TY - JOUR
T1 - Severe asthma exists despite suppressed tissue inflammation: findings of the U-BIOPRED study
AU - Wilson, Susan J.
AU - Ward, Jonathan A.
AU - Sousa, Ana R.
AU - Corfield, Julie
AU - Bansal, Aruna T.
AU - de Meulder, Bertrand
AU - Lefaudeux, Diane
AU - Auffray, Charles
AU - Loza, Matthew J.
AU - Baribaud, Frederic
AU - Fitch, Neil
AU - Sterk, Peter J.
AU - Chung, Kian Fan
AU - Gibeon, David
AU - Sun, Kai
AU - Guo, Yi-Ke
AU - Adcock, Ian
AU - Djukanovic, Ratko
AU - Dahlen, Barbro
AU - Chanez, Pascal
AU - Shaw, Dominick
AU - Krug, Norbert
AU - Hohlfeld, Jens
AU - Sandström, Thomas
AU - Howarth, Peter H.
PY - 2016
Y1 - 2016
N2 - 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
AB - 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
U2 - https://doi.org/10.1183/13993003.01129-2016
DO - https://doi.org/10.1183/13993003.01129-2016
M3 - Article
C2 - 27799384
SN - 0903-1936
VL - 48
SP - 1307
EP - 1319
JO - European respiratory journal
JF - European respiratory journal
IS - 5
ER -