. 2019 Jun 27;53(6):1900453.

doi: 10.1183/13993003.00453-2019. Print 2019 Jun.

Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Jeanne-Marie Perotin¹, James P R Schofield^{2

3}, Susan J Wilson⁴, Jonathan Ward⁴, Joost Brandsma², Fabio Strazzeri⁵, Aruna Bansal⁶, Xian Yang⁷, Anthony Rowe⁸, Julie Corfield⁹, Rene Lutter^{10

11}, Dominick E Shaw¹², Per S Bakke¹³, Massimo Caruso^{14

15}, Barbro Dahlén¹⁶, Stephen J Fowler¹⁷, Ildikó Horváth¹⁸, Peter Howarth², Norbert Krug¹⁹, Paolo Montuschi²⁰, Marek Sanak²¹, Thomas Sandström²², Kai Sun⁸, Ioannis Pandis⁸, Charles Auffray²³, Bertrand De Meulder²³, Diane Lefaudeux²³, John H Riley²⁴, Ana R Sousa²⁴, Sven-Erik Dahlen²⁵, Ian M Adcock²⁶, Kian Fan Chung²⁶, Peter J Sterk¹², Paul J Skipp³, Jane E Collins², Donna E Davies², Ratko Djukanović²; U-BIOPRED Study Group; U-BIOPRED:

Collaborators, Affiliations

Collaborators

I M Adcock, H Ahmed, C Auffray, P Bakke, A T Banssal, F Baribaud, S Bates, E H Bel, J Bigler, H Bisgaard, M J Boedigheimer, K Bønnelykke, J Brandsma, P Brinkman, E Bucchioni, D Burg, A Bush, M Caruso, A Chaiboonchoe, P Chanez, K F Chung, C H Compton, J Corfield, A D'Amico, S E Dahlen, B De Meulder, R Djukanovic, V J Erpenbeck, D Erzen, K Fichtner, N Fitch, L J Fleming, E Formaggio, S J Fowler, U Frey, M Gahlemann, T Geiser, Y Guo, S Hashimoto, J Haughney, G Hedlin, P W Hekking, T Higenbottam, J M Hohlfeld, C Holweg, I Horváth, P Howarth, A J James, R Knowles, A J Knox, N Krug, D Lefaudeux, M J Loza, R Lutter, A Manta, S Masefield, J G Matthews, A Mazein, A Meiser, R J M Middelveld, M Miralpeix, P Montuschi, N Mores, C S Murray, J Musial, D Myles, L Pahus, I Pandis, S Pavlidis, P Powell, G Praticò, M Puig Valls, N Rao, J Riley, A Roberts, G Roberts, A Rowe, T Sandström, W Seibold, A Selby, D E Shaw, R Sigmund, F Singer, P J Skipp, A R Sousa, P J Sterk, K Sun, B Thornton, W M van Aalderen, M van Geest, J Vestbo, N H Vissing, A H Wagener, S S Wagers, Z Weiszhart, C E Wheelock, S J Wilson, David Allen, Kjell Alving, P Badorrek, David Balgoma, S Ballereau, Clair Barber, Manohara Kanangana Batuwitage, An Bautmans, A Bedding, A F Behndig, Jorge Beleta, S A Almirall, A Berglind, A Berton, G Bochenek, A Braun, D Campagna, L Carayannopoulos, C Casaulta, Romanas Chaleckis, B Dahlén, T Davison, J De Alba, I De Lepeleire, T Dekker, I Delin, P Dennison, A Dijkhuis, P Dodson, Aleksandra Draper, K Dyson, J Edwards, L El Hadjam, R Emma, M Ericsson, C Faulenbach, Breda Flood, G Galffy, H Gallart, D Garissi, J Gent, M Gerhardsson de Verdier, D Gibeon, Cristina Gomez, K Gove, Neil Gozzard, E Guillmant-Farry, E Henriksson, L Hewitt, U Hoda, Richard Hu, S Hu, X Hu, E Jeyasingham, K Johnson, N Jullian, J Kamphuis, E J Kennington, D Kerry, G Kerry, M Klüglich, H Knobel, Johan Kolmert, J R Konradsen, M Kots, Kosmas Kretsos, L Krueger, S Kuo, M Kupczyk, B Lambrecht, A-S Lantz, Christopher Larminie, L X Larsson, P Latzin, N Lazarinis, N Lemonnier, S Lone-Latif, L A Lowe, A Manta, L Marouzet, J Martin, C Mathon, L McEvoy, S Meah, A Menzies-Gow, L Metcalf, M Mikus, P Monk, S Naz, K Nething, B Nicholas, U Nihlén, Peter Nilsson, R Niven, B Nordlund, S Nsubuga, J Östling, A Pacino, S Palkonen, J Pellet, G Pennazza, A Petrén, S Pink, C Pison, A Postle, M Rahman-Amin, L Ravanetti, E Ray, S Reinke, L Reynolds, K Riemann, Martine Robberechts, J P Rocha, C Rossios, K Russell, M Rutgers, G Santini, M Santoninco, M Saqi, C Schoelch, J P R Schofield, S Scott, N Sehgal, M Sjödin, B Smids, Caroline Smith, J Smith, K M Smith, P Söderman, A Sogbessan, F Spycher, D Staykova, S Stephan, J Stokholm, K Strandberg, M Sunther, M Szentkereszty, L Tamasi, K Tariq, J-O Thörngren, Jonathan Thorsen, S Valente, Marianne van de Pol, C M van Drunen, J Van Eyll, J Versnel, A Vink, C von Garnier, A Vyas, F Wald, S Walker, J Ward, K Wetzel, C Wiegman, S Williams, X Yang, E Yeyasingham, W Yu, W Zetterquist, Z Zolkipli, A H Zwinderman, J-B Prins, M Gahlemann, L Visintin, H Evans, M Puhl, L Buzermaniene, V Hudson, L Bond, P de Boer, G Widdershoven, R Sigmund, D Supple, D Hamerlijnck, J Negus, J Kamphuis, L Sergison, L Visintin, P de Boer, S Onstein, R Bernardini, Louis Bont, P-A Wecksell, P de Boer, M Gahlemann, R Sigmund

