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Association between neutrophil extracellular traps in bronchoalveolar lavage fluid and severity of drug-induced lung injury - 23/08/25

Doi : 10.1016/j.resmer.2025.101195 
Genki Inui a, , Miki Takata a, Yoshihiro Funaki a, Aditya Sri Listyoko a, b, Miyu Nishigami a, Hiroyuki Tanaka a, Hiroki Ishikawa a, Hiroki Kohno a, Tomoya Harada a, Ryota Okazaki a, Masato Morita a, Akira Yamasaki a
a Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Tottori 683-8504, Japan 
b Pulmonary and Respiratory Medicine Department, Faculty of Medicine, Brawijaya University-Dr. Saiful Anwar General Hospital, Malang 65112, Indonesia 

Corresponding author at: Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of Medicine, Tottori University, Tottori 683-8504, Japan.Division of Respiratory Medicine and Rheumatology, Department of Multidisciplinary Internal Medicine, Faculty of MedicineTottori UniversityTottori683-8504Japan

Highlights

We evaluated the relationship between NETs and DLI, which has not yet been explored.
NETs levels in BALF were significantly elevated in cases of severe DLI.
They were also elevated in cases showing DAD patterns on HRCT.
Measuring NETs may guide future treatments and aid in diagnosis clinical phenotypes.

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Abstract

Background

Neutrophil extracellular traps (NETs) play a pivotal role in early immune responses and are implicated in various respiratory diseases, such as acute respiratory distress syndrome (ARDS). A correlation between NETs in bronchoalveolar lavage fluid (BALF) and the severity of ARDS has been reported. NETs are also associated with drug-induced organ disorders. However, the relationship between drug-induced lung injury (DLI) and NETs remains unclear. This study aimed to establish and substantiate this relationship.

Methods

We conducted a retrospective observational study. We extracted DLI cases in which BAL was performed at Tottori university hospital. Based on the need for glucocorticoid treatment, patients were classified into the “moderate severity or above” group (PaO2 < 80 mmHg) and “mild” group (PaO2 ≧ 80 mmHg). We examined myeloperoxidase, neutrophil elastase, and double-strand-DNA levels in BALFs, and examined their association with clinical findings and severity, with non-parametric Mann-Whitney U test.

Results

We studied 46 patients with DLI. The “moderate severity or above” group had 32 patients, while the “mild” group had 14 patients, and NETs in BALF were significantly higher in the former group. Three cases showed a diffuse alveolar damage (DAD) pattern on high-resolution computed tomography (HRCT), with significantly higher NET levels that those with non-DAD patterns.

Conclusion

In DLI, NETs in BALF were found to be related with disease severity and the presence of DAD patterns in HRCT images. Measuring NETs in BALF offer potential utility in guiding future treatment selection and aiding the differential diagnosis of clinical phenotypes.

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Keywords : ds-DNA (double-strand-DNA)

Abbreviations : ARDS, BAL, BALF, COVID-19, CT, DAD, DILI, DLI, DNA, DOI, FEV1, FiO2, FVC, GGO, HP, HRCT, IQR, JASP, KL-6, LDH, MPO, NE, NETs, NSIP, OP, PaO2, PCR, P/F, SP, sPEo, SpO2, VAP, WBC


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© 2025  The Author(s). Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 88

Article 101195- novembre 2025 Retour au numéro
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