Evaluation of the severity of small airways obstruction and alveolar destruction in chronic obstructive pulmonary disease

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 Delta N-2 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., while VEGF levels decreased with increasing severity of LAA grade. Pentosidine levels were positively correlated with Delta N-2 in COPD patients with mild emphysema. In contrast, VEGF levels were inversely correlated with Delta N-2 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.