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1,267 results on '"Sterk, Peter J."'

1. Prospective Detection of Early Lung Cancer in Patients With COPD in Regular Care by Electronic Nose Analysis of Exhaled Breath

Author

de Vries, Rianne, Farzan, Niloufar, Fabius, Timon, De Jongh, Frans H.C., Jak, Patrick M.C., Haarman, Eric G., Snoey, Erik, In ’T Veen, Johannes C.C.M., Dagelet, Yennece W.F., Maitland-Van Der Zee, Anke-Hilse, Lucas, Annelies, Van Den Heuvel, Michel M., Wolf-Lansdorf, Marguerite, Muller, Mirte, Baas, Paul, and Sterk, Peter J.

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

Author

Hou, Ruihua, Ye, Gang, Cheng, Xiaojing, Shaw, Dominick E., Bakke, Per S., Caruso, Massimo, Dahlen, Barbro, Dahlen, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Howarth, Peter, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Auffray, Charles, De Meulder, Bertrand, Sousa, Ana R., Adcock, Ian M., Fan Chung, Kian, Sterk, Peter J., Skipp, Paul J., Schofield, James, and Djukanović, Ratko

Published
2023
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3. Stratification of asthma by lipidomic profiling of induced sputum supernatant

Author

Brandsma, Joost, Schofield, James P.R., Yang, Xian, Strazzeri, Fabio, Barber, Clair, Goss, Victoria M., Koster, Grielof, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Dahlén, Sven-Erik, Fowler, Stephen J., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Shaw, Dominick E., Chung, Kian Fan, Singer, Florian, Fleming, Louise J., Adcock, Ian M., Pandis, Ioannis, Bansal, Aruna T., Corfield, Julie, Sousa, Ana R., Sterk, Peter J., Sánchez-García, Rubén J., Skipp, Paul J., Postle, Anthony D., and Djukanović, Ratko

Published
2023
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5. Biomarker Predictors of Clinical Efficacy of the Anti-IgE Biologic Omalizumab in Severe Asthma in Adults: Results of the SoMOSA Study.

Author

Djukanović, Ratko, Brinkman, Paul, Kolmert, Johan, Gomez, Cristina, Schofield, James, Brandsma, Joost, Shapanis, Andy, Skipp, Paul J. S., Postle, Anthony, Wheelock, Craig, Dahlen, Sven-Erik, Sterk, Peter J., Brown, Thomas, Jackson, David J., Mansur, Adel, Pavord, Ian, Patel, Mitesh, Brightling, Christopher, Siddiqui, Salman, and Bradding, Peter

Subjects
OMALIZUMAB, ASTHMA, RECEIVER operating characteristic curves, WHEEZE, BIOLOGICALS, BIOMARKERS
Abstract

Background: The anti-IgE monoclonal antibody omalizumab is widely used for severe asthma. This study aimed to identify biomarkers that predict clinical improvement during 1 year of omalizumab treatment. Methods: One-year open-label Study of Mechanisms of action of Omalizumab in Severe Asthma (SoMOSA) involving 216 patients with severe (Global Initiative for Asthma step 4/5) uncontrolled atopic asthma (at least two severe exacerbations in the previous year) taking high-dose inhaled corticosteroids and long-acting β-agonists with or without maintenance oral corticosteroids. It had two phases: 0–16 weeks, to assess early clinical improvement by Global Evaluation of Therapeutic Effectiveness (GETE); and 16–52 weeks, to assess late responses based on ⩾50% reduction in exacerbations or mOCS dose. All participants provided samples (exhaled breath, blood, sputum, urine) before and after 16 weeks of omalizumab treatment. Measurements and Main Results: A total of 191 patients completed phase 1; 63% had early improvement. Of 173 who completed phase 2, 69% had reduced exacerbations by ⩾50% and 57% (37 of 65) taking mOCSs had reduced their dose by ⩾50%. The primary outcomes 2,3-dinor-11-β-PGF2α, GETE score, and standard clinical biomarkers (blood and sputum eosinophils, exhaled nitric oxide, serum IgE) did not predict either clinical response. Five volatile organic compounds and five plasma lipid biomarkers strongly predicted the ⩾50% reduction in exacerbations (receiver operating characteristic areas under the curve of 0.780 and 0.922, respectively) and early responses (areas under the curve of 0.835 and 0.949, respectively). In an independent cohort, gas chromatography/mass spectrometry biomarkers differentiated between severe and mild asthma. Conclusions: This is the first discovery of omics biomarkers that predict improvement in asthma with biologic agent treatment. Prospective validation and development for clinical use is justified. [ABSTRACT FROM AUTHOR]

Published
2024
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9. 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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11. 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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12. Modules, networks and systems medicine for understanding disease and aiding diagnosis

