title: Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study.
abstract: The U-BIOPRED study is a multicentre European study aimed at a better understanding of severe asthma. It included three steroid-treated adult asthma groups (severe nonsmokers (SAn group), severe current/ex-smokers (SAs/ex group) and those with mild-moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.In 158 participants, bronchial biopsies and bronchial epithelial brushings were collected for immunopathologic and transcriptomic analysis. Immunohistochemical analysis of glycol methacrylate resin-embedded biopsies showed there were more mast cells in submucosa of the HC group (33.6 mm-2) compared with both severe asthma groups (SAn: 17.4 mm-2, p<0.001; SAs/ex: 22.2 mm-2, p=0.01) and with the MMA group (21.2 mm-2, p=0.01). The number of CD4+lymphocytes was decreased in the SAs/ex group (4.7 mm-2) compared with the SAn (11.6 mm-2, p=0.002), MMA (10.1 mm-2, p=0.008) and HC (10.6 mm-2, p<0.001) groups. No other differences were observed.Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to COX-2 (cyclo-oxygenase-2), ADAM-7 (disintegrin and metalloproteinase domain-containing protein 7), SLCO1A2 (solute carrier organic anion transporter family member 1A2), TMEFF2 (transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and TRPM-1 (transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway wall.
authors: Faculty of Medicine, University of Southampton and NIHR Respiratory Biomedical Research Unit, University of Southampton NHS Foundation Trust, Southampton, UK S.J.Wilson@southampton.ac.uk.
authors: Susan J
authors: SJ
authors: Wilson
authors: Faculty of Medicine, University of Southampton and NIHR Respiratory Biomedical Research Unit, University of Southampton NHS Foundation Trust, Southampton, UK.
authors: Jonathan A
authors: JA
authors: Ward
authors: GlaxoSmithKline, Stevenage, UK.
authors: Ana R
authors: AR
authors: Sousa
authors: AstraZeneca, Mölndal, Sweden.|Areteva, Nottingham, UK.
authors: Julie
authors: J
authors: Corfield
authors: Acclarogen, Cambridge, UK.
authors: Aruna T
authors: AT
authors: Bansal
authors: European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Lyon, France.
authors: Bertrand
authors: B
authors: De Meulder
authors: European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Lyon, France.
authors: Diane
authors: D
authors: Lefaudeux
authors: European Institute for Systems Biology and Medicine, CIRI UMR5308, CNRS-ENS-UCBL-INSERM, Lyon, France.
authors: Charles
authors: C
authors: Auffray
authors: Janssen R&D, Spring House, PA, USA.
authors: Matthew J
authors: MJ
authors: Loza
authors: Janssen R&D, Spring House, PA, USA.
authors: Frederic
authors: F
authors: Baribaud
authors: BioSciConsulting, Maasmechelen, Belgium.
authors: Neil
authors: N
authors: Fitch
authors: Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors: Peter J
authors: PJ
authors: Sterk
authors: Imperial College London, London, UK.
authors: Kian Fan
authors: KF
authors: Chung
authors: Imperial College London, London, UK.
authors: David
authors: D
authors: Gibeon
authors: Imperial College London, London, UK.
authors: Kai
authors: K
authors: Sun
authors: Imperial College London, London, UK.
authors: Yi-Ke
authors: YK
authors: Guo
authors: Imperial College London, London, UK.
authors: Ian
authors: I
authors: Adcock
authors: Faculty of Medicine, University of Southampton and NIHR Respiratory Biomedical Research Unit, University of Southampton NHS Foundation Trust, Southampton, UK.
authors: Ratko
authors: R
authors: Djukanovic
authors: Centre for Allergy Research, Karolinska Institute, Stockholm, Sweden.
authors: Barbro
authors: B
authors: Dahlen
authors: Université de la Médierranee, Marseille, France.
authors: Pascal
authors: P
authors: Chanez
authors: Centre for Respiratory Research, University of Nottingham, Nottingham, UK.
authors: Dominick
authors: D
authors: Shaw
authors: Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
authors: Norbert
authors: N
authors: Krug
authors: Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover, Germany.
authors: Jens
authors: J
authors: Hohlfeld
authors: Dept of Respiratory Medicine, Umeå University, Umeå, Sweden.
authors: Thomas
authors: T
authors: Sandström
authors: Faculty of Medicine, University of Southampton and NIHR Respiratory Biomedical Research Unit, University of Southampton NHS Foundation Trust, Southampton, UK.
authors: Peter H
authors: PH
authors: Howarth
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry; D000328:Adult; D001249:Asthma / Q000503:physiopathology* / Q000628:therapy*; D001706:Biopsy; D001980:Bronchi / Q000276:immunology / Q000503:physiopathology*; D001999:Bronchoscopy; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005060:Europe; D005260:Female; D006801:Humans; D007120:Immunochemistry; D007249:Inflammation / Q000188:drug therapy*; D008297:Male; D008689:Methacrylates / Q000737:chemistry; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012907:Smoking; D059467:Transcriptome
chemical_list: D000180:Acrylic Resins; D008689:Methacrylates; C005044:hydroxyethyl methacrylate