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1. Blood transcriptomic signature in type-2 biomarker-low severe asthma and asthma control

Author

Zeng, Xue, Qing, Jing, Li, Chi-Ming, Lu, Jiamiao, Yamawaki, Tracy, Hsu, Yi-Hsiang, Vander Lugt, Bryan, Hsu, Hailing, Busby, John, McDowell, P.J., Jackson, David J., Djukanovic, Ratko, Matthews, John G., Arron, Joseph R., Bradding, Peter, Brightling, Christopher E., Chaudhuri, Rekha, Choy, David F., Cowan, D., Fowler, S.J., Hardman, Timothy C., Harrison, Tim, Howarth, Peter, Lordan, James, Mansur, A.H., Menzies-Gow, Andrew, Pavord, Ian D., Walker, Samantha, Woodcock, Ashley, and Heaney, Liam G.

Published
2023
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2. A Randomized Trial of a Composite T2-Biomarker Strategy Adjusting Corticosteroid Treatment in Severe Asthma: A Post Hoc Analysis by Sex

Author

Eastwood, Matthew C., Busby, John, Jackson, David J., Pavord, Ian D., Hanratty, Catherine E., Djukanovic, Ratko, Woodcock, Ashley, Walker, Samantha, Hardman, Timothy C., Arron, Joseph R., Choy, David F., Bradding, Peter, Brightling, Chris E., Chaudhuri, Rekha, Cowan, Douglas, Mansur, Adel H., Fowler, Stephen J., Howarth, Peter, Lordan, James, Menzies-Gow, Andrew, Harrison, Timothy, Robinson, Douglas S., Holweg, Cecile T.J., Matthews, John G., and Heaney, Liam G.

Published
2023
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3. Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial

Author

Adcock, Ian M, Azim, Adnam, Bellamy, Mary, Borg, Catherine, Bourne, Michelle, Connolly, Clare, Costello, Richard W, Corrigan, Chris J, Davies, Sarah, Davies, Gareth, Chung, Kian F, Gainsborough, Gabrielle, Grandison, Traceyanne, Hargadon, Beverley, Horn, Avril, Hudson, Val, Jackson, David, Johnston, Sebastian, Jones, Geraldine, McCourt, Paula, Nunez, Maria, Shaw, Dominic E, Smith, Katherine, Solis, Joel, Stone, Roisin, Yang, Freda, Heaney, Liam G, Busby, John, Hanratty, Catherine E, Djukanovic, Ratko, Woodcock, Ashley, Walker, Samantha M, Hardman, Timothy C, Arron, Joseph R, Choy, David F, Bradding, Peter, Brightling, Christopher E, Chaudhuri, Rekha, Cowan, Douglas C, Mansur, Adel H, Fowler, Stephen J, Niven, Robert M, Howarth, Peter H, Lordan, James L, Menzies-Gow, Andrew, Harrison, Tim W, Robinson, Douglas S, Holweg, Cecile T J, Matthews, John G, and Pavord, Ian D

Published
2021
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7. Efficacy and safety of lebrikizumab in patients with uncontrolled asthma (LAVOLTA I and LAVOLTA II): replicate, phase 3, randomised, double-blind, placebo-controlled trials

Author

Hanania, Nicola A, Korenblat, Phillip, Chapman, Kenneth R, Bateman, Eric D, Kopecky, Petr, Paggiaro, Pierluigi, Yokoyama, Akihito, Olsson, Julie, Gray, Sarah, Holweg, Cecile T J, Eisner, Mark, Asare, Charles, Fischer, Saloumeh K, Peng, Kun, Putnam, Wendy S, and Matthews, John G

Published
2016
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8. Exacerbation Profile and Risk Factors in a Type-2–Low Enriched Severe Asthma Cohort: A Clinical Trial to Assess Asthma Exacerbation Phenotypes

Author

McDowell, P. Jane, primary, Busby, John, additional, Hanratty, Catherine E., additional, Djukanovic, Ratko, additional, Woodcock, Ashley, additional, Walker, Samantha, additional, Hardman, Timothy Colin, additional, Arron, Joseph R., additional, Choy, David F., additional, Bradding, Peter, additional, Brightling, Chris E., additional, Chaudhuri, Rekha, additional, Cowan, Douglas, additional, Mansur, Adel H., additional, Fowler, Stephen J., additional, Diver, Sarah E., additional, Howarth, Peter, additional, Lordan, James, additional, Menzies-Gow, Andrew, additional, Harrison, Timothy, additional, Robinson, Douglas S., additional, Holweg, Cecile T. J., additional, Matthews, John G., additional, Pavord, Ian D., additional, and Heaney, Liam G., additional

Published
2022
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9. Efficacy, safety, and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma (ACOUSTICS)

Author

Szefler, Stanley J., primary, Roberts, Graham, additional, Rubin, Adalberto S., additional, Zielen, Stefan, additional, Kuna, Piotr, additional, Alpan, Oral, additional, Anzures‐Cabrera, Judith, additional, Chen, Qiang, additional, Holweg, Cécile T. J., additional, Kaminski, Janusz, additional, Putnam, Wendy S., additional, Matthews, John G., additional, and Kamath, Nikhil, additional

Published
2022
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10. Exacerbation Profile and Risk Factors in a T2-Low Severe Asthma Population

