Correspondence
We welcome the commentary, “COPD: an overlooked cause of excess mortality in patients with rheumatoid arthritis” by Charlotte Hyldgaard and colleagues.1 This report is relevant to our clinical experience because of the 56 (8%) of 726 male rheumatoid arthritis deaths at the Royal Cornwall Hospital, UK— from February, 2015, to August, 2016— 35 (62%) of 56 deaths were respiratory related. 21 (37%) of 56 deaths recorded chronic obstructive pulmonary disease (COPD), bronchiectasis, or emphysema as contributory to the cause of death. This strikingly high respiratory mortality might be explained by exposures that are typical in a male rheumatoid arthritis population: in our cohort 561 (77%) of 726 had been smokers and 546 (75%) of 726 had occupational exposure to vapour, gas, dust, or fumes (VGDF).2 Marked similarities in interactive risks for COPD and male rheumatoid arthritis have been reviewed.3 VGDF exposure combined with smoking shows an increased risk of COPD (odds ratio [OR] 14·1; 95% CI 9·33–21·2) compared with ever smoking alone (OR 6·71; 95% CI 4·58–9·82). An interactive risk for male anticitrullinated protein antibody positive (ACPA) rheumatoid arthritis exists when silica and cigarette exposure (>20 pack years) are combined (OR 14·9; 95% CI 5·32–37·84), far higher than ever smoking alone (OR 2·53; 95% CI 1·72–3·72) or silica exposure alone (OR 1·67; 95% CI 1·13– 2·48).3 Nurses with seropositive rheumatoid arthritis show increased respiratory disease mortality (hazard ratio 2·67; 95% CI 1·89–3·77), independent
of cigarette smoking. 25 (57%) of 44 were COPD related, compared with 6 (14%) of 44 deaths from interstitial lung disease.4 Given the low propensity of VGDF exposure in this population, we suggest an intrinsic propensity to lung citrullination, inducing functional impairment of protective proteins, induction of cytotoxic cells and autoantibodies, and overproduction of neutrophil extracellular traps. We previously hypothesised that adsorption of cadmium derived from cigarette smoke onto previously inhaled fine particulate matter enhances local production of ACPA and triggers rheumatoid arthritis.3 Cadmium oxide nanoparticle exposure facilitates protein citrullination in lung epithelial cells.5 Many occupations associated with COPD development might have been overlooked with regard to toxic elements, such as cadmium, because no account of co-exposure has been made; cigarette smoke acts as the provider source of toxins, subsequently adsorbed (rather than exhaled) on to dusts (silica, coal, kaolin, clay earth) and tars resident within the lung of the co-exposed individual. We believe that rheumatoid arthritis and COPD are linked by shared en vironmental exposures and common
processes of post-translational protein modification, which drive lung citrul lination. Further research into these processes is required.
Lancet Respir Med 2018 Published Online May 11, 2018 http://dx.doi.org/10.1016/ S2213-2600(18)30188-7
We declare no competing interests.
*Dan Murphy, Katy Bellis, David Hutchinson
[email protected] St Austell Healthcare Group, Wheal Northey Surgery, Saint Austell, Cornwall PL25 3EF, UK (DM); Rheumatology Department, Royal Cornwall Hospital, Truro, Cornwall, UK (DM, KB, DH); and University of Exeter Medical School, Knowledge Spa Building, Royal Cornwall Hospital, Truro, Cornwall, UK (DM, DH) 1
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Hyldgaard C, Ellingsen T, Bendstrup E. COPD: an overlooked cause of excess mortality in patients with rheumatoid arthritis. Lancet Respir Med 2018; 6: 326–27. Murphy D, Bellis K, Hutchinson D. Vapour, gas, dust and fume occupational exposures in male rheumatoid arthritis patients resident in Cornwall (UK) and their association with rheumatoid factor and anti-cyclic protein antibodies: a retrospective observational study. BMJ Open (in press). Murphy D, Hutchinson D. Is male rheumatoid arthritis an occupational disease? A review. Open Rheumatol J 2017; 11: 88–105. Sparks JA, Chang SC, Liao KP, et al. Rheumatoid arthritis and mortality among women during 36 years of prospective follow‐up: results from the Nurses’ Health Study. Arthritis Care Res 2016; 68: 753–62. Hutchinson D, Müller J, McCarthy JE, et al. Cadmium nanoparticles citrullinate cytokeratins within lung epithelial cells: cadmium as a potential cause of citrullination in chronic obstructive pulmonary disease. Int J Chron Obstruct Pulmon Dis 2018; 13: 441–49.
www.thelancet.com/respiratory Published online May 11, 2018 http://dx.doi.org/10.1016/S2213-2600(18)30188-7
A Benoist/BSIP/Science Photo Library
Occupational dust and cigarette smoke exposure might link rheumatoid arthritis to COPD
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