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1. Determinants of Severe Asthma – A Long-Term Cohort Study in Northern Sweden

Author

Backman H, Stridsman C, Hedman L, Rönnebjerg L, Nwaru BI, Sandström T, Kankaanranta H, Lindberg A, and Rönmark E

Subjects
epidemiology, phenotype, precision medicine, prognosis, risk factors, Immunologic diseases. Allergy, RC581-607
Abstract

Helena Backman,1 Caroline Stridsman,2 Linnea Hedman,1 Lina Rönnebjerg,3 Bright I Nwaru,3,4 Thomas Sandström,2 Hannu Kankaanranta,3,5,6 Anne Lindberg,2 Eva Rönmark1 1Department of Public Health and Clinical Medicine, Section of Sustainable Health/the OLIN unit, Umeå University, Umeå, Sweden; 2Department of Public Health and Clinical Medicine, Section of Medicine/the OLIN unit, Umeå University, Umeå, Sweden; 3Krefting Research Centre, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 4Wallenberg Centre for Molecular and Translational Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden; 5Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland; 6Faculty of Medicine and Health Technology, Tampere University, Tampere, FinlandCorrespondence: Helena Backman, Department of Public Health and Clinical Medicine, Section of Sustainable Health/the OLIN Unit, Umeå University, Umeå, Sweden, Email helena.backman@norrbotten.seBackground: Risk factors for severe asthma are not well described. The aim was to identify clinical characteristics and risk factors at study entry that are associated with severe asthma at follow-up in a long-term prospective population-based cohort study of adults with asthma.Methods: Between 1986 and 2001, 2055 adults with asthma were identified by clinical examinations of population-based samples in northern Sweden. During 2012– 2014, n = 1006 (71% of invited) were still alive, residing in the study area and participated in a follow-up, of which 40 were identified as having severe asthma according to ERS/ATS, 131 according to GINA, while 875 had other asthma. The mean follow-up time was 18.7 years.Results: Obesity at study entry and adult-onset asthma were associated with severe asthma at follow-up. While severe asthma was more common in those with adult-onset asthma in both men and women, the association with obesity was observed in women only. Sensitization to mites and moulds, but not to other allergens, as well as NSAID-related respiratory symptoms was more common in severe asthma than in other asthma. Participants with severe asthma at follow-up had lower FEV1, more pronounced FEV1 reversibility, and more wheeze, dyspnea and nighttime awakenings already at study entry than those with other asthma.Conclusion: Adult-onset asthma is an important risk factor for development of severe asthma in adults, and obesity increased the risk among women. The high burden of respiratory symptoms already at study entry also indicate long-term associations with development of severe asthma.Keywords: epidemiology, phenotype, precision medicine, prognosis, risk factors

Published
2022

2. The phenotype of concurrent chronic bronchitis and frequent exacerbations in patients with severe COPD attending Swedish secondary care units

Author

Sundh J, Johansson G, Larsson K, Lindén A, Löfdahl CG, Sandström T, and Janson C

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Josefin Sundh,1 Gunnar Johansson,2 Kjell Larsson,3 Anders Lindén,3 Claes-Göran Löfdahl,4 Thomas Sandström,5 Christer Janson6 1Department of Respiratory Medicine, Örebro University, Örebro, Sweden; 2Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 3Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 4Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden; 5Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden; 6Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden Background: Chronic bronchitis and previous exacerbations are both well-known risk factors for new exacerbations, impaired health-related quality of life, and increased mortality in COPD. The aim of the study was to characterize the phenotype of concurrent chronic bronchitis and frequent exacerbation in severe COPD. Methods: Information on patient characteristics, comorbidity, and exacerbations from the previous year (total number and number requiring hospitalization) was collected from 373 patients with stage III and IV COPD attending 27 secondary care respiratory units in Sweden. Logistic regression used chronic bronchitis and frequent exacerbations (≥2 exacerbations or ≥1 hospitalized exacerbations in the previous year) as response variables. Stratification and interaction analyses examined effect modification by sex. Results: Chronic bronchitis was associated with current smoking (adjusted odds ratio [OR] [95% CI], 2.75 [1.54–4.91]; P=0.001), frequent exacerbations (OR [95% CI], 1.93 [1.24–3.01]; P=0.004), and musculoskeletal symptoms (OR [95% CI], 1.74 [1.05–2.86]; P=0.031), while frequent exacerbations were associated with lung function (forced expiratory volume in 1 second as a percentage of predicted value [FEV1% pred]) (OR [95% CI] 0.96 [0.94–0.98]; P=0.001) and chronic bronchitis (OR [95% CI] 1.73 [1.11–2.68]; P=0.015). The phenotype with both chronic bronchitis and frequent exacerbations was associated with FEV1% pred (OR [95% CI] 0.95 [0.92–0.98]; P=0.002) and musculoskeletal symptoms (OR [95% CI] 2.55 [1.31–4.99]; P=0.006). The association of smoking with the phenotype of chronic bronchitis and exacerbations was stronger in women than in men (interaction, P=0.040). Conclusion: Musculoskeletal symptoms and low lung function are associated with the phenotype of combined chronic bronchitis and frequent exacerbations in severe COPD. In women, current smoking is of specific importance for this phenotype. This should be considered in clinical COPD care. Keywords: lung function, smoking, chronic obstructive lung disease, musculoskeletal symptoms

