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

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

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.

Electronic nose technology, eosinophils, exhaled breath, follow-up, neutrophils, oral corticosteroids, severe asthma, unbiased clustering, volatile organic compound
0091-6749
Brinkman, Paul
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Wagener, Ariane H.
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Hekking, Pieter Paul
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Bansal, Aruna T.
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Maitland-van der Zee, Anke Hilse
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Wang, Yuanyue
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Weda, Hans
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Knobel, Hugo H.
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Vink, Teunis J.
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Rattray, Nicholas J.
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D'Amico, Arnaldo
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Pennazza, Giorgio
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Santonico, Marco
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Lefaudeux, Diane
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De Meulder, Bertrand
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Auffray, Charles
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Bakke, Per S.
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Caruso, Massimo
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Chanez, Pascal
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Chung, Kian F.
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Corfield, Julie
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Dahlén, Sven Erik
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Djukanovic, Ratko
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Geiser, Thomas
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Horvath, Ildiko
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Krug, Nobert
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Musial, Jacek
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Sun, Kai
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Riley, John H.
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Shaw, Dominic E.
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Sandström, Thomas
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Sousa, Ana R.
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Montuschi, Paolo
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Fowler, Stephen J.
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Sterk, Peter J.
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U-BIOPRED Study Group
Brinkman, Paul
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Wagener, Ariane H.
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Hekking, Pieter Paul
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Bansal, Aruna T.
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Maitland-van der Zee, Anke Hilse
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Wang, Yuanyue
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Weda, Hans
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Knobel, Hugo H.
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Vink, Teunis J.
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Rattray, Nicholas J.
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D'Amico, Arnaldo
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Pennazza, Giorgio
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Santonico, Marco
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Lefaudeux, Diane
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De Meulder, Bertrand
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Auffray, Charles
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Bakke, Per S.
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Caruso, Massimo
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Chanez, Pascal
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Chung, Kian F.
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Corfield, Julie
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Dahlén, Sven Erik
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Djukanovic, Ratko
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Geiser, Thomas
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Horvath, Ildiko
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Krug, Nobert
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Musial, Jacek
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Sun, Kai
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Riley, John H.
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Shaw, Dominic E.
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Sandström, Thomas
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Sousa, Ana R.
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Montuschi, Paolo
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Fowler, Stephen J.
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Sterk, Peter J.
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Brinkman, Paul, Wagener, Ariane H., Hekking, Pieter Paul, Bansal, Aruna T., Maitland-van der Zee, Anke Hilse, Wang, Yuanyue, Weda, Hans, Knobel, Hugo H., Vink, Teunis J., Rattray, Nicholas J., D'Amico, Arnaldo, Pennazza, Giorgio, Santonico, Marco, Lefaudeux, Diane, De Meulder, Bertrand, Auffray, Charles, Bakke, Per S., Caruso, Massimo, Chanez, Pascal, Chung, Kian F., Corfield, Julie, Dahlén, Sven Erik, Djukanovic, Ratko, Geiser, Thomas, Horvath, Ildiko, Krug, Nobert, Musial, Jacek, Sun, Kai, Riley, John H., Shaw, Dominic E., Sandström, Thomas, Sousa, Ana R., Montuschi, Paolo, Fowler, Stephen J. and Sterk, Peter J. , U-BIOPRED Study Group (2018) Identification and prospective stability of electronic nose (eNose)–derived inflammatory phenotypes in patients with severe asthma. Journal of Allergy and Clinical Immunology. (doi:10.1016/j.jaci.2018.10.058).

Record type: Article

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.

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Identification and prospective stability of eNose derived inflammatory phenotypes - Accepted Manuscript
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More information

Accepted/In Press date: 22 October 2018
e-pub ahead of print date: 6 December 2018
Keywords: Electronic nose technology, eosinophils, exhaled breath, follow-up, neutrophils, oral corticosteroids, severe asthma, unbiased clustering, volatile organic compound

Identifiers

Local EPrints ID: 428269
URI: https://eprints.soton.ac.uk/id/eprint/428269
ISSN: 0091-6749
PURE UUID: fa90496e-ca10-4bfe-ac4e-5629438e287e
ORCID for Ratko Djukanovic: ORCID iD orcid.org/0000-0001-6039-5612

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Date deposited: 19 Feb 2019 17:30
Last modified: 14 Mar 2019 01:56

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Contributors

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

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