Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals

Our plain-English summary of Prediction of pneumoconiosis by serum and urinary biomarkers in workers exposed to asbestos-contaminated minerals, by H.Y. Yang (PloS One, 2019).

The study

• Author: H.Y. Yang
• Journal: PloS One
• Published: 2019;14(4):e0214808
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Workers processing nephrite, antigorite, or talc may be exposed to paragenetic asbestos minerals. An effective screening method for pneumoconiosis in workers exposed to asbestos-contaminated minerals is still lacking. The objective of this study was to assess the diagnostic accuracy of serum and urinary biomarkers for pneumoconiosis in workers exposed to asbestos-contaminated minerals. We conducted a case-control study in a cohort of stone craft workers in Hualien, where asbestos, nephrite, antigorite, and talc are produced. A total of 140 subjects were screened between March 2013 and July 2014. All subjects received a questionnaire survey and a health examination that included a physical examination; chest X-ray; and tests for standard pulmonary function, fractional exhaled nitric oxide, serum soluble mesothelin-related peptide (SMRP), fibulin-3, carcinoembryonic antigen (CEA), and urinary 8-Oxo-2'-deoxyguanosine (8-OHdG)/creatinine. After excluding subjects with uraemia and chronic obstructive pulmonary disease (COPD), we included 48 subjects with pneumoconiosis and 90 control subjects without pneumoconiosis for analysis. In terms of occupational history, 43/48 (90%) case subjects and 68% (61/90) of the control subjects had processed asbestos-contaminated minerals, including nephrite, antigorite, and talc. The case group had decreased pulmonary function in forced vital capacity (FVC), forced expiratory volume in one second, and forced expiratory flow between 25% and 75% of the FVC. The levels of SMRP, fibulin-3, urinary 8-OHdG/creatinine, and CEA were higher in the case group than in the control group. Subjects exposed to nephrite had significantly higher SMRP levels (0.84 ± 0.52 nM) than subjects exposed to other types of minerals (0.60 ± 0.30 nM). A dose-response relationship was observed between the SMRP level and the severity of pneumoconiosis. Machine learning algorithms, including variables of sex, age, SMRP, fibulin-3, CEA, and 8-OHdG/creatinine, can predict pneumoconiosis with high accuracy. The areas under the receiver operating characteristic curves ranged from 0.7 to 1.0. We suggest that SMRP and fibulin-3 could be used as biomarkers of pneumoconiosis in workers exposed to asbestos-contaminated minerals.

In plain English

This case-control study examined stone workers in Hualien, Taiwan, an area producing nephrite, antigorite and talc, where chrysotile, tremolite and actinolite asbestos were once produced. Of 140 workers screened in 2013 and 2014, 138 were analysed: 48 with pneumoconiosis diagnosed from chest X-rays and clinical findings, and 90 without. Processing asbestos-contaminated minerals was reported by 43 of 48 cases and 61 of 90 controls. The author measured blood SMRP, fibulin-3 and CEA and urinary 8-OHdG. The text says these were higher in cases, but the table's differences were not statistically significant (SMRP 0.7 versus 0.68 nM, p 0.89). Nephrite workers had higher SMRP than workers with other minerals (0.84 versus 0.60 nM, one-tailed p 0.04). Comparing 27 never-smoking cases with 27 age-matched controls, fibulin-3 was higher in cases (41.07 versus 16.67 ng/mL, p less than 0.05), while SMRP did not differ significantly. Models combining sex, age and the four biomarkers had areas under the curve of 0.7 to 1.0. The author concluded these biomarkers could help screen such workers, while noting that models cannot replace a clinical workup.