Published
2015

3. Predicting energy requirement with pedometer-determined physical-activity level in women with chronic obstructive pulmonary disease

Author

Farooqi N, Slinde F, Carlsson M, Håglin L, and Sandström T

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Nighat Farooqi,1 Frode Slinde,2 Maine Carlsson,3 Lena Håglin,4 Thomas Sandström1 1Department of Public Health and Clinical Medicine, Division of Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden; 2Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 3Department of Community Medicine and Rehabilitation, Division of Geriatric Medicine, Umeå University, Umeå, Sweden; 4Department of Public Health and Clinical Medicine, Division of Family Medicine, Umeå University, Umeå, Sweden Background: In clinical practice, in the absence of objective measures, simple methods to predict energy requirement in patients with chronic obstructive pulmonary disease (COPD) needs to be evaluated. The aim of the present study was to evaluate predicted energy requirement in females with COPD using pedometer-determined physical activity level (PAL) multiplied by resting metabolic rate (RMR) equations. Methods: Energy requirement was predicted in 18 women with COPD using pedometer-determined PAL multiplied by six different RMR equations (Harris–Benedict; Schofield; World Health Organization; Moore; Nordic Nutrition Recommendations; Nordenson). Total energy expenditure (TEE) was measured by the criterion method: doubly labeled water. The predicted energy requirement was compared with measured TEE using intraclass correlation coefficient (ICC) and Bland–Altman analyses. Results: The energy requirement predicted by pedometer-determined PAL multiplied by six different RMR equations was within a reasonable accuracy (±10%) of the measured TEE for all equations except one (Nordenson equation). The ICC values between the criterion method (TEE) and predicted energy requirement were: Harris–Benedict, ICC =0.70, 95% confidence interval (CI) 0.23–0.89; Schofield, ICC =0.71, 95% CI 0.21–0.89; World Health Organization, ICC =0.74, 95% CI 0.33–0.90; Moore, ICC =0.69, 95% CI 0.21–0.88; Nordic Nutrition Recommendations, ICC =0.70, 95% CI 0.17–0.89; and Nordenson, ICC =0.40, 95% CI -0.19 to 0.77. Bland–Altman plots revealed no systematic bias for predicted energy requirement except for Nordenson estimates. Conclusion: For clinical purposes, in absence of objective methods such as doubly labeled water method and motion sensors, energy requirement can be predicted using pedometer-determined PAL and common RMR equations. However, for assessment of nutritional status and for the purpose of giving nutritional treatment, a clinical judgment is important regarding when to accept a predicted energy requirement both at individual and group levels. Keywords: pedometer-determined PAL, women with COPD, energy expenditure, DLW method

Published
2015

4. Comorbidity and health-related quality of life in patients with severe chronic obstructive pulmonary disease attending Swedish secondary care units

