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109 results on '"Erzen, D."'

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. 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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3. 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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4. 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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5. 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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6. 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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8. 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

10. 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

12. 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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13. Patrones de progresión de la actividad física en pacientes con EPOC

Author

Koreny, M, Demeyer, H, Benet, M, Arbillaga-Etxarri, A, Balcells, E, Barberan-Garcia, A, Gimeno-Santos, E, Hopkinson, NS, De Jong, C, Karlsson, N, Louvaris, Z, Polkey, MI, Puhan, MA, Rabinovich, RA, Rodríguez-Roisin, R, Vall-Casas, P, Vogiatzis, I, Troosters, T, Garcia-Aymerich, J, Urban Training Study Group and PROactive Consortium members, Urban Training Study Group, Delgado, A, Torrent-Pallicer, J, Vilaró, J, Chiaradía, DAR, Marín, A, Ortega, P, Celorrio, N, Teagudo, MM, Montellà, N, Muñoz, L, Toran, P, Simonet, P, Jané, C, Martín-Cantera, C, Borrell, E, PROactive Consortium members, Ivanoff, N, Corriol-Rohou, S, Jarrod, I, Erzen, D, Brindicci, C, Higenbottam, T, Scuri, M, McBride, P, Kamel, N, Tabberer, M, Dobbels, F, De Boer, P, Kulich, K, Glendenning, A, Rudell, K, Wilson, FJ, Nikai, E, Van der Molen, T, MacNee, B, Frei, A, Groningen Research Institute for Asthma and COPD (GRIAC), and EU/IMI Joint Undertaking

Subjects
Male, PROactive Consortium members, Respiratory System, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Medicine and Health Sciences, Pooled data, Determinants, COPD, biology, Patrones de progresión, General Medicine, Lama, Análisis de conglomerados, Respiratory Function Tests, MPOC, Female, EPOC, Determinantes, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Patrons de progressió, Physical activity, 616.2, 03 medical and health sciences, FEV1/FVC ratio, Cluster analysis, Multinomial logistic regression model, Internal medicine, Urban Training Study Group, medicine, Humans, Anàlisi de clústers, In patient, Exercise, Patterns of progression, business.industry, 1103 Clinical Sciences, medicine.disease, biology.organism_classification, C600, Urban Training Study Group and PROactive Consortium members, B900, Dyspnea, 030228 respiratory system, Usual care, Actividad física, Sedentary Behavior, Activitat física, business
Abstract

Introduction: Although mean physical activity in COPD patients declines by 400–500 steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants. Methods: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns. Results: In 291 COPD patients (mean ± SD 68 ± 8 years, 81% male, FEV1 59 ± 19%pred) we identified three distinct physical activity progression patterns: Inactive (n = 173 [59%], baseline: 4621 ± 1757 steps/day, 12-month change (Δ): −487 ± 1201 steps/day), Active Improvers (n = 49 [17%], baseline: 7727 ± 3275 steps/day, Δ: + 3378 ± 2203 steps/day) and Active Decliners (n = 69 [24%], baseline: 11 267 ± 3009 steps/day, Δ: −2217 ± 2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90–0.98] per 10 m, P = .001) and a higher mMRC dyspnea score (1.71 [1.12–2.60] per 1 point, P = .012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver. Conclusions: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline. Introducción: Aunque la actividad física en pacientes con EPOC declina una media anual de 400-500 pasos/día, se desconoce si esta progresión es igual en todos los pacientes. Este estudio pretendió identificar los patrones de progresión de la actividad física mediante métodos libres de hipótesis y evaluar sus determinantes. Métodos: Se estudiaron 291 pacientes con EPOC estable (media ± DE: 68 ± 8 años, 81% hombres, VEMS 59 ± 19%pred) de dos cohortes europeas con actividad física basal y a 12 meses (acelerómetro Dynaport MoveMonitor). Se identificaron conglomerados (patrones) de progresión de actividad física basados en los niveles y cambios de pasos/día usando k-means, y se compararon entre patrones las características sociodemográficas, interpersonales, ambientales, clínicas y psicosociales basales. Resultados: Se identificaron tres patrones: inactivo (n = 173 [59%], basal: 4.621 ± 1.757 pasos/día, cambio en 12 meses (Δ): −487 ± 1.201 pasos/día), activo que aumenta (n = 49 [17%], basal: 7.727 ± 3.275 pasos/día, Δ: +3.378 ± 2.203 pasos/día) y activo que reduce (n = 69 [24%], basal: 11.267 ± 3.009 pasos/día, Δ: −2.217 ± 2.085 pasos/día). La distancia en la prueba de la marcha de 6 minutos (6MWD) y la disnea se asociaron independientemente con ser inactivo: RRR [IC 95%] 0,94 [0,90-0,98] por cada 10 m de 6MWD (p = 0,001) y 1,71 [1,12-2,60] por cada punto en la escala mMRC (p = 0,012), respectivamente, en comparación con el patrón activo que reduce. No se encontraron variables basales independientemente asociadas con ser activo que aumenta. Conclusiones: La progresión natural de la actividad física en pacientes con EPOC es heterogénea. Mientras que el patrón de pacientes inactivo se relaciona con peores características clínicas de EPOC, no se pudo predecir la evolución de los activos a aumentar o reducir. info:eu-repo/semantics/acceptedVersion

Published
2021

14. Patient-reported outcomes in adults with type 1 diabetes in global real-world clinical practice: the SAGE study

Author

Wilmot E, Close K, Jurisic-Erzen D, Bruttomesso D, Ampudia-Blasco F, Bosnyak Z, de Climens A, Bigot G, Peters A, Renard E, Berard L, Calliari L, and Seufert J

Abstract

AIMS: This secondary analysis of the SAGE study aimed to evaluate the association between glycaemic control and patient-reported outcomes (PROs), in adults with type 1 diabetes (T1DM) across different age groups and regions. MATERIALS AND METHODS: SAGE was a multinational, cross-sectional, observational study in adults with T1DM. Data were collected at a single visit, analysed according to predefined age groups (26-44, 45-64, and =65years), and reported across different regions. PRO questionnaires were applied to assess hypoglycaemia fear (Hypoglycemia Fear Survey-II [HFS-II]), diabetes-related distress (Problem Areas In Diabetes [PAID]), insulin treatment satisfaction (Insulin Treatment Satisfaction Questionnaire [ITSQ]), and diabetes-specific quality of life (Audit of Diabetes Dependent Quality of Life [ADDQoL]). Multivariable analysis was performed to evaluate the relationship between HbA1c target achievement (

Published
2021

15. Patterns of Physical Activity Progression in Patients With COPD [Patrones de progresión de la actividad física en pacientes con EPOC]

Author

Koreny, M. Demeyer, H. Benet, M. Arbillaga-Etxarri, A. Balcells, E. Barberan-Garcia, A. Gimeno-Santos, E. Hopkinson, N.S. De Jong, C. Karlsson, N. Louvaris, Z. Polkey, M.I. Puhan, M.A. Rabinovich, R.A. Rodríguez-Roisin, R. Vall-Casas, P. Vogiatzis, I. Troosters, T. Garcia-Aymerich, J. Delgado, A. Torrent-Pallicer, J. Vilaró, J. Rodriguez-Roisín, R. Chiaradía, D.A.R. Marín, A. Ortega, P. Celorrio, N. Monteagudo, M. Montellà, N. Muñoz, L. Toran, P. Simonet, P. Jané, C. Martín-Cantera, C. Borrell, E. Ivanoff, N. Corriol-Rohou, S. Jarrod, I. Erzen, D. Brindicci, C. Higenbottam, T. Scuri, M. McBride, P. Kamel, N. Tabberer, M. Dobbels, F. de Boer, P. Kulich, K. Glendenning, A. Rudell, K. Wilson, F.J. Hopkinson, N.S. Nikai, E. van der Molen, T. MacNee, B. Frei, A. The Urban Training Study Group PROactive Consortium members The Urban Training Study Group The PROactive Consortium members

