Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis
Background: Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. Methods: The U-BIOPRED severe asthma patients c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
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European Respiratory Society
2018
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| Online Access: | https://eprints.nottingham.ac.uk/51846/ |
| _version_ | 1848798587674165248 |
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| author | Takahashi, Kentaro Pavlidis, Stelios Ng Kee Kwong, Francois Hoda, Uruj Rossios, Christos Sun, Kai Loza, Matthew Baribaud, Fred Chanez, Pascal Fowler, Steve J. Horvath, Ildiko Montuschi, Paolo Singer, Florian Musial, Jacek Dahlen, Barbro Dahlen, Sven-Eric Krug, Norbert Sandstrom, Thomas Shaw, Dominic E. Lutter, Rene Bakke, Per Fleming, Louise J. Howarth, Peter H. Caruso, Massimo Sousa, Ana R. Corfield, Julie Auffray, Charles De Meulder, Bertrand Lefaudeux, Diane Djukanovic, Ratko Sterk, Peter J. Guo, Yike Adcock, Ian M. Chung, Kian Fan |
| author_facet | Takahashi, Kentaro Pavlidis, Stelios Ng Kee Kwong, Francois Hoda, Uruj Rossios, Christos Sun, Kai Loza, Matthew Baribaud, Fred Chanez, Pascal Fowler, Steve J. Horvath, Ildiko Montuschi, Paolo Singer, Florian Musial, Jacek Dahlen, Barbro Dahlen, Sven-Eric Krug, Norbert Sandstrom, Thomas Shaw, Dominic E. Lutter, Rene Bakke, Per Fleming, Louise J. Howarth, Peter H. Caruso, Massimo Sousa, Ana R. Corfield, Julie Auffray, Charles De Meulder, Bertrand Lefaudeux, Diane Djukanovic, Ratko Sterk, Peter J. Guo, Yike Adcock, Ian M. Chung, Kian Fan |
| author_sort | Takahashi, Kentaro |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background: Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes.
Methods: The U-BIOPRED severe asthma patients containing current-smokers (CSA), exsmokers (ESA), non-smokers (NSA) and healthy non-smokers (NH) was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed.
Results: Colony stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene Set Variation Analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated.
Conclusion: Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level with CSA having increased CSF2 expression and ESA patients showed sustained loss of epithelial barrier processes. |
| first_indexed | 2025-11-14T20:22:09Z |
| format | Article |
| id | nottingham-51846 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T20:22:09Z |
| publishDate | 2018 |
| publisher | European Respiratory Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-518462020-05-04T19:51:04Z https://eprints.nottingham.ac.uk/51846/ Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis Takahashi, Kentaro Pavlidis, Stelios Ng Kee Kwong, Francois Hoda, Uruj Rossios, Christos Sun, Kai Loza, Matthew Baribaud, Fred Chanez, Pascal Fowler, Steve J. Horvath, Ildiko Montuschi, Paolo Singer, Florian Musial, Jacek Dahlen, Barbro Dahlen, Sven-Eric Krug, Norbert Sandstrom, Thomas Shaw, Dominic E. Lutter, Rene Bakke, Per Fleming, Louise J. Howarth, Peter H. Caruso, Massimo Sousa, Ana R. Corfield, Julie Auffray, Charles De Meulder, Bertrand Lefaudeux, Diane Djukanovic, Ratko Sterk, Peter J. Guo, Yike Adcock, Ian M. Chung, Kian Fan Background: Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi-omic analysis will enable the definition of smoking and ex-smoking severe asthma molecular phenotypes. Methods: The U-BIOPRED severe asthma patients containing current-smokers (CSA), exsmokers (ESA), non-smokers (NSA) and healthy non-smokers (NH) was examined. Blood and sputum cell counts, fractional exhaled nitric oxide and spirometry were obtained. Exploratory proteomic analysis of sputum supernatants and transcriptomic analysis of bronchial brushings, biopsies and sputum cells was performed. Results: Colony stimulating factor (CSF)2 protein levels were increased in CSA sputum supernatants with azurocidin 1, neutrophil elastase and CXCL8 upregulated in ESA. Phagocytosis and innate immune pathways were associated with neutrophilic inflammation in ESA. Gene Set Variation Analysis of bronchial epithelial cell transcriptome from CSA showed enrichment of xenobiotic metabolism, oxidative stress and endoplasmic reticulum stress compared to other groups. CXCL5 and matrix metallopeptidase 12 genes were upregulated in ESA and the epithelial protective genes, mucin 2 and cystatin SN, were downregulated. Conclusion: Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level with CSA having increased CSF2 expression and ESA patients showed sustained loss of epithelial barrier processes. European Respiratory Society 2018-05-01 Article PeerReviewed Takahashi, Kentaro, Pavlidis, Stelios, Ng Kee Kwong, Francois, Hoda, Uruj, Rossios, Christos, Sun, Kai, Loza, Matthew, Baribaud, Fred, Chanez, Pascal, Fowler, Steve J., Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Dahlen, Sven-Eric, Krug, Norbert, Sandstrom, Thomas, Shaw, Dominic E., Lutter, Rene, Bakke, Per, Fleming, Louise J., Howarth, Peter H., Caruso, Massimo, Sousa, Ana R., Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Djukanovic, Ratko, Sterk, Peter J., Guo, Yike, Adcock, Ian M. and Chung, Kian Fan (2018) Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis. European Respiratory Journal, 51 (5). p. 1702173. ISSN 0903-1936 http://erj.ersjournals.com/content/early/2018/02/15/13993003.02173-2017 doi:10.1183/13993003.02173-2017 doi:10.1183/13993003.02173-2017 |
| spellingShingle | Takahashi, Kentaro Pavlidis, Stelios Ng Kee Kwong, Francois Hoda, Uruj Rossios, Christos Sun, Kai Loza, Matthew Baribaud, Fred Chanez, Pascal Fowler, Steve J. Horvath, Ildiko Montuschi, Paolo Singer, Florian Musial, Jacek Dahlen, Barbro Dahlen, Sven-Eric Krug, Norbert Sandstrom, Thomas Shaw, Dominic E. Lutter, Rene Bakke, Per Fleming, Louise J. Howarth, Peter H. Caruso, Massimo Sousa, Ana R. Corfield, Julie Auffray, Charles De Meulder, Bertrand Lefaudeux, Diane Djukanovic, Ratko Sterk, Peter J. Guo, Yike Adcock, Ian M. Chung, Kian Fan Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis |
| title | Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis |
| title_full | Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis |
| title_fullStr | Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis |
| title_full_unstemmed | Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis |
| title_short | Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis |
| title_sort | sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in u-biopred: an exploratory analysis |
| url | https://eprints.nottingham.ac.uk/51846/ https://eprints.nottingham.ac.uk/51846/ https://eprints.nottingham.ac.uk/51846/ |