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182 results on '"Hedlin, G."'

1. Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status

Author

Alcantara-Neves, N., Almeida, P.C.A., Amorim, L., Araujo, M.I., Barnes, K.C., Barreto, M.L., Belitardo, E., Bião-Lima, V., Cardoso, L., Camargos, P.A., Chatkin, J.M., Costa, R.S., Coelho, A.C.C., Cooper, P.J., Cruz, A.A., Cruz, C.S., Cunha, J., de Jesus, J.V., Fernandes, J., Franco, R.A., Gomes-Filho, I., Lima-Matos, A., Figueiredo, C.A., Lessa, M.A., Lins, L., Mello, L.M., Moura-Santos, P., Muniz, I.S., Paixao-Araujo, I., Pinheiro, G.P., Ponte, E.V., Rodrigues, L.C., Santana, C.V.N., Santos-Lima, G., Souza, T.M.O., Souza-Machado, A., Souza-Machado, C., Stelmach, R., Vasquez, V.S., Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Baribaud, F., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Compton, C.H., Corfield, J., D'Amico, A., Dahlén, B., Dahlén, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y.-K., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., James, A.J., Knowles, R.G., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., Matthews, J.G., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Praticò, G., Puig Valls, M., Rao, N., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Schofield, J.P.R., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Cruz, Alvaro A., Riley, John H., Bansal, Aruna T., Ponte, Eduardo V., Souza-Machado, Adelmir, Almeida, Paula C.A., Biao-Lima, Valmar, Davis, Maggie, Bates, Stewart, Adcock, Ian M., Sterk, Peter J., and Chung, Kian Fan

Published
2020
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2. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K.F., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., Howarth, P., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Lutter, R., Manta, A., Masefield, S., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Praticò, G., Rao, M. Puig N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P., Balgoma, David, Ballereau, S., Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, A., Bedding, A., Behndig, A.F., Beleta, Jorge, Berglind, A., Berton, A., Bochenek, Grazyna, Braun, Armin, Campagna, D., Carayannopoulos, Leon, Casaulta, C., Chaleckis, Romanas, Dahlén, B., Davison, imothy, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Delin, Ingrid, Dennison, P., Dijkhuis, Annemiek, Dodson, Paul, Draper, Aleksandra, Dyson, K., Edwards, Jessica, El Hadjam, L., Emma, Rosalia, Ericsson, Magnus, Faulenbach, C., Flood, Breda, Galffy, G., Gallart, Hector, Garissi, D., Gent, J., Gerhardsson de Verdier, M., Gibeon, D., Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Guillmant-Farry, E., Henriksson, E., Hewitt, Lorraine, Hoda, U., Hu, Richard, Hu, Sile, Hu, X., Jeyasingham, E., Johnson, K., Jullian, N., Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Kerry, G., Klüglich, M., Knobel, Hugo, Kolmert, Johan, Konradsen, J.R., Kots, Maxim, Kretsos, Kosmas, Krueger, L., Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lantz, A.-S., Larminie, Christopher, Larsson, L.X., Latzin, P., Lazarinis, N., Lemonnier, N., Lone-Latif, Saeeda, Lowe, L.A., Manta, Alexander, Marouzet, Lisa, Martin, Jane, Mathon, Caroline, McEvoy, L., Meah, Sally, Menzies-Gow, A., Metcalf, Leanne, Mikus, Maria, Monk, Philip, Naz, Shama, Nething, K., Nicholas, Ben, Nihlén, U., Nilsson, Peter, Niven, R., Nordlund, B., Nsubuga, S., Pacino, Antonio, Palkonen, Susanna, Pellet, J., Pennazza, Giorgio, Petrén, Anne, Pink, Sandy, Pison, C., Postle, Anthony, Rahman-Amin, Malayka, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Riemann, K., Robberechts, Martine, Rocha, J.P., Rossios, C., Russell, Kirsty, Rutgers, Michael, Santini, G., Santoninco, Marco, Saqi, M., Schoelch, Corinna, Schofield, James P.R., Scott, S., Sehgal, N., Sjödin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Söderman, P., Sogbessan, A., Spycher, F., Staykova, Doroteya, Stephan, S., Stokholm, J., Strandberg, K., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Thörngren, John-Olof, Thorsen, Jonathan, Valente, S., van de Pol, Marianne, van Drunen, C.M., Van Eyll, Jonathan, Versnel, Jenny, Vink, Anton, von Garnier, C., Vyas, A., Wald, Frans, Walker, Samantha, Ward, Jonathan, Wetzel, Kristiane, Wiegman, Coen, Williams, Siân, Yang, Xian, Yeyasingham, Elizabeth, Amgen, W. Yu, Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Östling, Jörgen, van Geest, Marleen, Jevnikar, Zala, Wilson, Susan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanović, Ratko, and Vaarala, Outi

Published
2019
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3. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Author

Adcock, I.M., Ahmed, H., Auffray, C., Bakke, P., Bansal, A.T., Baribaud, F., Bates, S., Bel, E.H., Bigler, J., Bisgaard, H., Boedigheimer, M.J., Bønnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, F.K., Compton, C.H., Corfield, J., D'Amico, A., Dahlen, S.E., De Meulder, B., Djukanovic, R., Erpenbeck, V.J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L.J., Formaggio, E., Fowler, S.J., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P.W., Higenbottam, T., Hohlfeld, J.M., Holweg, C., Horváth, I., James, A.J., Knowles, R., Knox, A.J., Krug, N., Lefaudeux, D., Loza, M.J., Manta, A., Matthews, J.G., Mazein, A., Meiser, A., Middelveld, R.J.M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C.S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Praticò, G., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Schofield, J.P.R., Seibold, W., Selby, A., Shaw, D.E., Sigmund, R., Singer, F., Skipp, P.J., Sousa, A.R., Sterk, P.J., Sun, K., Thornton, B., van Aalderen, W.M., van Geest, M., Vestbo, J., Vissing, N.H., Wagener, A.H., Wagers, S.S., Weiszhart, Z., Wheelock, C.E., Wilson, S.J., Jevnikar, Zala, Östling, Jörgen, Ax, Elisabeth, Calvén, Jenny, Thörn, Kristofer, Israelsson, Elisabeth, Öberg, Lisa, Singhania, Akul, Lau, Laurie C.K., Wilson, Susan J., Ward, Jonathan A., Chauhan, Anoop, Sousa, Ana R., De Meulder, Bertrand, Loza, Matthew J., Baribaud, Frédéric, Sterk, Peter J., Chung, Kian Fan, Sun, Kai, Guo, Yike, Adcock, Ian M., Payne, Debbie, Dahlen, Barbro, Chanez, Pascal, Shaw, Dominick E., Krug, Norbert, Hohlfeld, Jens M., Sandström, Thomas, Djukanovic, Ratko, James, Anna, Hinks, Timothy S.C., Howarth, Peter H., Vaarala, Outi, van Geest, Marleen, and Olsson, Henric

Published
2019
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4. Identification of oropharyngeal microbiome-driven asthma and wheezing clusters in children

Author

Abdel-Aziz, M I, primary, Thorsen, J, additional, Hashimoto, S, additional, Vijverberg, S J H, additional, Neerincx, A H, additional, Brinkman, P, additional, Aalderen, W V, additional, Stokholm, J, additional, Roggenbuck-Wedemeyer, M, additional, Vissing, N H, additional, Mortensen, M S, additional, Brejnrod, A D, additional, Fleming, L J, additional, Murray, C S, additional, Fowler, S J, additional, Frey, U, additional, Bush, A, additional, Singer, F, additional, Hedlin, G, additional, Nordlund, B, additional, Shaw, D E, additional, Chung, K F, additional, Adcock, I M, additional, Djukanovic, R, additional, Auffray, C, additional, Bansal, A T, additional, Sousa, A R, additional, Wagers, S S, additional, Chawes, B L, additional, Bønnelykke, K, additional, Sørensen, S J, additional, Kraneveld, A D, additional, Sterk, P J, additional, Roberts, G, additional, Bisgaard, H, additional, and Maitland-Van Der Zee, A H, additional

Published
2022
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5. Early food intervention and skin emollients to prevent preschool asthma

Author

Lie, A, primary, Leblanc, M, additional, Färdig, M, additional, Vettukattil, R, additional, Ådalen, S, additional, Skrindo, I, additional, Gerdin, S W, additional, Granum, B, additional, Gudmundsdottir, H K, additional, Hedlin, G, additional, Hoyer, A, additional, Jonassen, C M, additional, Nordlund, B, additional, Rehbinder, E M, additional, Staff, A C, additional, Söderhall, C, additional, Tedner, S G, additional, Aaneland, H, additional, Carlsen, K C L, additional, and Skjerven, H O, additional

Published
2022
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6. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

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

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.

Published
2022

7. Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation

Author

Mikus, M. S., Kolmert, J., Andersson, L. I., Ostling, J., Knowles, R. G., Gomez, C., Ericsson, M., Thorngren, J. -O., Khoonsari, P. E., Dahlen, B., Kupczyk, M., de Meulder, B., Auffray, C., Bakke, P. S., Beghe, Bianca, Bel, E. H., Caruso, M., Chanez, P., Chawes, B., Fowler, S. J., Gaga, M., Geiser, T., Gjomarkaj, M., Horvath, I., Howarth, P. H., Johnston, S. L., Joos, G., Krug, N., Montuschi, P., Musial, J., Nizankowska-Mogilnicka, E., Olsson, H. K., Papi, A., Rabe, K. F., Sandstrom, T., Shaw, D. E., Siafakas, N. M., Uhlen, M., Riley, J. H., Bates, S., Middelveld, R. J. M., Wheelock, C. E., Chung, K. F., Adcock, I. M., Sterk, P. J., Djukanovic, R., Nilsson, P., Dahlen, S. -E., James, A., Ahmed, H., Balgoma, D., Bansal, A. T., Baribaud, F., Bigler, J., Billing, B., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Checa, T., Compton, C. H., Corfield, J., Cunoosamy, D., D'Amico, A., Emma, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Frey, U., Gahlemann, M., Goss, V., Guo, Y. -K., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. -P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C. T. J., Knox, A. J., Konradsen, J., Lazarinis, N., Lefaudeux, D., Li, T., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Miralpeix, M., Mores, N., Murray, C. S., Myles, D., Naz, S., Nordlund, B., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Rao, N., Reinke, S., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Singer, F., Sjodin, M., Skipp, P. J., Sousa, A. R., Sun, K., Thornton, B., Uddin, M., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, A., Wilson, S. J., Yasinska, V., Brusselle, G. G., Campbell, D. A., Contoli, M., Damm, K., de Rudder, I., Delin, I., Devautour, C., Duplaga, M., Eduards, M., Ek, A., Ekstrom, T., Figiel, E., Gaber, F., Gauw, S., Gawlewicz-Mroczka, A., Gerding, D., Haque, S., Hewitt, L., Hiemstra, P. S., Holgate, S. T., Holloway, J., Kania, A., Kanniess, F., Karlsson, O., Kips, J. C., Kumlin, M., Lantz, A. -S., Magnussen, H., Mallia, P., Martling, I., Meziane, L., Oikonomidou, E., Olsson, M., Pace, E., Papadopouli, E., Papadopoulos, N., Plataki, M., Profita, M., Reinius, L. E., Richter, K., Robinson, D. S., Romagnoli, M., Samara, K., Schelfhout, V., Skedinger, M., Stamataki, E., ten Brinke, A., Vachier, I., Wallen-Nielsen, E., van Veen, I., Weersink, E., Zervas, E., and Ziolkowska-Graca, B.

