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

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

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.

0903-1936
1307-1319
Wilson, Susan J.
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Ward, Jonathan A.
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Sousa, Ana
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Corfield, Julie
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Bansal, Aruna
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Meulder, Bertrand
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Lefaudeux, Diane
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Auffray, Charles
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Loza, Matthew
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Baribaud, Frederic
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Fitch, Neil
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Sterk, Peter
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Chung, Kian
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Gibeon, David
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Sun, Kai
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Yi-ke, Guo
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Adcock, Ian
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Djukanovic, Ratko
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Dahlen, Barbro
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Chanez, Pascal
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Shaw, Dominick
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Krug, Norbert
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Hohlfeld, Jens
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Sandtrom, Thomas
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Howarth, Peter H.
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on behalf of the U-BIOPRED Study Group
Wilson, Susan J.
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Ward, Jonathan A.
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Sousa, Ana
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Corfield, Julie
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Bansal, Aruna
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Meulder, Bertrand
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Lefaudeux, Diane
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Auffray, Charles
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Loza, Matthew
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Baribaud, Frederic
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Fitch, Neil
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Sterk, Peter
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Chung, Kian
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Gibeon, David
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Sun, Kai
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Yi-ke, Guo
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Adcock, Ian
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Djukanovic, Ratko
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Dahlen, Barbro
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Chanez, Pascal
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Shaw, Dominick
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Krug, Norbert
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Hohlfeld, Jens
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Sandtrom, Thomas
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Howarth, Peter H.
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Wilson, Susan J., Ward, Jonathan A., Sousa, Ana, Corfield, Julie, Bansal, Aruna, Meulder, Bertrand, Lefaudeux, Diane, Auffray, Charles, Loza, Matthew, Baribaud, Frederic, Fitch, Neil, Sterk, Peter, Chung, Kian, Gibeon, David, Sun, Kai, Yi-ke, Guo, Adcock, Ian, Djukanovic, Ratko, Dahlen, Barbro, Chanez, Pascal, Shaw, Dominick, Krug, Norbert, Hohlfeld, Jens, Sandtrom, Thomas and Howarth, Peter H. , on behalf of the U-BIOPRED Study Group (2016) Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study. European Respiratory Journal, 48 (5), 1307-1319. (doi:10.1183/13993003.01129-2016). (PMID:27799384)

Record type: 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.

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Accepted/In Press date: 10 August 2016
e-pub ahead of print date: 6 October 2016
Published date: November 2016
Organisations: Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 405428
URI: https://eprints.soton.ac.uk/id/eprint/405428
ISSN: 0903-1936
PURE UUID: 3abb73b2-6b6d-46e5-861d-f5d1c250fc2f
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 03 Feb 2017 14:30
Last modified: 10 Dec 2019 01:58

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Contributors

Author: Susan J. Wilson
Author: Jonathan A. Ward
Author: Ana Sousa
Author: Julie Corfield
Author: Aruna Bansal
Author: Bertrand Meulder
Author: Diane Lefaudeux
Author: Charles Auffray
Author: Matthew Loza
Author: Frederic Baribaud
Author: Neil Fitch
Author: Peter Sterk
Author: Kian Chung
Author: David Gibeon
Author: Kai Sun
Author: Guo Yi-ke
Author: Ian Adcock
Author: Barbro Dahlen
Author: Pascal Chanez
Author: Dominick Shaw
Author: Norbert Krug
Author: Jens Hohlfeld
Author: Thomas Sandtrom

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