caa a22 4500 555306070 20200410094045.0 cr unu---uuuuu 190206s2018 xx s 000 0 eng 1932-6203 10.1371/journal.pone.0203874 doi 10.1371/journal.pone.0203874 doi (BORIS)oai:boris.unibe.ch:123336 (ZORA)oai:www.zora.uzh.ch:158961 610 ddc 30240401 pmid Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort [Elektronische Daten] [Rosalia Emma, Aruna T Bansal, Johan Kolmert, Craig E Wheelock, Swen-Erik Dahlen, Matthew J Loza, Bertrand De Meulder, Diane Lefaudeux, Charles Auffray, Barbro Dahlen, Per S Bakke, Pascal Chanez, Stephen J Fowler, Ildiko Horvath, Paolo Montuschi, Norbert Krug, Marek Sanak, Thomas Sandstrom, Dominick E Shaw, Louise J Fleming, Ratko Djukanovic, Peter H Howarth, Florian Singer, Ana R Sousa, Peter J Sterk, Julie Corfield, Ioannis Pandis, Kian F Chung, Ian M Adcock, René Lutter, Lorena Fabbella, Massimo Caruso] publishedVersion openAccess eu-repo Oxidative stress is believed to be a major driver of inflammation in smoking asthmatics. The U-BIOPRED project recruited a cohort of Severe Asthma smokers/ex-smokers (SAs/ex) and non-smokers (SAn) with extensive clinical and biomarker information enabling characterization of these subjects. We investigated oxidative stress in severe asthma subjects by analysing urinary 8-iso-PGF2α and the mRNA-expression of the main pro-oxidant (NOX2; NOSs) and anti-oxidant (SODs; CAT; GPX1) enzymes in the airways of SAs/ex and SAn. All the severe asthma U-BIOPRED subjects were further divided into current smokers with severe asthma (CSA), ex-smokers with severe asthma (ESA) and non-smokers with severe asthma (NSA) to deepen the effect of active smoking. Clinical data, urine and sputum were obtained from severe asthma subjects. A bronchoscopy to obtain bronchial biopsy and brushing was performed in a subset of subjects. The main clinical data were analysed for each subset of subjects (urine-8-iso-PGF2α; IS-transcriptomics; BB-transcriptomics; BBr-transcriptomics). Urinary 8-iso-PGF2α was quantified using mass spectrometry. Sputum, bronchial biopsy and bronchial brushing were processed for mRNA expression microarray analysis. Urinary 8-iso-PGF2α was increased in SAs/ex, median (IQR) = 31.7 (24.5-44.7) ng/mmol creatinine, compared to SAn, median (IQR) = 26.6 (19.6-36.6) ng/mmol creatinine (p< 0.001), and in CSA, median (IQR) = 34.25 (24.4-47.7), vs. ESA, median (IQR) = 29.4 (22.3-40.5), and NSA, median (IQR) = 26.5 (19.6-16.6) ng/mmol creatinine (p = 0.004). Sputum mRNA expression of NOX2 was increased in SAs/ex compared to SAn (probe sets 203922_PM_s_at fold-change = 1.05 p = 0.006; 203923_PM_s_at fold-change = 1.06, p = 0.003; 233538_PM_s_at fold-change = 1.06, p = 0.014). The mRNA expression of antioxidant enzymes were similar between the two severe asthma cohorts in all airway samples. NOS2 mRNA expression was decreased in bronchial brushing of SAs/ex compared to SAn (fold-change = -1.10; p = 0.029). NOS2 mRNA expression in bronchial brushing correlated with FeNO (Kendal's Tau = 0.535; p< 0.001). From clinical and inflammatory analysis, FeNO was lower in CSA than in ESA in all the analysed subject subsets (p< 0.01) indicating an effect of active smoking. Results about FeNO suggest its clinical limitation, as inflammation biomarker, in severe asthma active smokers. These data provide evidence of greater systemic oxidative stress in severe asthma smokers as reflected by a significant changes of NOX2 mRNA expression in the airways, together with