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153 results on '"De Meulder B"'

1. Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

Author

Badorrek, P., Broeders, M., Boersma, W.G., Chetta, A., Cukier, A., D'Amato, M., Djukanovic, R., Foschino, M.P., Gessner, C., Hanania, N., Martin, R., Milleri, S., Olivenstein, R., Paggiaro, P., Pizzichini, E., Plaza Moral, V., Postma, D.S., Scichilone, N., Schilz, R., Spanevello, A., Stelmach, R., Vroegop, J.S., Usmani, O.S., Zhang, Q., Ahmed, H., Allen, D., Ballereau, S., Batuwitage, M.K., Bedding, A., Behndig, A.F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M.J., Bønnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J.M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klüglich, M., Knowles, R., Konradsen, J.R., Kretsos, K., Krueger, L., Lantz, A-S., Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L.A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C.S., Nething, K., Nihlén, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Praticò, G., Puig Valls, M., Riemann, K., Rocha, J.P., Rossios, C., Santini, G., Sagi, M., Scott, S., Sehgal, N., Selby, A., Söderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S, Van Aalderen, W.M., Van Drunen, C.M., Van Eyll, J., Vyas, A., Yu, W., Zetterguist, W., Zolkipli, Z., Zwinderman, A.H., Agusti, A., Wedzicha, J.A., Donaldson, G.C., Faner, R., Breyer-Kohansal, R., Maitland-van der Zee, A.H., Melén, E., Allinson, J.P., Vanfleteren, L.E.G.W., Vestbo, J., Adcock, I.M., Lahousse, L., Van den Berge, M., Alter, P., Barbe, F., Brightling, C.E., Breyer, M.K., Burghuber, O.C., Casas, M., Chung, K.F., Cosío, B.G., Crispi, F., De Batlle, J., Fitting, J.W., Garcia, J., Hallberg, J., Hartl, S., Jarvis, D., Mathioudakis, A., Nicod, L., Papi, A., Ritchie, A., Sigsgaard, T., Sterk, P.J., Ullman, A., Vellvé, K., Vogelmeier, C., Wheelock, A.M., Wheelock, C.E., Kole, Tessa M, Vanden Berghe, Elise, Kraft, Monica, Vonk, Judith M, Nawijn, Martijn C, Siddiqui, Salman, Sun, Kai, Fabbri, Leonardo M, Rabe, Klaus F, Chung, Kian Fan, Nicolini, Gabriele, Papi, Alberto, Brightling, Chris, Singh, Dave, van der Molen, Thys, Dahlén, Sven-Erik, Agusti, Alvar, Faner, Rosa, Wedzicha, Jadwiga A, Donaldson, Gavin C, Adcock, Ian M, Lahousse, Lies, Kerstjens, Huib A M, and van den Berge, Maarten

Published
2023
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2. Analysis of clinical characteristics in metastatic hormone-sensitive prostate cancer. A comparative study of patients from cal trials to patients from real life using Big Data

Author

Ibanez Vazquez, L., primary, Gómez Rivas, J., additional, Nicoletti, R., additional, Golozar, A., additional, Steinbeißer, C., additional, De Meulder, B., additional, Snijder, R., additional, Axelsson, S.E., additional, Ayman, H., additional, Feng, Q., additional, Bjartell, A., additional, Cornford, P., additional, Murtola, T.J., additional, Willemse, P., additional, Moreno Sierra, J., additional, and N’dow, J., additional

Published
2024
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3. Development of a predictive model for death amongst patients with Metastatic Hormone Sensitive Prostate Cancer (mHSPC) treated with one of the approved treatment plans, on characteristics present at admission using Big data: Preliminary results from the European network of excellence for big data in prostate cancer (PIONEER)

Author

Nicoletti, R., primary, Gomez Rivas, J., additional, Ibánez, L., additional, Steinbeisse, C., additional, de Meulder, B., additional, Ayman, H., additional, Golozar, A., additional, Snijder, R., additional, Van Hemelrijck, M., additional, Beyer, K., additional, Willemse, P-P., additional, Murtola, T., additional, Roobol, M.J., additional, Moreno-Sierra, J., additional, Campi, R., additional, Gacci, M., additional, Mottet, N., additional, Merseburger, A., additional, Cornford, P., additional, and Ndow, J., additional

Published
2024
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4. 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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5. 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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6. Stratification of asthma phenotypes by airway proteomic signatures

Author

Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Bedding, A., Behndig, A.F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M.J., Bønnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Gent, J., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J.M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klüglich, M., Knowles, R., Konradsen, J.R., Kretsos, K., Krueger, L., Lantz, A.-S., Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L.A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C.S., Nething, K., Nihlén, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Praticò, G., Valls, M. Puig, Riemann, K., Rocha, J.P., Rossios, C., Santini, G., Saqi, M., Scott, S., Sehgal, N., Selby, A., Söderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S., van Aalderen, W.M., van Drunen, C.M., Van Eyll, J., Vyas, A., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A.H., Schofield, James P.R., Burg, Dominic, Nicholas, Ben, Strazzeri, Fabio, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna T., Xian, Yang, Guo, Yike, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Sun, Kai, Pandis, Ioannis, Riley, John, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., and Djukanović, Ratko

Published
2019
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7. 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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8. Analysis of clinical characteristics in metastatic hormone-sensitive prostate cancer: Bridging the gap between randomized controlled trials and real-world data

Author

Gómez Rivas, J., primary, Nicoletti, R., additional, Ibanez, L., additional, Golozar, A., additional, Steinbeißer, C., additional, De Meulder, B., additional, Snijder, R., additional, Axelsson, S.E., additional, Ayman, H., additional, Feng, Q., additional, Bjartell, A., additional, Cornford, P., additional, Murtola, T., additional, Willemse, P.P., additional, Prinsen, P., additional, and N dow, J., additional

Published
2023
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9. Real-world data analysis of treatment outcomes for patients with metastatic hormone-sensitive prostate cancer: development of a survival prediction model. Results from the European network of excellence for big data in prostate cancer (PIONEER)

Author

Gómez Rivas, J., primary, Nicoletti, R., additional, Golozar, A., additional, Ayman, H., additional, Steinbeißer, C., additional, Ibañez, L., additional, De Meulder, B., additional, Axelsson, S.E., additional, Snijder, R., additional, Feng, Q., additional, Bjartell, A., additional, Cornford, P., additional, Willemse, P., additional, Prinsen, P., additional, Murtola, T.J., additional, and N´dow, J., additional

Published
2023
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10. Real-world data analysis of clinical characteristics in metastatic hormone-sensitive prostate cancer: Are patients from RCTs the same from real life? Data from the European network of excellence for big data in prostate cancer (PIONEER).

Author

Gómez Rivas, J., primary, Nicoletti, R., additional, Golozar, A., additional, Steinbeißer, C., additional, De Meulder, B., additional, Snijder, R., additional, Ibañez, L., additional, Axelsson, S.E., additional, Ayman, H., additional, Feng, Q., additional, Murtola, T.J., additional, Bjartell, A., additional, Cornford, P., additional, Willemse, P., additional, Prinsen, P., additional, and N´dow, J., additional

Published
2023
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11. Towards a European health research and innovation cloud (HRIC)

Author

Aarestrup, F. M., Albeyatti, A., Armitage, W. J., Auffray, C., Augello, L., Balling, R., Benhabiles, N., Bertolini, G., Bjaalie, J. G., Black, M., Blomberg, N., Bogaert, P., Bubak, M., Claerhout, B., Clarke, L., De Meulder, B., D’Errico, G., Di Meglio, A., Forgo, N., Gans-Combe, C., Gray, A. E., Gut, I., Gyllenberg, A., Hemmrich-Stanisak, G., Hjorth, L., Ioannidis, Y., Jarmalaite, S., Kel, A., Kherif, F., Korbel, J. O., Larue, C., Laszlo, M., Maas, A., Magalhaes, L., Manneh-Vangramberen, I., Morley-Fletcher, E., Ohmann, C., Oksvold, P., Oxtoby, N. P., Perseil, I., Pezoulas, V., Riess, O., Riper, H., Roca, J., Rosenstiel, P., Sabatier, P., Sanz, F., Tayeb, M., Thomassen, G., Van Bussel, J., Van den Bulcke, M., and Van Oyen, H.

