Radiographic evidence of pulmonary fibrosis and possible etiologic factors at a nickel refinery in Norway

Our plain-English summary of Radiographic evidence of pulmonary fibrosis and possible etiologic factors at a nickel refinery in Norway, by S.R. Berge, K. Skyberg (Journal of Environmental Monitoring, 2003).

The study

• Authors: S.R. Berge, K. Skyberg
• Journal: Journal of Environmental Monitoring
• Published: 2003;5(4):681-8
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Animal studies have shown that nickel compounds may induce pulmonary fibrosis, but so far only limited documentation in humans has been available. Radiographs of 1046 workers in a nickel refinery in Norway were read blindly and independently by three NIOSH certified B-readers, according to the ILO standards. Pulmonary fibrosis (PF) was defined as a median reading of ILO score > or = 1/0 and following this criterion, 47 cases (4.5%) were identified. In logistic regression models, controlling for age and smoking, there was evidence of increased risk of PF with cumulative exposure to soluble nickel or sulfidic nickel (p = 0.04 for both). For metallic nickel a p-value of 0.07 was found. For soluble nickel there was a dose-response trend for 4 categories of cumulated exposure. In the group with the highest cumulative exposure to soluble nickel (low exposure as reference), the crude odds ratio for PF was 4.34 (95% CI 1.75-10.77). The risk adjusted for age, smoking, asbestos and sulfidic nickel was 2.24 (0.82-6.16), with a dose-response trend. The corresponding figures for sulfidic nickel were 5.06 (1.70-15.09, crude) and 2.04 (0.54-7.70, adjusted for age, smoking, asbestos and soluble nickel). However, the dose-response trend was less clear for sulfidic nickel. Controlling for estimated asbestos exposure at the refinery tended to increase the odds ratios of soluble and sulfidic nickel. This study indicates that in addition to age and smoking exposure to soluble and sulfidic nickel compounds are risk factors of PF in humans. Since the number of cases identified in this study is small and undetected confounders may have been present, further studies in other cohorts are appropriate.

In plain English

The authors examined chest X-rays, taken between 1989 and 1996, of 1046 male present and retired workers at a nickel refinery in Kristiansand, Norway. Three certified B-readers scored each film blind using the ILO system. A worker counted as a case of pulmonary fibrosis (lung scarring) if at least two readers scored 1/0 or higher. Each worker's exposure to four forms of nickel, to asbestos (never measured, and estimated from years in departments where it was used), and to tobacco was estimated. There were 47 cases (4.5%). Allowing for age and smoking, cumulative exposure to soluble nickel and to sulfidic nickel were each significantly associated with fibrosis (p equal to 0.04). The refinery asbestos score was not. Longer work in asbestos departments was associated with pleural plaques. The authors concluded that soluble and sulfidic nickel are risk factors for pulmonary fibrosis. They noted the small number of cases, possible undetected confounders, and variation between readers that was not negligible. They also noted that asbestos exposure outside the plant could not be taken into account.

