title: Severe asthma in childhood:  recent advances in phenotyping and pathogenesis.
abstract: OBJECTIVE
  Children with severe asthma have a high degree of respiratory morbidity despite treatment with high doses of inhaled corticosteroids and are therefore very difficult to treat. This review will discuss phenotypic and pathogenic aspects of severe asthma in childhood, as well as remaining knowledge gaps.
  
  
  RESULTS
  As a group, children with severe asthma have a number of distinct phenotypic features compared with children with mild-to-moderate asthma. Clinically, children with severe asthma are differentiated by greater allergic sensitization, increased exhaled nitric oxide, and significant airflow limitation and air trapping that worsens as a function of age. These findings are accompanied by structural airway changes and increased and dysregulated airway inflammation and oxidant stress which may explain the differential nature of corticosteroid responsiveness in this population. Because children with severe asthma themselves are a heterogeneous group, current efforts are focused on improved definition and sub-phenotyping of the disorder. Whereas the clinical relevance of phenotyping approaches in severe asthma is not yet clear, they may provide important insight into the mechanisms underlying the disorder.
  
  
  CONCLUSIONS
  Improved classification of severe asthma through unified definitions, careful phenotypic analyses, and mechanism-focused endotyping approaches may ultimately advance knowledge and personalized treatment.
authors.affiliation: Emory University Department of Pediatrics, Atlanta, Georgia, USA. anne.fitzpatrick@emory.edu
authors.forename: Anne M
authors.initials: AM
authors.lastname: Fitzpatrick
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Baena-Cagnani
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Bacharier
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use; D001249:Asthma / Q000145:classification* / Q000188:drug therapy / Q000503:physiopathology; D001944:Breath Tests; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000145:classification* / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D018384:Oxidative Stress / Q000502:physiology; D012720:Severity of Illness Index
chemical_list: D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D009569:Nitric Oxide