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Original Research: COPD |

Supplementing Defect in Club Cell Secretory Protein Attenuates Airway Inflammation in COPDClub Cell Secretory Protein in COPD

Anne Sophie Gamez, MD; Delphine Gras, PhD; Aurélie Petit, PhD; Lucie Knabe, MSc; Nicolas Molinari, PhD; Isabelle Vachier, PhD; Pascal Chanez, MD, PhD; Arnaud Bourdin, MD, PhD
Author and Funding Information

From the Département de Pneumologie et Addictologie (Drs Gamez, Petit, Vachier, and Bourdin and Ms Knabe), Hôpital Arnaud de Villeneuve, CHU Montpellier; INSERM CNRS U1067 UMR7333 (Drs Gras and Chanez), Aix Marseille Université, Marseille; Département de l’Information Médicale (Dr Molinari), CHU Montpellier, Montpellier; UMR729 MISTEA (Dr Molinari), Montpellier SupAgro, Montpellier; Département des Maladies Respiratoires (Dr Chanez), Hôpital Nord, AP-HM, Marseille; and INSERM U1046 (Ms Knabe and Dr Bourdin), Université Montpellier 1 et 2, Hôpital Arnaud de Villeneuve, CHU Montpellier, France.

CORRESPONDENCE TO: Arnaud Bourdin, MD, PhD, Département de Pneumologie et Addictologie, Hôpital Arnaud de Villeneuve, 371 ave Doyen Gaston Giraud, CHU Montpellier, 34295 Montpellier Cedex 5, France; e-mail: a-bourdin@chu-montpellier.fr


FOR EDITORIAL COMMENT SEE PAGE 1447

FUNDING/SUPPORT: Master’s degree support was provided to Dr Gamez by Association Pour Assistance Respiratoire à Domicile.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(6):1467-1476. doi:10.1378/chest.14-1174
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BACKGROUND:  Club cell secretory protein (CCSP) is a protective biomarker associated with annual decline in lung function. COPD progression results from an imbalance between injury and repair initially triggered by cigarette smoking.

OBJECTIVE:  We investigated the effect of CCSP as a therapeutic strategy to restore the balance between injury and repair in COPD simultaneously, validating an ex vivo air-liquid interface (ALI) culture of human bronchial epithelial cells.

METHODS:  Endobronchial biopsy specimens (EBBs) were obtained from 13 patients with COPD, eight smokers, and eight control subjects. Morphometric analysis of the initial EBBs was performed. ALI cultures derived from the same EBBs were exposed to cigarette smoke extract (CSE) with or without exogenous recombinant human CCSP (rhCCSP) supplementation. CCSP and IL-8 concentrations were assessed at steady state and after CSE exposure.

RESULTS:  Morphometric analysis of the initial EBBs showed increased cell density but decreased immunostaining of CCSP+ cells in EBBs of patients with COPD (P = .03 vs control subjects). At steady state, lower CCSP (P = .04) and higher IL-8 levels (P < .0001) were found in COPD ALI epithelium. Exogenous rhCCSP supplementation dampened CSE-induced IL-8-release in patients with COPD and returned to levels similar to those of smokers and control subjects (P = .0001). A negative correlation was found between IL-8-release in ALI and CCSP+ cell density in initial biopsy specimens (P = .0073).

CONCLUSIONS:  In vitro, rhCCSP exogenous supplementation can reverse CSE-induced IL-8 release in biopsy specimens from patients with COPD, indicating a potential use of this strategy in vivo.

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