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Thrombomodulin for Acute Exacerbations of Idiopathic Pulmonary Fibrosis

Background: Acute exacerbation (AE) is known as a leading cause of morbidity and mortality in chronic fibrosing group includes idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP). There is no standardizes drug therapy with comparative studies. The clinical application of recombinant human soluble thrombomodulin (rhTM) has recently been expected against AE-IPF/NSIP, however, the impact of rhTM remains unestablished. Thus, this review assessed the impact of rhTM on mortality in patients with AE-IPF/NSIP.
Methods: PubMED database was investigated for studies in English on May 2017 by two independent reviewers. The investigated period was restricted to previous 10 years. Studies was included adults with AE of IPF or idiopathic interstitial pneumonias, and treatment with thrombomodulin. Key data on study design, patient characteristics, outcome measures and adverse events were extracted for the review. We pooled mortality using random-effects meta-analysis

Results: Three prospective and two retrospective studies were included. The five studies recruited a total of 77 patients receiving rhTM treatment (rhTM group). Corticosteroid therapy was examined in all studies for both rhTM groups and non-rhTM group. Mortality at 28 days or one month was evaluated in all three prospective studies, and was significantly lower in the rhTM group than in nonrhTM group. The pooled 1-month mortality was significantly lower in rhTM group (Odds Ratio (OR): 0.25 (95% CI, 0.08-0.77)). Mortality at 3 months was also lower in rhTM group. In patients with AE-IPF/NSIP, rhTM administration was of significant prognostic value of 3-month mortality by univariate analysis and by multivariate analysis. Two retrospective studies reported adverse effect in rhTM group and/or non-rhTM group.

Conclusion: In this study, a decline in mortality was confirmed when rhTM was administered in treating AE-IPF/ NSIP, in conjunction with steroid therapy and immunosuppressive drugs. It indicated a possibility of rhTM administration being effective against AE-IPF/NSIP.


Yasunori Ichimura, Kenji Tsushima, Takuma Matsumura, Mitsuhiro Abe, Koichiro Tatsumi

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