Author

Gustafsson, Mika, Nestor, Colm E, Zhang, Huan, Barabási, Albert-László, Baranzini, Sergio, Brunak, Sören, Chung, Kian Fan, Federoff, Howard J, Gavin, Anne-Claude, Meehan, Richard R, Picotti, Paola, Pujana, Miguel Ángel, Rajewsky, Nikolaus, Smith, Kenneth GC, Sterk, Peter J, Villoslada, Pablo, and Benson, Mikael

Subjects
Biological Sciences, Genetics, Biotechnology, Lung, Obesity, Aetiology, 2.1 Biological and endogenous factors, Generic health relevance, Good Health and Well Being, Clinical Sciences
Abstract

Many common diseases, such as asthma, diabetes or obesity, involve altered interactions between thousands of genes. High-throughput techniques (omics) allow identification of such genes and their products, but functional understanding is a formidable challenge. Network-based analyses of omics data have identified modules of disease-associated genes that have been used to obtain both a systems level and a molecular understanding of disease mechanisms. For example, in allergy a module was used to find a novel candidate gene that was validated by functional and clinical studies. Such analyses play important roles in systems medicine. This is an emerging discipline that aims to gain a translational understanding of the complex mechanisms underlying common diseases. In this review, we will explain and provide examples of how network-based analyses of omics data, in combination with functional and clinical studies, are aiding our understanding of disease, as well as helping to prioritize diagnostic markers or therapeutic candidate genes. Such analyses involve significant problems and limitations, which will be discussed. We also highlight the steps needed for clinical implementation.

Published
2014

13. 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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14. Identification and prospective stability of electronic nose (eNose)–derived inflammatory phenotypes in patients with severe asthma

Author

Brinkman, Paul, Wagener, Ariane H., Hekking, Pieter-Paul, Bansal, Aruna T., Maitland-van der Zee, Anke-Hilse, Wang, Yuanyue, Weda, Hans, Knobel, Hugo H., Vink, Teunis J., Rattray, Nicholas J., D'Amico, Arnaldo, Pennazza, Giorgio, Santonico, Marco, Lefaudeux, Diane, De Meulder, Bertrand, Auffray, Charles, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Chung, Kian F., Corfield, Julie, Dahlén, Sven-Erik, Djukanovic, Ratko, Geiser, Thomas, Horvath, Ildiko, Krug, Nobert, Musial, Jacek, Sun, Kai, Riley, John H., Shaw, Dominic E., Sandström, Thomas, Sousa, Ana R., Montuschi, Paolo, Fowler, Stephen J., and Sterk, Peter J.

Published
2019
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15. 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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16. Moderate-to-severe asthma in individuals of European ancestry: a genome-wide association study

Author

Shrine, Nick, Portelli, Michael A, John, Catherine, Soler Artigas, María, Bennett, Neil, Hall, Robert, Lewis, Jon, Henry, Amanda P, Billington, Charlotte K, Ahmad, Azaz, Packer, Richard J, Shaw, Dominick, Pogson, Zara E K, Fogarty, Andrew, McKeever, Tricia M, Singapuri, Amisha, Heaney, Liam G, Mansur, Adel H, Chaudhuri, Rekha, Thomson, Neil C, Holloway, John W, Lockett, Gabrielle A, Howarth, Peter H, Djukanovic, Ratko, Hankinson, Jenny, Niven, Robert, Simpson, Angela, Chung, Kian Fan, Sterk, Peter J, Blakey, John D, Adcock, Ian M, Hu, Sile, Guo, Yike, Obeidat, Maen, Sin, Don D, van den Berge, Maarten, Nickle, David C, Bossé, Yohan, Tobin, Martin D, Hall, Ian P, Brightling, Christopher E, Wain, Louise V, and Sayers, Ian

Published
2019
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18. Data-driven model links BMIz to gene expression in pediatric asthma

Author

Dandenault, Vincent, primary, Hachem, Nehme, additional, Adcock, Ian M, additional, Andersson, Lars I., additional, Auffray, Charles, additional, Chung, Fan K, additional, Dahlén, Sven-Erik, additional, De Meulder, Bertrand, additional, Djukanovic, Ratko, additional, Howarth, Peter, additional, Knowles, Richard G, additional, Krug, Norbert, additional, Roberts, Amanda, additional, Sousa, Ana R, additional, Sterk, Peter J., additional, Supple, David, additional, Rao, Navin, additional, Roberts, Graham, additional, Uddin, Mohib, additional, Wagers, Scott, additional, Maitland-Van Der Zee, Anke-Hilse, additional, and Longo, Cristina, additional

Published
2023
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19. Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Author

Yasinska, Valentyna, primary, Gómez, Cristina, additional, Kolmert, Johan, additional, Ericsson, Magnus, additional, Pohanka, Anton, additional, James, Anna, additional, Andersson, Lars I., additional, Sparreman-Mikus, Maria, additional, Sousa, Ana R., additional, Riley, John H., additional, Bates, Stewart, additional, Bakke, Per S., additional, Zounemat Kermani, Nazanin, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fowler, Stephen J., additional, Geiser, Thomas, additional, Howarth, Peter H., additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Behndig, Annelie, additional, Shaw, Dominick E., additional, Knowles, Richard G., additional, Dahlén, Barbro, additional, Maitland-van der Zee, Anke-Hilse, additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Adcock, Ian M., additional, Fan Chung, Kian, additional, Wheelock, Craig E., additional, Dahlén, Sven-Erik, additional, and Wikström Jonsson, Eva, additional

