Asthma and allergies may be associated with increased risk of rheumatoid arthritis (RA), but passive smoke exposure and smoking earlier in life do not appear to influence risk of RA, according to a study.


 

In previous studies, researchers have hypothesized that rheumatoid arthritis (RA)—one of the most common autoimmune diseases—originates from inflammation in the respiratory tract, resulting in the formation of autoantibodies that later lead to RA. “Some studies have shown an association between asthma and RA, but these did not control for important confounders that could mediate this relationship, such as urban environment, allergy, and passive smoke,” explains Vanessa L. Kronzer, MD. “In addition, few studies have looked into whether second-hand smoke exposure and passive smoke exposure could increase the risk of RA. These are important issues that may help us better understand risk factors for RA and how the disease might develop.”

 

Seeking Clarification

To gain better clarify on the knowledge gaps relating to oral-respiratory factors that might lead to the development of RA, Vanessa L. Kronzer, MD, and colleagues conducted a study to determine the association of RA with asthma and allergies after controlling for allergic diseases, urban environment, and passive smoke. The investigation, published in Arthritis & Rheumatology, also examined passive smoke exposure both at home and work and the age at which people started smoking.

In the case-control study, the authors identified 1,023 cases of RA, 175 of which were incident, within the Mayo Clinic Biobank. “This resource has questionnaire and biological data on over 56,000 participants but had never been used to study RA before,” says Dr. Kronzer. Exposures were self-reported on biobank questionnaires, which had detailed questions about several respiratory-related conditions, including smoking history, comorbidities (eg, asthma), and allergies, in addition to other important control variables. Logistic regression models were used to calculate the association of exposures with RA, with adjustments being made for potential confounders.

 

Highlighting Key Findings

According to Dr. Kronzer, a key finding was that there appears to be an association between RA and asthma, even after adjusting for allergies, urban environment, and passive smoke exposure (Table). A possible reason for this latter finding was that people who develop RA earlier and later may be different from an immunologic standpoint. For example, those who develop RA earlier in life may have more immunologic dysfunction, which in turn can also predispose them to allergies.

“Importantly, we unexpectedly found an association between allergy and RA, especially food allergies,” Dr. Kronzer says. The finding was surprising because the classic thinking has been that RA and allergy occupy distinct and separate immunological pathways.  “Furthermore, our study also found that passive smoke exposure was not associated with higher odds of developing RA except at the highest intensity of combined home and work exposure (40+ pack-years),” says Dr. Kronzer. “Of note, we also confirmed smoking as a strong risk factor for RA.”

 

Interpreting the Data

Dr. Kronzer says that, unlike what was previously believed, autoimmune diseases like RA and allergic diseases like asthma or food allergies may be related. “Our research suggests that having an allergic disease may predispose patients to autoimmune diseases and vice versa,” she says. “As clinicians, we can inform our patients about this relationship. It is possible the underlying causes of this association may be a broader problem relating to immune dysregulation, but more research into this relationship is required. In addition, people who are concerned about their risk for RA can be counseled that they probably do not need to be worried about passive smoke exposure. However, personal smoking remains the strongest known modifiable risk factor for RA. Those with RA or at risk for it should be counseled to quit.”

Based on the study findings, clinicians should have heightened clinical suspicion of RA or other autoimmune diseases when managing any patient with evidence of other immune dysfunction, such as asthma or allergies. Plans are currently underway to conduct more research into these associations, including studies involving other international patient cohorts and investigations that will further explore the association between RA and allergy on a cellular level.

References

Kronzer VL, Crowson CS, Sparks JA, Vassallo R, Davis JM III. Investigating asthma, allergic disease, passive smoke exposure, and risk of rheumatoid arthritis. Arthritis Rheumatol. 2019 Feb 12 [Epub ahead of print]. Available at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/art.40858?referrer_access_token=93FluWAqd4YlYAXyfBiYA04keas67K9QMdWULTWMo8OiujD5ogI4BP8L98d_3oAraQw6R5Gy5t8H6UyCcEE0xaqqy-fMewuKucprQnsuC_Nbf5-Sx3gDKwRTVjtA6Nk8mG-LZjfnFVEfVtjMvYto-g%3D%3D or at https://www.ncbi.nlm.nih.gov/pubmed/30747496.

Lai NS, Tsai TY, Koo M, Lu MC. Association of rheumatoid arthritis with allergic diseases: a nationwide population-based cohort study. Allergy Asthma Proc. 2015;36(5):99-103.

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.