Identification and prospective stability of electronic nose (eNose)–derived inflammatory phenotypes in patients with severe asthma - 04/05/19
, Ariane H. Wagener, MD, PhD a, Pieter-Paul Hekking, MD, PhD a, Aruna T. Bansal, PhD b, Anke-Hilse Maitland-van der Zee, PhD a, Yuanyue Wang, MSc c, Hans Weda, PhD c, Hugo H. Knobel, MSc d, Teunis J. Vink, PhD c, Nicholas J. Rattray, PhD e, Arnaldo D'Amico, PhD f, Giorgio Pennazza, PhD g, Marco Santonico, PhD g, Diane Lefaudeux, MSc h, Bertrand De Meulder, PhD h, Charles Auffray, PhD h, Per S. Bakke, MD, PhD i, Massimo Caruso, MD, PhD j, Pascal Chanez, MD, PhD k, Kian F. Chung, MD, PhD l, Julie Corfield, MSc m, n, Sven-Erik Dahlén, PhD o, Ratko Djukanovic, MD, PhD p, Thomas Geiser, MD, PhD q, Ildiko Horvath, MD, PhD r, Nobert Krug, MD, PhD s, Jacek Musial, MD, PhD t, Kai Sun, PhD u, John H. Riley, PhD v, Dominic E. Shaw, MD, PhD w, Thomas Sandström, MD, PhD x, Ana R. Sousa, PhD v, Paolo Montuschi, MD, PhD y, Stephen J. Fowler, MD, PhD z, aa, Peter J. Sterk, MD, PhD aon behalf of the
U-BIOPRED Study Group∗
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.
Le texte complet de cet article est disponible en PDF.Key words : Electronic nose technology, exhaled breath, volatile organic compound, follow-up, severe asthma, unbiased clustering, eosinophils, neutrophils, oral corticosteroids
Abbreviations used : eNose, ERS, GC-MS, IQR, OCS, PAM, TAC, TDA, VOC
Plan
| U-BIOPRED has received funding from the Innovative Medicines Initiative (IMI) Joint Undertaking under grant agreement no. 115010, resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (FP7/2007–2013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in-kind contributions (www.imi.europa.eu). |
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| Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts no interest. |
Vol 143 - N° 5
P. 1811 - mai 2019 Retour au numéro
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