Isshiki Takuma, Sakamoto Susumu, Kinoshita Arisa, Sugino Keishi, Kurosaki Atsuko, Homma Sakae
Division of Respiratory Medicine, Toho University Omori Medical Center, Tokyo, Japan.
Respiration. 2015;89(3):201-7. doi: 10.1159/000369828. Epub 2015 Feb 5.
Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) can be fatal, and abnormalities in the coagulation system of patients with AE-IPF have been reported. Recombinant human soluble thrombomodulin (rhTM) forms a complex with thrombin to inactivate coagulation. It also inhibits high-mobility group box protein 1 (HMGB-1), which results in the suppression of inflammation.
We aimed to evaluate the effectiveness of rhTM for the treatment of AE-IPF.
We retrospectively reviewed the medical records of 41 patients with AE-IPF who were admitted to our institution during the period 2006-2013. The clinical features and outcomes of 16 patients treated with rhTM (rhTM group) were compared with those of 25 patients treated with conventional therapy (control group). Patients were treated with corticosteroid (CS) pulse therapy for 3 days, followed by maintenance treatment with a tapered dose of CS. Patients in the rhTM group also received rhTM (0.06 mg/kg/day) for 6 days as an initial treatment, in combination with CS.
Except for D-dimer level, there were no significant differences in the baseline characteristics of the 2 groups. When compared with the control group, the rhTM group had a significantly higher survival rate at 3 months (40 vs. 69%, p = 0.048). A univariate Cox proportional hazards regression model showed that the predictive factors for survival were lactate dehydrogenase level and rhTM treatment. Regarding adverse events, 1 patient in the rhTM group developed mild bleeding events.
rhTM as an add-on to conventional treatment may improve survival in patients with AE-IPF.
特发性肺纤维化急性加重（AE-IPF）可能致命，且已有报道称AE-IPF患者的凝血系统存在异常。重组人可溶性血栓调节蛋白（rhTM）与凝血酶形成复合物以灭活凝血。它还抑制高迁移率族蛋白1（HMGB-1），从而抑制炎症。
我们旨在评估rhTM治疗AE-IPF的有效性。
我们回顾性分析了2006年至2013年期间我院收治的41例AE-IPF患者的病历。将16例接受rhTM治疗的患者（rhTM组）的临床特征和结局与25例接受传统治疗的患者（对照组）进行比较。患者接受为期3天的糖皮质激素（CS）冲击治疗，随后接受逐渐减量的CS维持治疗。rhTM组患者还在初始治疗时接受6天的rhTM（0.06 mg/kg/天）治疗，并联合CS。
除D-二聚体水平外，两组的基线特征无显著差异。与对照组相比，rhTM组在3个月时的生存率显著更高（40%对69%，p = 0.048）。单因素Cox比例风险回归模型显示，生存的预测因素为乳酸脱氢酶水平和rhTM治疗。关于不良事件，rhTM组有1例患者发生轻度出血事件。
rhTM作为传统治疗的附加治疗可能提高AE-IPF患者的生存率。
