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Author Hekking, P.-P.; Loza, M.J.; Pavlidis, S.; de Meulder, B.; Lefaudeux, D.; Baribaud, F.; Auffray, C.; Wagener, A.H.; Brinkman, P.I.; Lutter, R.I.; Bansal, A.T.; Sousa, A.R.; Bates, S.A.; Pandis, Y.; Fleming, L.J.; Shaw, D.E.; Fowler, S.J.; Guo, Y.; Meiser, A.; Sun, K.; Corfield, J.; Howarth, P.H.; Bel, E.H.; Adcock, I.M.; Chung, K.F.; Djukanovic, R.; Sterk, P.J. url  doi
  Title Pathway discovery using transcriptomic profiles in adult-onset severe asthma Type Journal Article
  Year (down) 2017 Publication The Journal of Allergy and Clinical Immunology Abbreviated Journal J Allergy Clin Immunol  
  Volume Issue Pages  
  Keywords Adult-onset asthma; Ilc3; eosinophils; gene set variation analysis; mast cells; mechanisms; phenotyping; severe asthma; transcriptomics  
  Abstract BACKGROUND: Adult-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. OBJECTIVE: We sought to identify gene profiles associated with adult-onset severe asthma. METHODS: This 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. RESULTS: Significant 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. CONCLUSIONS: Adult-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.  
  Address Respiratory Medicine, Academic Medical Centre, Amsterdam, The Netherlands  
  Corporate Author U-BIOPRED Study Group Thesis  
  Impact Factor 11,476 First Author Hekking, P.-P. Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Senior Author Sterk, P.J.  
  ISSN 0091-6749 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28756296 Approved no  
  Call Number Serial 359  
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