Author

Sundh J, Johansson G, Larsson K, Lindén A, Löfdahl CG, Janson C, and Sandström T

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Josefin Sundh,1 Gunnar Johansson,2 Kjell Larsson,3 Anders Lindén,3 Claes-Göran Löfdahl,4 Christer Janson,5 Thomas Sandström6 1Department of Respiratory Medicine, Örebro University, Örebro, Sweden; 2Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 3Unit for Lung and Airway Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; 4Department of Respiratory Medicine and Allergology, Lund University, Lund, Sweden; 5Department of Medical Sciences: Respiratory Medicine and Allergology, Uppsala University, Uppsala, Sweden; 6Department of Public Health and Clinical Medicine, Division of Medicine/Respiratory Medicine, Umeå University, Umeå, Sweden Introduction: Our understanding of how comorbid diseases influence health-related quality of life (HRQL) in patients with chronic obstructive pulmonary disease (COPD) is limited and in need of improvement. The aim of this study was to examine the associations between comorbidities and HRQL as measured by the instruments EuroQol-5 dimension (EQ-5D) and the COPD Assessment Test (CAT). Methods: Information on patient characteristics, chronic bronchitis, cardiovascular disease, diabetes, renal impairment, musculoskeletal symptoms, osteoporosis, depression, and EQ-5D and CAT questionnaire results was collected from 373 patients with Forced Expiratory Volume in one second (FEV1)

Published
2015

8. 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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9. 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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10. Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma

Author

Tariq, K., Schofield, J.P.R., Nicholas, B.L., Burg, D., Brandsma, J., Bansal, A.T., Wilson, S.J., Lutter, R., Fowler, S.J., Bakke, Caruso, M., Dahlen, B., Horváth, I., Krug, N., Montuschi, P., Sanak, M., Sandström, T., Geiser, T., Pandis, I., Sousa, A.R., Adcock, I.M., Shaw, D.E., Auffray, C., Howarth, P.H., Sterk, P.J., Chung, K.F., Skipp, P.J., Dimitrov, B., and Djukanović, R.

Published
2019
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11. 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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13. Stratification of asthma by lipidomic profiling of induced sputum supernatant

Author

Brandsma, J, Schofield, JPR, Yang, X, Strazzeri, F, Barber, C, Goss, VM, Koster, G, Bakke, PS, Caruso, M, Chanez, P, Dahlén, S-E, Fowler, SJ, Horváth, I, Krug, N, Montuschi, P, Sanak, M, Sandström, T, Shaw, DE, Chung, KF, Singer, F, Fleming, LJ, Adcock, IM, Pandis, I, Bansal, AT, Corfield, J, Sousa, AR, Sterk, PJ, Sánchez-García, RJ, Skipp, PJ, Postle, AD, Djukanović, R, U-BIOPRED Study Group, and Publica

Subjects
Immunology, Immunology and Allergy, 610 Medicine & health
Abstract

BACKGROUND Asthma is a chronic respiratory disease with significant heterogeneity in its clinical presentation and pathobiology. There is need for improved understanding of respiratory lipid metabolism in asthma patients and its relation to observable clinical features. OBJECTIVE To perform a comprehensive, prospective, cross-sectional analysis of the lipid composition of induced sputum supernatant obtained from asthma patients with a range of disease severities, as well as healthy controls. METHODS Induced sputum supernatant was collected from 211 asthmatic adults and 41 healthy individuals enrolled in the U-BIOPRED study. Sputum lipidomes were characterised by semi-quantitative shotgun mass spectrometry, and clustered using topological data analysis to identify lipid phenotypes. RESULTS Shotgun lipidomics of induced sputum supernatant revealed a spectrum of nine molecular phenotypes, highlighting not just significant differences between the sputum lipidomes of asthmatics and healthy controls, but within the asthmatic population as well. Matching clinical, pathobiological, proteomic and transcriptomic data informed on the underlying disease processes. Sputum lipid phenotypes with higher levels of non-endogenous, cell-derived lipids were associated with significantly worse asthma severity, worse lung function, and elevated granulocyte counts. CONCLUSION We propose a novel mechanism of increased lipid loading in the epithelial lining fluid of asthmatics, resulting from the secretion of extracellular vesicles by granulocytic inflammatory cells, which could reduce the ability of pulmonary surfactant to lower surface tension in asthmatic small airways, as well as compromise its role as an immune regulator. CLINICAL IMPLICATION Immunomodulation of extracellular vesicle secretion in the lungs may provide a novel therapeutic target for severe asthma.

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

Author

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

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

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

Published
2023
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15. P07-16 Biometrics for the impact of acute air pollution on human peripheral immunity

Author

Mohamed, A., primary, Ohtonen, S., additional, Giudice, L., additional, Schroderus, A.-M., additional, Závodná, T., additional, Krejčik, Z., additional, Rössner, P., additional, Kanninen, K.M., additional, Kinnunen, T., additional, Topinka, J., additional, Muala, A., additional, Sandström, T., additional, Korhonen, P., additional, and Malm, T., additional

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

Author

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

Abstract

Rationale Asthma phenotyping requires novel biomarker discovery. Objectives To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterised cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, COPD subjects and healthy controls (HCs). Methods An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HCs in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a 2-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HCs. 10 proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, TNF receptor superfamily member 11a, transforming growth factor-β and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, high-sensitivity C-reactive protein and body mass index, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2independent biomarkers and validated several proteins with established involvement in the pathophysiology of SA. © 2022 European Respiratory Society. All rights reserved.

