Evidence map›Paper›PMID 40074958›Full record

ArticleLung2025

Serum Soluble Toll-Like Receptor 4 is a Predictive Biomarker for Acute Exacerbation and Prognosis of Idiopathic Pulmonary Fibrosis: A Retrospective Study.

Erika Kitadai, Kakuhiro Yamaguchi, Hiroshi Iwamoto, Kiyofumi Shimoji, Shinjiro Sakamoto, Yasushi Horimasu, Takeshi Masuda, Taku Nakashima, Shinichiro Ohshimo, Hironobu Hamada and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Lung, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Acute exacerbation in fibrotic interstitial lung disease: an international working group report.American journal of respiratory and critical care medicine · 2026
    Review
  2. [Surgical Management of Lung Cancer in Patients with Interstitial Lung Disease].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026
    Review
  3. Article
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Erika KitadaiDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Kakuhiro YamaguchiDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. yamaguchikakuhiro@gmail.com.
Hiroshi IwamotoDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Kiyofumi ShimojiDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Shinjiro SakamotoDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Yasushi HorimasuDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Takeshi MasudaDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Taku NakashimaDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.
Shinichiro OhshimoDepartment of Emergency and Critical Care Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Hironobu HamadaDepartment of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Noboru HattoriDepartment of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

purposeToll-like receptor 4 (TLR4) is a transmembrane receptor promoting pro-inflammatory signalling, that is associated with the pathogenesis of pulmonary fibrosis. TLR4 is abundantly expressed on monocytes and the acceleration of TLR4 signalling induces the secretion of soluble TLR4 isoforms (sTLR4) in circulation. The aim of study was to evaluate the association of serum levels of sTLR4 with acute exacerbation (AE) and prognosis of patients with idiopathic pulmonary fibrosis (IPF).

methodsThis retrospective cohort study included 97 patients with IPF and 76 healthy participants. The association of serum sTLR4 levels with the onset of AE and the prognosis in 97 patients with IPF was analyzed.

resultsNo significant difference in sTLR4 serum level was observed between the patients with IPF and healthy participants. Kaplan-Meier curves showed that patients with sTLR4 ≥ 2.2 ng/mL had a significantly higher incidence of AE-IPF and a significantly lower 5-year survival rate. Univariate and multivariate Cox hazard analyses demonstrated that sTLR4 ≥ 2.2 ng/mL was significantly associated with higher incidence of AE and poorer survival. In an exploratory analysis, a weak correlation was observed between sTLR4 levels and monocyte counts, and the incidence of AE-IPF was the highest in the patients with sTLR4 ≥ 2.2 ng/mL and monocyte counts ≥ 381/μL.

conclusionHigh sTLR4 level is associated with an increased incidence of AE-IPF and poor prognosis in patients with IPF. The combination of sTLR4 level and monocyte count might be used to stratify patients with IPF according to the risk for AE via reflecting monocyte activation.

Indexed as

Idiopathic Pulmonary FibrosisToll-Like Receptor 4AgedBiomarkersCase-Control StudiesDisease ProgressionFemaleHumansKaplan-Meier EstimateMaleMiddle AgedMonocytesPrognosisRetrospective StudiesBiomarkersTLR4 protein, humanToll-Like Receptor 4Acute exacerbationIdiopathic pulmonary fibrosisMonocytePrognosisSoluble toll-like receptor 4

Identifiers

PMID40074958
PMCPMC11903555

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.