Elevated anticitrullinated protein antibodies (ACPA) before diagnosis of rheumatoid arthritis (RA) is associated with an increased risk for new-onset chronic obstructive pulmonary disease (COPD), according to study results published in Arthritis Care & Research. However, regardless of ACPA status, risk for asthma was found to be increased among women who later developed RA.

The objective of the current study was to determine the association between ACPA status prior to diagnosis of RA and risk for COPD or asthma.

Using data from the Nurses’ Health Studies, women who donated blood and later developed RA were matched with control participants for age, cohort, year, and menopausal factors, as well as time from blood draw to index date, to determine the risk for asthma or COPD. All patients with RA were compared with matched control participants, and separately as well. Both patients with elevated ACPAs before RA diagnosis and those without elevated ACPAs pre-RA were each compared with a group of control participants.

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Pre-RA ACPA positivity was defined as a greater than 99% percentile of control distribution by an assay or cyclic citrullinated peptide in a subset.

The study sample included 283 women with RA and 842 matched control participants without RA. Of patients with RA, 59 (20.8%) had elevated ACPA before RA diagnosis; in 224 patients, ACPA levels were not elevated before diagnosis of RA.

During follow-up, 105 patients were diagnosed with asthma and 107 with COPD, including 34 patients with both COPD and asthma.

Independent of smoking and other potential confounders, the risk for incident COPD was 3-fold greater for patients with elevated ACPA prior to RA onset (hazard ratio, 3.04; 95% CI, 1.33-7.00). However, women without elevated ACPA before RA diagnosis were not at an increased risk for COPD.

Risk for asthma was also increased among patients with RA compared with matched control participants, regardless of ACPA status prior to diagnosis of RA. Women with elevated ACPA before RA diagnosis had a 74% increased risk for asthma (hazard ratio [HR], 1.74; 95% CI, 0.72-4.24), and those without elevated ACPA before RA diagnosis had a 65% increased risk for asthma (HR, 1.65; 95% CI, 1.11-2.46).

The study had several limitations, including the use of different assays to measure ACPA with potential misclassification bias, the fact that measurement was based on a single blood test and later seroconversion prior to RA diagnosis could not be ruled out, and that the diagnoses of asthma and COPD were collected by self-report or in-person assessments.

“[O]ur results emphasize that clinicians should closely monitor seropositive patients for airways abnormalities, even prior to RA onset. Future work is needed to elucidate the bidirectional link between RA and chronic airways diseases,” the researchers concluded.

Disclosure: One of the study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Zaccardelli A, Liu X, Ford JA, et al. Elevated anti-citrullinated protein antibodies prior to rheumatoid arthritis diagnosis and risks for chronic obstructive pulmonary disease or asthma. Arthritis Care Res (Hoboken). 2021;73(4):498-509. doi:10.1002/acr.24140