Imperial College London
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DrLouiseFleming

Faculty of Medicine, National Heart & Lung Institute

Honorary Senior Research Fellow
 
 
 
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Contact

 

+44 (0)20 7352 8121 ext 2938l.fleming

 
 
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Location

 

Department of Respiratory PaediaRoyal BromptonRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hoda:2022:10.1002/ctm2.816,
author = {Hoda, U and Pavlidis, S and Bansal, AT and Takahashi, K and Hu, S and Ng, Kee Kwong F and Rossios, C and Sun, K and Bhavsar, P and Loza, M and Baribaud, F and Chanez, P and Fowler, SJ and Horvath, I and Montuschi, P and Singer, F and Musial, J and Dahlen, B and Krug, N and Sandstrom, T and Shaw, DE and Lutter, R and Fleming, LJ and Howarth, PH and Caruso, M and Sousa, AR and Corfield, J and Auffray, C and De, Meulder B and Lefaudeux, D and Dahlen, S-E and Djukanovic, R and Sterk, PJ and Guo, Y and Adcock, IM and Chung, KF and Chung, KF},
doi = {10.1002/ctm2.816},
journal = {Clinical and Translational Medicine},
title = {Clinical and transcriptomic features of persistent exacerbation-prone  severe asthma in U-BIOPRED cohort},
url = {http://dx.doi.org/10.1002/ctm2.816},
volume = {12},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Background:  Exacerbation-prone asthma is a feature of severe disease. Yet, the basis for its persistency remains unclear. Objectives: To determine the clinical and transcriptomic features of the frequent-exacerbator (FE) and of persistent FEs (PFE) in U-BIOPRED cohort. Methods: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, <2 exacerbations) and of PFE with repeat ≥2 exacerbations during the following year to persistent IE (PIE). Transcriptomic data in blood, bronchial and nasal epithelial brushings, bronchial biopsies and sputum cells were analysed by gene set variation analysis for 103 gene signatures.Results: Of 317 patients, 62.4 % were FE of whom 63.6% were PFE, while 37.6% were IE of whom 61.3% were PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE with eczema, short-acting beta-agonist use and asthma control index. CEA Cell Adhesion Molecule 5 (CEACAM5) was the only differentially-expressed transcript in bronchial biopsies between PE and IE. There were no differentially-expressed genes in the other 4 compartments. There were higher expression scores  for Type 2 , T-helper type-17 and Type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while higher expression scores of Type 2, Type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.Conclusion: FE group and its PFE subgroup are associated with poor asthma control while expressing higher Type 1 and Type 2 activation pathways compared to IE and PIE, respectively.
AU  - Hoda,U
AU  - Pavlidis,S
AU  - Bansal,AT
AU  - Takahashi,K
AU  - Hu,S
AU  - Ng,Kee Kwong F
AU  - Rossios,C
AU  - Sun,K
AU  - Bhavsar,P
AU  - Loza,M
AU  - Baribaud,F
AU  - Chanez,P
AU  - Fowler,SJ
AU  - Horvath,I
AU  - Montuschi,P
AU  - Singer,F
AU  - Musial,J
AU  - Dahlen,B
AU  - Krug,N
AU  - Sandstrom,T
AU  - Shaw,DE
AU  - Lutter,R
AU  - Fleming,LJ
AU  - Howarth,PH
AU  - Caruso,M
AU  - Sousa,AR
AU  - Corfield,J
AU  - Auffray,C
AU  - De,Meulder B
AU  - Lefaudeux,D
AU  - Dahlen,S-E
AU  - Djukanovic,R
AU  - Sterk,PJ
AU  - Guo,Y
AU  - Adcock,IM
AU  - Chung,KF
AU  - Chung,KF
DO  - 10.1002/ctm2.816
PY  - 2022///
SN  - 2001-1326
TI  - Clinical and transcriptomic features of persistent exacerbation-prone  severe asthma in U-BIOPRED cohort
T2  - Clinical and Translational Medicine
UR  - http://dx.doi.org/10.1002/ctm2.816
UR  - http://hdl.handle.net/10044/1/96689
VL  - 12
ER  -
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