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

Takahashi, Kentaro; Pavlidis, Stelios; Ng Kee Kwong, Francois; Hoda, Uruj; Rossios, Christos; Sun, Kai; Loza, Matthew; Baribaud, Fred; Chanez, Pascal; Fowler, Steve J; Horvath, Ildiko; Montuschi, Paolo; Singer, Florian; Musial, Jacek; Dahlen, Barbro; Dahlen, Sven-Eric; Krug, Norbert; Sandstrom, Thomas; Shaw, Dominic E; Lutter, Rene; ... (2018). Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis. European respiratory journal, 51(5) European Respiratory Society 10.1183/13993003.02173-2017

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Pneumologie (Pädiatrie)
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine > Paediatric Pneumology

UniBE Contributor:

Singer, Florian

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0903-1936

Publisher:

European Respiratory Society

Language:

English

Submitter:

Anette van Dorland

Date Deposited:

19 Feb 2019 11:39

Last Modified:

20 Jul 2022 10:01

Publisher DOI:

10.1183/13993003.02173-2017

PubMed ID:

29650557

BORIS DOI:

10.7892/boris.123337

URI:

https://boris.unibe.ch/id/eprint/123337

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