Affiliations

¹ NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK j-m.perotin-collard@soton.ac.uk.
² NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
³ Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, UK.
⁴ The Histochemistry Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
⁵ Mathematical Sciences, University of Southampton, Southampton, UK.
⁶ Acclarogen Ltd, Cambridge, UK.
⁷ Data Science Institute, Imperial College London, London, UK.
⁸ Janssen Research and Development, High Wycombe, UK.
⁹ Areteva Ltd, Nottingham, UK.
¹⁰ Amsterdam UMC, Dept of Experimental Immunology (Amsterdam Infection and Immunity Institute), University of Amsterdam, Amsterdam, The Netherlands.
¹¹ Amsterdam UMC, Dept of Respiratory Medicine, University of Amsterdam, Amsterdam, The Netherlands.
¹² NIHR Biomedical Respiratory Research Centre, University of Nottingham, Nottingham, UK.
¹³ Institute of Medicine, University of Bergen, Bergen, Norway.
¹⁴ Dept of Clinical and Experimental Medicine Hospital University, University of Catania, Catania, Italy.
¹⁵ Dept of Biomedical and Biotechnological Sciences (Biometec), University of Catania, Catania, Italy.
¹⁶ Dept of Respiratory Diseases and Allergy, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Respiratory and Allergy Research Group, University of Manchester, Manchester, UK.
¹⁸ Dept of Pulmonology, Semmelweis University, Budapest, Hungary.
¹⁹ Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany.
²⁰ Faculty of Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Rome, Italy.
²¹ Laboratory of Molecular Biology and Clinical Genetics, Medical College, Jagiellonian University, Krakow, Poland.
²² Dept of Medicine, Dept of Public Health and Clinical Medicine Respiratory Medicine Unit, Umeå University, Umeå, Sweden.
²³ European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Université de Lyon, Lyons, France.
²⁴ Respiratory Therapeutic Unit, GSK, Uxbridge, UK.
²⁵ The Centre for Allergy Research, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
²⁶ Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.

PMID: 31023846
PMCID: PMC7610816
DOI: 10.1183/13993003.00453-2019

Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Jeanne-Marie Perotin et al. Eur Respir J. 2019.

. 2019 Jun 27;53(6):1900453.

doi: 10.1183/13993003.00453-2019. Print 2019 Jun.