Published
2023
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21. Oropharyngeal Microbiota Clusters in Children with Asthma/Wheeze Associate with Allergy, Blood Transcriptomic Immune Pathways and Exacerbations Risk

Author

Abdel-Aziz, Mahmoud I., primary, Thorsen, Jonathan, additional, Hashimoto, Simone, additional, Vijverberg, Susanne J H, additional, Neerincx, Anne H, additional, Brinkman, Paul, additional, van Aalderen, Wim, additional, Stokholm, Jakob, additional, Rasmussen, Morten Arendt, additional, Roggenbuck-Wedemeyer, Michael, additional, Vissing, Nadja H, additional, Mortensen, Martin Steen, additional, Brejnrod, Asker Daniel, additional, Fleming, Louise J, additional, Murray, Clare S, additional, Fowler, Stephen J, additional, Frey, Urs, additional, Bush, Andrew, additional, Singer, Florian, additional, Hedlin, Gunilla, additional, Nordlund, Björn, additional, Shaw, Dominick E, additional, Chung, Kian Fan, additional, Adcock, Ian M, additional, Djukanovic, Ratko, additional, Auffray, Charles, additional, Bansal, Aruna T, additional, Sousa, Ana R, additional, Wagers, Scott S, additional, Chawes, Bo Lund, additional, Bønnelykke, Klaus, additional, Sørensen, Søren Johannes, additional, Kraneveld, Aletta D., additional, Sterk, Peter J, additional, Roberts, Graham, additional, Bisgaard, Hans, additional, and Maitland-van der Zee, Anke H., additional

Published
2023
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24. Low levels of endogenous anabolic androgenic steroids in females with severe asthma taking corticosteroids

Author

Yasinska, Valentyna, Gómez, Cristina, Kolmert, Johan, Ericsson, Magnus, Pohanka, Anton, James, Anna, Andersson, Lars I., Sparreman-Mikus, Maria, Sousa, Ana R., Riley, John H., Bates, Stewart, Bakke, Per S., Kermani, Nazanin Zounemat, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter H., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Behndig, Annelie F., Shaw, Dominick E., Knowles, Richard G., Dahlén, Barbro, van der Zee, Anke-Hilse Maitland, Sterk, Peter J., Djukanovic, Ratko, Adcock, Ian M., Chung, Kian Fan, Wheelock, Craig E., Dahlén, Sven-Erik, Jonsson, Eva Wikström, Yasinska, Valentyna, Gómez, Cristina, Kolmert, Johan, Ericsson, Magnus, Pohanka, Anton, James, Anna, Andersson, Lars I., Sparreman-Mikus, Maria, Sousa, Ana R., Riley, John H., Bates, Stewart, Bakke, Per S., Kermani, Nazanin Zounemat, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter H., Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Behndig, Annelie F., Shaw, Dominick E., Knowles, Richard G., Dahlén, Barbro, van der Zee, Anke-Hilse Maitland, Sterk, Peter J., Djukanovic, Ratko, Adcock, Ian M., Chung, Kian Fan, Wheelock, Craig E., Dahlén, Sven-Erik, and Jonsson, Eva Wikström

Abstract

Rationale: Patients with severe asthma are dependent upon treatment with high doses of inhaled corticosteroids (ICS) and often also oral corticosteroids (OCS). The extent of endogenous androgenic anabolic steroid (EAAS) suppression in asthma has not previously been described in detail. The objective of the present study was to measure urinary concentrations of EAAS in relation to exogenous corticosteroid exposure. Methods: Urine collected at baseline in the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease outcomes) study of severe adult asthmatics (SA, n=408) was analysed by quantitative mass spectrometry. Data were compared to that of mild-to-moderate asthmatics (MMA, n=70) and healthy subjects (HC, n=98) from the same study. Measurements and main results: The concentrations of urinary endogenous steroid metabolites were substantially lower in SA than in MMA or HC. These differences were more pronounced in SA patients with detectable urinary OCS metabolites. Their dehydroepiandrosterone sulfate (DHEA-S) concentrations were <5% of those in HC, and cortisol concentrations were below the detection limit in 75% of females and 82% of males. The concentrations of EAAS in OCS-positive patients, as well as patients on high-dose ICS only, were more suppressed in females than males (p<0.05). Low levels of DHEA were associated with features of more severe disease and were more prevalent in females (p<0.05). The association between low EAAS and corticosteroid treatment was replicated in 289 of the SA patients at follow-up after 12–18 months. Conclusion: The pronounced suppression of endogenous anabolic androgens in females might contribute to sex differences regarding the prevalence of severe asthma.

