Pulmonary hypertension associated with interstitial lung disease (PH-ILD) is a complex condition in which 2 consequential diseases interact and increase negative outcomes. Although the pathophysiologic mechanisms of PH-ILD are not yet well understood, the pronounced effect on functional status, supplemental oxygen requirements, health care resource utilization, and mortality that frequently accompany this diagnosis are well documented. A critical feature that complicates pathophysiologic understanding of PH-ILD is that progression of the pulmonary vascular disease does not always appear to be driven by the underlying lung disease. As PH-ILD is a progressive disease, early recognition and treatment initiation have the potential to delay the increased burden it creates. Historically, therapeutic development within pulmonary hypertension has concentrated on pulmonary arterial hypertension (PAH). However, PH-ILD and PAH are categorically distinct-belonging to distinct PH groups owing to differing pathophysiological mechanisms and therapeutic implications. PAH and PH-ILD may have numerous similarities; however, when PAH therapies have been studied in patients with PH-ILD, inconclusive efficacy (bosentan, sildenafil, tadalafil, iloprost) and at times deleterious safety findings (riociguat, ambrisentan) have been observed. Despite the paucity of evidence to support PAH therapy use in this patient population, widespread off-label use of PAH therapies arose as a result of a historical lack of PH-ILD-approved treatment. Recently, inhaled treprostinil-a prostacyclin analog-has become the first therapy approved for treatment of PH-ILD. In the phase 3 INCREASE trial, inhaled treprostinil was effective in improving 6-minute walk distance (the primary endpoint; P < 0.001) as well as N-terminal pro-B-type natriuretic peptide levels (P < 0.001). The approval of inhaled treprostinil in 2022 facilitates evidence-based therapeutic management. In addition, the 7th World Symposium on Pulmonary Hypertension has recently published an extensive summary of clinical research to date in PH-ILD. The proceedings from the 7th World Symposium on Pulmonary Hypertension provide timely recommendations for investigation of PH-ILD and a framework for assessing treatment needs. The therapeutic landscape advances are poised to transform PH-ILD care and improve outcomes for patients with PH-ILD.