Authors

Collaborators

I M Adcock, H Ahmed, C Auffray, P Bakke, A T Banssal, F Baribaud, S Bates, E H Bel, J Bigler, H Bisgaard, M J Boedigheimer, K Bønnelykke, J Brandsma, P Brinkman, E Bucchioni, D Burg, A Bush, M Caruso, A Chaiboonchoe, P Chanez, K F Chung, C H Compton, J Corfield, A D'Amico, S E Dahlen, B De Meulder, R Djukanovic, V J Erpenbeck, D Erzen, K Fichtner, N Fitch, L J Fleming, E Formaggio, S J Fowler, U Frey, M Gahlemann, T Geiser, Y Guo, S Hashimoto, J Haughney, G Hedlin, P W Hekking, T Higenbottam, J M Hohlfeld, C Holweg, I Horváth, P Howarth, A J James, R Knowles, A J Knox, N Krug, D Lefaudeux, M J Loza, R Lutter, A Manta, S Masefield, J G Matthews, A Mazein, A Meiser, R J M Middelveld, M Miralpeix, P Montuschi, N Mores, C S Murray, J Musial, D Myles, L Pahus, I Pandis, S Pavlidis, P Powell, G Praticò, M Puig Valls, N Rao, J Riley, A Roberts, G Roberts, A Rowe, T Sandström, W Seibold, A Selby, D E Shaw, R Sigmund, F Singer, P J Skipp, A R Sousa, P J Sterk, K Sun, B Thornton, W M van Aalderen, M van Geest, J Vestbo, N H Vissing, A H Wagener, S S Wagers, Z Weiszhart, C E Wheelock, S J Wilson, David Allen, Kjell Alving, P Badorrek, David Balgoma, S Ballereau, Clair Barber, Manohara Kanangana Batuwitage, An Bautmans, A Bedding, A F Behndig, Jorge Beleta, S A Almirall, A Berglind, A Berton, G Bochenek, A Braun, D Campagna, L Carayannopoulos, C Casaulta, Romanas Chaleckis, B Dahlén, T Davison, J De Alba, I De Lepeleire, T Dekker, I Delin, P Dennison, A Dijkhuis, P Dodson, Aleksandra Draper, K Dyson, J Edwards, L El Hadjam, R Emma, M Ericsson, C Faulenbach, Breda Flood, G Galffy, H Gallart, D Garissi, J Gent, M Gerhardsson de Verdier, D Gibeon, Cristina Gomez, K Gove, Neil Gozzard, E Guillmant-Farry, E Henriksson, L Hewitt, U Hoda, Richard Hu, S Hu, X Hu, E Jeyasingham, K Johnson, N Jullian, J Kamphuis, E J Kennington, D Kerry, G Kerry, M Klüglich, H Knobel, Johan Kolmert, J R Konradsen, M Kots, Kosmas Kretsos, L Krueger, S Kuo, M Kupczyk, B Lambrecht, A-S Lantz, Christopher Larminie, L X Larsson, P Latzin, N Lazarinis, N Lemonnier, S Lone-Latif, L A Lowe, A Manta, L Marouzet, J Martin, C Mathon, L McEvoy, S Meah, A Menzies-Gow, L Metcalf, M Mikus, P Monk, S Naz, K Nething, B Nicholas, U Nihlén, Peter Nilsson, R Niven, B Nordlund, S Nsubuga, J Östling, A Pacino, S Palkonen, J Pellet, G Pennazza, A Petrén, S Pink, C Pison, A Postle, M Rahman-Amin, L Ravanetti, E Ray, S Reinke, L Reynolds, K Riemann, Martine Robberechts, J P Rocha, C Rossios, K Russell, M Rutgers, G Santini, M Santoninco, M Saqi, C Schoelch, J P R Schofield, S Scott, N Sehgal, M Sjödin, B Smids, Caroline Smith, J Smith, K M Smith, P Söderman, A Sogbessan, F Spycher, D Staykova, S Stephan, J Stokholm, K Strandberg, M Sunther, M Szentkereszty, L Tamasi, K Tariq, J-O Thörngren, Jonathan Thorsen, S Valente, Marianne van de Pol, C M van Drunen, J Van Eyll, J Versnel, A Vink, C von Garnier, A Vyas, F Wald, S Walker, J Ward, K Wetzel, C Wiegman, S Williams, X Yang, E Yeyasingham, W Yu, W Zetterquist, Z Zolkipli, A H Zwinderman, J-B Prins, M Gahlemann, L Visintin, H Evans, M Puhl, L Buzermaniene, V Hudson, L Bond, P de Boer, G Widdershoven, R Sigmund, D Supple, D Hamerlijnck, J Negus, J Kamphuis, L Sergison, L Visintin, P de Boer, S Onstein, R Bernardini, Louis Bont, P-A Wecksell, P de Boer, M Gahlemann, R Sigmund

