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369 results on '"Dahlen, Sven-Erik"'

4. 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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5. 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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6. 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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10. Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

Author

Peltrini, Rosa, Cordell, Rebecca L., Wilde, Michael, Abuhelal, Shahd, Quek, Eleanor, Zounemat-Kermani, Nazanin, Ibrahim, Wadah, Richardson, Matthew, Brinkman, Paul, Schleich, Florence, Stefanuto, Pierre-Hugues, Aung, Hnin, Greening, Neil, Dahlen, Sven Erik, Djukanovic, Ratko, Adcock, Ian M., Brightling, Christopher, Monks, Paul, and Siddiqui, Salman

Subjects
RECEIVER operating characteristic curves, GAS chromatography/Mass spectrometry (GC-MS), ASTHMA, THERMAL desorption
Abstract

Rationale: Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker signature to predict sputum eosinophilia in asthma. Methods: VOCs emitted into the space above sputum samples (headspace) from patients with severe asthma (n = 36) were collected onto sorbent tubes and analyzed using thermal desorption gas chromatography–mass spectrometry (GC-MS). Elastic net regression identified stable VOCs associated with sputum eosinophilia ⩾ 3% and generated a volatile biomarker signature. This VOC signature was validated in breath samples from: 1) patients with acute asthma according to blood eosinophilia ⩾0.3 × 109cells/L or sputum eosinophilia of ⩾3% in the UK EMBER (East Midlands Breathomics Pathology Node) consortium (n = 65) and 2) U-BIOPRED-IMI (Unbiased Biomarkers in Prediction of Respiratory Disease Outcomes Innovative Medicines Initiative) consortium (n = 42). Breath samples were collected onto sorbent tubes (EMBER) or Tedlar bags (U-BIOPRED) and analyzed by GC-MS (GC × GC-MS for EMBER or GC-MS for U-BIOPRED). Measurements and Main Results: The in vitro headspace identified 19 VOCs associated with sputum eosinophilia, and the derived VOC signature yielded good diagnostic accuracy for sputum eosinophilia ⩾3% in headspace (area under the receiver operating characteristic curve [AUROC] 0.90; 95% confidence interval [CI], 0.80–0.99; P < 0.0001), correlated inversely with sputum eosinophil percentage (rs = −0.71; P < 0.0001), and outperformed fractional exhaled nitric oxide (AUROC 0.61; 95% CI, 0.35–0.86). Analysis of exhaled breath in replication cohorts yielded a VOC signature AUROC (95% CI) for acute asthma exacerbations of 0.89 (0.76–1.0) (EMBER cohort) with sputum eosinophilia and 0.90 (0.75–1.0) in U-BIOPRED, again outperforming fractional exhaled nitric oxide in U-BIOPRED (0.62 [0.33–0.90]). Conclusions: We have discovered and provided early-stage clinical validation of a volatile biomarker signature associated with eosinophilic airway inflammation. Further work is needed to translate our discovery using point-of-care clinical sensors. [ABSTRACT FROM AUTHOR]

Published
2024
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11. 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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12. Endotypes of severe neutrophilic and eosinophilic asthma from multi‐omics integration of U‐BIOPRED sputum samples.

Author

Kermani, Nazanin Zounemat, Li, Chuan‐Xing, Versi, Ali, Badi, Yusef, Sun, Kai, Abdel‐Aziz, Mahmoud I, Bonatti, Martina, Maitland‐van der Zee, Anke‐Hilse, Djukanovic, Ratko, Wheelock, Åsa, Dahlen, Sven‐Erik, Howarth, Peter, Guo, Yike, Chung, Kian Fan, and Adcock, Ian M.

Subjects
ASTHMATICS, MORAXELLA catarrhalis, HAEMOPHILUS influenzae, NASAL polyps, ALLERGIC rhinitis
Abstract

