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

Abstract

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.

Citation

Takahashi, K., Pavlidis, S., Ng Kee Kwong, F., Hoda, U., Rossios, C., Sun, K., Loza, M., Baribaud, F., Chanez, P., Fowler, S. J., Horvath, I., Montuschi, P., Singer, F., Musial, J., Dahlen, B., Dahlen, S.-E., Krug, N., Sandstrom, T., Shaw, D. E., Lutter, R., …Chung, K. F. (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), https://doi.org/10.1183/13993003.02173-2017

• Journal Article Type: Article
• Acceptance Date: Dec 17, 2017
• Online Publication Date: Apr 12, 2018
• Publication Date: May 1, 2018
• Deposit Date: May 17, 2018
• Journal: European Respiratory Journal
• Print ISSN: 0903-1936
• Electronic ISSN: 1399-3003
• Publisher: European Respiratory Society
• Peer Reviewed: Peer Reviewed
• Volume: 51
• Issue: 5
• DOI: https://doi.org/10.1183/13993003.02173-2017
• Public URL: https://nottingham-repository.worktribe.com/output/961556
• Publisher URL: http://erj.ersjournals.com/content/early/2018/02/15/13993003.02173-2017
• Contract Date: May 17, 2018