Published
2022

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

Author

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

Subjects
Inflammation, Steroids, Asthma
Abstract

Rationale: Asthma phenotyping requires novel biomarker discovery. Objectives: To identify plasma biomarkers associated with asthma phenotypes by application of a new proteomic panel to samples from two well-characterized cohorts of severe (SA) and mild-to-moderate (MMA) asthmatics, chronic obstructive pulmonary disease (COPD) subjects and healthy controls (HC). Methods: An antibody-based array targeting 177 proteins predominantly involved in pathways relevant to inflammation, lipid metabolism, signal transduction and extracellular matrix was applied to plasma from 525 asthmatics and HC in the U-BIOPRED cohort, and 142 subjects with asthma and COPD from the validation cohort BIOAIR. Effects of oral corticosteroids (OCS) were determined by a two-week, placebo-controlled OCS trial in BIOAIR, and confirmed by relation to objective OCS measures in U-BIOPRED. Results: In U-BIOPRED, 110 proteins were significantly different, mostly elevated, in SA compared to MMA and HC. Ten proteins were elevated in SA versus MMA in both U-BIOPRED and BIOAIR (alpha-1-antichymotrypsin, apolipoprotein-E, complement component 9, complement factor I, macrophage inflammatory protein-3, interleukin-6, sphingomyelin phosphodiesterase 3, RANK, TGF-?1, and glutathione S-transferase). OCS treatment decreased most proteins, yet differences between SA and MMA remained following correction for OCS use. Consensus clustering of U-BIOPRED protein data yielded six clusters associated with asthma control, quality of life, blood neutrophils, hsCRP, and BMI, but not Type-2 inflammatory biomarkers. The mast cell specific enzyme carboxypeptidase A3 was one major contributor to cluster differentiation. Conclusions: The plasma proteomic panel revealed previously unexplored yet potentially useful Type-2-independent biomarkers, and validated several proteins with established involvement in the pathophysiology of severe asthma.

Published
2022

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

Author

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

Published
2021
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24. Airway Elastin is increased in severe asthma and relates to proximal wall area: Histological and computed tomography findings from the U-BIOPRED severe asthma study

Author

Wilson, S.J., Ward, J.A., Pickett, H.M., Baldi, S., Sousa, A.R., Sterk, P.J., Chung, K.F., Djukanovic, R., Dahlen, B., Billing, B., Shaw, D., Krug, N., Sandström, T., Brightling, C., Howarth, P.H., and Publica

Abstract

Background Airway remodelling, which may include goblet cell hyperplasia / hypertrophy, changes in epithelial integrity, accumulation of extracellular matrix components, smooth muscle hypertrophy and thickening of the lamina reticularis, is a feature of severe asthma and contributes to the clinical phenotype. Objective Within the U-BIOPRED severe asthma study, we have assessed histological elements of airway remodelling and their relationship to computed tomography (CT) measures of proximal airway dimensions. Methods Bronchial biopsies were collected from two severe asthma groups, one non-smoker (SAn, n = 28) and one current/ex-smoker (SAs/ex, n = 13), and a mild-moderate asthma group (MMA, n = 28) classified and treated according to GINA guidelines, plus a healthy control group (HC, n = 33). Movat's pentachrome technique was used to identify mucin, elastin and total collagen in these biopsies. The number of goblet cells (mucin+) was counted as a percentage of the total number of epithelial cells and the percentage mucin epithelial area measured. The percentage area of elastic fibres and total collagen within the submucosa was also measured, and the morphology of the elastic fibres classified. Participants in the asthma groups also had a CT scan to assess large airway morphometry. Results The submucosal tissue elastin percentage was higher in both severe asthma groups (16.1% SAn, 18.9% SAs/ex) compared with the HC (9.7%) but did not differ between asthma groups. There was a positive relationship between elastin and airway wall area measured by CT (n = 18-20, rho=0.544, p = 0.024), which also related to an increase in elastic fibres with a thickened lamellar morphological appearance. Mucin epithelial area and total collagen were not different between the four groups. Due to small numbers of suitable CT scans, it was not feasible to compare airway morphometry between the asthma groups. Conclusion These findings identify a link between extent of elastin deposition and airway wall thickening in severe asthma.