Background: Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi‐omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development. Objectives: To determine whether multi‐omics integration of sputum leads to improved granularity of the molecular classification of severe asthma. Methods: We analyzed six ‐omics data blocks–microarray transcriptomics, gene set variation analysis of microarray transcriptomics, SomaSCAN proteomics assay, shotgun proteomics, 16S microbiome sequencing, and shotgun metagenomic sequencing–from induced sputum samples of 57 severe asthma patients, 15 mild‐moderate asthma patients, and 13 healthy volunteers in the U‐BIOPRED European cohort. We used Monti consensus clustering algorithm for aggregation of clustering results and Similarity Network Fusion to integrate the 6 multi‐omics datasets of the 72 asthmatics. Results: Five stable omics‐associated clusters were identified (OACs). OAC1 had the best lung function with the least number of severe asthmatics with sputum paucigranulocytic inflammation. OAC5 also had fewer severe asthma patients but the highest incidence of atopy and allergic rhinitis, with paucigranulocytic inflammation. OAC3 comprised only severe asthmatics with the highest sputum eosinophilia. OAC2 had the highest sputum neutrophilia followed by OAC4 with both clusters consisting of mostly severe asthma but with more ex/current smokers in OAC4. Compared to OAC4, there was higher incidence of nasal polyps, allergic rhinitis, and eczema in OAC2. OAC2 had microbial dysbiosis with abundant Moraxella catarrhalis and Haemophilus influenzae. OAC4 was associated with pathways linked to IL‐22 cytokine activation, with the prediction of therapeutic response to anti‐IL22 antibody therapy. Conclusion: Multi‐omics analysis of sputum in asthma has defined with greater granularity the asthma endotypes linked to neutrophilic and eosinophilic inflammation. Modelling diverse types of high‐dimensional interactions will contribute to a more comprehensive understanding of complex endotypes. Key Points: Unsupervised clustering on sputum multi‐omics of asthma subjects identified 3 out of 5 clusters with predominantly severe asthma.One severe asthma cluster was linked to type 2 inflammation and sputum eosinophilia while the other 2 clusters to sputum neutrophilia.One severe neutrophilic asthma cluster was linked to Moraxella catarrhalis and to a lesser extent Haemophilus influenzae while the second cluster to activation of IL‐22. [ABSTRACT FROM AUTHOR]

Published
2024
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14. 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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16. 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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18. 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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19. Analysis of human lung mast cells by single cell RNA sequencing

Author

Ronnberg, Elin, Ravindran, Avinash, Mazzurana, Luca, Gong, Yitao, Safholm, Jesper, Lorent, Julie, Dethlefsen, Olga, Orre, Ann-Charlotte, Al-Ameri, Mamdoh, Adner, Mikael, Dahlen, Sven-Erik, Dahlin, Joakim S., Mjosberg, Jenny, Nilsson, Gunnar, Ronnberg, Elin, Ravindran, Avinash, Mazzurana, Luca, Gong, Yitao, Safholm, Jesper, Lorent, Julie, Dethlefsen, Olga, Orre, Ann-Charlotte, Al-Ameri, Mamdoh, Adner, Mikael, Dahlen, Sven-Erik, Dahlin, Joakim S., Mjosberg, Jenny, and Nilsson, Gunnar

Abstract

Mast cells are tissue-resident cells playing major roles in homeostasis and disease conditions. Lung mast cells are particularly important in airway inflammatory diseases such as asthma. Human mast cells are classically divided into the subsets MCT and MCTC, where MCT express the mast cell protease tryptase and MCTC in addition express chymase, carboxypeptidase A3 (CPA3) and cathepsin G. Apart from the disctintion of the MCT and MCTC subsets, little is known about the heterogeniety of human lung mast cells and a deep analysis of their heterogeniety has previously not been performed. We therefore performed single cell RNA sequencing on sorted human lung mast cells using SmartSeq2. The mast cells showed high expression of classical mast cell markers. The expression of several individual genes varied considerably among the cells, however, no subpopulations were detected by unbiased clustering. Variable genes included the protease-encoding transcripts CMA1 (chymase) and CTSG (cathepsin G). Human lung mast cells are predominantly of the MCT subset and consistent with this, the expression of CMA1 was only detectable in a small proportion of the cells, and correlated moderately to CTSG. However, in contrast to established data for the protein, CPA3 mRNA was high in all cells and the correlation of CPA3 to CMA1 was weak.

