The University of Southampton
University of Southampton Institutional Repository
Warning ePrints Soton is experiencing an issue with some file downloads not being available. We are working hard to fix this. Please bear with us.

Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort

Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort
Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort
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.
1932-6203
Emma, Rosalia
7eabb6ea-3ef0-45d6-9084-d263bd5e9104
Bansal, Aruna
1efe9f74-e8e6-444c-85d9-d2f196436c8d
Kolmert, Johan
031a7e44-0f44-45b0-a2ed-0d095d20f449
Wheelock, Craig E.
a22e130a-c8b7-4fdf-ad52-fc39635063bc
Dahlén, Sven-Erik
9e18ae23-c6a1-413c-93fe-203949a4dcda
Loza, Matthew J.
32a95cbe-77e2-4175-917e-47ada1e3e181
de Meulder, Bertrand
bbe29253-06c5-4bb3-a367-9460811b5407
Lefaudeux, Diane
924a38e0-ace4-4344-a2a4-33e41df1805d
Auffray, Charles
16fdf8f6-e7bc-4559-b6b6-d425160867c6
Dahlen, Barbro
3ca8df3c-d35a-40db-ad02-9356480468e6
Bakke, Per S.
14e4943c-16b0-4f9f-ab31-a72c6f02b581
Chanez, Pascal
695ba8e7-e6b7-49db-a88f-e5f5a366b869
Fowler, Stephen J.
7a077c2e-22e7-4a0c-b781-eec92fb931c8
Horvath, Ildiko
57682232-afd3-47ac-8725-ba6e92dc06ae
Montuschi, Paolo
10568e50-5a5f-47b3-9ac8-6a630c30882c
Krug, Norbert
eee1c70e-5c60-4344-ac06-3e689491a771
Sanak, Marek
2d614d0e-797e-4941-869a-9987521fb92c
Sandström, Thomas
77a4c11d-a84f-4a52-9bfe-4ec83f62363a
Shaw, Dominick E.
83e98e0a-fd2d-4c44-9249-6ac3ebd9614f
Fleming, Louise J.
9c75632b-dc6d-44c4-acea-ae13d116bd44
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Singer, Florian
48b6d2f7-f961-4609-beb4-7f56a544d3b3
Sousa, Ana R.
66270f3e-43c9-4d6a-a82f-ae83f5b02944
Sterk, Peter J.
cffc8681-7dc8-4328-ac93-4d5d5c4319b9
Corfield, Julie
662175c2-d799-4c6b-b2e7-feea13a59915
Pandis, Ioannis
c1091877-074d-40c0-a7e2-aa14c3af3318
Chung, Kian Fan
33cf2f88-c721-4573-8d6d-ea8da6b0498f
Adcock, Ian M.
e803eb97-a3dc-4de6-a090-9f41498cca1e
Lutter, Rene
8f82687b-826c-4d4a-b2fa-a30cf7d26da2
Fabbella, Lorena
02b77263-b399-4941-b7ef-f51abc6a8a02
Caruso, Massimo
d6a59da8-4f93-4926-93a6-e7c3b90b480f
Emma, Rosalia
7eabb6ea-3ef0-45d6-9084-d263bd5e9104
Bansal, Aruna
1efe9f74-e8e6-444c-85d9-d2f196436c8d
Kolmert, Johan
031a7e44-0f44-45b0-a2ed-0d095d20f449
Wheelock, Craig E.
a22e130a-c8b7-4fdf-ad52-fc39635063bc
Dahlén, Sven-Erik
9e18ae23-c6a1-413c-93fe-203949a4dcda
Loza, Matthew J.
32a95cbe-77e2-4175-917e-47ada1e3e181
de Meulder, Bertrand
bbe29253-06c5-4bb3-a367-9460811b5407
Lefaudeux, Diane
924a38e0-ace4-4344-a2a4-33e41df1805d
Auffray, Charles
16fdf8f6-e7bc-4559-b6b6-d425160867c6
Dahlen, Barbro
3ca8df3c-d35a-40db-ad02-9356480468e6
Bakke, Per S.
14e4943c-16b0-4f9f-ab31-a72c6f02b581
Chanez, Pascal
695ba8e7-e6b7-49db-a88f-e5f5a366b869
Fowler, Stephen J.
7a077c2e-22e7-4a0c-b781-eec92fb931c8
Horvath, Ildiko
57682232-afd3-47ac-8725-ba6e92dc06ae
Montuschi, Paolo
10568e50-5a5f-47b3-9ac8-6a630c30882c
Krug, Norbert
eee1c70e-5c60-4344-ac06-3e689491a771
Sanak, Marek
2d614d0e-797e-4941-869a-9987521fb92c
Sandström, Thomas
77a4c11d-a84f-4a52-9bfe-4ec83f62363a
Shaw, Dominick E.
83e98e0a-fd2d-4c44-9249-6ac3ebd9614f
Fleming, Louise J.
9c75632b-dc6d-44c4-acea-ae13d116bd44
Djukanovic, Ratko
d9a45ee7-6a80-4d84-a0ed-10962660a98d
Howarth, Peter
ff19c8c4-86b0-4a88-8f76-b3d87f142a21
Singer, Florian
48b6d2f7-f961-4609-beb4-7f56a544d3b3
Sousa, Ana R.
66270f3e-43c9-4d6a-a82f-ae83f5b02944
Sterk, Peter J.
cffc8681-7dc8-4328-ac93-4d5d5c4319b9
Corfield, Julie
662175c2-d799-4c6b-b2e7-feea13a59915
Pandis, Ioannis
c1091877-074d-40c0-a7e2-aa14c3af3318
Chung, Kian Fan
33cf2f88-c721-4573-8d6d-ea8da6b0498f
Adcock, Ian M.
e803eb97-a3dc-4de6-a090-9f41498cca1e
Lutter, Rene
8f82687b-826c-4d4a-b2fa-a30cf7d26da2
Fabbella, Lorena
02b77263-b399-4941-b7ef-f51abc6a8a02
Caruso, Massimo
d6a59da8-4f93-4926-93a6-e7c3b90b480f

