TY - JOUR
T1 - Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED
T2 - An exploratory analysis
AU - U-BIOPRED Study Group
AU - Takahashi, Kentaro
AU - Pavlidis, Stelios
AU - Ng Kee Kwong, Francois
AU - Hoda, Uruj
AU - Rossios, Christos
AU - Sun, Kai
AU - Loza, Matthew
AU - Baribaud, Fred
AU - Chanez, Pascal
AU - Fowler, Steve J.
AU - Horvath, Ildiko
AU - Montuschi, Paolo
AU - Singer, Florian
AU - Musial, Jacek
AU - Dahlen, Barbro
AU - Dahlen, Sven Eric
AU - Krug, Norbert
AU - Sandstrom, Thomas
AU - Shaw, Dominic E.
AU - Lutter, Rene
AU - Bakke, Per
AU - Fleming, Louise J.
AU - Howarth, Peter H.
AU - Caruso, Massimo
AU - Sousa, Ana R.
AU - Corfield, Julie
AU - Auffray, Charles
AU - De Meulder, Bertrand
AU - Lefaudeux, Diane
AU - Djukanovic, Ratko
AU - Sterk, Peter J.
AU - Guo, Yike
AU - Adcock, Ian M.
AU - Chung, Kian Fan
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=85047303818&partnerID=8YFLogxK
U2 - 10.1183/13993003.02173-2017
DO - 10.1183/13993003.02173-2017
M3 - Article
AN - SCOPUS:85047303818
SN - 0903-1936
VL - 51
JO - European Respiratory Journal
JF - European Respiratory Journal
IS - 5
M1 - 1702173
ER -