Abstract

Introduction: Although mean physical activity in COPD patients declines by 400–500 steps/day annually, it is unknown whether the natural progression is the same for all patients. We aimed to identify distinct physical activity progression patterns using a hypothesis-free approach and to assess their determinants. Methods: We pooled data from two cohorts (usual care arm of Urban Training [NCT01897298] and PROactive initial validation [NCT01388218] studies) measuring physical activity at baseline and 12 months (Dynaport MoveMonitor). We identified clusters (patterns) of physical activity progression (based on levels and changes of steps/day) using k-means, and compared baseline sociodemographic, interpersonal, environmental, clinical and psychological characteristics across patterns. Results: In 291 COPD patients (mean ± SD 68 ± 8 years, 81% male, FEV1 59 ± 19%pred) we identified three distinct physical activity progression patterns: Inactive (n = 173 [59%], baseline: 4621 ± 1757 steps/day, 12-month change (Δ): −487 ± 1201 steps/day), Active Improvers (n = 49 [17%], baseline: 7727 ± 3275 steps/day, Δ: + 3378 ± 2203 steps/day) and Active Decliners (n = 69 [24%], baseline: 11 267 ± 3009 steps/day, Δ: −2217 ± 2085 steps/day). After adjustment in a mixed multinomial logistic regression model using Active Decliners as reference pattern, a lower 6-min walking distance (RRR [95% CI] 0.94 [0.90–0.98] per 10 m, P =.001) and a higher mMRC dyspnea score (1.71 [1.12–2.60] per 1 point, P =.012) were independently related with being Inactive. No baseline variable was independently associated with being an Active Improver. Conclusions: The natural progression in physical activity over time in COPD patients is heterogeneous. While Inactive patients relate to worse scores for clinical COPD characteristics, Active Improvers and Decliners cannot be predicted at baseline. © 2020 SEPAR

Published
2021

16. Validity and responsiveness of the Daily-and Clinical visit-PROactive Physical Activity in COPD (D-PPAC and C-PPAC) instruments

Author

Garcia-Aymerich, J. Puhan, M.A. Corriol-Rohou, S. De Jong, C. Demeyer, H. Dobbels, F. Erzen, D. Frei, A. Gimeno-Santos, E. Hopkinson, N.S. Ivanoff, N. Karlsson, N. Louvaris, Z. Polkey, M.I. Rabinovich, R.A. Scuri, M. Tabberer, M. Vogiatzis, I. Troosters, T.

Abstract

Background The Daily-PROactive and Clinical visit-PROactive Physical Activity (D-PPAC and C-PPAC) instruments in chronic obstructive pulmonary disease (COPD) combines questionnaire with activity monitor data to measure patients' experience of physical activity. Their amount, difficulty and total scores range from 0 (worst) to 100 (best) but require further psychometric evaluation. Objective To test reliability, validity and responsiveness, and to define minimal important difference (MID), of the D-PPAC and C-PPAC instruments, in a large population of patients with stable COPD from diverse severities, settings and countries. Methods We used data from seven randomised controlled trials to evaluate D-PPAC and C-PPAC internal consistency and construct validity by sex, age groups, COPD severity, country and language as well as responsiveness to interventions, ability to detect change and MID. Results We included 1324 patients (mean (SD) age 66 (8) years, forced expiratory volume in 1 s 55 (17)% predicted). Scores covered almost the full range from 0 to 100, showed strong internal consistency after stratification and correlated as a priori hypothesised with dyspnoea, health-related quality of life and exercise capacity. Difficulty scores improved after pharmacological treatment and pulmonary rehabilitation, while amount scores improved after behavioural physical activity interventions. All scores were responsive to changes in self-reported physical activity experience (both worsening and improvement) and to the occurrence of COPD exacerbations during follow-up. The MID was estimated to 6 for amount and difficulty scores and 4 for total score. Conclusions The D-PPAC and C-PPAC instruments are reliable and valid across diverse COPD populations and responsive to pharmacological and non-pharmacological interventions and changes in clinically relevant variables. © Author(s) (or their employer(s)) 2021.

Published
2021

19. 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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20. 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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22. 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., Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, 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., Djukanovi?, Ratko, Ahmed, H., Allen, D., Badorrek, P., Ballereau, S., Baribaud, F., Bedding, A., Behndig, A. F., Berglind, A., Berton, A., Bigler, J., Boedigheimer, M. J., 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., 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., and Nething, K.

Abstract

© 2019 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.

Published
2019

23. 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

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

Author

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

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

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

Published
2019
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25. 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, 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, and Wecksell, Per-Ake

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.

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

Author

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

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

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

Published
2018
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28. Empagliflozin and Kidney Function Decline in Patients with Type 2 Diabetes: A Slope Analysis from the EMPA-REG OUTCOME Trial

Author

Wanner, Christoph, Heerspink, Hiddo J. L., Zinman, Bernard, Inzucchi, Silvio E., Koitka-Weber, Audrey, Mattheus, Michaela, Hantel, Stefan, Woerle, Hans-Juergen, Broedl, Uli C., von Eynatten, Maximilian, Groop, Per-Henrik, Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, Luc, Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, Katrien, Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., Magee, M., Hippert, R., Sofley, C., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Kidney Center (GKC), Methods in Medicines evaluation & Outcomes research (M2O), and EMPA-REG OUTCOME Investigators

Subjects
Male, Placebo-controlled study, PROGRESSION, Type 2 diabetes, 030204 cardiovascular system & hematology, PLACEBO-CONTROLLED TRIAL, GLOMERULAR-FILTRATION-RATE, HYPERFILTRATION, law.invention, ESTABLISHED CARDIOVASCULAR-DISEASE, Cohort Studies, MELLITUS, 0302 clinical medicine, Randomized controlled trial, Glucosides, law, Medicine, Diabetic Nephropathies, GFR DECLINE, General Medicine, Middle Aged, Nephrology, diabetes mellitus, randomized controlled trials, Disease Progression, Female, Glomerular Filtration Rate, medicine.medical_specialty, Urology, Renal function, 030209 endocrinology & metabolism, Placebo, 03 medical and health sciences, Double-Blind Method, Clinical Research, Diabetes mellitus, BASE-LINE CHARACTERISTICS, END-POINTS, Empagliflozin, Humans, Benzhydryl Compounds, Sodium-Glucose Transporter 2 Inhibitors, Aged, COTRANSPORTER 2 INHIBITION, Models, Statistical, Dose-Response Relationship, Drug, business.industry, chronic kidney disease, medicine.disease, Confidence interval, Diabetes Mellitus, Type 2, Human medicine, business
Abstract

BACKGROUND: Empagliflozin slowed the progression of CKD in patients with type 2 diabetes and cardiovascular disease in the EMPA-REG OUTCOME Trial. In a prespecified statistical approach, we assessed treatment differences in kidney function by analyzing slopes of eGFR changes.METHODS: Participants (n=7020) were randomized (1:1:1) to empagliflozin 10 mg/d, empagliflozin 25 mg/d, or placebo added to standard of care. We calculated eGFR slopes using random-intercept/random-coefficient models for prespecified study periods: treatment initiation (baseline to week 4), chronic maintenance treatment (week 4 to last value on treatment), and post-treatment (last value on treatment to follow-up).RESULTS: Compared with placebo, empagliflozin was associated with uniform shifts in individual eGFR slopes across all periods. On treatment initiation, adjusted mean slope (eGFR change per week, ml/min per 1.73 m2) decreased with empagliflozin (-0.77; 95% confidence interval, -0.83 to -0.71; placebo: 0.01; 95% confidence interval, -0.08 to 0.10; PCONCLUSIONS: The hemodynamic effects of empagliflozin, associated with reduction in intraglomerular pressure, may contribute to long-term preservation of kidney function.

