Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study

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Loza, M. J. (author)

Validated and longitudinally stable asthma phenotypes based on cluster analysis of the ADEPT study

Article/chapterEnglish2016

Publisher, publication year, extent ...

2016-12-15
Springer Nature,2016
printrdacarrier

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LIBRIS-ID:oai:DiVA.org:kth-280494
https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-280494URI
https://doi.org/10.1186/s12931-016-0482-9DOI
http://kipublications.ki.se/Default.aspx?queryparsed=id:134843388URI

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Language:English
Summary in:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

QC 20200910
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.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Lungmedicin och allergi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Respiratory Medicine and Allergy hsv//eng
Biological markers
Cluster analysis
Observational study
biological marker
interleukin 13
interleukin 4
autacoid
IL4 protein
human
interleukin-13
human
adult
airway obstruction
Article
asthma
bronchus biopsy
controlled study
disease classification
disease severity
female
gene expression
human
lung function
major clinical study
male
phenotype
respiratory tract disease assessment
Th2 cell
classification
cross-sectional study
forced expiratory volume
fuzzy logic
gene expression regulation
genetics
genotype
immunology
longitudinal study
lung
pathophysiology
predictive value
prognosis
reproducibility
severity of illness index
time factor
validation study
vital capacity
Cross-Sectional Studies
Humans
Inflammation Mediators
Interleukin-13
Interleukin-4
Longitudinal Studies
Predictive Value of Tests
Reproducibility of Results
Th2 Cells
Time Factors

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Djukanovic, R. (author)
Chung, K. F. (author)
Horowitz, D. (author)
Ma, K. (author)
Branigan, P. (author)
Barnathan, E. S. (author)
Susulic, V. S. (author)
Silkoff, P. E. (author)
Sterk, P. J. (author)
Baribaud, F. (author)
Strambu, I. (author)
Laviolette, M. (author)
Singh, D. (author)
FitzGerald, J. M. (author)
Lam, S. (author)
Kelsen, S. (author)
Eich, A. (author)
Ludwig-Sengpiel, A. (author)
hupp, G.C. (author)
Backer, V. (author)
Porsbjerg, C. (author)
Girodet, P. O. (author)
Berger, P. (author)
Leigh, R. (author)
Kline, J. (author)
Dransfield, M. (author)
Calhoun, W. (author)
Hussaini, A. (author)
Khatri, S. (author)
Chanez, P. (author)
Ian, A. (author)
Fleming Louis, J. (author)
David, G. (author)
Sile, H. (author)
Scott, K. (author)
Sally, M. (author)
Andrea, M. (author)
Stelios, P. (author)
Christos, R. (author)
Kirsty, R. (author)
Kai, S. (author)
Coen, W. (author)
Xian, Y. (author)
Nora, A. (author)
Ariane, W. (author)
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Saeeda, L. -L (author)
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Navin, R. (author)
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De Jorge, A. (author)
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Skipp Paul, J. (author)
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Rocha João Pedro, C. P. (author)
Julaiha, G. (author)
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Adesimbo, S. (author)
Amphun, C. (author)
Romanas, C. (author)
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Pascal, C. (author)
Courtney, C. (author)
Jessica, E. (author)
Val, H. (author)
Kennington Erika, J. (author)
Leanne, M. (author)
Malayka, R. -A (author)
Leanne, R. (author)
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Jenny, V. (author)
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Breda, F. (author)
Amanda, R. (author)
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Chris, C. (author)
David, M. (author)
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Sousa Ana, R. (author)
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Arnaldo, D'Amico (author)
Giorgio, P. (author)
Marco, S. (author)
Barbro, D. (author)
Ann-Sofie, L. (author)
Pim, B. (author)
Patrick, D. (author)
Kamran, T. (author)
Clair, B. (author)
Kerry, G. (author)
Aleksandra, D. (author)
Neil, F. (author)
Trevor, G. (author)
Scott, W. (author)
Rosalia, E. (author)
Davide, C. (author)
Magnus, E. (author)
Veit, E. (author)
Damijan, E. (author)
Klaus, F. (author)
Katja, N. (author)
Corinna, S. (author)
Frans, W. (author)
Kathrin, R. (author)
Matthias, Klüglich (author)
Fowler Stephen, J. (author)
Murray Clare, S. (author)
Jorgen, V. (author)
Ashley, W. (author)
Urs, F. (author)
Martina, G. (author)
Gabriella, G. (author)
Ildiko, H. (author)
Marton, S. (author)
Lilla, T. (author)
Zsoka, W. (author)
Thomas, G. (author)
Neil, G. (author)
Yi-ke, G. (author)
John, H. (author)
Siân, W. (author)
Elisabeth, H. (author)
Nikos, L. (author)
Karin, S. (author)
Lorraine, H. (author)
Lisa, M. (author)
Jane, M. (author)
Sandy, P. (author)
Emma, R. (author)
Caroline, S. (author)
Tim, H. (author)
Uruj, H. (author)
Cecile, H. (author)
Matthews John, G. (author)
Peter, H. (author)
Graham, R. (author)
Juliette, K. (author)
Dyson, K. (author)
Hugo, K. (author)
Anton, V. (author)
Richard, K. (author)
Alan, K. (author)
Shaw Dominick, E. (author)
Maxim, K. (author)
Linn, K. (author)
Bart, L. (author)
Sarah, M. (author)
Pippa, P. (author)
Alexander, M. (author)
Mikus, MariaKTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u1qjoszn (author)
Nilsson, PeterKTH,Science for Life Laboratory, SciLifeLab,Affinitets-proteomik(Swepub:kth)u1ws88sk (author)
Montse, M. (author)
Philip, M. (author)
Paolo, M. (author)
Nadia, M. (author)
Giuseppe, S. (author)
Salvatore, V. (author)
Antonio, P. (author)
Laurie, P. (author)
Susanna, P. (author)
Ioannis, P. (author)
Anthony, R. (author)
Wolfgang, S. (author)
Kristiane, W. (author)
Florian, S. (author)
Smith Katherine, M. (author)
Päivi, S. (author)
John-Olof, T. (author)
von Christophe, G. (author)
Jonathan, W. (author)
Wilson Susan, J. (author)
Elizabeth, Y. (author)
Therapeutics), For the ADEPT (Airways Disease Endotyping for Personalized (author)
investigators, U-BIOPRED (Unbiased Biomarkers for the Prediction of Respiratory Disease Outcome Consortium) (author)
KTHScience for Life Laboratory, SciLifeLab (creator_code:org_t)

