal crisis has been observed in children with asthma after excessive use of large amounts of ICS in clinical trials; therefore, ICS doses should be selected appropriately.
Central nervous system effects, such as insomnia and hyperexcitability, may occur with ICS use, but no central nervous system changes have been observed with inhaled budesonide in 2 large clinical studies with controls.
Local adverse effects (thrush and hoarseness) are not a major problem with long-term use of ICS and OCS in children. The appearance of thrush may be associated with concomitant antibiotic use, large and frequent inhalation of CS and incorrect use of the inhalation device. The use of a storage mist canister and rinsing the mouth after CS inhalation may reduce oral Candida infections. In addition, ICS did not increase the incidence of glaucoma, dental caries, or lower respiratory tract infections including tuberculosis, and inhaled budesonide was no more likely to cause hoarseness than the control group.
Treatment of acute exacerbation of asthma CS
Acute exacerbations of asthma in children mainly present with acute and subacute onset of wheezing, dyspnea, increased cough (especially at night), decreased activity tolerance, drowsiness or reduced feeding, and poor response to relieving medications. In acute exacerbations, in addition to rapid-acting β2-agonists to dilate the bronchi, oxygen and close monitoring as soon as possible, CS therapy should be reasonably administered under the guidance of a physician. For children who were not on ICS before the exacerbation, the initial ICS dose is twice the recommended low-dose ICS and is maintained for several weeks to months. For children already on ICS, doubling the dose is not certain to be effective. OCS is more effective early in acute exacerbations and can reduce the severity of the attack. The recommended dose of oral prednisone is 1 to 2 mg/(kg?d), with a maximum dose of 20 mg/day for children under 2 years of age and 30 mg/day for children 2 to 5 years of age, with significant efficacy 3 to 4 h after administration. In children with severe asthma, hydrocortisone succinate 5-10mg/(kg?) or methylprednisolone 1-2mg/(kg?) can be administered intravenously and repeated at intervals of 4-8h.
ICS is the first-line drug for asthma control, which can improve lung function, control symptoms and reduce acute exacerbations. Low doses of ICS do not cause significant systemic adverse effects. The use of OCS should only be considered for acute exacerbations of asthma, and during maintenance ICS therapy for asthma, physicians should regularly evaluate the treatment regimen and associated adverse effects to ensure the effectiveness and safety of treatment.