Systemic manifestations of COPD.
ABSTRACT COPD is characterized by a poorly reversible airflow limitation resulting from chronic inflammation, mainly due to tobacco exposure. Over the past few years, the understanding of COPD has evolved from it being a disease affecting the lungs to it being a complex, heterogeneous, and generalized disorder in an aging population. Extrapulmonary comorbidities significantly complicate the management and influence the prognosis of patients with COPD. Although certain comorbidities like cardiovascular diseases share some risk factors with COPD, such as cigarette smoking, other frequently observed comorbidities, including musculoskeletal wasting, metabolic syndrome, and depression, cannot be easily attributed to smoking. There is increasing evidence that chronic inflammation is a key factor in COPD and that inflammation might be the common pathway linking these comorbidities and explaining why they typically develop together. Physicians treating patients with COPD need to become aware of these extrapulmonary aspects. Any patient with COPD should be carefully evaluated for comorbidities and the systemic consequences of COPD since they not only influence the prognosis but also have an impact on disease management. The treatment of COPD is no longer focused exclusively on inhaled therapy but is taking on a multidimensional approach, especially because the treatment of the comorbidities might positively affect the course of COPD itself.
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ABSTRACT: 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.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]).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.Respiratory Research 11/2014; 15(1):151. · 3.13 Impact Factor
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