Published
2018

29. Both moderate and severe exacerbations accelerate physical activity decline in COPD patients

Author

Demeyer, H. Costilla-Frias, M. Louvaris, Z. Gimeno-Santos, E. Tabberer, M. Rabinovich, R.A. De Jong, C. Polkey, M.I. Hopkinson, N.S. Karlsson, N. Serra, I. Vogiatzis, I. Troosters, T. Garcia-Aymerich, J. Ivanoff, N. Karlsson, N. Corriol-Rohou, S. Jarrod, I. Erzen, D. Scuri, M. Montacchini, R. McBride, P. Kamel, N. Tabberer, M. Troosters, T. Janssens, W. Demeyer, H. Dobbels, F. De Boer, P. Kulich, K. Polkey, M.I. Hopkinson, N.S. Vogiatzis, I. Nikai, E. Van Der Molen, T. De Jong, C. Rabinovich, R.A. MacNee, B. Puhan, M.A. Frei, A.

Published
2018

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

Author

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

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

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

Published
2018
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31. 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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32. 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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34. Empagliflozin and Cerebrovascular Events in Patients With Type 2 Diabetes Mellitus at High Cardiovascular Risk

Author

Zinman, Bernard, Inzucchi, Silvio E., Lachin, John M., Wanner, Christoph, Fitchett, David, Kohler, Sven, Mattheus, Michaela, Biomath, Dipl, Woerle, Hans J., Broedl, Uli C., Johansen, Odd Erik, Albers, Gregory W., Diener, Hans Christoph, Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, L., Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, K., Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., III, Magee, M., Hippert, R., Sofley, C., Jr., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Jr., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., III, Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., and EMPA REG OUTCOME Investigators

Subjects
riesgo, compuestos de bencidrilo, type 2 diabetes mellitus, Original Contributions, humanos, Medizin, 030204 cardiovascular system & hematology, blood pressure, cardiovascular diseases, hematocrit, stroke, 0302 clinical medicine, Glucosides, glucósidos, 030212 general & internal medicine, Myocardial infarction, Stroke, mediana edad, anciano, OUTCOMES, Hazard ratio, Middle Aged, ISCHEMIC-STROKE, Anesthesia, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Cardiology, TRIAL, Cardiology and Cardiovascular Medicine, Life Sciences & Biomedicine, Risk, medicine.medical_specialty, Clinical Sciences, enfermedades cardiovasculares, Clinical Neurology, Placebo, 03 medical and health sciences, Outcome Assessment (Health Care), Internal medicine, medicine, Empagliflozin, Diabetes Mellitus, Humans, Hypoglycemic Agents, accidente cerebrovascular, Benzhydryl Compounds, METAANALYSIS, Aged, Advanced and Specialized Nursing, Science & Technology, business.industry, MORTALITY, Type 2 Diabetes Mellitus, medicine.disease, Confidence interval, Blood pressure, hipoglicemiantes, Peripheral Vascular Disease, evaluación de resultados (asistencia sanitaria), Cardiovascular System & Cardiology, Neurology (clinical), Neurosciences & Neurology, business, FOLLOW-UP
Abstract

Supplemental Digital Content is available in the text., Background and Purpose— In the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), empagliflozin added to standard of care in patients with type 2 diabetes mellitus and high cardiovascular risk reduced the risk of 3-point major adverse cardiovascular events, driven by a reduction in cardiovascular mortality, with no significant difference between empagliflozin and placebo in risk of myocardial infarction or stroke. In a modified intent-to-treat analysis, the hazard ratio for stroke was 1.18 (95% confidence interval, 0.89–1.56; P=0.26). We further investigated cerebrovascular events. Methods— Patients were randomized to empagliflozin 10 mg, empagliflozin 25 mg, or placebo; 7020 patients were treated. Median observation time was 3.1 years. Results— The numeric difference in stroke between empagliflozin and placebo in the modified intent-to-treat analysis was primarily because of 18 patients in the empagliflozin group with a first event >90 days after last intake of study drug (versus 3 on placebo). In a sensitivity analysis based on events during treatment or ≤90 days after last dose of drug, the hazard ratio for stroke with empagliflozin versus placebo was 1.08 (95% confidence interval, 0.81–1.45; P=0.60). There were no differences in risk of recurrent, fatal, or disabling strokes, or transient ischemic attack, with empagliflozin versus placebo. Patients with the largest increases in hematocrit or largest decreases in systolic blood pressure did not have an increased risk of stroke. Conclusions— In patients with type 2 diabetes mellitus and high cardiovascular risk, there was no significant difference in the risk of cerebrovascular events with empagliflozin versus placebo. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01131676.

Published
2017

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

Author

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

Published
2018
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37. Heart failure outcomes with empagliflozin in patients with type 2 diabetes at high cardiovascular risk: results of the EMPA-REG OUTCOME (R) trial