Published
2023
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28. Asthma and Wheeze Severity and the Oropharyngeal Microbiota in Children and Adolescents

Author

Thorsen, Jonathan, primary, Stokholm, Jakob, additional, Rasmussen, Morten Arendt, additional, Roggenbuck-Wedemeyer, Michael, additional, Vissing, Nadja H., additional, Mortensen, Martin S., additional, Brejnrod, Asker D., additional, Fleming, Louise, additional, Bush, Andrew, additional, Roberts, Graham, additional, Singer, Florian, additional, Frey, Urs, additional, Hedlin, Gunilla, additional, Nordlund, Björn, additional, Murray, Clare S., additional, Abdel-Aziz, Mahmoud I., additional, Hashimoto, Simone, additional, van Aalderen, Wim, additional, Maitland-van der Zee, Anke H., additional, Shaw, Dominick, additional, Fowler, Stephen J., additional, Sousa, Ana, additional, Sterk, Peter J., additional, Chung, Kian Fan, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, Auffray, Charles, additional, Bansal, Aruna T., additional, Wagers, Scott, additional, Chawes, Bo, additional, Bønnelykke, Klaus, additional, Sørensen, Søren Johannes, additional, and Bisgaard, Hans, additional

Published
2022
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31. Sputum transcriptomics reveal upregulation of IL-1 receptor family members in patients with severe asthma

Author

Rossios, Christos, Pavlidis, Stelios, Hoda, Uruj, Kuo, Chih-Hsi, Wiegman, Coen, Russell, Kirsty, Sun, Kai, Loza, Matthew J., Baribaud, Frederic, Durham, Andrew L., Ojo, Oluwaseun, Lutter, Rene, Rowe, Anthony, Bansal, Aruna, Auffray, Charles, Sousa, Ana, Corfield, Julie, Djukanovic, Ratko, Guo, Yike, Sterk, Peter J., Chung, Kian Fan, and Adcock, Ian M.

Published
2018
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33. Lipid phenotyping of lung epithelial lining fluid in healthy human volunteers

Author

Brandsma, Joost, Goss, Victoria M., Yang, Xian, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Dahlén, Sven-Erik, Fowler, Stephen J., Horvath, Ildiko, Krug, Norbert, Montuschi, Paolo, Sanak, Marek, Sandström, Thomas, Shaw, Dominick E., Chung, Kian Fan, Singer, Florian, Fleming, Louise J., Sousa, Ana R., Pandis, Ioannis, Bansal, Aruna T., Sterk, Peter J., Djukanović, Ratko, Postle, Anthony D., and The U-BIOPRED Study Group

Published
2018
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34. A computational framework for complex disease stratification from multiple large-scale datasets

Author

De Meulder, Bertrand, Lefaudeux, Diane, Bansal, Aruna T., Mazein, Alexander, Chaiboonchoe, Amphun, Ahmed, Hassan, Balaur, Irina, Saqi, Mansoor, Pellet, Johann, Ballereau, Stéphane, Lemonnier, Nathanaël, Sun, Kai, Pandis, Ioannis, Yang, Xian, Batuwitage, Manohara, Kretsos, Kosmas, van Eyll, Jonathan, Bedding, Alun, Davison, Timothy, Dodson, Paul, Larminie, Christopher, Postle, Anthony, Corfield, Julie, Djukanovic, Ratko, Chung, Kian Fan, Adcock, Ian M., Guo, Yi-Ke, Sterk, Peter J., Manta, Alexander, Rowe, Anthony, Baribaud, Frédéric, Auffray, Charles, and the U-BIOPRED Study Group and the eTRIKS Consortium

Published
2018
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38. Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort

Author

Hoda, Uruj, Pavlidis, Stelios, Bansal, Aruna T, Takahashi, Kentaro, Hu, Sile, Ng Kee Kwong, Francois, Rossios, Christos, Sun, Kai, Bhavsar, Pankaj, Loza, Matthew, Baribaud, Frederic, Chanez, Pascal, Fowler, Stephen J, Horvath, Ildiko, Montuschi, Paolo, Singer, Florian, Musial, Jacek, Dahlen, Barbro, Krug, Norbert, Sandstrom, Thomas, Shaw, Dominic E, Lutter, Rene, Fleming, Louise J, Howarth, Peter H, Caruso, Massimo, Sousa, Ana R, Corfield, Julie, Auffray, Charles, De Meulder, Bertrand, Lefaudeux, Diane, Dahlen, Sven-Erik, Djukanovic, Ratko, Sterk, Peter J, Guo, Yike, Adcock, Ian M, Chung, Kian Fan, Pulmonology, AII - Inflammatory diseases, and Commission of the European Communities

Subjects
severe asthma, Bronchi/pathology, Medicine (miscellaneous), PHENOTYPES, 1110 Nursing, 610 Medicine & health, Bronchi, Research & Experimental Medicine, Sputum/metabolism, Cohort Studies, Humans, CEACAM5, Asthma/genetics, Science & Technology, STATEMENT, Sputum, Transcriptome/genetics, Asthma, frequent exacerbators, Oncology, Medicine, Research & Experimental, asthma exacerbations, Molecular Medicine, U-BIOPRED study group, 610 Medizin und Gesundheit, Transcriptome, Life Sciences & Biomedicine, persistent frequent exacerbators, LUNG
Abstract