Published
2020
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12. Predictors and associations of the persistent airflow limitation phenotype in asthma: a post-hoc analysis of the ATLANTIS study

Author

Kole, Tessa M, primary, Vanden Berghe, Elise, additional, Kraft, Monica, additional, Vonk, Judith M, additional, Nawijn, Martijn C, additional, Siddiqui, Salman, additional, Sun, Kai, additional, Fabbri, Leonardo M, additional, Rabe, Klaus F, additional, Chung, Kian Fan, additional, Nicolini, Gabriele, additional, Papi, Alberto, additional, Brightling, Chris, additional, Singh, Dave, additional, van der Molen, Thys, additional, Dahlén, Sven-Erik, additional, Agusti, Alvar, additional, Faner, Rosa, additional, Wedzicha, Jadwiga A, additional, Donaldson, Gavin C, additional, Adcock, Ian M, additional, Lahousse, Lies, additional, Kerstjens, Huib A M, additional, van den Berge, Maarten, additional, Badorrek, P., additional, Broeders, M., additional, Boersma, W.G., additional, Chetta, A., additional, Cukier, A., additional, D'Amato, M., additional, Djukanovic, R., additional, Foschino, M.P., additional, Gessner, C., additional, Hanania, N., additional, Martin, R., additional, Milleri, S., additional, Olivenstein, R., additional, Paggiaro, P., additional, Pizzichini, E., additional, Plaza Moral, V., additional, Postma, D.S., additional, Scichilone, N., additional, Schilz, R., additional, Spanevello, A., additional, Stelmach, R., additional, Vroegop, J.S., additional, Usmani, O.S., additional, Zhang, Q., additional, Ahmed, H., additional, Allen, D., additional, Ballereau, S., additional, Batuwitage, M.K., additional, Bedding, A., additional, Behndig, A.F., additional, Berglind, A., additional, Berton, A., additional, Bigler, J., additional, Boedigheimer, M.J., additional, Bønnelykke, K., additional, Brinkman, P., additional, Bush, A., additional, Campagna, D., additional, Casaulta, C., additional, Chaiboonchoe, A., additional, Davison, T., additional, De Meulder, B., additional, Delin, I., additional, Dennison, P., additional, Dodson, P., additional, El Hadjam, L., additional, Erzen, D., additional, Faulenbach, C., additional, Fichtner, K., additional, Fitch, N., additional, Formaggio, E., additional, Gahlemann, M., additional, Galffy, G., additional, Garissi, D., additional, Garret, T., additional, Guillmant-Farry, E., additional, Henriksson, E., additional, Hoda, U., additional, Hohlfeld, J.M., additional, Hu, X., additional, James, A., additional, Johnson, K., additional, Jullian, N., additional, Kerry, G., additional, Klüglich, M., additional, Knowles, R., additional, Konradsen, J.R., additional, Kretsos, K., additional, Krueger, L., additional, Lantz, A-S., additional, Larminie, C., additional, Latzin, P., additional, Lefaudeux, D., additional, Lemonnier, N., additional, Lowe, L.A., additional, Lutter, R., additional, Manta, A., additional, Mazein, A., additional, McEvoy, L., additional, Menzies-Gow, A., additional, Mores, N., additional, Murray, C.S., additional, Nething, K., additional, Nihlén, U., additional, Niven, R., additional, Nordlund, B., additional, Nsubuga, S., additional, Pellet, J., additional, Pison, C., additional, Praticò, G., additional, Puig Valls, M., additional, Riemann, K., additional, Rocha, J.P., additional, Rossios, C., additional, Santini, G., additional, Sagi, M., additional, Scott, S., additional, Sehgal, N., additional, Selby, A., additional, Söderman, P., additional, Sogbesan, A., additional, Spycher, F., additional, Stephan, S., additional, Stokholm, J., additional, Sunther, M., additional, Szentkereszty, M., additional, Tamasi, L., additional, Tariq, K., additional, Valente, S, additional, Van Aalderen, W.M., additional, Van Drunen, C.M., additional, Van Eyll, J., additional, Vyas, A., additional, Yu, W., additional, Zetterguist, W., additional, Zolkipli, Z., additional, Zwinderman, A.H., additional, Agusti, A., additional, Wedzicha, J.A., additional, Donaldson, G.C., additional, Faner, R., additional, Breyer-Kohansal, R., additional, Maitland-van der Zee, A.H., additional, Melén, E., additional, Allinson, J.P., additional, Vanfleteren, L.E.G.W., additional, Vestbo, J., additional, Adcock, I.M., additional, Lahousse, L., additional, Van den Berge, M., additional, Alter, P., additional, Barbe, F., additional, Brightling, C.E., additional, Breyer, M.K., additional, Burghuber, O.C., additional, Casas, M., additional, Chung, K.F., additional, Cosío, B.G., additional, Crispi, F., additional, De Batlle, J., additional, Fitting, J.W., additional, Garcia, J., additional, Hallberg, J., additional, Hartl, S., additional, Jarvis, D., additional, Mathioudakis, A., additional, Nicod, L., additional, Papi, A., additional, Ritchie, A., additional, Sigsgaard, T., additional, Sterk, P.J., additional, Ullman, A., additional, Vellvé, K., additional, Vogelmeier, C., additional, Wheelock, A.M., additional, and Wheelock, C.E., additional

Published
2023
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13. The role of inflammation in anxiety and depression in the European U-BIOPRED asthma cohorts

Author

Hou, R, Ye, G, Cheng, X, Shaw, DE, Bakke, PS, Caruso, M, Dahlen, B, Dahlen, S-E, Fowler, SJ, Horváth, I, Howarth, P, Krug, N, Montuschi, P, Sanak, M, Sandström, T, Auffray, C, De Meulder, B, Sousa, AR, Adcock, IM, Fan Chung, K, Sterk, PJ, Skipp, PJ, Schofield, J, Djukanović, R, U-BIOPRED Study Group, and Publica

Subjects
Inflammation, Psychiatry, Behavioral Neuroscience, Endocrine and Autonomic Systems, Depression, U-BIOPRED, Respiratory Medicine and Allergy, Immunology, Anxiety, Asthma, Psykiatri, Lungmedicin och allergi
Abstract

BACKGROUND: Growing evidence indicates high comorbid anxiety and depression in patients with asthma. However, the mechanisms underlying this comorbid condition remain unclear. The aim of this study was to investigate the role of inflammation in comorbid anxiety and depression in three asthma patient cohorts of the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project.METHODS: U-BIOPRED was conducted by a European Union consortium of 16 academic institutions in 11 European countries. A subset dataset from subjects with valid anxiety and depression measures and a large blood biomarker dataset were analysed, including 198 non-smoking patients with severe asthma (SAn), 65 smoking patients with severe asthma (SAs), 61 non-smoking patients with mild-to-moderate asthma (MMA), and 20 healthy non-smokers (HC). The Hospital Anxiety and Depression Scale was used to measure anxiety and depression and a series of inflammatory markers were analysed by the SomaScan v3 platform (SomaLogic, Boulder, Colo). ANOVA and the Kruskal-Wallis test were used for multiple-group comparisons as appropriate.RESULTS: There were significant group effects on anxiety and depression among the four cohort groups (p < 0.05). Anxiety and depression of SAn and SAs groups were significantly higher than that of MMA and HC groups (p < 0.05. There were significant differences in serum IL6, MCP1, CCL18, CCL17, IL8, and Eotaxin among the four groups (p < 0.05). Depression was significantly associated with IL6, MCP1, CCL18 level, and CCL17; whereas anxiety was associated with CCL17 only (p < 0.05).CONCLUSIONS: The current study suggests that severe asthma patients are associated with higher levels of anxiety and depression, and inflammatory responses may underlie this comorbid condition.

