Occupational Exposures and Smoking in Eosinophilic Granulomatosis With Polyangiitis: A Case–Control Study

Abstract

Objective Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis. Environmental agents and occupational exposures may confer susceptibility to EGPA, but data are scarce. This study was undertaken to investigate the association between occupational exposures (e.g., silica, farming, asbestos, and organic solvents) and other environmental agents (e.g., smoking) and the risk of EGPA. Methods Patients with newly diagnosed EGPA (n = 111) and general population controls (n = 333) who were matched for age, sex, and geographic area of origin were recruited at a national referral center for EGPA. Exposures were assessed using a dedicated questionnaire administered by a specialist in occupational medicine, under blinded conditions. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated. Results Exposures to silica (OR 2.79 [95% CI 1.55–5.01], P = 0.001), organic solvents (OR 3.19 [95% CI 1.91–5.34], P < 0.001), and farming (OR 2.71 [95% CI 1.71–4.29], P < 0.001) were associated with an increased risk of EGPA. Co‐exposure to silica and farming yielded an OR of 9.12 (95% CI 3.06–27.19, P < 0.001), suggesting a multiplicative effect between these 2 exposures. Smoking (current and former smokers combined) was significantly less frequent among patients with EGPA compared to controls (OR 0.49 [95% CI 0.29–0.70], P < 0.001). The pack‐year index was also lower among patients with EGPA (OR 0.96 [95% CI 0.94–0.98], P < 0.001). The association of silica and farming was primarily aligned with ANCA‐positive EGPA, while the association of smoking status and organic solvents was primarily aligned with ANCA‐negative EGPA. Conclusion The environment can influence susceptibility to EGPA. Exposure to silica, farming, or organic solvents is associated with an increased risk of EGPA, while smoking is associated with a lower risk. These exposures seem to have distinct effects on different EGPA subsets.

Pneumoconiosis combined with connective tissue disease in China: a cross-sectional study

“…4 Numerous studies have shown that autoantibodies increase with excessive exposure to mineral dust, including antinuclear antibodies (ANA), rheumatoid factor (RF), antineutrophil cytoplasmic antibodies (ANCA) and so on. [5][6][7] In addition, various studies have demonstrated that connective tissue disease (CTD) can be complicated in patients with pneumoconiosis, [8][9][10][11][12][13][14][15] such as Caplan's syndrome and Erasmus syndrome, which have been reported histologically. 16 17 In these pneumoconiosis patients, though the incidence of CTD is markedly lower than the incidence of positive autoantibodies, it is not known if patients with positive autoantibodies will develop CTD later.…”

Biologics for eosinophilic granulomatosis with polyangiitis

“…Evidence of a restricted HLA repertoire along with a clonal T cell expansion indicates a critical role of selected antigens in EGPA pathogenesis. A recent study demonstrated an association between occupational exposures to organic solvents, silica, and farming and the risk of EGPA [22], while tobacco exposure resulted protective particularly in ANCA-negative EGPA, by suppressing the immune system at mucosal level. The role of mucosal disfunction in EGPA is also supported by the evidence of an imbalance in gut mucosal immune response secondary to an enrichment of intestinal pathobionts [23].…”

Environmental factors influencing the risk of ANCA-associated vasculitis

“…However, Haubitz et al (85) found that smoking may have a potential protective effect against AAV disease. Additionally, studies have linked exposure to silica, tillage, or organic solvents to an increased risk of EGPA, whereas smoking is associated with a lower risk (74). The immunosuppressive effects of nicotine have been suggested as a potential explanation for these findings (86).…”