Abstract
Background The remodeling 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. It remains, however, unclear, whether fibrocytes are present in bronchial tissue of COPD patients.
Objective We aimed to quantify fibrocytes density in bronchial specimens from both control subjects and COPD patients, and to define associations with clinical, functional and computed tomography relevant parameters.
Methods 17 COPD patients and 25 control subjects with normal lung function testing and no chronic symptoms, all of them requiring thoracic surgery, were recruited. LFT and CT-scan were performed before surgery. Using co-immunostaining and image analysis, we identify CD45+ FSP1+ cells as tissue fibrocytes and quantify their density in distal and proximal bronchial specimens from the whole series.
Results Here, we demonstrate that fibrocytes are increased in both distal and proximal tissue specimens of COPD patients, compared to those of controls. The density of fibrocytes is negatively correlated with lung function parameters, such as FEV1 and FEV1/FVC, and positively with bronchial wall thickness assessed by CT scan. High density of distal bronchial fibrocytes predicts presence of COPD with a sensitivity of 83% and a specificity of 70%.
Conclusions Our results thus suggest that recruitment of fibrocytes in the bronchi may participate to lung function decline during COPD progression.
Clinical Implications High density of tissue fibrocytes is associated with a deteriorated lung function and an increase in airway wall thickness. A low density tissue fibrocytes virtually eliminates the presence of COPD.
Capsule summary Blood fibrocytes assessed during exacerbation is a predictor of mortality in COPD. This study shows an increase of bronchial fibrocytes, that is associated with lower lung function, increased bronchial thickness and air trapping in COPD.
- Abbreviations
- APC
- Allophycocyanin
- BEC
- Bronchial Epithelial Cells
- CSA
- Cross Section Area
- CSN
- Cross Section Number
- GOLD
- Global Initiative for Chronic Obstructive Lung Disease
- COPD
- Chronic Obstructive Pulmonary Disease
- CT
- Computed tomography
- FEV1
- Forced Expiratory Volume in 1 second
- FITC
- Fluorescein isothiocyanate
- FVC
- Forced Vital Capacity
- FSP1
- Fibroblast-Specific Protein 1
- LA
- Lumen Area
- LAA
- Low Attenuation Area
- MLA
- Mean Lung Attenuation
- PaCO2
- Arterial Partial Pressure of Carbon Dioxide
- PaO2
- Arterial Partial Pressure of Oxygen
- PE
- Phycoerythrin
- PBMC
- Peripheral Blood Mononuclear Cells
- TLCO
- Transfer Lung capacity of Carbon monoxide
- WA
- Wall Area
- WT
- Wall Thickness
Footnotes
Disclosure of potential conflict of interest: I. Dupin has received research support from Fondation Bordeaux Université. P-O. Girodet has received research support from Novartis, Chiesi, Boehringer Ingelheim, GlaxoSmithKline and AstraZeneca outside the submitted work. P. Berger has received research support from Nycomed, Takeda, Fondation du Souffle-Fonds de dotation Recherche en Santé Respiratoire, Novartis, Pierre Fabre, Chiesi, Boehringer Ingelheim, AstraZeneca, and GlaxoSmithKline. I. Dupin, P. Berger and P-O. Girodet have a patent pending (EP No. 15152886.6; ie, New compositions and methods of treating and/or preventing chronic obstructive pulmonary disease). The rest of the authors declare that they have no relevant conflicts of interest.
Funding: This study was sponsored and supported by Bordeaux University Hospital (i.e. “CHU 33 de Bordeaux”). This study was supported by a grant from the “Fondation Bordeaux Université”, 34 with funding from “Assistance Ventilatoire á Domicile” (AVAD) and “Fédération Girondine de 35 Lutte contre les Maladies Respiratoires” (FGLMR).