Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity
Jeanne-Marie Perotin, Damien Adam, Juliette Vella-Boucaud, Gonzague Delepine, Sebastian Sandu, Anne-Carole Jonvel, Alain Prevost, Gérard Berthiot, Christophe Pison, François Lebargy, Philippe Birembaut, Christelle Coraux and Gaëtan Deslee
Uni Hospital Reims
Background: Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier.
Recurrent epithelial injuries require a complex mechanism of repair to restore its integrity. In chronic obstructive
pulmonary disease (COPD), an abnormal airway epithelial repair may participate in airway remodeling. The objective
was to determine if airway epithelial wound repair of airway epithelium is abnormal in COPD.
Methods: Patients scheduled for lung resection were prospectively recruited. Demographic, clinical data and
pulmonary function tests results were recorded. Emphysema was visually scored and histological remodeling
features were noted. Primary bronchial epithelial cells (BEC) were extracted and cultured for wound closure assay.
We determined the mean speed of wound closure (MSWC) and cell proliferation index, matrix metalloprotease
(MMP)-2, MMP-9 and cytokines levels in supernatants of BEC 18 hours after cell wounding. In a subset of patients,
bronchiolar epithelial cells were also cultured for wound closure assay for MSWC analyze.
Results: 13 COPD and 7 non COPD patients were included. The severity of airflow obstruction and the severity of
emphysema were associated with a lower MSWC in BEC (p = 0.01, 95% CI [0.15-0.80]; p = 0.04, 95% CI [−0.77;-0.03]
respectively). Cell proliferation index was decreased in COPD patients (19 ± 6% in COPD vs 27 ± 3% in non COPD,
p = 0.04). The severity of COPD was associated with a lower level of MMP-2 (7.8 ± 2 105 AU in COPD GOLD D vs
12.8 ± 0.13 105 AU in COPD GOLD A, p = 0.04) and a lower level of IL-4 (p = 0.03, 95% CI [0.09;0.87]). Moreover,
higher levels of IL-4 and IL-2 were associated with a higher MSWC (p = 0.01, 95% CI [0.17;0.89] and p = 0.02, 95% CI
[0.09;0.87] respectively). Clinical characteristics and smoking history were not associated with MSWC, cell proliferation
index or MMP and cytokines levels. Finally, we showed an association of the MSWC of bronchial and corresponding
bronchiolar epithelial cells obtained from the same patients (p = 0.02, 95% CI [0.12;0.89]).
Conclusion: Our results showed an abnormal bronchial epithelial wound closure process in severe COPD. Further
studies are needed to elucidate the contribution and the regulation of this mechanism in the complex
pathophysiology of COPD.