BibTex format
@article{Takahashi:2018:10.1183/13993003.02173-2017,
author = {Takahashi, K and Pavlidis, S and Ng, Kee Kwong F and Hoda, U and Rossios, C and Sun, K and Loza, M and Baribaud, F and Chanez, P and Fowler, SJ and Horvath, I and Montuschi, P and Singer, F and Musial, J and Dahlen, B and Dahlen, SE and Krug, N and Sandstrom, T and Shaw, DE and Lutter, R and Bakke, P and Fleming, LJ and Howarth, PH and Caruso, M and Sousa, AR and Corfield, J and Auffray, C and De, Meulder B and Lefaudeux, D and Djukanovic, R and Sterk, PJ and Guo, Y and Adcock, I and Chung, KF},
doi = {10.1183/13993003.02173-2017},
journal = {European Respiratory Journal},
title = {Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis},
url = {http://dx.doi.org/10.1183/13993003.02173-2017},
volume = {51},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Background: Severe asthma patients with a significant smoking history have airflow obstruction with reported neutrophilia. We hypothesise that multi1omic analysis will enable the definition of smoking and ex1smoking severe asthma molecular phenotypes.Methods The U1BIOPRED severe asthma patients containing current1smokers (CSA), ex1smokers (ESA), non1smokers (NSA) and healthy non1smokers (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.
AU - Takahashi,K
AU - Pavlidis,S
AU - Ng,Kee Kwong F
AU - Hoda,U
AU - Rossios,C
AU - Sun,K
AU - Loza,M
AU - Baribaud,F
AU - Chanez,P
AU - Fowler,SJ
AU - Horvath,I
AU - Montuschi,P
AU - Singer,F
AU - Musial,J
AU - Dahlen,B
AU - Dahlen,SE
AU - Krug,N
AU - Sandstrom,T
AU - Shaw,DE
AU - Lutter,R
AU - Bakke,P
AU - Fleming,LJ
AU - Howarth,PH
AU - Caruso,M
AU - Sousa,AR
AU - Corfield,J
AU - Auffray,C
AU - De,Meulder B
AU - Lefaudeux,D
AU - Djukanovic,R
AU - Sterk,PJ
AU - Guo,Y
AU - Adcock,I
AU - Chung,KF
DO - 10.1183/13993003.02173-2017
PY - 2018///
SN - 0903-1936
TI - Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis
T2 - European Respiratory Journal
UR - http://dx.doi.org/10.1183/13993003.02173-2017
UR - http://hdl.handle.net/10044/1/57478
VL - 51
ER -
