Evidence map›Paper›PMID 30240401›Full record

ArticlePloS one2018

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

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 and 23 more

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01976767 (Protocol for the European Multi-Centre Study Understanding Severe Asthma Longitudinal Assessment of Adults With Severe Asthma), which is not on this map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01976767 completednot on this map

Protocol for the European Multi-Centre Study Understanding Severe Asthma Longitudinal Assessment of Adults With Severe Asthma

TypeobservationalSponsorAcademisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)Ran2011 to 2014Enrolled725ConditionsAsthma
3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 24 citations in OpenAlex.

  1. Article
  2. Phenotype overlap in the natural history of asthma.European respiratory review : an official journal of the European Respiratory Society · 2023
    Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Features of Oxidative and Nitrosative Metabolism in Lung Diseases.Oxidative medicine and cellular longevity · 2019
    Review
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

33 authors at 20 institutions in 11 countries.

Rosalia EmmaDepartment of Clinical and Experimental Medicine - University of Catania, Catania, Italy.ORCID 0000-0002-2564-553X
Aruna T BansalAcclarogen Ltd, St John's Innovation Centre, Cambridge, United Kingdom.ORCID 0000-0002-7262-6534
Johan KolmertDivision of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Craig E WheelockDivision of Physiological Chemistry 2, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Swen-Erik DahlenCentre for Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Matthew J LozaJanssen Research & Development, LLC, Springhouse, Pennsylvania, United States of America.
Bertrand De MeulderEuropean Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, CIRI-UMR5308, Lyon, France.
Diane LefaudeuxEuropean Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, CIRI-UMR5308, Lyon, France.
Charles AuffrayEuropean Institute for Systems Biology and Medicine, CNRS-ENS-UCBL-INSERM, CIRI-UMR5308, Lyon, France.
Barbro DahlenKarolinska University Hospital & Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
Per S BakkeDepartment of Clinical Science, University of Bergen, Bergen, Norway.
Pascal ChanezDépartement des Maladies Respiratoires, CIC Nord, INSERM U1067 Aix Marseille Université Marseille, Marseille, France.
Stephen J FowlerCentre for Respiratory Medicine and Allergy, The University of Manchester, Manchester Academic Health Science Centre, University Hospital of South Manchester NHS Foundation Trust, Clinic, Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom.
Ildiko HorvathDepartment of Pulmonology, Semmelweis University, Budapest, Hungary.
Paolo MontuschiFaculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy.
Norbert KrugFraunhofer Institute for Toxicology and Experimental Medicine Hannover, Germany.
Marek SanakDepartment of Medicine, Jagiellonian University Medical School, Krakow, Poland.
Thomas SandstromDept of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.
Dominick E ShawRespiratory Research Unit, University of Nottingham, Nottingham, United Kingdom.ORCID 0000-0003-4106-8469
Louise J FlemingNational Heart & Lung Institute, Imperial College, London, United Kingdom.ORCID 0000-0002-7268-7433
Ratko DjukanovicNIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
Peter H HowarthNIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Southampton, United Kingdom.
Florian SingerUniversity Children's Hospital Bern, Bern, Switzerland.ORCID 0000-0003-3471-5664
Ana R SousaRespiratory Therapy Unit, GlaxoSmithKline, London, United Kingdom.
Peter J SterkDept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Julie CorfieldAstraZeneca R&D, Mölndal, Sweden.
Ioannis PandisData Science Institute, South Kensington Campus, Imperial College London, London, United Kingdom.
Kian F ChungNational Heart & Lung Institute, Imperial College, London, United Kingdom.
Ian M AdcockNational Heart & Lung Institute, Imperial College, London, United Kingdom.ORCID 0000-0003-2101-8843
René LutterDept of Respiratory Medicine, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
Lorena FabbellaDepartment of Clinical and Experimental Medicine - University of Catania, Catania, Italy.
Massimo CarusoDepartment of Clinical and Experimental Medicine - University of Catania, Catania, Italy.ORCID 0000-0002-4412-2080
U-BIOPRED Study Group
Imperial College London · GBKarolinska Institutet · SEUniversité Claude Bernard Lyon 1 · FRUniversity of Catania · ITNIHR Southampton Respiratory Biomedical Research Unit · GBUniversity of Amsterdam · NLArete (United Kingdom) · GBFraunhofer Institute for Toxicology and Experimental Medicine · DEGlaxoSmithKline (United Kingdom) · GBInserm · FRJagiellonian University · PLKarolinska University Hospital · SELancashire Teaching Hospitals NHS Foundation Trust · GBSemmelweis University · HUSpringhouse · USUmeå University · SEUniversità Cattolica del Sacro Cuore · ITUniversity Children’s Hospital Bern · CHUniversity of Bergen · NOUniversity of Nottingham · GB

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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. Trial registration ClinicalTrials.gov-Identifier: NCT01976767.

Indexed as

AdultAsthmaBiomarkersBronchoscopyCohort StudiesFemaleHumansInflammationMaleMiddle AgedOxidative StressSmokingSputumTobacco SmokingBiomarkers

Identifiers

PMID30240401
PMCPMC6150501
OpenAlexW2902060873

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.