Author

Fitchett, David, Zinman, Bernard, Wanner, Christoph, Lachin, John M., Hantel, Stefan, Salsali, Afshin, Johansen, Odd Erik, Woerle, Hans J., Broedl, Uli C., Inzucchi, Silvio E., Aizenberg, D., Ulla, M., Waitman, J., De Loredo, L., Farias, J., Fideleff, H., Lagrutta, M., Maldonado, N., Colombo, H., Ferre Pacora, F., Wasserman, A., Maffei, L., Lehman, R., Selvanayagam, J., d'Emden, M., Fasching, P., Paulweber, B., Toplak, H., Luger, A., Drexel, H., Prager, R., Schnack, C., Schernthaner, G., Fliesser-Goerzer, E., Kaser, S., Scheen, A., Van Gaal, L., Hollanders, G., Kockaerts, Y., Capiau, L., Chachati, A., Persu, A., Hermans, M., Vantroyen, D., Vercammen, C., Van de Borne, P., Mathieu, C., Benhalima, K., Lienart, F., Mortelmans, J., Strivay, M., Vereecken, G., Keymeulen, B., Lamkanfi, F., Chacra, A., Eliaschewitz, F., Zanella, M., Faludi, A., Bertolami, M., Hayashida, C., Nunes Salles, J., Monte, O., Dinato, M., Manenti, E., Rassi, N., Halpern, A., Lima Filho, M., Ayoub, J., Felicio, J., Borges, J., Gross, J., Sgarbi, J., Betti, R., Tiburcio, A., Purisch, S., Schmid, H., Takahashi, M., Castro, M., Rea, R., Hissa, M., Geloneze Neto, B., Saraiva, J., Henein, S., Lochnan, H., Imran, S. A., Clayton, D., Bayly, K., Berlingieri, J., Boucher, P., Chan, Y., Gupta, M., Chehayeb, R., Ouellett, A., Ur, E., Woo, V., Zinman, B., St Amour, E., Terront Lozano, M., Yupanqui Lozno, H., Urina, M., Lopez Jaramillo, P., Jaramillo, N., Sanchez, G., Perez, G., Tusek, S., Mirosevic, G., Goldoni, V., Jurisic-Erzen, D., Balasko, A., Balic, S., Drvodelic-Sunic, E., Varzic, S. Canecki, Machkova, M., Weiner, P., Lastuvka, J., Olsovsky, J., Krarup, T., Ridderstrale, M., Tarnow, L., Boesgaard, T. Wellov, Lihn, A. Saetre, Christensen, P., Juhl, H., Urhammer, S., Lund, P., Adojaan, B., Jakovlev, U., Lanno, R., Lubi, M., Marandi, T., Gouet, D., Courreges, J., Zaoui, P., Choukroun, G., Petit, C., Formagne, L., Estour, B., Mabire, P., Daugenet, C., Lemarie, B., Clavel, S., Aure, P., Remaud, P., Halimi, J., Hadjadj, S., Couffinhal, T., Glonti, S., Metreveli, D., Lominadze, Z., Giorgadze, E., Burtchuladze, T., Javashvili, L., Kurashvili, G., Kurashvili, R., Virsaladze, D., Nadareishvili, L., Khomasuridze, A., Cahill, T., Green, F., MacRury, S., Waldron, M., Middleton, A., McKnight, J., Pearson, E., Butler, M., Choksi, M., Caldwell, I., Farmer, I., Wyatt, N., Patrick, J., O'Brien, I., Devers, M., Bousboulas, S., Pappas, S., Piaditis, G., Vryonidou, A., Tentolouris, N., Karamitsos, K., Manes, C., Benroubi, M., Avramidis, I., Ozaki, R., Tan, K., Siu, S., Tsang, C., Dudas, M., Nagy, K., Salamon, C., Ip, T., Geroo, L., Patkay, J., Tabak, A., Juhasz, F., Szentpeteri, I., Tamas, G., Ghaisas, N., Bantwal, G., Mohan, V., Gupta, J., Sadhu, N., Kulkarni, A., Garg, N., Reddy, S., Deshpande, N., Gutlapalli, K., Pillai, M., Premchand, R., Badgandi, M., Jain, S., Aravind, S., Shamanna, P., Pandey, A., Gupta, S., Pramono, B., Saksono, H. Dante, Agung, P., Wahono, S. Djoko, Suastika, K., Tanggo, Y., Juwana, Y., Siswanto, B., Adawi, F., Efrati, S., Mazen, E., Bashkin, A., Herskovits, T., Jaffe, A., Schiff, E., Wainstein, J., Taddei, S., Aiello, A., Arca, M., Calabro, P., Cignarelli, M., Fioretto, P., Reggiani, G. Marchesini, Gnasso, A., Marchionni, N., Marsilii, A., Bucci, M., Mezzetti, A., Pozzilli, P., Colivicchi, F., Santini, M., Moro, E., Toscano, V., Fucili, A., Semplicini, A., Monno, S., Furui, K., Higashiue, S., Hiramatsu, N., Kawamitsu, K., Takenaka, T., Takahashi, H., Hojo, F., Onishi, Y., Izumino, K., Okubo, M., Wakida, Y., Kondo, Y., Hieshima, K., Jinnouchi, H., Suzuki, A., Ito, M., Park, S., Kim, Y., Hong, T., Park, H., Gwon, H., Kim, H., Kang, K., Jeong, M., Seung, K., Lim, D., Rha, S., Tahk, S., Yang, J., Yoon, J., Shin, M., Kim, D., Jeong, J., Ahmad, N. Nik, Mustafa, N., Mohamed, W. Wan, Fung, Y., Ghani, R. Abdul, Chandramouli, A., Chee, K., Kadir, K. Abdul, Ling, K., Abu Hassan, M., Foo, S., Lee, S., Garcia Hernandez, P., Aguilar-Salinas, C., Vidrio Velazquez, M., Flores, F., Alpizar Salazar, M., Micher Escalante, D., Garcia Soria, M., Cardona Munoz, E., Storms, G., Schaper, N., Kooy, A., Krekels, M., van Bemmel, T., Verhoeven, R., Mulder, H., Oldenburg-Ligtenberg, P., Gonkel, F., de Jong, A., van Soest, J., Viergever, P., Mevissen, H., Lochorn, G., Zwiers, G., Hoogslag, P., Ronner, E., Nierop, P., Al-Windy, N., Kragten, J., Dekelver, P., Benatar, J., Krebs, J., Scott, R., Heggen, E., Berz, A., Fossum, C., Hurtig, U., Langslet, G., Baranowski, M., Sparby, J., Karlsson, T., Karlsson, Thomas, Delgado Torres, C., Rodriguez Escudero, A., Lisson, R., Allemant Maldonado, A., Gallardo Rojas, W., Gonzales Bravo, L., Lema Osores, J., Farfan, J., Zapata, L., Godoy Junchaya, J., Roldan Concha, Y., Urquiaga Calderon, J., Sy, R., Tan, G., Aquitania, G., De Los Santos, G., Panelo, A., Roderos, O., Rosales, R., Toledo, R., Liwag, A., Ramoncito, H., Skokowska, E., Krzyzagorska, E., Ogorek, M., Wojnowski, L., Spyra, J., Konieczny, M., Piesiewicz, W., Kus, W., Ocicka-Kozakiewicz, A., Orlowska-Kunikowska, E., Zmuda, W., Duarte, S., Leitao, A., Monteiro, P., Rita, H., Salgado, V., Pinto, L., Queiros, J., Teixeira, J., Rogado, C., Duarte, R., Sobral do Rosario, F., Silva, A., Andrade, L., Velez, M., Brazao, M., Istratoaie, O., Lichiardopol, R., Catrinoiu, D., Militaru, C., Zetu, C., Barbonta, D., Cosma, D., Crisan, C., Pop, L., Esip, V., Khetagurova, F., Petrov, A., Arutyunov, G., Boyarkin, M., Agafyina, A., Vorokhobina, N., Petunina, N., Libov, I., Zalevskaya, A., Nikolaev, K., Barbarash, O., Potemkin, V., Bystrova, A., Krasilnikova, E., Barbarich, V., Chumakova, G., Tarasov, N., Meleshkevich, T., Zateyshchikov, D., Lantseva, O., Belenkiy, D., Obrezan, A., Rossolko, L., Fillipova, E., Yakhontova, P., Khokhlov, A., Tan, R., Sum, C., Chang, H., Distiller, L., Pretorius, M., Nortje, H., Mitha, E., Burgess, L., Blignaut, S., Venter, T., Moodley, R., Lombaard, J., Govind, U., Naidoo, V., Mookadam, M., Engelbrecht, J., Omar, M., Jurgens, J., Podgorski, G., Vawda, H., Naidoo, D., Emanuel, S., Roodt, A., Amod, A., Van Zyl, L., Segura, J., Brito, M., Fernandez-Cruz, A., Artola, S., Iglesias, R., Toural, E., Garcia-Ortiz, L., Saban, J., Mesa, J., Vidal, J., Linares, J., del Canizo, F., Rigla, M., Suarez, C., Llorente, I., Moreno, B., Antoli, A., Gomez Peralta, F., Iglesias, M., Pereg, V., de Teresa, L., Camafort, M., Trescoli, C., Satarasinghe, R., Somasundaram, N., Siyambalapitiya, S., Antonypillai, C., Bulugahapitiya, D., Medagama, U., Huang, C., Lu, Y., Hwang, J., Chiang, C., Wen, M., Chen, J., Lai, W., Chang, K., Wang, J., Yeh, H., Kriangsak, P., Deerochanawong, C., Suwanwalaikorn, S., Mangklabruks, A., Kaewsuwanna, P., Piyayotai, D., Iabluchanskyi, M., Samoylov, O., Godlevska, O., Kovalyova, O., Voloshyna, O., Tseluyko, V., Zotov, S., Vykhovanyuk, I., Dulgeroff, A., Mayfield, R., Zaniewski-Singh, M., Ullal, J., Aloi, J., De La Rosa, R., Mosely, J., Wittmer, B., Aronoff, S., Rosenfeld, J., Seidner, M., Warren, M., Fishman, N., Weiss, R., Arif, A., Sandberg, M., Lewis, D., Ball, E., Graf, R., Breton, C., Tamayo, R., Richards, R., Cefalu, W., Uwaifo, G., Zayour, D., Hoffman, J., Fitz-Patrick, D., Khan, B., Blaze, K., Bressler, P., Halpern, S., Chappell, D., Bergenstal, R., Cuddihy, R., Matfin, G., Freedman, Z., Gonzalez-Campoy, J., Lerman, S., Rendell, M., Sitar, S., Reeves, M., Howard, T., Soufer, J., Miranda-Palma, B., Laliotis, A., Shomali, M., Teltser, M., Hurley, D., Morawski, E., Cherlin, R., Houchin, V., Welch, M., Goytia-Leos, D., Syed, M., Kowaloff, E., Weinrauch, L., Peniston, J., Brockmyre, A., First, B., Feld, L., Huffman, D., Nassim, O., Gottschlich, G., Patel, A., Knopke, C., Hernandez, M., Diaz, J., Giugliano, G., Nicasio, J., Eagerton, D., Huntley, R., Reed, J., III, Magee, M., Hippert, R., Sofley, C., Jr., Alzohaili, O., Levins, P., Anspach, R., Shah, S., Brusco, O., Naidu, J., Lindenbaum, J., Jacks, R., Hammond, G., Arena, C., Saxman, K., Mach, M., Kerstein, H., Kereiakes, D., Wahlen, J., Wehmeier, K., Chaykin, L., Rothman, J., Fogelfeld, L., Stroger, John H., Jr., Bittar, N., Rosenstock, J., Kayne, D., Navarro, J., Colfer, H., Mokshagundam, S., Shandilya, L., Connery, L., Wysham, C., Dela Llana, A., Jardula, M., MacAdams, M., Flippo, G., Heurich, E., Curtis, C., Sanders, D., Rawls, R., Velazquez, F., Osea, E., Mahood, K., Feldman, G., Eder, F., Riley, E., Fowler, W., Jain, M., Shepard, M., Schear, M., Barker, B., Strout, C., Obiekwe, O., Shanik, M., Green, C., Blakney, E., Roberson, K., Bretton, E., Pish, R., Kaveh, K., Maynard, B., Barager, W., Soldyshev, R., Austin, B., Parmar, P., Simpson, R., Chauhan, A., Kasper, J., Burr, R., Patel, N., Mariano, H., Pluto, T., Bratcher, C., Juarez, M., Levinson, L., Awad, A., Longshaw, K., Hoffman, K., Richwine, R., Molter, D., Boscia, J., III, Kowalyk, S., Lemis, P., Liss, J., Orr, R., Riser, J., Wood, J., Ubani, A., Paine, W., Hassani, F., Miranda, F., Hansen, V., Hansen, Val R., Farris, N., Bowden, R., Ajani, D., Maw, K., Andersen, J., Bergman, B., Dunmyer, S., Brandon, D., Anderson, M., Bononi, P., Prawer, J., Seidman, B., Cruz, H., Wilks, K., DiSanto, L., Buynak, R., Christensen, T., Denker, P., Koppel, W., Stedman, M., Lewy-Alterbaum, L., Karim, S., Shapiro, J., Gardner, T., Oskin, T., Gabra, N., Malano, J., EMPA-REG OUTCOME Trial, and EMPA-REG OUTCOME(R) trial investigators