Published
2023
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20. MACVIA clinical decision algorithm in adolescents and adults with allergic rhinitis

Author

Aberer, Werner, Adachi, Mitsuru, Agache, Ioana, Akdis, Cezmi, Akdis, Mubeccel, Annesi-Maesano, Isabella, Ansotegui, Ignacio J., Anto, Josep M., Arshad, S. Hasan, Baiardini, Ilaria, Baigenzhin, Abay K., Barbara, Cristina, Bateman, Eric D., Beghé, Bianca, Bel, Elisabeth H., Ben Kheder, Ali, Bennoor, Kazi S., Benson, Michael, Bernstein, David, Michael, Bewick, Thomas, Bieber, Bindslev-Jensen, Carsten, Bjermer, Leif, Blain, Hubert, Boner, Attilio, Bonini, Matteo, Bonini, Sergio, Bosse, Isabelle, Bouchard, Jacques, Boulet, Louis-Philippe, Bourret, Rodolphe A., Bousquet, Philippe J., Braido, Fulvio, Briggs, Andrew H., Brightling, Christopher E., Buhl, Roland, Burney, Peter, Bush, Andrew, Caballero-Fonseca, Fernando, Caimmi, Davide P., Camargos, Paulo, Camuzat, Thierry, Carlsen, Kai-Hakon, Carr, Warner, Casale, Thomas B., Sarabia, Alfonso Cepeda, Chatzi, Leda, Chen, Yuzhi, Chiron, Raphaël, Chkhartishvili, Ekaterine, Chuchalin, Alexander, Ciprandi, Georgio, Cirule, Ieva, Correia de Sousa, Jaime, Costa, David, Crooks, George, Custovic, Adnan, Dahlen, Sven-Erik, Darsow, Ulf, De Blay, Frédéric, De Manuel Keenoy, Esteban, Dedeu, Tony, Deleanu, Diana, Denburg, Judah, Didier, Alain, Dinh-Xuan, Anh-Tuan, Dokic, Dejan, Douagui, Habib B., Dubakiene, Ruta, Durham, Stephen, Dykewicz, Mark, El-Gamal, Yehia, Emuzyte, Regina, Fink-Wagner, Antje, Fiocchi, Alessandro, Forastiere, Francesco, Gamkrelidze, Amiran, Gemicioğlu, Bilun, Gereda, Jose E., Gerth van Wijk, Roy, Gotua, Maia, Grisle, Ineta, Guzmán, M. Antonieta, Haahtela, Tari, Heinrich, Joachim, Hellquist-Dahl, Birthe, Horak, Friedrich, Howarth, Peter H., Humbert, Marc, Hyland, Michael, Ivancevich, Juan-Carlos, Jares, Edgardo J., Johnston, Sebastian L., Jonquet, Olivier, Joos, Guy, Jung, Ki-Suck, Just, Jocelyne, Jutel, Marek, Kaidashev, Igor P., Khaitov, Musa, Kalayci, Omer, Kalyoncu, Fuat, Keith, Paul, Khaltaev, Nikolai, Kleine-Tebbe, Jorg, Klimek, Ludger, N'Goran, Bernard Koffi, Kolek, Vitezlav, Koppelman, Gerard H., Kowalski, Marek, Kull, Inger, Kvedariene, Violeta, Lambrecht, Bart, Lau, Susanne, Laune, Daniel, Le Thi Tuyet, Lan, Li, Jing, Lieberman, Phillipe, Lipworth, Brian J., Renaud, Louis, Magard, Yves, Magnan, Antoine, Mahboub, Bassam, Majer, Ivan, Makela, Mika, Manning, Peter J., Masjedi, Mohamad