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

Wilson, Susan J. and Ward, Jonathan A. and Sousa, Ana R. and Corfield, Julie and Bansal, Aruna T. and De Meulder, Bertrand and Lefaudeux, Diane and Auffray, Charles and Loza, Matthew J. and Baribaud, Frederic and Fitch, Neil and Sterk, Peter J. and Chung, Kian Fan and Gibeon, David and Sun, Kai and Guo, Yi-ke and Adcock, Ian M. and Djukanovic, Ratko and Dahlen, Barbro and Chanez, Pascal and Shaw, Dominick E. and Krug, Norbert and Hohlfeld, Jens and Sandström, Thomas and Howarth, Peter H. (2016) Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study. European Respiratory Journal, 48 (5). pp. 1307-1319. ISSN 1399-3003

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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.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine
Identification Number: 10.1183/13993003.01129-2016
Depositing User: Eprints, Support
Date Deposited: 09 May 2017 07:44
Last Modified: 13 May 2017 06:51
URI: http://eprints.nottingham.ac.uk/id/eprint/42607

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