Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study.

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Title: Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study.
Authors: Wilson, SJ
Ward, JA
Sousa, AR
Corfield, J
Bansal, AT
De Meulder, B
Lefaudeux, D
Auffray, C
Loza, MJ
Baribaud, F
Fitch, N
Sterk, PJ
Chung, KF
Gibeon, D
Sun, K
Guo, YK
Adcock, I
Djukanovic, R
Dahlen, B
Chanez, P
Shaw, D
Krug, N
Hohlfeld, J
Sandström, T
Howarth, PH
U-BIOPRED Study Group
Item Type: Journal Article
Abstract: The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild-moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm(-2)) compared with both severe asthma groups (SAn: 17.4 mm(-2), p<0.001; SAs/ex: 22.2 mm(-2), p=0.01) and with the MMA group (21.2 mm(-2), p=0.01). The number of CD4(+) lymphocytes was decreased in the SAs/ex group (4.7 mm(-2)) compared with the SAn (11.6 mm(-2), p=0.002), MMA (10.1 mm(-2), p=0.008) and HC (10.6 mm(-2), p<0.001) groups. No other differences were observed.Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall.
Issue Date: 6-Oct-2016
Date of Acceptance: 10-Aug-2016
URI: http://hdl.handle.net/10044/1/42609
DOI: https://dx.doi.org/10.1183/13993003.01129-2016
ISSN: 1399-3003
Publisher: European Respiratory Society: ERJ
Start Page: 1307
End Page: 1319
Journal / Book Title: European Respiratory Journal
Volume: 48
Issue: 5
Copyright Statement: © 2016 ERS. This is an author-submitted, peer-reviewed version of a manuscript that has been accepted for publication in the European Respiratory Journal, prior to copy-editing, formatting and typesetting. This version of the manuscript may not be duplicated or reproduced without prior permission from the copyright owner, the European Respiratory Society. The publisher is not responsible or liable for any errors or omissions in this version of the manuscript or in any version derived from it by any other parties. The final, copy-edited, published article, which is the version of record, is available without a subscription 18 months after the date of issue publication.
Sponsor/Funder: Commission of the European Communities
National Institute for Health Research
Funder's Grant Number: 115010
BRU 6535
Keywords: Respiratory System
11 Medical And Health Sciences
Publication Status: Published
Conference Place: England
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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