R., Maurer, Marcus, Mavale-Manuel, Sandra, Melén, Erik, Melo-Gomes, Elisabete, Mercier, Jacques, Merk, Hans, Miculinic, Neven, Mihaltan, Florin, Milenkovic, Branislava, Mohammad, Yousser, Molimard, Mathieu, Momas, Isabelle, Montilla-Santana, Anna, Morais-Almeida, Mario, Mösges, Ralph, Nadif, Rachel, Namazova-Baranova, Leyla, Neffen, Hugo, Nekam, Kristof, Neou, Angelos, Niggemann, Bodo, Nyembue, Dieudonné, O'Hehir, Robyn, Ohta, Ken, Okamoto, Yoshitaka, Okubo, Kim, Ouedraogo, Solange, Paggiaro, Pier-Luigi, Pali-Schöll, Isabella, Palmer, Stephen, Panzner, Petr, Papi, Alberto, Park, Hae-Sim, Pavord, Ian, Pawankar, Ruby, Pfaar, Oliver, Picard, Robert, Pigearias, Bernard, Pin, Isabelle, Plavec, Davor, Pohl, Wolfgang, Popov, Todor, Postma, Dirkje S., Potter, Paul, Poulsen, Lars K., Rabe, Klaus F., Raciborski, Filip, Pontal, Françoise Radier, Reitamo, Sakari, Repka-Ramirez, Maria-Susana, Robalo-Cordeiro, Carlos, Roberts, Graham, Rodenas, Francisco, Rolland, Christine, Rodriguez, Miguel Roman, Romano, Antonino, Rosado-Pinto, José, Rosario, Nelson A., Rosenwasser, Larry, Rottem, Menachem, Sanchez-Borges, Mario, Sastre-Dominguez, Joaquim, Schmid-Grendelmeier, Peter, Serrano, Eli, Simons, F. Estelle R., Sisul, Juan-Carlos, Skrindo, Ingebjorg, Smit, Henriette A., Solé, Dirceu, Sooronbaev, Talant, Spranger, Otto, Stelmach, Rafael, Strandberg, Timo, Sunyer, Jordi, Thijs, Carel, Todo-Bom, Ana-Maria, Triggiani, Massimo, Valenta, Rudolf, Valero, Antonio L., van Hage, Marianne, Vandenplas, Olivier, Vezzani, Giorgio, Vichyanond, Pakit, Viegi, Giovanni, Wagenmann, Martin, Wahn, Ulrich, De Yun, Wang, Williams, Denis, Wright, John, Yawn, Barbara P., Yiallouros, Panayiotis, Yusuf, Osman M., Zar, Heather J., Zernotti, Mario, Zhang, Luo, Zhong, Nanshan, Zidarn, Mihaela, Bousquet, Jean, Schünemann, Holger J., Hellings, Peter W., Arnavielhe, Sylvie, Bachert, Claus, Bedbrook, Anna, Bergmann, Karl-Christian, Bosnic-Anticevich, Sinthia, Brozek, Jan, Calderon, Moises, Canonica, G. Walter, Chavannes, Niels H., Cox, Linda, Chrystyn, Henry, Cruz, Alvaro A., Dahl, Ronald, De Carlo, Giuseppe, Demoly, Pascal, Devillier, Phillipe, Dray, Gérard, Fletcher, Monica, Fokkens, Wytske J., Fonseca, Joao, Gonzalez-Diaz, Sandra N., Grouse, Lawrence, Keil, Thomas, Kuna, Piotr, Larenas-Linnemann, Désirée, Lodrup Carlsen, Karin C., Meltzer, Eli O., Mullol, Jaoquim, Muraro, Antonella, Naclerio, Robert N., Palkonen, Susanna, Papadopoulos, Nikolaos G., Passalacqua, Giovanni, Price, David, Ryan, Dermot, Samolinski, Boleslaw, Scadding, Glenis K., Sheikh, Aziz, Spertini, François, Valiulis, Arunas, Valovirta, Erkka, Walker, Samantha, Wickman, Magnus, Yorgancioglu, Arzu, and Zuberbier, Torsten