BACKGROUND: Exacerbation-prone asthma is a feature of severe disease. However, the basis for its persistency remains unclear.OBJECTIVES: To determine the clinical and transcriptomic features of frequent exacerbators (FEs) and persistent FEs (PFEs) in the U-BIOPRED cohort.METHODS: We compared features of FE (≥2 exacerbations in past year) to infrequent exacerbators (IE, RESULTS: Of 317 patients, 62.4% had FE, of whom 63.6% had PFE, while 37.6% had IE, of whom 61.3% had PIE. Using multivariate analysis, FE was associated with short-acting beta-agonist use, sinusitis and daily oral corticosteroid use, while PFE was associated with eczema, short-acting beta-agonist use and asthma control index. CEA cell adhesion molecule 5 (CEACAM5) was the only differentially expressed transcript in bronchial biopsies between PE and IE. There were no differentially expressed genes in the other four compartments. There were higher expression scores for type 2, T-helper type-17 and type 1 pathway signatures together with those associated with viral infections in bronchial biopsies from FE compared to IE, while there were higher expression scores of type 2, type 1 and steroid insensitivity pathway signatures in bronchial biopsies of PFE compared to PIE.CONCLUSION: The FE group and its PFE subgroup are associated with poor asthma control while expressing higher type 1 and type 2 activation pathways compared to IE and PIE, respectively.

Published
2022

39. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie F., Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M., Wheelock, Craig E., Reinke, Stacey N., Naz, Shama, Chaleckis, Romanas, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z., Tiotiu, Angelica, Broadhurst, David I., Lundqvist, Anders, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnus, Sousa, Ana R., Riley, John H., Bates, Stewart, Scholfield, James, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J., Geiser, Thomas, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie F., Singer, Florian, Musial, Jacek, Shaw, Dominick E., Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J., Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M., and Wheelock, Craig E.

Abstract

INTRODUCTION: Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication. METHODS: Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods. RESULTS: A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6×10-20), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5×10-4), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings. CONCLUSIONS: This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carn

Published
2022
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40. Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma

Author

Badi, Yusef Eamon, Pavel, Ana B., Pavlidis, Stelios, Riley, John H., Bates, Stewart, Kermani, Nazanin Zounemat, Knowles, Richard, Kolmert, Johan, Wheelock, Craig E., Worsley, Sally, Uddin, Mohib, Alving, Kjell, Bakke, Per S., Behndig, Annelie, Caruso, Massimo, Chanez, Pascal, Fleming, Louise J., Fowler, Stephen J., Frey, Urs, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Maitland-van der Zee, Anke H., Montuschi, Paolo, Roberts, Graham, Sanak, Marek, Shaw, Dominick E., Singer, Florian, Sterk, Peter J., Djukanovic, Ratko, Dahlen, Sven-Eric, Guo, Yi-Ke, Chung, Kian Fan, Guttman-Yassky, Emma, Adcock, Ian M., Badi, Yusef Eamon, Pavel, Ana B., Pavlidis, Stelios, Riley, John H., Bates, Stewart, Kermani, Nazanin Zounemat, Knowles, Richard, Kolmert, Johan, Wheelock, Craig E., Worsley, Sally, Uddin, Mohib, Alving, Kjell, Bakke, Per S., Behndig, Annelie, Caruso, Massimo, Chanez, Pascal, Fleming, Louise J., Fowler, Stephen J., Frey, Urs, Howarth, Peter, Horvath, Ildiko, Krug, Norbert, Maitland-van der Zee, Anke H., Montuschi, Paolo, Roberts, Graham, Sanak, Marek, Shaw, Dominick E., Singer, Florian, Sterk, Peter J., Djukanovic, Ratko, Dahlen, Sven-Eric, Guo, Yi-Ke, Chung, Kian Fan, Guttman-Yassky, Emma, and Adcock, Ian M.

