Optimizing Care in Pulmonary Hypertension Associated with Lung Disease: Evidence-Based Strategies and Emerging Therapies

Pulmonary hypertension (PH) related to chronic lung disease (group 3 PH) frequently complicates conditions such as chronic obstructive pulmonary disease (COPD) and interstitial lung diseases. Outcomes worsen considerably once pulmonary pressures become severe, yet therapeutic options remain limited. This review examined randomized trials, observational studies, and guidelines addressing treatment strategies for Group 3 PH. Literature searches were performed in PubMed, Scopus, and Web of Science up to September 2025. Eligible publications included randomized controlled trials, large observational cohorts, and international guidelines. Outcomes of interest included 6-minute walk distance (6MWD), clinical events, and safety. The INCREASE trial demonstrated a clinically meaningful improvement in 6MWD (mean increase of 31 m at 16 weeks) and fewer respiratory hospitalizations with inhaled treprostinil in patients with PH associated with interstitial lung disease, findings that supported regulatory approval. In contrast, riociguat was associated with excess adverse events and mortality in idiopathic interstitial pneumonia and is contraindicated in this population. Evidence for phosphodiesterase-5 inhibitors in COPD-associated PH remains inconsistent, with limited benefit and potential safety concerns. Endothelin receptor antagonists have not shown reliable efficacy. As a result, supportive measures—including long-term oxygen therapy, pulmonary rehabilitation, noninvasive ventilation, and management of sleep-related breathing disorders—remain central to care. Management of Group 3 PH should priorities optimization of the underlying lung disease, correction of hypoxemia, and timely consideration of lung transplantation. At present, inhaled treprostinil is the only PH-targeted therapy supported by randomized evidence in this population. Ongoing research should focus on patient phenotyping and long-term outcome assessment.