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Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Jeanne-Marie Perotin, James P.R. Schofield, Susan J. Wilson, Jonathan Ward, Joost Brandsma, Fabio Strazzeri, Aruna Bansal, Xian Yang, Anthony Rowe, Julie Corfield, Rene Lutter, Dominick E. Shaw, Per S. Bakke, Massimo Caruso, Barbro Dahlén, Stephen J. Fowler, Ildikó Horváth, Peter Howarth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Kai Sun, Ioannis Pandis, Charles Auffray, Bertrand De Meulder, Diane Lefaudeux, John H. Riley, Ana R. Sousa, Sven-Erik Dahlen, Ian M. Adcock, Kian Fan Chung, Peter J. Sterk, Paul J. Skipp, Jane E. Collins, Donna E. Davies, Ratko Djukanović on behalf of the U-BIOPRED Study Group
European Respiratory Journal 2019 53: 1900453; DOI: 10.1183/13993003.00453-2019
Jeanne-Marie Perotin
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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  • For correspondence: j-m.perotin-collard@soton.ac.uk
James P.R. Schofield
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
2Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, UK
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Susan J. Wilson
3The Histochemistry Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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Jonathan Ward
3The Histochemistry Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK
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Joost Brandsma
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Fabio Strazzeri
4Mathematical Sciences, University of Southampton, Southampton, UK
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Aruna Bansal
5Acclarogen Ltd, Cambridge, UK
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Xian Yang
6Data Science Institute, Imperial College London, London, UK
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Anthony Rowe
7Janssen Research and Development, High Wycombe, UK
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Julie Corfield
8Areteva Ltd, Nottingham, UK
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Rene Lutter
9Amsterdam UMC, Dept of Experimental Immunology (Amsterdam Infection and Immunity Institute), University of Amsterdam, Amsterdam, The Netherlands
10Amsterdam UMC, Dept of Respiratory Medicine, University of Amsterdam, Amsterdam, The Netherlands
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Dominick E. Shaw
11NIHR Biomedical Respiratory Research Centre, University of Nottingham, Nottingham, UK
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  • ORCID record for Dominick E. Shaw
Per S. Bakke
12Institute of Medicine, University of Bergen, Bergen, Norway
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Massimo Caruso
13Dept of Clinical and Experimental Medicine Hospital University, University of Catania, Catania, Italy
14Dept of Biomedical and Biotechnological Sciences (Biometec), University of Catania, Catania, Italy
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  • ORCID record for Massimo Caruso
Barbro Dahlén
15Dept of Respiratory Diseases and Allergy, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden
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Stephen J. Fowler
16Respiratory and Allergy Research Group, University of Manchester, Manchester, UK
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Ildikó Horváth
17Dept of Pulmonology, Semmelweis University, Budapest, Hungary
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Peter Howarth
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Norbert Krug
18Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany
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Paolo Montuschi
19Faculty of Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Rome, Italy
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Marek Sanak
20Laboratory of Molecular Biology and Clinical Genetics, Medical College, Jagiellonian University, Krakow, Poland
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Thomas Sandström
21Dept of Medicine, Dept of Public Health and Clinical Medicine Respiratory Medicine Unit, Umeå University, Umeå, Sweden
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Kai Sun
7Janssen Research and Development, High Wycombe, UK
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Ioannis Pandis
7Janssen Research and Development, High Wycombe, UK
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Charles Auffray
22European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Université de Lyon, Lyons, France
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Bertrand De Meulder
22European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Université de Lyon, Lyons, France
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Diane Lefaudeux
22European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Université de Lyon, Lyons, France
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  • ORCID record for Diane Lefaudeux
John H. Riley
23Respiratory Therapeutic Unit, GSK, Uxbridge, UK
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Ana R. Sousa
23Respiratory Therapeutic Unit, GSK, Uxbridge, UK
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Sven-Erik Dahlen
24The Centre for Allergy Research, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
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Ian M. Adcock
25Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
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Kian Fan Chung
25Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK
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Peter J. Sterk
11NIHR Biomedical Respiratory Research Centre, University of Nottingham, Nottingham, UK
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Paul J. Skipp
2Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, UK
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Jane E. Collins
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Donna E. Davies
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Ratko Djukanović
1NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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    FIGURE 1

    Severe asthma clusters based on epithelial transcriptomics. a) Topological data analysis network constructed with transcripts from bronchial brushings using density analysis by Morse theory, with b) the identified clusters 1–3 coloured yellow, pink and orange. Applying c) body mass index (BMI), d) gastro-oesophageal reflux disease (GORD) treatment and e) blood eosinophil counts as metadata, nodes are coloured by intensity from blue (low intensity) to red (high intensity). f) Heat map of the three top upregulated and three top downregulated differentially expressed genes of wingless tail (WNT)/β-catenin, triggering receptor expressed on myeloid cells (TREM)1 and calcium signalling in the obesity–GORD–proton pump inhibitor treatment (OGP) cluster and in airway epithelial cells exposed to proton pump inhibitors (lansoprazole (L) and rabeprazole (R)) and bile acids (glycodeoxycholic acid (G) and taurodeoxycholic acid (T)). Cmap: connectivity mapping.

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Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux
Jeanne-Marie Perotin, James P.R. Schofield, Susan J. Wilson, Jonathan Ward, Joost Brandsma, Fabio Strazzeri, Aruna Bansal, Xian Yang, Anthony Rowe, Julie Corfield, Rene Lutter, Dominick E. Shaw, Per S. Bakke, Massimo Caruso, Barbro Dahlén, Stephen J. Fowler, Ildikó Horváth, Peter Howarth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Kai Sun, Ioannis Pandis, Charles Auffray, Bertrand De Meulder, Diane Lefaudeux, John H. Riley, Ana R. Sousa, Sven-Erik Dahlen, Ian M. Adcock, Kian Fan Chung, Peter J. Sterk, Paul J. Skipp, Jane E. Collins, Donna E. Davies, Ratko Djukanović
European Respiratory Journal Jun 2019, 53 (6) 1900453; DOI: 10.1183/13993003.00453-2019

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Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux
Jeanne-Marie Perotin, James P.R. Schofield, Susan J. Wilson, Jonathan Ward, Joost Brandsma, Fabio Strazzeri, Aruna Bansal, Xian Yang, Anthony Rowe, Julie Corfield, Rene Lutter, Dominick E. Shaw, Per S. Bakke, Massimo Caruso, Barbro Dahlén, Stephen J. Fowler, Ildikó Horváth, Peter Howarth, Norbert Krug, Paolo Montuschi, Marek Sanak, Thomas Sandström, Kai Sun, Ioannis Pandis, Charles Auffray, Bertrand De Meulder, Diane Lefaudeux, John H. Riley, Ana R. Sousa, Sven-Erik Dahlen, Ian M. Adcock, Kian Fan Chung, Peter J. Sterk, Paul J. Skipp, Jane E. Collins, Donna E. Davies, Ratko Djukanović
European Respiratory Journal Jun 2019, 53 (6) 1900453; DOI: 10.1183/13993003.00453-2019
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