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Could the significantly increased risk of rheumatoid arthritis reported in Italian male steel workers be explained by occupational exposure to cadmium?
Journal of Occupational Medicine and Toxicologyvolume 11, Article number: 21 (2016)
Multiple chronic disease risks have been identified in Italian furnace workers. A range of potential toxins have been identified in foundry dust. We suggest that the heavy metal cadmium (Cd) plays an important role in the development of chronic diseases, notably rheumatoid arthrits, and propose that research into the mechanism of action be undertaken to discover the aetiology of this link.
We read with interest by Cappelletti et al. “Health status of male steel workers at an electric arc furnace in Trentino, Italy ”. The authors demonstrated significantly increased disease risk; specifically, rheumatoid arthritis (RA), hypertension and cardiovascular diseases in exposed workers. The relative risk for RA was observed to be 6.18 (95 % confidence interval (CI) 2.00–19.02, p = 0.013). Cappelletti et al. also observed that the foundry dust studied contained iron, aluminum, zinc, manganese, lead, chromium, nickel, cadmium, mercury, arsenic, polycyclic aromatic hydrocarbons, polychlorinated biphenyls and dioxins. Therefore a number of potential toxins may have contributed to the high risk of RA development. We suggest here that cadmium inhalation is a plausible trigger for RA.
Cadmium has been demonstrated to be consistently and significantly raised in steel workers . There is an emerging literature to suggest that male RA is associated with a number of occupations associated with cadmium exposure . These include underground mining work (odds ratio (OR) 8.47 (95 % CI 2.59 to 27.66), bricklaying and working with concrete (OR: 2.6, 95 % CI: 1.3–4.9), working with electrics and electronics (OR: 1.8, 95 % CI: 1.0–3), workers exposed to mineral oils (relative risk (RR): 1.4, 95 % CI: 1.0–2.02), workers exposed to hydraulic oils (RR: 1.7, 95 % CI: 1.1–2.6), asphalters (OR: 14.0, 95 % CI 1.2–799.0), and conductors, freight and transport workers (OR: 4.7, 95 % CI 1.4–16.3). Further studies demonstrate a link with smelting and working in metal foundries (OR 2.8, 95 % confidence interval (CI): 1.0–7.4) .
Cadmium is inhaled in the work place either as a dust or a fume and is associated with chronic obstructive pulmonary disease (COPD) . It has been suggested that RA is initiated in the lung via the inflammatory process citrullination which involves post-translational changes to proteins and peptides resulting in loss of immune tolerance . Interestingly RA is associates with COPD independent of cigarette smoking. Four retrospective cohort studies with 32,675 RA patients and 122,204 controls were analysed. The pooled risk ratio of incident COPD in patients with RA versus control was 1.99 (95 % CI, 1.61–2.45) . Male RA is strongly associated with smoking which is the most important environmental cause of raised bodily cadmium levels . Moreover, in non-smoking RA patients, hair cadmium levels are consistent with occupational exposure to cadmium (raised 3-fold compared to controls) .
Clear associations between chronic disease and occupations with cadmium inhalation as described by Cappelletti et al.  and others [3–5] have been demonstrated. Further epidemiological work related to occupational cadmium exposure and disease development, particularly with regard to RA, is required to modify behaviour influencing development of future chronic disease.
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chronic obstructive pulmonary disease
Cappelletti R, Ceppi M, Claudatus J, Gennaro V. Health status of male steel workers at an electric arc furnace (EAF) in Trentino, Italy. J Occup Med Toxicol. 2016;11:7.
Afridi HI, Kazi TG, Jamali MK, Kazi GH, Arain MB, Jalbani N, Shar GQ, Sarfaraz RA. Evaluation of toxic metals in biological samples (scalp hair, blood and urine) of steel mill workers by electrothermal atomic absorption spectrometry. Toxicol Ind Health. 2006;22(9):381–93.
Hutchinson D. Cadmium, one of the villains behind the curtain: has exposure to cadmium helped to pull the strings of seropositive rheumatoid arthritis pathogenesis all along? Int J Rheum Dis. 2015;18(5):570–3.
Ilar A, Wiebert P, Klareskog L, Alfredsson L, Bengtsson C. Occupation and risk of developing rheumatoid arthritis. In: American College of Rheumatology Meeting Abstracts number:2016. 2014. http://acrabstracts.org/abstract/occupation-and-risk-of-developing-rheumatoid-arthritis/accessed 4th March 2016.
Davison AG, Fayers PM, Taylor AJ, Venables KM, Darbyshire J, Pickering CA, Chettle DR, Franklin D, Guthrie CJ, Scott MC, et al. Cadmium fume inhalation and emphysema. Lancet. 1988;1(8587):663–7.
Perry E, Kelly C, Eggleton P, De Soyza A, Hutchinson D. The lung in ACPA-positive rheumatoid arthritis: an initiating site of injury? Rheumatology. 2014;53(11):1940–50.
Ungprasert P, Srivali N, Cheungpasitporn W, Davis Iii JM. Risk of incident chronic obstructive pulmonary disease in patients with rheumatoid arthritis: A systematic review and meta-analysis. Joint Bone Spine. 2015. doi: 10.1016/j.jbspin.2015.05.016. [Epub ahead of print].
Afridi HI, Kazi TG, Brabazon D, Naher S. Interaction between zinc, cadmium, and lead in scalp hair samples of Pakistani and Irish smokers rheumatoid arthritis subjects in relation to controls. Biol Trace Elem Res. 2012;148(2):139–47.
General funding for research in the area of occupational related exposures of rheumatoid arthritis provided to the authors by Cornwall Arthritis Trust. The funding organisation had no involvement in the preparation of this commentary.
Charity contact: Cornwall Arthritis Trust, c/o Mr Peter Cloke, Duke of Cornwall Department, Royal Cornwall Hospital, Truro, Cornwall, TR1 3LJ.
The authors declare they have no competing interests. The authors confirm that all authors have approved the manuscript for submission. The content of this manuscript has not been published or submitted for publication elsewhere. Support for research by ourselves into occupational triggers of rheumatoid arthritis has been provided by the Cornwall Arthritis Trust.
DH- original conception. DM- re-drafting, final submission. All authors read and approved the final manuscript.