Author

McDowell, P Jane, Busby, John, Hanratty, Catherine E, Djukanovic, Ratko, Woodcock, Ashley, Walker, Samantha, Hardman, Timothy Colin, Arron, Joseph R, Choy, David F, Bradding, Peter, Brightling, Chris E, Chaudhuri, Rekha, Cowan, Douglas, Mansur, Adel H, Fowler, Stephen J, Diver, Sarah E, Howarth, Peter, Lordan, James, Menzies-Gow, Andrew, Harrison, Timothy, Robinson, Douglas S, Holweg, Cecile T J, Matthews, John G, Pavord, Ian D, and Heaney, Liam G

Abstract

Although present in a minority of severe asthmatics, very little is known about the mechanisms underlying T2-low asthma, making it a significant unmet need in asthma research.METHODS: Exacerbation assessment was a pre-specified secondary analysis of data from a RCT comparing the use of biomarkers & symptoms to adjust steroid treatment in a T2-low severe asthma-enriched cohort. Participants were phenotyped as T2LOW(fractional exhaled nitric oxide [FeNO] ≤20 ppb & blood eosinophil count [PBE] ≤150 cells/µL) or T2HIGH ( FeNO>20 or PBE>150) at study enrolment & at each exacerbation. We report comparison of exacerbators & non-exacerbators, physiological changes at exacerbation in T2LOW & T2HIGH ,& stability of inflammatory phenotypes.RESULTS: 60.8% (183/301) ≥1 self-reported exacerbations (total of 390). Exacerbators were more likely to be female, have a higher BMI & more exacerbations requiring oral corticosteroid (OCS) & unscheduled primary care attendances for exacerbations. At enrolment, 23.6% (71/301) were T2LOW, & 76.4% (230/301) T2HIGH. The T2LOW group had more asthma primary care attendances, were more likely to have a previous admission to HDU/ICU & to be receiving maintenance OCS. At exacerbation the T2LOW events were indistinguishable from T2HIGH exacerbations in terms of lung function & symptom increase, with no increase in T2 biomarkers from stable to exacerbation state in the T2LOW exacerbations.CONCLUSION: Asthma exacerbations demonstrating a T2LOW phenotype were physiologically & symptomatically similar to T2HIGHexacerbations. The clinically significant T2LOW exacerbations highlights the unmet & pressing need to further understand the mechanisms at play in non-T2 asthma.

Published
2022
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12. Research in progress: Medical Research Council United Kingdom Refractory Asthma Stratification Programme (RASP-UK)

Author

Heaney, Liam G, Djukanovic, Ratko, Woodcock, Ashley, Walker, Samantha, Matthews, John G, Pavord, Ian D, Bradding, Peter, Niven, Robert, Brightling, Chris E, Chaudhuri, Rekha, Arron, Joseph R, Choy, David F, Cowan, Douglas, Mansur, Adel, Menzies-Gow, Andrew, Adcock, Ian, Chung, Kian F, Corrigan, Chris, Coyle, Peter, Harrison, Timothy, Johnston, Sebastian, Howarth, Peter, Lordan, James, Sabroe, Ian, Bigler, Jeannette, Smith, Dirk, Catley, Matthew, May, Richard, Pierre, Lisa, Stevenson, Chris, Crater, Glenn, Keane, Frank, Costello, Richard W, Hudson, Val, Supple, David, and Hardman, Tim

Published
2016
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15. Factors affecting adherence with treatment advice in a clinical trial of patients with severe asthma

Author

Busby, John, primary, Matthews, John G., additional, Chaudhuri, Rekha, additional, Pavord, Ian D., additional, Hardman, Timothy C., additional, Arron, Joseph R., additional, Bradding, Peter, additional, Brightling, Christopher E., additional, Choy, David F., additional, Cowan, Douglas C., additional, Djukanovic, Ratko, additional, Hanratty, Catherine E., additional, Harrison, Tim W., additional, Holweg, Cecile T., additional, Howarth, Peter H., additional, Fowler, Stephen J., additional, Lordan, James L., additional, Mansur, Adel H., additional, Menzies-Gow, Andrew, additional, Niven, Robert M., additional, Robinson, Douglas S., additional, Walker, Samantha M., additional, Woodcock, Ashley, additional, and Heaney, Liam G., additional

Published
2021
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17. Composite type-2 biomarker strategy versus a symptom–risk-based algorithm to adjust corticosteroid dose in patients with severe asthma: a multicentre, single-blind, parallel group, randomised controlled trial

Author

Heaney, Liam G, primary, Busby, John, additional, Hanratty, Catherine E, additional, Djukanovic, Ratko, additional, Woodcock, Ashley, additional, Walker, Samantha M, additional, Hardman, Timothy C, additional, Arron, Joseph R, additional, Choy, David F, additional, Bradding, Peter, additional, Brightling, Christopher E, additional, Chaudhuri, Rekha, additional, Cowan, Douglas C, additional, Mansur, Adel H, additional, Fowler, Stephen J, additional, Niven, Robert M, additional, Howarth, Peter H, additional, Lordan, James L, additional, Menzies-Gow, Andrew, additional, Harrison, Tim W, additional, Robinson, Douglas S, additional, Holweg, Cecile T J, additional, Matthews, John G, additional, Pavord, Ian D, additional, Adcock, Ian M, additional, Azim, Adnam, additional, Bellamy, Mary, additional, Borg, Catherine, additional, Bourne, Michelle, additional, Connolly, Clare, additional, Costello, Richard W, additional, Corrigan, Chris J, additional, Davies, Sarah, additional, Davies, Gareth, additional, Chung, Kian F, additional, Gainsborough, Gabrielle, additional, Grandison, Traceyanne, additional, Hargadon, Beverley, additional, Horn, Avril, additional, Hudson, Val, additional, Jackson, David, additional, Johnston, Sebastian, additional, Jones, Geraldine, additional, McCourt, Paula, additional, Nunez, Maria, additional, Shaw, Dominic E, additional, Smith, Katherine, additional, Solis, Joel, additional, Stone, Roisin, additional, and Yang, Freda, additional

Published
2021
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21. Lebrikizumab Treatment in Adults with Asthma

Author

Corren, Jonathan, Lemanske, Robert F., Jr., Hanania, Nicola A., Korenblat, Phillip E., Parsey, Merdad V., Arron, Joseph R., Harris, Jeffrey M., Scheerens, Heleen, Wu, Lawren C., Su, Zheng, Mosesova, Sofia, Eisner, Mark D., Bohen, Sean P., and Matthews, John G.