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: Cross-sectional study of the most recent chest X-rays in a refinery workforce, scored blind by three B-readers, with prevalence odds ratios from logistic regression
• Who was studied: 1046 male present (767) and retired (279) employees of a nickel refinery in Kristiansand, Norway. Each had at least one year of employment before May 1, 1994 and an X-ray taken between June 1, 1989 and November 1, 1996.
• Exposure: Cumulative exposure, from a job-exposure matrix, to four nickel species: metallic, soluble (mainly nickel sulfate and nickel chloride), sulfidic and oxidic. Asbestos (fiber type not stated) was never measured. It was estimated as years worked in departments graded as having asbestos exposure (roasting, smelting and maintenance). Cumulative tobacco consumption was also estimated.
• Main results:
  • 47 of the 1046 refinery workers (4.5%) met the case definition for pulmonary fibrosis.
  • Fibrosis was mostly moderate: the median ILO score exceeded 1/1 for only 6 of the cases.
  • In models controlling for age and smoking, cumulative exposure to soluble nickel and to sulfidic nickel were each significantly associated with pulmonary fibrosis (p 0.04 for each).
  • The estimated refinery asbestos score, total nickel, metallic nickel (p 0.07) and oxidic nickel were not significantly associated with being a case.
  • Highest versus lowest soluble nickel category: crude odds ratio for pulmonary fibrosis 4.34 (95% CI 1.75–10.77).
  • Soluble nickel, highest category: odds ratio 2.60 (0.97–7.00) adjusted for age, smoking and asbestos. It was 2.24 (0.82–6.16) when also adjusted for sulfidic nickel (Table 5).
  • In a later model with a different lowest reference category, the highest soluble nickel category had an odds ratio of 4.35 (1.17–16.22), adjusted for age, tobacco, asbestos and sulfidic nickel.
  • Highest versus lowest sulfidic nickel category: crude odds ratio 5.06 (1.70–15.09).
  • Sulfidic nickel, highest category: odds ratio 2.95 (0.87–10.07) adjusted for age, smoking and asbestos. It was 2.04 (0.54–7.70) when also adjusted for soluble nickel (Table 6).
  • Age at X-ray and total tobacco smoked were each independently associated with pulmonary fibrosis.
  • Among the refinery workers, 74 had unilateral pleural plaques and 60 had bilateral pleural plaques, as described by at least two readers.
  • Pleural plaques, adjusted for smoking and age: odds ratio 2.96 (1.84–4.79) for workers with more than 12 years in departments where asbestos had been used, compared with unexposed workers. The odds ratio was 1.05 (1.03–1.07) per year of asbestos-exposed work.
  • Adjusting for asbestos tended to slightly increase the risk estimates for pulmonary fibrosis linked to soluble, sulfidic and metallic nickel.
  • 83% of the pulmonary fibrosis cases did not show bilateral pleural plaques.
  • The three readers classified 12.2%, 3.2% and 5.2% of the refinery workers as cases. Agreement between readers (kappa 0.27 to 0.40) was described as fair.
• The authors' conclusion: The authors concluded that this study and experimental data both indicate soluble and sulfidic nickel are risk factors for pulmonary fibrosis. They added that metallic nickel might also be a risk factor.
• Limitations the authors state:
  • The number of cases was small and undetected confounders may have been present.
  • Workers who left without a pension, or who died before July 1989, were not included. The authors said this selection could lead to underestimating the risk.
  • Asbestos fibers were not measured at the workplace, and asbestos exposure from work outside the plant could not be taken into account.
  • Variation between the three readers was not negligible.
  • The categorical models were sensitive to the choice of exposure intervals, and confidence intervals were wide.
  • No lung function tests were done to compare with the X-ray findings.

Topics

Medical terms in this study, explained in our Lexicon: Pulmonary Fibrosis, NIOSH, B-Reader, ILO Classification, Cumulative Exposure, P-Value, Dose-response relationship, Odds Ratio.

Related studies

• Can lung cancer risk among nickel refinery workers be explained by occupational exposures other than nickel? — T.K. Grimsrud, S.R. Berge, et al. (2005)
• Interaction of asbestos, age, and cigarette smoking in producing radiographic evidence of diffuse pulmonary fibrosis — K.H. Kilburn, R. Lilis, et al. (1986)
• Chrysotile dissolution in the rhizosphere of the nickel hyperaccumulator Leptoplax emarginata — V. Chardot-Jacques, C. Calvaruso, et al. (2013)
• Radiographic abnormalities in asbestos insulators: effects of duration from onset of exposure and smoking. Relationships of dyspnea with parenchymal and pleural fibrosis — R. Lilis, A. Miller, et al. (1991)
• Distribution of transforming growth factor-beta 1, fibronectin, and smooth muscle actin in asbestos-induced pulmonary fibrosis in rats — T.D. Perdue, A.R. Brody (1994)
• Alveolar macrophage cytokine and growth factor production in a rat model of crocidolite-induced pulmonary inflammation and fibrosis — K.E. Driscoll, J.K. Maurer, et al. (1995)

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