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PH due to chronic lung diseases and/or hypoxia

Most chronic lung diseases, including chronic obstructive pulmonary disease (COPD) and diffuse parenchymal lung diseases, not only affect the airways but also to some extent the pulmonary vasculature. PH in these conditions may follow a decrease in number of vessels or a decrease in vessel luminal surface, which can result from hypoxic vasoconstriction, vessel obstruction and vessel remodelling. In most instances, the increase in mean pulmonary artery pressure is relatively mild.10


altitude residence (>2500m above sea level) is an important cause of PH on a global scale.11

Regardless of its

underlying cause, the presence of PH in chronic lung disease is associated with a worse prognosis. Even so, it remains to be determined whether PH in chronic lung disease is a true cause of early death or merely a marker of more severe lung disease. While long-term oxygen therapy delays the progression of PH in COPD,12

there are no specific

drugs available for this particular form of PH.13

Chronic thromboembolic PH Chronic thromboembolic PH (CTEPH) is a rare but potentially deadly complication of pulmonary embolism. Pengo et al estimated that 4% of patients with a proven acute episode of pulmonary embolism developed CTEPH,14,

while a much lower

percentage was found in a Dutch prospective cohort study.15

In a recent

prospective study, 4.8% of acute pulmonary embolism patients were diagnosed with CTEPH after a subsequent median follow-up of 26 months.16

The majority of CTEPH

patients already had signs of PH during the initial episode of acute pulmonary embolism, suggesting that a first clinical presentation of CTEPH may mimic acute pulmonary embolism. 20–25% of CTEPH cases occur in patients without a history of venous thromboembolic disease.17;18

Because organised pulmonary emboli are easily overlooked on standard computed tomography (CT) angiography, ventilation/perfusion scintigraphy is still the central diagnostic procedure to exclude CTEPH in a patient with PH. CTEPH treatment is primarily surgical and consists of a pulmonary endarterectomy. During this

Figure 1: Diagnostic algorithm, 2015 Guidelines.

Reproduced with permission of the European Society of Cardiology & European Respiratory Society© European Respiratory Journal Oct 2015, 46 (4) 903–975; DOI:10.1183/13993003.01032-2015.

procedure, thrombotic material is removed together with the inner layers of the pulmonary arteries, to allow reperfusion of previously obstructed segments of the pulmonary circulation. Thirty per cent of patients deemed inoperable will require medical therapy. Interventional balloon pulmonary angioplasty (BPA) may be considered in patients who are technically non- operable or carry an unfavourable risk:benefit ratio for pulmonary endarterectomy (PEA). BPA should only be performed in experienced and high-volume CTEPH centres.19


A diagnosis of PAH can only be made after the exclusion of significant heart or lung disease and chronic thromboembolism. PAH is characterised by an abnormal growth pattern of endothelial and smooth muscle cells in pulmonary arterioles, partially obstructing or occluding the vascular lumen. The hallmark lesion of


PAH is the so-called plexiform lesion, which is a glomeruloid structure consisting of functionally and morphologically altered endothelial and smooth muscle cells. PAH occurs in four forms: idiopathic, hereditary, drug- induced and associated with an underlying condition. A number of diseases are associated with the development of PAH, including systemic sclerosis, systemic lupus erythematosus, hepatic disease, HIV infections and the existence of congenital systemic to pulmonary shunts. Among the first pharmaceutical compounds known to induce PAH in susceptible subjects were appetite suppressants, such as Ponderal. Recently, a relationship was established between the development of PAH and the use of the tyrosine kinase inhibitor, dasatinib.20

When PAH occurs in a

hereditary form, it is mostly related to a mutation in the gene encoding the bone morphogenic protein receptor type II. In the absence of an underlying risk


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