Background Extra-articular manifestations (EAMs) are common in patients with rheumatoid arthritis (RA) and are associated with increased morbidity and early mortality. It has been revealed that anti-citrullinated protein antibody (ACPA) may be associated with increased risk for further EAMs. However, an inconsistent association has been reported between the serum ACPA level and RA-related pulmonary disease risk.
Objectives We collected the inconsistent studies and systematically analysed whether serum ACPA positivity increased the risk of pulmonary disease in patients with RA.
Methods An electronic search was performed in the PubMed, ScienceDirect, and SpringerLink databases for studies published up to August 2013. The distributions of the serum ACPA level in cases and controls were obtained from eligible studies. The risk of RA-related pulmonary disease associated with the serum ACPA positivity was estimated by the odds ratio (OR) and 95% confidence interval (95% CI). According to the heterogeneity results, a fixed-effects model or a random-effects model was used to calculate the pooled OR. Publication bias and sensitivity analyses were conducted.
Results Overall, 243 patients with RA-related pulmonary disease and 1442 RA patients as controls were included in the meta-analysis. The results showed that the pooled OR was 2.621 (95% CI, 1.561-4.403, p≤0.001) for the increased risk of RA-related pulmonary disease due to the serum ACPA positivity. In the Caucasian population subgroup, an increased OR was 3.453 (95% CI, 1.798-6.630, p≤0.001), whereas no association was found in the Asian population subgroup. Additionally, we further revealed that serum ACPA positivity indicated a higher risk for interstitial lung disease and fibrosis (ILD, IPF) among RA patients (OR=4.679, 95% CI, 2.071-10.572, p≤0.001). The heterogeneity, publication bias, and sensitivity analyses had no statistical significance in all groups.
Conclusions This is the first meta-analysis to reveal that serum ACPA positivity is highly associated with the risk of RA-related pulmonary disease, particularly RA-related ILD and IPF.
Limitations includ that subgroup analyses were performed only for patients with RA and concurrent ILD or IPF. Other RA-related pulmonary disease risk analyses were conducted using pooled data. No further subgroup analysis was performed according to the confounding factors due to the limitation from the original research.
Further more careful prospective studies with larger sample sizes and well-controlled confounding factors are required to confirm our findings.
Disclosure of Interest None declared