Published
2023

14. 917P OPTIMA: Improve care for patients with prostate, breast, and lung cancer through artificial intelligence

Author

N’Dow, J., primary, Smith, E.J., additional, Polychronopoulos, K., additional, Cannon, A., additional, Roobol, M., additional, Auweter, S., additional, Thomas, M., additional, Kremer, A., additional, De Meulder, B., additional, Dellamonica, D., additional, Alhambra, D.P., additional, Asiimwe, A., additional, Bussmann, M., additional, Ji, X., additional, Torremante, P., additional, Keller, S., additional, Kube, F., additional, and Krueger, H., additional

Published
2022
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15. 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

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

Author

Mikus MS, Kolmert J, Andersson LI, Östling J, Knowles RG, Gómez C, Ericsson M, Thörngren JO, Khoonsari PE, Dahlén B, Kupczyk M, De Meulder B, Auffray C, Bakke PS, Beghe B, Bel EH, Caruso M, Chanez P, Chawes B, Fowler SJ, Gaga M, Geiser T, Gjomarkaj M, Horváth I, Howarth PH, Johnston SL, Joos G, Krug N, Montuschi P, Musial J, Ni?ankowska-Mogilnicka E, Olsson HK, Papi A, Rabe KF, Sandström T, Shaw DE, Siafakas NM, Uhlen M, Riley JH, Bates S, Middelveld RJM, Wheelock CE, Chung KF, Adcock IM, Sterk PJ, Djukanovic R, Nilsson P, Dahlén SE, James A, U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcome) Study Group, BIOAIR (Longitudinal Assessment of Clinical Course, and Biomarkers in Severe Chronic Airway Disease) Consortium.

Subjects
Inflammation, Steroids, Asthma
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-characterized cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, chronic obstructive pulmonary disease (COPD) subjects and healthy controls (HC). 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 HC 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 two-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 HC. Ten 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, RANK, TGF-?1, 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, hsCRP, and BMI, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers, and validated several proteins with established involvement in the pathophysiology of severe asthma.

Published
2022

17. 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

18. The PIONEER watchful waiting for prostate cancer apps - a first practical application of using big data for prostate cancer

Author

Hulsen, T., primary, Moinat, M., additional, Van Bochove, K., additional, Gorbachev, A., additional, Kaduk, D., additional, Argyriou, G., additional, Cossin, S., additional, Herrera, R., additional, Golozar, A., additional, Prinsen, P., additional, Beyer, K., additional, Van Hemelrijck, M., additional, Oja, M., additional, Axelsson, S., additional, Steinbeisser, C., additional, and De Meulder, B., additional

Published
2022
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19. Introducing PIONEER: a project to harness big data in prostate cancer research

Author

Omar M. I., Roobol M. J., Ribal M. J., Abbott T., Agapow P. -M., Araujo S., Asiimwe A., Auffray C., Balaur I., Beyer K., Bernini C., Bjartell A., Briganti A., Butler-Ransohoff J. -E., Campi R., Cavelaars M., De Meulder B., Devecseri Z., Voss M. D., Dimitropoulos K., Evans-Axelsson S., Franks B., Fullwood L., Horgan D., Smith E. J., Kiran A., Kivinummi K., Lambrecht M., Lancet D., Lindgren P., MacLennan S., Nogueira M. M., Moen F., Moinat M., Papineni K., Reich C., Reiche K., Rogiers S., Sartini C., van Bochove K., van Diggelen F., Van Hemelrijck M., Van Poppel H., Zong J., N'Dow J., Andersson E., Arala H., Auvinen A., Bangma C., Burke D., Cardone A., Casariego J., Cuperus G., Dabestani S., Esperto F., Fossati N., Fridhammar A., Gandaglia G., Tandefelt D. G., Horn F., Huber J., Hugosson J., Huisman H., Josefsson A., Kilkku O., Kreuz M., Lardas M., Lawson J., Lefresne F., Lejeune S., Longden-Chapman E., McVie G., Moris L., Mottet N., Murtola T., Nicholls C., Pang K. H., Pascoe K., Picozzi M., Plass K., Pohjanjousi P., Reaney M., Remmers S., Robinson P., Schalken J., Schravendeel M., Seisen T., Servan A., Shiranov K., Snijder R., Steinbeisser C., Taibi N., Talala K., Tilki D., Van den Broeck T., Vassilev Z., Voima O., Vradi E., Waldeck R., Weistra W., Willemse P. -P., Wirth M., Wolfinger R., Kermani N. Z., Omar, M. I., Roobol, M. J., Ribal, M. J., Abbott, T., Agapow, P. -M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J. -E., Campi, R., Cavelaars, M., De Meulder, B., Devecseri, Z., Voss, M. D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E. J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., Maclennan, S., Nogueira, M. M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., van Bochove, K., van Diggelen, F., Van Hemelrijck, M., Van Poppel, H., Zong, J., N'Dow, J., Andersson, E., Arala, H., Auvinen, A., Bangma, C., Burke, D., Cardone, A., Casariego, J., Cuperus, G., Dabestani, S., Esperto, F., Fossati, N., Fridhammar, A., Gandaglia, G., Tandefelt, D. G., Horn, F., Huber, J., Hugosson, J., Huisman, H., Josefsson, A., Kilkku, O., Kreuz, M., Lardas, M., Lawson, J., Lefresne, F., Lejeune, S., Longden-Chapman, E., Mcvie, G., Moris, L., Mottet, N., Murtola, T., Nicholls, C., Pang, K. H., Pascoe, K., Picozzi, M., Plass, K., Pohjanjousi, P., Reaney, M., Remmers, S., Robinson, P., Schalken, J., Schravendeel, M., Seisen, T., Servan, A., Shiranov, K., Snijder, R., Steinbeisser, C., Taibi, N., Talala, K., Tilki, D., Van den Broeck, T., Vassilev, Z., Voima, O., Vradi, E., Waldeck, R., Weistra, W., Willemse, P. -P., Wirth, M., Wolfinger, R., Kermani, N. Z., Publica, and Urology

Subjects
0301 basic medicine, Prioritization, Knowledge management, Urology, media_common.quotation_subject, education, Big data, Disease, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Multidisciplinary approach, Urological cancers Radboud Institute for Molecular Life Sciences [Radboudumc 15], Medicine, Quality (business), media_common, business.industry, Patient-centered outcomes, medicine.disease, 3. Good health, Patient management, 030104 developmental biology, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 030220 oncology & carcinogenesis, business
Abstract

Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. Launched by the Innovative Medicines Initiative 2 and part of the Big Data for Better Outcomes Programme (BD4BO), the overarching goal of PIONEER is to provide high-quality evidence on prostate cancer management by unlocking the potential of big data. The project has identified critical evidence gaps in prostate cancer care, via a detailed prioritization exercise including all key stakeholders. By standardizing and integrating existing high-quality and multidisciplinary data sources from patients with prostate cancer across different stages of the disease, the resulting big data will be assembled into a single innovative data platform for research. Based on a unique set of methodologies, PIONEER aims to advance the field of prostate cancer care with a particular focus on improving prostate-cancer-related outcomes, health system efficiency by streamlining patient management, and the quality of health and social care delivered to all men with prostate cancer and their families worldwide.Prostate Cancer Diagnosis and Treatment Enhancement Through the Power of Big Data in Europe (PIONEER) is a European network of excellence for big data in prostate cancer, consisting of 32 private and public stakeholders from 9 countries across Europe. In this Perspectives article, the authors introduce the PIONEER project and describe its aims and plans for ultimately improving prostate cancer care through the use of big data.

