Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis

File Description SizeFormat 
KENTARO reply file PDF.PDFFile embargoed until 03 November 20192.74 MBAdobe PDF    Request a copy
Title: Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis
Author(s): Takahashi, K
Pavlidis, S
Ng Kee Kwong, F
Hoda, U
Rossios, C
Sun, K
Loza, M
Baribaud, F
Chanez, P
Fowler, SJ
Horvath, I
Montuschi, P
Singer, F
Musial, J
Dahlen, B
Dahlen, SE
Krug, N
Sandstrom, T
Shaw, DE
Lutter, R
Bakke, P
Fleming, LJ
Howarth, PH
Caruso, M
Sousa, AR
Corfield, J
Auffray, C
De Meulder, B
Lefaudeux, D
Djukanovic, R
Sterk, PJ
Guo, Y
Adcock, I
Chung, KF
Item Type: Journal Article
Abstract: 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.
Publication Date: 3-May-2018
Date of Acceptance: 22-Feb-2018
URI: http://hdl.handle.net/10044/1/57478
DOI: https://dx.doi.org/10.1183/13993003.02173-2017
ISSN: 0903-1936
Publisher: European Respiratory Society
Journal / Book Title: European Respiratory Journal
Volume: 51
Issue: 5
Copyright Statement: © ERS 2018
Sponsor/Funder: Commission of the European Communities
Funder's Grant Number: 115010
Keywords: , on behalf of the U-BIOPRED study group
11 Medical And Health Sciences
Respiratory System
Publication Status: Published
Article Number: 1702173
Embargo Date: 2019-11-03
Appears in Collections:Faculty of Engineering
Computing
National Heart and Lung Institute
Airway Disease
Faculty of Medicine



Items in Spiral are protected by copyright, with all rights reserved, unless otherwise indicated.

Creative Commons