Published
2011
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22. Using prednisolone and cortisol assays to assess adherence in oral corticosteroid dependant asthma: An analysis of test-retest repeatability

Author

Busby, John, primary, Holweg, Cecile, additional, Chai, Akiko, additional, Bradding, Peter, additional, Chaudhuri, Rekha, additional, Mansur, Adel, additional, Matthews, John G., additional, Menzies-Gow, Andrew, additional, Lordan, James, additional, Niven, Rob, additional, and Heaney, Liam G., additional

Published
2020
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23. A Randomized, Placebo‐Controlled Trial Evaluating Effects of Lebrikizumab on Airway Eosinophilic Inflammation and Remodeling in Uncontrolled Asthma (CLAVIER)

Author

Austin, Cary D., primary, Edick, Melissa Gonzalez, additional, Ferrando, Ronald E., additional, Solon, Margaret, additional, Baca, Miriam, additional, Mesh, Kathryn, additional, Bradding, Peter, additional, Gauvreau, Gail M., additional, Sumino, Kaharu, additional, Fitzgerald, Mark, additional, Israel, Eliott, additional, Bjermer, Leif, additional, Bourdin, Arnaud, additional, Arron, Joseph R., additional, Choy, David F., additional, Olsson, Julie K., additional, Abreu, Francis D., additional, Howard, Monet D., additional, Wong, Kit D., additional, Cai, Fang D., additional, Peng, Kun D., additional, Putman, Wendy S., additional, Holweg, Cécile T. J., additional, Matthews, John G., additional, Kraft, Monica, additional, and Woodruff, Prescott G., additional

Published
2020
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26. Hession, Ronan. Leonard and Hungry Paul

Author

Matthews, John G.

Subjects
Leonard and Hungry Paul (Novel) -- Hession, Ronan, Library and information science
Abstract

* Hession, Ronan. Leonard and Hungry Paul. Melville House. Aug. 2020. 256p. ISBN 9781612198484. $25.99. F [DEBUT] Leonard ghostwrites children's encyclopedias. Hungry Paul is a substitute postman. They are best [...]

Published
2020

27. McBride, Eimear. Strange Hotel

Author

Matthews, John G.

Subjects
Strange Hotel (Novel) -- McBride, Eimear, Library and information science
Abstract

McBride, Eimear. Strange Hotel. Farrar. May 2020. 160p. ISBN 9780374270629. $25. r An anonymous middle-aged woman from someplace undisclosed travels the world to stay in hotels. Though cultured and possessing [...]

Published
2020

29. A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care: Study protocol for a randomised trial

Author

Hanratty, Catherine E., Matthews, John G., Arron, Joseph R., Choy, David F., Pavord, Ian D., Bradding, P., Brightling, Christopher E., Chaudhuri, Rekha, Cowan, Douglas C., Djukanovic, Ratko, Gallagher, Nicola, Fowler, Stephen J., Hardman, Tim C., Harrison, Tim, Holweg, Cécile T., Howarth, Peter H., Lordan, James, Mansur, Adel H., Menzies-Gow, Andrew, Mosesova, Sofia, Niven, Robert M., Robinson, Douglas S., Shaw, Dominick E., Walker, Samantha, Woodcock, Ashley, Heaney, Liam G., Adcock, I., Boriello, A., Catley, M., Chung, K. F., Costello, R. W., Johnston, S., Keane, F., May, R., Pierre, L., Smith, D., Stevenson, C., Hudson, V., Supple, D., Gainsborough, G., and Horn, A.

Abstract

Background: Patients with difficult-to-control asthma consume 50-60% of healthcare costs attributed to asthma and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been called 'T2-low asthma' and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and optimized corticosteroid dose. However, it has been challenging to move induced sputum into the clinical setting. There is therefore a need to examine novel algorithms to target appropriate levels of corticosteroid treatment in difficult asthma, particularly in T2-low asthmatics. This study examines whether a composite non-invasive biomarker algorithm predicts exacerbation risk in patients with asthma on high-dose inhaled corticosteroids (ICS) (± long-acting beta agonist) treatment, and evaluates the utility of this composite score to facilitate personalized biomarker-specific titration of corticosteroid therapy. Methods/design: Patients recruited to this pragmatic, multi-centre, single-blinded randomised controlled trial are randomly allocated into either a biomarker controlled treatment advisory algorithm or usual care group in a ratio of 4:1. The primary outcome measure is the proportion of patients with any reduction in ICS or oral corticosteroid dose from baseline to week 48. Secondary outcomes include the rate of protocol-defined severe exacerbations per patient per year, time to first severe exacerbation from randomisation, dose of inhaled steroid at the end of the study, cumulative dose of inhaled corticosteroid during the study, proportion of patients on oral corticosteroids at the end of the study, proportion of patients who decline to progress to oral corticosteroids despite composite biomarker score of 2, frequency of hospital admission for asthma, change in the 7-item Asthma Control Questionnaire (ACQ-7), Asthma Quality of Life Questionnaire (AQLQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide, blood eosinophil count, and periostin levels from baseline to week 48. Blood will also be taken for whole blood gene expression; serum, plasma, and urine will be stored for validation of additional biomarkers. Discussion: Multi-centre trials present numerous logistical issues that have been addressed to ensure minimal bias and robustness of study conduct.

