Pulmonary Hypertension in COPD: Pathophysiology and Therapeutic Targets

Author(s): E. Zakynthinos, Z. Daniil, J. Papanikolaou, D. Makris.

Journal Name: Current Drug Targets

Volume 12 , Issue 4 , 2011

Abstract:

The incidence of mild to moderate pulmonary hypertension (PH) is highly prevalent, reaching to 50% in advanced chronic obstructive pulmonary disease (COPD). However, a subpopulation (1-4% in most studies) with grim prognosis despite moderate airflow limitation, present with “out-of-proportion” severe PH, as arbitrarily defined by a mean PH≥40 mmHg, at rest. The sequence of changes that lead to PH in COPD begins at early disease stages by the impairment of endothelial function, which is associated with impaired release of endothelium-derived vasodilating (nitric oxide, prostacyclin) and vasoconstrictive agents (endothelin-1) and imbalance among them. PH in COPD is caused by vasoconstriction and remodelling of pulmonary arteries, which is characterized by the intimal proliferation of poorly differentiated smooth muscle cells and the deposition of elastic and collagen fibres. Hypoxia, inflammation and toxic effects of cigarette smoke, independently or additively interacting, are confirmed factors leading to PH. To date, longterm supplemental oxygen remains the primary treatment in COPD patients with PH. The administration of new vasodilators (prostanoids, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors) dedicated to idiopathic pulmonary arterial hypertension in the disproportionate subgroup of patients with “out-of-proportion” PH may be considered in the setting of clinical trials. The use of these drugs in COPD patients with PH < 40 mmHg may worsen gas exchange, and to date, has no proven benefit. Future treatments must target more directly pathogenetic mechanisms. Therefore, novel agents have been proposed and are under active investigation, including 5-HT receptor antagonists, Rhokinase inhibitors, statins and stem cell therapy.

Keywords: Chronic obstructive pulmonary disease, pulmonary hypertension, remodelling, hypoxia, cigarette smoke, nitric oxide, inflammation, exacerbation, hyperplasia, vasoactive substances, potassium channels

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Article Details

VOLUME: 12
ISSUE: 4
Year: 2011
Page: [501 - 513]
Pages: 13
DOI: 10.2174/138945011794751483
Price: $58

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