Subjects
Blood Proteins, Humans, Inflammation, Proteomics, Severity of Illness Index, Steroids, Asthma, Quality of Life
Published
2022

8. Diagnosing atopic dermatitis in infancy using established diagnostic criteria: a cohort study

Author

Endre, K.M.A., primary, Landrø, L., additional, LeBlanc, M., additional, Gjersvik, P., additional, Lødrup Carlsen, K.C., additional, Haugen, G., additional, Hedlin, G., additional, Jonassen, C.M., additional, Nordlund, B., additional, Rudi, K., additional, Skjerven, H.O., additional, Staff, A.C., additional, Söderhäll, C., additional, Vettukattil, R., additional, and Rehbinder, E.M., additional

Published
2022
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9. Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy*

Author

Hoyer, A., primary, Rehbinder, E.M., additional, Färdig, M., additional, Asad, S., additional, Lødrup Carlsen, K.C., additional, Endre, K.M.A., additional, Granum, B., additional, Haugen, G., additional, Hedlin, G., additional, Monceyron Jonassen, C., additional, Katayama, S., additional, Konradsen, J.R., additional, Landrø, L., additional, LeBlanc, M., additional, Olsson Mägi, C.A., additional, Rudi, K., additional, Skjerven, H.O., additional, Staff, A.C., additional, Vettukattil, R., additional, Bradley, M., additional, Nordlund, B., additional, and Söderhäll, C., additional

Published
2021
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10. Medication Adherence in Patients With Severe Asthma Prescribed Oral Corticosteroids in the U-BIOPRED Cohort

Author

Alahmadi, Fahad H., primary, Simpson, Andrew J., additional, Gomez, Cristina, additional, Ericsson, Magnus, additional, Thörngren, John-Olof, additional, Wheelock, Craig E., additional, Shaw, Dominic E., additional, Fleming, Louise J., additional, Roberts, Graham, additional, Riley, John, additional, Bates, Stewart, additional, Sousa, Ana R., additional, Knowles, Richard, additional, Bansal, Aruna T., additional, Corfield, Julie, additional, Pandis, Ioannis, additional, Sun, Kai, additional, Bakke, Per S., additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Dahlén, Barbro, additional, Horvath, Ildiko, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Singer, Florian, additional, Wagers, Scott, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, Chung, Kian Fan, additional, Sterk, Peter J., additional, Dahlen, Sven-Erik, additional, Fowler, Stephen J., additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, F.K., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlèn, B., additional, Dahlén, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R.G., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J.G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, Valls, M. Puig, additional, Rao, N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J.P.R., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, and Wilson, S.J., additional

Published
2021
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11. Preschool wheezing and asthma in children:a systematic review of guidelines and quality appraisal with the AGREE II instrument

Author

Ruszczyński, M. (Marek), Ambrożej, D. (Dominika), Adamiec, A. (Aleksander), Ryczaj, K. (Klaudia), Elenius, V. (Varpu), Cavkaytar, O. (Ozlem), Maggina, P. (Paraskevi), Makrinioti, H. (Heidi), Papadopoulos, N. (Nikolaos), Hedlin, G. (Gunilla), Konradsen, J. R. (Jon R), Schaub, B. (Bianca), Smits, H. (Hermelijn), Jartti, T. (Tuomas), Feleszko, W. (Wojciech), and E. T. (EAACI Task Force onClinical Practice Recommendations on Preschool Wheeze)

Subjects
AGREE, children, systematic review, preschool wheezing, guidelines, asthma
Abstract

Background: Asthma‐like symptoms in preschool children, such as wheezing and dyspnea, are common time‐ and resource‐consuming diagnostic and management challenges. Quality of wheezing and asthma recommendations varies. The purpose of this study, carried out by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force for Preschool Wheeze, was to systematically review and assess the quality of guidelines for diagnosis and treatment of preschool wheezing and/or asthma. Methods: The Cochrane Library, MEDLINE, and EMBASE were searched until June 2018. The methodological rigor, quality, and transparency of relevant guidelines were assessed with the use of the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. Results: We identified 26 guidelines. The quality scores for each domain varied. Of all domains, clarity and presentation had the highest mean score, whereas applicability and stakeholder involvement had the lowest. The scores (median) for individual domains were as follows: score and purpose 86%; stakeholder involvement 49%; rigor of development 54%; clarity of presentation 85%; applicability 51%; and editorial independence 63%. Conclusion: Although several guidelines on asthma management in children are available, however, their quality varies. Additionally, there is a considerable gap in reliable recommendations on the management and treatment of non‐asthmatic preschool wheeze.

Published
2021

12. Childhood asthma outcomes during the COVID-19 pandemic: Findings from the PeARL multi-national cohort

Author

Papadopoulos, N.G. Mathioudakis, A.G. Custovic, A. Deschildre, A. Phipatanakul, W. Wong, G. Xepapadaki, P. Abou-Taam, R. Agache, I. Castro-Rodriguez, J.A. Chen, Z. Cros, P. Dubus, J.-C. El-Sayed, Z.A. El-Owaidy, R. Feleszko, W. Fierro, V. Fiocchi, A. Garcia-Marcos, L. Goh, A. Hossny, E.M. Huerta Villalobos, Y.R. Jartti, T. Le Roux, P. Levina, J. López García, A.I. Ramos, Á.M. Morais-Almeida, M. Murray, C. Nagaraju, K. Nagaraju, M.K. Navarrete Rodriguez, E.M. Namazova-Baranova, L. Nieto Garcia, A. Pozo Beltrán, C.F. Ratchataswan, T. Rivero Yeverino, D. Rodríguez Zagal, E. Schweitzer, C.E. Tulkki, M. Wasilczuk, K. Xu, D. Alekseeva, A. Almeida, B. Andre, M. Arimova, P. Blonde, A. Cunningham, A. Da Mota, S. Efendieva, K. Kalugina, V. Kiefer, S. Klein, A. López, C.G.C. López, J.J.R. Moratellti, C. Fuentes Pérez, M. Simermann, M. Tapia, J.S.P. Tatopoulos, A. Vishneva, E. Volkov, Κ. Bacharier, L. Bonini, M. Craig, T. Diamant, Z. Ducharme, F.M. Gern, J.E. Grigg, J. Hamelmann, E.H. Hedlin, G. Jartti, T. Kalayci, O. Kaplan, A. Konradsen, J. Kuna, P. Lau, S. Le Souef, P. Lemanske, R.F. Makela, M.J. Matricardi, P.M. Gómez, R.-M. Miligkos, M. Pitrez, P.M.C. Price, D. Pohunek, P. Roberts, G.C. Sheikh, A. Tsiligianni, I. Turner, S. Valiulis, A. Winders, T. Yusuf, O.M. Zar, H. PeARL collaborators, on behalf of the PeARL Think Tank

Subjects
respiratory tract diseases
Abstract

Background: The interplay between COVID-19 pandemic and asthma in children is still unclear. We evaluated the impact of COVID-19 pandemic on childhood asthma outcomes. Methods: The PeARL multinational cohort included 1,054 children with asthma and 505 non-asthmatic children aged between 4 and 18 years from 25 pediatric departments, from 15 countries globally. We compared the frequency of acute respiratory and febrile presentations during the first wave of the COVID-19 pandemic between groups and with data available from the previous year. In children with asthma, we also compared current and historical disease control. Results: During the pandemic, children with asthma experienced fewer upper respiratory tract infections, episodes of pyrexia, emergency visits, hospital admissions, asthma attacks, and hospitalizations due to asthma, in comparison with the preceding year. Sixty-six percent of asthmatic children had improved asthma control while in 33% the improvement exceeded the minimal clinically important difference. Pre-bronchodilatation FEV1 and peak expiratory flow rate were improved during the pandemic. When compared to non-asthmatic controls, children with asthma were not at increased risk of LRTIs, episodes of pyrexia, emergency visits, or hospitalizations during the pandemic. However, an increased risk of URTIs emerged. Conclusion: Childhood asthma outcomes, including control, were improved during the first wave of the COVID-19 pandemic, probably because of reduced exposure to asthma triggers and increased treatment adherence. The decreased frequency of acute episodes does not support the notion that childhood asthma may be a risk factor for COVID-19. Furthermore, the potential for improving childhood asthma outcomes through environmental control becomes apparent. © 2021 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

Published
2021

13. Microarray technology may reveal the contribution of allergen exposure and rhinovirus infections as possible triggers for acute wheezing attacks in preschool children

Author

Niespodziana, K. Stenberg-Hammar, K. Papadopoulos, N.G. Focke-Tejkl, M. Errhalt, P. Konradsen, J.R. Söderhäll, C. van Hage, M. Hedlin, G. Valenta, R.

Subjects
respiratory tract diseases
Abstract

Allergen exposure and rhinovirus (RV) infections are common triggers of acute wheezing exacerbations in early childhood. The identification of such trigger factors is difficult but may have therapeutic implications. Increases of IgE and IgG in sera, were shown against allergens and the N-terminal portion of the VP1 proteins of RV species, respectively, several weeks after allergen exposure or RV infection. Hence, increases in VP1-specific IgG and in allergen-specific IgE may serve as biomarkers for RV infections or allergen exposure. The MeDALL-allergen chip containing comprehensive panels of allergens and the PreDicta RV chip equipped with VP1-derived peptides, representative of three genetic RV species, were used to measure allergen-specific IgE levels and RV-species-specific IgG levels in sera obtained from 120 preschool children at the time of an acute wheezing attack and convalescence. Nearly 20% of the children (22/120) showed specific IgE sensitizations to at least one of the allergen molecules on the MeDALL chip. For 87% of the children, increases in RV-specific IgG could be detected in the follow-up sera. This percentage of RV-specific IgG increases was equal in IgE-positive and-negative children. In 10% of the children, increases or de novo appearances of IgE sensitizations indicative of allergen exposure could be detected. Our results suggest that, in the majority of preschool children, RV infections trigger wheezing attacks, but, in addition, allergen exposure seems to play a role as a trigger factor. RV-induced wheezing attacks occur in IgE-sensitized and non-IgE-sensitized children, indicating that allergic sensitization is not a prerequisite for RV-induced wheeze. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Published
2021

14. Urinary leukotriene E4 and prostaglandin D2 metabolites increase in adult and childhood severe asthma characterized by type-2 inflammation

Author

Kolmert, J, Gómez, C, Balgoma, D, Sjödin, M, Bood, J, Konradsen, Jr, Ericsson, M, Thörngren, Jo, James, A, Mikus, M, Sousa, Ar, Riley, Jh, Bates, S, Bakke, Ps, Pandis, I, Caruso, M, Chanez, P, Fowler, Sj, Geiser, T, Howarth, P, Horváth, I, Krug, N, Montuschi, P, Sanak, M, Behndig, A, Shaw, De, Knowles, Rg, Holweg, Ctj, Wheelock, Åm, Dahlén, B, Nordlund, B, Alving, K, Hedlin, G, Chung, Kf, Adcock, Im, Sterk, Pj, Djukanovic, R, Dahlén, Se, Wheelock, Ce, U-BIOPRED Study, Group., and Commission of the European Communities

Subjects
severe asthma, Adult, Inflammation, Leukotriene E4, Male, U-BIOPRED Study Group, on behalf of the U-BIOPRED Study Group, U-BIOPRED, type 2 inflammation, Respiratory System, Middle Aged, Asthma, Type-2 inflammation, urinary eicosanoid metabolites, Prostaglandins, Humans, lipids (amino acids, peptides, and proteins), Female, Swedish Search, Biomarkers, 11 Medical and Health Sciences, mass spectrometry
Abstract

