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. 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

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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.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/961556
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Respiratory Medicine
Identification Number: https://doi.org/10.1183/13993003.02173-2017
Depositing User: Eprints, Support
Date Deposited: 17 May 2018 08:18
Last Modified: 04 May 2020 19:51
URI: https://eprints.nottingham.ac.uk/id/eprint/51846

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