Abstract

BackgroundAirway 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.MethodsPatients 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.Results13 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]).ConclusionOur 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12931-014-0151-9) contains supplementary material, which is available to authorized users.

Highlights

  • Airway epithelium integrity is essential to maintain its role of mechanical and functional barrier

  • To test the hypothesis that wound repair of airway epithelium is abnormal in chronic obstructive pulmonary disease (COPD), we studied primary bronchial and bronchiolar epithelial cells from non COPD and COPD patients in a model of wound closure

  • COPD patients had a lower PaO2 level compared to non COPD patients (74 ± 11 vs 90 ± 9 mmHg respectively, p = 0.02)

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Summary

Introduction

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. Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by progressive airflow limitation, variously associating airway inflammation and remodeling, lung parenchymal destruction, systemic inflammation and comorbidities as cardiovascular disease and metabolic syndrome [1,2]. Allergens, airborne particulates, infectious agents and noxious gases can induce injuries of airway epithelium, requiring a regulated repair mechanism to restore its functionality [4]. Whether there is an abnormal wound repair process in COPD airways resulting in altered structure and function of airway epithelium is not established

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