Abstract
The remodelling mechanism and cellular players causing persistent airflow limitation in 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 six 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.
Abstract
A high density of tissue fibrocytes is associated with reduced lung function and an increase in airway wall thickness bit.ly/2JO71Dq
Footnotes
This article has supplementary material available from erj.ersjournals.com
This study is registered at ClinicalTrials.gov with identifier number NCT01692444.
Conflict of interest: I. Dupin reports grants from Fondation Bordeaux Université, during the conduct of the study. In addition, she has a patent (EP 15152886.6: New compositions and methods of treating and/or preventing Chronic Obstructive Pulmonary Disease) pending.
Conflict of interest: M. Thumerel has nothing to disclose.
Conflict of interest: E. Maurat has nothing to disclose.
Conflict of interest: F. Coste has nothing to disclose.
Conflict of interest: E. Eyraud has nothing to disclose.
Conflict of interest: H. Begueret has nothing to disclose.
Conflict of interest: T. Trian has nothing to disclose.
Conflict of interest: M. Montaudon has nothing to disclose.
Conflict of interest: R. Marthan has nothing to disclose.
Conflict of interest: P-O. Girodet reports personal fees from Novartis, Chiesi, Boehringer Ingelheim, AstraZeneca and GlaxoSmithKline, outside the submitted work. In addition, he has a patent (EP 15152886.6: New compositions and methods of treating and/or preventing Chronic Obstructive Pulmonary Disease) pending.
Conflict of interest: P. Berger reports grants from Nycomed, Takeda and 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 nonfinancial support from AstraZeneca, Sanofi, and Chiesi, grants, personal fees and nonfinancial support from Boehringer Ingelheim, and personal fees from Menarinni and Teva, outside the submitted work. In addition, he has a patent (EP 15152886.6: New compositions and methods of treating and/or preventing Chronic Obstructive Pulmonary Disease) pending.
Support statement: This study was sponsored and supported by Bordeaux University Hospital (CHU de Bordeaux). This study was supported by a grant from the Fondation Bordeaux Université, with funding from Assistance Ventilatoire à Domicile (AVAD) and Fédération Girondine de Lutte contre les Maladies Respiratoires (FGLMR). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received November 14, 2018.
- Accepted May 28, 2019.
- Copyright ©ERS 2019
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