Subjects
medicine.medical_specialty, Cardiac & Cardiovascular Systems, Aha Fasttrack, BLOOD-PRESSURE, 030209 endocrinology & metabolism, Cardiovascular disease, Hospitalization, Mortality, Type 2 diabetes, 030204 cardiovascular system & hematology, COLLABORATION, GUIDELINES, DOUBLE-BLIND, MELLITUS, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Empagliflozin, Medicine, ddc:610, Adverse effect, Science & Technology, COTRANSPORTER 2 INHIBITION, business.industry, MORTALITY, Hazard ratio, Heart Failure/Cardiomyopathy, medicine.disease, INSULIN, Editor's Choice, Endocrinology, Blood pressure, DISEASES, SAFETY, Heart failure, Cardiovascular System & Cardiology, Number needed to treat, Cardiology, Fast Track, Cardiology and Cardiovascular Medicine, business, Life Sciences & Biomedicine
Abstract

Aims We previously reported that in the EMPA-REG OUTCOME(R) trial, empagliflozin added to standard of care reduced the risk of 3-point major adverse cardiovascular events, cardiovascular and all-cause death, and hospitalization for heart failure in patients with type 2 diabetes and high cardiovascular risk. We have now further investigated heart failure outcomes in all patients and in subgroups, including patients with or without baseline heart failure. Methods and results Patients were randomized to receive empagliflozin 10 mg, empagliflozin 25 mg, or placebo. Seven thousand and twenty patients were treated; 706 (10.1%) had heart failure at baseline. Heart failure hospitalization or cardiovascular death occurred in a significantly lower percentage of patients treated with empagliflozin [265/4687 patients (5.7%)] than with placebo [198/2333 patients (8.5%)] [hazard ratio, HR: 0.66 (95% confidence interval: 0.55-0.79); P < 0.001], corresponding to a number needed to treat to prevent one heart failure hospitalization or cardiovascular death of 35 over 3 years. Consistent effects of empagliflozin were observed across subgroups defined by baseline characteristics, including patients with vs. without heart failure, and across categories of medications to treat diabetes and/or heart failure. Empagliflozin improved other heart failure outcomes, including hospitalization for or death from heart failure [2.8 vs. 4.5%; HR: 0.61 (0.47-0.79); P < 0.001] and was associated with a reduction in all-cause hospitalization [36.8 vs. 39.6%; HR: 0.89 (0.82-0.96); P = 0.003]. Serious adverse events and adverse events leading to discontinuation were reported by a higher proportion of patients with vs. without heart failure at baseline in both treatment groups, but were no more common with empagliflozin than with placebo. Conclusion In patients with type 2 diabetes and high cardiovascular risk, empagliflozin reduced heart failure hospitalization and cardiovascular death, with a consistent benefit in patients with and without baseline heart failure., This work was supported by Boehringer Ingelheim and Eli Lilly and Company. Boehringer Ingelheim was involved in the design and conduct of the study; collection, analysis, and interpretation of data; and preparation of this manuscript. Eli Lilly's involvement was limited to co-funding of the study. Funding to pay the Open Access publication charges for this article was provided by Boehringer Ingelheim.

Published
2016

40. Effet de l’association tiotropium et olodaterol prise une fois par jour pendant 8 et 12 semaines, seule et combinée à l’entraînement physique, sur l’endurance à l’exercice lors de la marche chez les patients atteints de BPCO

Author

Troosters, T., primary, Bourbeau, J., additional, Maltais, F., additional, Leidy, N., additional, Erzen, D., additional, De Sousa, D., additional, Lavoie, K.L., additional, Janssens, W., additional, Hamilton, A., additional, and Derom, E., additional

Published
2017
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42. Validity of physical activity monitors during daily life in patients with COPD

Author

Rabinovich, R.A. Louvaris, Z. Raste, Y. Langer, D. Van Remoortel, H. Giavedoni, S. Burtin, C. Regueiro, E.M.G. Vogiatzis, I. Hopkinson, N.S. Polkey, M.I. Wilson, F.J. MacNee, W. Westerterp, K.R. Troosters, T. Brindicci, C. Higenbottam, T. Dobbels, F. Tabberer, M.X. Garcia-Aymerich, J. Puhan, M. Frei, A. van der Molen, T. De Jong, C. de Boer, P. Jarrod, I. McBride, P. Kamel, N. Rudell, K. Ivanoff, N. Kulich, K. Glendenning, A. Karlsson, N.X. Corriol-Rohou, S. Nikai, E. Erzen, D.

Abstract

Symptoms during physical activity and physical inactivity are hallmarks of chronic obstructive pulmonary disease (COPD). Our aim was to evaluate the validity and usability of six activity monitors in patients with COPD against the doubly labelled water (DLW) indirect calorimetry method. 80 COPD patients (mean±SD age 68±6 years and forced expiratory volume in 1 s 57±19% predicted) recruited in four centres each wore simultaneously three or four out of six commercially available monitors validated in chronic conditions for 14 consecutive days. A priori validity criteria were defined. These included the ability to explain total energy expenditure (TEE) variance through multiple regression analysis, using TEE as the dependent variable with total body water (TBW) plus several physical activity monitor outputs as independent variables; and correlation with activity energy expenditure (AEE) measured by DLW. The Actigraph GT3X (Actigraph LLC, Pensacola, FL, USA), and DynaPort MoveMonitor (McRoberts BV, The Hague, the Netherlands) best explained the majority of the TEE variance not explained by TBW (53% and 70%, respectively) and showed the most significant correlations with AEE (r=0.71, p

Published
2013

44. The Effects of Diabetes Mellitus Type 1 on Regeneration Capacity of Rat Skeletal Muscle

Author

Jurisic-Erzen, D., Vranic, Ts, Juraj Arbanas, and Jerkovic, R.