Published
2020

20. Author Correction: Introducing PIONEER: a project to harness big data in prostate cancer research (Nature Reviews Urology, (2020), 17, 6, (351-362), 10.1038/s41585-020-0324-x)

Author

Omar M. I., Roobol M. J., Ribal M. J., Abbott T., Agapow P. -M., Araujo S., Asiimwe A., Auffray C., Balaur I., Beyer K., Bernini C., Bjartell A., Briganti A., Butler-Ransohoff J. -E., Campi R., Cavelaars M., De Meulder B., Devecseri Z., Voss M. D., Dimitropoulos K., Evans-Axelsson S., Franks B., Fullwood L., Horgan D., Smith E. J., Kiran A., Kivinummi K., Lambrecht M., Lancet D., Lindgren P., MacLennan S., Nogueira M. M., Moen F., Moinat M., Papineni K., Reich C., Reiche K., Rogiers S., Sartini C., van Bochove K., van Diggelen F., Van Hemelrijck M., Van Poppel H., Zong J., N'Dow J., Andersson E., Arala H., Auvinen A., Bangma C., Burke D., Cardone A., Casariego J., Cuperus G., Dabestani S., Esperto F., Fossati N., Fridhammar A., Gandaglia G., Tandefelt D. G., Horn F., Huber J., Hugosson J., Huisman H., Josefsson A., Kilkku O., Kreuz M., Lardas M., Lawson J., Lefresne F., Lejeune S., Longden-Chapman E., McVie G., Moris L., Mottet N., Murtola T., Nicholls C., Pang K. H., Pascoe K., Picozzi M., Plass K., Pohjanjousi P., Reaney M., Remmers S., Robinson P., Schalken J., Schravendeel M., Seisen T., Servan A., Shiranov K., Snijder R., Steinbeisser C., Taibi N., Talala K., Tilki D., Van den Broeck T., Vassilev Z., Voima O., Vradi E., Waldeck R., Weistra W., Willemse P. -P., Wirth M., Wolfinger R., Kermani N. Z., Omar, M. I., Roobol, M. J., Ribal, M. J., Abbott, T., Agapow, P. -M., Araujo, S., Asiimwe, A., Auffray, C., Balaur, I., Beyer, K., Bernini, C., Bjartell, A., Briganti, A., Butler-Ransohoff, J. -E., Campi, R., Cavelaars, M., De Meulder, B., Devecseri, Z., Voss, M. D., Dimitropoulos, K., Evans-Axelsson, S., Franks, B., Fullwood, L., Horgan, D., Smith, E. J., Kiran, A., Kivinummi, K., Lambrecht, M., Lancet, D., Lindgren, P., Maclennan, S., Nogueira, M. M., Moen, F., Moinat, M., Papineni, K., Reich, C., Reiche, K., Rogiers, S., Sartini, C., van Bochove, K., van Diggelen, F., Van Hemelrijck, M., Van Poppel, H., Zong, J., N'Dow, J., Andersson, E., Arala, H., Auvinen, A., Bangma, C., Burke, D., Cardone, A., Casariego, J., Cuperus, G., Dabestani, S., Esperto, F., Fossati, N., Fridhammar, A., Gandaglia, G., Tandefelt, D. G., Horn, F., Huber, J., Hugosson, J., Huisman, H., Josefsson, A., Kilkku, O., Kreuz, M., Lardas, M., Lawson, J., Lefresne, F., Lejeune, S., Longden-Chapman, E., Mcvie, G., Moris, L., Mottet, N., Murtola, T., Nicholls, C., Pang, K. H., Pascoe, K., Picozzi, M., Plass, K., Pohjanjousi, P., Reaney, M., Remmers, S., Robinson, P., Schalken, J., Schravendeel, M., Seisen, T., Servan, A., Shiranov, K., Snijder, R., Steinbeisser, C., Taibi, N., Talala, K., Tilki, D., Van den Broeck, T., Vassilev, Z., Voima, O., Vradi, E., Waldeck, R., Weistra, W., Willemse, P. -P., Wirth, M., Wolfinger, R., and Kermani, N. Z.

Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2020

21. 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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22. Instability of sputum molecular phenotypes in U-BIOPRED severe asthma

Author

Kermani, NZ, Pavlidis, S, Xie, J, Sun, K, Loza, M, Baribaud, F, Fowler, SJ, Shaw, DE, Fleming, LJ, Howarth, PH, Sousa, AR, Corfield, J, Auffray, C, De Meulder, B, Sterk, PJ, Guo, Y, Uddin, M, Djukanovic, R, Adcock, IM, Chung, KF, U-BIOPRED study group, Pulmonology, and Commission of the European Communities

Subjects
Pulmonary and Respiratory Medicine, Download, media_common.quotation_subject, Respiratory System, Shareholder, Nothing, Health care, Medicine, Humans, Agora, 11 Medical and Health Sciences, media_common, business.industry, Conflict of interest, Sputum, Payment, Research Letters, Asthma, respiratory tract diseases, Eosinophils, Phenotype, Law, Honorarium, U-BIOPRED study group, Part-time employment, business
Abstract

The Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED) project has described phenotypic differences of severe asthma using a systems biology approach. We obtained three molecular phenotypes termed transcription-associated clusters (TACs) using hierarchical clustering of differentially expressed transcripts between T2-high and T2-low [1]. TAC1 was characterised by receptors IL33R, CCR3 and TSLPR, with the highest enrichment of gene signatures for IL-13/type-2 (T2) inflammation with sputum eosinophilia; TAC2 by inflammasome-associated genes, interferon-α (IFN-α) and tumour necrosis factor-α (TNF-α)-associated genes with sputum neutrophilia; and TAC3 by metabolic and mitochondrial function genes with pauci-granulocytic inflammation. Given that sputum eosinophilia may vary with time in many asthmatic subjects [2, 3], we hypothesised that TAC status may also change with time., At 1 year, 45% of severe asthma change molecular phenotype as determined by sputum transcriptomic analysis. Together with concomitant shift in sputum granulocytic markers, this may indicate variability of driving mechanisms in this unstable group. https://bit.ly/35aj489

Published
2021

23. COVID-19 Disease Map, a computational knowledge repository of virus-host interaction mechanisms (vol 17, e10387, 2021)

Author

Ostaszewski, M, Niarakis, A, Mazein, A, Kuperstein, I, Phair, R, Orta-Resendiz, A, Singh, V, Aghamiri, S, Acencio, M, Glaab, E, Ruepp, A, Fobo, G, Montrone, C, Brauner, B, Frishman, G, Gomez, L, Somers, J, Hoch, M, Gupta, S, Scheel, J, Borlinghaus, H, Czauderna, T, Schreiber, F, Montagud, A, de Leon, M, Funahashi, A, Hiki, Y, Hiroi, N, Yamada, T, Drager, A, Renz, A, Naveez, M, Bocskei, Z, Messina, F, Bornigen, D, Fergusson, L, Conti, M, Rameil, M, Nakonecnij, V, Vanhoefer, J, Schmiester, L, Wang, M, Ackerman, E, Shoemaker, J, Zucker, J, Oxford, K, Teuton, J, Kocakaya, E, Summak, G, Hanspers, K, Kutmon, M, Coort, S, Eijssen, L, Ehrhart, F, Rex, D, Slenter, D, Martens, M, Pham, N, Haw, R, Jassal, B, Matthews, L, Orlic-Milacic, M, Senff-Ribeiro, A, Rothfels, K, Shamovsky, V, Stephan, R, Sevilla, C, Varusai, T, Ravel, J, Fraser, R, Ortseifen, V, Marchesi, S, Gawron, P, Smula, E, Heirendt, L, Satagopam, V, Gm, W, Riutta, A, Golebiewski, M, Owen, S, Goble, C, Xm, H, Overall, R, Maier, D, Bauch, A, Gyori, B, Bachman, J, Vega, C, Groues, V, Vazquez, M, Porras, P, Licata, L, Iannuccelli, M, Sacco, F, Nesterova, A, Yuryev, A, de Waard, A, Turei, D, Luna, A, Babur, O, Soliman, S, Valdeolivas, A, Esteban-Medina, M, Pena-Chilet, M, Rian, K, Helikar, T, Puniya, B, Modos, D, Treveil, A, Olbei, M, De Meulder, B, Ballereau, S, Dugourd, A, Naldi, A, Noel, V, Calzone, L, Sander, C, Demir, E, Korcsmaros, T, Freeman, T, Auge, F, Beckmann, J, Hasenauer, J, Wolkenhauer, O, Willighagen, E, Pico, A, Evelo, C, Gillespie, M, Stein, L, Hermjakob, H, D'Eustachio, P, Saez-Rodriguez, J, Dopazo, J, Valencia, A, Kitano, H, Barillot, E, Auffray, C, Balling, R, and Schneider, R

Subjects
Settore BIO/18, Settore BIO/11
Published
2021

24. P129 - Real-world data analysis of treatment outcomes for patients with metastatic hormone-sensitive prostate cancer: development of a survival prediction model. Results from the European network of excellence for big data in prostate cancer (PIONEER)

Author

Gómez Rivas, J., Nicoletti, R., Golozar, A., Ayman, H., Steinbeißer, C., Ibañez, L., De Meulder, B., Axelsson, S.E., Snijder, R., Feng, Q., Bjartell, A., Cornford, P., Willemse, P., Prinsen, P., Murtola, T.J., and N´dow, J.

