Problematic severe asthma: a proposed approach to identifying children who are severely resistant to therapy

Pediatr Allergy Immunol. 2011 Feb;22(1 Pt 1):9-18. doi: 10.1111/j.1399-3038.2010.01098.x. Epub 2010 Sep 30.


Children with problematic severe asthma (PA) are either difficult to treat because of the presence of aggravating factors or else severely resistant to therapy. We investigated a cohort of school-aged children with PA and compared these children to age-matched peers with controlled persistent asthma (CA). The aims were to characterize features of children suffering from PA and identify children who were severely resistant to therapy. In this cross-sectional, multicenter comparison of children with different manifestations of persistent asthma, PA was defined as insufficient asthma control despite level 4 treatment, according to GINA. The protocol included questionnaires, spirometry, methacholine provocation, measurement of fraction of nitric oxide in exhaled (FE(NO) ) and nasal air, blood sampling for inflammatory biomarkers and atopy, and computerized tomography of sinuses and lungs (in the PA group only). Of the 54 children with PA, 61% had therapy-resistant asthma, with the remaining being difficult to treat because of identified aggravating factors. Children with PA more often had parents with asthma (p=0.003), came from families with a lower socioeconomic status (p=0.01), were less physically active (p=0.04), and had more comorbidity with rhinoconjunctivitis (p=0.01) than did the 39 children with CA. The former also exhibited lower FEV(1) values (p=0.02) and increased bronchial hyper-responsiveness (p=0.01), but there were no differences in atopy (p=0.81) or FE(NO) (p=0.16). A non-invasive protocol, involving a standardized and detailed clinical characterization, revealed distinguishing features of children with PA and enabled the identification of children with therapy-resistant asthma.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Asthma / diagnosis
  • Asthma / drug therapy*
  • Asthma / genetics
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity
  • Bronchial Provocation Tests
  • Child
  • Cross-Sectional Studies
  • Exhalation
  • Female
  • Forced Expiratory Volume
  • Humans
  • Lung / physiology
  • Male
  • Methacholine Chloride / therapeutic use
  • Nitric Oxide / metabolism
  • Respiratory Function Tests
  • Rhinitis / complications*
  • Severity of Illness Index*
  • Spirometry
  • Surveys and Questionnaires


  • Methacholine Chloride
  • Nitric Oxide