RATIONALE: New approaches are needed to guide personalized treatment of asthma. OBJECTIVE: To test if urinary eicosanoid metabolites can direct asthma phenotyping. METHODS: Urinary metabolites of prostaglandins (PGs), cysteinyl-leukotrienes (LTs) and isoprostanes were quantified in the Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes (U-BIOPRED) study including 86 adults with mild-to-moderate asthma (MMA), 411 with severe asthma (SA), and 100 healthy controls (HC). Validation was performed internally in 302 SA subjects followed-up after 12-18 months, and externally in 95 adolescents with asthma. MEASUREMENT AND MAIN RESULTS: Metabolite levels in HC were unrelated to age, BMI and sex, except for the PGE2-pathway. Eicosanoid levels were generally greater in MMA relative to HC, with further elevations in SA. However, PGE2-metabolite levels were either the same or lower in male non-smoking asthmatics as in HC. Metabolite levels were unchanged in asthmatics adherent to oral corticosteroid treatment as documented by urinary prednisolone detection, whereas SA treated with omalizumab had lower levels of LTE4 and the PGD2 metabolite 2,3-dinor-11β-PGF2α. High levels of LTE4 and PGD2-metabolites were associated with lower lung-function, and increased levels of exhaled nitric oxide and eosinophil markers in blood, sputum and urine in U-BIOPRED and in adolescents with asthma. These type-2 (T2) asthma associations were reproduced in the follow-up visit of the U-BIOPRED study, and found to be as sensitive to detect T2 inflammation as the established biomarkers. CONCLUSIONS: Monitoring of urinary eicosanoids can identify T2 asthma and introduces a new non-invasive approach for molecular phenotyping of adult and adolescent asthma. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Published
2020

15. Impact of COVID-19 on Pediatric Asthma: Practice Adjustments and Disease Burden

Author

Papadopoulos, N.G. Custovic, A. Deschildre, A. Mathioudakis, A.G. Phipatanakul, W. Wong, G. Xepapadaki, P. Agache, I. Bacharier, L. Bonini, M. Castro-Rodriguez, J.A. Chen, Z. Craig, T. Ducharme, F.M. El-Sayed, Z.A. Feleszko, W. Fiocchi, A. Garcia-Marcos, L. Gern, J.E. Goh, A. Gómez, R.M. Hamelmann, E.H. Hedlin, G. Hossny, E.M. Jartti, T. Kalayci, O. Kaplan, A. Konradsen, J. Kuna, P. Lau, S. Le Souef, P. Lemanske, R.F. Mäkelä, M.J. Morais-Almeida, M. Murray, C. Nagaraju, K. Namazova-Baranova, L. Garcia, A.N. Yusuf, O.M. Pitrez, P.M.C. Pohunek, P. Pozo Beltrán, C.F. Roberts, G.C. Valiulis, A. Zar, H.J. Taam, R.A. Azuara, H. Brouard, J. Cros, P. De Lira, C. Dubus, J.-C. Dunder, T. Efendieva, K. Egron, C. Emeryk, A. Huerta Villalobos, Y.R. Karen, N. Le Roux, P. Levina, J. Medley, M. Najaraju, M. Yeverino, D.R. Ruotsalainen, M. Szefler, S. Schweitzer, C. Benhumea, B.V. Villarreal, R. Weiss, L. Zawadzka-Krajewska, A.

Abstract

Background: It is unclear whether asthma may affect susceptibility or severity of coronavirus disease 2019 (COVID-19) in children and how pediatric asthma services worldwide have responded to the pandemic. Objective: To describe the impact of the COVID-19 pandemic on pediatric asthma services and on disease burden in their patients. Methods: An online survey was sent to members of the Pediatric Asthma in Real Life think tank and the World Allergy Organization Pediatric Asthma Committee. It included questions on service provision, disease burden, and the clinical course of confirmed cases of COVID-19 infection among children with asthma. Results: Ninety-one respondents, caring for an estimated population of more than 133,000 children with asthma, completed the survey. COVID-19 significantly impacted pediatric asthma services: 39% ceased physical appointments, 47% stopped accepting new patients, and 75% limited patients' visits. Consultations were almost halved to a median of 20 (interquartile range, 10-25) patients per week. Virtual clinics and helplines were launched in most centers. Better than expected disease control was reported in 20% (10%-40%) of patients, whereas control was negatively affected in only 10% (7.5%-12.5%). Adherence also appeared to increase. Only 15 confirmed cases of COVID-19 were reported among the population; the estimated incidence is not apparently different from the reports of general pediatric cohorts. Conclusions: Children with asthma do not appear to be disproportionately affected by COVID-19. Outcomes may even have improved, possibly through increased adherence and/or reduced exposures. Clinical services have rapidly responded to the pandemic by limiting and replacing physical appointments with virtual encounters. © 2020 American Academy of Allergy, Asthma & Immunology

Published
2020

16. Research Priorities in Pediatric Asthma: Results of a Global Survey of Multiple Stakeholder Groups by the Pediatric Asthma in Real Life (PeARL) Think Tank

Author

Mathioudakis, A.G. Custovic, A. Deschildre, A. Ducharme, F.M. Kalayci, O. Murray, C. Garcia, A.N. Phipatanakul, W. Price, D. Sheikh, A. Agache, I. Bacharier, L. Bonini, M. Castro-Rodriguez, J.A. De Carlo, G. Craig, T. Diamant, Z. Feleszko, W. Ierodiakonou, D. Gern, J.E. Grigg, J. Hedlin, G. Hossny, E.M. Jartti, T. Kaplan, A. Lemanske, R.F. Le Souef, P. Makela, M.J. Matricardi, P.M. Miligkos, M. Morais-Almeida, M. Pite, H. Pitrez, P.M.C. Pohunek, P. Roberts, G. Sanchez-Garcia, S. Tsiligianni, I. Turner, S. Winders, T.A. Wong, G. Xepapadaki, P. Zar, H.J. Papadopoulos, N.G.

Abstract

Background: Pediatric asthma remains a public health challenge with enormous impact worldwide. Objective: The aim of this study was to identify and prioritize unmet clinical needs in pediatric asthma, which could be used to guide future research and policy activities. Methods: We first identified unmet needs through an open-question survey administered to international experts in pediatric asthma who were members of the Pediatric Asthma in Real Life Think Tank. Prioritization of topics was then achieved through a second, extensive survey with global reach, of multiple stakeholders (leading experts, researchers, clinicians, patients, policy makers, and the pharmaceutical industry). Differences across responder groups were compared. Results: A total of 57 unmet clinical need topics identified by international experts were prioritized by 412 participants from 5 continents and 60 countries. Prevention of disease progression and prediction of future risk, including persistence into adulthood, emerged as the most urgent research questions. Stratified care, based on biomarkers, clinical phenotypes, the children's age, and demographics were also highly rated. The identification of minimum diagnostic criteria in different age groups, cultural perceptions of asthma, and best treatment by age group were priorities for responders from low-middle-income countries. There was good agreement across different stakeholder groups in all domains with some notable exceptions that highlight the importance of involving the whole range of stakeholders in formulation of recommendations. Conclusions: Different stakeholders agree in the majority of research and strategic (eg, prevention, personalized approach) priorities for pediatric asthma. Stakeholder diversity is crucial for highlighting divergent issues that future guidelines should consider. © 2020 American Academy of Allergy, Asthma & Immunology

Published
2020

19. Toward personalization of asthma treatment according to trigger factors

Author

Niespodziana, K. Borochova, K. Pazderova, P. Schlederer, T. Astafyeva, N. Baranovskaya, T. Barbouche, M.-R. Beltyukov, E. Berger, A. Borzova, E. Bousquet, J. Bumbacea, R.S. Bychkovskaya, S. Caraballo, L. Chung, K.F. Custovic, A. Docena, G. Eiwegger, T. Evsegneeva, I. Emelyanov, A. Errhalt, P. Fassakhov, R. Fayzullina, R. Fedenko, E. Fomina, D. Gao, Z. Giavina-Bianchi, P. Gotua, M. Greber-Platzer, S. Hedlin, G. Ilina, N. Ispayeva, Z. Idzko, M. Johnston, S.L. Kalayci, Ö. Karaulov, A. Karsonova, A. Khaitov, M. Kovzel, E. Kowalski, M.L. Kudlay, D. Levin, M. Makarova, S. Matricardi, P.M. Nadeau, K.C. Namazova-Baranova, L. Naumova, O. Nazarenko, O. O'Byrne, P.M. Osier, F. Pampura, A.N. Panaitescu, C. Papadopoulos, N.G. Park, H.-S. Pawankar, R. Pohl, W. Renz, H. Riabova, K. Sampath, V. Sekerel, B.E. Sibanda, E. Siroux, V. Sizyakina, L.P. Sun, J.-L. Szepfalusi, Z. Umanets, T. Van Bever, H.P.S. van Hage, M. Vasileva, M. von Mutius, E. Wang, J.-Y. Wong, G.W.K. Zaikov, S. Zidarn, M. Valenta, R.

Subjects
immune system diseases, respiratory tract diseases
Abstract

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma. © 2020 The Authors

Published
2020

22. Acute wheeze-specific gene module shows correlation with vitamin D and asthma medication

Author

Katayama, S., Stenberg Hammar, K., Krjutškov, K., Einarsdottir, Elisabeth, Hedlin, G., Kere, J., Söderhäll, C., Katayama, S., Stenberg Hammar, K., Krjutškov, K., Einarsdottir, Elisabeth, Hedlin, G., Kere, J., and Söderhäll, C.

Abstract

BACKGROUND: Airway obstruction and wheezing in preschool children with recurrent viral infections are a major clinical problem, and are recognised as a risk factor for the development of chronic asthma. We aimed to analyse whether gene expression profiling provides evidence for pathways that delineate distinct groups of children with wheeze, and in combination with clinical information could contribute to diagnosis and prognosis of disease development. METHODS: We analysed leukocyte transcriptomes from preschool children (6 months-3 years) at acute wheeze (n=107), and at a revisit 2-3 months later, comparing them to age-matched healthy controls (n=66). RNA-sequencing applying GlobinLock was used. The cases were followed clinically until age 7 years. Differential expression tests, weighted correlation network analysis and logistic regression were applied and correlations to 76 clinical traits evaluated. FINDINGS: Significant enrichment of genes involved in the innate immune responses was observed in children with wheeze. We identified a unique acute wheeze-specific gene-module, which was associated with vitamin D levels (p<0.005) in infancy, and asthma medication and FEV1%/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio several years later, at age 7 years (p<0.005). A model that predicts leukotriene receptor antagonist medication at 7 years of age with high accuracy was developed (area under the curve 0.815, 95% CI 0.668-0.962). INTERPRETATION: Gene expression profiles in blood from preschool wheezers predict asthma symptoms at school age, and therefore serve as biomarkers. The acute wheeze-specific gene module suggests that molecular phenotyping in combination with clinical information already at an early episode of wheeze may help to distinguish children who will outgrow their wheeze from those who will develop chronic asthma., QC 20200305

Published
2020
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23. Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status

Author

Cruz, Alvaro A., primary, Riley, John H., additional, Bansal, Aruna T., additional, Ponte, Eduardo V., additional, Souza-Machado, Adelmir, additional, Almeida, Paula C.A., additional, Biao-Lima, Valmar, additional, Davis, Maggie, additional, Bates, Stewart, additional, Adcock, Ian M., additional, Sterk, Peter J., additional, Chung, Kian Fan, additional, Alcantara-Neves, N., additional, Almeida, P.C.A., additional, Amorim, L., additional, Araujo, M.I., additional, Barnes, K.C., additional, Barreto, M.L., additional, Belitardo, E., additional, Bião-Lima, V., additional, Cardoso, L., additional, Camargos, P.A., additional, Chatkin, J.M., additional, Costa, R.S., additional, Coelho, A.C.C., additional, Cooper, P.J., additional, Cruz, A.A., additional, Cruz, C.S., additional, Cunha, J., additional, de Jesus, J.V., additional, Fernandes, J., additional, Franco, R.A., additional, Gomes-Filho, I., additional, Lima-Matos, A., additional, Figueiredo, C.A., additional, Lessa, M.A., additional, Lins, L., additional, Mello, L.M., additional, Moura-Santos, P., additional, Muniz, I.S., additional, Paixao-Araujo, I., additional, Pinheiro, G.P., additional, Ponte, E.V., additional, Rodrigues, L.C., additional, Santana, C.V.N., additional, Santos-Lima, G., additional, Souza, T.M.O., additional, Souza-Machado, A., additional, Souza-Machado, C., additional, Stelmach, R., additional, Vasquez, V.S., additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Baribaud, F., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlén, B., additional, Dahlén, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Goss, V., additional, Guo, Y.-K., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R.G., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J.G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, Puig Valls, M., additional, Rao, N., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J.P.R., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, and Wilson, S.J., additional

Published
2020
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24. Filaggrin mutations in relation to skin barrier and atopic dermatitis in early infancy*.

