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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
European Respiratory Society
2016
|
| Online Access: | https://eprints.nottingham.ac.uk/42607/ |
| _version_ | 1848796525495320576 |
|---|---|
| author | Wilson, Susan J. Ward, Jonathan A. Sousa, Ana R. Corfield, Julie Bansal, Aruna T. De Meulder, Bertrand Lefaudeux, Diane Auffray, Charles Loza, Matthew J. Baribaud, Frederic Fitch, Neil Sterk, Peter J. Chung, Kian Fan Gibeon, David Sun, Kai Guo, Yi-ke Adcock, Ian M. Djukanovic, Ratko Dahlen, Barbro Chanez, Pascal Shaw, Dominick E. Krug, Norbert Hohlfeld, Jens Sandström, Thomas Howarth, Peter H. |
| author_facet | Wilson, Susan J. Ward, Jonathan A. Sousa, Ana R. Corfield, Julie Bansal, Aruna T. De Meulder, Bertrand Lefaudeux, Diane Auffray, Charles Loza, Matthew J. Baribaud, Frederic Fitch, Neil Sterk, Peter J. Chung, Kian Fan Gibeon, David Sun, Kai Guo, Yi-ke Adcock, Ian M. Djukanovic, Ratko Dahlen, Barbro Chanez, Pascal Shaw, Dominick E. Krug, Norbert Hohlfeld, Jens Sandström, Thomas Howarth, Peter H. |
| author_sort | Wilson, Susan J. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:49:22Z |
| format | Article |
| id | nottingham-42607 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:49:22Z |
| publishDate | 2016 |
| publisher | European Respiratory Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-426072024-08-15T15:20:43Z https://eprints.nottingham.ac.uk/42607/ Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study Wilson, Susan J. Ward, Jonathan A. Sousa, Ana R. Corfield, Julie Bansal, Aruna T. De Meulder, Bertrand Lefaudeux, Diane Auffray, Charles Loza, Matthew J. Baribaud, Frederic Fitch, Neil Sterk, Peter J. Chung, Kian Fan Gibeon, David Sun, Kai Guo, Yi-ke Adcock, Ian M. Djukanovic, Ratko Dahlen, Barbro Chanez, Pascal Shaw, Dominick E. Krug, Norbert Hohlfeld, Jens Sandström, Thomas Howarth, Peter H. 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. European Respiratory Society 2016-10-06 Article PeerReviewed Wilson, Susan J., Ward, Jonathan A., Sousa, Ana R., Corfield, Julie, Bansal, Aruna T., De Meulder, Bertrand, Lefaudeux, Diane, Auffray, Charles, Loza, Matthew J., Baribaud, Frederic, Fitch, Neil, Sterk, Peter J., Chung, Kian Fan, Gibeon, David, Sun, Kai, Guo, Yi-ke, Adcock, Ian M., Djukanovic, Ratko, Dahlen, Barbro, Chanez, Pascal, Shaw, Dominick E., Krug, Norbert, Hohlfeld, Jens, 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 https://doi.org/10.1183/13993003.01129-2016 doi:10.1183/13993003.01129-2016 doi:10.1183/13993003.01129-2016 |
| spellingShingle | Wilson, Susan J. Ward, Jonathan A. Sousa, Ana R. Corfield, Julie Bansal, Aruna T. De Meulder, Bertrand Lefaudeux, Diane Auffray, Charles Loza, Matthew J. Baribaud, Frederic Fitch, Neil Sterk, Peter J. Chung, Kian Fan Gibeon, David Sun, Kai Guo, Yi-ke Adcock, Ian M. Djukanovic, Ratko Dahlen, Barbro Chanez, Pascal Shaw, Dominick E. Krug, Norbert Hohlfeld, Jens Sandström, Thomas Howarth, Peter H. Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study |
| title | Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study |
| title_full | Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study |
| title_fullStr | Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study |
| title_full_unstemmed | Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study |
| title_short | Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study |
| title_sort | severe asthma exists despite suppressed tissue inflammation: findings of the u-biopred study |
| url | https://eprints.nottingham.ac.uk/42607/ https://eprints.nottingham.ac.uk/42607/ https://eprints.nottingham.ac.uk/42607/ |