Published
2023
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25. P096 - Real-world data analysis of clinical characteristics in metastatic hormone-sensitive prostate cancer: Are patients from RCTs the same from real life? Data from the European network of excellence for big data in prostate cancer (PIONEER).

Author

Gómez Rivas, J., Nicoletti, R., Golozar, A., Steinbeißer, C., De Meulder, B., Snijder, R., Ibañez, L., Axelsson, S.E., Ayman, H., Feng, Q., Murtola, T.J., Bjartell, A., Cornford, P., Willemse, P., Prinsen, P., and N´dow, J.

Published
2023
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27. Towards a European health research and innovation cloud (HRIC)

Author

Aarestrup, F.M. Albeyatti, A. Armitage, W.J. Auffray, C. Augello, L. Balling, R. Benhabiles, N. Bertolini, G. Bjaalie, J.G. Black, M. Blomberg, N. Bogaert, P. Bubak, M. Claerhout, B. Clarke, L. De Meulder, B. D'Errico, G. Di Meglio, A. Forgo, N. Gans-Combe, C. Gray, A.E. Gut, I. Gyllenberg, A. Hemmrich-Stanisak, G. Hjorth, L. Ioannidis, Y. Jarmalaite, S. Kel, A. Kherif, F. Korbel, J.O. Larue, C. Laszlo, M. Maas, A. Magalhaes, L. Manneh-Vangramberen, I. Morley-Fletcher, E. Ohmann, C. Oksvold, P. Oxtoby, N.P. Perseil, I. Pezoulas, V. Riess, O. Riper, H. Roca, J. Rosenstiel, P. Sabatier, P. Sanz, F. Tayeb, M. Thomassen, G. Van Bussel, J. Van Den Bulcke, M. Van Oyen, H.

Abstract

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe. © 2020 The Author(s).

Published
2020

28. Towards a European health research and innovation cloud (HRIC)

Author

Aarestrup, Frank Møller, Albeyatti, A., Armitage, W. J., Auffray, C., Augello, L., Balling, R., Benhabiles, N., Bertolini, G., Bjaalie, J. G., Black, M., Blomberg, N., Bogaert, P., Bubak, M., Claerhout, B., Clarke, L., De Meulder, B., D'Errico, G., Di Meglio, A., Forgo, N., Gans-Combe, C., Gray, A. E., Gut, I., Gyllenberg, A., Hemmrich-Stanisak, G., Hjorth, L., Ioannidis, Y., Jarmalaite, S., Kel, A., Kherif, F., Korbel, J. O., Larue, C., Laszlo, M., Maas, A., Magalhaes, L., Manneh-Vangramberen, I., Morley-Fletcher, E., Ohmann, C., Oksvold, P., Oxtoby, N. P., Perseil, I., Pezoulas, V., Riess, O., Riper, H., Roca, J., Rosenstiel, P., Sabatier, P., Sanz, F., Tayeb, M., Thomassen, G., Van Bussel, J., Van Den Bulcke, M., Van Oyen, H., Aarestrup, Frank Møller, Albeyatti, A., Armitage, W. J., Auffray, C., Augello, L., Balling, R., Benhabiles, N., Bertolini, G., Bjaalie, J. G., Black, M., Blomberg, N., Bogaert, P., Bubak, M., Claerhout, B., Clarke, L., De Meulder, B., D'Errico, G., Di Meglio, A., Forgo, N., Gans-Combe, C., Gray, A. E., Gut, I., Gyllenberg, A., Hemmrich-Stanisak, G., Hjorth, L., Ioannidis, Y., Jarmalaite, S., Kel, A., Kherif, F., Korbel, J. O., Larue, C., Laszlo, M., Maas, A., Magalhaes, L., Manneh-Vangramberen, I., Morley-Fletcher, E., Ohmann, C., Oksvold, P., Oxtoby, N. P., Perseil, I., Pezoulas, V., Riess, O., Riper, H., Roca, J., Rosenstiel, P., Sabatier, P., Sanz, F., Tayeb, M., Thomassen, G., Van Bussel, J., Van Den Bulcke, M., and Van Oyen, H.

Abstract

The European Union (EU) initiative on the Digital Transformation of Health and Care (Digicare) aims to provide the conditions necessary for building a secure, flexible, and decentralized digital health infrastructure. Creating a European Health Research and Innovation Cloud (HRIC) within this environment should enable data sharing and analysis for health research across the EU, in compliance with data protection legislation while preserving the full trust of the participants. Such a HRIC should learn from and build on existing data infrastructures, integrate best practices, and focus on the concrete needs of the community in terms of technologies, governance, management, regulation, and ethics requirements. Here, we describe the vision and expected benefits of digital data sharing in health research activities and present a roadmap that fosters the opportunities while answering the challenges of implementing a HRIC. For this, we put forward five specific recommendations and action points to ensure that a European HRIC: i) is built on established standards and guidelines, providing cloud technologies through an open and decentralized infrastructure; ii) is developed and certified to the highest standards of interoperability and data security that can be trusted by all stakeholders; iii) is supported by a robust ethical and legal framework that is compliant with the EU General Data Protection Regulation (GDPR); iv) establishes a proper environment for the training of new generations of data and medical scientists; and v) stimulates research and innovation in transnational collaborations through public and private initiatives and partnerships funded by the EU through Horizon 2020 and Horizon Europe.

Published
2020

29. Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study

Author

Kolmert, Johan, primary, Gómez, Cristina, additional, Balgoma, David, additional, Sjödin, Marcus, additional, Bood, Johan, additional, Konradsen, Jon R., additional, Ericsson, Magnus, additional, Thörngren, John-Olof, additional, James, Anna, additional, Mikus, Maria, additional, Sousa, Ana R., additional, Riley, John H., additional, Bates, Stewart, additional, Bakke, Per S., additional, Pandis, Ioannis, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fowler, Stephen J., additional, Geiser, Thomas, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Behndig, Annelie, additional, Shaw, Dominick E., additional, Knowles, Richard G., additional, Holweg, Cécile T. J., additional, Wheelock, Åsa M., additional, Dahlén, Barbro, additional, Nordlund, Björn, additional, Alving, Kjell, additional, Hedlin, Gunilla, additional, Chung, Kian Fan, additional, Adcock, Ian M., additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Dahlén, Sven-Erik, additional, Wheelock, Craig E., additional, Ahmed, H., additional, Auffray, C., additional, Bansal, A. T., additional, Bel, E. H., additional, Bigler, J., additional, Billing, B., additional, Baribaud, F., 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, Chaiboonchoe, A., additional, Compton, C. H., additional, Corfield, J., additional, Cunoosamy, D., additional, D’Amico, A., additional, De Meulder, B., additional, Erpenbeck, V. J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L. J., additional, Formaggio, E., additional, Frey, U., additional, Gahlemann, M., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hekking, P. W., additional, Higenbottam, T., additional, Hohlfeld, J. M., additional, Knox, A. J., additional, Lazarinis, 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, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, PuigValls, 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, Sigmund, R., additional, Singer, F., additional, Skipp, P. J., additional, Smicker, M., additional, Sun, K., additional, Thornton, B., additional, Uddin, M., 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, Wilson, S. J., additional, and Östling, J., additional

Published
2021
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30. PIONEER: European Commission Innovative Medicines Initiative funded BD4BO (Big data for better outcome) project on prostate cancer

Author

Evans Axelsson, S., primary, Abbott, T., additional, Fullwood, L., additional, Omar, M.I., additional, Cavelaars, M., additional, Asiimwe, A., additional, Roobol, M., additional, Ribal, M.J., additional, Auffray, C., additional, Devecseri, Z., additional, Smith, E.J., additional, Van Hemelrijck, M., additional, MacLennan, S., additional, Horgan, D., additional, Reich, C., additional, De Meulder, B., additional, Lancet, D., additional, Bangma, C., additional, Briganti, A., additional, Tilki, D., additional, Van Poppel, H., additional, Wirth, M.P., additional, N’Dow, J., additional, and Bjartell, A., additional

