Vascular endothelial growth factor: an angiogenic factor reflecting airway inflammation in healthy smokers and in patients with bronchitis type of chronic obstructive pulmonary disease?

Nikoletta Rovina,Andreas Papapetropoulos,Makrina Michailidou,Davina Cm Simoes,Charis Roussos,Christina Gratziou,Androniki Kollintza

doi:10.1186/1465-9921-8-53

Abstract

BackgroundPatients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum. This has been associated with the pathogenesis of COPD through apoptotic and oxidative stress mechanisms. Since, chronic airway inflammation is an important pathological feature of COPD mainly initiated by cigarette smoking, aim of this study was to assess smoking as a potential cause of raised airway VEGF levels in bronchitis type COPD and to test the association between VEGF levels in induced sputum and airway inflammation in these patients.Methods14 current smokers with bronchitis type COPD, 17 asymptomatic current smokers with normal spirometry and 16 non-smokers were included in the study. VEGF, IL-8, and TNF-α levels in induced sputum were measured and the correlations between these markers, as well as between VEGF levels and pulmonary function were assessed.ResultsThe median concentrations of VEGF, IL-8, and TNF-α were significantly higher in induced sputum of COPD patients (1,070 pg/ml, 5.6 ng/ml and 50 pg/ml, respectively) compared to nonsmokers (260 pg/ml, 0.73 ng/ml, and 15.4 pg/ml, respectively, p < 0.05) and asymptomatic smokers (421 pg/ml, 1.27 ng/ml, p < 0.05, and 18.6 pg/ml, p > 0.05, respectively). Significant correlations were found between VEGF levels and pack years (r = 0.56, p = 0.046), IL-8 (r = 0.64, p = 0.026) and TNF-α (r = 0.62, p = 0.031) levels both in asymptomatic and COPD smokers (r = 0.66, p = 0.027, r = 0.67, p = 0.023, and r = 0.82, p = 0.002, respectively). No correlation was found between VEGF levels in sputum and pulmonary function parameters.ConclusionVEGF levels are raised in the airways of both asymptomatic and COPD smokers. The close correlation observed between VEGF levels in the airways and markers of airway inflammation in healthy smokers and in smokers with bronchitis type of COPD is suggestive of VEGF as a marker reflecting the inflammatory process that occurs in smoking subjects without alveolar destruction.

Highlights

Patients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum
VEGF's expression is often excessive in chronic inflammation and fibrosis, and it has been implicated in the pathogenesis of emphysema through apoptotic and oxidative stress mechanisms [9,10,11]
The main finding of this study is that cigarette smoking is an important determinant of vascular endothelial growth factor (VEGF) upregulation in the airways, as assessed by VEGF's levels in induced sputum, since it correlated significantly with pack years but not with other clinical and functional parameters

Summary

Introduction

Patients with bronchitis type of chronic obstructive pulmonary disease (COPD) have raised vascular endothelial growth factor (VEGF) levels in induced sputum. This has been associated with the pathogenesis of COPD through apoptotic and oxidative stress mechanisms. Chronic airway inflammation is an important pathological feature of COPD mainly initiated by cigarette smoking, aim of this study was to assess smoking as a potential cause of raised airway VEGF levels in bronchitis type COPD and to test the association between VEGF levels in induced sputum and airway inflammation in these patients. Long-term cigarette smoking is the most important risk factor that may initiate the disease, as a result of inflammatory cells into the lung (leading to chronic airway inflammation), imbalance between proteolytic and anti-proteolytic activity, oxidative stress and apoptosis [2]. There is increasing evidence of the implication of VEGF in the pathogenesis of COPD its role at different stages of the disease seems to be controversial; it is suggested that it has a detrimental function in the bronchi and a protective role in the alveoli [13]

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