Changes in circulating thrombomodulin levels with exercise in patients with chronic obstructive pulmonary disease

The functional properties of endothelial cells in pulmonary microvessels are affected by elevations in the level of vascular endothelial growth factor (VEGF) in inflamed airways. An increase in the level of circulating thrombomodulin (TM), a molecular marker of endothelial cells, with exercise is associated with the VEGF level in asthmatic airways. This study investigated whether the airway VEGF level reflects changes in circulating TM levels with exercise in patients with COPD.

VEGF levels in induced sputum were measured in 26 COPD patients (12 chronic bronchitis and 14 emphysema) and 11 control subjects. Incremental exercise testing was performed, and TM levels in arterial blood samples were measured pre-exercise and post-exercise at 0, 5 and 60 min.

VEGF levels were significantly lower in patients with emphysema (520 +/- 290 pg/mL) than in control subjects (1860 +/- 1220 pg/mL), and were significantly higher in patients with bronchitis (4110 +/- 1190 pg/mL). Pre-exercise TM levels were comparable among the three study groups. TM levels in control subjects and emphysema patients did not change after exercise. However, maximum TM levels after exercise were significantly increased in chronic bronchitis patients (P = 0.02). The increase in TM level with exercise closely correlated with the VEGF level in bronchitis patients (r = 0.90, P = 0.003).

In chronic bronchitis, but not in emphysema, patients exercise induced an increase in circulating TM levels. The potential causal relationship between circulating levels of TM and those of VEGF in the airways deserve further exploration.