Published
2020
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31. 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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32. Stratification of asthma phenotypes by airway proteomic signatures

Author

Schofield, James P. R., Burg, Dominic, Nicholas, Ben, Strazzeri, Fabio, Brandsma, Joost, Staykova, Doroteya, Folisi, Caterina, Bansal, Aruna T., Xian, Yang, Guo, Yike, Rowe, Anthony, Corfield, Julie, Wilson, Susan, Ward, Jonathan, Lutter, Rene, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandstrom, Thomas, Sun, Kai, Pandis, Ioannis, Riley, John, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Sousa, Ana R., Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Skipp, Paul J., Djukanovic, Ratko, Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Batuwitage, M. K., Bedding, A., Behndig, A. F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M. J., Bonnelykke, K., Brinkman, P., Bush, A., Campagna, D., Casaulta, C., Chaiboonchoe, A., Davison, T., De Meulder, B., Delin, I., Dennison, P., Dodson, P., El Hadjam, L., Erzen, D., Faulenbach, C., Fichtner, K., Fitch, N., Formaggio, E., Gahlemann, M., Galffy, G., Garissi, D., Garret, T., Gent, J., Guillmant-Farry, E., Henriksson, E., Hoda, U., Hohlfeld, J. M., Hu, X., James, A., Johnson, K., Jullian, N., Kerry, G., Klueglich, M., Knowles, R., Konradsen, J. R., Kretsos, K., Krueger, L., Lantz, A. -S, Larminie, C., Latzin, P., Lefaudeux, D., Lemonnier, N., Lowe, L. A., Lutter, R., Manta, A., Mazein, A., McEvoy, L., Menzies-Gow, A., Mores, N., Murray, C. S., Nething, K., Nihlen, U., Niven, R., Nordlund, B., Nsubuga, S., Pellet, J., Pison, C., Pratico, G., Puig Valls, M., Riemann, K., Rocha, J. P., Rossios, C., Santini, G., Saqi, M., Scott, S., Sehgal, N., Selby, A., Soderman, P., Sogbesan, A., Spycher, F., Stephan, S., Stokholm, J., Sunther, M., Szentkereszty, M., Tamasi, L., Tariq, K., Valente, S., van Aalderen, W. M., van Drunen, C. M., Van Eyll, J., Vyas, A., Yu, W., Zetterquist, W., Zolkipli, Z., Zwinderman, A. H., Adriaens, Nora, Aliprantis, Antonios, Alving, Kjell, Bakke, Per, Balgoma, David, Barber, Clair, Baribaud, Frederic, Bates, Stewart, Bautmans, An, Beleta, Jorge, Bochenek, Grazyna, Braun, Armin, Carayannopoulos, Leon, Rocha, Joao Pedro Carvalho da Purificacao, Chaleckis, Romanas, D'Amico, Arnaldo, De Alba, Jorge, De Lepeleire, Inge, Dekker, Tamara, Dijkhuis, Annemiek, Draper, Aleksandra, Edwards, Jessica, Emma, Rosalia, Ericsson, Magnus, Flood, Breda, Gallart, Hector, Gomez, Cristina, Gove, Kerry, Gozzard, Neil, Haughney, John, Hewitt, Lorraine, Hohlfeld, Jens, Holweg, Cecile, Hu, Richard, Hu, Sile, Kamphuis, Juliette, Kennington, Erika J., Kerry, Dyson, Knobel, Hugo, Kolmert, Johan, Kots, Maxim, Kuo, Scott, Kupczyk, Maciej, Lambrecht, Bart, Lone-Latif, Saeeda, Loza, Matthew J., Marouzet, Lisa, Martin, Jane, Masefield, Sarah, Mathon, Caroline, Meah, Sally, Meiser, Andrea, Metcalf, Leanne, Mikus, Maria, Miralpeix, Montse, Monk, Philip, Naz, Shama, Nilsson, Peter, Ostling, Jorgen, Pacino, Antonio, Palkonen, Susanna, Pavlidis, Stelios, Pennazza, Giorgio, Petren, Anne, Pink, Sandy, Postle, Anthony, Powell, Pippa, Rahman-Amin, Malayka, Rao, Navin, Ravanetti, Lara, Ray, Emma, Reinke, Stacey, Reynolds, Leanne, Robberechts, Martine, Roberts, Amanda, Russell, Kirsty, Rutgers, Michael, Santoninco, Marco, Schoelch, Corinna, Sjodin, Marcus, Smids, Barbara, Smith, Caroline, Smith, Jessica, Smith, Katherine M., Thorngren, John-Olof, Thornton, Bob, Thorsen, Jonathan, van de Pol, Marianne, van Geest, Marleen, Versnel, Jenny, Vink, Anton, Wald, Frans, Walker, Samantha, Weiszhart, Zsoka, Wetzel, Kristiane, Wheelock, Craig E., Wiegman, Coen, Williams, Sian, Wilson, Susan J., Woodcock, Ashley, Yang, Xian, Yeyasingham, Elizabeth, Prins, Jan-Bas, Gahlemann, Martina, Visintin, Luigi, Evans, Hazel, Puhl, Martine, Buzermaniene, Lina, Hudson, Val, Bond, Laura, de Boer, Pim, Widdershoven, Guy, Sigmund, Ralf, Supple, David, Hamerlijnck, Dominique, Negus, Jenny, Kamphuis, Julitte, Sergison, Lehanne, Onstein, Susanne, MacNee, William, Bernardini, Renato, Bont, Louis, Wecksell, Per-Ake, Graduate School, AII - Inflammatory diseases, Pulmonology, Ear, Nose and Throat, Epidemiology and Data Science, APH - Methodology, Publica, and Commission of the European Communities

Subjects
0301 basic medicine, Male, Proteomics, Allergy, Proteome, Neutrophils, Respiratory Medicine and Allergy, Transcriptome, 0302 clinical medicine, neutrophils, Forced Expiratory Volume, Immunology and Allergy, CD44, 610 Medicine & health, Lungmedicin och allergi, phenotypes, Middle Aged, medicine.anatomical_structure, Phenotype, 1107 Immunology, Female, eosinophils, medicine.symptom, Life Sciences & Biomedicine, Adult, Settore BIO/14 - FARMACOLOGIA, Immunology, Computational biology, 03 medical and health sciences, Young Adult, proteomics, Eosinophilia, medicine, Humans, U-BIOPRED Study Group, Asthma, Aged, Science & Technology, Microarray analysis techniques, business.industry, Sputum, biomarkers, DEGRADATION, Eosinophil, medicine.disease, Eosinophils, EXACERBATIONS, 030104 developmental biology, 030228 respiratory system, business
Abstract

Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies. asthma proteomics biomarkers eosinophils neutrophils

Published
2019

33. 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

34. Morse-clustering of a Topological Data Analysis Network Identifies Phenotypes of Asthma Based on Blood Gene Expression Profiles

Author

Ben D. MacArthur, Ioannis Pandis, Ramanan D, Fabio Strazzeri, Paul Skipp, P. J. Sterk, K.F. Chung, John H. Riley, Jeanette Bigler, Aruna T. Bansal, Richard G. Knowles, Diane Lefaudeux, Craig E. Wheelock, Sven-Erik Dahlén, Charles Auffray, Rubén J. Sánchez-García, Schofield Jpr, Michael Boedigheimer, Ratko Djukanovic, Rob M. Ewing, I.M. Adcock, Kaiyuan Sun, De Meulder B, and Ana R. Sousa

Subjects
Untranslated region, 0303 health sciences, Microarray, Discrete Morse theory, Computational biology, Biology, Phenotype, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Glucocorticoid receptor, 030228 respiratory system, Gene expression, Topological data analysis, Cluster analysis, 030304 developmental biology
Abstract

Stratified medicine requires discretisation of disease populations for targeted treatments. We have developed and applied a discrete Morse theory clustering algorithm to a Topological Data Analysis (TDA) network model of 498 gene expression profiles of peripheral blood from asthma and healthy participants. The Morse clustering algorithm defined nine clusters, BC1-9, representing molecular phenotypes with discrete phenotypes including Type-1, 2 & 17 cytokine inflammatory pathways. The TDA network model and clusters were also characterised by activity of glucocorticoid receptor signalling associated with different expression profiles of glucocorticoid receptor (GR), according to microarray probesets targeted to the start or end of the GR mRNA’s 3’ UTR; suggesting differential GR mRNA processing as a possible driver of asthma phenotypes including steroid insensitivity.