Subjects
muscle regeneration, diabetes mellitus type I
Abstract

Muscle fibers are dynamic structures capable of altering their phenotype under altered hormonal profiles. Skeletal muscle is able to complete a rapid and extensive regeneration process in response to various pathological conditions. The aim of our study was to explore the effects of experimentaly induced diabetes mellitus type 1 on muscle regeneration process in fast and slow rat skeletal muscle. Two-months-old male Wistar rats were randomly assigned to control and diabetic group. Regeneration process was induced in slow (m.soleus, SOL) and fast (m.extensor digitorum longus, EDL) skeletal muscles by injection of local anaesthetic, bupivacain. Morphometric analysis was performed 10 days, 4 and 8 weeks after bupivacaine treatment. Ten days after bupivacaine treatment control SOL muscle is composed of 89% of type I fibers and 11% of type II A fibers. In diabetic SOL muscles type I fibers became predominant after 8 weeks of regeneration. Ten days after bupivacaine treatment control EDL muscle is composed of 9% of type I fibers, 24% of type II A, 10% of type II X, and of 57% of type II B fibers. After 8 weeks of regeneration diabetic EDL muscles were composed of fibers with mainly oxidative metabolism i.e. type I and type IIA fibers. Diabetic muscles, both SOL and EDL, showed a considerable degree of muscle atrophy at all time-point of muscle regeneration comparing to normal muscles. After 8 weeks of diabetes type I fibers showed statistically significant reduction in cross-sectional areas, while type IIA fibers completely disappeared. In diabetic EDL muscles the cross areas of all fiber types were significant smaller than in normal muscles in all investigated periods of regeneration with exception of type I fibers after 10 days of diabetes. Diabetes mellitus type 1 have changed the morphological properties in slow (SOL) and fast (EDL) muscles during the process of regeneration. These changes are evident in redistribution of muscle fibers and significant level of muscle atrophy. The changes of redistribution of muscle fibers depend on duration of diabetes.

Published
2005

46. Potential Formation in Front of an Electron Emitting Electrode in a Two-Electron Temperature Plasma.

Author

Gyergyek, T., Cercek, M., and Erzen, D.

Subjects
ELECTRON emission, PLASMA gases, ELECTRIC currents, ACCELERATION potential
Abstract

Plasma potential formation in the pre-sheath region of a floating electron emitting electrode (collector) is studied theoretically in a two-electron-temperature plasma using a static kinetic plasma-sheath model. Dependence of the collector floating potential, the plasma potential in the pre-sheath region, and the critical emission coefficient on the hot electron density and temperature is calculated. It is found that for high hot to cool electron temperature ratio a double layer like solutions exist in a certain range of hot to cool electron densities. [ABSTRACT FROM AUTHOR]