Author

Hoyer, A., Rehbinder, E.M., Färdig, M., Asad, S., Lødrup Carlsen, K.C., Endre, K.M.A., Granum, B., Haugen, G., Hedlin, G., Monceyron Jonassen, C., Katayama, S., Konradsen, J.R., Landrø, L., LeBlanc, M., Olsson Mägi, C.A., Rudi, K., Skjerven, H.O., Staff, A.C., Vettukattil, R., and Bradley, M.

Subjects
FILAGGRIN, ECZEMA, ATOPIC dermatitis, GENETIC mutation, ODDS ratio, CONFIDENCE intervals, INFANTS
Abstract

Summary: Background: Loss‐of‐function mutations in the skin barrier gene filaggrin (FLG) increase the risk of atopic dermatitis (AD), but their role in skin barrier function, dry skin and eczema in infancy is unclear. Objectives: To determine the role of FLG mutations in impaired skin barrier function, dry skin, eczema and AD at 3 months of age and throughout infancy. Methods: FLG mutations were analysed in 1836 infants in the Scandinavian population‐based PreventADALL study. Transepidermal water loss (TEWL), dry skin, eczema and AD were assessed at 3, 6 and 12 months of age. Results: FLG mutations were observed in 166 (9%) infants. At 3 months, carrying FLG mutations was not associated with impaired skin barrier function (TEWL > 11·3 g m−2 h−1) or dry skin, but was associated with eczema [odds ratio (OR) 2·89, 95% confidence interval (CI) 1·95–4·28; P < 0·001]. At 6 months, mutation carriers had significantly higher TEWL than nonmutation carriers [mean 9·68 (95% CI 8·69–10·68) vs. 8·24 (95% CI 7·97–8·15), P < 0·01], and at 3 and 6 months mutation carriers had an increased risk of dry skin on the trunk (OR 1·87, 95% CI 1·25–2·80; P = 0·002 and OR 2·44, 95% CI 1·51–3·95; P < 0·001) or extensor limb surfaces (OR 1·52, 95% CI 1·04–2·22; P = 0·028 and OR 1·74, 95% CI 1·17–2·57; P = 0·005). FLG mutations were associated with eczema and AD in infancy. Conclusions: FLG mutations were not associated with impaired skin barrier function or dry skin in general at 3 months of age, but increased the risk for eczema, and for dry skin on the trunk and extensor limb surfaces at 3 and 6 months. [ABSTRACT FROM AUTHOR]

Published
2022
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25. Treatable traits in the European U-BIOPRED adult asthma cohorts

Author

Simpson, Andrew J., Hekking, Pieter-Paul, Shaw, Dominick E., Fleming, L. J., Roberts, Graham, Riley, John H., Bates, Stewart, Sousa, A. R., Bansal, A. T., Pandis, Ioannis, Sun, K., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Dahlen, Sven-Erik, Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sandstrom, Thomas, Singer, Florian, Adcock, I. M., Wagers, Scott S., Djukanovic, R., Chung, Kian Fan, Sterk, P. J., Fowler, S. J., Ahmed, H., Auffray, C., Bakke, P., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, B., Dahlen, S. E., De Meulder, B., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Goss, V., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Postle, A., Powel, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandstrom, T., Schofield, J. P. R., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., and Wilson, S. J.

Abstract

mprovements in asthma outcomes have stalled over the past decade, which may be attributed to treating patients on the basis of a generic diagnostic label. The taxonomy “Treatable Traits” was proposed by Agusti et al (2016) as a precision medicine approach for the diagnosis and management of chronic airway diseases that is based on the identification of genetic, phenotypic and psychosocial characteristics for which therapeutic interventions are known to improve respiratory health ...

Published
2019

26. Pediatric asthma: An unmet need for more effective, focused treatments

Author

Papadopoulos, NG, Custovic, A, Cabana, MD, Dell, SD, Deschildre, A, Hedlin, G, Hossny, E, Le Souef, P, Matricardi, PM, Nieto, A, Phipatanakul, W, Pitrez, PM, Pohunek, P, Gavornikova, M, Jaumont, X, and Price, DB

Subjects
omalizumab, unmet need, asthma management, pediatric asthma
Abstract

Background Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. Methods A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. Results These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients

Published
2019

27. The importance of real-life research in respiratory medicine: Manifesto of the Respiratory Effectiveness Group

Author

Roche, N. Anzueto, A. Anticevich, S.B. Kaplan, A. Miravitlles, M. Ryan, D. Soriano, J.B. Usmani, O. Papadopoulos, N.G. Canonica, G.W. Agache, I. Barnes, P. Bateman, E. Behr, J. Bjermer, L. Blakey, J. Bouros, D. Bousquet, J. Brown, K. Brusselle, G. Calderon, M. Campbell, J. Cardell, L.O. Castro-Rodriguez, J.A. Chaudhuri, N. Chavannes, N. Corte, T. Costello, R. Cottin, V. Custovic, A. Dandurand, R. Diamant, Z. Demoly, P. Ducharme, F. Feleszko, W. Fitzgerald, M. Fokkens, W. Freeman, D. Gaga, M. Geiser, T. Glaspole, I. Gouder, C. Haughney, J. Heaney, L. Hedlin, G. Hellings, P. Hoe, T.O. Israel, E. Jartti, T. Jones, M. Jones, R. Josephs, L. Kalayci, O. Keane, M. Kocks, J. Lemanske, R. Magnussen, H. Makela, M. Mazzei, M. Matricardi, P. McIvor, A. Molina, M. Morais-Almeida, M. Morell, F. Mosges, R. Mullol, J. Murray, C. Nathan, S. Navarrete, B.A. Pappi, A. Paton, J.Y. Phipatanakul, W. Price, D. Quint, J. Rhee, C.K. Ortega, P.R. Roberts, G. Sadatsafavi, M. Sastre, J. Scadding, G. Selman, M. Singh, D. Sliwinski, P. Small, I. Smith, P. Thomas, M. Tsiligianni, I. van Aalderen, W. van Bowen, J. van den Berge, M. van Ganse, E. Vetsbo, J. Vogelmeier, C. Walsh, S. Xepapadaki, V. Zar, H. the Respiratory Effectiveness Group Collaborators

Published
2019

28. Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Author

Perotin, Jeanne-Marie, Schofield, James PR, Wilson, Susan J, Ward, Jonathan, Brandsma, Joost, Strazzeri, Fabio, Bansal, Aruna, Yang, Xian, Rowe, Anthony, Corfield, Julie, Lutter, Rene, Shaw, Dominick E, Bakke, Per S, Caruso, Massimo, Dahlen, Barbro, Fowler, Stephen J, Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Riley, John H, Sousa, Ana R, Dahlen, Sven-Erik, Adcock, Ian M, Chung, Kian Fan, Sterk, Peter J, Skipp, Paul J, Collins, Jane E, Davies, Donna E, Djukanovic, Ratko, Adcock, IM, Ahmed, H, Auffray, C, Bakke, P, Banssal, AT, Baribaud, F, Bates, S, Bel, EH, Bigler, J, Bisgaard, H, Boedigheimer, MJ, Bonnelykke, K, Brandsma, J, Brinkman, P, Bucchioni, E, Burg, D, Bush, A, Caruso, M, Chaiboonchoe, A, Chanez, P, Chung, KF, Compton, CH, Corfield, J, D'Amico, A, Dahlen, SE, De Meulder, B, Djukanovic, R, Erpenbeck, VJ, Erzen, D, Fichtner, K, Fitch, N, Fleming, LJ, Formaggio, E, Fowler, SJ, Frey, U, Gahlemann, M, Geiser, T, Guo, Y, Hashimoto, S, Haughney, J, Hedlin, G, Hekking, PW, Higenbottam, T, Hohlfeld, JM, Holweg, C, Horvath, I, Howarth, P, James, AJ, Knowles, R, Knox, AJ, Krug, N, Lefaudeux, D, Loza, MJ, Lutter, R, Manta, A, Masefield, S, Matthews, JG, Mazein, A, Meiser, A, Middelveld, RJM, Miralpeix, M, Montuschi, P, Mores, N, Murray, CS, Musial, J, Myles, D, Pahus, L, Pandis, I, Pavlidis, S, Powell, P, Pratico, G, Puig Valls, M, Rao, N, Riley, J, Roberts, A, Roberts, G., Rowe, A, Sandstrom, T, Seibold, W, Selby, A, Shaw, DE, Sigmund, R, Singer, F, Skipp, PJ, Sousa, AR, Sterk, PJ, Sun, K, Thornton, B, van Aalderen, WM, van Geest, M, Vestbo, J, Vissing, NH, Wagener, AH, Wagers, SS, Weiszhart, Z, Wheelock, CE, Wilson, SJ, Aliprantis, Antonios, Allen, David, Alving, Kjell, Badorrek, P, Balgoma, David, Ballereau, S, Barber, Clair, Batuwitage, Manohara Kanangana, Bautmans, An, Bedding, A, Behndig, AF, Beleta, Jorge, Berglind, A, Berton, A, Bochenek, G, Braun, A, Campagna, D, Carayannopoulos, L, Casaulta, C, Chaleckis, Romanas, Dahlen, B, Davison, T, De Alba, J, De Lepeleire, I, Dekker, T, Delin, I, Dennison, P, Dijkhuis, A, Dodson, P, Dyson, K, Edwards, J, El Hadjam, L, Emma, R, Ericsson, M, Faulenbach, C, Flood, Breda, Galffy, G, Gallart, H, Garissi, D, Gent, J., Gerhardsson de Verdier, M, Gibeon, D, Gomez, Cristina, Gove, K, Guillmant-Farry, E, Henriksson, E, Hewitt, L, Hoda, U, Hu, Richard, Hu, S, Hu, X, Jeyasingham, E, Johnson, K, Jullian, N, Kamphuis, J, Kennington, EJ, Kerry, D, Kerry, G, Klueglich, M, Knobel, H, Kolmert, Johan, Konradsen, JR, Kots, M, Kretsos, Kosmas, Krueger, L, Kuo, S, Kupczyk, M, Lambrecht, Bart, Lantz, A-S, Larminie, Christopher, Larsson, LX, Latzin, P, Lazarinis, N, Lemonnier, N, Lone-Latif, S, Lowe, LA, Marouzet, L, Martin, J, Mathon, C, McEvoy, L, Meah, S, Menzies-Gow, A, Metcalf, L, Mikus, M, Monk, P, Naz, S, Nething, K, Nicholas, B, Nihlen, U, Nilsson, Peter, Niven, R, Nordlund, B, Nsubuga, S, Ostling, J, Pacino, A, Palkonen, S, Pellet, J, Pennazza, G, Petren, A, Pink, S, Pison, C, Postle, A, Rahman-Amin, M, Ravanetti, L, Ray, E, Reinke, S, Reynolds, L, Riemann, K, Robberechts, Martine, Rocha, JP, Rossios, C, Russell, K, Rutgers, M, Santini, G, Santoninco, M, Saqi, M, Schoelch, C, Schofield, JPR, Scott, S, Sehgal, N, Sjodin, M, Smids, B, Smith, Caroline, Smith, J, Smith, KM, Soderman, P, Sogbessan, A, Spycher, F, Staykova, D, Stephan, S, Stokholm, J, Strandberg, K, Sunther, M, Szentkereszty, M, Tamasi, L, Tariq, K, Thorngren, J-O, Thorsen, Jonathan, Valente, S, van de Pol, Marianne, van Drunen, CM, Van Eyll, J, Versnel, J, Vink, A, von Garnier, C, Vyas, A, Wald, F, Walker, S, Ward, J, Wetzel, K, Wiegman, C, Williams, S, Yang, X, Yeyasingham, E, Yu, W, Zetterquist, W, Zolkipli, Z, Zwinderman, AH, Prins, J-B, Visintin, L, Evans, H, Puhl, M, Buzermaniene, L, Hudson, V, Bond, L, de Boer, P, Widdershoven, G, Supple, D, Hamerlijnck, D, Negus, J, Sergison, L, Onstein, S, MacNee, W, Bernardini, R, Bont, Louis, Wecksell, P-A, Draper, Aleksandra, Gozzard, Neil, Commission of the European Communities, Publica, Pulmonology, AII - Inflammatory diseases, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, and NIHR Southampton Biomedical Research Centre

