Passive Exposure to Smoking May Increase Rheumatoid Arthritis Risk

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EULAR—Passive exposure to smoking during childhood or adulthood increases the risk of developing rheumatoid arthritis (RA), according to a large prospective cohort study of healthy French women presented during EULAR’s 2021 virtual European Congress of Rheumatology. Moreover, the association was mainly observed among women who had themselves never smoked.¹

“In this study, we found an increased risk between passive smoking [exposure] and the development of RA,” says lead author Yann Nguyen, MD, MPH, assistant clinic manager of the Department of Internal Medicine at Nord-Hôpital Beaujon, AP–HP, Clichy, Paris, France. “This risk was already found for active cigarette smoking, which is a major risk factor for RA.”

Active cigarette smoking has been reported as a risk factor for developing anti-citrullinated protein antibody (ACPA) positive RA, particularly in patients carrying the HLA-DRB1-shared epitope alleles. However, despite the connection between active smoking and RA, the available data on passive exposure to smoking and the risk of developing RA are conflicting.

The Data

Dr. Nguyen

In 2018, a Swedish case-control study by Hedström et al. reported no association between the exposure to passive smoking and the risk of developing ACPA-positive or ACPA-negative RA. The study included 589 never-smokers exposed to passive smoking and 1,764 never-smokers who were never exposed to passive smoking.²

The following year, Kronzer et al. reported on the association between RA and asthma, exposure to passive smoking and age at the start of smoking. The case-control study identified 1,023 cases of RA. Although asthma and allergies were linked to an increased risk of RA, passive exposure to smoking and starting smoking at an early age were not found to influence the risk of developing RA.³

In 2019, the French E3N prospective cohort study by Seror et al. confirmed that active smoking is associated with an increased risk of developing RA and identified a trend toward a positive association between exposure to passive smoking during childhood and the development of RA. Since 1990, the study has followed 98,995 healthy French women, mainly teachers and their partners, covered by national health insurance. RA cases were identified by questionnaires and medication reimbursements. The researchers cited the importance of avoiding environ­ments with tobacco for children, especially those with a family history of RA.⁴

Passive Smoking Link

Dr. Kronzer

To further investigate the possible association between passive exposure to smoking and the development of RA, Nguyen et al. analyzed data from the follow-up E3N-EPIC study. Women were considered to have been exposed to passive smoking if they reported being in a smoky room for several hours a day in childhood or at least one hour a day in adulthood.

The E3N-EPIC study included 79,806 women, with a mean age of 49 years at baseline, of whom 13.5% reported exposure to passive smoking during childhood, 53.6% during adulthood and 8.25% during both periods. A total of 698 incident cases of RA were identified and diagnosed at a mean of 11.7 years after baseline.

Passive smoking exposure during childhood was positively associated with the risk of developing RA (HR 1.24, 95% CI 1.01–1.51) and was associated with RA only among women who themselves had never smoked (HR 1.42, 95% CI 1.07–1.88). Similarly, passive smoking exposure during adulthood was positively associated with the risk of developing RA (HR 1.19, 95% CI 1.02–1.40) and was associated with RA only among those who themselves had never smoked (HR 1.27, 95% CI 1.02–1.57).

Dr. Nguyen noted the findings suggest smoking byproducts, whether actively or passively inhaled, may generate auto­immunity toward antigens involved in the pathogenesis of RA.

Smoking byproducts, whether actively or passively inhaled, may generate autoimmunity toward antigens involved in the pathogenesis of RA.

Tell Your Patients

“For patients already diagnosed with RA, this study will not change the clinical practice. But practicing rheumatologists and practitioners could warn their patients of this risk, especially for relatives at risk, such as children, for example,” Dr. Nguyen says.

Commenting on the results, Vanessa Kronzer, MD, assistant professor of medicine and rheumatology fellow at the Mayo Clinic, Rochester, Minn., says, “The results from Nguyen et al. are important because they show that decisions or exposures from decades ago can influence risk of disease today. Similarly, decisions and exposures today can impact us decades from now.”

Dr. Kronzer adds, “This lag helps us to understand the pathogenesis of RA and argues for the importance of long-term thinking with decisions and policy making.”

Despite finding no association between passive smoking exposure and RA risk in her earlier study, Dr. Kronzer found, in a 2021 review, evidence that supports the belief that RA originates at mucosal sites, augmented by genetic predisposition and mediated by certain cell types.

Kronzer et al. summarized key findings from research over the past few years on the etiology of RA. Along with the avoidance of smoking, they suggest weight loss, physical activity and diet are additional modifiable factors that may reduce the risk of developing RA.⁵

“The link between passive smoking and RA means that smoking is not only a risk to the smoker him- or herself, but also to his or her family and friends,” Dr. Kronzer says. “This provides yet another reason to encourage smoking cessation in our patients, their family members and society as a whole.”

Katie Robinson is a medical writer based in New York.

References

1. Nguyen Y, Salliot C, Mariette X, et al. Association between passive smoking in childhood and adulthood, and rheumatoid arthritis: Results from the French E3N-EPIC cohort study. Ann Rheum Dis. 2021;80:7–8.
2. Hedström AK, Klareskog L, Alfredsson L. Exposure to passive smoking and rheumatoid arthritis risk: Results from the Swedish EIRA study. Ann Rheum Dis. 2018;77(7):970–972.
3. Kronzer VL, Crowson CS, Sparks JA, et al. Investigating asthma, allergic disease, passive smoke exposure and risk of rheumatoid arthritis. Arthritis Rheumatol. 2019 Aug;71(8):1217–1224.
4. Seror R, Henry J, Gusto G, et al. Passive smoking in childhood increases the risk of developing rheumatoid arthritis. Rheumatology (Oxford). 2019 Jul;58(7):1154–1162.
5. Kronzer VL, Davis JM 3rd. Etiologies of rheumatoid arthritis: Update on mucosal, genetic and cellular pathogenesis. Curr Rheumatol Rep. 2021 Mar 1;23(4):21.