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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

Authors

Kentaro Takahashi

Stelios Pavlidis

Francois Ng Kee Kwong

Uruj Hoda

Christos Rossios

Kai Sun

Matthew Loza

Fred Baribaud

Pascal Chanez

Steve J. Fowler

Ildiko Horvath

Paolo Montuschi

Florian Singer

Jacek Musial

Barbro Dahlen

Sven-Eric Dahlen

Norbert Krug

Thomas Sandstrom

Dominic E. Shaw

Rene Lutter

Per Bakke

Louise J. Fleming

Peter H. Howarth

Massimo Caruso

Ana R. Sousa

Julie Corfield

Charles Auffray

Bertrand De Meulder

Diane Lefaudeux

Ratko Djukanovic

Peter J. Sterk

Yike Guo

Ian M. Adcock

Kian Fan Chung



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.

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 0903-1936
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


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