dinoprost and Idiopathic-Pulmonary-Fibrosis

Sarcoidosis and idiopathic pulmonary fibrosis (IPF) are both associated with deregulated inflammatory mechanisms partially triggered by aggravated oxidative stress. 8-Isoprostane has been proposed as a reliable marker of oxidative stress, linked to several pulmonary diseases. We aimed to explore differences in 8-isoprostane levels in IPF and sarcoidosis patients, and controls.. We included 16 IPF and 55 sarcoidosis patients, as well as 17 controls in the study. 8-Isoprostane levels were measured in serum and in bronchoalveolar lavage (BAL).. Serum 8-isoprostane levels were increased in all patient groups vs controls (p<0.001). The systemic 8-isoprostane concentrations were higher in sarcoidosis patients as compared to IPF subjects and controls (p=0.017 and p<0.001, respectively). IPF patients exhibited increased serum 8-isoprostane levels when compared to controls (p<0.001). Sarcoidosis patients presented significantly increased 8-isoprostane BAL levels when compared to IPF patients (p=0.002).. Our data indicate that the level of oxidative stress, as reflected by 8-isoprostane concentrations, is enhanced in patients with sarcoidosis, and to a lesser extent, in IPF patients when compared to controls, suggesting a potential implication of redox imbalance in both diseases.

Topics: Aged; Biomarkers; Bronchoalveolar Lavage Fluid; Case-Control Studies; Dinoprost; Female; Humans; Idiopathic Pulmonary Fibrosis; Male; Middle Aged; Oxidative Stress; Sarcoidosis

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 F2α (PGF2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF2α, a stable metabolite of PGF2α.. We measured plasma concentrations of 15-keto-dihydro PGF2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF2α concentrations with disease severity and mortality.. Plasma concentrations of 15-keto-dihydro PGF2α 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 PGF2α concentrations (relative risk = 1.005, p = 0.002) were independently associated with an increased risk of mortality.. We demonstrated significant associations of plasma concentrations of PGF2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF2α in human IPF.

Topics: Dinoprost; Echocardiography, Doppler; Humans; Idiopathic Pulmonary Fibrosis; Immunoenzyme Techniques; Proportional Hazards Models