Affiliations

¹ NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK j-m.perotin-collard@soton.ac.uk.
² NIHR Southampton Biomedical Research Centre, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.
³ Centre for Proteomic Research, Biological Sciences, University of Southampton, Southampton, UK.
⁴ The Histochemistry Research Unit, Faculty of Medicine, University of Southampton, Southampton, UK.
⁵ Mathematical Sciences, University of Southampton, Southampton, UK.
⁶ Acclarogen Ltd, Cambridge, UK.
⁷ Data Science Institute, Imperial College London, London, UK.
⁸ Janssen Research and Development, High Wycombe, UK.
⁹ Areteva Ltd, Nottingham, UK.
¹⁰ Amsterdam UMC, Dept of Experimental Immunology (Amsterdam Infection and Immunity Institute), University of Amsterdam, Amsterdam, The Netherlands.
¹¹ Amsterdam UMC, Dept of Respiratory Medicine, University of Amsterdam, Amsterdam, The Netherlands.
¹² NIHR Biomedical Respiratory Research Centre, University of Nottingham, Nottingham, UK.
¹³ Institute of Medicine, University of Bergen, Bergen, Norway.
¹⁴ Dept of Clinical and Experimental Medicine Hospital University, University of Catania, Catania, Italy.
¹⁵ Dept of Biomedical and Biotechnological Sciences (Biometec), University of Catania, Catania, Italy.
¹⁶ Dept of Respiratory Diseases and Allergy, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
¹⁷ Respiratory and Allergy Research Group, University of Manchester, Manchester, UK.
¹⁸ Dept of Pulmonology, Semmelweis University, Budapest, Hungary.
¹⁹ Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany.
²⁰ Faculty of Medicine, Catholic University of the Sacred Heart, Fondazione Policlinico Universitario, Agostino Gemelli IRCCS, Rome, Italy.
²¹ Laboratory of Molecular Biology and Clinical Genetics, Medical College, Jagiellonian University, Krakow, Poland.
²² Dept of Medicine, Dept of Public Health and Clinical Medicine Respiratory Medicine Unit, Umeå University, Umeå, Sweden.
²³ European Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, Université de Lyon, Lyons, France.
²⁴ Respiratory Therapeutic Unit, GSK, Uxbridge, UK.
²⁵ The Centre for Allergy Research, The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
²⁶ Cell and Molecular Biology Group, Airways Disease Section, National Heart and Lung Institute, Imperial College London, London, UK.

PMID: 31023846
PMCID: PMC7610816
DOI: 10.1183/13993003.00453-2019

No abstract available

PubMed Disclaimer

Conflict of interest statement

Conflict of interest: J.M. Perotin has nothing to disclose. Conflict of interest: J.P.R. Schofield has nothing to disclose. Conflict of interest: S.J. Wilson has nothing to disclose. Conflict of interest: J. Ward has nothing to disclose. Conflict of interest: J. Brandsma has nothing to disclose. Conflict of interest: F. Strazzeri has nothing to disclose. Conflict of interest: A. Bansal has nothing to disclose. Conflict of interest: X. Yang has nothing to disclose. Conflict of interest: A. Rowe is a full-time employee and shareholder of Janssen Pharmaceutical Companies of Johnson and Johnson. Conflict of interest: J. Corfield has nothing to disclose. Conflict of interest: R. Lutter has nothing to disclose. Conflict of interest: D.E. Shaw reports fees for lectures at company sponsored symposia and support to attend an international conference from AstraZeneca, fees for lectures at company sponsored symposia and investigator-initiated research funding from Boehringer Ingelheim, fees for lectures at company sponsored symposia from Novartis and Teva, a fee for presentation from Circassia, and a grant for an investigator led study from GSK, outside the submitted work. Conflict of interest: P.S. Bakke reports personal fees from GSK, AZ, Novartis andTeva, outside the submitted work. Conflict of interest: M. Caruso has no conflict of interest to disclose. Conflict of interest: B. Dahlén has nothing to disclose. Conflict of interest: S.J. Fowler reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, and personal fees from Novartis and Teva, outside the submitted work. Conflict of interest: I. Horváth reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, CSL, Chiesi, Roche, GSK, Berlin-Chemie and Sandoz, outside the submitted work. Conflict of interest: P. Howarth reports personal fees from GSK, outside the submitted work. Conflict of interest: N. Krug has nothing to disclose. Conflict of interest: P. Montuschi has nothing to disclose. Conflict of interest: M. Sanak has nothing to disclose. Conflict of interest: T. Sandström reports Fees for lectures and course arrangement from Boehringer Ingelheim, outside the submitted work. Conflict of interest: K. Sun has nothing to disclose. Conflict of interest: I. Pandis has nothing to disclose. Conflict of interest: C. Auffray reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: B. De Meulder reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: D. Lefaudeux reports grants from Innovative Medicine Initiative, grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: J.H. Riley reports that he has shares in and is employed by GSK. Conflict of interest: A.R. Sousa has nothing to disclose. Conflict of interest: S-E. Dahlén has nothing to disclose. Conflict of interest: I.M. Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: K.F. Chung has received honoraria for participating in Advisory Board meetings of GSK, AZ, BI, Teva, Novartis and Merck regarding treatments for asthma and chronic obstructive pulmonary disease, and has also been renumerated for speaking engagements. Conflict of interest: P.J. Sterk reports grants from Innovative Medicines Initiative, during the conduct of the study. Conflict of interest: P.J. Skipp has nothing to disclose. Conflict of interest: J.E. Collins reports a patent application for use of a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease and uses to screen the impact of such genes. Conflict of interest: D.E. Davies has nothing to disclose. Conflict of interest: R. Djukanović reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. He is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.

