BackgroundThe mechanism underlying severe asthma with fungal sensitization (SAFS) is unknown. IL-33 is important in fungus-induced asthma exacerbations, but its role in fungal sensitization is unexplored.ObjectiveWe sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33.MethodsEighty-two children (median age, 11.7 years; 63% male) with severe therapy-resistant asthma were included. SAFS (n = 38) was defined as specific IgE or skin prick test response positivity to Aspergillus fumigatus, Alternaria alternata, or Cladosporium herbarum. Clinical features and airway immunopathology were assessed. Chronic exposure to house dust mite and A alternata were compared in a neonatal mouse model.ResultsChildren with SAFS had earlier symptom onset (0.5 vs 1.5 years, P = .006), higher total IgE levels (637 vs 177 IU/mL, P = .002), and nonfungal inhalant allergen-specific IgE. Significantly more children with SAFS were prescribed maintenance oral steroids (42% vs 14%, P = .02). SAFS was associated with higher airway IL-33 levels. In neonatal mice A alternata exposure induced higher serum IgE levels, pulmonary IL-33 levels, and IL-13+ innate lymphoid cell (ILC) and TH2 cell numbers but similar airway hyperresponsiveness (AHR) compared with those after house dust mite exposure. Lung IL-33 levels, IL-13+ ILC numbers, TH2 cell numbers, IL-13 levels, and AHR remained increased with inhaled budesonide during A alternata exposure, but all features were significantly reduced in ST2−/− mice lacking a functional receptor for IL-33.ConclusionPediatric SAFS was associated with more oral steroid therapy and higher IL-33 levels. A alternata exposure resulted in increased IL-33–mediated ILC2 numbers, TH2 cell numbers, and steroid-resistant AHR. IL-33 might be a novel therapeutic target for SAFS.

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Preschool referral to a PCD center was not associated with better spirometry or BMI. PCD children and adolescents receiving centralized care show steady BMI and spirometry during medium term follow-up. There was a high prevalence of Pseudomonas aeruginosa infection, but the evolution of spirometry or BMI was not affected by this microorganism in medium term. Despite our longitudinal analysis showed no differences between the three centers, the assessment of spirometry and BMI over time represents a quality improvement tool. Future studies are needed to highlight the role of spirometry and BMI in long term PCD management and identify subgroups of patients with a higher risk of early lung failure or nutritional problems.

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