Published
2021

25. An experimental exposure study revealing composite airway effects of physical exercise in a subzero environment

Author

Eklund, L., Schagatay, F., Tufvesson, E., Sjöström, R., Söderström, L., Hanstock, Helen, Sandström, T., Stenfors, N., Eklund, L., Schagatay, F., Tufvesson, E., Sjöström, R., Söderström, L., Hanstock, Helen, Sandström, T., and Stenfors, N.

Abstract

Exposure to a cold climate is associated with an increased morbidity and mortality, but the specific mechanisms are largely unknown. People with cardiopulmonary disease and winter endurance athletes are particularly vulnerable. This study aimed to map multiple domains of airway responses to exercise in subzero temperature in healthy individuals. Thirty-one healthy subjects underwent whole-body exposures for 50 minutes on two occasions in an environmental chamber with intermittent moderate-intensity exercise in +10 °C and -10 °C. Lung function, plasma/urine CC16 , and symptoms were investigated before and after exposures. Compared to baseline, exercise in -10 °C decreased FEV1 (p=0.002), FEV1/FVC (p<0.001), and increased R20Hz (p=0.016), with no differences between exposures. Reactance increased after +10 °C (p=0.005), which differed (p=0.042) from a blunted response after exercise in -10 °C. Plasma CC16 increased significantly within exposures, without differences between exposures. Exercise in -10 °C elicited more intense symptoms from the upper airways, compared to +10 °C. Symptoms from the lower airways were few and mild. Short-duration moderate-intensity exercise in -10 °C induces mild symptoms from the lower airways, no lung function decrements or enhanced leakage of biomarkers of airway epithelial injury, and no peripheral bronchodilatation, compared to exercise in +10 °C.

Published
2021
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28. Urinary Leukotriene E4 and Prostaglandin D2 Metabolites Increase in Adult and Childhood Severe Asthma Characterized by Type 2 Inflammation. A Clinical Observational Study

Author

Kolmert, Johan, primary, Gómez, Cristina, additional, Balgoma, David, additional, Sjödin, Marcus, additional, Bood, Johan, additional, Konradsen, Jon R., additional, Ericsson, Magnus, additional, Thörngren, John-Olof, additional, James, Anna, additional, Mikus, Maria, additional, Sousa, Ana R., additional, Riley, John H., additional, Bates, Stewart, additional, Bakke, Per S., additional, Pandis, Ioannis, additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Fowler, Stephen J., additional, Geiser, Thomas, additional, Howarth, Peter, additional, Horváth, Ildikó, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Behndig, Annelie, additional, Shaw, Dominick E., additional, Knowles, Richard G., additional, Holweg, Cécile T. J., additional, Wheelock, Åsa M., additional, Dahlén, Barbro, additional, Nordlund, Björn, additional, Alving, Kjell, additional, Hedlin, Gunilla, additional, Chung, Kian Fan, additional, Adcock, Ian M., additional, Sterk, Peter J., additional, Djukanovic, Ratko, additional, Dahlén, Sven-Erik, additional, Wheelock, Craig E., additional, Ahmed, H., additional, Auffray, C., additional, Bansal, A. T., additional, Bel, E. H., additional, Bigler, J., additional, Billing, B., additional, Baribaud, F., additional, Bisgaard, H., additional, Boedigheimer, M. J., additional, Bønnelykke, K., additional, Brandsma, J., additional, Brinkman, P., additional, Bucchioni, E., additional, Burg, D., additional, Bush, A., additional, Chaiboonchoe, A., additional, Compton, C. H., additional, Corfield, J., additional, Cunoosamy, D., additional, D’Amico, A., additional, De Meulder, B., additional, Erpenbeck, V. J., additional, Erzen, D., additional, Fichtner, K., additional, Fitch, N., additional, Fleming, L. J., additional, Formaggio, E., additional, Frey, U., additional, Gahlemann, M., additional, Goss, V., additional, Guo, Y., additional, Hashimoto, S., additional, Haughney, J., additional, Hekking, P. W., additional, Higenbottam, T., additional, Hohlfeld, J. M., additional, Knox, A. J., additional, Lazarinis, N., additional, Lefaudeux, D., additional, Loza, M. J., additional, Lutter, R., additional, Manta, A., additional, Masefield, S., additional, Matthews, J. G., additional, Mazein, A., additional, Meiser, A., additional, Middelveld, R. J. M., additional, Miralpeix, M., additional, Mores, N., additional, Murray, C. S., additional, Musial, J., additional, Myles, D., additional, Pahus, L., additional, Pavlidis, S., additional, Postle, A., additional, Powel, P., additional, Praticò, G., additional, PuigValls, M., additional, Rao, N., additional, Roberts, A., additional, Roberts, G., additional, Rowe, A., additional, Sandström, T., additional, Schofield, J. P. R., additional, Seibold, W., additional, Selby, A., additional, Sigmund, R., additional, Singer, F., additional, Skipp, P. J., additional, Smicker, M., additional, Sun, K., additional, Thornton, B., additional, Uddin, M., additional, van Aalderen, W. M., additional, van Geest, M., additional, Vestbo, J., additional, Vissing, N. H., additional, Wagener, A. H., additional, Wagers, S. S., additional, Weiszhart, Z., additional, Wilson, S. J., additional, and Östling, J., additional