Abstract

Background: Transcriptomic changes in patients who respond clinically to biological therapies may identify responses in other tissues or diseases. Objective: We sought to determine whether a disease signature identified in atopic dermatitis (AD) is seen in adults with severe asthma and whether a transcriptomic signature for patients with AD who respond clinically to anti-IL-22 (fezakinumab [FZ]) is enriched in severe asthma. Methods: An AD disease signature was obtained from analysis of differentially expressed genes between AD lesional and nonlesional skin biopsies. Differentially expressed genes from lesional skin from therapeutic superresponders before and after 12 weeks of FZ treatment defined the FZ-response signature. Gene set variation analysis was used to produce enrichment scores of AD and FZ-response signatures in the Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes asthma cohort. Results: The AD disease signature (112 upregulated genes) encompassing inflammatory, T-cell, T(H)2, and T(H)17/T(H)22 pathways was enriched in the blood and sputum of patients with asthma with increasing severity. Patients with asthma with sputum neutrophilia and mixed granulocyte phenotypes were the most enriched (P < .05). The FZ-response signature (296 downregulated genes) was enriched in asthmatic blood (P < .05) and particularly in neutrophilic and mixed granulocytic sputum (P < .05). These data were confirmed in sputum of the Airway Disease Endotyping for Personalized Therapeutics cohort. IL-22 mRNA across tissues did not correlate with FZ-response enrichment scores, but this response signature correlated with T(H)22/IL-22 pathways. Conclusions: The FZ-response signature in AD identifies severe neutrophilic asthmatic patients as potential responders to FZ therapy. This approach will help identify patients for future asthma clinical trials of drugs used successfully in other chronic diseases.

Published
2022
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41. A multi-omics approach to delineate sputum microbiome-associated asthma inflammatory phenotypes

Author

Abdel-Aziz, Mahmoud I., Vijverberg, Susanne J.H., Neerincx, Anne H., Brinkman, Paul, Wagener, Ariane H., Riley, John H., Sousa, Ana R., Bates, Stewart, Wagers, Scott S., De Meulder, Bertrand, Auffray, Charles, Wheelock, Åsa M., Bansal, Aruna T., Caruso, Massimo, Chanez, Pascal, Uddin, Mohib, Corfield, Julie, Horvath, Ildiko, Krug, Norbert, Musial, Jacek, Sun, Kai, Shaw, Dominick E., Sandström, Thomas, Montuschi, Paolo, Fowler, Stephen J., Lutter, René, Djukanovic, Ratko, Howarth, Peter, Skipp, Paul, Sanak, Marek, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Kraneveld, Aletta D., Maitland-Van der Zee, Anke H., Abdel-Aziz, Mahmoud I., Vijverberg, Susanne J.H., Neerincx, Anne H., Brinkman, Paul, Wagener, Ariane H., Riley, John H., Sousa, Ana R., Bates, Stewart, Wagers, Scott S., De Meulder, Bertrand, Auffray, Charles, Wheelock, Åsa M., Bansal, Aruna T., Caruso, Massimo, Chanez, Pascal, Uddin, Mohib, Corfield, Julie, Horvath, Ildiko, Krug, Norbert, Musial, Jacek, Sun, Kai, Shaw, Dominick E., Sandström, Thomas, Montuschi, Paolo, Fowler, Stephen J., Lutter, René, Djukanovic, Ratko, Howarth, Peter, Skipp, Paul, Sanak, Marek, Adcock, Ian M., Chung, Kian Fan, Sterk, Peter J., Kraneveld, Aletta D., and Maitland-Van der Zee, Anke H.

Abstract

A multi-omics approach revealed the underlying biological pathways in the microbiome-driven severe asthma phenotypes. This may help to elucidate new leads for treatment development, particularly for the therapeutically challenging neutrophilic asthma.

Published
2022
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42. Urinary metabotype of severe asthma evidences decreased carnitine metabolism independent of oral corticosteroid treatment in the U-BIOPRED study

Author

Reinke, Stacey N, Naz, Shama, Chaleckis, Romana, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z, Tiotiu, Angelica, Broadhurst, David I, Lundqvist, Ander, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnu, Sousa, Ana R, Riley, John H, Bates, Stewart, Scholfield, Jame, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J, Geiser, Thoma, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E, Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J, Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M, Wheelock, Craig E, Montuschi, Paolo (ORCID:0000-0001-5589-1750), Reinke, Stacey N, Naz, Shama, Chaleckis, Romana, Gallart-Ayala, Hector, Kolmert, Johan, Kermani, Nazanin Z, Tiotiu, Angelica, Broadhurst, David I, Lundqvist, Ander, Olsson, Henric, Ström, Marika, Wheelock, Åsa M, Gómez, Cristina, Ericsson, Magnu, Sousa, Ana R, Riley, John H, Bates, Stewart, Scholfield, Jame, Loza, Matthew, Baribaud, Frédéric, Bakke, Per S, Caruso, Massimo, Chanez, Pascal, Fowler, Stephen J, Geiser, Thoma, Howarth, Peter, Horváth, Ildikó, Krug, Norbert, Montuschi, Paolo, Behndig, Annelie, Singer, Florian, Musial, Jacek, Shaw, Dominick E, Dahlén, Barbro, Hu, Sile, Lasky-Su, Jessica, Sterk, Peter J, Chung, Kian Fan, Djukanovic, Ratko, Dahlén, Sven-Erik, Adcock, Ian M, Wheelock, Craig E, and Montuschi, Paolo (ORCID:0000-0001-5589-1750)

