Abstract
Background Extra-articular disease in rheumatoid arthritis (RA) occurs in nearly 50% of patients, the lung being a common site of complication. (1) Raised RF and anti-CCP titers have been associated with the development of pulmonary disease. Smoking in genetically susceptible individuals can result in protein citrullination and enhancement of autoimmune reactivity (2). Objectives Our aim was to explore the relationship between the presences of RhF and anti-CCP antibody with pulmonary manifestations in the following groups: RF positive only (group 1), Anti-CCP factors positive only (group 2) RF and anti-CCP positive in combination (group 3) we also explored the relationship between smoking, seropositivity and lung disease. Methods In this retrospective cross-sectional observational study of 2088 patients who had a RF and anti-CCP antibodies tested during Nov-2015 and Oct-2016 at Royal Wolverhampton Trust. Out of 2088, 1662 patients tested negative for both anti-CCP and RF and were excluded from analysis. 426 out of 2088 tested positive, of which 89 patients were anti-CCP only positive, 100 patients were RF only positive and 237 patients were positive for both antibodies. Data was collected on 89 patients from each group. Data collection included patient age, gender, smoking status, pulmonary manifestations, RF and anti-CCP titer, background of RA and current medications including DMARDS and biologics. Results In group 1 (30) 33.7% of RF positive patients suffered from RA, with (63) 70.7% in group 2 and (82) 92.1% in group 3(P=0.00001). In group 1 17% were current or ex-smokers, 29% in group 2 and 52.7% in group 3(P=0.02). Lung disease was present in 13.4% from group 1, 7.8% from group 2 and 12.3% from group 3 with no significant statically difference between the three groups (p=0.376). In group 2 and 3 all patients with lung disease had RA. From group 1, 50% of those with lung disease had a diagnosis of COPD, followed by 20% with bronchiectasis and 10% with ILD. Of note patients with a diagnosis of COPD had a higher titer of RF. In group 2 a third of patients with lung disease had a diagnosis of COPD and ILD respectively, and again these patients had higher titers of anti-CCP. In group 3 13.4% suffered from lung manifestations and 37.5% had a diagnosis of pulmonary fibrosis, 12.5% diagnosed with ILD and the remaining 50% had COPD and pleural disease. Conclusion Antibody positivity was associated with higher prevalence of RA. Our data provide evidence for the association between smoking and raised antibody titers, especially with anti-CCP antibodies. Lung disease was more strongly associated with RF than anti CCP even though the proportion of smokers was higher in patients with positive anti CCP compared than RF. However lung pathology varied with airway obstruction being more prevalent in RF positive patients compared with fibrosis in patients who were RF and CCP positive. Furthermore, our findings suggest that RF is more strongly associated with lung disease than anti CCP though citrullination is thought to start in the lungs. Our findings demonstrate that lung disease is prevalent in patients with RA and should be anticipated and treated accordingly in order to reduce mortality. Seropositivity of both RF and anti-CCP can be linked with a higher prevalence and greater severity of pulmonary disease activity however this requires replication in a larger cohort.
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