Figures

None — **Severe asthma clusters based on epithelial transcriptomics.**
(a) TDA network constructed with transcripts from bronchial brushings using density analysis by Morse theory, with (b) the identified clusters 1-3 colored yellow, pink and orange. (c-e) Applying BMI, GORD treatment and blood eosinophil counts as meta data, nodes are colored 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 WNT/β-catenin, TREM1 and Calcium signalling in the OGP cluster and in airway epithelial cells exposed to PPI (column L for Lansoprazole and column R for Rabeprazole) and bile acids (column G for Glycodeoxycholic acid and T for Taurodeoxycholic acid).

See this image and copyright information in PMC

Comment in

Regarding epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux.
Ward C, Kharaba ZJ. Ward C, et al. Eur Respir J. 2019 Oct 10;54(4):1901376. doi: 10.1183/13993003.01376-2019. Print 2019 Oct. Eur Respir J. 2019. PMID: 31601720 No abstract available.
Regarding epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux.
Perotin JM, Djukanovic R, Davies DE. Perotin JM, et al. Eur Respir J. 2019 Oct 10;54(4):1901805. doi: 10.1183/13993003.01805-2019. Print 2019 Oct. Eur Respir J. 2019. PMID: 31601724 No abstract available.

References

1. Tariq K, Schofield JPR, Nicholas BL, Burg D, Brandsma J, Bansal AT, Wilson SJ, Lutter R, Fowler SJ, Bakke PS, Caruso M, et al. Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma. Respiratory Medicine. 2019 - PubMed
1. Shaw DE, Sousa AR, Fowler SJ, Fleming LJ, Roberts G, Corfield J, Pandis I, Bansal AT, Bel EH, Auffray C, Compton CH, et al. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort. Eur Respir J. 2015;46:1308–1321. - PubMed
1. Larry W. Topological Data Analysis. Annual Review of Statistics and Its Application. 2018;5:501–532.
1. Baarsma HA, Königshoff M. WNT signalling in chronic lung diseases. Thorax. 2017;72:746–759. - PMC - PubMed
1. Yiew NKH, Chatterjee TK, Tang YL, Pellenberg R, Stansfield BK, Bagi Z, Fulton DJ, Stepp DW, Chen W, Patel V, Kamath VM, et al. A novel role for the Wnt inhibitor APCDD1 in adipocyte differentiation: Implications for diet-induced obesity. J Biol Chem. 2017;292:6312–6324. - PMC - PubMed

Publication types

Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions
Actions
Actions

Grants and funding

789384/ERC_/European Research Council/International

LinkOut - more resources

Full Text Sources
Medical
- MedlinePlus Consumer Health Information
- MedlinePlus Health Information
Molecular Biology Databases
- NIAID Data Ecosystem - Find datasets on Infectious and Immune-mediated Diseases

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Collaborators

Affiliations

Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Authors

Collaborators

Affiliations

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Medical

Molecular Biology Databases