Abstract
Pulmonary hypertensive diseases have been classified by the World Health Organization (WHO) into five groups based on the pathophysiology and characteristics of each disease state. Several targeted therapeutic agents have been developed that combat the vascular remodeling in WHO Group 1 pulmonary arterial hypertension, however, the search for treatment solutions in other WHO Groups has been less fruitful. In this review, we focus on therapeutic options for patients with pulmonary hypertension and interstitial lung disease (PH-ILD). Investigations of targeted WHO Group 1 PAH therapies have largely failed to improve functional capacity, hemodynamics, oxygenation, quality of life, or survival in PH-ILD. In contrast, inhaled treprostinil was shown effective in the INCREASE Trial, a placebo-controlled study in which patients with PH-ILD treated with inhaled treprostinil demonstrated a 31-meter placebo-corrected improvement in the primary endpoint, 6-minute walk distance. Treatment with inhaled treprostinil was also associated with improvement in time to clinical worsening, fewer exacerbations of underlying lung disease, decrease in N-terminal pro-B-type natriuretic protein (NT-proBNP) levels, and improvement in forced vital capacity compared to placebo. In this review, we also elaborate on the current understanding of the pathobiology leading to PH-ILD with emphasis on the role of newer signaling pathways and mediators of vascular biology that may expand treatment options. Strategy and innovations for early detection and diagnosis are highlighted while underscoring the importance of early detection and diagnosis. A holistic and collaborative approach to the treatment of PH-ILD is outlined including a variety of adjunctive measures and the consideration of patient-reported outcome data in order to improve disease management outcomes.