Recent advances in the management of pulmonary hypertension with interstitial lung disease

Abstract

Pulmonary hypertension (PH) is known to complicate various forms of interstitial lung disease (ILD), including idiopathic pulmonary fibrosis, the interstitial pneumonias and chronic hypersensitivity pneumonitis. Pathogenesis of PH-ILD remains incompletely understood, and probably has overlap with other forms of pre-capillary pulmonary hypertension. PH-ILD carries a poor prognosis, and is associated with increased oxygen requirements, and a decline in functional capacity and exercise tolerance. Despite most patients having mild-moderate pulmonary hypertension, more severe pulmonary hypertension and signs of right heart failure are observed in a subset of cases. Clinical suspicion and findings on pulmonary function, computed tomography and echocardiography are often the initial steps towards diagnosis. Definitive diagnosis is obtained by right heart catheterisation demonstrating pre-capillary pulmonary hypertension. Drugs approved for pulmonary arterial hypertension have been investigated in several randomised controlled trials in PH-ILD patients, leading to discouraging results until the recent INCREASE study. This review provides an overview of the current understanding, approach to diagnosis and recent advances in treatment.

FIGURE 1

World Symposium on Pulmonary Hypertension classification of pulmonary hypertension. mPAP: mean pulmonary artery pressure; PVR: pulmonary vascular resistance.

FIGURE 2

Algorithm for diagnosis of pulmonary hypertension. SoB: shortness of breath; ECG: electrocardiogram; NT-proBNP: N-terminal pro-brain natriuretic peptide; D_LCO: diffusing capacity of the lung for carbon monoxide; FVC: forced vital capacity; K_CO: transfer coefficient of the lung for carbon monoxide; 6MWT: 6-min walk test; CT: computed tomography; PA: pulmonary artery; CPET: cardiopulmonary exercise testing; V′/Q′: ventilation/perfusion ratio; P_A–aO2: alveolar–arterial oxygen tension difference; V_D: dead space volume; V_T: tidal volume; P_aETCO2: end-tidal arterial carbon dioxide tension; V′_E: minute ventilation; V′_CO2: carbon dioxide production; O₂: oxygen; TRV: tricuspid regurgitant velocity; RA: right atrium; RV: right ventricle; TAPSE: tricuspid annular plane systolic excursion; S′: systolic velocity.