A74-03 A Novel Biologic and Physiologic Assessment of Disease Progression in PH-ILD

Rationale The development of pulmonary hypertension in patients with interstitial lung disease (PH-ILD) occurs in approximately half of people with interstitial lung disease (ILD). However, the lack of therapeutic options has historically led to low rates of screening for the presence of pulmonary hypertension in these patients. Now that Tyvasso has been approved by the FDA to treat PH-ILD, there is an opportunity to treat a large population of patients who were previously without therapeutic options. Pro-fibrotic cytokines, like transforming growth factor-beta (TGF-β), induce the activity of elastases and proteinases, which degrade mature elastin and create elastin degradation products (EDPs or elastokines) in the lung parenchyma and pulmonary arteries. We hypothesize that elastin turnover is higher in patients with PH-ILD compared to those with either Group 1 PAH or Idiopathic Pulmonary Fibrosis (IPF) due to enhanced lung and arterial remodeling. We have previously demonstrated that higher EDP concentrations in patients with IPF are associated with greater lung function impairment and worse 3-year transplant-free survival. Our group has also shown that assessing cardiac effort (total heart beats/6-minute walk distance) is a more sensitive and specific assessment of work performed during a 6-minute walk test compared to distance alone (6MWD). Importantly, this led to earlier identification of patients who required treatment intensification. This study assesses the utility of using the combination of novel biologic (EDPs) and physiologic (cardiac effort) assessments to better identify those with PH-ILD who are at risk for disease progression. Methods To measure plasma EDP levels (isodesmosine), we used commercially available ELISA kits (mybiosource.com) from patients with IPF, PAH, and PH-ILD. We then examined for associations between clinical parameters (NT pro-BNP, 6MWD, and cardiac effort) and circulating EDP concentrations using linear regression analysis (PRISM v10); a p value < 0.05 was considered statistically significant. Results We demonstrate that circulating EDP levels are elevated in patients with IPF and PAH compared with healthy volunteers; they were further elevated in patients with PH-ILD. Elevated EDP concentrations positively correlate with elevated NT pro-BNP levels and cardiac effort. There was a suggestion of a negative correlation between increased EDP concentration and decreased 6MWD but statistical significance was not achieved, likely due to our limited sample size. Conclusions The use of circulating EDP concentrations combined with cardiac effort, may improve timely recognition of patients with PH-ILD who are at risk of clinical decompensation and thereby lead to improved outcomes through early medication administration.