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

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

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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.

Original languageEnglish
Pages (from-to)1811-1820.e7
Number of pages17
JournalJournal of Allergy and Clinical Immunology
Issue number5
Early online date6 Dec 2018
Publication statusPublished - 31 May 2019


  • electronic nose technology
  • eosinophils
  • exhaled breath
  • follow-up
  • neutrophils
  • oral corticosteroids
  • severe asthma
  • unbiased clustering
  • volatile organic compound


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