Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case-control study

Our plain-English summary of Serum concentrations of Krebs von den Lungen-6, surfactant protein D, and matrix metalloproteinase-2 as diagnostic biomarkers in patients with asbestosis and silicosis: a case-control study, by C. Xue, N. Wu, X. Li, et al (BMC Pulmonary Medicine, 2017).

The study

• Authors: C. Xue, N. Wu, X. Li, M. Qiu, X. Du, Q. Ye
• Journal: BMC Pulmonary Medicine
• Published: 2017;17(1):144
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Asbestosis and silicosis are progressive pneumoconioses characterized by interstitial fibrosis following exposure to asbestos or silica dust. We evaluated the potential diagnostic biomarkers for these diseases.

Methods: The serum concentrations of Krebs von den Lungen-6 (KL-6), surfactant protein D (SP-D), and matrix metalloproteinase-2 (MMP-2), MMP-7, and MMP-9 were measured in 43 patients with asbestosis, 45 patients with silicosis, 40 dust-exposed workers (DEWs) without pneumoconiosis, and 45 healthy controls (HCs). Chest high-resolution computed tomography (HRCT) images were reviewed by experts blinded to the clinical data. According to the receiver operating characteristic (ROC) curve, the ideal level of each biomarker and its diagnostic sensitivity were obtained.

Results: The serum KL-6 and MMP-2 concentrations were highest in patients with asbestosis, particularly in comparison with those in DEWs and HCs (P<0.05). The serum SP-D concentration was significantly higher in patients with asbestosis than in patients with silicosis, DEWs, and HCs (P<0.01), whereas no significant difference was noted among patients with silicosis, DEWs, and HCs. No significant difference in the serum MMP-7 or -9 concentration was found among patients with asbestosis, patients with silicosis, DEWs, or HCs. Among patients with asbestosis, the serum KL-6 concentration was significantly correlated with the lung fibrosis scores on HRCT and negatively correlated with the forced vital capacity (FVC) % predicted and diffusing capacity of the lung for carbon monoxide (DLCO) % predicted. The serum SP-D and MMP-2 concentrations were negatively correlated with the DLCO % predicted (all P<0.05). The order of diagnostic accuracy according to the ROC curve was KL-6, SP-D, and MMP-2 in patients with asbestosis alone and in the combination of both patients with asbestosis and those with silicosis. The combination of all three biomarkers may increase the possibility of diagnosing asbestosis (sensitivity, 93%; specificity, 57%) and both asbestosis and silicosis (sensitivity, 83%; specificity, 62%).

Conclusions: KL-6, SP-D, and MMP-2 are available biomarkers for the adjuvant diagnosis of asbestosis and silicosis. The combination of all three biomarkers may improve the diagnostic sensitivity for asbestosis and silicosis.

In plain English

This case-control study, done at Beijing Chao-Yang Hospital in China from January 2015 to December 2016, measured five blood markers (KL-6, SP-D, MMP-2, MMP-7 and MMP-9). The people tested were 43 newly diagnosed asbestosis patients, 45 silicosis patients, 40 dust-exposed workers without pneumoconiosis and 45 healthy volunteers. The asbestosis patients had been exposed to chrysotile, mostly while making asbestos textiles or asbestos-based products. The silicosis patients had processed jade. KL-6 and MMP-2 were highest in the asbestosis group and differed significantly from the dust-exposed workers and healthy controls. SP-D was significantly higher in asbestosis patients than in all three other groups. MMP-7 and MMP-9 did not differ significantly among the groups. Among asbestosis patients, higher KL-6 was linked with higher CT fibrosis scores and lower lung function. KL-6 identified asbestosis best of the three markers (sensitivity 88.4%, specificity 73.1%). Combining KL-6, SP-D and MMP-2 gave 93% sensitivity but 57% specificity for asbestosis. The authors concluded that these three markers can support the diagnosis of asbestosis and silicosis. They noted they could not track the markers over time.

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: Case-control study comparing blood (serum) marker levels between patient groups and control groups
• Who was studied: 43 outpatients with newly diagnosed asbestosis, 45 with silicosis and 40 dust-exposed workers without pneumoconiosis, recruited at the Department of Occupational Medicine and Toxicology, Beijing Chao-Yang Hospital, January 2015 to December 2016. A fourth group was 45 age-, sex- and smoking-matched healthy volunteers.
• Exposure: The asbestosis patients had been exposed to chrysotile dust or fibers. Of these, 36 (83.7%) worked in manufacturing asbestos textiles or asbestos-based products, and 7 (16.3%) were exposed to asbestos products at work, such as heat insulation and boiler maintenance workers. The silicosis patients were exposed to silica dust while processing jade. Exposure was recorded only as years of exposure; there were no air measurements.
• Main results:
  • Serum KL-6 and MMP-2 were highest in the asbestosis patients (second highest in the silicosis patients) and differed significantly from the dust-exposed workers and healthy controls (P less than 0.05).
  • Serum SP-D was significantly higher in asbestosis patients than in silicosis patients, dust-exposed workers or healthy controls (P less than 0.01). There was no significant difference among the silicosis, dust-exposed worker and healthy control groups.
  • Serum MMP-7 and MMP-9 did not differ significantly among the four groups.
  • In the silicosis patients, KL-6, SP-D and MMP-2 did not differ significantly among the stages of silicosis (Stage I n=21, Stage II n=8, Stage III n=16).
  • Among asbestosis patients, serum KL-6 was positively correlated with lung fibrosis scores on HRCT and negatively correlated with FVC % predicted and DLCO % predicted.
  • Among asbestosis patients, serum SP-D and MMP-2 were negatively correlated with DLCO % predicted (P less than 0.05).
  • Distinguishing asbestosis patients from silicosis patients, dust-exposed workers and healthy controls: KL-6 had an area under the curve of 0.874 (95% CI 0.815-0.919) at a cut-off of 216 U/ml, with sensitivity 88.4% and specificity 73.1%. The areas for SP-D and MMP-2 were 0.757 and 0.641.
  • Combining all three markers gave sensitivity 93% and specificity 57% for diagnosing asbestosis. For diagnosing asbestosis and silicosis together, sensitivity was 83% and specificity 62%.
• The authors' conclusion: The authors concluded that KL-6, SP-D and MMP-2 are readily available biomarkers that can support (as an adjunct) the diagnosis of asbestosis and silicosis. They added that combining all three may improve sensitivity, and that further study is warranted.
• Limitations the authors state:
  • The authors could not monitor biomarker levels over time in each patient to follow how asbestosis and silicosis progressed.
  • The authors noted that other biomarkers may be effective for monitoring disease progression and prognosis.
  • There were no air measurements and no detailed information on how often each job involved exposure, so exposure was measured only as number of years.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Asbestosis.

Medical terms in this study, explained in our Lexicon: Biomarker, Silicosis, Case-Control Study, Interstitial Fibrosis, Pneumoconiosis, High-Resolution CT (HRCT), Fibrosis, Diffusing Capacity (DLCO).

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