Published
2019

35. 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

36. Asthma Sub-Phenotyping in Plasma from U-BIOPRED and BIOAIR Using Array-Based Proteomics

Author

Mikus, Maria, Kolmert, J., Andersson, L. I., James, A., Gomez, C., Dahlen, B. U., De Meulder, B., Djukanovic, R., Sterk, P. J., Adcock, I. M., Nilsson, Peter, Dahlen, S. K., Mikus, Maria, Kolmert, J., Andersson, L. I., James, A., Gomez, C., Dahlen, B. U., De Meulder, B., Djukanovic, R., Sterk, P. J., Adcock, I. M., Nilsson, Peter, and Dahlen, S. K.

Abstract

QC 20190716

Published
2019

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

Author

Perotin, Jm, Schofield, Jpr, Wilson, Sj, Ward, J, Brandsma, J, Strazzeri, F, Bansal, A, Yang, X, Rowe, A, Corfield, J, Lutter, R, Shaw, De, Bakke, P, Caruso, Massimo, Dahlén, B, Fowler, Sj, Horváth, I, Howarth, P, Krug, N, Montuschi, Paolo, Sanak, M, Sandström, T, Sun, K, Pandis, I, Auffray, C, De Meulder, B, Lefaudeux, D, Riley, Jh, Sousa, Ar, Dahlen, Se, Adcock, Im, Chung, Kf, Sterk, Pj, Skipp, Pj, Collins, Je, Davies, De, Djukanović, R, Montuschi P (ORCID:0000-0001-5589-1750), Perotin, Jm, Schofield, Jpr, Wilson, Sj, Ward, J, Brandsma, J, Strazzeri, F, Bansal, A, Yang, X, Rowe, A, Corfield, J, Lutter, R, Shaw, De, Bakke, P, Caruso, Massimo, Dahlén, B, Fowler, Sj, Horváth, I, Howarth, P, Krug, N, Montuschi, Paolo, Sanak, M, Sandström, T, Sun, K, Pandis, I, Auffray, C, De Meulder, B, Lefaudeux, D, Riley, Jh, Sousa, Ar, Dahlen, Se, Adcock, Im, Chung, Kf, Sterk, Pj, Skipp, Pj, Collins, Je, Davies, De, Djukanović, R, and Montuschi P (ORCID:0000-0001-5589-1750)

Abstract

N/A

Published
2019

39. Stratification of asthma phenotypes by airway proteomic signatures

Author

Schofield, Jpr, Burg, D, Nicholas, B, Strazzeri, F, Brandsma, J, Staykova, D, Folisi, C, Bansal, At, Xian, Y, Guo, Y, Rowe, A, Corfield, J, Wilson, S, Ward, J, Lutter, R, Shaw, De, Bakke, P, Caruso, M, Dahlen, Se, Fowler, Sj, Horváth, I, Howarth, P, Krug, N, Montuschi, Paolo, Sanak, M, Sandström, T, Sun, K, Pandis, I, Riley, J, Auffray, C, De Meulder, B, Lefaudeux, D, Sousa, Ar, Adcock, Im, Chung, Kf, Sterk, Pj, Skipp, Pj, Djukanović, R, Mores, Nadia, Montuschi P (ORCID:0000-0001-5589-1750), Nadia, Mores. (ORCID:0000-0002-4197-0914), Schofield, Jpr, Burg, D, Nicholas, B, Strazzeri, F, Brandsma, J, Staykova, D, Folisi, C, Bansal, At, Xian, Y, Guo, Y, Rowe, A, Corfield, J, Wilson, S, Ward, J, Lutter, R, Shaw, De, Bakke, P, Caruso, M, Dahlen, Se, Fowler, Sj, Horváth, I, Howarth, P, Krug, N, Montuschi, Paolo, Sanak, M, Sandström, T, Sun, K, Pandis, I, Riley, J, Auffray, C, De Meulder, B, Lefaudeux, D, Sousa, Ar, Adcock, Im, Chung, Kf, Sterk, Pj, Skipp, Pj, Djukanović, R, Mores, Nadia, Montuschi P (ORCID:0000-0001-5589-1750), and Nadia, Mores. (ORCID:0000-0002-4197-0914)

Abstract

Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy to predict treatment responses and a need for better understanding of the underlying mechanisms. Objective: Identify molecular sub-phenotypes of asthma defined by proteomic signatures for improved stratification. Methods:Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyse the proteomes of sputum supernatants from 246 participants (206 asthmatics) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters, proteotypes, based on similarity in proteomics features, representing discrete molecular sub-phenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined three of these as highly eosinophilic, three as highly neutrophilic, and two as highly atopic with relatively low granulocytic inflammation. For each of these three phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified by quantifying granulocytic inflammation and gives additional insight into their underlying mechanisms which could become targets for novel therapies

Published
2019

40. Identification and prospective stability of electronic nose (eNose)-derived inflammatory phenotypes in patients with severe asthma

Author

Brinkman, P, Wagener, Ah, Hekking, Pp, Bansal, At, Maitland-van der Zee, Ah, Wang, Y, Weda, H, Knobel, Hh, Vink, Tj, Rattray, Nj, D'Amico, Arnaldo, Pennazza, G, Santonico, M, Lefaudeux, D, De Meulder, B, Auffray, C, Bakke, P, Caruso, Massimo, Chanez, P, Chung, Kf, Corfield, J, Dahlén, Se, Djukanovic, R, Geiser, T, Horvath, I, Krug, N, Musial, J, Sun, K, Riley, Jh, Shaw, De, Sandström, T, Sousa, Ar, Montuschi, Paolo, Fowler, Sj, Sterk, Pj, Montuschi P (ORCID:0000-0001-5589-1750), Brinkman, P, Wagener, Ah, Hekking, Pp, Bansal, At, Maitland-van der Zee, Ah, Wang, Y, Weda, H, Knobel, Hh, Vink, Tj, Rattray, Nj, D'Amico, Arnaldo, Pennazza, G, Santonico, M, Lefaudeux, D, De Meulder, B, Auffray, C, Bakke, P, Caruso, Massimo, Chanez, P, Chung, Kf, Corfield, J, Dahlén, Se, Djukanovic, R, Geiser, T, Horvath, I, Krug, N, Musial, J, Sun, K, Riley, Jh, Shaw, De, Sandström, T, Sousa, Ar, Montuschi, Paolo, Fowler, Sj, Sterk, Pj, and Montuschi P (ORCID:0000-0001-5589-1750)

Abstract

Background: Severe asthma is a heterogeneous condition, as shown by independent cluster analyses based on demographic, clinical, and inflammatory characteristics. A next step is to identify molecularly driven phenotypes using “omics” technologies. Molecular fingerprints of exhaled breath are associated with inflammation and can qualify as noninvasive assessment of severe asthma phenotypes. Objectives: We aimed (1) to identify severe asthma phenotypes using exhaled metabolomic fingerprints obtained from a composite of electronic noses (eNoses) and (2) to assess the stability of eNose-derived phenotypes in relation to within-patient clinical and inflammatory changes. Methods: In this longitudinal multicenter study exhaled breath samples were taken from an unselected subset of adults with severe asthma from the U-BIOPRED cohort. Exhaled metabolites were analyzed centrally by using an assembly of eNoses. Unsupervised Ward clustering enhanced by similarity profile analysis together with K-means clustering was performed. For internal validation, partitioning around medoids and topological data analysis were applied. Samples at 12 to 18 months of prospective follow-up were used to assess longitudinal within-patient stability. Results: Data were available for 78 subjects (age, 55 years [interquartile range, 45-64 years]; 41% male). Three eNose-driven clusters (n = 26/33/19) were revealed, showing differences in circulating eosinophil (P =.045) and neutrophil (P =.017) percentages and ratios of patients using oral corticosteroids (P =.035). Longitudinal within-patient cluster stability was associated with changes in sputum eosinophil percentages (P =.045). Conclusions: We have identified and followed up exhaled molecular phenotypes of severe asthma, which were associated with changing inflammatory profile and oral steroid use. This suggests that breath analysis can contribute to the management of severe asthma

