Imperial College London
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ProfessorAndrewBush

Faculty of Medicine, National Heart & Lung Institute

Professor of Paediatric Respirology
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 2255a.bush

 
 
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Location

 

Chelsea WingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hekking:2017:10.1016/j.jaci.2017.06.037,
author = {Hekking, PP and Loza, MJ and Pavlidis, S and De, Meulder B and Lefaudeux, D and Baribaud, F and Auffray, C and Wagener, A and Brinkman, P and Lutter, I and Bansal, A and Sousa, A and Bates, S and Pandis, Y and Fleming, L and Shaw, DE and Fowler, SJ and Guo, Y and Meiser, A and Sun, K and Corfield, J and Howarth, P and Bel, EH and Adcock, IM and Chung, KF and Djukanovic, R and Sterk, PJ and U-BIOPRED, Study Group},
doi = {10.1016/j.jaci.2017.06.037},
journal = {Journal of Allergy and Clinical Immunology},
pages = {1280--1290},
title = {Pathway discovery using transcriptomic profiles in adult-onset severe asthma},
url = {http://dx.doi.org/10.1016/j.jaci.2017.06.037},
volume = {141},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - RationaleAdult-onset severe asthma is characterized by highly symptomatic disease despite high intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease needed for the development of targeted treatments. Gene Set Variation Analysis (GSVA) is a statistical technique to identify gene profiles in heterogeneous samples.ObjectiveTo identify gene profiles associated with adult-onset severe asthma.MethodsThis was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at ≥18yrs old) as compared to childhood-onset severe asthma (<18 yrs) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n=83), nasal brushings (n=41), and endobronchial brushings (n=65) and biopsies (n=47) (Affymetrix HT HG-U133+ PM). GSVA was used to identify differentially enriched pre-defined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.ResultsSignificant differentially enriched gene signatures in patients with adult-onset as compared to childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures) and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells and group 3 innate lymphoid cells (ILC3) were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma.ConclusionsAdult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells and ILC3s. These pathways could represent useful targets for the treatment of adult-onset severe asthma.
AU  - Hekking,PP
AU  - Loza,MJ
AU  - Pavlidis,S
AU  - De,Meulder B
AU  - Lefaudeux,D
AU  - Baribaud,F
AU  - Auffray,C
AU  - Wagener,A
AU  - Brinkman,P
AU  - Lutter,I
AU  - Bansal,A
AU  - Sousa,A
AU  - Bates,S
AU  - Pandis,Y
AU  - Fleming,L
AU  - Shaw,DE
AU  - Fowler,SJ
AU  - Guo,Y
AU  - Meiser,A
AU  - Sun,K
AU  - Corfield,J
AU  - Howarth,P
AU  - Bel,EH
AU  - Adcock,IM
AU  - Chung,KF
AU  - Djukanovic,R
AU  - Sterk,PJ
AU  - U-BIOPRED,Study Group
DO  - 10.1016/j.jaci.2017.06.037
EP  - 1290
PY  - 2017///
SN  - 1097-6825
SP  - 1280
TI  - Pathway discovery using transcriptomic profiles in adult-onset severe asthma
T2  - Journal of Allergy and Clinical Immunology
UR  - http://dx.doi.org/10.1016/j.jaci.2017.06.037
UR  - http://hdl.handle.net/10044/1/49601
VL  - 141
ER  -
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