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 within a health surveillance cohort of stone workers, assessing the diagnostic accuracy of biomarkers and machine-learning prediction models
• Who was studied: Stone workers in Hualien, Taiwan, recruited from a health surveillance programme between March 2013 and July 2014. Of 140 screened, 138 were analysed after excluding one worker with uraemia and one with COPD: 48 with pneumoconiosis (cases) and 90 without (controls).
• Exposure: Occupational processing of nephrite, antigorite and talc, described as possibly containing paragenetic asbestos. The area also produced chrysotile, tremolite and actinolite asbestos between 1938 and 1985. 43 of 48 cases (90%) and 61 of 90 controls (68%) had processed these asbestos-contaminated minerals. No fiber measurements were reported in this study.
• Main results:
  • In Table 1, mean serum SMRP was 0.7 nM (SD 0.6) in the case group and 0.68 nM (SD 0.6) in the control group (p 0.89). The text nonetheless states that SMRP, fibulin-3, CEA and urinary 8-OHdG were higher in cases.
  • In Table 1, mean fibulin-3 was 29.4 ng/mL (SD 35.4) in cases and 23.5 ng/mL (SD 30.4) in controls (p 0.30). CEA was 1.5 versus 1.2 ng/mL (p 0.32). Urinary 8-OHdG/creatinine was 185.1 versus 133.1 ng/mg (p 0.37).
  • Workers exposed to nephrite had mean SMRP of 0.84 nM (SD 0.52), compared with 0.60 nM (SD 0.30) in workers exposed to other minerals (one-tailed Wilcoxon p = 0.04).
  • Mean fibulin-3 was 35.4 ng/mL (SD 44.4) in workers exposed to nephrite and 24.1 ng/mL (SD 30.4) in workers exposed to other minerals (one-tailed Wilcoxon p = 0.12).
  • After excluding current and former smokers and matching for age within 5 years, mean SMRP was 0.63 nM (SD 0.63) in 27 cases and 0.41 nM (SD 0.57) in 27 controls (p = 0.18).
  • In the same smoking-excluded, age-matched comparison, mean fibulin-3 was 41.07 ng/mL (SD 38.28) in cases and 16.67 ng/mL (SD 22.06) in controls (p less than 0.05).
  • Cases had lower FVC (85.3% versus 94.7% of predicted, p less than 0.01) and lower FEV1 (87.1% versus 95.4%, p less than 0.01) than controls. FEF25-75 was 83.3% in cases versus 86.7% in controls (p 0.44).
  • The author reported a dose-response relationship between SMRP level and pneumoconiosis severity, graded by X-ray profusion, restrictive lung function and audible crackles. This was shown in a figure; no numbers were given in the text.
  • Six machine-learning models using sex, age, SMRP, fibulin-3, CEA and 8-OHdG/creatinine had areas under the receiver operating characteristic curve ranging from 0.7 to 1.0.
  • A single test of exhaled nitric oxide, FEV1 or FVC did not predict pneumoconiosis.
  • No cases of malignant pleural mesothelioma were found among those screened.
• The authors' conclusion: The author concluded that SMRP and fibulin-3 were increased in workers with pneumoconiosis, suggesting possible asbestos exposure. The author also concluded that a combination of serum SMRP, fibulin-3, CEA and urinary 8-OHdG can be used in health examinations to screen for pneumoconiosis in workers exposed to asbestos-contaminated minerals.
• Limitations the authors state:
  • The case group had a higher proportion of current smokers (35.4% versus 15.7%).
  • CEA and 8-OHdG are not specific to dust exposure and should not be used alone to predict pneumoconiosis.
  • Machine learning emphasizes prediction, and the relationships between the variables may not be well understood.
  • Laboratory data and statistical modelling cannot replace a clinical workup.
  • Lung function testing alone had low predictive accuracy because most cases were at an early stage without clinical symptoms.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Talc and vermiculite.

Medical terms in this study, explained in our Lexicon: Pneumoconiosis, Biomarker, Antigorite, Talc, Asbestos, Case-Control Study, Chest X-Ray, Mesothelin.

Related studies

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• HMGB1 and Its Hyperacetylated Isoform are Sensitive and Specific Serum Biomarkers to Detect Asbestos Exposure and to Identify Mesothelioma Patients — A. Napolitano, D.J. Antoine, et al. (2016)
• Quantitative x ray microanalysis of pulmonary mineral particles in a patient with pneumoconiosis and two primary lung tumours — S. Anttila, S. Sutinen, et al. (1984)
• 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 — C. Xue, N. Wu, et al. (2017)
• An epidemiologic study of a group of talc workers — J.F. Gamble, W. Fellner, et al. (1979)
• Sensitivity of urinary mesothelin in patients with malignant mesothelioma — J. Creaney, A.W. Musk, et al. (2010)

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