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

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.