TY - JOUR
TI - Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation
AU - Mikus, M.S.
AU - Kolmert, J.
AU - Andersson, L.I.
AU - Östling, J.
AU - Knowles, R.G.
AU - Gómez, C.
AU - Ericsson, M.
AU - Thörngren, J.-O.
AU - Khoonsari, P.E.
AU - Dahlén, B.
AU - Kupczyk, M.
AU - de Meulder, B.
AU - Auffray, C.
AU - Bakke, P.S.
AU - Beghe, B.
AU - Bel, E.H.
AU - Caruso, M.
AU - Chanez, P.
AU - Chawes, B.
AU - Fowler, S.J.
AU - Gaga, M.
AU - Geiser, T.
AU - Gjomarkaj, M.
AU - Horváth, I.
AU - Howarth, P.H.
AU - Johnston, S.L.
AU - Joos, G.
AU - Krug, N.
AU - Montuschi, P.
AU - Musial, J.
AU - Niżankowska-Mogilnicka, E.
AU - Olsson, H.K.
AU - Papi, A.
AU - Rabe, K.F.
AU - Sandström, T.
AU - Shaw, D.E.
AU - Siafakas, N.M.
AU - Uhlén, M.
AU - Riley, J.H.
AU - Bates, S.
AU - Middelveld, R.J.M.
AU - Wheelock, C.E.
AU - Chung, K.F.
AU - Adcock, I.M.
AU - Sterk, P.J.
AU - Djukanovic, R.
AU - Nilsson, P.
AU - Dahlén, S.-E.
AU - James, A.
AU - Ahmed, H.
AU - Balgoma, D.
AU - Bansal, A.T.
AU - Baribaud, F.
AU - Bigler, J.
AU - Billing, B.
AU - Bisgaard, H.
AU - Boedigheimer, M.J.
AU - Bønnelykke, K.
AU - Brandsma, J.
AU - Brinkman, P.
AU - Bucchioni, E.
AU - Burg, D.
AU - Bush, A.
AU - Chaiboonchoe, A.
AU - Checa, T.
AU - Compton, C.H.
AU - Corfield, J.
AU - Cunoosamy, D.
AU - D’Amico, A.
AU - Emma, R.
AU - Erpenbeck, V.J.
AU - Erzen, D.
AU - Fichtner, K.
AU - Fitch, N.
AU - Fleming, L.J.
AU - Formaggio, E.
AU - Frey, U.
AU - Gahlemann, M.
AU - Goss, V.
AU - Guo, Y.-K.
AU - Hashimoto, S.
AU - Haughney, J.
AU - Hedlin, G.
AU - Hekking, P.-P.W.
AU - Higenbottam, T.
AU - Hohlfeld, J.M.
AU - Holweg, C.T.J.
AU - Knox, A.J.
AU - Konradsen, J.
AU - Lazarinis, N.
AU - Lefaudeux, D.
AU - Li, T.
AU - Loza, M.J.
AU - Lutter, R.
AU - Manta, A.
AU - Masefield, S.
AU - Matthews, J.G.
AU - Mazein, A.
AU - Meiser, A.
AU - Miralpeix, M.
AU - Mores, N.
AU - Murray, C.S.
AU - Myles, D.
AU - Naz, S.
AU - Nordlund, B.
AU - Pahus, L.
AU - Pandis, I.
AU - Pavlidis, S.
AU - Postle, A.
AU - Powel, P.
AU - Rao, N.
AU - Reinke, S.
AU - Roberts, A.
AU - Roberts, G.
AU - Rowe, A.
AU - Schofield, J.P.R.
AU - Seibold, W.
AU - Selby, A.
AU - Sigmund, R.
AU - Singer, F.
AU - Sjödin, M.
AU - Skipp, P.J.
AU - Sousa, A.R.
AU - Sun, K.
AU - Thornton, B.
AU - Uddin, M.
AU - van Aalderen, W.M.
AU - van Geest, M.
AU - Vestbo, J.
AU - Vissing, N.H.
AU - Wagener, A.H.
AU - Wagers, S.S.
AU - Weiszhart, Z.
AU - Wheelock, C.E.
AU - Wheelock, Å.
AU - Wilson, S.J.
AU - Yasinska, V.
AU - Brusselle, G.G.
AU - Campbell, D.A.
AU - Contoli, M.
AU - Damm, K.
AU - de Rudder, I.
AU - Delin, I.
AU - Devautour, C.
AU - Duplaga, M.
AU - Eduards, M.
AU - Ek, A.
AU - Ekström, T.
AU - Figiel, E.
AU - Gaber, F.
AU - Gauw, S.
AU - Gawlewicz-Mroczka, A.
AU - Gerding, D.
AU - Haque, S.
AU - Hewitt, L.
AU - Hiemstra, P.S.
AU - Holgate, S.T.
AU - Holloway, J.
AU - Kania, A.
AU - Kanniess, F.
AU - Karlsson, Ö.
AU - Kips, J.C.
AU - Kumlin, M.
AU - Lantz, A.-S.
AU - Lazarinis, N.
AU - Magnussen, H.
AU - Mallia, P.
AU - Martling, I.
AU - Meziane, L.
AU - Oikonomidou, E.
AU - Olsson, M.
AU - Pace, E.
AU - Papadopouli, E.
AU - Papadopoulos, N.
AU - Plataki, M.
AU - Profita, M.
AU - Reinius, L.E.
AU - Richter, K.
AU - Robinson, D.S.
AU - Romagnoli, M.
AU - Samara, K.
AU - Schelfhout, V.
AU - Skedinger, M.
AU - Stamataki, E.
AU - ten Brinke, A.
AU - Vachier, I.
AU - Wallén-Nielsen, E.
AU - van Veen, I.
AU - Weersink, E.
AU - Wilson, S.J.
AU - Yasinska, V.
AU - Zervas, E.
AU - Ziolkowska-Graca, B.
AU - U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group
AU - BIOAIR (Longitudinal Assessment of Clinical Course
AU - Biomarkers in Severe Chronic Airway Disease) Consortium
JO - European Respiratory Journal
PY - 2022
VL - 59
TODO - 2
SP - null
PB - European Respiratory Society
SN - 0903-1936, 1399-3003
TODO - 10.1183/13993003.00142-2021
TODO - alpha 1 antichymotrypsin;  apolipoprotein E;  C reactive protein;  carboxypeptidase;  carboxypeptidase A3;  complement component C9;  complement factor I;  glutathione transferase;  interleukin 6;  macrophage inflammatory protein;  macrophage inflammatory protein 3;  placebo;  plasma protein;  prednisolone;  receptor activator of nuclear factor kappa B;  sphingomyelin phosphodiesterase;  sphingomyelin phosphodiesterase 3;  transforming growth factor beta;  unclassified drug, abnormally high substrate concentration in blood;  adult;  Article;  asthma;  body mass;  chronic obstructive lung disease;  cohort analysis;  controlled study;  disease association;  disease severity;  double blind procedure;  extracellular matrix;  female;  human;  human cell;  inflammation;  lipid metabolism;  major clinical study;  male;  middle aged;  neutrophil count;  phenotype;  protein blood level;  protein targeting;  quality of life;  signal transduction;  treatment duration;  validation study
TODO - 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-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. © 2022 European Respiratory Society. All rights reserved.
ER -