Clinical relevance of plasma prostaglandin f2α metabolite concentrations in patients with idiopathic pulmonary fibrosis.

Abstract

[Background]Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F_{2α}(PGF_{2α}) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF_{2α} in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF_{2α} in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF_{2α}, a stable metabolite of PGF_{2α}. [Methods]We measured plasma concentrations of 15-keto-dihydro PGF_{2α} in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF_{2α} concentrations with disease severity and mortality. [Results]Plasma concentrations of 15-keto-dihydro PGF_{2α} were significantly higher in IPF patients than controls (p<0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (Rs [correlation coefficient] = −0.34, p = 0.004), forced vital capacity (Rs = −0.33, p = 0.005), diffusing capacity for carbon monoxide (Rs = −0.36, p = 0.003), the composite physiologic index (Rs = 0.40, p = 0.001), 6-minute walk distance (Rs = −0.24, p = 0.04) and end-exercise oxygen saturation (Rs = −0.25, p = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, p = 0.002) and plasma 15-keto-dihydro PGF_{2α} concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality. [Conclusions]We demonstrated significant associations of plasma concentrations of PGF_{2α} metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF_{2α} in human IPF.