Published
2016
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22. Haemophilus influenzae and Moraxella catarrhalis in sputum of severe asthma with inflammasome and neutrophil activation.

Author

Versi, Ali, Ivan, Fransiskus Xaverius, Abdel‐Aziz, Mahmoud I., Bates, Stewart, Riley, John, Baribaud, Frederic, Kermani, Nazanin Zounemat, Montuschi, Paolo, Dahlen, Sven‐Erik, Djukanovic, Ratko, Sterk, Peter, Maitland‐Van Der Zee, Anke H., Chotirmall, Sanjay H., Howarth, Peter, Adcock, Ian M., Chung, Kian Fan, Andersson, LI, Auffray, C, Badi, YE, and Bakke, P

Subjects
HAEMOPHILUS influenzae, MORAXELLA catarrhalis, SPUTUM, ASTHMA, ASTHMATICS, HAEMOPHILUS diseases
Abstract

Background: Because of altered airway microbiome in asthma, we analysed the bacterial species in sputum of patients with severe asthma. Methods: Whole genome sequencing was performed on induced sputum from non‐smoking (SAn) and current or ex‐smoker (SAs/ex) severe asthma patients, mild/moderate asthma (MMA) and healthy controls (HC). Data were analysed by asthma severity, inflammatory status and transcriptome‐associated clusters (TACs). Results: α‐diversity at the species level was lower in SAn and SAs/ex, with an increase in Haemophilus influenzae and Moraxella catarrhalis, and Haemophilus influenzae and Tropheryma whipplei, respectively, compared to HC. In neutrophilic asthma, there was greater abundance of Haemophilus influenzae and Moraxella catarrhalis and in eosinophilic asthma, Tropheryma whipplei was increased. There was a reduction in α‐diversity in TAC1 and TAC2 that expressed high levels of Haemophilus influenzae and Tropheryma whipplei, and Haemophilus influenzae and Moraxella catarrhalis, respectively, compared to HC. Sputum neutrophils correlated positively with Moraxella catarrhalis and negatively with Prevotella, Neisseria and Veillonella species and Haemophilus parainfluenzae. Sputum eosinophils correlated positively with Tropheryma whipplei which correlated with pack‐years of smoking. α‐ and β‐diversities were stable at one year. Conclusions: Haemophilus influenzae and Moraxella catarrhalis were more abundant in severe neutrophilic asthma and TAC2 linked to inflammasome and neutrophil activation, while Haemophilus influenzae and Tropheryma whipplei were highest in SAs/ex and in TAC1 associated with highest expression of IL‐13 type 2 and ILC2 signatures with the abundance of Tropheryma whipplei correlating positively with sputum eosinophils. Whether these bacterial species drive the inflammatory response in asthma needs evaluation. [ABSTRACT FROM AUTHOR]

Published
2023
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31. 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

32. Immunoprofiling Reveals Novel Mast Cell Receptors and the Continuous Nature of Human Lung Mast Cell Heterogeneity

Author

Ronnberg, Elin, Boey, Daryl Zhong Hao, Ravindran, Avinash, Safholm, Jesper, Orre, Ann-Charlotte, Al-Ameri, Mamdoh, Adner, Mikael, Dahlen, Sven-Erik, Dahlin, Joakim S., Nilsson, Gunnar, Ronnberg, Elin, Boey, Daryl Zhong Hao, Ravindran, Avinash, Safholm, Jesper, Orre, Ann-Charlotte, Al-Ameri, Mamdoh, Adner, Mikael, Dahlen, Sven-Erik, Dahlin, Joakim S., and Nilsson, Gunnar

Abstract

Background: Immunohistochemical analysis of granule-associated proteases has revealed that human lung mast cells constitute a heterogeneous population of cells, with distinct subpopulations identified. However, a systematic and comprehensive analysis of cell-surface markers to study human lung mast cell heterogeneity has yet to be performed.Methods: Human lung mast cells were obtained from lung lobectomies, and the expression of 332 cell-surface markers was analyzed using flow cytometry and the LEGENDScreen (TM) kit. Markers that exhibited high variance were selected for additional analyses to reveal whether they were correlated and whether discrete mast cell subpopulations were discernable.Results: We identified the expression of 102 surface markers on human lung mast cells, 23 previously not described on mast cells, of which several showed high continuous variation in their expression. Six of these markers were correlated: SUSD2, CD49a, CD326, CD34, CD66 and HLA-DR. The expression of these markers was also correlated with the size and granularity of mast cells. However, no marker produced an expression profile consistent with a bi- or multimodal distribution.Conclusions: LEGENDScreen analysis identified more than 100 cell-surface markers on mast cells, including 23 that, to the best of our knowledge, have not been previously described on human mast cells. The comprehensive expression profiling of the 332 surface markers did not identify distinct mast cell subpopulations. Instead, we demonstrate the continuous nature of human lung mast cell heterogeneity.

Published
2022
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33. Activation of succinate receptor 1 boosts human mast cell reactivity and allergic bronchoconstriction

Author

Tang, Xiao, Ronnberg, Elin, Safholm, Jesper, Thulasingam, Madhuranayaki, Trauelsen, Mette, Schwartz, Thue W., Wheelock, Craig E., Dahlen, Sven-Erik, Nilsson, Gunnar, Haeggstrom, Jesper Z., Tang, Xiao, Ronnberg, Elin, Safholm, Jesper, Thulasingam, Madhuranayaki, Trauelsen, Mette, Schwartz, Thue W., Wheelock, Craig E., Dahlen, Sven-Erik, Nilsson, Gunnar, and Haeggstrom, Jesper Z.

