Imperial College London
Portrait Picture

ProfessorRobertSnelgrove

Faculty of Medicine, National Heart & Lung Institute

Professor of Respiratory Science
 
 
 
//

Contact

 

+44 (0)20 7594 8192robert.snelgrove

 
 
//

Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Castanhinha:2015:10.1016/j.jaci.2015.01.016,
author = {Castanhinha, S and Sherburn, RT and Walker, SA and Gupta, A and Bossley, CJ and Buckley, J and Ullmann, N and Grychtol, R and Campbell, GA and Maglione, M and Koo, S and Fleming, LJ and Gregory, LG and Snelgrove, RJ and Bush, AJ and Lloyd, CM and Saglani, S},
doi = {10.1016/j.jaci.2015.01.016},
journal = {Journal of Allergy and Clinical Immunology},
pages = {312--322.e7},
title = {Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33},
url = {http://dx.doi.org/10.1016/j.jaci.2015.01.016},
volume = {136},
year = {2015}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - 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.
AU  - Castanhinha,S
AU  - Sherburn,RT
AU  - Walker,SA
AU  - Gupta,A
AU  - Bossley,CJ
AU  - Buckley,J
AU  - Ullmann,N
AU  - Grychtol,R
AU  - Campbell,GA
AU  - Maglione,M
AU  - Koo,S
AU  - Fleming,LJ
AU  - Gregory,LG
AU  - Snelgrove,RJ
AU  - Bush,AJ
AU  - Lloyd,CM
AU  - Saglani,S
DO  - 10.1016/j.jaci.2015.01.016
EP  - 322
PY  - 2015///
SN  - 1097-6825
SP  - 312
TI  - Pediatric severe asthma with fungal sensitization is mediated by steroid-resistant IL-33
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2015.01.016
UR  - http://hdl.handle.net/10044/1/25197
VL  - 136
ER  -
Download