Subjects
severe asthma, Pulmonary and Respiratory Medicine, endotyping, Gastrointestinal, phenotyping, Settore BIO/14 - FARMACOLOGIA, [SDV]Life Sciences [q-bio], Respiratory System, ROWE, Gene Expression, Article, Endoscopy, Gastrointestinal, Epithelium, CCN Intercellular Signaling Proteins, Patent application, 03 medical and health sciences, 0302 clinical medicine, Shareholder, gatroesophageal reflux, Nothing, Proto-Oncogene Proteins, Medicine and Health Sciences, Humans, Medicine, Obesity, 030212 general & internal medicine, ComputingMilieux_MISCELLANEOUS, 11 Medical and Health Sciences, U-BIOPRED Study Group, Science & Technology, business.industry, U-BIOPRED, digestive, oral, and skin physiology, Airway inflammation, Conflict of interest, Biology and Life Sciences, Endoscopy, Asthma, digestive system diseases, 3. Good health, 030228 respiratory system, Spin out, Case-Control Studies, Law, Honorarium, Gastroesophageal Reflux, business, Life Sciences & Biomedicine
Abstract

Gastro-oesophageal reflux disease (GORD) and obesity are associated with frequent exacerbations and poor quality of life in asthmatics. Multiple mechanisms have been proposed for the effect of obesity, including modification of inflammation affecting epithelial cell proliferation and wound repair, while the role of GORD is poorly understood and proton pump inhibitor (PPI) are of variable efficacy. GORD might exert a deleterious effect by inducing vagal reflex, neuroinflammation and directly ( via microaspiration) triggering airway inflammation. Studies of reflux in animal models and human bronchial epithelial cell culture show varying impact on inflammation and airway remodelling. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Dr PEROTIN has nothing to disclose. Conflict of interest: Dr Schofield has nothing to disclose. Conflict of interest: Dr Wilson has nothing to disclose. Conflict of interest: Dr Ward has nothing to disclose. Conflict of interest: Dr Brandsma has nothing to disclose. Conflict of interest: Dr Strazzeri has nothing to disclose. Conflict of interest: Dr Bansal has nothing to disclose. Conflict of interest: Dr Yang has nothing to disclose. Conflict of interest: Dr Rowe reports and a full time employee and shareholder of Janssen Pharmaceutical Companies of Johnson and Johnson. Conflict of interest: Miss Corfield has nothing to disclose. Conflict of interest: Dr Lutter has nothing to disclose. Conflict of interest: Prof. Shaw reports personal fees and non-financial support from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, personal fees from Circassia, and a grant from GSK, outside the submitted work. Conflict of interest: Dr Bakke reports personal fees from GSK, AZ, Novartis andTeva, outside the submitted work. Conflict of interest: MC have no conflict of interest to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Fowler reports personal fees and non-financial support from AstraZeneca, grants and personal fees from Boehringer Ingelheim, personal fees from Novartis, personal fees from Teva, outside the submitted work. Conflict of interest: Dr Horvath reports personal fees from Astra Zeneca, Boehringer Ingelheim, Novartis, CSL, Chiesi, Roche, GSK, Berlin-Chemie and Sandoz, outside the submitted work. Conflict of interest: Dr Howarth reports personal fees from GSK, outside the submitted work. Conflict of interest: Dr Krug has nothing to disclose. Conflict of interest: Dr Montuschi has nothing to disclose. Conflict of interest: Dr Sanak has nothing to disclose. Conflict of interest: Dr Sandstrom reports other monetary support from Boehringer Ingelheim, outside the submitted work. Conflict of interest: Dr Sun has nothing to disclose. Conflict of interest: Dr Pandis has nothing to disclose. Conflict of interest: Dr Auffray reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr De Meulder reports grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Ms. Lefaudeux reports grants from Innovative Medicine Initiative, grants from Innovative Medicine Initiative, during the conduct of the study. Conflict of interest: Dr Riley reports and I have shares in and I am employed by GSK. Conflict of interest: Dr Sousa has nothing to disclose. Conflict of interest: Dr Dahlen has nothing to disclose. Conflict of interest: Dr Adcock reports grants from EU-IMI, during the conduct of the study. Conflict of interest: KFC has received honoraria for participating in Advisory Board meetings of GSK, AZ, BI, Teva, Novartis and Merck regarding treatments for asthma and chronic obstructive pulmonary disease and has also been renumerated for speaking engagements. Conflict of interest: Dr Sterk reports grants from Innovative Medicines Initiative, during the conduct of the study. Conflict of interest: Dr Skipp has nothing to disclose. Conflict of interest: Dr Collins reports a patent application for use of a genetically modified Drosophila line carrying one or more mammalian genes associated with a chronic respiratory disease and uses to screen the impact of such genes. Conflict of interest: Dr Davies has nothing to disclose. Conflict of interest: Dr Djukanovic reports receiving fees for lectures at symposia organised by Novartis, AstraZeneca and TEVA, consultation for TEVA and Novartis as member of advisory boards, and participation in a scientific discussion about asthma organised by GlaxoSmithKline. He is a co-founder and current consultant, and has shares in Synairgen, a University of Southampton spin out company.

Published
2019
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29. Pediatric asthma: An unmet need for more effective, focused treatments

Author

Papadopoulos, N.G. Čustović, A. Cabana, M.D. Dell, S.D. Deschildre, A. Hedlin, G. Hossny, E. Le Souëf, P. Matricardi, P.M. Nieto, A. Phipatanakul, W. Pitrez, P.M. Pohunek, P. Gavornikova, M. Jaumont, X. Price, D.B.

Abstract

Background: Despite remarkable advances in our understanding of asthma, there are still several unmet needs associated with the management of pediatric asthma. Methods: A two-day, face-to-face meeting was held in London, United Kingdom, on October 28 and 29, 2017, involving a group of international expert clinicians and scientists in asthma management to discuss the challenges and unmet needs that remain to be addressed in pediatric asthma. Results: These unmet needs include a lack of clinical efficacy and safety evidence, and limited availability of non-steroid-based alternative therapies in patients

Published
2019

30. IL-17-high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, van Geest, Marleen, Schofield, James P. R., Jevnikar, Zala, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Vaarala, Outi, Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K. F., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, S. E., De Meulder, B., Djukanovic, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Pratico, G., Valls, M. Puig, Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., Sousa, A. R., Sterk, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., Wilson, S. J., Östling, Jörgen, van Geest, Marleen, Schofield, James P. R., Jevnikar, Zala, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Auffray, Charles, Sousa, Ana R., Guo, Yike, Adcock, Ian M., Howarth, Peter, Chung, Kian Fan, Bigler, Jeanette, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Vaarala, Outi, Ahmed, H., Auffray, C., Bakke, P., Bansal, A. T., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brandsma, J., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Caruso, M., Chaiboonchoe, A., Chanez, P., Chung, K. F., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, S. E., De Meulder, B., Djukanovic, R., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Fleming, L. J., Formaggio, E., Fowler, S. J., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Horvath, I., Howarth, P., James, A. J., Knowles, R., Knox, A. J., Krug, N., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Montuschi, P., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pandis, I., Pavlidis, S., Powell, P., Pratico, G., Valls, M. Puig, Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Sandström, T., Seibold, W., Selby, A., Shaw, D. E., Sigmund, R., Singer, F., Skipp, P. J., Sousa, A. R., Sterk, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., and Wilson, S. J.

Abstract

Background: The role of IL-17 immunity is well established in patients with inflammatory diseases, such as psoriasis and inflammatory bowel disease, but not in asthmatic patients, in whom further study is required. Objective: We sought to undertake a deep phenotyping study of asthmatic patients with upregulated IL-17 immunity. Methods: Whole-genome transcriptomic analysis was performed by using epithelial brushings, bronchial biopsy specimens (91 asthmatic patients and 46 healthy control subjects), and whole blood samples (n = 498) from the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) cohort. Gene signatures induced in vitro by IL-17 and IL-13 in bronchial epithelial cells were used to identify patients with IL-17–high and IL-13–high asthma phenotypes. Results: Twenty-two of 91 patients were identified with IL-17, and 9 patients were identified with IL-13 gene signatures. The patients with IL-17–high asthma were characterized by risk of frequent exacerbations, airway (sputum and mucosal) neutrophilia, decreased lung microbiota diversity, and urinary biomarker evidence of activation of the thromboxane B2 pathway. In pathway analysis the differentially expressed genes in patients with IL-17-high asthma were shared with those reported as altered in psoriasis lesions and included genes regulating epithelial barrier function and defense mechanisms, such as IL1B, IL6, IL8, and β-defensin. Conclusion: The IL-17–high asthma phenotype, characterized by bronchial epithelial dysfunction and upregulated antimicrobial and inflammatory response, resembles the immunophenotype of psoriasis, including activation of the thromboxane B2 pathway, which should be considered a biomarker for this phenotype in further studies, including clinical trials targeting IL-17.

