title: 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 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Respiratory Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.
authors.forename: Kensaku
authors.initials: K
authors.lastname: Aihara
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Handa
authors.forename: Toru
authors.initials: T
authors.lastname: Oga
authors.forename: Kizuku
authors.initials: K
authors.lastname: Watanabe
authors.forename: Kiminobu
authors.initials: K
authors.lastname: Tanizawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Ikezoe
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Taguchi
authors.forename: Hiroe
authors.initials: H
authors.lastname: Sato
authors.forename: Kazuo
authors.initials: K
authors.lastname: Chin
authors.forename: Sonoko
authors.initials: S
authors.lastname: Nagai
authors.forename: Shuh
authors.initials: S
authors.lastname: Narumiya
authors.forename: Athol U
authors.initials: AU
authors.lastname: Wells
authors.forename: Michiaki
authors.initials: M
authors.lastname: Mishima
mesh_terms: D015237:Dinoprost / Q000031:analogs & derivatives* / Q000097:blood; D015150:Echocardiography, Doppler; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood* / Q000473:pathology*; D007124:Immunoenzyme Techniques; D016016:Proportional Hazards Models
chemical_list: C026528:15-ketoprostaglandin F2alpha; D015237:Dinoprost