Comment on “Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures”

Murphy, Daniel; Pay, James B.; Benham, Rebecca S.; James, Benjamin; Hutchinson, David

doi:10.1289/ehp730

Cited by 3 publications

(4 citation statements)

References 9 publications

(9 reference statements)

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“…Metal fumes from welding have been associated with increased RA risk amongst spouses of farmers [ 20 ]. We have previously suggested that heavy metal-laden particle inhalation may be an RA risk factor for farmers using pesticides and fertilisers [ 26 ]. Maneb and mancozeb fungicides are approximately 21% manganese by weight.…”

Section: Limitations Of Evidencementioning

confidence: 99%

“…Citrullination of proteins in the lungs, as found in the longevity-associated RA risk identified in cigarette smoke inhalation [ 24 ], could equally be applied to other inhalational exposures [ 25 ]. Such exposures predominantly relate to occupation in male populations, though evidence exists linking RA risk to female occupational inhalation, such as recently seen in textile workers [ 21 ] and inhalational exposures in the wider environment [ 20 , 22 , 25 , 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Is Male Rheumatoid Arthritis an Occupational Disease? A Review

Hutchinson

2017

TORJ

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Background:Rheumatoid arthritis (RA) is a systemic, inflammatory disease with an estimated global prevalence of 0.3–1.0%. An unexplained association exists between low formal education and the development of RA independent of smoking. It is established that RA is initiated in the lungs and that various occupations associated with dust, fume and metal inhalation can increase the risk of RA development.Objective:The objective of this review is to evaluate published clinical reports related to occupations associated with RA development. We highlight the concept of a “double-hit” phenomenon involving adsorption of toxic metals from cigarette smoke by dust residing in the lung as a result of various work exposures. We discuss the relevant pathophysiological consequences of these inhalational exposures in relation to RA associated autoantibody production.Method:A thorough literature search was performed using available databases including Pubmed, Embase, and Cochrane database to cover all relative reports, using combinations of keywords: rheumatoid arthritis, rheumatoid factor, anti-citrullinated peptide antibody silica, dust, fumes, metals, cadmium, cigarette smoking, asbestos, mining, bronchial associated lymphoid tissue, heat shock protein 70, and adsorption.Conclusion:We postulate that the inhalation of dust, metals and fumes is a significant trigger factor for RA development in male patients and that male RA should be considered an occupational disease. To the best of our knowledge, this is the first review of occupations as a risk factor for RA in relation to the potential underlying pathophysiology.

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Section: Limitations Of Evidencementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

Hutchinson

2017

TORJ

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“…Nitrates are commonly found in high-nitrogen fertilizers and have been linked to hypothyroidism (Aschebrook-Kilfoy et al, 2012), albeit inconsistently (Ward et al, 2010). This may also be related to exposure to heavy metal cadmium present in fertilizers, as suggested for association between chemical fertilizer and rheumatoid arthritis (Murphy et al, 2016; Parks et al, 2016). Elevated thyroid disease risk associated with grinding metals observed in our study further supports this hypothesis.…”

Section: Discussionmentioning

confidence: 94%

“…These fungicides are metabolized to an anti-thyroid compound ethylene-thiourea (classified as a probable carcinogen by the US EPA based on cancer data) which may bring about hypothyroid-like effects in humans and animals (Axelstad et al, 2011; Goldner et al, 2010; Mallem et al, 2006; Steenland et al, 1997). Another hypothesis is involvement of heavy metal manganese in pathogenesis of autoimmune thyroid conditions, as suggested for rheumatoid arthritis, also an autoimmune disease, in the AHS (Murphy et al, 2016; Parks et al, 2016). Chlorothalonil may alter thyroid gland pathophysiology in frogs and increase serum T4 in female rats, although the Endocrine Disruptor Screening Program (EDSP) report concluded no convincing evidence for chlorothalonil-thyroid-pathway interaction (U.S.…”

Section: Discussionmentioning

confidence: 99%

Incident thyroid disease in female spouses of private pesticide applicators

Shrestha

Parks

Goldner

et al. 2018

Environment International

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Farming tasks and the development of rheumatoid arthritis in the agricultural health study

Parks

Meyer²,

Freeman

et al. 2019

Occup Environ Med

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ObjectivesFarming has been associated with rheumatoid arthritis (RA). Some studies have evaluated the effects of pesticides, but other agricultural exposures may also affect immune response.MethodsWe investigated non-pesticide agricultural exposures in relation to RA in licensed pesticide applicators (n=27 175, mostly male farmers) and their spouses (n=22 231) in the Agricultural Health Study (AHS) cohort (1993–1997) who completed at least one follow-up survey through 2015. Incident RA cases (n=229 applicators and 249 spouses) were identified based on self-report confirmed by use of disease-modifying antirheumatic drugs or medical records. Hazard Ratios (HRs) and 95% Confidence Intervals (CIs) were estimated by Cox proportional hazard models adjusting for applicator status, state, smoking, education and specific pesticide use, allowing estimates to vary by median age when hazards assumptions were not met.ResultsOverall, RA was associated with regularly applying chemical fertilisers (HR=1.50; 95% CI 1.11 to 2.02), using non-gasoline solvents (HR=1.40; 95% CI 1.09 to 1.80), and painting (HR=1.26; 95% CI 1.00 to 1.59). In older applicators (>62 years), RA was associated with driving combines (HR=2.46; 95% CI 1.05 to 5.78) and milking cows (HR=2.56; 95% CI 1.01 to 6.53). In younger participants (≤62 years), RA was inversely associated with raising animals as well as crops (HR=0.68; 95% CI 0.51 to 0.89 vs crops only). Associations with specific crops varied by age: some (eg, hay) were inversely associated with RA in younger participants, while others (eg, alfalfa) were associated with RA in older participants.ConclusionThese findings suggest several agricultural tasks and exposures may contribute to development of RA.

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Comment on “Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures”

Cited by 3 publications

References 9 publications

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

Is Male Rheumatoid Arthritis an Occupational Disease? A Review

Incident thyroid disease in female spouses of private pesticide applicators

Farming tasks and the development of rheumatoid arthritis in the agricultural health study

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