{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:49:30Z","timestamp":1790794170886,"version":"4.1.0"},"reference-count":42,"publisher":"European Respiratory Society (ERS)","issue":"5","content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2018,2,22]]},"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>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.<\/jats:p><jats:p>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.<\/jats:p><jats:p>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.<\/jats:p><jats:p>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.<\/jats:p>","DOI":"10.1183\/13993003.02173-2017","type":"journal-article","created":{"date-parts":[[2018,4,12]],"date-time":"2018-04-12T11:05:12Z","timestamp":1523531112000},"page":"1702173","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":85,"title":["Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis"],"prefix":"10.1183","volume":"51","author":[{"given":"Kentaro","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stelios","family":"Pavlidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francois","family":"Ng Kee Kwong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uruj","family":"Hoda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christos","family":"Rossios","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Loza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred","family":"Baribaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Chanez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steve J.","family":"Fowler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ildiko","family":"Horvath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Montuschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Singer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacek","family":"Musial","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbro","family":"Dahlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven-Eric","family":"Dahlen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Krug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Sandstrom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4106-8469","authenticated-orcid":false,"given":"Dominic E.","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Lutter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Bakke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise\u00a0J.","family":"Fleming","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Howarth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4412-2080","authenticated-orcid":false,"given":"Massimo","family":"Caruso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana R.","family":"Sousa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Corfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Auffray","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bertrand","family":"De Meulder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7075-5781","authenticated-orcid":false,"given":"Diane","family":"Lefaudeux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ratko","family":"Djukanovic","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Sterk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yike","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian\u00a0M.","family":"Adcock","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kian Fan","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"81","published-online":{"date-parts":[[2018,4,12]]},"reference":[{"key":"2024102100225184000_51.5.1702173.1","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00202013"},{"key":"2024102100225184000_51.5.1702173.2","doi-asserted-by":"publisher","DOI":"10.1159\/000330900"},{"key":"2024102100225184000_51.5.1702173.3","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1097\/MCP.0b013e32831da894","article-title":"Asthma in smokers: challenges and opportunities","volume":"15","author":"Thomson","year":"2009","journal-title":"Curr Opinion Pulm Med"},{"key":"2024102100225184000_51.5.1702173.4","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1016\/j.jaci.2016.08.048","article-title":"U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics","volume":"139","author":"Lefaudeux","year":"2017","journal-title":"J Allergy Clin Immunol"},{"key":"2024102100225184000_51.5.1702173.5","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00216013"},{"key":"2024102100225184000_51.5.1702173.6","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2678"},{"key":"2024102100225184000_51.5.1702173.7","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.00779-2015"},{"key":"2024102100225184000_51.5.1702173.8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1164\/rccm.201512-2452OC","article-title":"A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED","volume":"195","author":"Kuo","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"2024102100225184000_51.5.1702173.9","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.02135-2016"},{"key":"2024102100225184000_51.5.1702173.10","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gku1003"},{"key":"2024102100225184000_51.5.1702173.11","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7"},{"key":"2024102100225184000_51.5.1702173.12","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1182\/blood.V77.6.1131.1131","article-title":"Molecular physiology of granulocyte-macrophage colony-stimulating