Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion

Our plain-English summary of Significance of secretory leukocyte peptidase inhibitor in pleural fluid for the diagnosis of benign asbestos pleural effusion, by T. Kishimoto, Y. Kojima, N. Fujimoto (Scientific Reports, 2021).

The study

• Authors: T. Kishimoto, Y. Kojima, N. Fujimoto
• Journal: Scientific Reports
• Published: 2021;11(1):12965
• Cited by: 2 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Secretory leukocyte peptidase inhibitor (SLPI) is a biomarker present in the respiratory tract that protects against tissue destruction and aids in wound healing. We examined whether SLPI in pleural effusion can be used to distinguish benign asbestos pleural effusion (BAPE) from early-stage malignant pleural mesothelioma (MPM) and other diseases. We measured the levels of SLPI, hyaluronic acid (HA), soluble mesothelin-related peptides (SMRP), CCL2, galectin-3, and CYFRA21-1 in 51 patients with BAPE, 37 patients with early-stage MPM, 77 patients with pleural effusions due to non-small-cell lung cancer (LCa), and 74 patients with other pleural effusions. SLPI levels in the pleural fluid of patients with BAPE were significantly lower than those in patients with MPM, LCa, and other pleural effusions (p < 0.0001). The area under the curve (AUC) for SLPI's ability to distinguish BAPE from MPM was 0.902, with a sensitivity of 82.4% and a specificity of 86.5%. This AUC was not only favourable but was better than the AUC for the ability of CYFRA21-1 to distinguish BAPE (0.853). The combination of SLPI and CYFRA21-1 achieved an AUC of 0.965 for the differentiation between BAPE and MPM. Pleural fluid SLPI as well as CYFRA21-1 and HA is useful as a biomarker to diagnose BAPE, which needs to be distinguished from early-stage MPM.

In plain English

This study, from Okayama Rosai Hospital, Japan, examined whether a protein called secretory leukocyte peptidase inhibitor (SLPI) in the fluid around the lungs (pleural fluid) could help tell benign asbestos pleural effusion (BAPE) from early-stage malignant pleural mesothelioma (MPM). The authors analysed pleural fluid from 51 patients with BAPE, 37 with early-stage MPM, 77 with non-small-cell lung cancer, and 74 with heart failure or bacterial pleurisy, all diagnosed between 2015 and 2019. SLPI was 57.8 ng/mL in BAPE patients. This was significantly lower than in MPM (173.0 ng/mL), lung cancer (103.5 ng/mL) and other diseases (124.8 ng/mL). With a cut-off of 82.9 ng/mL, SLPI distinguished BAPE from MPM with a sensitivity of 82.4%, a specificity of 86.5% and an area under the curve (AUC; higher is better) of 0.902. For the same comparison, the AUCs were 0.853 for CYFRA21-1, 0.802 for hyaluronic acid, 0.746 for SMRP, 0.679 for galectin-3 and 0.652 for CCL2. Combining SLPI with CYFRA21-1 gave an AUC of 0.965. The authors proposed including SLPI, with CYFRA21-1, as a pleural fluid marker for this diagnosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic biomarker study comparing pleural fluid marker levels across patient groups, with ROC (receiver operating characteristic) curve analysis. The article does not state whether it was retrospective or prospective.
• Who was studied: Patients diagnosed at Okayama Rosai Hospital, Japan, between 2015 and 2019: 51 with BAPE; 37 with early-stage MPM (31 epithelial, six sarcoma-type); 77 with malignant pleural effusions due to non-small-cell lung cancer; 27 with heart failure; and 47 with bacterial pleurisy. The heart failure and bacterial pleurisy patients (74 in all) were grouped as "other".
• Exposure: BAPE was diagnosed in people with a history of occupational exposure to asbestos. The article reports no fiber types, jobs or doses. The study measured six substances in pleural fluid: SLPI, hyaluronic acid (HA), SMRP, CCL2, galectin-3 and CYFRA21-1.
• Main results:
  • Pleural fluid SLPI was 57.8 ± 25.7 ng/mL in BAPE patients. This was significantly lower than in MPM patients (173.0 ± 134.5 ng/mL, p less than 0.0001), lung cancer patients (103.5 ± 85.7 ng/mL, p less than 0.01) and patients with other diseases (124.8 ± 12.9 ng/mL, p less than 0.05).
  • For distinguishing BAPE from MPM, SLPI with a cut-off of 82.9 ng/mL had a sensitivity of 82.4%, a specificity of 86.5% and an AUC of 0.902.
  • For distinguishing BAPE from MPM, HA with a cut-off of 47.1 μg/mL had a sensitivity of 77.0%, a specificity of 75.0% and an AUC of 0.802.
  • For distinguishing BAPE from MPM, SMRP with a cut-off printed as 9.0 ng/mL had a sensitivity of 72.3%, a specificity of 71.4% and an AUC of 0.746.
  • For distinguishing BAPE from MPM, CYFRA21-1 with a cut-off of 37.3 (no unit given) had a sensitivity of 85.3% and a specificity printed as 70.3.
  • In the discussion, the authors summarised the AUCs for distinguishing BAPE from MPM: 0.902 for SLPI, compared with 0.853 for CYFRA21-1, 0.802 for HA and 0.746 for SMRP.
  • For distinguishing BAPE from MPM, CCL2 with a cut-off of 1.8 pg/mL had a sensitivity of 62.7%, a specificity of 44.4% and an AUC of 0.652.
  • For distinguishing BAPE from MPM, galectin-3 with a cut-off of 11.4 ng/mL had a sensitivity of 67.9%, a specificity of 59.5% and an AUC of 0.679.
  • Combining SLPI and CYFRA21-1 gave an AUC of 0.965 for distinguishing BAPE from early-stage MPM.
  • HA in pleural fluid was 38.7 ± 4.0 μg/mL in BAPE patients, significantly lower than in MPM patients (192.4 ± 40.4 μg/mL, p less than 0.01).
• The authors' conclusion: The authors concluded that SLPI levels in pleural fluid were significantly lower in BAPE than in MPM, lung cancer and other diseases. They proposed including SLPI, along with CYFRA21-1, as a pleural fluid marker for the differential diagnosis of early-stage MPM.
• Limitations the authors state:
  • The authors noted significant individual variation in CCL2 levels among mesothelioma patients, most of whom had the epithelial type. They said they intend to conduct a study with a larger sample size.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis, Pleural plaques and thickening.

Medical terms in this study, explained in our Lexicon: Benign Asbestos Pleural Effusion, Biomarker, Pleural Effusion, Pleural Mesothelioma, Hyaluronic Acid, Soluble Mesothelin-Related Peptides (SMRP), Lung Cancer.

Related studies

• Vascular endothelial growth factor in pleural fluid for differential diagnosis of benign and malignant origin and its clinical applications — A. Fiorelli, G. Vicidomini, et al. (2011)
• Utility of hyaluronic acid in pleural fluid for differential diagnosis of pleural effusions: likelihood ratios for malignant mesothelioma — S. Atagi, M. Ogawara, et al. (1997)
• Diagnostic usefulness of tumour marker levels in pleural effusions of malignant and benign origin — F. Kuralay, Z. Tokgöz, et al. (2000)
• Retrospective investigation on diagnostic process for benign asbestos pleural effusion (BAPE) using checklist — T. Kishimoto, N. Fujimoto, et al. (2020)
• Diagnostic value of total and differential leukocyte counts in pleural effusions — T. Pettersson, H. Riska (1981)
• Benign asbestos pleural effusion: diagnosis and course — B.W. Robinson, A.W. Musk (1981)

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