PH in COPD was an independent prognostic factor. Indeed, patients with similar airflow limitation had lower life expectancy when PH was resent. Patients with PH had a significantly lower survival rate at 5 yrs compared with patients without PH (33 versus 66%). Pathologic studies that stemmed from long-term oxygen trials pointed to the fact that pulmonary vascular remodeling in chronic obstructive pulmonary disease (COPD) is more than just medial hypertrophy from long-lasting hypoxic vasoconstriction. In these patients, all vessel wall layers appear to be involved, with intimal changes actually being the most prominent. Major remodeling of all pulmonary arterial vessel layers explains why pulmonary hypertension in COPD is often not,or minimally, reversible by supplemental oxygen, acutely or chronically. The pathobiology of pulmonary artery remodeling in advanced COPD remains incompletely explored. There are data supporting an endothelium-derived vasoconstrictor-dilator imbalance, mainly from a decreased endothelial nitric oxide expression. Plasma levels of ET-1 are increased both in patients with severe COPD and there is evidence that ETA and ETB receptor expression is increased in the pulmonary arteries of patients with COPD.