| Abstract | BACKGROUND AND PURPOSE: Chronic obstructive pulmonary disease (COPD) is a major health problem, it is caused predominantly by cigarette smoking. In COPD, the airway epithelium undergoes alterations, which are partially attributed to activation of the epidermal growth factor receptor (EGFR). The aim of this study was to study the expression of EGFR in the bronchial epithelium of patients with COPD and in smokers without COPD in comparison to its expression in normal bronchial epithelium, in a trial to investigate its role in the pathogenesis of COPD, and in the epithelial alterations that characterize this disease.
SUBJECTS AND METHODS:
This study included 50 subjects, who where admitted in Chest Department, Tanta University Hospital. They were classified into 3 groups: group I (apparently healthy non-smoking control volunteer subjects), group II (apparently healthy smoker volunteers), and group III (patients with COPD). Group III was further subdivided into: subgroup IIIA (current smokers with COPD) and subgroup IIIB (ex-smokers with COPD). The following was done for all of the studied subjects: thorough history taking and full clinical examination, chest X-ray, pulmonary function tests, and fiberoptic bronchoscopy.
Bronchoscopic biopsies from all the studied subjects were subjected to histopathological, histochemical and immunohistochemical staining using antibody against EGFR.
RESULTS:
Non-COPD current smokers and COPD patients showed evident epithelial alterations compared to the normal bronchial epithelium of the control subjects. These alterations were significantly exaggerated in COPD patients compared to non-COPD smokers (P<0.05), however, no significant differences were found between current and ex-smokers with COPD (P>0.05). The expression of EGFR was significantly higher in group II and III compared to group I (P<0.05). Moreover, group III showed significantly higher EGFR expression compared to group II (P<0.05). Subgroup analysis revealed that subgroup IIIB "ex-smokers with COPD" displayed significantly higher (P<0.05) EGFR expression compared to subgroup IIIA "current smokers with COPD". Statistically significant positive correlations were found between EGFR expression and both goblet cell hyperplasia, and bronchial epithelial hyperplasia in groups II and III (P<0.05), while there was a significant negative correlation between EGFR expression and FEV1 in groups II and III (P<0.05). There was a significant positive correlation (P<0.05) between EGFR expression and smoking index in group II.
CONCLUSION:
There is increasing evidence that EGFR may play an important role in the epithelial phenotypic alterations observed in the bronchial epithelium of COPD patients through active smoking, and that it has a significant role in regulating mucus production in airway epithelium and in the repair of epithelium after injury. Disruption of the EGFR cascade may provide a mechanism and a strategy for therapy in airway inflammatory (hypersecretory) diseases by blocking EGFR activation with subsequent inhibition of goblet cell production and reduction of mucus secretion, which is the main cause of airway limitation in COPD patients. However, further studies evaluating these new therapeutic modalities are required. |