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Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease

Advances in Pathophysiology and Management

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Abstract

Pulmonary hypertension (PH) is an important complication in the natural history of chronic obstructive pulmonary disease (COPD). Its presence is associated with reduced survival and greater use of healthcare resources. The prevalence of PH is high in patients with advanced COPD, whereas in milder forms it might not be present at rest but may develop during exercise. In COPD, PH is usually of moderate severity and progresses slowly, without altering right ventricular function in the majority of patients. Nevertheless, a small subgroup of patients (1–3%) may present with out-of-proportion PH, that is, with pulmonary arterial pressure largely exceeding the severity of airway impairment. These patients depict a clinical picture similar to more severe forms of PH and have higher mortality rates.

PH in COPD is caused by the 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. 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 agents (nitric oxide, prostacyclin) and increased expression of growth factors. Products contained in cigarette smoke play a critical role in the initiation of pulmonary endothelial cell alterations.

Recognition of PH can be difficult because symptoms due to PH are not easy to differentiate from the clinical picture of COPD. Suspicion of PH should be high if clinical deterioration is not matched by the decline in pulmonary function, and in the presence of profound hypoxaemia or markedly reduced carbon monoxide diffusing capacity. Patients with suspected PH should be evaluated by Doppler echocardiography and, if confirmed, undergo right-heart catheterization in those circumstances where the result of the procedure can determine clinical management.

To date, long-term oxygen therapy is the treatment of choice in COPD patients with PH and hypoxaemia because it slows or reverses its progression. Conventional vasodilators are not recommended because of their potential detrimental effects on gas exchange, produced by the inhibition of hypoxic pulmonary vasoconstriction and their lack of effectiveness after long-term treatment. In the subgroup of patients with out-of-proportion PH, new specific therapy available for pulmonary arterial hypertension (PAH) [prostanoids, endothelin-1 receptor antagonists and phosphodiesterase-5 inhibitors] may be considered in the setting of clinical trials. The use of specific PAH therapy in COPD patients with moderate PH is discouraged because of the potential detrimental effect of some of these drugs on gas exchange and there are no data demonstrating their efficacy.

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Acknowledgements

This work has been funded by research grants from the EU (6th Framework Programme, LSHM-CT-2005-018725) and the Fondo de Investigación Sanitaria (07/90049) of the Spanish Ministry of Science and Innovation, and a research fellowship grant of the Spanish Society of Respiratory Medicine (SEPAR). Dr Barberà has received consultancy fees from Pfizer, Glaxo SmithKline, Actelion, Praxis and Encysive, and unrestricted research grant funding from Actelion, Schering and Praxis. Dr Blanco has no conflicts of interest to declare.

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Correspondence to Joan Albert Barberà.

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Barberà, J.A., Blanco, I. Pulmonary Hypertension in Patients with Chronic Obstructive Pulmonary Disease. Drugs 69, 1153–1171 (2009). https://doi.org/10.2165/00003495-200969090-00002

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