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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Despite its extensive use, there is no evidence that spirometry is useful in the assessment of progression of lung disease in primary ciliary dyskinesia (PCD). We hypothesize that high-resolution computed tomography (HRCT) is a better indicator of PCD lung disease progression than spirometry. We retrospectively evaluated two paired spirometry and HRCT examinations from 20 PCD patients (age, 11.6 years; range, 6.5-27.5 years). The evaluations were performed in stable state and during unstable lung disease. HRCT scans were scored blind by two raters. Compared to the first assessment, at the second evaluation spirometry did not change while HRCT scores significantly worsened (P < 0.01). Age was significantly related to HRCT total (r = 0.5; P = 0.02) and bronchiectasis scores (r = 0.5; P = 0.02). At both evaluations, HRCT total score correlated with FEV(1) (r = -0.5, P = 0.01; r = -0.7, P = 0.001, respectively) and FVC Z scores (r = -0.6, P = 0.006; r = -0.7, P = 0.001, respectively), and bronchiectasis score was related to FEV(1) (r = -0.5, P = 0.03; r = -0.6; P = 0.002, respectively) and FVC Z scores (r = -0.6, P = 0.008; r = -0.7, P = 0.001, respectively). No relationship was found between the change in HRCT scores and the change in spirometry. In PCD, structural lung disease may worsen despite spirometry being stable.

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Background: Non-cystic fibrosis (CF) bronchiectasis is now identified more often than in the past. Objectives: It was the aim of this study to assess the high-resolution computed tomography (HRCT) localization and extent of bronchiectasis and to determine whether asthma status, atopy and bronchiectasis distribution are associated with the etiology of bronchiectasis. Methods: We retrospectively analyzed clinical, laboratory, functional and HRCT data of 105 children with non-CF bronchiectasis at 2 tertiary respiratory units in Italy. Forty cases had bronchiectasis associated with ongoing underlying conditions, namely primary ciliary dyskinesia, primary immunodeficiency or aspiration. Results: Age at the onset of chronic cough/wheeze and at the first X-ray-documented pneumonia as well as atopy prevalence were lower in patients with ongoing underlying conditions than in those without (p = 0.049, p = 0.003 and p = 0.0008, respectively). In most cases, bronchiectasis was multilobar, and a mean of 2.5 lobes were involved. The right side was more often involved than the left (88 vs. 70%; p = 0.002), and the upper lobes were relatively spared (p < 0.000001). Right lung involvement and multilobar disease were more prevalent in children younger than 2 years at first pneumonia (p < 0.05). Conclusions: Clinical information combined with laboratory data provides additional insights into the characteristics of non-CF bronchiectasis in a large population of Italian children. This study highlights the need for longitudinal evaluations, also using HRCT, of severe and non-resolving pneumonia in children.

In children with IBS a mixture of Bifidobacterium infantis M-63, breve M-16V, and longum BB536 is associated with improvement in AP and QoL. These findings were not confirmed in FD subjects. Trial identifier: NCT02566876 (http://www.clinicaltrial.gov).