Published
2019

43. 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

44. 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

45. 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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47. 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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48. Host Transcription Profile In Nasal Epithelium And Whole Blood of Hospitalised Children under two years of age with Respiratory Syncytial Virus Infection

Author

Do, LAH, Pellet, J, van Doorn, HR, Tran, AT, Nguyen, BH, Tran, TTL, Tran, QH, Vo, QB, Tran Dac, NA, Trinh, HN, Nguyen, TTH, Le Binh, BT, Nguyen, HMK, Nguyen, MT, Thai, QT, Vo, TV, Ngo, NQM, Dang, TKH, Cao, NH, Tran, TV, Ho, LV, De Meulder, B, Auffray, C, Hofstra, JJ, Farrar, J, Bryant, JE, de Jong, M, and Hibberd, ML

Abstract

Most insights into the cascade of immune events following acute respiratory syncytial virus (RSV) infection have been obtained from animal experiments or in vitro models. Here we investigated host gene expression profiles in nasopharyngeal swabs (NP) and whole blood samples during natural RSV and rhinovirus (hRV) infection (acute versus early recovery phase) in 83 hospitalised patients

Published
2017

49. Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma

Author

Hekking, PP, Loza, MJ, Pavlidis, S, De Meulder, B, Lefaudeux, D, Baribaud, F, Auffray, C, Wagener, AH, Brinkman, P, Lutter, R, Bansal, AT, Sousa, AR, Bates, S, Pandis, Y, Fleming, LJ, Shaw, DE, Fowler, SJ, Guo, Y, Meiser, A, Sun, K, Corfield, J, Howarth, P, Bel, EH, Adcock, IM, Chung, KF, Djukanovic, R, Sterk, PJ, U-BIOPRED Study Group, Pulmonology, AII - Inflammatory diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, and ARD - Amsterdam Reproduction and Development

Subjects
Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Sputum Cytology, Vital capacity, Bronchoconstriction, Respiratory System, Vital Capacity, Bronchi, Severity of Illness Index, Transcriptome, Leukocyte Count, 03 medical and health sciences, 0302 clinical medicine, Forced Expiratory Volume, Gene expression, Journal Article, medicine, Humans, Prospective Studies, Respiratory system, Prospective cohort study, U-BIOPRED Study Group, Aged, Netherlands, Interleukin-13, business.industry, Gene Expression Profiling, Sputum, 11 Medical And Health Sciences, Middle Aged, respiratory system, Asthma, respiratory tract diseases, Eosinophils, Gene expression profiling, Cross-Sectional Studies, 030104 developmental biology, 030228 respiratory system, Immunology, Female, medicine.symptom, business, Biomarkers
Abstract

Rationale: A proportion of severe asthma patients suffers fro m persistent airflow limitation, often associated with more symptoms and exacerbations . Little is known about the underlying mechanisms. Aiming for discovery of unexplored potential mechanisms, we used Gene Set Variation Analysis (GSVA), a sensitive technique that can detect underlying pathways in heterogeneous samples. Methods: Severe asthma patients from the U -BIOPRED cohort with persistent airflow limitation (post -bronchodilator FEV 1 /FVC ratio < lower limit of normal) were compared to those without persistent airflow limitation. Gene expression was assessed on the total RNA of sputum cells, nasal brushin gs and endobronchial brushings and biopsies. GSVA was applied to identify differentially - enriched pre -defined gene signatures based on all available gene expression publications and data on airways disease. Results: Differentially -enriched gene signatures were identified in nasal brushings (1), sputum (9), bronchial brushings (1) and bronchial biopsies (4), that were associated with response to inhaled steroids, eosinophils, IL -13, IFN -alpha, specific CD4+ T -cells and airway remodeling. Conclusion: Persiste nt airflow limitation in severe asthma has distinguishable underlying gene networks that are associated with treatment, inflammatory pathways and airway remodeling. These results point towards targets for the therapy of persistent airflow limitation in sev ere asthma.

Published
2017

50. A transcriptome-driven analysis of epithelial brushings and bronchial biopsies to define asthma phenotypes in U-BIOPRED

Author

Kuo, CS, Pavlidis, S, Loza, M, Baribaud, F, Rowe, A, Pandis, I, Hoda, U, Rossios, C, Sousa, A, Wilson, SJ, Howarth, P, Dahlen, B, Dahlen, SE, Chanez, P, Shaw, D, Krug, N, Sandström, T, De Meulder, B, Lefaudeux, D, Fowler, S, Fleming, L, Corfield, J, Auffray, C, Sterk, PJ, Djukanovic, R, Guo, Y, Adcock, IM, Chung, KF, U-BIOPRED Project Team, Commission of the European Communities, Medical Research Council (MRC), National Institute for Health Research, Publica, AII - Inflammatory diseases, and Pulmonology

Subjects
0301 basic medicine, Male, Pathology, Biopsy, Respiratory System, Drug Resistance, HUMAN AIRWAY, Critical Care and Intensive Care Medicine, Severity of Illness Index, Transcriptome, Cohort Studies, U-BIOPRED Project Team ‡, Leukocyte Count, 0302 clinical medicine, Adrenal Cortex Hormones, OXIDATIVE STRESS, INTERLEUKIN-5, 11 Medical and Health Sciences, GENE-EXPRESSION, medicine.diagnostic_test, T-helper type 2, Middle Aged, gene set variation analysis, Phenotype, Breath Tests, Female, medicine.symptom, Life Sciences & Biomedicine, Pulmonary and Respiratory Medicine, severe asthma, Adult, medicine.medical_specialty, T-helpertype 2, corticosteroid insensitivity, Inflammation, Bronchi, 03 medical and health sciences, Th2 Cells, Critical Care Medicine, MICROARRAY, General & Internal Medicine, Bronchoscopy, medicine, Humans, Interleukin 5, Asthma, CLUSTER-ANALYSIS, Science & Technology, business.industry, Gene Expression Profiling, CYTOKINES, Sputum, medicine.disease, respiratory tract diseases, Gene expression profiling, CLINICAL PHENOTYPES, Eosinophils, 030104 developmental biology, 030228 respiratory system, Exhaled nitric oxide, Immunology, CELLS, exhaled nitric oxide, business, Biomarkers
Abstract

Rationale: Asthma is a heterogeneous disease driven by diverse immunologic and inflammatory mechanisms. Objectives: Using transcriptomic profiling of airway tissues, we sought to define the molecular phenotypes of severe asthma. Methods: The transcriptome derived from bronchial biopsies and epithelial brushings of 107 subjects with moderate to severe asthma were annotated by gene set variation analysis using 42 gene signatures relevant to asthma, inflammation, and immune function. Topological data analysis of clinical and histologic data was performed to derive clusters, and the nearest shrunken centroid algorithm was used for signature refinement. Measurements and Main Results: Nine gene set variation analysis signatures expressed in bronchial biopsies and airway epithelial brushings distinguished two distinct asthma subtypes associated with high expression of T-helper cell type 2 cytokines and lack of corticosteroid response (group 1 and group 3). Group 1 had the highest submucosal eosinophils, as well as high fractional exhaled nitric oxide levels, exacerbation rates, and oral corticosteroid use, whereas group 3 patients showed the highest levels of sputum eosinophils and had a high body mass index. In contrast, group 2 and group 4 patients had an 86% and 64% probability, respectively, of having noneosinophilic inflammation. Using machine learning tools, we describe an inference scheme using the currently available inflammatory biomarkers sputum eosinophilia and fractional exhaled nitric oxide levels, along with oral corticosteroid use, that could predict the subtypes of gene expression within bronchial biopsies and epithelial cells with good sensitivity and specificity. Conclusions: This analysis demonstrates the usefulness of a transcriptomics-driven approach to phenotyping that segments patients who may benefit the most from specific agents that target T-helper cell type 2-mediated inflammation and/or corticosteroid insensitivity.

Published
2017

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