{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:36:19Z","timestamp":1788543379987,"version":"build-2803163510"},"reference-count":41,"publisher":"European Respiratory Society (ERS)","issue":"5","funder":[{"name":"Innovative Medicines Initiative (IMI) funding provided by the European Union (EU) and the European Federation of Pharmaceutical Industries and Associations"}],"content-domain":{"domain":["publications.ersnet.org"],"crossmark-restriction":true},"short-container-title":["Eur Respir J"],"accepted":{"date-parts":[[2016,8,10]]},"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>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\u2013moderate disease (MMA group)) and healthy controls (HC group). The aim of this cross-sectional, bronchoscopy substudy was to compare bronchial immunopathology between these groups.<\/jats:p><jats:p>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\u2005mm<jats:sup>\u22122<\/jats:sup>) compared with both severe asthma groups (SAn: 17.4\u2005mm<jats:sup>\u22122<\/jats:sup>, p&lt;0.001; SAs\/ex: 22.2\u2005mm<jats:sup>\u22122<\/jats:sup>, p=0.01) and with the MMA group (21.2\u2005mm<jats:sup>\u22122<\/jats:sup>, p=0.01). The number of CD4<jats:sup>+<\/jats:sup>lymphocytes was decreased in the SAs\/ex group (4.7\u2005mm<jats:sup>\u22122<\/jats:sup>) compared with the SAn (11.6\u2005mm<jats:sup>\u22122<\/jats:sup>, p=0.002), MMA (10.1\u2005mm<jats:sup>\u22122<\/jats:sup>, p=0.008) and HC (10.6\u2005mm<jats:sup>\u22122<\/jats:sup>, p&lt;0.001) groups. No other differences were observed.<\/jats:p><jats:p>Affymetrix microarray analysis identified seven probe sets in the bronchial brushing samples that had a positive relationship with submucosal eosinophils. These mapped to<jats:italic>COX-2<\/jats:italic>(cyclo-oxygenase-2),<jats:italic>ADAM-7<\/jats:italic>(disintegrin and metalloproteinase domain-containing protein 7),<jats:italic>SLCO1A2<\/jats:italic>(solute carrier organic anion transporter family member 1A2),<jats:italic>TMEFF2<\/jats:italic>(transmembrane protein with epidermal growth factor like and two follistatin like domains 2) and<jats:italic>TRPM-1<\/jats:italic>(transient receptor potential cation channel subfamily M member 1); the remaining two are unnamed.<\/jats:p><jats:p>We conclude that in nonsmoking and smoking patients on currently recommended therapy, severe asthma exists despite suppressed tissue inflammation within the proximal airway 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