Abstract

Introduction Asthma is a heterogeneous disease with poorly defined phenotypes. Patients with severe asthma often receive multiple treatments including oral corticosteroids (OCS). Treatment may modify the observed metabotype, rendering it challenging to investigate underlying disease mechanisms. Here, we aimed to identify dysregulated metabolic processes in relation to asthma severity and medication.Methods Baseline urine was collected prospectively from healthy participants (n=100), patients with mild-to-moderate asthma (n=87) and patients with severe asthma (n=418) in the cross-sectional U-BIOPRED cohort; 12-18-month longitudinal samples were collected from patients with severe asthma (n=305). Metabolomics data were acquired using high-resolution mass spectrometry and analysed using univariate and multivariate methods.Results A total of 90 metabolites were identified, with 40 significantly altered (p<0.05, false discovery rate <0.05) in severe asthma and 23 by OCS use. Multivariate modelling showed that observed metabotypes in healthy participants and patients with mild-to-moderate asthma differed significantly from those in patients with severe asthma (p=2.6x10(-20)), OCS-treated asthmatic patients differed significantly from non-treated patients (p=9.5x10(-4)), and longitudinal metabotypes demonstrated temporal stability. Carnitine levels evidenced the strongest OCS-independent decrease in severe asthma. Reduced carnitine levels were associated with mitochondrial dysfunction via decreases in pathway enrichment scores of fatty acid metabolism and reduced expression of the carnitine transporter SLC22A5 in sputum and bronchial brushings.Conclusions This is the first large-scale study to delineate disease- and OCS-associated metabolic differences in asthma. The widespread associations with different therapies upon the observed metabotypes demonstrate the need to evaluate potential modulating effects on a treatment- and metabolite-specific basis. Altered carniti

Published
2022

43. Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma

Author

Tiotiu, Angelica, Badi, Yusef, Kermani, Nazanin Zounemat, Sanak, Marek, Kolmert, Johan, Wheelock, Craig E., Hansbro, Philip M., Dahlén, Sven-Erik, Sterk, Peter J., Djukanovic, Ratko, Guo, Yike, Mumby, Sharon, U-BIOPRED Consortium Project Team, Tiotiu, Angelica, Badi, Yusef, Kermani, Nazanin Zounemat, Sanak, Marek, Kolmert, Johan, Wheelock, Craig E., Hansbro, Philip M., Dahlén, Sven-Erik, Sterk, Peter J., Djukanovic, Ratko, Guo, Yike, Mumby, Sharon, and U-BIOPRED Consortium Project Team

Abstract

Rationale: Mast cells (MCs) play a role in inflammation and both innate and adaptive immunity, but their involvement in severe asthma (SA) remains undefined. Objectives: We investigated the phenotypic characteristics of the U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Diseases Outcomes) asthma cohort by applying published MC activation signatures to the sputum cell transcriptome. Methods: Eighty-four participants with SA, 20 with mild/moderate asthma (MMA), and 16 healthy participants without asthma were studied. We calculated enrichment scores (ESs) for nine MC activation signatures by asthma severity, sputum granulocyte status, and three previously defined sputum molecular phenotypes or transcriptome-associated clusters (TACs) 1, 2, and 3 using gene set variation analysis. Measurements and Main Results: MC signatures except unstimulated, repeated FceR1-stimulated and IFN-g–stimulated signatures were enriched in SA. A FceR1-IgE–stimulated and a single-cell signature from asthmatic bronchial biopsies were highly enriched in eosinophilic asthma and in the TAC1 molecular phenotype. Subjects with a high ES for these signatures had elevated sputum amounts of similar genes and pathways. IL-33– and LPS-stimulated MC signatures had greater ES in neutrophilic and mixed granulocytic asthma and in the TAC2 molecular phenotype. These subjects exhibited neutrophil, NF-kB (nuclear factor-kB), and IL-1b/TNF-a (tumor necrosis factor-a) pathway activation. The IFN-g–stimulated signature had the greatest ES in TAC2 and TAC3 that was associated with responses to viral infection. Similar results were obtained in an independent ADEPT (Airway Disease Endotyping for Personalized Therapeutics) asthma cohort. Conclusions: Gene signatures of MC activation allow the detection of SA phenotypes and indicate that MCs can be induced to take on distinct transcriptional phenotypes associated with specific clinical phenotypes. IL-33–stimulated MC signature was associated with se

Published
2022

45. A Transcriptome-driven Analysis of Epithelial Brushings and Bronchial Biopsies to Define Asthma Phenotypes in U-BIOPRED

Author

Kuo, Chih-Hsi Scott, Pavlidis, Stelios, Loza, Matthew, Baribaud, Fred, Rowe, Anthony, Pandis, Ioannis, Hoda, Uruj, Rossios, Christos, Sousa, Ana, Wilson, Susan J., Howarth, Peter, Dahlen, Barbro, Dahlen, Sven-Erik, Chanez, Pascal, Shaw, Dominick, Krug, Norbert, Sandström, Thomas, De Meulder, Bertrand, Lefaudeux, Diane, Fowler, Stephen, Fleming, Louise, Corfield, Julie, Auffray, Charles, Sterk, Peter J., Djukanovic, Ratko, Guo, Yike, Adcock, Ian M., and Chung, Kian Fan

