Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD): Back to the Future

Abstract

Pulmonary hypertension (PH) is a progressive syndrome characterized by increased pulmonary artery pressure. PH often complicates chronic lung diseases, thus contributing to a substantial disease burden and poor prognosis. The WHO Group 3 Pulmonary Hypertension has many subcategories, including sleep-hypoventilation PH, high altitude-PH, chronic obstructive pulmonary disease (COPD)-PH, and interstitial lung disease (PH-ILD), the latter carrying the worst prognosis. ILD is a heterogeneous group of disorders characterized by cough and shortness of breath and, in progressive forms, irreversible loss of function and respiratory failure. The development of PH in patients with ILD worsens exercise capacity and exertional dyspnea and impairs quality of life. Thus, suspicion and early detection of PH following thorough cardiologic evaluation (i.e., echocardiography, pro-BNP, and right heart catheterization) is paramount for appropriate patient management. For PH secondary to chronic respiratory diseases, current guidelines recommend optimizing the treatment of the underlying respiratory condition and offering long-term oxygen therapy. In recent years, several clinical trials have failed to identify drugs beneficial for group 3 PH. Conversely, the INCREASE trial of inhaled treprostinil has recently provided hope for treating PH-ILD. In this review, we summarize and critically discuss the present and future of the pharmacological management of PH-ILD.

Keywords: Chronic lung diseases; Interstitial lung disease; Pulmonary hypertension; Therapy; Treatment; Treprostinil.

Fig. 1

Different signaling pathways implicated in PH and corresponding pharmacological approaches