Published
2018

30. A randomised pragmatic trial of corticosteroid optimization in severe asthma using a composite biomarker algorithm to adjust corticosteroid dose versus standard care:study protocol for a randomised trial

Author

Hanratty, Catherine E., Matthews, John G., Arron, Joseph R., Choy, David F., Pavord, Ian D., Bradding, P., Brightling, Christopher E., Chaudhuri, Rekha, Cowan, Douglas C., Djukanovic, Ratko, Gallagher, Nicola, Fowler, Stephen J., Hardman, Tim C., Harrison, Tim, Holweg, Cécile T., Howarth, Peter H., Lordan, James, Mansur, Adel H., Menzies-Gow, Andrew, Mosesova, Sofia, Niven, Robert M., Robinson, Douglas S., Shaw, Dominick E., Walker, Samantha, Woodcock, Ashley, and Heaney, Liam G.

Subjects
Journal Article
Abstract

Background: Patients with difficult-to-control asthma consume 50–60% of healthcare costs attributed to asthma\ud and cost approximately five-times more than patients with mild stable disease. Recent evidence demonstrates that\ud not all patients with asthma have a typical type 2 (T2)-driven eosinophilic inflammation. These asthmatics have been\ud called ‘T2-low asthma’ and have a minimal response to corticosteroid therapy. Adjustment of corticosteroid treatment\ud using sputum eosinophil counts from induced sputum has demonstrated reduced severe exacerbation rates and\ud optimized corticosteroid dose. However, it has been challenging to move induced sputum into the clinical setting.\ud There is therefore a need to examine novel algorithms to target appropriate levels of corticosteroid treatment in\ud difficult asthma, particularly in T2-low asthmatics. This study examines whether a composite non-invasive biomarker\ud algorithm predicts exacerbation risk in patients with asthma on high-dose inhaled corticosteroids (ICS) (± long-acting\ud beta agonist) treatment, and evaluates the utility of this composite score to facilitate personalized biomarker-specific\ud titration of corticosteroid therapy.\ud Methods/design: Patients recruited to this pragmatic, multi-centre, single-blinded randomised controlled trial are\ud randomly allocated into either a biomarker controlled treatment advisory algorithm or usual care group in a ratio\ud of 4:1. The primary outcome measure is the proportion of patients with any reduction in ICS or oral corticosteroid\ud dose from baseline to week 48. Secondary outcomes include the rate of protocol-defined severe exacerbations\ud per patient per year, time to first severe exacerbation from randomisation, dose of inhaled steroid at the end of the study,\ud cumulative dose of inhaled corticosteroid during the study, proportion of patients on oral corticosteroids at the end of\ud the study, proportion of patients who decline to progress to oral corticosteroids despite composite biomarker score of 2,\ud frequency of hospital admission for asthma, change in the 7-item Asthma Control Questionnaire (ACQ-7), Asthma Quality\ud of Life Questionnaire (AQLQ), forced expiratory volume in 1 s (FEV1), exhaled nitric oxide, blood eosinophil count, and\ud periostin levels from baseline to week 48. Blood will also be taken for whole blood gene expression; serum, plasma, and\ud urine will be stored for validation of additional biomarkers.\ud Discussion: Multi-centre trials present numerous logistical issues that have been addressed to ensure minimal bias and\ud robustness of study conduct.\ud Trial registration: ClinicalTrials.gov, NCT02717689. Registered on 16 March 2016.

Published
2018
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32. Change in type-2 biomarkers and related cytokines with prednisolone in uncontrolled severe oral corticosteroid dependent asthmatics: an interventional open-label study

Author

Busby, John, primary, Holweg, Cecile T J, additional, Chai, Akiko, additional, Bradding, Peter, additional, Cai, Fang, additional, Chaudhuri, Rekha, additional, Mansur, Adel H, additional, Lordan, James Laurence, additional, Matthews, John G, additional, Menzies-Gow, Andrew, additional, Niven, Robert, additional, Staton, Tracy, additional, and Heaney, Liam G, additional

Published
2019
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33. Lally, Caitriona. Eggshells

Author

Matthews, John G.

Subjects
Eggshells (Novel) -- Lally, Caitriona -- Book reviews, Library and information science
Abstract

* Lally, Caitriona. Eggshells. Melville House. Feb. 2017.272p. ISBN 9781612195971. pap. $16.99; ebk. ISBN 9781612195988. F Currently unemployed, Vivian lives in the Dublin house a deceased aunt bequeathed to her [...]

