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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA<jats:italic>versus<\/jats:italic>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-\u03b2 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.1183\/13993003.00142-2021","type":"journal-article","created":{"date-parts":[[2021,11,4]],"date-time":"2021-11-04T17:00:30Z","timestamp":1636045230000},"page":"2100142","update-policy":"https:\/\/doi.org\/10.1183\/ers-crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation"],"prefix":"10.1183","volume":"59","author":[{"given":"Maria","family":"Sparreman 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