Abstract
BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive disease often complicated by pulmonary hypertension (PH), leading to a worse prognosis. In this study, we use the term “secondary PH” to refer to PH that develops as a complication of IPF (i.e., IPF-PH), and “the ERPE (Exercise-Responsive PAP Elevation) group, defined as patients without resting PH but with potential PAP elevation during exertion, indicating early pulmonary vascular stress.” This study aimed to evaluate the impact of pulmonary vascular resistance (PVR) on the clinical course, activities of daily living (ADL), and exercise tolerance in IPF patients. Additionally, we sought to determine whether PVR influences prognosis within a short-term period of just two years. METHODS: This exploratory single-center study was conducted as an interim analysis of a prospective trial targeting patients with IPF complicated by secondary PH or ERPE. The analysis included 49 IPF patients who received conventional IPF management without pulmonary arterial hypertension (PAH)-specific therapies and completed a two-year follow-up. Pulmonary circulation parameters, including PVR and pulmonary artery pressure (PAP), were assessed via right heart catheterization. Lung function, ADL, and exercise tolerance were also evaluated. Statistical analyses were performed to assess the association between PVR and prognosis. RESULTS: Higher PVR was significantly associated with poorer prognosis and worsening restrictive lung impairment. PVR correlated with modified Medical Research Council (mMRC) scores (Spearman’s ρ = 0.47, p = 0.0007) and 6-minute walk distance (Spearman’s ρ = -0.41, p = 0.0042). Proportional hazard analysis identified PVR as a significant predictor of overall survival (hazard ratio [HR]: 1.28, 95% confidence interval [CI]: 1.0055–1.53, p = 0.013). PVR also strongly correlated with maximum exercise tolerance (Spearman’s ρ = -0.60, p < 0.0001). Importantly, even within the short two-year follow-up, elevated PVR significantly impacted both home-stay survival (HR: 1.20, 95% CI: 1.0072–1.41, p = 0.032) and overall survival, underscoring its predictive value over a short time frame. CONCLUSIONS: PVR is associated with prognosis, ADL, and exercise tolerance in IPF patients. Importantly, even within a short two-year period, PVR was significantly linked to clinical outcomes. While causality cannot be established, our findings suggest that PVR may serve as a potentially useful early prognostic marker. Regular PVR monitoring could provide valuable insights into disease progression and may support earlier therapeutic interventions to improve outcomes. TRIAL REGISTRATION: This study is registered in the UMIN Clinical Trials Registry (UMIN000055468). Trial registration at 10/09/2024. Retrospectively registered. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12890-025-03837-0.