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Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis
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2018 (English)In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 51, no 5, article id 1702173Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
EUROPEAN RESPIRATORY SOC JOURNALS LTD , 2018. Vol. 51, no 5, article id 1702173
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Respiratory Medicine and Allergy
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URN: urn:nbn:se:umu:diva-150700DOI: 10.1183/13993003.02173-2017ISI: 000435212900008PubMedID: 29650557OAI: oai:DiVA.org:umu-150700DiVA, id: diva2:1245536
Available from: 2018-09-05 Created: 2018-09-05 Last updated: 2018-09-05Bibliographically approved

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Sandström, Thomas

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CiteExportLink to record
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Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
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  • Other style
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  • de-DE
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  • fi-FI
  • nn-NO
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