Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33.

BACKGROUND: The 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. OBJECTIVE: We sought to determine whether fungal sensitization in children with severe therapy-resistant asthma is mediated by IL-33. METHODS: Eighty-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. RESULTS: Children 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. CONCLUSION: Pediatric 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.

Bombesin staining in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILD).

AIMS: We have analysed levels of bombesin-positive neuroendocrine cells (NECs) in neuroendocrine cell hyperplasia of infancy (NEHI) and other childhood interstitial lung diseases (chILDs) in order to validate proposed histological criteria for NEHI and investigate its aetiology. METHODS AND RESULTS: The extent of bombesin-positive cells within airway epithelium was analysed in lung biopsies from seven patients diagnosed with NEHI, including two classified previously as non-diagnostic, and other chILDs (n = 64) with age ranges of 1 month-18 years. NECs were counted and calculated as a percentage of airways containing NECs, average percentage of NECs per airway, percentage of airways with >10% NECs and number of neuroendocrine bodies (NEBs). Correlation with age and gender was also undertaken. Patients with NEHI had the highest average percentage of bombesin-positive NECs per airway compared to other chILDs. However, NEH was also seen in many other chILDs, and appears to be most prominent in disorders associated with lung immaturity such as histological patterns associated with surfactant protein-related disorders and pulmonary interstitial glycogenosis. CONCLUSIONS: NEH may, to a degree, be a marker of airway immaturity rather than the direct cause of NEHI. This possibility is supported by the fact that the number of bombesin-positive NECs decreased with age in this cohort, independent of disease type. The average percentage of bombesin-positive NECs per airway appears to be the best histological criterion for assessing the extent of NECs in the context of NEHI.

Cardiovascular symptoms and signs in evaluating cardiac murmurs in children.

BACKGROUND: The aim of the present study was to determine the usefulness of cardiovascular symptoms and signs in the recognition of significant congenital heart lesions that required surgical or catheter interventions in different pediatric age groups. METHODS: A retrospective chart review was carried out of 110 patients with significant heart anomalies that required surgical or catheter interventions (group I) and 113 children, presenting with cardiac murmurs, with congenital heart conditions not requiring any interventions. (group II). RESULTS: Clinical symptoms or signs were significantly more common in group I than in group II subjects (85% vs 32%, P < 0.0001). The odds of having significant lesions requiring interventions in the presence of either cardiovascular symptoms or signs were 37.5 (95% confidence interval [CI]: 6.5-218.1) for neonates, 14.5 (95%CI: 4.7-51.7) for infants, and 8.0 (95%CI: 3.3-19.2) for children and adolescents. In neonates, the negative predictive values of the absence of symptoms or signs in isolation were relatively low at 64% and 65%, respectively. In children beyond infancy, the positive predictive values of the presence of symptoms or signs in isolation were also low at 62% and 68%, respectively. CONCLUSIONS: Clinical assessment of cardiovascular symptoms and signs remains useful in the evaluation of the significance of pathological cardiac murmurs in children in the present era of technology. Nonetheless, the predictive values vary with different pediatric age groups.

Ethnic Variation in Response to IM Triamcinolone in Children With Severe Therapy-Resistant Asthma.

BACKGROUND: Although ethnicity may influence response to treatment of patients with asthma, this approach is controversial. The objective of this study was to determine if ethnicity influences the response to IM steroid use (eliminating adherence as an issue). METHODS: Children with severe therapy-resistant asthma who had previously undergone a detailed assessment (including a nurse-led hospital and home visit in which potentially modifiable factors had been identified and addressed) were admitted for further evaluation; this evaluation included assessment of steroid response. Children were classified as white, black, Asian, or mixed white/black. Steroid responsiveness was defined according to symptoms (Asthma Control Test), inflammation (sputum eosinophil count and exhaled nitric oxide), and spirometry (FEV1); these variables were measured before and 4 weeks after IM triamcinolone use. Data were collected regarding exacerbations. Fractional exhaled nitric oxide (Feno) response was defined as a decrease to < 24 parts per billion (ppb). RESULTS: Seventy-nine subjects were identified (white, n = 54 [68%]; black, n = 16 [20%]; Asian, n = 5 [6%]; and mixed white/black, n = 4 [5%]). After administration of triamcinolone, there was a significant drop in median Feno in white children (46.8 to 23.1 ppb; P < .001) but not in black children (52.2 to 34.5 ppb; P = .58). More black children than white children (86.7%) were Feno nonresponders (86.7% vs 45.3%; P < .05), and more black children had exacerbations compared with white children (61% vs 17%; P < .05). CONCLUSIONS: Black children with asthma were less likely to report an Feno response and had more exacerbations 4 weeks after administration of triamcinolone than white children. Further research is needed to understand the mechanisms of these differences, but they cannot be due to differences in adherence or access to care.

Prevalence of scoliosis in cystic fibrosis.

BACKGROUND: The prevalence of idiopathic scoliosis in the general pediatric population is reported to be between 0.5% and 3.2%. Previous studies have reported an increased prevalence of scoliosis in children with cystic fibrosis (CF). HYPOTHESIS: The prevalence of scoliosis in CF children is greater than in the normal population. METHODS: Chest X-rays of 319 patients attending the Royal Brompton CF Centre were reviewed. The Cobb angle of any spinal lateral curvature was measured. Scoliosis was defined as a Cobb angle of more than 10°. RESULTS: Median age of the whole group of patients was 10.9 years (range 1.1-18 years), 53% were females. Seven patients (2.2%) had radiological signs of scoliosis, their mean age was 14.5 ± 2.3 years (range: 11.5-18 years), 5 were females. Age at onset of scoliosis was between 5 and 10 years for three patients and over 10 years for the others. All the curves were thoracic and with right convexity: apices between T7 and T9 for the single curves (n = 5) and between T4 and T5 (n = 2) for the double curves. CONCLUSION: CF patients showed a similar prevalence of scoliosis as in the normal population (2.2% vs. 0.5-3.2%). There was the same gender (female) and side (right-sided) predilection as in normal population.