Emma, Rosalia, Bansal, Aruna, Kolmert, Johan, Wheelock, Craig E., Dahlén, Sven-Erik, Loza, Matthew J., de Meulder, Bertrand, Lefaudeux, Diane, Auffray, Charles, Dahlen, Barbro, Bakke, Per S., Chanez, Pascal, Fowler, Stephen J., Horvath, Ildiko, Montuschi, Paolo, Krug, Norbert, Sanak, Marek, Sandström, Thomas, Shaw, Dominick E., Fleming, Louise J., Djukanovic, Ratko, Howarth, Peter, Singer, Florian, Sousa, Ana R., Sterk, Peter J., Corfield, Julie, Pandis, Ioannis, Chung, Kian Fan, Adcock, Ian M., Lutter, Rene, Fabbella, Lorena and Caruso, Massimo (2018) Enhanced oxidative stress in smoking and ex-smoking severe asthma in the U-BIOPRED cohort. PLoS ONE, 13 (9), [e0203874]. (doi:10.1371/journal.pone.0203874).

Record type: Article

Abstract

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.

Text
PONE_D_18_07290R2_FTC2_revised (1) - Accepted Manuscript
Available under License Creative Commons Attribution.
Download (164kB)

More information

Accepted/In Press date: 29 August 2018
e-pub ahead of print date: 21 September 2018

Identifiers

Local EPrints ID: 423167
URI: http://eprints.soton.ac.uk/id/eprint/423167
ISSN: 1932-6203
PURE UUID: 2461a1bf-5a81-426c-be07-bbb466e046db
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

Catalogue record

Date deposited: 19 Sep 2018 16:30
Last modified: 26 Nov 2021 06:09

Export record

Altmetrics

Contributors

Author: Rosalia Emma
Author: Aruna Bansal
Author: Johan Kolmert
Author: Craig E. Wheelock
Author: Sven-Erik Dahlén
Author: Matthew J. Loza
Author: Bertrand de Meulder
Author: Diane Lefaudeux
Author: Charles Auffray
Author: Barbro Dahlen
Author: Per S. Bakke
Author: Pascal Chanez
Author: Stephen J. Fowler
Author: Ildiko Horvath
Author: Paolo Montuschi
Author: Norbert Krug
Author: Marek Sanak
Author: Thomas Sandström
Author: Dominick E. Shaw
Author: Louise J. Fleming
Author: Peter Howarth
Author: Florian Singer
Author: Ana R. Sousa
Author: Peter J. Sterk
Author: Julie Corfield
Author: Ioannis Pandis
Author: Kian Fan Chung
Author: Ian M. Adcock
Author: Rene Lutter
Author: Lorena Fabbella
Author: Massimo Caruso

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×