PT - JOURNAL ARTICLE AU - Isabelle Dupin AU - Matthieu Thumerel AU - Elise Maurat AU - Florence Coste AU - Edmée Eyraud AU - Hugues Begueret AU - Thomas Trian AU - Michel Montaudon AU - Roger Marthan AU - Pierre-Olivier Girodet AU - Patrick Berger TI - Fibrocyte accumulation in the airway walls of COPD patients AID - 10.1183/13993003.02173-2018 DP - 2019 Jan 01 TA - European Respiratory Journal PG - 1802173 4099 - http://erj.ersjournals.com/content/early/2019/05/30/13993003.02173-2018.short 4100 - http://erj.ersjournals.com/content/early/2019/05/30/13993003.02173-2018.full AB - The remodelling mechanism and cellular players causing persistent airflow limitation in chronic obstructive pulmonary disease (COPD) remain largely elusive. We have recently demonstrated that circulating fibrocytes, a rare population of fibroblast-like cells produced by the bone marrow stroma, are increased in COPD patients during an exacerbation. We aimed to quantify fibrocyte density in situ in bronchial specimens from both control subjects and COPD patients, to define associations with relevant clinical, functional and computed tomography (CT) parameters and to investigate the effect of the epithelial microenvironment on fibrocyte survival in vitro (“Fibrochir” study).A total of 17 COPD patients and 25 control subjects, all requiring thoracic surgery, were recruited. Using co-immunostaining and image analysis, we identified CD45+ FSP1+ cells as tissue fibrocytes and quantified their density in distal and proximal bronchial specimens. Fibrocytes, cultured from the blood samples of 6 COPD patients, were exposed to primary bronchial epithelial cell secretions from control subjects or COPD patients.We demonstrate that fibrocytes are increased in both distal and proximal tissue specimens of COPD patients. The density of fibrocytes is negatively correlated with lung function parameters and positively correlated with bronchial wall thickness as assessed by CT scan. A high density of distal bronchial fibrocytes predicts the presence of COPD with a sensitivity of 83% and a specificity of 70%. Exposure of fibrocytes to COPD epithelial cell supernatant favours cell survival.Our results thus demonstrate an increased density of fibrocytes within the bronchi of COPD patients, which may be promoted by epithelial-derived survival-mediating factors.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Thumerel has nothing to disclose.Conflict of interest: Dr. Maurat has nothing to disclose.Conflict of interest: Dr. Coste has nothing to disclose.Conflict of interest: Dr. Eyraud has nothing to disclose.Conflict of interest: Dr. Begueret has nothing to disclose.Conflict of interest: Dr. Trian has nothing to disclose.Conflict of interest: Dr. Montaudon has nothing to disclose.Conflict of interest: Dr. Marthan has nothing to disclose.Conflict of interest: Dr. Girodet reports personal fees from Novartis, personal fees from Chiesi, personal fees from Boehringer Ingelheim, personal fees from AstraZeneca, personal fees from GlaxoSmithKline, outside the submitted work; In addition, Dr. Girodet has a patent (EP N°15152886.6 i.e. New compositions and methods of treating and/or preventing Chronic Obstructive Pulmonary Disease) pending.Conflict of interest: Dr. Berger reports grants from Nycomed, grants from Takeda, grants from Fondation du Souffle–Fonds de dotation Recherche en Santé Respiratoire, during the conduct of the study; grants and personal fees from Novartis, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from AstraZeneca, personal fees and non-financial support from Sanofi, personal fees from Menarinni, personal fees from TEVA, outside the submitted work; In addition, Dr. Berger has a patent (EP N°15152886.6 i.e. New compositions and methods of treating and/or preventing Chronic Obstructive Pulmonary Disease) pending.Conflict of interest: Dr. Dupin reports grants from Fondation Bordeaux Université, during the conduct of the study; In addition, Dr. Dupin has a patent (EP N°15152886.6 i.e. New compositions and methods of treating and/or preventing Chronic Obstructive Pulmonary Disease) pending.