Published
2003

49. Alogliptin after acute coronary syndrome in patients with type 2 diabetes

Author

White, W. B., Cannon, C. P., Heller, S. R., Nissen, S. E., Bergenstal, R. M., Bakris, G. L., Perez, A. T., Fleck, P. R., Mehta, C. R., Kupfer, S., Wilson, C., Cushman, W. C., Zannad, F., Aiub, J., Albisu, J., Alvarez, C., Astesiano, A., Barcudi, R., Bendersky, M., Bono, J., Bustos, B., Cartasegna, L., Caruso, O., Casabe, H., Castro, R., Colombo, H., Cuneo, C., Cura, F., Loredo, L., Dran, R., Fernandez, H., Garcia Pinna, J., Hrabar, A., Klyver Saleme, M., Luquez, H., Mackinnon, I., Maffei, L., Majul, C., Mallagray, M., Marino, J., Martinez, D., Martingano, R., Nul, D., Parody, M. L., Petrucci, J., Pieroni, M., Daniel Piskorz, Prado, A., Ramos, H., Resk, J., Rodriguez, M., Rojas, C., Sarjanovich, R., Sarries, A., Sessa, H., Silveiro, S., Sosa Liprandi, M. I., Tartaglione, J., Tonin, H., Vallejos, J., Vigo, S., Visco, V., Vita, N., Vogel, D., Vogelmann, O., Zaidman, C., Zangroniz, P., Colquhoun, D., Coverdale, S., Flecknoe-Brown, S., Hii, C. S., Roberts-Thomson, P., Drexel, H., Luger, A., Pieber, T., Cools, F., Ruige, J., Schoors, D., Vercammen, C., Wollaert, B., Alves Da Costa, F., Amodeo, C., Baggenstoss, R., Barbosa, E., Barroso Souza, W. K., Bassan, R., Borges, J. L., Botelho, R., Braile, M. C., Castello, H., Chrisman, C., Dos Santos, F., Faria Neto, J., Farsky, P., Fernandes Da Costa, A., Fraige Filho, F., Garbelini, B., Garcia, M. F., Garzon, P., Guimaraes, A. E., Herdy, A., Hernandes, M., Hilgemberg, S., Hissa, M., Jatene, J. A., Kormann, A., Leaes, P., Lima, F., Lisboa, H. R., Maia, L., Maia Da Silva, F., Maldonado Franco, D., Martin, J. F., Medeiros, A., Michalaros, Y., Miguel Leitao, A., Montenegro, S., Moraes Junior, J., Mota Gomes, M., Paiva, M. S., Precoma, D., Rabelo, A., Reis, G., Reis, H., Rossi, P., Saporito, W., Sarmento Leite, R., Silva, R. P., Silva Junior, D., Sousa, L., Sousa, A. C., Ueda, R., Vilas-Boas, F., Wainstein, M., Zago, A., Angelova, M., Apostolova, E., Daskalova, I., Delchev, A., Hristozov, K., Ilieva, M., Kovacheva, S., Lucheva, M., Temelkova, M., Toneva, A., Videva, V., Vuchkova, E., Bakbak, A., Carpentier, A., Chan, Y. K., Cheema, A., Chouinard, G., Conway, J., Dery, J. P., Dowell, A., Frechette, A., Jakubowski, M., Kelly, A., Ma, P., Maung, T. Z., Mehta, S., Parker, D., Pesant, Y., Polasek, P., Ransom, T., Syan, G., Vizel, S., Albornoz, F., Castro Galvez, P., Cobos, J. L., Conejeros, C., D Acuña Apablaza, M., Fajardo, G., Illanes Brochet, G., Lazcano, M. O., Pincetti, C., Potthoff, S., Raffo, C., Saavedra, V., Schnettler, M., Sepulveda, P., Stockins, B., Vejar, M., Accini, J. L., Cotes Aroca, C. H., Fernandez Ruiz, R. L., Orozco Linares, L. A., Vesga Angarita, B. E., Aganovic, I., Bagatin, J., Canecki-Varzic, S., Erzen, D. J., Knezevic, A., Maric, A., Milicevic, G., Popovic, Z., Rubes, J., Weiss, S. S., Dresslerova, I., Havelkova, J., Kucera, D., Machacek, J., Pumprla, J., May, O., Perrild, H., Aziz, M. A., El Badry, M., Hasanein, M., Airaksinen, J., Laine, M., Nyman, K., Vikman, S., Bonnet, J., Elbaz, M., Henry, P., Paillard, F., Petit, C., Tropeano, A. I., Behnke, T., Bornstein, S., Busch, K., Ebelt, H., Faghih, M., Fischer, H., Heuer, H., Paschke, R., Porner, T. C., Tangerding, G., Vöhringer, H. F., Adamson, K., Beatt, K., Bellary, S., Chapman, J., Cooke, A., Fisher, M., Gnudi, L., Jones, H., Kumar, S., Nagi, D., Oldroyd, K., Richardson, T., Robertson, D., Robinson, A., Saravanan, P., Viljoen, A., Wilding, J., Wilkinson, P., Wong, Y. K., Zoupas, C., Arango, J., Castellanos, J., Ceren Flores, C., Corona, V., Granados-Fuentes, A., Haase, F., Montenegro, P., Prado, J. H., Villalobos, R., Chow, F., Li, S. K., Li, J., Yan, P. Y., Yeung, V., Abel, T., Benedek, A., Dezso, E., Dudas, M., Édes, I., Fulop, G., Kovács, A., Lupkovics, G., Merkely, B., Nagy, A., Oroszlan, T., Palinkas, A., Papp, A., Patkay, J., Simon, E., Sitkei, E., Tabak, A., Tomcsányi, J., Abdullakutty, J., Abhyankar, A., Akalkotkar, U., Alexander, T., Arneja, J., Aslam, N., Babu, P. R., Babu, B. R., Banker, D., Bantwal, G., Bhimashankar, P. R., Calton, R. K., Chopda, M., Dande, A., Dani, S., Deshpande, N., Dhanwal, D., Dharmadhikari, A., Gadkari, M., Garg, N., Ghaisas, N., Goyal, N. K., Gupta, J. B., Jawahirani, A., Joseph, S., Kumar, R., Kumble, M., Mathavan, A., Mathur, A., Mohanan, P. P., Nair, A., Nair, T., Namjoshi, D., Pinto, R., Prakash, G., Purushotham, R., Raju, S., Ramachandran, P., Ramesh, S. S., Rao, B., Ravikishore, A., Reddy, G. R., Roy, S., Sadhu, N., Sastry, B. K., Singh, P., Srinivas, A., Thacker, H., Thanvi, S., Thomas, J., Adawi, F., Bashkin, A., Cohen, J., Harman-Boehm, I., Hasin, Y., Hayek, T., Iakobishvili, Z., Katz, A., Kracoff, O., Minuchin, O., Moriel, M., Mosseri, M., Omary, M., Wainstein, J., Weiss, A., Zeltser, D., Calabro, P., Derosa, G., Genovese, S., Novo, S., Olivieri, C., Piatti, P., Violini, R., Volpe, M., Ajioka, M., Amano, T., Arasaki, O., Daida, H., Fujimoto, K., Fujinaga, H., Higashiue, S., Hirohata, A., Hosokawa, S., Ikefuji, H., Inagaki, M., Iseki, H., Iwabuchi, M., Iwasaki, T., Kakishita, M., Katsuda, Y., Kawada, K., Kawajiri, K., Kawamitsu, K., Kobayashi, K., Komada, F., Komura, Y., Machida, M., Maemura, K., Matsubara, T., Matsubayashi, S., Matsumoto, T., Matsumoto, N., Mima, T., Miyamoto, N., Momiyama, Y., Morimoto, T., Murakami, M., Nakashima, E., Niijima, Y., Noda, T., Node, K., Nozaki, A., Nunohiro, T., Ogawa, T., Ono, Y., Saeki, T., Sakota, S., Sakuragi, S., Sasaki, T., Sato, Y., Sueyoshi, A., Suzuki, M., Takagi, G., Tanabe, J., Tanaka, S., Tei, I., Yamamoto, M., Yanagihara, K., Hong, T. J., Jeon, H. K., Kang, D. H., Kim, C. H., Kim, D. S., Kim, H. S., Kim, J. H., Kim, S. K., Kim, W. S., Kim, Y. K., Lee, S. R., Lee, K. W., Park, H. S., Pyun, W. B., Rha, S. W., Yoon, J., Yoon, K. H., Bennakhi, A., Geldnere, K., Sokolova, J., Teterovska, D., Dautaraite, V., Kakariekiene, V., Kavaliauskiene, R., Kucinskiene, A., Lasiene, J., Mickuviene, N., Palinauskas, A., Urboniene, A., Zilaitiene, B., Abdul Manap, H., Abidin, I. Z., Isa, S. H., Khir, A. M., Ng, K. H., Tan, F., Yusof, Z., Yusoff, K., Zambahari, R., Aguila-Marin, J., Aguilera Real, M., Alvarado-Ruiz, R., Alvarez Lopez, H., Arenas Leon, J., Bayram Llamas, E. A., Calvo Vargas, C., Carrillo Calvillo, J., Los Rios Ibarra, M., Dominguez-Reyes, C. A., Duarte, M., Elizondo, E., Fajardo Campos, P., Fanghanel-Salmon, G., Figueroa Sauceda, S., Gallegos Martinez, J., Garcia-Cantu, E., Garza Ruiz, J. A., Gonzalez Gonzalez, J. G., Guerrero Garza, M., Hernandez Herrera, C., Hernandez Munuzuri, J., Hernandez-Garcia, H., Jimenez Ramos, S., Laviada Molina, H., Lopez Villezca, D., Montano-Gonzalez, E., Nevarez Ruiz, L., Ramos Lopez, G., Reyes Araiza, R., Salazar-Gaytan, A., Salcido Vazquez, E., Sanchez Mijangos, H., Solis Morales, L., Benatar, J., Dixon, P., Nirmalaraj, K., Rosen, I., Scott, R., Young, S., Araoz Tarco, O., Barreda Cáceres, L., Benites Lopez, C., Camacho Cosavalente, L., Chavez Huapalla, E., Chois Malaga, A., Copaja Flores, A., Farfan Aspilcueta, J., Gallardo Rojas, W., Gallegos Cazorla, A., Galvez Caballero, D., Garcia Matheus, J., Garrido Carrasco, E., Gomez Sanchez, J., Hernandez