Published
2017

37. Nasal Biomarkers Characterization In Lebrikizumab Bronchoscopy Study (CLAVIER)

Author

Cai, Fang, primary, Abreu, Francis, additional, Ding, Han Ting, additional, Choy, David, additional, Bremer, Meire, additional, Staton, Tracy, additional, Erickson, Rich, additional, Peng, Kun, additional, Wang, Jian Shuang, additional, Au-Yeung, Amelia, additional, Hansel, Trevor T., additional, Bjermer, Leif, additional, Holweg, Cecile, additional, Yen, Karl, additional, Matthews, John G., additional, and Scheerens, Heleen, additional

Published
2018
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38. Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study

Author

Loza, M. J., Djukanovic, R., Chung, K. F., Horowitz, D., Ma, K., Branigan, P., Barnathan, E. S., Susulic, V. S., Silkoff, P. E., Sterk, P. J., Baribaud, F., Strambu, I., Laviolette, M., Singh, D., Fitzgerald, J. M., Lam, S., Kelsen, S., Eich, A., Ludwig-Sengpiel, A., Hupp, G. C., Backer, V., Porsbjerg, C., Girodet, P. O., Berger, P., Leigh, R., Kline, J., Dransfield, M., Calhoun, W., Hussaini, A., Khatri, S., Chanez, P., Ian, A., Fleming Louis, J., David, G., Sile, H., Scott, K., Sally, M., Andrea, M., Stelios, P., Christos, R., Kirsty, R., Kai, S., Coen, W., Xian, Y., Nora, A., Ariane, W., Kees, v. D., Marianne, v. d. P., Wim, v. A., Sterk Peter, J., Barbara, S., Lara, R., Rene, L., Paul, B., Elisabeth, B., Koos, Z., Tamara, D., Simone, H., Annemiek, D., Pieter-Paul, H., Saeeda, L. -L., Hassan, A., Betrand, D. M., Diane, L., Antonios, A., Kjell, A., Charles, A., Philipp, B., Per, B., David, B., Sven-Erik, D., Ingrid, D., Cristina, G., James Anna, J., Roelinde, M., Shama, N., Anne, P., Stacey, R., Wheelock Craig, E., Hector, G., Maciej, K., Johan, K., Marcus, S., Bansal Aruna, T., Frederic, B., Navin, R., An, B., Inge, D. L., Martine, R., Behndig Annelie, F., Thomas, S., Jorge, B., De Jorge, A., Ann, B., Gunilla, H., Nordlund, Bjorn, Jon, K., Wilhelm, Z., Alix, B., Jorgen, O., van Marleen, G., de Maria, G. V., Lars, L., Ulf, N., Jeannette, B., Boedigheimer Michel, J., Richard, H., Xugang, H., Wen, Y., Hans, B., Klaus, B., Jonathan, T., Nadja, V., Grazyna, B., Jacek, M., Joost, B., Ben, N., Anthony, P., Doroteya, S., Armin, B., Jens, H., Norbert, K., Dominic, B., Schofield James, P. R., Skipp Paul, J., Leon, C., Bob, T., Caruso, Massimo, Rocha Joao Pedro, C. P., Julaiha, G., Andrew, M. -G., Adesimbo, S., Amphun, C., Romanas, C., Caroline, M., Pascal, C., Courtney, C., Jessica, E., Val, H., Kennington Erika, J., Leanne, M., Malayka, R. -A., Leanne, R., Jessica, S., Jenny, V., Samantha, W., Breda, F., Amanda, R., David, S., Chris, C., David, M., John, R., Sousa Ana, R., Julie, C., D'Amico, Arnaldo, Giorgio, P., Marco, S., Barbro, D., Ann-Sofie, L., Pim, B., Patrick, D., Kamran, T., Clair, B., Kerry, G., Aleksandra, D., Neil, F., Trevor, G., Scott, W., Rosalia, E., Davide, C., Magnus, E., Veit, E., Damijan, E., Klaus, F., Katja, N., Corinna, S., Frans, W., Kathrin, R., Kluglich, Matthias, Fowler Stephen, J., Murray Clare, S., Jorgen, V., Ashley, W., Urs, F., Martina, G., Gabriella, G., Ildiko, H., Marton, S., Lilla, T., Zsoka, W., Thomas, G., Neil, G., Yi-ke, G., John, H., Sian, W., Elisabeth, H., Nikos, L., Karin, S., Lorraine, H., Lisa, M., Jane, M., Sandy, P., Emma, R., Caroline, S., Tim, H., Uruj, H., Cecile, H., Matthews John, G., Peter, H., Graham, R., Juliette, K., Dyson, K., Hugo, K., Anton, V., Richard, K., Alan, K., Shaw Dominick, E., Maxim, K., Linn, K., Bart, L., Sarah, M., Pippa, P., Alexander, M., Maria, M., Peter, N., Montse, M., Philip, M., Paolo, M., Nadia, M., Giuseppe, S., Salvatore, V., Antonio, P., Laurie, P., Susanna, P., Ioannis, P., Anthony, R., Wolfgang, S., Kristiane, W., Florian, S., Smith Katherine, M., Paivi, S., John-Olof, T., von Christophe, G., Jonathan, W., Wilson Susan, J., Elizabeth, Y., AII - Amsterdam institute for Infection and Immunity, Pulmonology, Graduate School, Experimental Immunology, APH - Amsterdam Public Health, Epidemiology and Data Science, Medical Research Council (MRC), Commission of the European Communities, and National Institute for Health Research

