Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease

doi:10.1016/S0002-9343(02)01562-0

The American Journal of Medicine

Volume 114, Issue 5, 1 April 2003, Pages 354-358

https://doi.org/10.1016/S0002-9343(02)01562-0 Get rights and content

Abstract

Purpose

Expression of vascular endothelial growth factor (VEGF) is reduced in the lungs of patients with emphysema. We examined whether VEGF levels in sputum differed in patients with emphysema, bronchitis, or asthma, as compared with controls.

Methods

Fifty-nine patients with chronic obstructive pulmonary disease (COPD) (25 with emphysema, 19 with chronic bronchitis, and 15 with a mixed type), 20 patients with bronchial asthma, and 11 normal controls were included in the study. The concentration of VEGF in induced sputum and the correlations between VEGF levels and pulmonary function were examined.

Results

The mean (± SD) concentration of VEGF in induced sputum was significantly higher in patients with asthma (6440 ± 1820 pg/mL, P <0.0001) or bronchitis (4120 ± 1100 pg/mL, P <0.0001) than in normal controls (1860 ± 1220 pg/mL), but significantly lower in patients with emphysema (500 ± 300 pg/mL, P = 0.03). The concentration of VEGF in sputum from patients with bronchitis correlated inversely with forced expiratory volume in 1 second (r = −0.87; P = 0.0002); in contrast, there was a positive correlation between these two measurements in patients with emphysema (r = 0.82; P <0.0001). In addition, sputum VEGF concentrations correlated with the diffusing capacity of carbon monoxide in patients with emphysema (r = 0.87; P <0.0001), but not in those with bronchitis (r = −0.22; P = 0.36).

Conclusion

In patients with bronchitis, increased levels of VEGF in induced sputum were associated with airflow limitation. In contrast, decreased levels of VEGF were associated with airflow limitation and alveolar destruction in patients with emphysema. Thus, our findings suggest that VEGF may affect the pathogenesis of these two common types of COPD.

Section snippets

Subjects

Fifty-nine patients with COPD, 20 patients with asthma, and 11 normal controls were included in the study. All normal controls were healthy, lifelong nonsmokers who had no history of lung disease. All patients satisfied the American Thoracic Society criteria for COPD and asthma (9); they were selected from the respiratory outpatient clinic at our institution. All patients with COPD had a history of previous smoking (>20 pack-years) and an irreversible airflow limitation (reversibility <10%

Results

The three groups of patients with COPD had similar mean values for age, pack-years of smoking, arterial oxygen tension, FEV₁ (% predicted), and FEV₁/forced vital capacity (Table 1). However, the Dlco was significantly lower in patients with emphysema than in those with bronchitis (Table 1; P = 0.0003), and the percentage of neutrophils in induced sputum was significantly lower (P <0.0001) in patients with emphysema (39% ± 6%) than in those with either mixed-type COPD (56% ± 5%) or chronic

Discussion

Asthma and COPD are chronic inflammatory diseases associated with remodeling of airway walls. The structural alterations in asthmatic airways include epithelial desquamation, goblet cell hyperplasia, collagen deposition below the basement membrane, hypertrophy and hyperplasia of smooth muscle, and growth and proliferation of new blood vessels (12). Similarly, in chronic bronchitis, airway inflammation is associated with epithelial damage, goblet cell hyperplasia, enlarged submucosal

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Airflow limitation in COPD is caused by a mixture of small airways obstruction and alveolar destruction.
To evaluate the contributions of these factors to airflow limitation through measurement of two biomarkers, pentosidine and vascular endothelial growth factor (VEGF), which reflect pathology or function of the lower respiratory tract of COPD.
We measured pentosidine and VEGF levels in induced sputum from 23 non-smokers, 26 smokers without COPD, and 43 smokers with COPD. We evaluated the correlations of two biomarkers levels with the grade of low attenuation area (LAA) in high-resolution computed tomographic scans and the Δ N₂ from the nitrogen washout curve.
Pentosidine levels were significantly higher in smokers with COPD than in non-smokers and smokers without COPD. In contrast, VEGF levels were significantly lower in smokers without COPD than in non-smokers, and further decreased in smokers with COPD. In the four-stage classification of LAA grading, pentosidine levels steeply increased from grade I to Ⅳ, while VEGF levels decreased with increasing severity of LAA grade. Pentosidine levels were positively correlated with Δ N₂ in COPD patients with mild emphysema. In contrast, VEGF levels were inversely correlated with Δ N₂ in COPD patients with severe emphysema.
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^☆: This work was supported by a grant-in-aid for scientific research (1360611) from the Ministry of Education, Science and Culture, Japan.

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Clinical studyPossible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease☆

Abstract

Purpose

Methods

Results

Conclusion

Section snippets

Subjects

Results

Discussion

J Biol Chem

J Allergy Clin Immunol

J Allergy Clin Immunol

J Biol Chem

J Lab Clin Med

Cigarette smoking and lung destruction. Accumulation of neutrophils in the lungs of cigarette smokers

Am Rev Respir Dis

The role of free radicals and neutrophil elastase in development of pulmonary emphysema

Intern Med

Pulmonary emphysema with special reference to vascular change

Am Rev Respir Dis

Inhibition of VEGF receptors causes lung cell apoptosis and emphysema

J Clin Invest

Clinical study
Possible effects of vascular endothelial growth factor in the pathogenesis of chronic obstructive pulmonary disease☆