Care for flares: Therapy for acute asthma exacerbations and severe asthma in children

First-line asthma therapy requiring inhaled short-acting beta-agonists (SABA) and systemic corticosteroids is well-established and usually effective in most children with mild or moderate exacerbations.1 However, a minority of children fail to respond and require escalation treatment.1 With a large number of treatment options available in real life practice, it is important to document the best available evidence to assist healthcare providers and patients in making clinical decisions.1 An overview of Cochrane systematic reviews was carried out to evaluate the efficacy and safety of second-line escalation of therapy for children with asthma who failed to benefit from first-line therapy.1 Apart from the young patients resistant to standard therapy, there exists another group of severe asthma patients whose condition is poorly controlled due to low adherence to medication or poor inhaler technique. The therapeutic options for these two groups are also reviewed collectively.

Thirteen reviews including both randomized controlled trials (RCTs) and non-RCTs were evaluated.1 The treatments were categorized as inhaled bronchodilators, parenteral bronchodilators or interventions to lessen breathing effort.1 Primary outcomes included length of stay, outcome of ED visit (hospital or intensive care unit admission, or discharge) and adverse effects.1

The review showed that there was no effective treatment to reduce the risk of intensive care admission.1 Addition of inhaled anticholinergic agents to inhaled SABAs, intravenous magnesium sulfate and inhaled heliox reduced the rate of hospital admission.1 A multiple fixed-dose protocol of inhaled anticholinergic agents resulted in reduced risk of hospital admission compared with SABA alone (Risk ratio=0.72, 95% CI: 0.61-0.84).1 Despite not being as effective as β2 agonists, the addition of anticholinergic agents might lead to greater bronchodilation than using either agent alone.1 Intravenous infusion of magnesium sulfate showed high-certainty evidence in reducing the length of hospital stay (mean difference: -5.3 hours, 95% CI: -9.46 to -1.14 hours), although this was only demonstrated from a single trial with 47 patients.1 Subcutaneous or intravenous magnesium sulfate is an effective bronchodilator which might elicit a more rapid therapeutic response than inhaled β2 agonists.1 Low-certainty evidence suggests that the use of heliox leading to a small reduction in hospital admission compared to placebo (Risk ratio=0.69, 95% CI: 0.48-0.99).1 Heliox, the mixture of helium and oxygen, is less dense than room air and might reduce the turbulent airflow and airflow obstruction. It might also improve the delivery of nebulized therapy to distal airways.1

Serious adverse events were reduced by the addition of inhaled magnesium sulfate to usual bronchodilator therapy, and the addition of inhaled anticholinergic therapy to SABAs reduced the risk of nausea and tremor.1 However, methylxanthine aminophylline increased the rate of vomiting compared to placebo, and increased nausea compared to intravenous β2 agonists.1

Another review described the definitions, epidemiology and treatment of severe asthma in children.2 Severe asthma is characterized by troublesome daily asthma symptoms and/or frequent asthma attacks.2 There are various definitions of severe asthma but they have a common theme of poor control despite high dose inhaled corticosteroid treatment.2 The prevalence of severe childhood asthma might be up to 5% within asthma populations.2

There is a high level of evidence supporting that short bursts of oral corticosteroid treatment are effective in reducing the severity and duration of an asthma exacerbation in children, even though adverse effects such as vomiting, behavioral change and sleep disturbance might occur.2 The use of maintenance oral corticosteroids in severe childhood asthma remains unclear.2 Evidence supporting the use of intramuscular triamcinolone was weak and limited to case series studies only.2 However, triamcinolone treatment was associated with significant falls in exhaled nitric oxide and blood eosinophil count, and repeated monthly triamcinolone treatments lowered the number of exacerbations and hospital admissions.2 The anti-IgE antibody omalizumab was also safe and effective but not suitable for more than half of the trial patients as the subcutaneous injection was uncomfortable as well as costly.2 The anti-interleukin (IL) 5 drug mepolizumab reduced exacerbations by 39% to 52%, although most studies reported severe headaches among participants, while the IL-3 and IL-13 antibody dupilumab reduced exacerbations by 42%.2 Lastly, the evidence base of gastroesophageal reflux treatment was limited.2

Future research on severe asthma therapy could be focused on the roles of long-acting muscarinic agonists, macrolide antibiotics and bronchial thermoplasty.2 Additionally, the electronic logging of inhaled corticosteroid treatment could be explored as it is shown to improve asthma outcomes.2 Finally, the decision as to when to start or stop treatment should be supported by more robust evidence.2

  1. Craig S, et al. Interventions for escalation of therapy or acute exacerbations of asthma in children: An overview of Cochrane reviews. Paediatric Respiratory Reviews. 2020, S1526-0542(20)30122-6
  2. Ahmed H, et al. Severe asthma in children – a review of definitions, epidemiology, and treatment options in 2019. Pediatric Pulmonology. 2019; 1-10
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