Glycoprotein YKL-40 Levels in Plasma Are Associated with Fibrotic Changes on HRCT in Asbestos-Exposed Subjects

Our plain-English summary of Glycoprotein YKL-40 Levels in Plasma Are Associated with Fibrotic Changes on HRCT in Asbestos-Exposed Subjects, by T. Väänänen, L. Lehtimäki, K. Vuolteenaho, et al (Mediators of Inflammation, 2017).

The study

• Authors: T. Väänänen, L. Lehtimäki, K. Vuolteenaho, M. Hämäläinen, P. Oksa, T. Vierikko, R. Järvenpää, J. Uitti, H. Kankaanranta, E. Moilanen
• Journal: Mediators of Inflammation
• Published: 2017;2017:1797512
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

YKL-40 is a chitinase-like glycoprotein produced by alternatively activated macrophages that are associated with wound healing and fibrosis. Asbestosis is a chronic asbestos-induced lung disease, in which injury of epithelial cells and activation of alveolar macrophages lead to enhanced collagen production and fibrosis. We studied if YKL-40 is related to inflammation, fibrosis, and/or lung function in subjects exposed to asbestosis. Venous blood samples were collected from 85 men with moderate or heavy occupational asbestos exposure and from 28 healthy, age-matched controls. Levels of plasma YKL-40, CRP, IL-6, adipsin, and MMP-9 were measured with enzyme-linked immunosorbent assay (ELISA). Plasma YKL-40 levels were significantly higher in subjects with asbestosis (n = 19) than in those with no fibrotic findings in HRCT following asbestos exposure (n = 66) or in unexposed healthy controls. In asbestos-exposed subjects, plasma YKL-40 correlated negatively with lung function capacity parameters FVC (Pearson's r -0.259, p = 0.018) and FEV1 (Pearson's r -0.240, p = 0.028) and positively with CRP (Spearman's rho 0.371, p < 0.001), IL-6 (Spearman's rho 0.314, p = 0.003), adipsin (Spearman's rho 0.459, p < 0.001), and MMP-9 (Spearman's rho 0.243, p = 0.025). The present finding suggests YKL-40 as a biomarker associated with fibrosis and inflammation in asbestos-exposed subjects.

In plain English

This Finnish study measured a blood protein called YKL-40 in men with a history of moderate or heavy occupational asbestos exposure, followed at the Clinic of Occupational Medicine at Tampere University Hospital. The article did not name fiber types. After exclusions, 85 exposed men remained. Of these, 66 had normal or only borderline findings on high-resolution CT (HRCT) of the chest, and 19 had fibrosis in both lungs, that is, asbestosis. They were compared with 28 healthy unexposed men. Median plasma YKL-40 was 64.4 ng/ml in the asbestosis group. That was higher than in exposed men without asbestosis (36.4 ng/ml, p = 0.033) and in controls (32.8 ng/ml, p = 0.008). Among the 85 exposed men, higher YKL-40 went with lower lung capacity (FVC and FEV1). It also went with higher inflammation markers (CRP, IL-6) and fibrosis markers (adipsin, MMP-9). The authors concluded that YKL-40 could be a potential new biomarker for fibrosis and inflammation in asbestosis. They noted that the asbestosis cases were mostly mild, and that experimental studies are needed to confirm whether the correlations reflect cause and effect.

