Vascular involvement in idiopathic pulmonary fibrosis

Abstract

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing and progressive interstitial lung disease of unknown aetiology with a pathogenesis still partly unknown. Several microvascular and macrovascular abnormalities have been demonstrated in the pathogenesis of IPF and related pulmonary hypertension (PH), a complication of the disease.

Methods: We carried out a non-systematic, narrative literature review aimed at describing the role of the vasculature in the natural history of IPF.

Results: The main molecular pathogenetic mechanisms involving vasculature (i.e. endothelial-to-mesenchymal transition, vascular remodelling, endothelial permeability, occult alveolar haemorrhage, vasoconstriction and hypoxia) and the genetic basis of vascular remodelling are described. The prevalence and clinical relevance of associated PH are highlighted with focus on the vasculature as a prognostic marker. The vascular effects of current antifibrotic therapies, the role of pulmonary vasodilators in the treatment of disease, and new pharmacological options with vascular-targeted activity are described.

Conclusions: The vasculature plays a key role in the natural history of IPF from the early phases of disease until development of PH in a subgroup of patients, a complication related to a worse prognosis. Pulmonary vascular volume has emerged as a novel computed tomography finding and a predictor of mortality, independent of PH. New pharmacological options with concomitant vascular-directed activity might be promising in the treatment of IPF.

FIGURE 1

Diagnostic work-up for pulmonary hypertension (PH) in patients with interstitial lung disease (ILD)/idiopathic pulmonary fibrosis (IPF). FVC: forced vital capacity; D_LCO: diffusing capacity of the lung for carbon monoxide; CT: computed tomography; PA: pulmonary artery; RV: right ventricle; LV: left ventricle; 6MWT: 6-min walk test; CPET: cardiopulmonary exercise testing; P_ETCO2: end-tidal pressure of carbon dioxide; P_ECO2: mixed-expired carbon dioxide pressure; V′_E/V′_CO2: minute ventilation to carbon dioxide output ratio; BNP: brain natriuretic peptide; mPAP: mean pulmonary arterial pressure; PAWP: pulmonary artery wedge pressure; PVR: pulmonary vascular resistance; WU: wood unit.

FIGURE 2

Main molecular mechanisms involving vasculature in the pathogenesis of idiopathic pulmonary fibrosis (IPF). a) Endothelial-to-mesenchymal transition. b) Vascular remodelling. c) Endothelial permeability and occult alveolar haemorrhage. d) Hypoxia. e) Alveolar haemorrhage. f) Genetic basis. PH: pulmonary hypertension; ASCD: alveolar septal capillary density; PVOD: pulmonary venous occlusive disease; PCH: pulmonary capillary haemangiomatosis; ROS: reactive oxygen species.