WFRF:(Bakke I. M. B.)
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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 10940naa a2200841 4500 | |
| 001 | oai:prod.swepub.kib.ki.se:150324797 | |
| 003 | SwePub | |
| 008 | 240811s2022 | |||||||||||000 ||eng| | |
| 009 | oai:DiVA.org:umu-198227 | |
| 024 | 7 | a http://kipublications.ki.se/Default.aspx?queryparsed=id:1503247972 URI |
| 024 | 7 | a https://doi.org/10.1183/13993003.01733-20212 DOI |
| 024 | 7 | a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1982272 URI |
| 040 | a (SwePub)kid (SwePub)umu | |
| 041 | a engb eng | |
| 042 | 9 SwePub | |
| 072 | 7 | a ref2 swepub-contenttype |
| 072 | 7 | a art2 swepub-publicationtype |
| 100 | 1 | a Reinke, SNu Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Centre for Integrative Metabolomics and Computational Biology, School of Science, Edith Cowan University, Perth, Australia; Equal contribution4 aut |
| 245 | 1 0 | a Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study |
| 264 | c 2021-11-25 | |
| 264 | 1 | b European Respiratory Society (ERS),c 2022 |
| 520 | a Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.MethodsBaseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12–18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.ResultsA total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10−20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10−4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.ConclusionsThis is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carnitine metabolism is a potentially actionable therapeutic target that is independent of OCS treatment, highlighting the role of mitochondrial dysfunction in severe asthma. | |
| 650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Lungmedicin och allergi0 (SwePub)302192 hsv//swe |
| 650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Respiratory Medicine and Allergy0 (SwePub)302192 hsv//eng |
| 700 | 1 | a Naz, S4 aut |
| 700 | 1 | a Chaleckis, Ru Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Gunma Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Japan4 aut |
| 700 | 1 | a Gallart-Ayala, Hu Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden4 aut |
| 700 | 1 | a Kolmert, Ju Karolinska Institutet,Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden4 aut |
| 700 | 1 | a Kermani, NZu National Heart and Lung Institute, Imperial College, London, United Kingdom4 aut |
| 700 | 1 | a Tiotiu, Au National Heart and Lung Institute, Imperial College, London, United Kingdom; Dept of Pulmonology, University Hospital of Nancy, Nancy, France4 aut |
| 700 | 1 | a Broadhurst, DIu Karolinska Institutet4 aut |
| 700 | 1 | a Lundqvist, Au DMPK, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden4 aut |
| 700 | 1 | a Olsson, Hu Translational Science and Experimental Medicine, Research and Early Development, Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden4 aut |
| 700 | 1 | a Strom, Mu Karolinska Institutet,Respiratory Medicine Unit, K2 Dept of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden4 aut |
| 700 | 1 | a Wheelock, AMu Karolinska Institutet,Respiratory Medicine Unit, K2 Dept of Medicine Solna and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden4 aut |
| 700 | 1 | a Gomez, Cu Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden4 aut |
| 700 | 1 | a Ericsson, Mu Dept of Clinical Pharmacology, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden4 aut |
| 700 | 1 | a Sousa, ARu GlaxoSmithKline, London, United Kingdom4 aut |
| 700 | 1 | a Riley, JHu GlaxoSmithKline, London, United Kingdom4 aut |
| 700 | 1 | a Bates, Su GlaxoSmithKline, London, United Kingdom,Faculty of Medicine, Southampton University and NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom4 aut |
| 700 | 1 | a Scholfield, J4 aut |
| 700 | 1 | a Loza, Mu Janssen Research and Development, High Wycombe, United Kingdom4 aut |
| 700 | 1 | a Baribaud, Fu Janssen Research and Development, High Wycombe, United Kingdom4 aut |
| 700 | 1 | a Bakke, PSu Institute of Medicine, University of Bergen, Bergen, Norway4 aut |
| 700 | 1 | a Caruso, Mu Dept of Biomedical and Biotechnological Sciences and Dept of Clinical and Experimental Medicine, University of Catania, Catania, Italy4 aut |