Subjects
Oncology, Time Factors, AIRWAY INFLAMMATION, Respiratory System, Vital Capacity, Disease, Severity of Illness Index, 0302 clinical medicine, RESEARCH-PROGRAM, Forced Expiratory Volume, Observational study, Eosinophilic, Medicine and Health Sciences, 030212 general & internal medicine, Longitudinal Studies, Lung, SEVERE EOSINOPHILIC ASTHMA, INDUCED SPUTUM, Interleukin-13, Biological markers, Adept, Prognosis, ADEPT (Airways Disease Endotyping for Personalized Therapeutics) and U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome Consortium) investigators, Phenotype, 3. Good health, Cohort, Biomarker (medicine), Inflammation Mediators, Life Sciences & Biomedicine, medicine.drug, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Genotype, QUESTIONNAIRE, 610 Medicine & health, 1102 Cardiovascular Medicine And Haematology, 03 medical and health sciences, Th2 Cells, Cluster analysis, Fuzzy Logic, Predictive Value of Tests, Internal medicine, medicine, Humans, Asthma, Science & Technology, IDENTIFICATION, business.industry, MEPOLIZUMAB, Research, Biology and Life Sciences, Reproducibility of Results, 1103 Clinical Sciences, medicine.disease, Cross-Sectional Studies, 030228 respiratory system, Gene Expression Regulation, Immunology, Interleukin-4, business, Mepolizumab
Abstract

Background Asthma is a disease of varying severity and differing disease mechanisms. To date, studies aimed at stratifying asthma into clinically useful phenotypes have produced a number of phenotypes that have yet to be assessed for stability and to be validated in independent cohorts. The aim of this study was to define and validate, for the first time ever, clinically driven asthma phenotypes using two independent, severe asthma cohorts: ADEPT and U-BIOPRED. Methods Fuzzy partition-around-medoid clustering was performed on pre-specified data from the ADEPT participants (n = 156) and independently on data from a subset of U-BIOPRED asthma participants (n = 82) for whom the same variables were available. Models for cluster classification probabilities were derived and applied to the 12-month longitudinal ADEPT data and to a larger subset of the U-BIOPRED asthma dataset (n = 397). High and low type-2 inflammation phenotypes were defined as high or low Th2 activity, indicated by endobronchial biopsies gene expression changes downstream of IL-4 or IL-13. Results Four phenotypes were identified in the ADEPT (training) cohort, with distinct clinical and biomarker profiles. Phenotype 1 was “mild, good lung function, early onset”, with a low-inflammatory, predominantly Type-2, phenotype. Phenotype 2 had a “moderate, hyper-responsive, eosinophilic” phenotype, with moderate asthma control, mild airflow obstruction and predominant Type-2 inflammation. Phenotype 3 had a “mixed severity, predominantly fixed obstructive, non-eosinophilic and neutrophilic” phenotype, with moderate asthma control and low Type-2 inflammation. Phenotype 4 had a “severe uncontrolled, severe reversible obstruction, mixed granulocytic” phenotype, with moderate Type-2 inflammation. These phenotypes had good longitudinal stability in the ADEPT cohort. They were reproduced and demonstrated high classification probability in two subsets of the U-BIOPRED asthma cohort. Conclusions Focusing on the biology of the four clinical independently-validated easy-to-assess ADEPT asthma phenotypes will help understanding the unmet need and will aid in developing tailored therapies. Trial registration NCT01274507 (ADEPT), registered October 28, 2010 and NCT01982162 (U-BIOPRED), registered October 30, 2013. Electronic supplementary material The online version of this article (doi:10.1186/s12931-016-0482-9) contains supplementary material, which is available to authorized users.

Published
2016
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39. U-BIOPRED clinical adult asthma clusters linked to a subset of sputum omics

