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Original Research: Diffuse Lung Disease |

Recombinant Human Thrombomodulin in Acute Exacerbation of Idiopathic Pulmonary FibrosisRecombinant Human Thrombomodulin in AE-IPF

Kensuke Kataoka, MD, PhD; Hiroyuki Taniguchi, MD, PhD; Yasuhiro Kondoh, MD, PhD; Osamu Nishiyama, MD, PhD; Tomoki Kimura, MD, PhD; Toshiaki Matsuda, MD; Toshiki Yokoyama, MD, PhD; Koji Sakamoto, MD, PhD; Masahiko Ando, MD, PhD
Author and Funding Information

From the Department of Respiratory Medicine and Allergy (Drs Kataoka, Taniguchi, Kondoh, Kimura, Matsuda, and Yokoyama), Tosei General Hospital, Seto; Department of Respiratory Medicine and Allergology (Dr Nishiyama), Kinki University, Faculty of Medicine, Osaka; Department of Respiratory Medicine (Dr Sakamoto), Nagoya University Graduate School of Medicine, Nagoya; and Center for Advanced Medicine and Clinical Research (Dr Ando), Nagoya University Hospital, Nagoya, Japan.

CORRESPONDENCE TO: Hiroyuki Taniguchi, MD, PhD, Department of Respiratory Medicine and Allergy, Tosei General Hospital, 160 Nishioiwake-cho, Seto, Aichi 489-8642, Japan; e-mail: taniguchi@tosei.or.jp


FUNDING/SUPPORT: This study was partially supported by a grant to the Diffuse Lung Disease Research Group from the Ministry of Health, Labor and Welfare, Japan, and the NPO Respiratory Disease Conference.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(2):436-443. doi:10.1378/chest.14-2746
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BACKGROUND:  Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) presents as episodes of acute respiratory worsening closely associated with endothelial damage and disordered coagulopathy. Recombinant human soluble thrombomodulin (rhTM) regulates the coagulation pathway mainly by reducing thrombin-mediated clotting and enhancing protein C activation. We investigated the efficacy of rhTM for the treatment of patients with AE-IPF.

METHODS:  This historical control study comprised 40 patients with AE-IPF. Twenty patients treated with rhTM (0.06 mg/kg/d) for about 6 days (rhTM group) and 20 patients treated without rhTM (control group) were evaluated. The predictors of 3-month mortality (logistic regression model) were evaluated.

RESULTS:  There was no difference in baseline characteristics between the control group and the rhTM group. Three-month mortality of the rhTM group and control group was 30.0% and 65.0%, respectively. In univariate analysis, C-reactive protein and rhTM therapy were significant determinants for 3-month survival. In multivariate analysis, rhTM therapy (OR, 0.219; 95% CI, 0.049-0.978; P = 0.047) was an independent significant determinant for 3-month survival.

CONCLUSIONS:  We found that rhTM therapy improved 3-month survival of AE-IPF. The results observed here warrant further investigation of rhTM in randomized control trials.

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