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Elevated Anti–Citrullinated Protein Antibodies Prior to Rheumatoid Arthritis Diagnosis and Risks for Chronic Obstructive Pulmonary Disease or Asthma
Author(s) -
Zaccardelli Alessandra,
Liu Xinyi,
Ford Julia A.,
Cui Jing,
Lu Bing,
Chu Su H.,
Schur Peter H.,
Speyer Cameron B.,
Costenbader Karen H.,
Robinson William H.,
Sokolove Jeremy,
Karlson Elizabeth W.,
Camargo Carlos A.,
Sparks Jeffrey A.
Publication year - 2021
Publication title -
arthritis care and research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.032
H-Index - 163
eISSN - 2151-4658
pISSN - 2151-464X
DOI - 10.1002/acr.24140
Subject(s) - medicine , copd , asthma , rheumatoid arthritis , hazard ratio , cohort , proportional hazards model , rheumatoid factor , immunology , confidence interval
Objective To investigate elevation of anti–citrullinated protein antibodies (ACPAs) before diagnosis of rheumatoid arthritis (RA) 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 3 controls by age, cohort, year, and menopausal factors. Pre‐RA ACPA positivity was defined as >99th percentile of control distribution by a research assay or by cyclic citrullinated peptide in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated hazard ratios (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 women who were pre‐RA and 842 controls; blood was donated a mean ± SD of 9.7 ± 5.8 years 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% confidence interval (95% CI) 1.33–7.00]) after adjusting for covariates including smoking pack‐years. Pre‐RA ACPA+ had an 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 than controls, regardless of pre‐RA ACPA status.