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Identification and prospective stability of electronic nose (eNose)–derived inflammatory phenotypes in patients with severe asthma - 04/05/19

Doi : 10.1016/j.jaci.2018.10.058 
Paul Brinkman, MSc a, , 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 a
on behalf of the

U-BIOPRED Study Group

  See the supplementary U-BIOPRED Study Group contributors' list in this article's Online Repository.

a Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands 
b Acclarogen, St John's Innovation Centre, Cambridge, United Kingdom 
c Philips Research, Eindhoven, The Netherlands 
d Philips Lighting, Eindhoven, The Netherlands 
e Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, Conn 
f Department of Electronic Engineering, University of Rome “Tor Vergata,” Rome, Italy 
g Center for Integrated Research–CIR, Unit for Electronics for Sensor Systems, Campus Bio-Medico U, Rome, Italy 
h European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Lyon, France 
i Institute of Medicine, University of Bergen, Bergen, Norway 
j Department of Clinical and Experimental Medicine Hospital University, University of Catania, Catania, Italy 
k Département des Maladies Respiratoires APHM,U1067 INSERM, Aix Marseille Université Marseille, Marseille, Italy 
l National Heart and Lung Institute, Imperial College, London, UK Biomedical Research Unit, Royal Brompton & Harefield NHS Trust, London, United Kingdom 
m AstraZeneca R&D, Mölndal, Sweden 
n Areteva R&D, Nottingham, United Kingdom 
o Centre for Allergy Research, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden 
p NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom 
q the Department of Pulmonary Medicine, University Hospital Bern, Bern, Switzerland 
r Department of Pulmonology, Semmelweis University, Budapest, Hungary 
s Fraunhofer Institute for Toxicology and Experimental Medicine Hannover, Hannover, Germany 
t Department of Medicine, Jagiellonian University Medical College, Krakow, Poland 
u Data Science Institute, South Kensington Campus, Imperial College Londont, London, United Kingdom 
v Respiratory Therapeutic Unit, GlaxoSmithKline, Stockley Park, United Kingdom 
w Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom 
x Department of Public Health and Clinical Medicine, Department of Medicine, Respiratory Medicine Unit, Umeå University, Umeå, Sweden 
y Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Rome, Italy 
z Respiratory Research Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester Academic Healthy Science Centre, and NIHR Translational Research Faculty in Respiratory Medicine, University Hospital of South Manchester, Manchester, United Kingdom 
aa Lancashire Teaching Hospitals NHS Foundation Trust, Preston, United Kingdom 

Corresponding author: Paul Brinkman, MSc, Department of Respiratory Medicine, F5-259, Academic Medical Center (AMC)/University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands.Department of Respiratory MedicineF5-259Academic Medical Center (AMC)/University of AmsterdamMeibergdreef 9Amsterdam1105 AZThe Netherlands

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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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).
 Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts no interest.


© 2018  American Academy of Allergy, Asthma & Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 143 - N° 5

P. 1811 - mai 2019 Retour au numéro
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