Severe asthma in children is a complicated and heterogeneous disorder that is extremely challenging to treat. Although most children with asthma derive clinical benefit from daily administration of low-to-medium-dose inhaled corticosteroid (ICS) therapy, a small subset of children with "severe" or "refractory" asthma require high doses of ICS and even systemic corticosteroids to maintain symptom control. These children with severe asthma are at increased risk for adverse outcomes including medication-related side effects and recurrent and life-threatening exacerbations that significantly impair quality of life. This review highlights findings on severe asthma in school-age children (age 6-17 years) from the National Heart, Lung and Blood Institute's Severe Asthma Research Program (SARP) over a 10-year period, between 2001 and 2011. Although SARP has advanced knowledge of the unique clinical, biological, and molecular attributes of severe asthma in children, considerable gaps remain for which additional studies are needed.
Severe asthma in children is characterized by sustained symptoms despite treatment with high doses of inhaled corticosteroids or oral corticosteroids. Children with severe asthma may fall into 2 categories, difficult-to-treat asthma or severe therapy-resistant asthma. Difficult-to-treat asthma is defined as poor control due to an incorrect diagnosis or comorbidities, or poor adherence due to adverse psychological or environmental factors. In contrast, treatment resistant is defined as difficult asthma despite management of these factors. It is increasingly recognized that severe asthma is a highly heterogeneous disorder associated with a number of clinical and inflammatory phenotypes that have been described in children with severe asthma. Guideline-based drug therapy of severe childhood asthma is based primarily on extrapolated data from adult studies. The recommendation is that children with severe asthma be treated with higher-dose inhaled or oral corticosteroids combined with long-acting β-agonists and other add-on therapies, such as antileukotrienes and methylxanthines. It is important to identify and address the influences that make asthma difficult to control, including reviewing the diagnosis and removing causal or aggravating factors. Better definition of the phenotypes and better targeting of therapy based upon individual patient phenotypes is likely to improve asthma treatment in the future.