Published
2019
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31. A computational framework for complex disease stratification from multiple large-scale datasets

Author

De Meulder, B., Lefaudeux, D., Bansal, A. T., Mazein, A., Chaiboonchoe, A., Ahmed, H., Balaur, I., Saqi, M., Pellet, J., Ballereau, S., Lemonnier, N., Sun, K., Pandis, I., Yang, X., Batuwitage, M., Kretsos, K., van Eyll, J., Bedding, A., Davison, T., Dodson, P., Larminie, C., Postle, A., Corfield, J., Djukanovic, R., Chung, K. F., Adcock, I. M., Guo, Y. -K., Sterk, P. J., Manta, A., Rowe, A., Baribaud, F., Auffray, C., Gibeon, D., Hoda, U., Kuo, S., Meah, S., Meiser, A., Fleming, L. J., Hu, S., Pavlidis, S., Rossios, C., Russel, K., Wiegman, C., Nezhad, A. T., Oehmichen, A., O'Malley, D., Guitton, F., Emam, I., Agapow, P., Rice, P., Miles, S., Elyasigomari, V., Bel, E., Brinkman, P., Dekker, T., Dijkhuis, A., Hashimoto, S., Hekking, P. -P., Lone-Latif, S., Lutter, R., Ravanetti, L., Smids, B., van Aalderen, W., van de Pol, M., van Drunen, K., van Drunen, M., Wagener, A., Zwinderman, K., Adriaens, N., Carusi, A. M., Richard, F., Nogueira, M. M., Taibi, N., Brasier, O., Aliprantis, A., Alving, K., Faulenbach, C., Braun, A., Hohlfeld, J., Krug, N., Badorrek, P., Bakke, P., Berglind, A., Chaleckis, R., Dahlen, B., Delin, I., Gallart, H., Gomez, C., Hedlin, G., Henriksson, E., James, A. J., Kolmert, J., Konradsen, J., Kupczyk, M., Lantz, A. -S., Lazarinis, L., Mathon, C., Middelveld, R., Naz, S., Nordlund, B., Petren, A., Reinke, S., Sjodin, M., Soderman, P., Strandberg, K., Wheelock, C. E., Zetterquist, W., Balgoma, D., Brandsma, J., Burg, D., Dennison, P., Nicholas, B., Schofield, J. P. R., Skipp, P. J., Staykova, D., Tariq, K., Ward, J., Wilson, S. J., Barber, C., Loza, M. J., Bautmans, A., Sandstrom, T., Behndig, A. F., De Alba, J., Beleta, J., Berton, A., de Verdier, M. G., Nihlen, U., Ostling, J., Dalentoft, T., Lindgren, E., Boedigheimer, M. J., Hu, R., Hu, X., Yu, W., Bigler, J., Bonnelykke, K., Thorsen, J., Vising, N., Bisgaard, H., Bochenek, G., Caruso, M., Emma, R., Campagna, D., Thornton, B., Carayannopoulos, L., Gent, J., Manzies-Gow, A., Sogbesan, A., da Purificacao Rocha, P. C., Pedro, J., Chanez, P., Edwards, J., Flood, B., Hudson, V., Kennington, E. J., Metcalf, L., Rahman-Amin, M., Reynolds, L., Roberts, A., Smith, J., Supple, D., Versnel, J., Walker, S., Coleman, C., Hasan, S., Compton, C., Myles, D., Riley, J., Sousa, A. R., Yeyasingham, E., Pennazza, G., Santoninco, M., D'Amico, A., Dahlen, S. -E., de Boer, P., Robberechts, M., De Lepeleire, I., Fitch, N., Garret, T., Wagers, S., Draper, A., Thorngren, J. -O., Ericsson, M., Erpenbeck, V., Kluglich, M., Nething, K., Riemann, K., Schoelch, C., Seibold, W., Sigmund, R., Wald, F., Wetzel, K., Fichtner, K., Erzen, D., Galffy, G., Horvath, I., Szentkereszty, M., Tamasi, L., Fowler, S. J., Krueger, L., Singer, F., Frey, U., Gahlemann, M., Geiser, T., Hewitt, L., Howarth, P., Marouzet, L., Martin, J., Pink, S., Ray, E., Roberts, G., Smith, C., Gove, K., Gozzard, N., Williams, S., Haughney, J., Higgenbottam, T., Matthews, J. G., Holweg, C., Rutgers, M., Kamphuis, J., Kerry, D., Vink, A., Knobel, H., Knowles, R., Shaw, D. E., Smith, K. M., Know, A., Kots, M., Lambrecht, B., Masefield, S., Nilsson, P., Mikus, M., Miralpeix, M., Monk, P., Mores, N., Valente, S., Montuschi, P., Murray, C. S., Musial, J., Pacino, A., Pahus, L., Palkonen, S., Powel, P., Rao, N., Santini, G., Vestbo, J., von Garnier, C., Weiszhart, Z., Woodcock, A., Biryukov, M., Schneider, R., Herzinger, S., Satagopam, V., Gu, W., da Silva, A. B., Tielmann, A., Bergeron, J., Gaudette, A., Silberberg, A., Henderson, D., Hayat, S., Elefsinioti, A., Moltzen, E. K., Harbo, I. S., Birgitte, J., Bratfalean, D., Houston, P., Kisler, B., Capdevila, F. B., Verbeeck, D., Marchetti, G., Rahal, G., Schuermann, H. D., Mazuranok, L., Hendlich, M., Painell'S, L., Marren, D., Martasek, J., Rimell, J., Romacker, M., Braxenthaler, M., Sansone, S. -A., Rocca-Serra, P., Commission of the European Communities, Pulmonology, Graduate School, Experimental Immunology, Paediatric Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, ARD - Amsterdam Reproduction and Development, Consortium, U-Biopred Study Group And The Etriks, Rocca-Serra, P, Sansone, S, De Meulder, Bertrand [0000-0002-2108-7657], and Apollo - University of Cambridge Repository

Subjects
Quality Control, 0301 basic medicine, Computer science, Bioinformatics, Systems biology, Big data, Environmental data, Machine Learning, Set (abstract data type), 03 medical and health sciences, Structural Biology, Modelling and Simulation, Cluster Analysis, U-BIOPRED Study Group and the eTRIKS Consortium, Disease, False Positive Reactions, Cluster analysis, Molecular signatures, Molecular Biology, lcsh:QH301-705.5, ‘Omics data, 'Omics data, business.industry, Systems Biology, Applied Mathematics, 1199 Other Medical And Health Sciences, Data science, 3. Good health, Computer Science Applications, Systems medicine, 030104 developmental biology, lcsh:Biology (General), Feature (computer vision), Modeling and Simulation, Stratification, Scale (map), business, Biomarkers, Research Article
Abstract

Background Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-‘omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-‘omics signatures of disease states. Methods The framework is divided into four major steps: dataset subsetting, feature filtering, ‘omics-based clustering and biomarker identification. Results We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-‘omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes. Conclusions This framework will help health researchers plan and perform multi-‘omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine. Electronic supplementary material The online version of this article (10.1186/s12918-018-0556-z) contains supplementary material, which is available to authorized users.

Published
2018
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32. PreDicta chip-based high resolution diagnosis of rhinovirus-induced wheeze

Author

Niespodziana, K. Stenberg-Hammar, K. Megremis, S. Cabauatan, C.R. Napora-Wijata, K. Vacal, P.C. Gallerano, D. Lupinek, C. Ebner, D. Schlederer, T. Harwanegg, C. Söderhäll, C. Van Hage, M. Hedlin, G. Papadopoulos, N.G. Valenta, R.

Abstract

Rhinovirus (RV) infections are major triggers of acute exacerbations of severe respiratory diseases such as pre-school wheeze, asthma and chronic obstructive pulmonary disease (COPD). The occurrence of numerous RV types is a major challenge for the identification of the culprit virus types and for the improvement of virus type-specific treatment strategies. Here, we develop a chip containing 130 different micro-arrayed RV proteins and peptides and demonstrate in a cohort of 120 pre-school children, most of whom had been hospitalized due to acute wheeze, that it is possible to determine the culprit RV species with a minute blood sample by serology. Importantly, we identify RV-A and RV-C species as giving rise to most severe respiratory symptoms. Thus, we have generated a chip for the serological identification of RV-induced respiratory illness which should be useful for the rational development of preventive and therapeutic strategies targeting the most important RV types. © 2018 The Author(s).

Published
2018

33. Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers

Author

Brandsma, J., Goss, V., Yang, X., Bakke, P. S., Caruso, M., Chanez, P., Dahlen, S. -E., Fowler, S. J., Horvath, I., Krug, N., Montuschi, P., Sanak, M., Sandstrom, T., Shaw, D. E., Chung, K. F., Singer, F., Fleming, L. J., Sousa, A. R., Pandis, I., Bansal, A. T., Sterk, P. J., Djukanovic, R., Postle, A. D., Adcock, I. M., Ahmed, H., Auffray, C., Baribaud, F., Bates, S., Bel, E. H., Bigler, J., Bisgaard, H., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bucchioni, E., Burg, D., Bush, A., Chaiboonchoe, A., Chung, F. K., Compton, C. H., Corfield, J., D'Amico, A., Dahlen, B., De Meulder, B., Erpenbeck, V. J., Erzen, D., Fichtner, K., Fitch, N., Formaggio, E., Frey, U., Gahlemann, M., Geiser, T., Guo, Y., Hashimoto, S., Haughney, J., Hedlin, G., Hekking, P. W., Higenbottam, T., Hohlfeld, J. M., Holweg, C., Howarth, P., James, A. J., Knowles, R. G., Knox, A. J., Lefaudeux, D., Loza, M. J., Lutter, R., Manta, A., Masefield, S., Matthews, J. G., Mazein, A., Meiser, A., Middelveld, R. J. M., Miralpeix, M., Mores, N., Murray, C. S., Musial, J., Myles, D., Pahus, L., Pavlidis, S., Powel, P., Pratico, G., Puig Valls, M., Rao, N., Riley, J., Roberts, A., Roberts, G., Rowe, A., Schofield, J. P. R., Seibold, W., Selby, A., Sigmund, R., Skipp, P. J., Sun, K., Thornton, B., van Aalderen, W. M., van Geest, M., Vestbo, J., Vissing, N. H., Wagener, A. H., Wagers, S. S., Weiszhart, Z., Wheelock, C. E., Wilson, S. J., Pulmonology, AII - Inflammatory diseases, Commission of the European Communities, and Publica

Subjects
0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Epithelial lining fluid, Biochemistry, DISEASE, Analytical Chemistry, Cohort Studies, 0302 clinical medicine, Fibrosis, FIBROSIS, Induced sputum, Lung, COPD, Biochemistry and Molecular Biology, respiratory system, Middle Aged, Lipids, Healthy Volunteers, Cell biology, medicine.anatomical_structure, Phenotype, OBESITY, Original Article, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, Life Sciences & Biomedicine, 0301 Analytical Chemistry, Bronchoalveolar Lavage Fluid, Sputum/chemistry, EXPRESSION, Adult, Settore BIO/14 - FARMACOLOGIA, DYNAMIC LIPIDOMICS, Adolescent, SPUTUM CELL COUNTS, BIOMARKERS, Biology, chronic obstructive pulmonary disease, Bronchoalveolar Lavage Fluid/chemistry, Endocrinology & Metabolism, 03 medical and health sciences, Young Adult, Lipids/analysis, Lung/cytology, Lipidomics, medicine, Humans, SURFACTANT LIPIDS, Aged, Science & Technology, pulmonary fibrosis, Mass spectrometry, Sputum, 0601 Biochemistry And Cell Biology, 1103 Clinical Sciences, Lipid metabolism, Pulmonary surfactant, medicine.disease, Molecular medicine, respiratory tract diseases, Weight status, 030104 developmental biology, 030228 respiratory system, ASTHMA, Biokemi och molekylärbiologi, Homeostasis
Abstract

