title: Efficacy of thrombomodulin for acute exacerbation of idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia: a nonrandomized prospective study.
abstract: OBJECTIVE
  Acute exacerbation (AE) is an important outcome of idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). Recombinant human soluble thrombomodulin (rhTM) is a new drug for the treatment of disseminated intravascular coagulation in Japan. The objective of this study was to evaluate the efficacy of rhTM for AE of IPF/NSIP.
  
  
  METHODS
  Twenty-two patients with AE-idiopathic interstitial pneumonia (16 patients with IPF and six patients with NSIP) were enrolled in our study. Among them, eleven patients were treated with rhTM (rhTM group), and eleven patients were treated without rhTM (non-rhTM group). Patients admitted to our hospital prior to December 2013 were treated with rhTM, while those admitted after January 2014 were treated without rhTM. The primary endpoint was mortality at 90 days after AE treatment. The secondary endpoint was the safety of rhTM for AE-IPF/AE-NSIP. In addition, we examined prognostic factors of AE-IPF/AE-NSIP.
  
  
  RESULTS
  The mortality rate was significantly lower in the rhTM group than in the non-rhTM group (mortality rate at 90 days: 36% vs 90%, P=0.023; median survival time: not reached vs 15.0 days, P=0.019). A univariate analysis revealed the respiratory rate (hazard ratio [HR] 1.09, 95% confidence interval [CI] 1.00-1.18, P=0.039) and rhTM administration (HR 0.21, 95% CI 0.06-0.77, P=0.013) as predictors of mortality at 90 days, and a multivariate analysis identified rhTM administration (HR 0.025, 95% CI 0.0006-0.94, P=0.046) as an independent predictor of mortality at 90 days. No serious adverse events were observed.
  
  
  CONCLUSIONS
  The administration of rhTM is associated with reductions in mortality in patients with AE-IPF/NSIP, without causing adverse events.
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Abe
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Tsushima
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takuma
authors.initials: T
authors.lastname: Matsumura
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ishiwata
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Ichimura
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ikari
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Jiro
authors.initials: J
authors.lastname: Terada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tada
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Seiichirou
authors.initials: S
authors.lastname: Sakao
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Tanabe
authors.affiliation: Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D053208:Kaplan-Meier Estimate; D017563:Lung Diseases, Interstitial / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D019141:Respiratory System Agents / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors; D018180:Thrombomodulin / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D011994:Recombinant Proteins; D019141:Respiratory System Agents; C546931:THBD protein, human; D018180:Thrombomodulin
keywords: acute exacerbation; idiopathic pulmonary fibrosis; nonspecific interstitial pneumonia; recombinant human soluble thrombomoduline