Delay of airway epithelial wound repair in COPD is associated with airflow obstruction severity.

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 10(5) AU in COPD GOLD D vs 12.8 ± 0.13 10(5) 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.

Endobronchial brachytherapy in combination with external beam irradiation in obstructing malignant bronchial tumors.

Endobronchial brachytherapy is commonly used in the palliative management of malignant airway obstructions. In the present study, we describe the results of brachytherapy (mean dose of 18 Gy), used in combination with external beam irradiation (mean dose of 50 Gy) in 30 patients who had primary bronchogenic carcinoma of the lung. The extent of airway obstruction was determined according to symptoms and by bronchoscopy. We found symptoms improved in nearly 37% of patients and 21 of 30 patients (70%), evaluated with bronchoscopy, showed a response when evaluated 3 to 6 months after brachytherapy. This endobronchial technique appeared to be a well-tolerated procedure with a low rate of acute toxicity. The immediate complication rate was 13%, during the follow-up 3 deaths were related to treatment, of which 2 were fatal haemoptysis (12 and 18 months after irradiation). We conclude that the combination of endobronchial brachytherapy with external beam irradiation may be useful and needs further comparisons with other irradiation procedures.