Background Lung epithelial lining fluid (ELF)—sampled through sputum induction—is a medium rich in cells, proteins and lipids. However, despite its key role in maintaining lung function, homeostasis and defences, the composition and biology of ELF, especially in respect of lipids, remain incompletely understood. Objectives To characterise the induced sputum lipidome of healthy adult individuals, and to examine associations between different ELF lipid phenotypes and the demographic characteristics within the study cohort. Methods Induced sputum samples were obtained from 41 healthy non-smoking adults, and their lipid compositions analysed using a combination of untargeted shotgun and liquid chromatography mass spectrometry methods. Topological data analysis (TDA) was used to group subjects with comparable sputum lipidomes in order to identify distinct ELF phenotypes. Results The induced sputum lipidome was diverse, comprising a range of different molecular classes, including at least 75 glycerophospholipids, 13 sphingolipids, 5 sterol lipids and 12 neutral glycerolipids. TDA identified two distinct phenotypes differentiated by a higher total lipid content and specific enrichments of diacyl-glycerophosphocholines, -inositols and -glycerols in one group, with enrichments of sterols, glycolipids and sphingolipids in the other. Subjects presenting the lipid-rich ELF phenotype also had significantly higher BMI, but did not differ in respect of other demographic characteristics such as age or gender. Conclusions We provide the first evidence that the ELF lipidome varies significantly between healthy individuals and propose that such differences are related to weight status, highlighting the potential impact of (over)nutrition on lung lipid metabolism. Electronic supplementary material The online version of this article (10.1007/s11306-018-1412-2) contains supplementary material, which is available to authorized users.

Published
2018
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34. IL-17–high asthma with features of a psoriasis immunophenotype

Author

Östling, Jörgen, primary, van Geest, Marleen, additional, Schofield, James P.R., additional, Jevnikar, Zala, additional, Wilson, Susan, additional, Ward, Jonathan, additional, Lutter, Rene, additional, Shaw, Dominick E., additional, Bakke, Per S., additional, Caruso, Massimo, additional, Dahlen, Sven-Erik, additional, Fowler, Stephen J., additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandström, Thomas, additional, Sun, Kai, additional, Pandis, Ioannis, additional, Auffray, Charles, additional, Sousa, Ana R., additional, Guo, Yike, additional, Adcock, Ian M., additional, Howarth, Peter, additional, Chung, Kian Fan, additional, Bigler, Jeanette, additional, Sterk, Peter J., additional, Skipp, Paul J., additional, Djukanović, Ratko, additional, Vaarala, Outi, additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, K.F., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlen, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Powell, P., additional, Praticò, G., additional, Rao, M. Puig N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, Wilson, S.J., additional, Aliprantis, Antonios, additional, Allen, David, additional, Alving, Kjell, additional, Badorrek, P., additional, Balgoma, David, additional, Ballereau, S., additional, Barber, Clair, additional, Batuwitage, Manohara Kanangana, additional, Bautmans, A., additional, Bedding, A., additional, Behndig, A.F., additional, Beleta, Jorge, additional, Berglind, A., additional, Berton, A., additional, Bochenek, Grazyna, additional, Braun, Armin, additional, Campagna, D., additional, Carayannopoulos, Leon, additional, Casaulta, C., additional, Chaleckis, Romanas, additional, Dahlén, B., additional, Davison, imothy, additional, De Alba, Jorge, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, P., additional, Dijkhuis, Annemiek, additional, Dodson, Paul, additional, Draper, Aleksandra, additional, Dyson, K., additional, Edwards, Jessica, additional, El Hadjam, L., additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Faulenbach, C., additional, Flood, Breda, additional, Galffy, G., additional, Gallart, Hector, additional, Garissi, D., additional, Gent, J., additional, Gerhardsson de Verdier, M., additional, Gibeon, D., additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guillmant-Farry, E., additional, Henriksson, E., additional, Hewitt, Lorraine, additional, Hoda, U., additional, Hu, Richard, additional, Hu, Sile, additional, Hu, X., additional, Jeyasingham, E., additional, Johnson, K., additional, Jullian, N., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Kerry, G., additional, Klüglich, M., additional, Knobel, Hugo, additional, Kolmert, Johan, additional, Konradsen, J.R., additional, Kots, Maxim, additional, Kretsos, Kosmas, additional, Krueger, L., additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, A.-S., additional, Larminie, Christopher, additional, Larsson, L.X., additional, Latzin, P., additional, Lazarinis, N., additional, Lemonnier, N., additional, Lone-Latif, Saeeda, additional, Lowe, L.A., additional, Manta, Alexander, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Mathon, Caroline, additional, McEvoy, L., additional, Meah, Sally, additional, Menzies-Gow, A., additional, Metcalf, Leanne, additional, Mikus, Maria, additional, Monk, Philip, additional, Naz, Shama, additional, Nething, K., additional, Nicholas, Ben, additional, Nihlén, U., additional, Nilsson, Peter, additional, Niven, R., additional, Nordlund, B., additional, Nsubuga, S., additional, Pacino, Antonio, additional, Palkonen, Susanna, additional, Pellet, J., additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Pison, C., additional, Postle, Anthony, additional, Rahman-Amin, Malayka, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, K., additional, Robberechts, Martine, additional, Rocha, J.P., additional, Rossios, C., additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, G., additional, Santoninco, Marco, additional, Saqi, M., additional, Schoelch, Corinna, additional, Scott, S., additional, Sehgal, N., additional, Sjödin, Marcus, additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, P., additional, Sogbessan, A., additional, Spycher, F., additional, Staykova, Doroteya, additional, Stephan, S., additional, Stokholm, J., additional, Strandberg, K., additional, Sunther, M., additional, Szentkereszty, M., additional, Tamasi, L., additional, Tariq, K., additional, Thörngren, John-Olof, additional, Thorsen, Jonathan, additional, Valente, S., additional, van de Pol, Marianne, additional, van Drunen, C.M., additional, Van Eyll, Jonathan, additional, Versnel, Jenny, additional, Vink, Anton, additional, von Garnier, C., additional, Vyas, A., additional, Wald, Frans, additional, Walker, Samantha, additional, Wetzel, Kristiane, additional, Wiegman, Coen, additional, Williams, Siân, additional, Yang, Xian, additional, Yeyasingham, Elizabeth, additional, Amgen, W. Yu, additional, Zetterquist, W., additional, Zolkipli, Z., additional, and Zwinderman, A.H., additional

Published
2019
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35. Epithelial IL-6 trans-signaling defines a new asthma phenotype with increased airway inflammation

Author

Jevnikar, Zala, primary, Östling, Jörgen, additional, Ax, Elisabeth, additional, Calvén, Jenny, additional, Thörn, Kristofer, additional, Israelsson, Elisabeth, additional, Öberg, Lisa, additional, Singhania, Akul, additional, Lau, Laurie C.K., additional, Wilson, Susan J., additional, Ward, Jonathan A., additional, Chauhan, Anoop, additional, Sousa, Ana R., additional, De Meulder, Bertrand, additional, Loza, Matthew J., additional, Baribaud, Frédéric, additional, Sterk, Peter J., additional, Chung, Kian Fan, additional, Sun, Kai, additional, Guo, Yike, additional, Adcock, Ian M., additional, Payne, Debbie, additional, Dahlen, Barbro, additional, Chanez, Pascal, additional, Shaw, Dominick E., additional, Krug, Norbert, additional, Hohlfeld, Jens M., additional, Sandström, Thomas, additional, Djukanovic, Ratko, additional, James, Anna, additional, Hinks, Timothy S.C., additional, Howarth, Peter H., additional, Vaarala, Outi, additional, van Geest, Marleen, additional, Olsson, Henric, additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, F.K., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlen, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, James, A.J., additional, Knowles, R., additional, Knox, A.J., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Manta, A., additional, Matthews, J.G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Montuschi, P., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, Rao, N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J.P.R., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, and Wilson, S.J., additional

Published
2019
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36. Maternal sensitization during pregnancy

Author

Tedner, S. G., Konradsen, J., Söderhäll, C., Hedlin, G., Carlsen, Lödrup K. C., Rehbinder, E. M., Skjerven, H. O., Carlsen, M. H., Fatnes, T. A., Fugelli, P., Granum, B., Haugen, G., Jonassen, C. M., Landrö, L., Lunde, J., Marsland, B. J., Rudi, K., Sjöborg, K., Staff, A. C., Vettukattil, R., Van Hage, M., Carlsen, K., Borres, Magnus P, Asarnoj, A., Nordlund, B., Tedner, S. G., Konradsen, J., Söderhäll, C., Hedlin, G., Carlsen, Lödrup K. C., Rehbinder, E. M., Skjerven, H. O., Carlsen, M. H., Fatnes, T. A., Fugelli, P., Granum, B., Haugen, G., Jonassen, C. M., Landrö, L., Lunde, J., Marsland, B. J., Rudi, K., Sjöborg, K., Staff, A. C., Vettukattil, R., Van Hage, M., Carlsen, K., Borres, Magnus P, Asarnoj, A., and Nordlund, B.

Published
2018
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37. Telomere length was similar in school-age children with bronchopulmonary dysplasia and allergic asthma

Author

Henckel, E., Svenson, Ulrika, Nordlund, B., Berggren Broström, E., Hedlin, G., Degerman, Sofie, Bohlin, K., Henckel, E., Svenson, Ulrika, Nordlund, B., Berggren Broström, E., Hedlin, G., Degerman, Sofie, and Bohlin, K.

Abstract

Aim: Inflammation is a major factor in the pathophysiology of bronchopulmonary dysplasia (BPD), and it contributes to accelerated telomere shortening and cellular ageing. This study aimed to determine its effect on telomere length and lung function in school-aged children born preterm with BPD. Methods: We examined 29 children with BPD, born preterm in Stockholm county 1998-99, along with 28 children with allergic asthma born at term matched for age and gender. At 10 years of age, we measured relative telomere length (RTL) in blood by quantitative polymerase chain reaction, lung function by spirometry and inflammation by fractional exhaled nitric oxide and blood cytokines. Results: RTL was not different in preterm born with BPD compared to term born children with asthma. The gender effect was strong in both groups; girls had significantly longer median RTL than boys (1.8 versus 1.5, p < 0.01). Short RTL was associated with low forced expiratory flow, also after adjusting for gender, but was not affected by severity of BPD or ongoing inflammation. Conclusion: Telomere length was similar in 10-year-old children born preterm with a history of BPD and term born children with allergic asthma. However, impaired lung function and male gender were associated wrth short telomeres.

Published
2018
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38. Clinical phenotypes of asthma in childhood and adolescence: clustering analysis from the paediatric u-biopred cohorts

Author

Hashimoto, S., Brinkman, P., Lefaudeux, D., Bansal, A., Meulder, B., Murray, C., Bush, A., Frey, U., Florian Singer, Hedlin, G., Nordlund, B., Bisgaard, H., Aalderen, W., Vissing, N., Zolkipli, Z., Selby, A., Fowler, S., Shaw, D., Sousa, A., Wagers, S., Corfield, J., Pandis, I., Rowe, A., Valls, M. Puig, Pratico, G., Auffray, C., Chung, K. F., Bel, E., Sterk, P. J., Fleming, L., and Roberts, G.