Published
2017
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47. Association of Differential Mast Cell Activation with Granulocytic Inflammation in Severe Asthma

Author

Tiotiu, Angelica, primary, Badi, Yusef, additional, Kermani, Nazanin Zounemat, additional, Sanak, Marek, additional, Kolmert, Johan, additional, Wheelock, Craig E., additional, Hansbro, Philip M., additional, Dahlén, Sven-Erik, additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Guo, Yike, additional, Mumby, Sharon, additional, Adcock, Ian M., additional, Chung, Kian Fan, additional, Hoda, Uruj, additional, Rossios, Christos, additional, Bel, Elisabeth, additional, Rao, Navin, additional, Myles, David, additional, Compton, Chris, additional, Van Geest, Marleen, additional, Howarth, Peter, additional, Roberts, Graham, additional, Lefaudeux, Diane, additional, De Meulder, Bertrand, additional, Bansal, Aruna T., additional, Knowles, Richard, additional, Erzen, Damijn, additional, Wagers, Scott, additional, Krug, Norbert, additional, Higenbottam, Tim, additional, Matthews, John, additional, Erpenbeek, Veit, additional, Carayannopoulos, Leon, additional, Roberts, Amanda, additional, Supple, David, additional, deBoer, Pim, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Horváth, Ildikó, additional, Musial, Jacek, additional, and Sandström, Thomas, additional

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

Author

Mikus, Maria Sparreman, Kolmert, Johan, Andersson, Lars I., Östling, Jörgen, Knowles, Richard G., Gómez, Cristina, Ericsson, Magnus, Thörngren, John Olof, Khoonsari, Payam Emami, Dahlén, Barbro, Kupczyk, Maciej, de Meulder, Bertrand, Auffray, Charles, Bakke, Per S., Beghe, Bianca, Bel, Elisabeth H., Caruso, Massimo, Chanez, Pascal, Chawes, Bo, Fowler, Stephen J., Gaga, Mina, Geiser, Thomas, Gjomarkaj, Mark, Horváth, Ildikó, Howarth, Peter H., Johnston, Sebastian L., Joos, Guy, Krug, Norbert, Montuschi, Paolo, Musial, Jacek, Niżankowska-Mogilnicka, Ewa, Olsson, Henric K., Papi, Alberto, Rabe, Klaus F., Sandström, Thomas, Shaw, Dominick E., Siafakas, Nikolaos M., Uhlén, Mathias, Riley, John H., Bates, Stewart, Middelveld, Roelinde J.M., Wheelock, Craig E., Chung, Kian Fan, Adcock, Ian M., Sterk, Peter J., Bisgaard, Hans, Bønnelykke, Klaus, Vestbo, Jørgen, Vissing, Nadja H., and Olsson, Marianne

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.

Published
2022

49. Corrigendum to 'eNose analysis for early immunotherapy response monitoring in non-small cell lung cancer' [Lung Cancer 160 (2021) 36–43] (Lung Cancer (2021) 160 (36–43), (S0169500221004827), (10.1016/j.lungcan.2021.07.017))

Author

Buma, Alessandra I. G., Muller, Mirte, de Vries, Rianne, Sterk, Peter J., van der Noort, Vincent, Wolf-Lansdorf, Marguerite, Farzan, Niloufar, Baas, Paul, van den Heuvel, Michel M., AII - Inflammatory diseases, Graduate School, Pulmonology, and Amsterdam Reproduction & Development (AR&D)

Abstract

The authors regret that absolute sensor differences were not calculated “by subtracting sensor values measured after six weeks of treatment from sensor values measured at baseline for each sensor”, as mentioned in the “Statistical analysis” section, page 3 of the Supplementary appendix, but “by subtracting sensor values measured at baseline from sensor values measured after six weeks of treatment for each sensor”. The authors would like to apologise for any inconvenience caused.

Published
2021

50. Mapping atopic dermatitis and anti–IL-22 response signatures to type 2–low severe neutrophilic asthma

Author

Badi, Yusef Eamon, primary, Pavel, Ana B., additional, Pavlidis, Stelios, additional, Riley, John H., additional, Bates, Stewart, additional, Kermani, Nazanin Zounemat, additional, Knowles, Richard, additional, Kolmert, Johan, additional, Wheelock, Craig E., additional, Worsley, Sally, additional, Uddin, Mohib, additional, Alving, Kjell, additional, Bakke, Per S., additional, Behndig, Annelie, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fleming, Louise J., additional, Fowler, Stephen J., additional, Frey, Urs, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Maitland-van der Zee, Anke H., additional, Montuschi, Paolo, additional, Roberts, Graham, additional, Sanak, Marek, additional, Shaw, Dominick E., additional, Singer, Florian, additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Dahlen, Sven-Eric, additional, Guo, Yi-Ke, additional, Chung, Kian Fan, additional, Guttman-Yassky, Emma, additional, and Adcock, Ian M., additional

Published
2022
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