December 12, 2019
2 min read

Asthma linked to elevated anti-citrullinated antibodies in rheumatoid arthritis

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Jeffrey A. Sparks
Jeffrey A. Sparks

A strong association was observed between asthma and anti-citrullinated antibody elevation in a cohort of women with rheumatoid arthritis, and this association was independent of smoking, according to recent findings.

“We know that elevated anti-citrullinated protein antibodies (ACPA) appear in the blood years prior to articular symptoms of rheumatoid arthritis,” Jeffrey A. Sparks, MD, assistant professor of medicine at Brigham and Women’s Hospital and Harvard Medical School, told Healio Pulmonology. “Previous studies suggest that immune tolerance loss and autoantibody production may occur at sites of mucosal inflammation after environmental triggers, such as infections or smoking. Therefore, we decided to study whether asthma, a common disease characterized by chronic mucosal inflammation, was related to ACPA elevation in blood banked years prior to clinical rheumatoid arthritis onset.”

The researchers performed a nested case-control study in women from the Nurses’ Health Study (NHS), which ran from 1976 to 2014, and the NHSII, which ran from 1989 to 2015. The analysis included 284 incident rheumatoid arthritis cases and 849 matched controls.

Blood draws were taken from a subset of patients from each of the NHS cohorts to determine ACPA or rheumatoid factor positivity, whereas asthma status was determined via biennial questionnaires before the blood was taken. Eligible participants met 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism rheumatoid arthritis criteria.

Each case patient was matched to three controls by age, cohort, year, time from blood draw to index date and menopause, according to the findings.

Results showed that 33.8% of rheumatoid arthritis cases had ACPA elevation before diagnosis. At the time of blood draw, 17.7% of patients who were ACPA-positive before rheumatoid arthritis had clinician-diagnosed asthma compared with just 6.3% of matched controls (P = .0008).

In an adjusted analysis that controlled for matching factors, smoking pack-years, passive smoking and BMI, pre-rheumatoid arthritis ACPA positivity among patients with rheumatoid arthritis remained significantly associated with asthma (OR = 3.57; 95% CI, 1.58-8.04).

“We were surprised to see how strong and specific the association of asthma was with pre-rheumatoid arthritis ACPA elevation,” Sparks said. “Even among nonsmokers, asthma was associated with a nearly fivefold increase in odds of pre-rheumatoid arthritis ACPA elevation.”

Other findings from the adjusted analysis showed no association between asthma and rheumatoid arthritis overall (OR = 1.45; 95% CI, 0.91-2.31). However, asthma carried a significant association with seropositive rheumatoid arthritis (OR = 1.79; 95% CI, 1.01-3.18).


“These findings suggest that patients with asthma may be at increased risk for developing ACPA-positive rheumatoid arthritis and should be closely monitored for signs and symptoms,” Sparks said. “Future studies should focus on whether asthma subtypes, severity or treatment may impact rheumatoid arthritis risk differently.”– by Rob Volansky

Disclosure: Sparks reports no relevant financial disclosures.