Sputum proteomics and airway cell transcripts of current and ex-smokers with severe asthma in U-BIOPRED: an exploratory analysis. Issue 5 (3rd May 2018)

• Record Type: Journal Article
• Authors: 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; Bakke, Per; Fleming, Louise J.; Howarth, Peter H.; Caruso, Massimo; Sousa, Ana R.; Corfield, Julie; Auffray, Charles; De Meulder, Bertrand; Lefaudeux, Diane; Djukanovic, Ratko; Sterk, Peter J.; Guo, Yike; Adcock, Ian M.; Chung, Kian Fan;
• Other Names: Adcock I.M. author non-byline.; Ahmed H. author non-byline.; Auffray C. author non-byline.; Bakke P. author non-byline.; Banssal A.T. author non-byline.; Baribaud F. author non-byline.; Bates S. author non-byline.; Bel E.H. author non-byline.; Bigler J. author non-byline.; Bisgaard H. author non-byline.; Boedigheimer M.J. author non-byline.; Bønnelykke K. author non-byline.; Brandsma J. author non-byline.; Brinkman P. author non-byline.; Bucchioni E. author non-byline.; Burg D. author non-byline.; Bush A. author non-byline.; Caruso M. author non-byline.; Chaiboonchoe A. author non-byline.; Chanez P. author non-byline.; Chung K.F. author non-byline.; Compton C.H. author non-byline.; Corfield J. author non-byline.; D'Amico A. author non-byline.; Dahlen S.E. author non-byline.; De Meulder B. author non-byline.; Djukanovic R. author non-byline.; Erpenbeck V.J. author non-byline.; Erzen D. author non-byline.; Fichtner K. author non-byline.; Fitch N. author non-byline.; Fleming L.J. author non-byline.; Formaggio E. author non-byline.; Fowler S.J. author non-byline.; Frey U. author non-byline.; Gahlemann M. author non-byline.; Geiser T. author non-byline.; Guo Y. author non-byline.; Hashimoto S. author non-byline.; Haughney J. author non-byline.; Hedlin G. author non-byline.; Hekking P.W. author non-byline.; Higenbottam T. author non-byline.; Hohlfeld J.M. author non-byline.; Holweg C. author non-byline.; Horváth I. author non-byline.; Howarth P. author non-byline.; James A.J. author non-byline.; Knowles R. author non-byline.; Knox A.J. author non-byline.; Krug N. author non-byline.; Lefaudeux D. author non-byline.; Loza M.J. author non-byline.; Lutter R. author non-byline.; Manta A. author non-byline.; Masefield S. author non-byline.; Matthews J.G. author non-byline.; Mazein A. author non-byline.; Meiser A. author non-byline.; Middelveld R.J.M. author non-byline.; Miralpeix M. author non-byline.; Montuschi P. author non-byline.; Mores N. author non-byline.; Murray C.S. author non-byline.; Musial J. author non-byline.; Myles D. author non-byline.; Pahus L. author non-byline.; Pandis I. author non-byline.; Pavlidis S. author non-byline.; Powell P. author non-byline.; Praticò G. author non-byline.; Puig Valls M. author non-byline.; Rao N. author non-byline.; Riley J. author non-byline.; Roberts A. author non-byline.; Roberts G. author non-byline.; Rowe A. author non-byline.; Sandström T. author non-byline.; Seibold W. author non-byline.; Selby A. author non-byline.; Shaw D.E. author non-byline.; Sigmund R. author non-byline.; Singer F. author non-byline.; Skipp P.J. author non-byline.; Sousa A.R. author non-byline.; Sterk P.J. author non-byline.; Sun K. author non-byline.; Thornton B. author non-byline.; van Aalderen W.M. author non-byline.; van Geest M. author non-byline.; Vestbo J. author non-byline.; Vissing N.H. author non-byline.; Wagener A.H. author non-byline.; Wagers S.S. author non-byline.; Weiszhart Z. author non-byline.; Wheelock C.E. author non-byline.; Wilson S.J. author non-byline.; Aliprantis Antonios author non-byline.; Allen David author non-byline.; Alving Kjell author non-byline.; Badorrek P. author non-byline.; Balgoma David author non-byline.; Ballereau S. author non-byline.; Barber Clair author non-byline.; Batuwitage Manohara Kanangana author non-byline.; Bautmans An author non-byline.; Bedding A. author non-byline.; Behndig A.F. author non-byline.; Beleta Jorge author non-byline.; Berglind A. author non-byline.; Berton A. author non-byline.; Bochenek Grazyna author non-byline.; Braun Armin author non-byline.; Campagna D. author non-byline.; Carayannopoulos Leon author non-byline.; Casaulta C. author non-byline.; Chaleckis Romanas author non-byline.; Dahlén B. author non-byline.; Davison Timothy author non-byline.; De Alba Jorge author non-byline.; De Lepeleire Inge author non-byline.; Dekker Tamara author non-byline.; Delin Ingrid author non-byline.; Dennison P. author non-byline.; Dijkhuis Annemiek author non-byline.; Dodson Paul author non-byline.; Draper Aleksandra author non-byline.; Dyson K. author non-byline.; Edwards Jessica author non-byline.; El Hadjam L. author non-byline.; Emma Rosalia author non-byline.; Ericsson Magnus author non-byline.; Faulenbach C. author non-byline.; Flood Breda author non-byline.; Galffy G. author non-byline.; Gallart Hector author non-byline.; Garissi D. author non-byline.; Gent J. author non-byline.; Gerhardsson de Verdier M. author non-byline.; Gibeon D. author non-byline.; Gomez Cristina author non-byline.; Gove Kerry author non-byline.; Gozzard Neil author non-byline.; Guillmant-Farry E. author non-byline.; Henriksson E. author