Author

Lefaudeux, Diane, primary, De Meulder, Bertrand, additional, Loza, Matthew J., additional, Peffer, Nancy, additional, Rowe, Anthony, additional, Baribaud, Frédéric, additional, Bansal, Aruna T., additional, Lutter, Rene, additional, Sousa, Ana R., additional, Corfield, Julie, additional, Pandis, Ioannis, additional, Bakke, Per S., additional, Caruso, Massimo, additional, Chanez, Pascal, additional, Dahlén, Sven-Erik, additional, Fleming, Louise J., additional, Fowler, Stephen J., additional, Horvath, Ildiko, additional, Krug, Norbert, additional, Montuschi, Paolo, additional, Sanak, Marek, additional, Sandstrom, Thomas, additional, Shaw, Dominic E., additional, Singer, Florian, additional, Sterk, Peter J., additional, Roberts, Graham, additional, Adcock, Ian M., additional, Djukanovic, Ratko, additional, Auffray, Charles, additional, Chung, Kian Fan, additional, Adriaens, Nora, additional, Ahmed, Hassan, additional, Aliprantis, Antonios, additional, Alving, Kjell, additional, Badorek, Philipp, additional, Balgoma, David, additional, Barber, Clair, additional, Bautmans, An, additional, Behndig, Annelie F., additional, Bel, Elisabeth, additional, Beleta, Jorge, additional, Berglind, Ann, additional, Berton, Alix, additional, Bigler, Jeanette, additional, Bisgaard, Hans, additional, Bochenek, Grazyna, additional, Boedigheimer, Michael J., additional, Bøonnelykke, Klaus, additional, Brandsma, Joost, additional, Braun, Armin, additional, Brinkman, Paul, additional, Burg, Dominic, additional, Campagna, Davide, additional, Carayannopoulos, Leon, additional, Carvalho da Purfição Rocha, João P., additional, Chaiboonchoe, Amphun, additional, Chaleckis, Romanas, additional, Coleman, Courtney, additional, Compton, Chris, additional, D'Amico, Arnaldo, additional, Dahlén, Barbro, additional, De Alba, Jorge, additional, de Boer, Pim, additional, De Lepeleire, Inge, additional, Dekker, Tamara, additional, Delin, Ingrid, additional, Dennison, Patrick, additional, Dijkhuis, Annemiek, additional, Draper, Aleksandra, additional, Edwards, Jessica, additional, Emma, Rosalia, additional, Ericsson, Magnus, additional, Erpenbeck, Veit, additional, Erzen, Damijan, additional, Faulenbach, Cornelia, additional, Fichtner, Klaus, additional, Fitch, Neil, additional, Flood, Breda, additional, Frey, Urs, additional, Gahlemann, Martina, additional, Galffy, Gabriella, additional, Gallart, Hector, additional, Garret, Trevor, additional, Geiser, Thomas, additional, Gent, Jilaiha, additional, Gerhardsson de Verdier, Maria, additional, Gibeon, David, additional, Gomez, Cristina, additional, Gove, Kerry, additional, Gozzard, Neil, additional, Guo, Yi-Ke, additional, Hashimoto, Simone, additional, Haughney, John, additional, Hedlin, Gunilla, additional, Hekking, Pieter-Paul, additional, Henriksson, Elisabeth, additional, Hewitt, Lorraine, additional, Higgenbottam, Tim, additional, Hoda, Uruj, additional, Hohlfeld, Jans, additional, Holweg, Cecile, additional, Howarth, Peter, additional, Hu, Richard, additional, Hu, Sile, additional, Hu, Xugang, additional, Hudson, Val, additional, James, Anna J., additional, Kamphuis, Juliette, additional, Kennington, Erika J., additional, Kerry, Dyson, additional, Klüglich, Matthias, additional, Knobel, Hugo, additional, Knowles, Richard, additional, Knox, Alan, additional, Kolmert, Johan, additional, Konradsen, Jon, additional, Kots, Maxim, additional, Krueger, Linn, additional, Kuo, Scott, additional, Kupczyk, Maciej, additional, Lambrecht, Bart, additional, Lantz, Ann-Sofie, additional, Larsson, Lars, additional, Lazarinis, Nikos, additional, Lone-Satif, Saeeda, additional, Marouzet, Lisa, additional, Martin, Jane, additional, Masefield, Sarah, additional, Mathon, Caroline, additional, Matthews, John G., additional, Mazein, Alexander, additional, Meah, Sally, additional, Maiser, Andrea, additional, Menzies-Gow, Andrew, additional, Metcalf, Leanne, additional, Middelveld, Roelinde, additional, Mikus, Maria, additional, Miralpeix, Montse, additional, Monk, Philips, additional, Mores, Nadia, additional, Murray, Clare S., additional, Musial, Jacek, additional, Myles, David, additional, Naz, Shama, additional, Nething, Katja, additional, Nicholas, Ben, additional, Nihlen, Ulf, additional, Nilsson, Peter, additional, Nordlund, Björn, additional, Östling, Jörgen, additional, Pacino, Antonio, additional, Pahus, Laurie, additional, Palkonnen, Susanna, additional, Pavlidis, Stelios, additional, Pennazza, Giorgio, additional, Petrén, Anne, additional, Pink, Sandy, additional, Postle, Anthony, additional, Powel, Pippa, additional, Rahman-Amin, Malayka, additional, Rao, Navin, additional, Ravanetti, Lara, additional, Ray, Emma, additional, Reinke, Stacey, additional, Reynolds, Leanne, additional, Riemann, Kathrin, additional, Riley, John, additional, Robberechts, Martine, additional, Roberts, Amanda, additional, Rossios, Christos, additional, Russell, Kirsty, additional, Rutgers, Michael, additional, Santini, Giuseppe, additional, Sentoninco, Marco, additional, Schoelch, Corinna, additional, Schofield, James P.R., additional, Seibold, Wolfgang, additional, Sigmund, Ralf, additional, Sjödin, Marcus, additional, Skipp, Paul J., additional, Smids, Barbara, additional, Smith, Caroline, additional, Smith, Jessica, additional, Smith, Katherine M., additional, Söderman, Päivi, additional, Sogbesan, Adesimbo, additional, Staykova, Doroteya, additional, Strandberg, Karin, additional, Sun, Kai, additional, Supple, David, additional, Szentkereszty, Marton, additional, Tamasi, Lilla, additional, Tariq, Kamran, additional, Thörngren, John-Olof, additional, Thornton, Bob, additional, Thorsen, Jonathan, additional, Valente, Salvatore, additional, van Aalderenm, Wim, additional, van de Pol, Marianne, additional, van Drunen, Kees, additional, van Geest, Marleen, additional, Versnel, Jenny, additional, Vestbo, Jorgen, additional, Vink, Anton, additional, Vissing, Nadja, additional, von Garnier, Christophe, additional, Wagerner, Arianne, additional, Wagers, Scott, additional, Wald, Frans, additional, Walker, Samantha, additional, Ward, Jonathan, additional, Weiszhart, Zsoka, additional, Wetzel, Kristiane, additional, Wheelock, Craig E., additional, Wiegman, Coen, additional, Williams, Siân, additional, Wilson, Susan J., additional, Woosdcock, Ashley, additional, Yang, Xian, additional, Yeyashingham, Elizabeth, additional, Yu, Wen, additional, Zetterquist, Wilhelm, additional, and Zwinderman, Koos, additional

Published
2017
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41. Clinical and inflammatory characteristics of the European U-BIOPRED adult severe asthma cohort

