Longitudinal reciprocal association between rheumatoid arthritis and chronic obstructive pulmonary disease and mediation of inflammation

Objectives: To elucidate the longitudinal reciprocal association between rheumatoid arthritis (RA) and chronic obstructive pulmonary disease (COPD), and the mediating role of systemic inflammation in the association.Methods: 403045 participants from UK Biobank were enrolled in this study. A cross-lagged panel model was used to investigate the longitudinal reciprocal association between RA and COPD. Cox-proportional hazard regression and logistic regression models were also conducted to examine the association between baseline RA and COPD during follow-up, and vice versa. Causal mediation analysis was then performed to explore the mediating roles of 160 systemic inflammatory biomarkers in the bidirectional association.Results: At baseline, 4755 (1.2%) and 6989 (1.7%) individuals were diagnosed with RA and COPD, respectively. After adjusting for the covariates, the result of cross-lagged panel model revealed a bidirectional association between RA and COPD (beta = 0.018, P < 0.001 for RA -> COPD path; beta = 0.010, P < 0.001 for COPD -> RA path). In the non-COPD population, the risk of future COPD was increased in RA patients (Cox: HR = 1.65, 95% CI, 1.50-1.83; logistic: OR = 1.85, 95% CI, 1.66-2.07). In the non-RA population, baseline COPD was associated with a higher risk of RA during follow-up (Cox: HR = 1.67, 95% CI, 1.44-1.92; logistic: OR = 1.70, 95% CI, 1.47-1.97). Five inflammatory factors mediated the RA -> COPD path, and C-reactive protein mediated the COPD -> RA path (FDR < 0.05).Conclusions: A significant bidirectional association exists between RA and COPD, and it is partially mediated by systemic inflammation.