PT  - JOURNAL ARTICLE
AU  - Kentaro Takahashi
AU  - Stelios Pavlidis
AU  - Francois Ng Kee Kwong
AU  - Uruj Hoda
AU  - Christos Rossios
AU  - Kai Sun
AU  - Matthew Loza
AU  - Fred Baribaud
AU  - Pascal Chanez
AU  - Steve J. Fowler
AU  - Ildiko Horvath
AU  - Paolo Montuschi
AU  - Florian Singer
AU  - Jacek Musial
AU  - Barbro Dahlen
AU  - Sven-Eric Dahlen
AU  - Norbert Krug
AU  - Thomas Sandstrom
AU  - Dominic E. Shaw
AU  - Rene Lutter
AU  - Per Bakke
AU  - Louise J. Fleming
AU  - Peter H. Howarth
AU  - Massimo Caruso
AU  - Ana R. Sousa
AU  - Julie Corfield
AU  - Charles Auffray
AU  - Bertrand De Meulder
AU  - Diane Lefaudeux
AU  - Ratko Djukanovic
AU  - Peter J. Sterk
AU  - Yike Guo
AU  - Ian M. Adcock
AU  - Kian Fan Chung
ED  - ,
TI  - Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis
AID  - 10.1183/13993003.02173-2017
DP  - 2018 May 01
TA  - European Respiratory Journal
PG  - 1702173
VI  - 51
IP  - 5
4099  - http://erj.ersjournals.com/content/51/5/1702173.short
4100  - http://erj.ersjournals.com/content/51/5/1702173.full
SO  - Eur Respir J2018 May 01; 51
AB  - 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.The U-BIOPRED cohort of severe asthma patients, containing current-smokers (CSA), ex-smokers (ESA), nonsmokers and healthy nonsmokers 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.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.Despite little difference in clinical characteristics, CSA were distinguishable from ESA subjects at the sputum proteomic level, with CSA patients having increased CSF2 expression and ESA patients showing sustained loss of epithelial barrier processes.Inflammatory, oxidative/ER stress and epithelial barrier pathways are differentially activated in current smoking and ex-smoking severe asthma patients http://ow.ly/BVv530j3iP3