Pulmonary veno-occlusive disease: recent progress and current challenges

Abstract

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary arterial hypertension characterised by a progressive obstruction of small pulmonary veins that leads to elevation in pulmonary vascular resistance and right ventricular failure. Despite improved understanding and more efficacious treatment options for PAH overall, the prognosis of PVOD remains dismal. Without therapeutic intervention few patients would be expected to survive more than two years. PVOD may occur in both idiopathic and heritable forms, or develop in association with connective tissue disease, chronic respiratory disease, malignancy or bone marrow transplantation, among other causes. A widespread fibrous intimal proliferation that predominantly involves the pulmonary venules and small veins is the key histopathological hallmark. Surgical lung biopsy is considered the definitive diagnostic test but is associated with significant risk and is not recommended. Distinguishing PVOD from PAH on clinical grounds alone is generally not possible, although PVOD is characterised by a higher male/female ratio and higher tobacco exposure. Instead, non-invasive tests may be helpful and the diagnosis is usually based on an integrated assessment that incorporates high resolution computed tomography (septal lines, ground-glass opacities and lymph node enlargement), pulmonary function testing (lower DLCO), arterial blood gas analysis (lower PaO(2) at rest) and bronchoalveolar lavage (occult alveolar haemorrhage). Treatment of PVOD remains challenging as exposure to pulmonary vasodilators and PAH-specific agents may precipitate acute pulmonary oedema. Nonetheless, a number of successful outcomes describing cautious use of prostanoids, endothelin antagonists and phosphodiesterase type-5 inhibitors have been described. Unfortunately, the long term effects of these agents are variable and lung transplantation remains the treatment of choice.