Elevated anti‐citrullinated protein antibodies prior to rheumatoid arthritis diagnosis and risks for chronic obstructive pulmonary disease or asthma

OBJECTIVE: To investigate elevation of anti-citrullinated protein antibodies (ACPA) before RA diagnosis and risks for chronic obstructive pulmonary disease (COPD) or asthma. METHODS: We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported then confirmed by medical records) were each matched to three controls by age, cohort, year, and menopausal factors. Pre-RA ACPA+ was defined as >99th percentile of control distribution by a research assay or by CCP2 in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated HRs for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls. RESULTS: We analyzed 283 pre-RA women and 842 controls; blood was donated mean of 9.7 years (SD 5.8) before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04, 95%CI 1.33,7.00) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had a HR for asthma of 1.74 (multivariable 95%CI 0.72,4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65, 95%CI 1.11,2.46). CONCLUSION: Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma, regardless of pre-RA ACPA status.