Children with problematic severe asthma (PA) have persistent symptoms and/or severe exacerbations despite treatment with several drugs. Classification of asthma severity is currently based on level of treatment and assessment of asthma control, but objective biomarkers of asthma severity are needed. To investigate the clinical relevance of basophil allergen threshold sensitivity (CD-sens) as a measure of allergen sensitivity in a well-characterized cohort of children with different manifestations of persistent allergic asthma. Cat-allergic children (6-18yr) with problematic severe asthma (n=11) according to GINA were compared with eleven age-matched children with controlled, but persistent asthma (CA). The protocol included standardized questionnaires, asthma control test (ACT), spirometry, methacholine challenges, measurement of FE NO, IgE, cat IgE and IgG antibodies, and analysis of CD-sens (CD63-expression) by flow cytometry. The 11 cat-allergic children with PA had a significantly lower ACT score (p<0.001), reduced FEV 1 (p=0.04), and increased numbers of blood eosinophils (p=0.03) compared with the 11 children with CA. The former exhibited a higher CD-sens to cat (p=0.02). No significant differences were detected with respect to FE NO (p=0.17), IgE (p=0.84), cat IgE (p=0.12), and the major cat-allergen rFel d 1 (p=0.30). CD-sens significantly correlated with ACT (p=0.002, r=-0.63) and FE NO (p=0.01, r=0.55). No significant differences between PA and CA were found regarding IgG antibodies to rFel d 1. Cat-allergic children with problematic severe asthma have higher sensitivity to cat allergen, as measured by CD-sens, compared with children with controlled asthma. This suggests that CD-sens could be used as an additional marker for identifying children with the most severe allergic asthma.