Zuniga, J., Lu Galarreta, L., Luna, A., Manrique Hurtado, H., Orihuela Pastor, B., Pando Alvarez, R. M., Sanchez Povis, J., Torres Eguiluz, P., Valdivia Portugal, A., Vargas Gonzales, R., Zapata Rincon, L., Aquitania, G., Fortinez, J. T., Go, A., Gomez, M. H., Habaluyas, R., Jasul, G., Magno, M., Manalo, C. J., Mirasol, R., Morales-Palomares, E., Salvador, D. R., Sy, R. A., Tirador, L., Yao, C., Arciszewska, M., Bartkowiak, R., Czajkowska-Kaczmarek, E., Gil, R., Gniot, J., Janik, K., Janion, M., Jaworska, K., Jozwa, R., Kawecka-Jaszcz, K., Kawka-Urbanek, T., Kondys, M., Korecki, J., Korzeniak, R., Kowalisko, A., Krzeminska-Pakula, M., Kwiecien, J., Nessler, J., Odrowaz-Pieniazek, P., Piepiorka, M., Rajzer, M., Skokowska, E., Spyra, J., Sroka, M., Stasinska, T., Szymczyk, I., Trznadel-Morawska, I., Wysokinski, A., Mateus, P., Matos, P., Mimoso, J., Monteiro, P., Caballero, B., Garcia-Rinaldi, R., Gonzalez, E., Ortiz-Carrasquillo, R., Roman, A., Sierra, Y., Unger, N., Vazquez-Tanus, J., Alexandru, T., Busegeanu, M., Cozman, D. C., Fica, S., Minescu, B., Morosanu, M., Negrisanu, G. D., Pintilei, E., Pop, L., Szilagyi, I., Teodorescu, I., Tomescu, M., Barbarash, O., Chumakova, G., Churina, S., Dogadin, S., Dvoryashina, I., Esip, V., Glezer, M., Gordeev, I., Gordienko, A., Gratsiansky, N., Grineva, E., Khasanov, N., Kostenko, V., Meleshkevich, T., Mikhin, V., Morugova, T., Motylev, I., Nikolaev, K., Ponomareva, A., Repin, M., Reshetko, O., Shustov, S., Shutemova, E., Shvarts, Y., Simanenkov, V., Sobolev, K., Sukmanova, I., Timofeev, A., Tsyba, L., Varvarina, G., Vertkin, A., Vishnevsky, A., Volkov, D., Vorobiev, S., Vorokhobina, N., Yakhontov, D., Zonova, E., Zrazhevskiy, K., Damjanovic, S., Djordjevic, D., Pavlovic, M., Perunicic, J., Ristic, A., Stojkovic, S., Tasic, N., Bolvanska, N., Buganova, I., Dulkova, K., Dzupina, A., Fulop, P., Gergel, V., Kokles, M., Micko, K., Svoren, P., Urban, M., Vadinova, S., Vargova, A., Burgess, L., Coetzee, K., Du Toit, J., Gani, M., Joshi, P., Naiker, P., Nortje, H., Sarvan, M., Seeber, M., Siebert, M., Zyl, L., Wellmann, H., Calvo, C., La Hera, J., Teresa, L., Melero-Pita, A., Mesa, J., Parra Barona, J., Serrano, P., Soto, A., Tofe, S., Hornestam, B., Kempe, A., Rosenqvist, U., Rydberg, E., Tengmark, B. O., Torstensson, I., Chang, C. T., Hsia, T. L., Hsieh, I. C., Lai, W. T., Wu, C. J., Hutayanon, P., Kosachunhanun, N., Marapracertsak, M., Piamsomboon, C., Seekaew, S., Srimahachota, S., Sukhum, P., Suraamornkul, S., Tantiwong, P., Wongvipaporn, C., Amosova, K., Barna, O., Bazylevych, A., Berenfus, V., Dyadyk, A., Fushtey, I., Gyrina, O., Iabluchanskyi, M., Karpenko, O., Kaydashev, I., Korzh, O., Kulynych, R., Legkonogov, O., Mankovsky, B., Mostovoy, Y., Parkhomenko, O., Popik, G., Rudenko, L., Rudyk, I., Shevchuk, S., Sirenko, Y., Suprun, Y., Tryshchuk, N., Tseluyko, V., Vakaliuk, I., Al Mahmeed, W., Acheatel, R., Ahmad, A., Akbar, S., Akhter, F., Albirini, A., Alexander, A., Al-Joundi, B., Al-Joundi, T., Allen, G., Aloi, J., Alvarado, O., Alzohaili, O., Anderson, C., Arastu, A., Arena, C., Argoud, G., Ariani, M., Arora, C., Awasty, V., Barker, B., Barnum, O., Bartkowiak, A. J., Barzilay, J., Behrens, P., Belledonne, M., Bergman, B., Bilnoski, W., Bisognano, J., Bissette, S., Blumberg, E., Bonabi, N., Bradley, A., Breton, C., Britos, M., Broadstone, V., Budoff, M., Burge, M., Butman, S., Carroll, M., Challappa, K., Chepuri, V., Cherlin, R., Cheung, D., Coats, P., Collins, J., Cruz, H., Daboul, N., Damberg, G., David, W., Dean, J., Dedeke, E., Deeb, W., Dehaven, J., Dobs, A., Donelan, T., Dy, J., Dykstra, G., Eisen, H., Farris, N., Fattal, P., Fishman, N., Foster, M., Fredrickson, S., Gabra, N., Gabriel, J., Gatien, L., Giddings, S., Ginsberg, B., Gips, S., Glandt, M., Goldfein, A., Gordon, M., Gould, R., Graf, R., Graham, B., Graves, M., Grena, P., Hahn, R., Hamilton, D., Hamroff, G., Hanke, F., Haque, I., Harper, J., Harris, A., Harris, S., Henson, B., Hermanns, D., Herndon, W., Hershberger, V., Hyman, D., Isserman, S., Iteld, B., Jacob, M., Jaffrani, N., Jamal, A., Johnson, D., Johnson, G., Kaluski, E., Keller, R., Kereiakes, D., Khan, M., Khan, S., Klein, M., Knutson, T., Korban, E., Kozinn, M., Kraft, P., Kroeze, J., Kukuy, E., Lader, E., Laliotis, A., Lambert, C., Landau, C., Latif, K., Lee, K., Lester, F., Levenson, D., Levinson, D., Lewis, D., Litt, M., Littlefield, R., Lo, E., Lovell, C., Mahal, S., Makam, S., Mandviwala, M., Marar, I., Masri, B., Mattson, S., Mays, M., Mcgrew, F., Meengs, M., Mikell, F., Miller, M., Miranda, F., Moll, D., Multani, P., Munuswamy, K., Nallasivan, M., Nayles, L., Ong, S., Pacheco, T., Paez, H., Patel, S., Phillips, R., Pierpont, B., Prasad, J., Quinlan, E., Quion, J., Qureshi, M., Rahman, A., Raikhel, M., Ramanathan, K., Randhawa, P., Ravi, R., Reddy, R., Rendell, M., Rickner, K., Rictor, K., Rivas, J., Rosenblit, P., Rosenstock, J., Ross, S., Salacata, A., Saririan, M., Schima, S., Schlau, A., Schmedtje, J., Scott, C., Scott, D., Serru-Paez, A., Shah, R., Shah, A., Shaoulian, E., Shomali, M., Shubrook, J., Silver, K., Singh, S., Speer, J., Stevens, J., Stringam, S., Taussig, A., Taylor, A., Tee, H., Teixeira, G., Tilley, A., Toggart, E., Twahirwa, M., Unks, D., Vakili, B., Vora, K., Wang, X., Warner, A., Wefald, F., Weinberg, B., Weinstein, D., White, L., Wu, P., Yasuda, T., Yazdani, S., Yetman, C., Zarich, S., Zebrack, J., Fonseca, V. A., Mccullough, P. A., Desouza, C., Goff, D. C., Harrell, F. E., Menon, V., Sila, C., Kalahasti, V., Ahmed, S., Al Solaiman, F., Bennett, M., Cavender, M., Heil, B., Katzan, I., Monteleone, P., O Brien, B., Oommen, S., Senn, T., Sharma, J., Stegman, B., Uchino, K., Zishiri, E., Pasca, N., Brown, K., Scebbi, T., Atanasovski, I., Mccue, M., Streit, J., Oh, R., Bueno, O., Lee, D., Camisasca, R., Miyata, Y., Rubin, A., Williamson, N., Vara, S., Keeter, K., Ross, B., Los Reyes, A., Donnelly, J., Koshy-Hunt, S., Beers, B., Black, S., Buckley, M., Ephrem, M., Riley, B., West, N., Harre, M., Hsieh, R., Oshinyemi, K., Oka, Y., Matsui, N., Hoang, M., Doyle, C., Koziol, M., Lam, H., Edmonds, A., Azooz, W., Cao, C., Kim, D., Boeshaar, A., Dewindt, A., Nicholson, K., Smith, N., Hisada, M., Harding, S., Yoshioka, N., Gujral-Sandhu, K., Gans, J., Gresk, C., Kujawski, M. R., Villinski, A., Cosner, S., Johannsen, C., Barchha, N., and Knapp, B.

50. PREGNANCY WITH TYPE I DIABETES TREATED WITH AN INSULIN PUMP. RISKS FOR LARGE FOR GESTATIONAL AGE INFANTS AND ALTERNATING BASAL-BOLUS INSULIN RATIO

Author

Leksic, G., Maja Baretić, Ivanisevic, M., and Jurisic-Erzen, D.

Subjects
type 1 diabetes mellitus, insulin pump, pregnancy, large for gestational age
Abstract

BACKGROUND AND AIMS: The aim of this study was to identify parameters that contribute the most to the development of large for gestational age (LGA) infants in a cohort of patients with type 1 diabetes mellitus (T1DM) treated with an insulin pump during pregnancy. Furthemore, basal and bolus insulin changes during pregnancy were also evaluated. METHODS: The data of patients was retrospectively analyzed. Inclusion criteria were HbA1c ≤7.0% (53mmol/mol) and BMI

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