LAUSR

BACKGROUND Airflow limitation in COPD is caused by a mixture of small airways obstruction and alveolar destruction. OBJECTIVE 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. METHODS 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. RESULTS 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. CONCLUSION Pentosidine level is responsible for the severity of small airways obstruction, while VEGF level reflects the magnitude of alveolar destruction. Thus, simultaneous measurement of pentosidine and VEGF levels may be a promising approach to discriminate the severity of small airways obstruction and alveolar destruction in the lower respiratory tract of COPD.