Safety of long-acting beta agonists and inhaled corticosteroids in children and adolescents with asthma

Abstract

The introduction of long-acting beta agonists (LABAs) was considered a major advance in bronchodilator therapy for adult, as well as pediatric, patients with asthma. However, the use of LABAs has raised safety concerns, especially the potential for severe asthma exacerbations (SAEs) resulting in hospitalizations or even death. Meanwhile, the use of inhaled corticosteroids (ICSs), a cornerstone in the treatment of mild-to-severe persistent asthma, has been associated with growth suppression in children. The purpose of this review was to identify and discuss the major published safety studies surrounding LABA, ICS, and combined LABA/ICS usage in children. By way of a critical search for influential published clinical trials, meta-analyses, and observational studies, six studies relevant to the safety of LABA monotherapy, seven studies relevant to ICS monotherapy, and four studies on the subject of LABA/ICS combination usage were identified and reviewed. Based on the reviewed literature, the controversy surrounding these anti-asthma medications was clearly exposed. On the one hand, there is some evidence that LABA monotherapy may be associated with SAEs and asthma-related death, while ICS monotherapy may be associated with a higher risk of growth suppression. On the other hand, the concurrent use of a LABA with an ICS has been associated with positive outcomes including symptom reduction and reduced rate and severity of exacerbations. Further clinical research is warranted and has been called for by the US Food and Drug Administration.

The efficacy and safety of fluticasone/salmeterol compared to fluticasone in children younger than four years of age

“…Worldwide, asthma is very common in children and is one of the leading causes of hospitalization, particularly in very young children . Diagnosis and treatment in this age group is difficult for many reasons …”

“…Worldwide, asthma is very common in children and is one of the leading causes of hospitalization, particularly in very young children. 1,2 Diagnosis and treatment in this age group is difficult for many reasons. [3][4][5] The combination of ICS and a long-acting beta-2-agonist (LABA) is widely used as maintenance therapy for children and adults with asthma in Japan and worldwide.…”

Omalizumab in children with uncontrolled allergic asthma: Review of clinical trial and real-world experience

“…6,8,9 Furthermore, conventional bronchodilatory and antiinflammatory therapeutics do not modify the underlying disease mechanism, and debate continues regarding the safety of prolonged high-dose ICS use in children. 10,11 The safe and appropriate use of long-acting b 2 -agonists (LABAs) has also been widely debated, although a recent randomized, double-blind trial showed that LABA given in combination with ICS did not result in a higher risk of severe asthma events among children versus those receiving ICS alone. 12 Consequently, a need remains for safe and efficacious targeted therapeutic options in children with uncontrolled severe asthma.…”

Long-acting muscarinic antagonists for the treatment of asthma in children—a new kid in town

“…The safety profile of SABAs—the most commonly used reliever medication for paediatric patients—is generally favourable, with reports of mild side effects such as tachycardia, dizziness and jitteriness [ 12 ]. LTRAs—which are a potential alternative first-line therapy, either as monotherapy or in combination with ICS—reduce exacerbation rates and use of SABAs in children with asthma of varying severity [ 13 ].…”