Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial

Kondoh, Yasuhiro; Azuma, Arata; Inoue, Yoshikazu; Ogura, Takashi; Sakamoto, Susumu; Tsushima, Kenji; Johkoh, Takeshi; Fujimoto, Kiminori; Ichikado, Kazuya; Mori, Yasuo; Saito, Takefumi; Kishi, Kazuma; Tomii, Keisuke; Sakamoto, Noriho; Aoshima, Masahiro; Araya, Jun; Izumi, Shinyu; Arita, Machiko; Abe, Mitsuhiro; Yamauchi, Hidemi; Shindoh, Joe; Suda, Takafumi; Okamoto, Masaki; Ebina, Masahito; Yamada, Yoshihito; Tohda, Yuji; Kawamura, Tomohiro; Terada, Yoshio; Ishii, Hiroshi; Hashimoto, Naozumi; Abe, Shinji; Taniguchi, Hiroyuki; Tagawa, Jun; Bessho, Koji; Yamamori, Natsuki; Homma, Sakae

doi:10.1164/rccm.201909-1818oc

Cited by 57 publications

(37 citation statements)

References 27 publications

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“…We thank Dr. Kobayashi and colleagues for their interest and insightful comments regarding our recent randomized trial (1). We agree that imbalances in some baseline factors could be a limitation of this study.…”

Section: From the Authorsmentioning

confidence: 78%

“…We read with interest the recent American Thoracic Society guideline regarding microbiological laboratory testing in the diagnosis of fungal infections in pulmonary and critical care practice (1). According to this guideline, if the results of serum and BAL galactomannan testing are both negative but invasive pulmonary aspergillosis (IPA) is still suspected, biopsy with histopathology and culture is suggested.…”

Section: Ultrasound-guided Transthoracic Needle Aspiration To Diagnosmentioning

confidence: 99%

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Reply to Kobayashi et al.: Too Premature to Deny the Potential of Thrombomodulin Alfa in Idiopathic Pulmonary Fibrosis

Kondoh

Azuma

Tagawa

et al. 2020

Am J Respir Crit Care Med

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Section: From the Authorsmentioning

confidence: 78%

Section: Ultrasound-guided Transthoracic Needle Aspiration To Diagnosmentioning

confidence: 99%

Reply to Kobayashi et al.: Too Premature to Deny the Potential of Thrombomodulin Alfa in Idiopathic Pulmonary Fibrosis

Kondoh

Azuma

Tagawa

et al. 2020

Am J Respir Crit Care Med

Self Cite

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“…Early case reports of AEIPF where corticosteroid therapy alone was used describe a range of survival outcomes (from 4% to 100%), most likely reflecting the heterogeneity in patient populations and disease severity [17,22,[26][27][28]. More recently, a randomised control study investigating the efficacy of thrombomodulin alfa in AEIPF treated 77 patients as baseline standard of care with pulse corticosteroid therapy followed by a taper [29]. While no significant difference was observed between the treatment (n=40) and placebo (n=37) groups, the overall survival at day 90 (n=62, 81%) was much higher than previous studies, possibly due to the clinical trial setting with a greater proportion having less severe disease.…”

Section: Corticosteroids In the Treatment Of Aeipfmentioning

confidence: 99%

Acute exacerbations of idiopathic pulmonary fibrosis and the role of corticosteroids

Brereton

2020

Breathe

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An acute exacerbation of idiopathic pulmonary fibrosis (AEIPF) is a potentially fatal complication of an already debilitating disease. Management is currently centred on delivering excellent supportive care and identifying reversible triggers. Despite growing international awareness and collaboration, no effective therapies have been identified. Corticosteroids are often the mainstay of treatment; however, the evidence base for their use is poor. Here, we review our current understanding of the disease process and how to manage it, with a focus on the role of corticosteroid therapy.

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“…However, this study failed to prove that the higher levels of su-PAR were associated with 3-month mortality. Kondoh et al reported that the thrombomodulin alfa did not improve the 3-month survival proportion in patients with AE-IPF [29]. Therefore, inflammatory factor storms may be more responsible for the short-term death of AE-IPF.…”

mentioning

confidence: 99%

Associations of Serological Biomarkers of sICAM-1, IL-1β, MIF, and su-PAR with 3-Month Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Zhou

Zou

et al. 2020

Mediators of Inflammation

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Objective. To investigate prognostic values of serum biomarkers of soluble intercellular adhesion molecule 1 (sICAM-1), macrophage migration inhibitor factor (MIF), interleukin 1β (IL-1β), and soluble urokinase plasminogen activator receptor (su-PAR) in patients with acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF). Methods. From August 2017 to November 2019, 122 consecutive IPF patients treated in our center were classified as stable IPF and AE-IPF based on the newly published international guidelines. Serum levels of four biomarkers at admission were measured by the enzyme-linked immunosorbent assay (ELISA). The primary endpoint was 3-month mortality. The log-rank test and logistic regression analysis were used to evaluate the effects of these biomarkers for survival in patients with AE-IPF. Cox proportional hazards analysis was performed to evaluate the prognostic values of serological biomarkers and clinical data. Results. Eighty-one patients were diagnosed with stable IPF, and 41 AE-IPF patients were enrolled in the study. Serum levels of sICAM-1 (p<0.001), IL-1β (p<0.001), MIF (p<0.001), and su-PAR (p<0.001) in patients with IPF were significantly increased compared to those in healthy controls. All the four biomarkers were elevated in patients with AE-IPF compared to those with stable IPF. The 3-month mortality in AE-IPF was 56.1% (23/41). Increased levels of MIF (p=0.01) and IL-1β (>5 pg/mL, p=0.033) were independent risk factors for 3-month mortality in patients with AE-IPF. Conclusions. We showed the higher serum levels of IL-1β, and MIF had prognostic values for 3-month mortality in AE-IPF. This study provided a clue to promote our understanding in the pathogenesis of the disease.

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Thrombomodulin Alfa for Acute Exacerbation of Idiopathic Pulmonary Fibrosis. A Randomized, Double-Blind Placebo-controlled Trial

Cited by 57 publications

References 27 publications

Reply to Kobayashi et al.: Too Premature to Deny the Potential of Thrombomodulin Alfa in Idiopathic Pulmonary Fibrosis

Reply to Kobayashi et al.: Too Premature to Deny the Potential of Thrombomodulin Alfa in Idiopathic Pulmonary Fibrosis

Acute exacerbations of idiopathic pulmonary fibrosis and the role of corticosteroids

Associations of Serological Biomarkers of sICAM-1, IL-1β, MIF, and su-PAR with 3-Month Mortality in Acute Exacerbation of Idiopathic Pulmonary Fibrosis

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