RT Journal Article
SR Electronic
T1 Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1702173
DO 10.1183/13993003.02173-2017
VO 51
IS 5
A1 Kentaro Takahashi
A1 Stelios Pavlidis
A1 Francois Ng Kee Kwong
A1 Uruj Hoda
A1 Christos Rossios
A1 Kai Sun
A1 Matthew Loza
A1 Fred Baribaud
A1 Pascal Chanez
A1 Steve J. Fowler
A1 Ildiko Horvath
A1 Paolo Montuschi
A1 Florian Singer
A1 Jacek Musial
A1 Barbro Dahlen
A1 Sven-Eric Dahlen
A1 Norbert Krug
A1 Thomas Sandstrom
A1 Dominic E. Shaw
A1 Rene Lutter
A1 Per Bakke
A1 Louise J. Fleming
A1 Peter H. Howarth
A1 Massimo Caruso
A1 Ana R. Sousa
A1 Julie Corfield
A1 Charles Auffray
A1 Bertrand De Meulder
A1 Diane Lefaudeux
A1 Ratko Djukanovic
A1 Peter J. Sterk
A1 Yike Guo
A1 Ian M. Adcock
A1 Kian Fan Chung
A1 ,
YR 2018
UL http://erj.ersjournals.com/content/51/5/1702173.abstract
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