factor","volume":"77","author":"Gasson","year":"1991","journal-title":"Blood"},{"key":"2024102100225184000_51.5.1702173.13","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2011-0421OC"},{"key":"2024102100225184000_51.5.1702173.14","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M201586200"},{"key":"2024102100225184000_51.5.1702173.15","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1111\/imr.12466","article-title":"Properdin: a tightly regulated critical inflammatory modulator","volume":"274","author":"Blatt","year":"2016","journal-title":"Immunol Rev"},{"key":"2024102100225184000_51.5.1702173.16","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2012.09.009"},{"key":"2024102100225184000_51.5.1702173.17","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.3RU0215-074R"},{"key":"2024102100225184000_51.5.1702173.18","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-9-187"},{"key":"2024102100225184000_51.5.1702173.19","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(93)90127-C"},{"key":"2024102100225184000_51.5.1702173.20","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-013-0368-6"},{"key":"2024102100225184000_51.5.1702173.21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0401422101"},{"key":"2024102100225184000_51.5.1702173.22","doi-asserted-by":"crossref","first-page":"4588","DOI":"10.1182\/blood.V90.11.4588","article-title":"The CXC-chemokine neutrophil-activating peptide-2 induces two distinct optima of neutrophil chemotaxis by differential interaction with interleukin-8 receptors CXCR-1 and CXCR-2","volume":"90","author":"Ludwig","year":"1997","journal-title":"Blood"},{"key":"2024102100225184000_51.5.1702173.23","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01098-2015"},{"key":"2024102100225184000_51.5.1702173.24","doi-asserted-by":"crossref","first-page":"e67057","DOI":"10.1371\/journal.pone.0067057","article-title":"Cystatin SN upregulation in patients with seasonal allergic rhinitis","volume":"8","author":"Imoto","year":"2013","journal-title":"PLoS One"},{"key":"2024102100225184000_51.5.1702173.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2011.11.002"},{"key":"2024102100225184000_51.5.1702173.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2013.03.013"},{"key":"2024102100225184000_51.5.1702173.27","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.10.6384"},{"key":"2024102100225184000_51.5.1702173.28","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200912-1794OC"},{"key":"2024102100225184000_51.5.1702173.29","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00076210"},{"key":"2024102100225184000_51.5.1702173.30","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05600.x"},{"key":"2024102100225184000_51.5.1702173.31","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00073312"},{"key":"2024102100225184000_51.5.1702173.32","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1111\/all.12865","article-title":"Relationships between adult asthma and oxidative stress markers and pH in exhaled breath condensate: a systematic review","volume":"71","author":"Aldakheel","year":"2016","journal-title":"Allergy"},{"key":"2024102100225184000_51.5.1702173.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2013.08.041"},{"key":"2024102100225184000_51.5.1702173.34","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2012.067249"},{"key":"2024102100225184000_51.5.1702173.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2015.08.009"},{"key":"2024102100225184000_51.5.1702173.36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0051784"},{"key":"2024102100225184000_51.5.1702173.37","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1517\/17460441.2014.913020","article-title":"Epigenetic mechanisms in COPD: implications for pathogenesis and drug discovery","volume":"9","author":"Schamberger","year":"2014","journal-title":"Expert Opin Drug Discov"},{"key":"2024102100225184000_51.5.1702173.38","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0055612"},{"key":"2024102100225184000_51.5.1702173.39","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0497-265"},{"key":"2024102100225184000_51.5.1702173.40","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100324200"},{"key":"2024102100225184000_51.5.1702173.41","doi-asserted-by":"crossref","first-page":"e0152724","DOI":"10.1371\/journal.pone.0152724","article-title":"Airway microbiota in severe asthma and relationship to asthma severity and phenotypes","volume":"11","author":"Zhang","year":"2016","journal-title":"PLoS One"},{"key":"2024102100225184000_51.5.1702173.42","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.jaci.2017.02.004","article-title":"Airway microbial dysbiosis in asthmatic patients: a target for prevention and treatment?","volume":"139","author":"Chung","year":"2017","journal-title":"J Allergy Clin Immunol"}],"container-title":["European Respiratory Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1183\/13993003.02173-2017","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T06:57:03Z","timestamp":1740380223000},"score":1,"resource":{"primary":{"URL":"https:\/\/publications.ersnet.org\/lookup\/doi\/10.1183\/13993003.02173-2017"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,12]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2018,5,3]]},"published-print":{"date-parts":[[2018,5]]}},"alternative-id":["10.1183\/13993003.02173-2017"],"URL":"https:\/\/doi.org\/10.1183\/13993003.02173-2017","relation":{},"ISSN":["0903-1936","1399-3003"],"issn-type":[{"value":"0903-1936","type":"print"},{"value":"1399-3003","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,12]]}}}