• Pieter-Paul Hekking, Matt J Loza, Stelios Pavlidis, Bertrand de Meulder, Diane Lefaudeux, Fred Baribaud, Charles Auffray, Ariane H Wagener, Paul Brinkman, Rene Lutter, Aruna T Bansal, Ana R Sousa, Steve A Bates, Yannis Pandis, Louise J Fleming, Dominique E Shaw, Stephen J Fowler, Y Guo, Andrea Meiser, Kai Sun, Julie Corfield, Peter H Howarth, Elisabeth H Bel, Ian M Adcock, Kian Fan Chung, Ratko Djukanovic, Peter J Sterk, and U-BIOPRED Study Group.
• Respiratory Medicine, Academic Medical Centre, Amsterdam, The Netherlands. Electronic address: p.w.hekking@amc.uva.nl.
• J. Allergy Clin. Immunol. 2018 Apr 1; 141 (4): 1280-1290.

BackgroundAdult-onset severe asthma is characterized by highly symptomatic disease despite high-intensity asthma treatments. Understanding of the underlying pathways of this heterogeneous disease is needed for the development of targeted treatments. Gene set variation analysis is a statistical technique used to identify gene profiles in heterogeneous samples.ObjectiveWe sought to identify gene profiles associated with adult-onset severe asthma.MethodsThis was a cross-sectional, observational study in which adult patients with adult-onset of asthma (defined as starting at age ≥18 years) as compared with childhood-onset severe asthma (<18 years) were selected from the U-BIOPRED cohort. Gene expression was assessed on the total RNA of induced sputum (n = 83), nasal brushings (n = 41), and endobronchial brushings (n = 65) and biopsies (n = 47) (Affymetrix HT HG-U133+ PM). Gene set variation analysis was used to identify differentially enriched predefined gene signatures of leukocyte lineage, inflammatory and induced lung injury pathways.ResultsSignificant differentially enriched gene signatures in patients with adult-onset as compared with childhood-onset severe asthma were identified in nasal brushings (5 signatures), sputum (3 signatures), and endobronchial brushings (6 signatures). Signatures associated with eosinophilic airway inflammation, mast cells, and group 3 innate lymphoid cells were more enriched in adult-onset severe asthma, whereas signatures associated with induced lung injury were less enriched in adult-onset severe asthma.ConclusionsAdult-onset severe asthma is characterized by inflammatory pathways involving eosinophils, mast cells, and group 3 innate lymphoid cells. These pathways could represent useful targets for the treatment of adult-onset severe asthma.Copyright © 2017. Published by Elsevier Inc.

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