Blood-based biomarkers associated with progressive pulmonary fibrosis in idiopathic inflammatory myositis-associated interstitial lung disease: A retrospective cohort study from a respiratory center
- 1Department of Respiratory Medicine, Tokyo Medical University Hospital, Tokyo, Japan
Abstract
Background: Interstitial lung disease (ILD) is a common extramuscular manifestation of idiopathic inflammatory myopathies (IIM). Progressive pulmonary fibrosis (PPF) can develop in a subset of patients with IIM-associated interstitial lung disease (IIM-ILD) and is associated with poor outcomes. This study aimed to evaluate the utility of blood-based biomarkers associated with PPF in patients with IIM-ILD.
Methods: We retrospectively reviewed 54 consecutive patients diagnosed with IIM-ILD between January 2018 and December 2023. Patients were categorized as having PPF or not based on 2022 ATS/ERS/JRS/ALAT guideline criteria within 1 year after the diagnosis of IIM-ILD. Lung-specific macromolecules and systemic inflammatory and nutritional indices were calculated using laboratory data obtained at the initial evaluation. These included “Krebs von den Lungen-6” (KL-6), surfactant protein-D, C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), fibrosis-4 index, prognostic nutritional index, and geriatric nutritional risk index. Receiver operating characteristic curve analysis was used to determine optimal cutoff values, and logistic regression analyses were performed to identify factors associated with PPF.
Results: Out of the 54 patients, 32 were classified as having PPF and 22 as not having PPF. The PPF group showed significantly lower hemoglobin levels and significantly higher platelet counts, neutrophil counts, C-reactive protein, and serum KL-6 levels than the non-PPF group. Several systemic inflammatory indices, including CAR, NLR, MLR, PLR, SII, SIRI, and AISI, were significantly higher in the PPF group. AISI showed the highest discriminative ability among the evaluated biomarkers, with an area under the curve of 0.786 and an optimal cutoff value of 278. In multivariable logistic regression analysis, serum KL-6 ≥626 U/mL and AISI ≥278 were independently associated with PPF, with adjusted odds ratios of 6.480 (95% confidence interval [CI]: 1.440–29.200; p = 0.015) and 9.940 (95% CI: 2.260–43.600; p = 0.002), respectively.
Conclusions: AISI and serum KL-6 may serve as accessible, non-invasive blood-based biomarkers associated with fibrotic progression in patients with IIM-ILD.
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BibTeX
@article{ishiwari2026bloodbased,
title = {{Blood-based biomarkers associated with progressive pulmonary fibrosis in idiopathic inflammatory myositis-associated interstitial lung disease: A retrospective cohort study from a respiratory center}},
author = {Mayuko Ishiwari and Yuta Kono and Kenichi Kobayashi and Ryota Kikuchi and Mariko Kogami and Takashi Okuma and Shinji Abe},
journal = {Multidisciplinary Respiratory Medicine},
year = {2026},
month = sep,
doi = {10.5826/mrm.2026.1112},
url = {https://doi.org/10.5826/mrm.2026.1112},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Blood-based biomarkers associated with progressive pulmonary fibrosis in idiopathic inflammatory myositis-associated interstitial lung disease: A retrospective cohort study from a respiratory center
AU - Mayuko Ishiwari
AU - Yuta Kono
AU - Kenichi Kobayashi
AU - Ryota Kikuchi
AU - Mariko Kogami
AU - Takashi Okuma
AU - Shinji Abe
PY - 2026
DA - 2026/09/15
JO - Multidisciplinary Respiratory Medicine
DO - 10.5826/mrm.2026.1112
UR - https://doi.org/10.5826/mrm.2026.1112
AB - Background: Interstitial lung disease (ILD) is a common extramuscular manifestation of idiopathic inflammatory myopathies (IIM). Progressive pulmonary fibrosis (PPF) can develop in a subset of patients with IIM-associated interstitial lung disease (IIM-ILD) and is associated with poor outcomes. This study aimed to evaluate the utility of blood-based biomarkers associated with PPF in patients with IIM-ILD. Methods: We retrospectively reviewed 54 consecutive patients diagnosed with IIM-ILD between January 2018 and December 2023. Patients were categorized as having PPF or not based on 2022 ATS/ERS/JRS/ALAT guideline criteria within 1 year after the diagnosis of IIM-ILD. Lung-specific macromolecules and systemic inflammatory and nutritional indices were calculated using laboratory data obtained at the initial evaluation. These included “Krebs von den Lungen-6” (KL-6), surfactant protein-D, C-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), aggregate index of systemic inflammation (AISI), fibrosis-4 index, prognostic nutritional index, and geriatric nutritional risk index. Receiver operating characteristic curve analysis was used to determine optimal cutoff values, and logistic regression analyses were performed to identify factors associated with PPF. Results: Out of the 54 patients, 32 were classified as having PPF and 22 as not having PPF. The PPF group showed significantly lower hemoglobin levels and significantly higher platelet counts, neutrophil counts, C-reactive protein, and serum KL-6 levels than the non-PPF group. Several systemic inflammatory indices, including CAR, NLR, MLR, PLR, SII, SIRI, and AISI, were significantly higher in the PPF group. AISI showed the highest discriminative ability among the evaluated biomarkers, with an area under the curve of 0.786 and an optimal cutoff value of 278. In multivariable logistic regression analysis, serum KL-6 ≥626 U/mL and AISI ≥278 were independently associated with PPF, with adjusted odds ratios of 6.480 (95% confidence interval [CI]: 1.440–29.200; p = 0.015) and 9.940 (95% CI: 2.260–43.600; p = 0.002), respectively. Conclusions: AISI and serum KL-6 may serve as accessible, non-invasive blood-based biomarkers associated with fibrotic progression in patients with IIM-ILD.
SN - 1828-695X
SN - 2049-6958
ER -