@article{3100415,
    title = "Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation",
    author = "Mikus, M.S. and Kolmert, J. and Andersson, L.I. and Östling, J. and Knowles, R.G. and Gómez, C. and Ericsson, M. and Thörngren, J.-O. and Khoonsari, P.E. and Dahlén, B. and Kupczyk, M. and de Meulder, B. and Auffray, C. and Bakke, P.S. and Beghe, B. and Bel, E.H. and Caruso, M. and Chanez, P. and Chawes, B. and Fowler, S.J. and Gaga, M. and Geiser, T. and Gjomarkaj, M. and Horváth, I. and Howarth, P.H. and Johnston, S.L. and Joos, G. and Krug, N. and Montuschi, P. and Musial, J. and Niżankowska-Mogilnicka, E. and Olsson, H.K. and Papi, A. and Rabe, K.F. and Sandström, T. and Shaw, D.E. and Siafakas, N.M. and Uhlén, M. and Riley, J.H. and Bates, S. and Middelveld, R.J.M. and Wheelock, C.E. and Chung, K.F. and Adcock, I.M. and Sterk, P.J. and Djukanovic, R. and Nilsson, P. and Dahlén, S.-E. and James, A. and Ahmed, H. and Balgoma, D. and Bansal, A.T. and Baribaud, F. and Bigler, J. and Billing, B. and Bisgaard, H. and Boedigheimer, M.J. and Bønnelykke, K. and Brandsma, J. and Brinkman, P. and Bucchioni, E. and Burg, D. and Bush, A. and Chaiboonchoe, A. and Checa, T. and Compton, C.H. and Corfield, J. and Cunoosamy, D. and D’Amico, A. and Emma, R. and Erpenbeck, V.J. and Erzen, D. and Fichtner, K. and Fitch, N. and Fleming, L.J. and Formaggio, E. and Frey, U. and Gahlemann, M. and Goss, V. and Guo, Y.-K. and Hashimoto, S. and Haughney, J. and Hedlin, G. and Hekking, P.-P.W. and Higenbottam, T. and Hohlfeld, J.M. and Holweg, C.T.J. and Knox, A.J. and Konradsen, J. and Lazarinis, N. and Lefaudeux, D. and Li, T. and Loza, M.J. and Lutter, R. and Manta, A. and Masefield, S. and Matthews, J.G. and Mazein, A. and Meiser, A. and Miralpeix, M. and Mores, N. and Murray, C.S. and Myles, D. and Naz, S. and Nordlund, B. and Pahus, L. and Pandis, I. and Pavlidis, S. and Postle, A. and Powel, P. and Rao, N. and Reinke, S. and Roberts, A. and Roberts, G. and Rowe, A. and Schofield, J.P.R. and Seibold, W. and Selby, A. and Sigmund, R. and Singer, F. and Sjödin, M. and Skipp, P.J. and Sousa, A.R. and Sun, K. and Thornton, B. and Uddin, M. and van Aalderen, W.M. and van Geest, M. and Vestbo, J. and Vissing, N.H. and Wagener, A.H. and Wagers, S.S. and Weiszhart, Z. and Wheelock, C.E. and Wheelock, Å. and Wilson, S.J. and Yasinska, V. and Brusselle, G.G. and Campbell, D.A. and Contoli, M. and Damm, K. and de Rudder, I. and Delin, I. and Devautour, C. and Duplaga, M. and Eduards, M. and Ek, A. and Ekström, T. and Figiel, E. and Gaber, F. and Gauw, S. and Gawlewicz-Mroczka, A. and Gerding, D. and Haque, S. and Hewitt, L. and Hiemstra, P.S. and Holgate, S.T. and Holloway, J. and Kania, A. and Kanniess, F. and Karlsson, Ö. and Kips, J.C. and Kumlin, M. and Lantz, A.-S. and Lazarinis, N. and Magnussen, H. and Mallia, P. and Martling, I. and Meziane, L. and Oikonomidou, E. and Olsson, M. and Pace, E. and Papadopouli, E. and Papadopoulos, N. and Plataki, M. and Profita, M. and Reinius, L.E. and Richter, K. and Robinson, D.S. and Romagnoli, M. and Samara, K. and Schelfhout, V. and Skedinger, M. and Stamataki, E. and ten Brinke, A. and Vachier, I. and Wallén-Nielsen, E. and van Veen, I. and Weersink, E. and Wilson, S.J. and Yasinska, V. and Zervas, E. and Ziolkowska-Graca, B. and U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group and BIOAIR (Longitudinal Assessment of Clinical Course and Biomarkers in Severe Chronic Airway Disease) Consortium",
    journal = "European Respiratory Journal",
    year = "2022",
    volume = "59",
    number = "2",
    publisher = "European Respiratory Society",
    issn = "0903-1936, 1399-3003",
    doi = "10.1183/13993003.00142-2021",
    keywords = "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",
    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-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. © 2022 European Respiratory Society. All rights reserved."
}