Subjects
Science & Technology, Critical Care Medicine, General & Internal Medicine, Respiratory System, 11 Medical And Health Sciences, Life Sciences & Biomedicine
Published
2017

39. Pathway discovery using transcriptomic profiles in adult-onset severe asthma

Author

Hekking, Pieter-Paul, primary, Loza, Matt J., additional, Pavlidis, Stelios, additional, de Meulder, Bertrand, additional, Lefaudeux, Diane, additional, Baribaud, Fred, additional, Auffray, Charles, additional, Wagener, Ariane H., additional, Brinkman, Paul, additional, Lutter, Rene, additional, Bansal, Aruna T., additional, Sousa, Ana R., additional, Bates, Steve A., additional, Pandis, Yannis, additional, Fleming, Louise J., additional, Shaw, Dominique E., additional, Fowler, Stephen J., additional, Guo, Y., additional, Meiser, Andrea, additional, Sun, Kai, additional, Corfield, Julie, additional, Howarth, Peter H., additional, Bel, Elisabeth H., additional, Adcock, Ian M., additional, Chung, Kian Fan, additional, Djukanovic, Ratko, additional, Sterk, Peter J., additional, Adcock, I.M., additional, Ahmed, H., additional, Auffray, C., additional, Bakke, P., additional, Bansal, A.T., additional, Baribaud, F., additional, Bates, S., additional, Bel, E.H., additional, Bigler, J., additional, Bisgaard, H., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Caruso, M., additional, Chaiboonchoe, A., additional, Chanez, P., additional, Chung, F.K., additional, Compton, C.H., additional, Corfield, J., additional, D'Amico, A., additional, Dahlen, S.E., additional, De Meulder, B., additional, Djukanovic, R., additional, Erpenbeck, V.J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L.J., additional, Formaggio, E., additional, Fowler, S.J., additional, Frey, U., additional, Gahlemann, M., additional, Geiser, T., additional, Hashimoto, S., additional, Haughney, J., additional, Hedlin, G., additional, Hekking, P.W., additional, Higenbottam, T., additional, Hohlfeld, J.M., additional, Holweg, C., additional, Horváth, I., additional, Howarth, P., additional, James, A.J., additional, Knowles, R., additional, Krug, N., additional, Lefaudeux, D., additional, Loza, M.J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J.G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R.J.M., additional, Miralpeix, M., additional, Mores, N., additional, Murray, C.S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pandis, I., additional, Pavlidis, S., additional, Powel, P., additional, Praticò, G., additional, Valls, M Puig, additional, Rao, N., additional, Riley, J., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Seibold, W., additional, Selby, A., additional, Shaw, D.E., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P.J., additional, Sousa, A.R., additional, Sterk, P.J., additional, Sun, K., additional, Thornton, B., additional, van Aalderen, W.M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N.H., additional, Wagener, A.H., additional, Wagers, S.S., additional, Weiszhart, Z., additional, Wheelock, C.E., additional, and Wilson, S.J., additional

Published
2018
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41. National and regional asthma programmes in Europe

Author

Selroos, O. Kupczyk, M. Kuna, P. Łacwik, P. Bousquet, J. Brennan, D. Palkonen, S. Contreras, J. FitzGerald, M. Hedlin, G. Johnston, S.L. Louis, R. Metcalf, L. Walker, S. Moreno-Galdó, A. Papadopoulos, N.G. Rosado-Pinto, J. Powell, P. Haahtela, T.

Abstract

This review presents seven national asthma programmes to support the European Asthma Research and Innovation Partnership in developing strategies to reduce asthma mortality and morbidity across Europe. From published data it appears that in order to influence asthma care, national/regional asthma programmes are more effective than conventional treatment guidelines. An asthma programme should start with the universal commitments of stakeholders at all levels and the programme has to be endorsed by political and governmental bodies. When the national problems have been identified, the goals of the programme have to be clearly defined with measures to evaluate progress. An action plan has to be developed, including defined re-allocation of patients and existing resources, if necessary, between primary care and specialised healthcare units or hospital centres. Patients should be involved in guided self-management education and structured follow-up in relation to disease severity. The three evaluated programmes show that, thanks to rigorous efforts, it is possible to improve patients’ quality of life and reduce hospitalisation, asthma mortality, sick leave and disability pensions. The direct and indirect costs, both for the individual patient and for society, can be significantly reduced. The results can form the basis for development of further programme activities in Europe. © ERS 2015.

Published
2015

42. Simultaneously elevated exhaled nitric oxide and serum-eosinophil cationic protein relate to recent asthma events in asthmatics in a cross-sectional population-based study.

Author

Mogensen, Ida, Alving, Kjell, Bjerg, A., Borres, Magnus P., Hedlin, G., Sommar, J., Dahlén, S-E, Janson, Christer, Malinovschi, Andrei, Mogensen, Ida, Alving, Kjell, Bjerg, A., Borres, Magnus P., Hedlin, G., Sommar, J., Dahlén, S-E, Janson, Christer, and Malinovschi, Andrei

Abstract

BACKGROUND: We have reported that increased fraction of exhaled nitric oxide (FeNO), a measure of TH2 -driven airway inflammation, and blood eosinophil count, a marker of systemic eosinophil inflammation, correlated with asthma attacks in a population-based study. OBJECTIVE: To investigate the relation between simultaneously elevated FeNO and serum eosinophil cationic protein (S-ECP) levels and asthma events among asthmatics. METHODS: Measurements of FeNO (elevated ≥ 25 ppb) and S-ECP (elevated ≥ 20 ng/mL) were performed in 339 adult asthmatics. Asthma events (attacks and symptoms) were self-reported. RESULTS: Simultaneously normal S-ECP and FeNO levels were found in 48% of the subjects. Subjects with simultaneously elevated S-ECP and FeNO (13% of the population) had a higher prevalence of asthma attacks in the preceding 3 months than subjects with normal S-ECP and FeNO (51% vs. 25%, P = 0.001). This was not found for subjects with singly elevated S-ECP (P = 0.14) or FeNO (P = 0.34) levels. Elevated S-ECP and FeNO levels were independently associated with asthma attacks in the preceding 3 months after adjusting for potential confounders (OR (95% CI) 4.2 (2.0-8.8). CONCLUSIONS: Simultaneously elevated FeNO and S-ECP levels were related to a higher likelihood of asthma attacks in the preceding 3 months. This indicates that there is a value in measuring both FeNO and systemic eosinophilic inflammation in patients with asthma to identify individuals at high risk of exacerbations. CLINICAL RELEVANCE: FeNO and S-ECP are markers for inflammation in asthma, but are dependent on different inflammatory pathways and weakly correlated. Simultaneous measurements of both offer better risk characterization of adult asthmatics.

Published
2016
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43. Important non-disease-related determinants of exhaled nitric oxide levels in mild asthma - results from the Swedish GA(2)LEN study

Author

Al-Shamkhi, Nasrin, Alving, Kjell, Dahlen, S. E., Hedlin, G., Middelveld, R., Bjerg, A., Ekerljung, L., Olin, A. C., Sommar, J., Forsberg, B., Janson, Christer, Malinovschi, Andrei, Al-Shamkhi, Nasrin, Alving, Kjell, Dahlen, S. E., Hedlin, G., Middelveld, R., Bjerg, A., Ekerljung, L., Olin, A. C., Sommar, J., Forsberg, B., Janson, Christer, and Malinovschi, Andrei

Abstract

Background Fractional exhaled nitric oxide (FeNO) has a potential clinical role in asthma management. Constitutive factors such as age, height and gender, as well as individual characteristics, such as IgE sensitization and smoking, affect the levels of FeNO in population-based studies. However, their effect on FeNO in subjects with asthma has been scarcely studied. Objective To study the effects on FeNO of these commonly regarded determinants, as demonstrated in healthy subjects, as well as menarche age and parental smoking, in a population of asthmatics. Material and Methods Fractional exhaled nitric oxide was measured in 557 subjects with asthma from the Swedish GA(2)LEN study. Allergic sensitization was assessed by skin prick tests to most common aeroallergens. Upper airway comorbidities, smoking habits, smoking exposure during childhood and hormonal status (for women) were questionnaire-assessed. Results Male gender (P < 0.001), greater height (P < 0.001) and sensitization to both perennial allergens and pollen (P < 0.001) are related to higher FeNO levels. Current smoking (P < 0.001) and having both parents smoking during childhood, vs. having neither (P < 0.001) or only one parent smoking (P = 0.002), are related to lower FeNO. Women with menarche between 9 and 11 years of age had lower FeNO than those with menarche between 12 and 14 years of age (P = 0.03) or 15 and 17 years of age (P = 0.003). Conclusions and Clinical relevance Interpreting FeNO levels in clinical practice is complex, and constitutional determinants, as well as smoking and IgE sensitisation, are of importance in asthmatic subjects and should be accounted for when interpreting FeNO levels. Furthermore, menarche age and parental smoking during childhood and their effects on lowering FeNO deserve further studies.

Published
2016
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44. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma

Author

Hamsten, C., Häggmark, Anna, Grundstrom, J., Mikus, Maria, Lindskog, C., Konradsen, J. R., Eklund, A., Pershagen, G., Wickman, M., Grunewald, J., Melen, E., Hedlin, G., Nilsson, Peter, van Hage, M., Hamsten, C., Häggmark, Anna, Grundstrom, J., Mikus, Maria, Lindskog, C., Konradsen, J. R., Eklund, A., Pershagen, G., Wickman, M., Grunewald, J., Melen, E., Hedlin, G., Nilsson, Peter, and van Hage, M.

Abstract

Asthma is a common chronic childhood disease with many different phenotypes that need to be identified. We analyzed a broad range of plasma proteins in children with well-characterized asthma phenotypes to identify potential markers of childhood asthma. Using an affinity proteomics approach, plasma levels of 362 proteins covered by antibodies from the Human Protein Atlas were investigated in a total of 154 children with persistent or intermittent asthma and controls. After screening, chemokine ligand 5 (CCL5) hematopoietic prostaglandin D synthase (HPGDS) and neuropeptide S receptor 1 (NPSR1) were selected for further investigation. Significantly lower levels of both CCL5 and HPGDS were found in children with persistent asthma, while NPSR1 was found at higher levels in children with mild intermittent asthma compared to healthy controls. In addition, the protein levels were investigated in another respiratory disease, sarcoidosis, showing significantly higher NPSR1 levels in sera from sarcoidosis patients compared to healthy controls. Immunohistochemical staining of healthy tissues revealed high cytoplasmic expression of HPGDS in mast cells, present in stroma of both airway epithelia, lung as well as in other organs. High expression of NPSR1 was observed in neuroendocrine tissues, while no expression was observed in airway epithelia or lung. In conclusion, we have utilized a broad-scaled affinity proteomics approach to identify three proteins with altered plasma levels in asthmatic children, representing one of the first evaluations of HPGDS and NPSR1 protein levels in plasma., QC 20161024

Published
2016
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50. Protein profiles of CCL5, HPGDS, and NPSR1 in plasma reveal association with childhood asthma

Author

Hamsten, C., primary, Häggmark, A., additional, Grundström, J., additional, Mikus, M., additional, Lindskog, C., additional, Konradsen, J. R., additional, Eklund, A., additional, Pershagen, G., additional, Wickman, M., additional, Grunewald, J., additional, Melén, E., additional, Hedlin, G., additional, Nilsson, P., additional, and van Hage, M., additional

Published
2016
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