Author

Shaw, Dominick E., Sousa, Ana R., Fowler, Stephen J., Fleming, Louise J., Roberts, Graham, Corfield, Julie, Pandis, Ioannis, Bansal, Aruna T., Bel, Elisabeth H., Auffray, Charles, Compton, Chris H., Bisgaard, Hans, Bucchioni, Enrica, Caruso, Massimo, Chanez, Pascal, Dahlen, Barbro, Dahlen, Sven-Erik, Dyson, Kerry, Frey, Urs, Geiser, Thomas, Gerhardsson de Verdier, Maria, Gibeon, David, Guo, Yi-ke, Hashimoto, Simone, Hedlin, Gunilla, Jeyasingham, Elizabeth, Hekking, Pieter-Paul W., Higenbottam, Tim, Knox, Alan J., Krug, Norbert, Erpenbeck, Veit J., Larsson, Lars X., Lazarinis, Nikos, Matthews, John G., Middelveld, Roelinde, Montuschi, Paolo, Musial, Jacek, Myles, David, Pahus, Laurie, Seibold, Wolfgang, Singer, Florian, Strandberg, Karin, Vestbo, Jorgen, Vissing, Nadja, von Garnier, Christophe, Adcock, Ian M., Wagers, Scott, Rowe, Anthony, Howarth, Peter, Wagener, Ariane H., Djukanovic, Ratko, Sterk, Peter J., and Chung, Kian Fan

Subjects
Pulmonary and Respiratory Medicine, respiratory tract diseases
Abstract

U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12?months; p

Published
2015

42. Change in biomarkers of type-2 inflammation following severe exacerbations of asthma.

Author

Semprini, Ruth, Shortt, Nick, Ebmeier, Stefan, Semprini, Alex, Varughese, Rachel, Holweg, Cecile T.J., Matthews, John G., Fingleton, James, Weatherall, Mark, Beasley, Richard, and Braithwaite, Irene

Subjects
ASTHMA, PRICE inflation, NITRIC oxide analysis, BREATH tests, CELL adhesion molecules, EOSINOPHILS, IMMUNOGLOBULINS, TIME, LEUKOCYTE count
Abstract

We investigated the time course of change of type-2 asthma biomarkers after a severe asthma exacerbation. Blood eosinophils were lowest immediately after treatment was initiated (0.07 vs 0.33×109/L, p<0.001) while serum IgE levels were at their highest (339 vs 249 U/L, p<0.001). Fractional exhaled Nitric Oxide levels were lowest 2 weeks after treatment (23 vs 33 ppb, p=0.06) and serum periostin levels were lowest 1 week after treatment (45·9 vs 50·9 ng/mL, p<0.001). A delay of 4-8 weeks following a severe exacerbation is required if these biomarkers are used to guide the ongoing management of patients with asthma. TRIAL REGISTRATION NUMBER: Post-results; The Australia New Zealand Trial Registry, >ACTRN12614000443695. [ABSTRACT FROM AUTHOR]

Published
2019
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43. Murray, Paul. The Mark and the Void

Author

Matthews, John G.

Subjects
The Mark and the Void (Novel) -- Murray, Paul -- Book reviews, Books -- Book reviews, Library and information science
Abstract

* Murray, Paul. The Mark and the Void. Farrar. Oct. 2015.480p. ISBN 9780865477551.$27; ebk. ISBN 9780374712983. F Paris native Claude Martingale works in Dublin as an analyst for an investment [...]

Published
2015

44. Gallagher, Mia. Beautiful Pictures of the Lost Homeland

Author

Matthews, John G.

Subjects
Beautiful Pictures of the Lost Homeland (Novel) -- Gallagher, Mia -- Book reviews, Library and information science
Abstract

* Gallagher, Mia. Beautiful Pictures of the Lost Homeland. New Island: Dufour. Feb. 2017. 512p. ISBN 9781848405066. pap. $25. F On a recent morning, Georgia (nee Georgie) Madden wakes in [...]

Published
2017

45. Jordan, Neil. Carnivalesque

Author

Matthews, John G.

Subjects
Carnivalesque (Novel) -- Jordan, Neil -- Book reviews, Library and information science
Abstract

* Jordan, Neil. Carnivalesque. Bloomsbury USA. Jun. 2017. 320p. ISBN 9781632868145. $27; ebk. ISBN 9781408881361. F In the summer of 2016, 14-year-old Dubliner Andy Rackard enters Burleigh's Amazing Hall of [...]

Published
2017

47. LATE-BREAKING ABSTRACT: LAVOLTA I and II: Results of 2 phase III studies to assess the efficacy and safety of lebrikizumab in patients with uncontrolled asthma

Author

Hanania, Nicola, primary, Korenblat, Phillip, additional, Chapman, Kenneth R., additional, Bateman, Eric D., additional, Kopecky, Petr, additional, Paggiaro, Pier L., additional, Yokoyama, Akihito, additional, Olsson, Julie, additional, Gray, Sarah, additional, Holweg, Cecile T.J., additional, Eisner, Mark, additional, Asare, Charles, additional, and Matthews, John G., additional

Published
2016
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49. Type 2 Biomarkers Define a Prevalent Phenotype in Moderate-to-Severe, Uncontrolled Asthma Patients: A Pooled Analysis from Lebrikizumab All-Comers Phase 2 Trials

Author

Korenblat, Phillip E., primary, Hanania, Nicola A., additional, Corren, Jonathan, additional, Olssen, Julie K., additional, Kamath, Nikhil, additional, Gray, Sarah, additional, Martin, Nicolas, additional, Holweg, Cecile T.J., additional, Matthews, John G., additional, Limb, Susan L., additional, and Korom, Stephan, additional

Published
2016
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