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 Takahashi, Kentaro
A1 Pavlidis, Stelios
A1 Ng Kee Kwong, Francois
A1 Hoda, Uruj
A1 Rossios, Christos
A1 Sun, Kai
A1 Loza, Matthew
A1 Baribaud, Fred
A1 Chanez, Pascal
A1 Fowler, Steve J.
A1 Horvath, Ildiko
A1 Montuschi, Paolo
A1 Singer, Florian
A1 Musial, Jacek
A1 Dahlen, Barbro
A1 Dahlen, Sven-Eric
A1 Krug, Norbert
A1 Sandstrom, Thomas
A1 Shaw, Dominic E.
A1 Lutter, Rene
A1 Bakke, Per
A1 Fleming, Louise J.
A1 Howarth, Peter H.
A1 Caruso, Massimo
A1 Sousa, Ana R.
A1 Corfield, Julie
A1 Auffray, Charles
A1 De Meulder, Bertrand
A1 Lefaudeux, Diane
A1 Djukanovic, Ratko
A1 Sterk, Peter J.
A1 Guo, Yike
A1 Adcock, Ian M.
A1 Chung, Kian Fan
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