Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug‐induced lung injury

Suzuki, Atsushi; Taniguchi, Hiroyuki; Kondoh, Yasuhiro; Ando, Masahiko; Watanabe, Naohiro; Kimura, Tomoki; Kataoka, Kensuke; Yokoyama, Toshiki; Sakamoto, Koji; Hasegawa, Yoshinori

doi:10.1111/resp.12965

Cited by 9 publications

(7 citation statements)

References 25 publications

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“…Previous studies demonstrated that thrombomodulin is excessively secreted into bloodstream in severe illnesses such as sepsis and ARDS [48,49]. Thrombomodulin was also reported to be elevated in bronchoalveolar lavage fluid (BALF) and shown to correlate with the prognosis of AE of IP [50]. This soluble thrombomodulin molecule detached from the endothelial cell surface may be unduly generated by proteolytic cleavage of the protein, which is mediated by a wide range of proteases augmented under these critical circumstances [48].…”

Section: Discussionmentioning

confidence: 99%

The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Kamiya

Panlaqui

2020

BMC Pulm Med

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Background: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is devastating with no established treatment. This phenomenon involves disordered coagulation and excessive inflammatory reactions. As recombinant human soluble thrombomodulin (rhsTM) possesses anti-coagulative and anti-inflammatory properties, the medicine is expected to improve the prognosis of the disease. The aim of this study was to summarize current evidence regarding benefits and harms of rhsTM treatment for AE of IPF. Method: Patients with AE of IPF were eligible for the review and all of the other types of interstitial pneumonias were excluded. The effect of rhsTM treatment on the outcomes such as all-cause mortality was estimated in comparison to conventional therapy. Primary studies of any design aside from a case report were reviewed. Electronic databases such as Medline and EMBASE were searched from 2002 through August 14, 2019. Two reviewers independently selected eligible reports and extracted relevant data. A risk of bias of individual studies was assessed similarly. Meta-analysis was conducted for univariate results if at least three studies were available for the same outcome. Result: Out of a total of 390 records identified, eight studies were first deemed eligible and four of them were finally focused for the review. Only one study was a prospective trial and a historical control was employed in all studies. An overall risk of bias was rated as serious in three out of four studies. A total of 169 subjects were included. Two out of three studies that reported 3-month all-cause mortality by univariate analysis demonstrated beneficial effects of rhsTM treatment and a pooled analysis demonstrated that rhsTM treatment improved 3-month all-cause mortality with a risk ratio of 0.50 (95% confidence interval (CI): 0.35-0.72). All two studies reporting multivariate results demonstrated that rhsTM treatment improved 3-month all-cause mortality with odds ratios of 0.21 (95% CI: 0.05-0.91) and 0.25 (95% CI: 0.09-0.68), respectively. There were no serious adverse events. Conclusion: The rhsTM treatment was demonstrated to improve 3-month all-cause mortality of AE of IPF with no serious adverse events. However, these findings should be interpreted with caution due to a small number of studies and serious risk of bias.

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Section: Discussionmentioning

confidence: 99%

The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Kamiya

Panlaqui

2020

BMC Pulm Med

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“…Recombinant human soluble thrombomodulin (rhTM), which has anti-inflammatory effects and mitigates the coagulation cascade, was also developed as a treatment for sepsis. In acute lung injury, there is both intense procoagulant activity and severe inflammation in the lung parenchyma [39]. Therefore, the mechanism of action of rhTMs suggests that it could be a plausible therapeutic agent for AEs of IPF.…”

Section: Managementmentioning

confidence: 99%

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Kishaba

2019

Medicina

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Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonia. Idiopathic pulmonary fibrosis is often seen in elderly men who smoke. A diagnosis of IPF is based on a combination of a detailed clinical history, specific physical examination, laboratory findings, pulmonary function tests, high-resolution computed tomography (HRCT) of the chest, and histopathology. Idiopathic pulmonary fibrosis has a heterogeneous clinical course, from an asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). Acute exacerbation of IPF has several important differential diagnoses, such as heart failure and volume overload. The International Working Group project proposed new criteria for defining AE of IPF in 2016, which divides it into triggered and idiopathic AE. On the basis of these criteria, physicians can detect AE of IPF more easily. The recent international IPF guidelines emphasized the utility of chest HRCT. In addition, two antifibrotic agents have become available. We should focus on both the management and prevention of AE. The diagnostic process, laboratory findings, typical chest imaging, management, and prognosis of AE are comprehensively reviewed in this article.

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“…rhTM is also developed as anti-sepsis agent. In acute lung injury,there is intensive procoagulant activity in lung parenchyma [34]. Therefore, rhTM is a promising agent with mechanism of action for AE of IPF.…”

Section: Managementmentioning

confidence: 99%

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Kishaba¹

2018

Preprint

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Idiopathic Pulmonary Fibrosis (IPF) is most common idiopathic interstitial pneumonias. IIPF is often seen in elderly smoker man. Diagnosis of IPF is integration of detailed clinical history, specific physical examination, laboratory findings, pulmonary function test, chest high-resolution computed tomography (HRCT) and pathology. IPF have heterogeneous clinical course from asymptomatic stable state to progressive respiratory failure or acute exacerbation (AE). AE of IPF have several important differential diagnosis such as heart failure and volume overload. International working project proposed new criteria of AE of IPF in 2016. They divided into triggered and idiopathic AE. On the basis of this criteria, physician can capture AE of IPF more easily. Recent international IPF guideline emphasized the utility of chest HRCT. In addition, two anti-fibrotic agents have been available. We should pay attention to not only management of AE, but also prevention it. I review diagnostic process, laboratory findings, typical chest imaging, management and prognosis of AE.

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Soluble thrombomodulin in bronchoalveolar lavage fluid is an independent predictor of severe drug‐induced lung injury

Abstract: Soluble TM in BALF is an independent predictor of severe DLI. These findings underscore the importance of pulmonary endothelial injuries in the pathogenesis of severe DLI.

Cited by 9 publications

References 25 publications

The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

The efficacy of recombinant human soluble thrombomodulin (rhsTM) treatment for acute exacerbation of idiopathic pulmonary fibrosis: a systematic review and meta-analysis

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

Acute Exacerbation of Idiopathic Pulmonary Fibrosis

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