The need to differentiate between adults and children when treating severe asthma

Abstract

Severe asthma at all ages is heterogeneous incorporating several phenotypes that are distinct in children and adults, however, there are also numerous similar features including the limitation that they may not remain stable longitudinally. Severe asthma in both children and adults is characterized by eosinophilic airway inflammation and evidence of airway remodeling. In adults, targeting eosinophilia with anti-IL-5 antibody therapy is very successful, resulting in the recommendation that sputum eosinophils should be used to guide treatment. In contrast, data for the efficacy of blocking IL-5 remain unavailable in children. However, its effectiveness is uncertain since many children with severe asthma have normal blood eosinophils and the dominance of Th2-mediated inflammation is controversial. Approaches that have revealed gene signatures and biomarkers such as periostin that are specific to adult disease now need to be adopted in children to identify effective pediatric specific therapeutics and minimize the extrapolation of adult therapeutics to children.

Keywords:

• asthma phenotype
• early-onset asthma
• innate cytokines
• lung development
• severe asthma
• steroid resistance

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Although there are some pathophysiological differences of severe asthma in children and adults (Table 1), many features including eosinophilic airway inflammation and significant airway remodeling are similar in both groups.

• In children blood eosinophil counts and sputum eosinophilia do not always reflect eosinophils in the airways and the dominance of Th2-mediated inflammation is controversial.

• Antenatal and postnatal lung development can be vulnerable to pathogens, allergens, smoking, pollution and diet with potential influence on asthma pathogenesis. Abnormal immune responses to allergens and pathogens in early life may have an influence on the development of allergic airways disease.

• Although evidence of reversible airflow obstruction is present in most children with severe asthma, there may be some patients with normal spirometry in whom an airway challenge test is needed to confirm the diagnosis.

• In children a definition of steroid responsiveness is lacking. Response to steroids cannot rely on lung function alone, but needs to take account of symptoms, inflammation and exacerbations.

• Innate epithelial cytokines such as IL-33 and type 2 innate lymphoid cells seem to have a role in steroid insensitivity and severe asthma pathogenesis.

• Early intervention on asthma development with individualized therapies specific for the pediatric age may prevent permanent respiratory impairment in later life.