Background While pulmonary arterial hypertension complicating ILD (PAH-ILD) is associated with markedly increased mortality, PAH directed therapy has not been adequately studied in this population. We previously demonstrated that PAH directed therapy with intravenous or subcutaneous prostacyclin (PGI2) in patients with PAH-ILD improves right heart haemodynamics (1). However, it remains unclear which patients with PAH-ILD will respond to therapy.
Objectives The present study seeks to investigate whether specific chemokines and growth factors, previously found to be associated with vascular remodeling, can be used to predict PAH directed therapy responsiveness. We hypothesized that PAH-ILD patients with augmented levels of specific CC chemokines (CCL2 and CCL5), as well as downstream growth factors (EGF, FGF-2, PDGF-AA and PGF-BB), may exhibit decreased responsiveness to PAH-directed therapy in ILD.
Methods In this single-center study, plasma samples (n=15) were collected prospectively prior to initiation of PGI2 therapy. Plasma concentrations of CCL2, CCL5, EGF, FGF-2, PDGF-AA and PDGF-BB were evaluated by fluorochrome (Luminex) technology. Response to PGI2 was assessed as a reduction in PVR from right heart catherization at 12 months. A Kendall's tau (τ) rank correlation coefficient was used to measure the association between baseline concentrations of specific chemokines and growth factors and PGI2 response.
Results In our cohort of 15 patients with ILD (8 idiopathic pulmonary fibrosis, 3 combined pulmonary fibrosis/emphysema, 2 non-specific interstitial pneumonia, 1 sarcoid, and 1 hypersensitivity pneumonitis) and PAH (baseline mean pulmonary artery pressure of 47.2 mmHg and pulmonary vascular resistance of 697.9 dyn s/cm5), higher concentrations of the CC chemokine CCL5 (τ =0.49, p=0.0138), as well as the growth factors PDGF-AA (τ =0.47, p=0.0186) (See Figure 1), and PDGF-BB (τ =0.49, p=0.0138) were negatively correlated with a relative change in PVR in response to PGI2 therapy.
Conclusions Elevated baseline concentrations of plasma chemokine CCL5 and growth factors PDGF-AA and PDGF-BB affecting vascular fibroproliferation may be associated with irreversible remodeling of the pulmonary circulation in response to PGI2 therapy in ILD associated PAH.
Saggar R et al. Thorax 2014; 69:123-129.
Disclosure of Interest None declared