Abstract

Background SUCNR1 is a sensor of extracellular succinate, a Krebs cycle intermediate generated in excess during oxidative stress and has been linked to metabolic regulation and inflammation. While mast cells express SUCNR1, its role in mast cell reactivity and allergic conditions such as asthma remains to be elucidated. Methods Cord blood-derived mast cells and human mast cell line LAD-2 challenged by SUCNR1 ligands were analyzed for the activation and mediator release. Effects on mast cell-dependent bronchoconstriction were assessed in guinea pig trachea and isolated human small bronchi challenged with antigen and anti-IgE, respectively. Results SUCNR1 is abundantly expressed on human mast cells. Challenge with succinate, or the synthetic non-metabolite agonist cis-epoxysuccinate, renders mast cells hypersensitive to IgE-dependent activation, resulting in augmented degranulation and histamine release, de novo biosynthesis of eicosanoids and cytokine secretion. The succinate-potentiated mast cell reactivity was attenuated by SUCNR1 knockdown and selective SUCNR1 antagonists and could be tuned by pharmacologically targeting protein kinase C and extracellular signal-regulated kinase. Both succinate and cis-epoxysuccinate dose-dependently potentiated antigen-induced contraction in a mast cell-dependent guinea pig airway model, associated with increased generation of cysteinyl-leukotrienes and histamine in trachea. Similarly, cis-epoxysuccinate aggravated IgE-receptor-induced contraction of human bronchi, which was blocked by SUCNR1 antagonism. Conclusion SUCNR1 amplifies IgE-receptor-induced mast cell activation and allergic bronchoconstriction, suggesting a role for this pathway in aggravation of allergic asthma, thus linking metabolic perturbations to mast cell-dependent inflammation.

Published
2022
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34. 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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36. Additional file 1 of A novel non-invasive method allowing for discovery of pathologically relevant proteins from small airways

Author

Östling, Jörgen, Van Geest, Marleen, Olsson, Henric K., Dahlen, Sven-Erik, Viklund, Emilia, Gustafsson, Per M., Mirgorodskaya, Ekaterina, and Olin, Anna-Carin

Abstract

Additional file 1: Table S1. Proteins considered being detected in PEx samples using the SOMAscan 1.3 K platform. Table S2. Result from differential abundance analysis. Table S3. Result from manual reviewing the scientific literature on proteins found to be differentially abundant in A-hLCI as compared to NA group. Table S4. Demographic and clinical characteristics of groups based on smoking history.

Published
2022
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37. Leukotriene A4 Hydrolase Activity in Xenopus laevis

Author

Strömberg, Filippa, Rosenqvist, Urban, Dahlén, Sven-Erik, Haeggström, Jesper Z., Sinzinger, Helmut, editor, Samuelsson, Bengt, editor, Vane, John R., editor, Paoletti, Rodolfo, editor, Ramwell, Peter, editor, and Wong, Patrick Y.-K., editor

Published
1997
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42. 3TR: a pan-European cross-disease research consortium aimed at improving personalised biological treatment of asthma and COPD

Author

Porsbjerg, Celeste, primary, Maitland-van der Zee, Anke H., additional, Brusselle, Guy, additional, Canonica, Giorgio Walter, additional, Agusti, Alvar, additional, Faner, Rosa, additional, Vogelmeier, Claus F., additional, Nawijn, Martijn, additional, van den Berge, Maarten, additional, Rusconi, Franca, additional, Pilette, Charles, additional, Ramiconi, Valeria, additional, Coleman, Courtney, additional, Chaudhuri, Rekha, additional, Chung, Kian Fan, additional, Wedzicha, Jadwiga, additional, Saglani, Sejla, additional, Van der Schee, Marc P., additional, Heaney, Liam, additional, Bourdin, Arnaud, additional, Roberts, Graham, additional, Djukanovic, Ratko, additional, Kuna, Piotr, additional, Kupczyk, Maciej, additional, Axmann, Judith, additional, Staudinger, Heribert, additional, Clarke, Graham W., additional, Dahlen, Sven Erik, additional, and Brightling, Chris, additional

Published
2021
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44. The carnitine pathway is dysregulated in asthma in an oral corticosteroid-independent mechanism

Author

Reinke, Stacey, primary, Naz, Shama, additional, Kermani, Nazanin, additional, Chaleckis, Romanas, additional, Kolmert, Johan, additional, Ström, Marika, additional, Wheelock, Åsa, additional, Djukanovic, Ratko, additional, Chung, Fan, additional, Adcock, Ian, additional, Dahlen, Sven-Erik, additional, Wheelock, Craig, additional, and Ubiopred Study Group, ., additional

Published
2021
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