non-byline.; Hewitt Lorraine author non-byline.; Hoda U. author non-byline.; Hu Richard author non-byline.; Hu Sile author non-byline.; Hu X. author non-byline.; Jeyasingham E. author non-byline.; Johnson K. author non-byline.; Jullian N. author non-byline.; Kamphuis Juliette author non-byline.; Kennington Erika J. author non-byline.; Kerry Dyson author non-byline.; Kerry G. author non-byline.; Klüglich M. author non-byline.; Knobel Hugo author non-byline.; Kolmert Johan author non-byline.; Konradsen J.R. author non-byline.; Kots Maxim author non-byline.; Kretsos Kosmas author non-byline.; Krueger L. author non-byline.; Kuo Scott author non-byline.; Kupczyk Maciej author non-byline.; Lambrecht Bart author non-byline.; Lantz A-S. author non-byline.; Larminie Christopher author non-byline.; Larsson L.X. author non-byline.; Latzin P. author non-byline.; Lazarinis N. author non-byline.; Lemonnier N. author non-byline.; Lone-Latif Saeeda author non-byline.; Lowe L.A. author non-byline.; Manta Alexander author non-byline.; Marouzet Lisa author non-byline.; Martin Jane author non-byline.; Mathon Caroline author non-byline.; McEvoy L. author non-byline.; Meah Sally author non-byline.; Menzies-Gow A. author non-byline.; Metcalf Leanne author non-byline.; Mikus Maria author non-byline.; Monk Philip author non-byline.; Naz Shama author non-byline.; Nething K. author non-byline.; Nicholas Ben author non-byline.; Nihlén U. author non-byline.; Nilsson Peter author non-byline.; Niven R. author non-byline.; Nordlund B. author non-byline.; Nsubuga S. author non-byline.; Östling Jörgen author non-byline.; Pacino Antonio author non-byline.; Palkonen Susanna author non-byline.; Pellet J. author non-byline.; Pennazza Giorgio author non-byline.; Petrén Anne author non-byline.; Pink Sandy author non-byline.; Pison C. author non-byline.; Postle Anthony author non-byline.; Rahman-Amin Malayka author non-byline.; Ravanetti Lara author non-byline.; Ray Emma author non-byline.; Reinke Stacey author non-byline.; Reynolds Leanne author non-byline.; Riemann K. author non-byline.; Robberechts Martine author non-byline.; Rocha J.P. author non-byline.; Rossios C. author non-byline.; Russell Kirsty author non-byline.; Rutgers Michael author non-byline.; Santini G. author non-byline.; Santoninco Marco author non-byline.; Saqi M. author non-byline.; Schoelch Corinna author non-byline.; Schofield James P.R. author non-byline.; Scott S. author non-byline.; Sehgal N. author non-byline.; Sjödin Marcus author non-byline.; Smids Barbara author non-byline.; Smith Caroline author non-byline.; Smith Jessica author non-byline.; Smith Katherine M. author non-byline.; Söderman P. author non-byline.; Sogbessan A. author non-byline.; Spycher F. author non-byline.; Staykova Doroteya author non-byline.; Stephan S. author non-byline.; Stokholm J. author non-byline.; Strandberg K. author non-byline.; Sunther M. author non-byline.; Szentkereszty M. author non-byline.; Tamasi L. author non-byline.; Tariq K. author non-byline.; Thörngren John-Olof author non-byline.; Thorsen Jonathan author non-byline.; Valente S. author non-byline.; van de Pol Marianne author non-byline.; van Drunen C.M. author non-byline.; Van Eyll Jonathan author non-byline.; Versnel Jenny author non-byline.; Vink Anton author non-byline.; von Garnier C. author non-byline.; Vyas A. author non-byline.; Wald Frans author non-byline.; Walker Samantha author non-byline.; Ward Jonathan author non-byline.; Wetzel Kristiane author non-byline.; Wiegman Coen author non-byline.; Williams Siân author non-byline.; Yang Xian author non-byline.; Yeyasingham Elizabeth author non-byline.; Yu W. author non-byline.; Zetterquist W. author non-byline.; Zolkipli Z. author non-byline.; Zwinderman A.H. author non-byline.; Prins Jan-Bas author non-byline.; Gahlemann Martina author non-byline.; Visintin Luigi author non-byline.; Evans Hazel author non-byline.; Puhl Martine author non-byline.; Buzermaniene Lina author non-byline.; Hudson Val author non-byline.; Bond Laura author non-byline.; de Boer Pim author non-byline.; Widdershoven Guy author non-byline.; Sigmund Ralf author non-byline.; Supple David author non-byline.; Hamerlijnck Dominique author non-byline.; Negus Jenny author non-byline.; Kamphuis Juliёtte author non-byline.; Sergison Lehanne author non-byline.; Visintin Luigi author non-byline.; de Boer Pim author non-byline.; Onstein Susanne author non-byline.; MacNee William author non-byline.; Bernardini Renato author non-byline.; Bont Louis author non-byline.; Wecksell Per-Ake author non-byline.; de Boer Pim author non-byline.; Gahlemann Martina author non-byline.; Sigmund Ralf author non-byline.;
• Is Part Of: European respiratory journal. Volume 51:Issue 5(2018)
• Publication Date: 2018-05-03
• Subjects: Respiratory organs -- Diseases -- Periodicals; Respiration -- Periodicals; 616.2
• DOI: 10.1183/13993003.02173-2017
• Languages: English
• ISSNs: 0903-1936

Abstract

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. Inflammatory, oxidative/ER stress and epithelial barrier pathways are differentially activated in current smoking and ex-smoking severe asthma patients http://ow.ly/BVv530j3iP3