Chest
Volume 148, Issue 2, August 2015, Pages 436-443
Journal home page for Chest

Original Research
Diffuse Lung Disease
Recombinant Human Thrombomodulin in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

https://doi.org/10.1378/chest.14-2746Get rights and content

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.

Section snippets

Baseline Characteristics

A patient flow diagram is shown in Figure 1. In the study period, 44 consecutive patients were admitted for AE-IPF. Four of these patients were excluded, including two with previous episodes of AE, one with complication of severe acute cholecystitis, and one who refused further medical treatment. The remaining 40 patients met the inclusion criteria. They included 36 men and four women, with a median age of 72 years (range, 43-90 years) (interquartile range, 66-78 years). Median Pao2/Fio2 at

Discussion

This is the first study, to our knowledge, to investigate the efficacy of rhTM for AE-IPF. We showed that rhTM was associated with a better outcome for 3-month mortality (30%). Using a logistic regression model, it was also shown to improve 3-month survival. Administration of rhTM appeared to be safe without any major adverse effects.

We found high levels of D-dimer in BALF in patients with AE-IPF, which reflect a disturbance in intraalveolaractivated coagulation. We also showed an elevated

Acknowledgments

Author contributions: K. K. served as principal author, had access to and takes responsibility for the integrity of the data and the accuracy of the data analysis. Y. K., O. N., and K. S. contributed to the study concept and design; T. K., T. M., and T. Y. contributed to data collection; H. T., T. K., T. M., T. Y., and M. A. contributed to data analysis; T. K., T. M., and T. Y. contributed to preparation and review of the manuscript; Y. K., O. N., K. S., and M. A. contributed to the writing and

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    originally published Online First March 26, 2015.

    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.

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