| 700 | 1 | a Chanez, Pu Assistance Publique des Hôpitaux de Marseille, Clinique des Bronches, Allergies et Sommeil, Aix Marseille Université, Marseille, France4 aut |
| 700 | 1 | a Fowler, SJu Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre and NIHR Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom4 aut |
| 700 | 1 | a Geiser, Tu Dept of Pulmonary Medicine, University Hospital, University of Bern, Bern, Switzerland4 aut |
| 700 | 1 | a Howarth, Pu Faculty of Medicine, Southampton University and NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom4 aut |
| 700 | 1 | a Horvath, Iu Dept of Pulmonology, Semmelweis University, Budapest, Hungary4 aut |
| 700 | 1 | a Krug, Nu Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany4 aut |
| 700 | 1 | a Montuschi, Pu Pharmacology, Catholic University of the Sacred Heart, Rome, Italy4 aut |
| 700 | 1 | a Behndig, Annelie F.,d 1963-u Umeå universitet,Lungmedicin4 aut0 (Swepub:umu)anbe0145 |
| 700 | 1 | a Singer, Fu Division of Paediatric Respiratory Medicine and Allergology, Dept of Paediatrics, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland4 aut |
| 700 | 1 | a Musial, Ju Dept of Medicine, Jagiellonian University Medical College, Krakow, Poland4 aut |
| 700 | 1 | a Shaw, DEu Karolinska Institutet4 aut |
| 700 | 1 | a Dahlen, Bu Karolinska Institutet,Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden4 aut |
| 700 | 1 | a Hu, SLu Data Science Institute, Imperial College, London, United Kingdom4 aut |
| 700 | 1 | a Lasky-Su, Ju Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, MA, Boston, United States4 aut |
| 700 | 1 | a Sterk, PJu Dept of Respiratory Medicine, University of Amsterdam, Amsterdam, Netherlands4 aut |
| 700 | 1 | a Chung, KFu National Heart and Lung Institute, Imperial College, London, United Kingdom4 aut |
| 700 | 1 | a Djukanovic, Ru Faculty of Medicine, Southampton University and NIHR Southampton Respiratory Biomedical Research Centre, University Hospital Southampton, Southampton, United Kingdom4 aut |
| 700 | 1 | a Dahlen, SEu Karolinska Institutet,Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden4 aut |
| 700 | 1 | a Adcock, IMu National Heart and Lung Institute, Imperial College, London, United Kingdom4 aut |
| 700 | 1 | a Wheelock, CEu Karolinska Institutet,Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Gunma Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Japan; Dept of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden4 aut |
| 710 | 2 | a Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Centre for Integrative Metabolomics and Computational Biology, School of Science, Edith Cowan University, Perth, Australia; Equal contributionb Division of Physiological Chemistry 2, Dept of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; Gunma Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Japan4 org |
| 773 | 0 | t The European respiratory journald : European Respiratory Society (ERS)g 59:6q 59:6x 1399-3003x 0903-1936 |
| 856 | 4 | u https://erj.ersjournals.com/content/erj/early/2021/11/04/13993003.01733-2021.full.pdf |
| 856 | 4 | u https://doi.org/10.1183/13993003.01733-2021y Fulltext |
| 856 | 4 | u https://umu.diva-portal.org/smash/get/diva2:1684127/FULLTEXT01.pdfx primaryx Raw objecty fulltext:print |
| 856 | 4 8 | u http://kipublications.ki.se/Default.aspx?queryparsed=id:150324797 |
| 856 | 4 8 | u https://doi.org/10.1183/13993003.01733-2021 |
| 856 | 4 8 | u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-198227 |
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- Reinke, SN
- Naz, S
- Chaleckis, R
- Gallart-Ayala, H
- Kolmert, J
- Kermani, NZ
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- Tiotiu, A
- Broadhurst, DI
- Lundqvist, A
- Olsson, H
- Strom, M
- Wheelock, AM
- Gomez, C
- Ericsson, M
- Sousa, AR
- Riley, JH
- Bates, S
- Scholfield, J
- Loza, M
- Baribaud, F
- Bakke, PS
- Caruso, M
- Chanez, P
- Fowler, SJ
- Geiser, T
- Howarth, P
- Horvath, I
- Krug, N
- Montuschi, P
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- Singer, F
- Musial, J
- Shaw, DE
- Dahlen, B
- Hu, SL
- Lasky-Su, J
- Sterk, PJ
- Chung, KF
- Djukanovic, R
- Dahlen, SE
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