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By the author/editor: Loza, M. J.; Djukanovic, R.; Chung, K. F.; Horowitz, D.; Ma, K.; Branigan, P.; show more...; 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, ...; 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, ...; Hector, G.; Maciej, K.; Johan, K.; Marcus, S.; Bansal Aruna, T.; Frédéric, B.; Navin, R.; An, B.; Inge, D. L.; Martine, R.; Behndig Annelie, ...; Thomas, S.; Jorge, B.; De Jorge, A.; Ann, B.; Gunilla, H.; Björn, Nordlund; Jon, K.; Wilhelm, Z.; Alix, B.; Jörgen, Ö.; van Marleen, G.; de Maria, G. V.; Lars, L.; Ulf, N.; Jeannette, B.; Boedigheimer Mic ...; 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, ...; Skipp Paul, J.; Leon, C.; Bob, T.; Massimo, C.; Rocha João Pedro ...; Julaiha, G.; Andrew, M. -G; Adesimbo, S.; Amphun, C.; Romanas, C.; Caroline, M.; Pascal, C.; Courtney, C.; Jessica, E.; Val, H.; Kennington Erika ...; 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.; Arnaldo, D'Amico; 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.; Matthias, Klügli ...; Fowler Stephen, ...; 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.; Siân, 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.; Mikus, Maria; Nilsson, Peter; 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, ...; Päivi, S.; John-Olof, T.; von Christophe, ...; Jonathan, W.; Wilson Susan, J.; Elizabeth, Y.; Therapeutics), F ...; investigators, U ...; show less...

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