Published
2021
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31. Asthma similarities across ProAR (Brazil) and U-BIOPRED (Europe) adult cohorts of contrasting locations, ethnicity and socioeconomic status

Author

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

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

Author

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

Abstract

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

Published
2019
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37. Epithelial dysregulation in obese severe asthmatics with gastro-oesophageal reflux

Author

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

Abstract

N/A

Published
2019

38. Sputum proteomic signature of gastro-oesophageal reflux in patients with severe asthma

Author

Tariq, K, Schofield, Jpr, Nicholas, Bl, Burg, D, Brandsma, J, Bansal, At, Wilson, Sj, Lutter, R, Fowler, Sj, Bakke, Caruso, M, Dahlen, B, Horváth, I, Krug, N, Montuschi, P, Sanak, M, Sandström, T, Geiser, T, Pandis, I, Sousa, Ar, Adcock, Im, Shaw, De, Auffray, C, Howarth, Ph, Sterk, Pj, Chung, Kf, Skipp, Pj, Dimitrov, B, Djukanović, R, Montuschi P (ORCID:0000-0001-5589-1750), Tariq, K, Schofield, Jpr, Nicholas, Bl, Burg, D, Brandsma, J, Bansal, At, Wilson, Sj, Lutter, R, Fowler, Sj, Bakke, Caruso, M, Dahlen, B, Horváth, I, Krug, N, Montuschi, P, Sanak, M, Sandström, T, Geiser, T, Pandis, I, Sousa, Ar, Adcock, Im, Shaw, De, Auffray, C, Howarth, Ph, Sterk, Pj, Chung, Kf, Skipp, Pj, Dimitrov, B, Djukanović, R, and Montuschi P (ORCID:0000-0001-5589-1750)

Abstract

Gastro-oesophageal reflux disease (GORD) has long been associated with poor asthma control without an established cause-effect relationship. 610 asthmatics (421 severe/88 mild-moderate) and 101 healthy controls were assessed clinically and a subset of 154 severe asthmatics underwent proteomic analysis of induced sputum using untargeted mass spectrometry, LC-IMS-MSE. Univariate and multiple logistic regression analyses (MLR) were conducted to identify proteins associated with GORD in this cohort. When compared to mild/moderate asthmatics and healthy individuals, respectively, GORD was three- and ten-fold more prevalent in severe asthmatics and was associated with increased asthma symptoms and oral corticosteroid use, poorer quality of life, depression/anxiety, obesity and symptoms of sino-nasal disease. Comparison of sputum proteomes in severe asthmatics with and without active GORD showed five differentially abundant proteins with described roles in anti-microbial defences, systemic inflammation and epithelial integrity. Three of these were associated with active GORD by multiple linear regression analysis: Ig lambda variable 1-47 (p = 0·017) and plasma protease C1 inhibitor (p = 0·043), both in lower concentrations, and lipocalin-1 (p = 0·034) in higher concentrations in active GORD. This study provides evidence which suggests that reflux can cause subtle perturbation of proteins detectable in the airways lining fluid and that severe asthmatics with GORD may represent a distinct phenotype of asthma

Published
2019

39. Stratification of asthma phenotypes by airway proteomic signatures

Author

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

Abstract

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

Published
2019

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

Author

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

Abstract

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

Published
2019

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

Author

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

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

Author

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

Published
2019
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