dc.contributor.author | Mikus, Maria Sparreman | |
dc.contributor.author | Kolmert, Johan | |
dc.contributor.author | Andersson, Lars I. | |
dc.contributor.author | Östling, Jörgen | |
dc.contributor.author | Knowles, Richard G. | |
dc.contributor.author | Gómez, Cristina | |
dc.contributor.author | Ericsson, Magnus | |
dc.contributor.author | Thörngren, John-Olof | |
dc.contributor.author | Khoonsari, Payam Emami | |
dc.contributor.author | Dahlén, Barbro | |
dc.contributor.author | Kupczyk, Maciej | |
dc.contributor.author | de Meulder, Bertrand | |
dc.contributor.author | Auffray, Charles | |
dc.contributor.author | Bakke, Per S. | |
dc.contributor.author | Beghe, Bianca | |
dc.contributor.author | Bel, Elisabeth H. | |
dc.contributor.author | Caruso, Massimo | |
dc.contributor.author | Chanez, Pascal | |
dc.contributor.author | Chawes, Bo | |
dc.contributor.author | Fowler, Stephen J. | |
dc.contributor.author | Gaga, Mina | |
dc.contributor.author | Geiser, Thomas | |
dc.contributor.author | Gjomarkaj, Mark | |
dc.contributor.author | Horváth, Ildikó | |
dc.contributor.author | Howarth, Peter H. | |
dc.contributor.author | Johnston, Sebastian L. | |
dc.contributor.author | Joos, Guy | |
dc.contributor.author | Krug, Norbert | |
dc.contributor.author | Montuschi, Paolo | |
dc.contributor.author | Musial, Jacek | |
dc.contributor.author | Niżankowska-Mogilnicka, Ewa | |
dc.contributor.author | Olsson, Henric K. | |
dc.contributor.author | Papi, Alberto | |
dc.contributor.author | Rabe, Klaus F. | |
dc.contributor.author | Sandström, Thomas | |
dc.contributor.author | Shaw, Dominick E. | |
dc.contributor.author | Siafakas, Nikolaos M. | |
dc.contributor.author | Uhlén, Mathias | |
dc.contributor.author | Riley, John H. | |
dc.contributor.author | Bates, Stewart | |
dc.contributor.author | Middelveld, Roelinde J.M. | |
dc.contributor.author | Wheelock, Craig E. | |
dc.contributor.author | Chung, Kian Fan | |
dc.contributor.author | Adcock, Ian M. | |
dc.contributor.author | Sterk, Peter J. | |
dc.contributor.author | Djukanovic, Ratko | |
dc.contributor.author | Nilsson, Peter | |
dc.contributor.author | Dahlén, Sven-Erik | |
dc.contributor.author | James, Anna | |
dc.date.accessioned | 2022-10-10T13:49:04Z | |
dc.date.available | 2022-10-10T13:49:04Z | |
dc.date.created | 2022-05-24T09:00:47Z | |
dc.date.issued | 2022 | |
dc.identifier.issn | 0903-1936 | |
dc.identifier.uri | https://hdl.handle.net/11250/3025166 | |
dc.description.abstract | Rationale Asthma phenotyping requires novel biomarker discovery.
Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs).
Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED.
Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation.
Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | ERS | en_US |
dc.rights | Navngivelse-Ikkekommersiell 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc/4.0/deed.no | * |
dc.title | Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation | en_US |
dc.type | Journal article | en_US |
dc.type | Peer reviewed | en_US |
dc.description.version | publishedVersion | en_US |
dc.rights.holder | Copyright 2022 The Author(s) | en_US |
dc.source.articlenumber | 2100142 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |
dc.identifier.doi | 10.1183/13993003.00142-2021 | |
dc.identifier.cristin | 2026773 | |
dc.source.journal | European Respiratory Journal | en_US |
dc.identifier.citation | European Respiratory Journal. 2022, 59, 2100142. | en_US |
dc.source.volume | 59 | en_US |
dc.source.issue | 2 | en_US |