Read comments from an expert whom Infectious Diseases in Children spoke with regarding ongoing concerns over the safety of asthma medications. We welcome you to share your own impression of the common misconceptions associated with asthma medication use among children by commenting online at Healio.com/Pediatrics.
The introduction of long-acting beta agonists, especially in combination with an inhaled corticosteroid, has been considered a significant improvement in bronchodilator therapy for pediatric patients with asthma. However, the use of long-acting beta agonists also has raised safety concerns, especially the potential for severe asthma exacerbations resulting in hospitalizations or death.
In addition, the use of inhaled corticosteroids, key to the treatment of mild-to-severe persistent asthma, has been associated with a risk for growth suppression in children. The risk for growth suppression is primarily limited to the first year of treatment, and it results in approximately 1 cm loss in height in the first year of treatment. This level of growth suppression is known to be persistent, but not progressive, with continued treatment.
Presently, there are two strategies in using bronchodilators in asthma. One is to provide quick relief that, in the United States, is primarily done with a short-acting beta agonist such as albuterol. The other strategy is to use a long-acting beta agonist as a supplemental medication added to an inhaled corticosteroid.
For the long-acting betaagonist, there are several limitations that we have in the United States associated with FDA concerns regarding safety. In asthma, long-acting beta agonists are really not used as a reliever agent, but rather as a long-term controller in combination with an inhaled steroid. The FDA strongly recommends that the two be in the same device — namely the inhaled steroid and the long-acting beta agonist.
There have been lingering concerns by the FDA regarding the risk of the long-acting beta agonists; however, a recently published study from an adult study has provided reassuring data for the safety of the long-acting beta agonist when combined with an inhaled steroid.
The initial safety risk for the long-acting beta agonists was identified early in the 1990s before the combination products were highly recommended. At the request of the FDA, a very large study has been carried out by three pharmaceutical firms over the past 5 years, the results of which are just starting to come out.
The safety concern that was mentioned in the black box warning is the risk for death with these medications, based on studies primarily conducted in the 1990s and primarily on adults; these studies were conducted just as the drug was coming into the market and raised the attention of the FDA. There were a small number of deaths, but they were noted to be more frequent in the long-acting beta agonist group, so it brought about these initial concerns.
Overall, what we have been seeing — despite the increasing use of the combination inhaled corticosteroid/long-acting beta agonist products — is a reduction in asthma deaths. The combination products, in particular, have been important in the management of severe asthma as they significantly reduce the number of exacerbations and reduce the requirement for significant dosing of oral steroid medications that carry their own risk of side effects. A similar study also was completed recently in children aged 5 to 11 years. The results of that will be reported when the analysis is complete.
Physicians use the information available on efficacy and safety of medications to make decisions regarding their use in individual patients. In managing children with asthma, growth is followed carefully when an inhaled corticosteroid is prescribed. In addition, the clinician balances the benefits of the medication with the risks of that medication as compared with the risk for uncontrolled asthma.
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Stanley Szefler, MD is the director of the Pediatric Asthma Research Program in the Breathing Institute of the Pediatric Pulmonary Section at Children's Hospital Colorado.
- Stempel DA, et al. N Engl J Med. 2016;doi:10.1056/NEJMoa1511049.
Disclosure: Szefler reports receiving grant funding through GlaxoSmithKline for a school-centered asthma program and has served on the advisory panel at the request of GlaxoSmithKline for the pediatric study. He also serves as a consultant to several pharmaceutical firms for the development of asthma medications to be used in children.