elevated urinary 8-iso-PGF2α in the smokers/ex-smokers group. Trial registration ClinicalTrials.gov-Identifier: NCT01976767. Medical Clinic zora Emma Rosalia joint author Bansal Aruna T. joint author Kolmert Johan joint author Wheelock Craig E. joint author Dahlen Swen-Erik joint author Loza Matthew J. joint author De Meulder Bertrand joint author Lefaudeux Diane joint author Auffray Charles joint author Dahlen Barbro joint author Bakke Per S. joint author Chanez Pascal joint author Fowler Stephen J. joint author Horvath Ildiko joint author Montuschi Paolo joint author Krug Norbert joint author Sanak Marek joint author Sandstrom Thomas joint author Shaw Dominick E. joint author Fleming Louise J. joint author Djukanovic Ratko joint author Howarth Peter H. joint author Singer Florian joint author Sousa Ana R. joint author Sterk Peter J. joint author Corfield Julie joint author Pandis Ioannis joint author Chung Kian F. joint author Adcock Ian M. joint author Lutter René joint author Fabbella Lorena joint author Caruso Massimo joint author PLoS ONE 13(9), e0203874 1932-6203 https://boris.unibe.ch/123336/1/Rosalia_et_all_PLoS%20One_Enhanced%20oxidative%20stress%20in%20smoking%20and%20ex%20smoking%20sever%20asthma%20in%20the%20UBiopred%20cohort.pdf text/html WWW-Backlink auf das Repository 1 info:eu-repo/semantics/article boris PeerReviewed boris peerstatus BORIS 856 40 https://boris.unibe.ch/123336/1/Rosalia_et_all_PLoS%20One_Enhanced%20oxidative%20stress%20in%20smoking%20and%20ex%20smoking%20sever%20asthma%20in%20the%20UBiopred%20cohort.pdf text/html WWW-Backlink auf das Repository BORIS 700 1- Emma Rosalia joint author BORIS 700 1- Bansal Aruna T. joint author BORIS 700 1- Kolmert Johan joint author BORIS 700 1- Wheelock Craig E. joint author BORIS 700 1- Dahlen Swen-Erik joint author BORIS 700 1- Loza Matthew J. joint author BORIS 700 1- De Meulder Bertrand joint author BORIS 700 1- Lefaudeux Diane joint author BORIS 700 1- Auffray Charles joint author BORIS 700 1- Dahlen Barbro joint author BORIS 700 1- Bakke Per S. joint author BORIS 700 1- Chanez Pascal joint author BORIS 700 1- Fowler Stephen J. joint author BORIS 700 1- Horvath Ildiko joint author BORIS 700 1- Montuschi Paolo joint author BORIS 700 1- Krug Norbert joint author BORIS 700 1- Sanak Marek joint author BORIS 700 1- Sandstrom Thomas joint author BORIS 700 1- Shaw Dominick E. joint author BORIS 700 1- Fleming Louise J. joint author BORIS 700 1- Djukanovic Ratko joint author BORIS 700 1- Howarth Peter H. joint author BORIS 700 1- Singer Florian joint author BORIS 700 1- Sousa Ana R. joint author BORIS 700 1- Sterk Peter J. joint author BORIS 700 1- Corfield Julie joint author BORIS 700 1- Pandis Ioannis joint author BORIS 700 1- Chung Kian F. joint author BORIS 700 1- Adcock Ian M. joint author BORIS 700 1- Lutter René joint author BORIS 700 1- Fabbella Lorena joint author BORIS 700 1- Caruso Massimo joint author BORIS 773 0- PLoS ONE 13(9), e0203874 1932-6203 ZORA 856 40 https://www.zora.uzh.ch/id/eprint/158961/1/pone.0203874.pdf text/html WWW-Backlink auf das Repository ZORA 700 1- Emma Rosalia joint author ZORA 700 1- Bansal Aruna T. joint author ZORA 700 1- Kolmert Johan joint author ZORA 700 -- et al joint author ZORA 700 1- Singer Florian joint author ZORA 773 0- PLoS ONE 13(9):e0203874 BK010053 XK010053 XK010000 BORIS BORIS BORIS info:eu-repo/semantics/article openAccess ZORA ZORA ZORA Journal Article openAccess