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: Clinical study comparing blood biomarker levels between asbestos-exposed men with and without asbestosis on HRCT and healthy unexposed controls, with correlation analyses
• Who was studied: 118 men with known moderate or heavy occupational asbestos exposure, followed at the Clinic of Occupational Medicine, Tampere University Hospital, Finland. All were nonsmokers or had quit over five years earlier. 33 were excluded (asthma or asthma medication, FEV1/FVC below 0.7, or bronchiectasis or emphysema on HRCT). That left 85 exposed men: 66 with HRCT class 0 to 1 (no fibrosis) and 19 with HRCT classes 2 to 5 (asbestosis). There were also 28 healthy nonsmoking unexposed men recruited from the community. Study dates were not given.
• Exposure: Moderate or heavy occupational asbestos exposure. Fiber types, jobs and doses were not specified. Mean time since the beginning of exposure was 43.6 years in exposed men without fibrosis and 46.2 years in men with asbestosis (p = 0.464).
• Main results:
  • Median plasma YKL-40 by group: men with asbestosis 64.4 ng/ml (IQR 35.1 to 138.1). Asbestos-exposed men without asbestosis 36.4 ng/ml (27.3 to 76.7), p = 0.033 versus asbestosis. Unexposed controls 32.8 ng/ml (23.5 to 59.3), p = 0.008 versus asbestosis. The difference between exposed men without fibrosis and controls was shown as not significant.
  • Among 53 exposed men with HRCT fibrotic change scores from 0.5 to 4, YKL-40 correlated positively with the degree of change (rho 0.392, p = 0.005).
  • In the 85 asbestos-exposed men, YKL-40 correlated negatively with FVC (r -0.259, p = 0.018) and FEV1 (r -0.240, p = 0.028). Its correlation with diffusing capacity (DL,CO) was r 0.127, p = 0.246.
  • In the 85 asbestos-exposed men, YKL-40 correlated positively with CRP (rho 0.371, p less than 0.001), IL-6 (rho 0.314, p = 0.003) and adipsin (rho 0.459, p less than 0.001).
  • In the 85 asbestos-exposed men, YKL-40 also correlated positively with MMP-9 (rho 0.243, p = 0.025).
  • Compared with exposed men without HRCT findings, men with asbestosis had 18% lower diffusing capacity for carbon monoxide (87.1 vs 106.4 % predicted, p less than 0.001). FVC and FEV1 did not differ between these groups.
  • Adipsin was higher in men with asbestosis than in exposed men without fibrosis (median 1022 vs 893 ng/ml, p = 0.004). So was MMP-9 (54.7 vs 28.1 ng/ml, p less than 0.001).
  • Men with asbestosis were older than exposed men without fibrosis (mean 68.5 vs 64.5 years, p = 0.015). YKL-40 did not correlate with age (r 0.102, p = 0.355).
• The authors' conclusion: The authors concluded that YKL-40 could be a potential novel biomarker for fibrosis and inflammation in asbestosis.
• Limitations the authors state:
  • On average, the men with asbestosis had mild disease with well-preserved lung function and had not developed severe restrictive lung function. The authors regarded this as a limitation.
  • The authors stated that additional experimental studies are needed to confirm whether the observed correlations reflect causality.

Topics

Medical terms in this study, explained in our Lexicon: Glycoprotein, High-Resolution CT (HRCT), Macrophage, Fibrosis, Alveolar Macrophage, Collagen, Inflammation, Asbestos Exposure.

Related studies

• Pulmonary inflammation in asbestos-exposed subjects with borderline parenchymal changes on HRCT — L. Lehtimäki, P. Oksa, et al. (2010)
• Increased alveolar nitric oxide concentration and high levels of leukotriene B(4) and 8-isoprostane in exhaled breath condensate in patients with asbestosis — H. Lehtonen, P. Oksa, et al. (2007)
• Adipokine adipsin is associated with the degree of lung fibrosis in asbestos-exposed workers — S. Leivo-Korpela, L. Lehtimäki, et al. (2012)
• Genetic susceptibility to asbestos-related fibrotic pleuropulmonary changes — M.K. Kukkonen, S. Hämäläinen, et al. (2011)
• Multiwalled carbon nanotube-induced pulmonary inflammatory and fibrotic responses and genomic changes following aspiration exposure in mice: A 1-year postexposure study — B.N. Snyder-Talkington, C. Dong, et al. (2016)
• Decline in annual lung function in workers exposed to asbestos with and without pre-existing fibrotic changes on chest radiography — T. Nakadate (1995)

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