Background/Purpose: Interstitial Lung Disease (ILD) is the commonest manifestation of lung disease in Rheumatoid Arthritis (RA) and the only complication reported to be increasing in prevalence, accounting for 6% of all RA deaths. High resolution computed tomography (HRCT) confirmed 25% of RA patients had radiological evidence of ILD.  This study examines predictive factors for RA-ILD in a large multi centre UK cohort.

Methods: Data from 14 UK centres was collected using a standard form for patients with both RA and ILD diagnosed over a 25 year period (1987-2012). Analysis included gender, age, duration of both RA and ILD, smoking history,rheumatoid factor (RF) and cyclic citrullinated peptide (CCP) antibody status. Results were compared to age and gender matched RA patients with neither clinical nor radiological evidence of lung disease.

Results: A total of 230 patients with proven RA-ILD were identified: 110 male patients (48%), median (range) age at diagnosis of RA-ILD was 64 (42-83) years, no significant difference between males and females. Articular disease predated ILD in 191 patients (82%), lung disease predated RA in 22 (10%) and synchronous in 17 (7%). The median (range) duration of RA at the time of diagnosis of ILD was 9 (0-31) years.  Median age at diagnosis of RA was 56 (23-76) years. 154 patients (67%) were past (121) or present (33) smokers, with a median (range) of 26 (5-88) pack years.  Smoking was significantly more frequent among males (75%) than females (60%), odds ratio 1.95 (95%CI 1.11 – 3.43).The median number of pack years was greater in males (35) than females (20) [p=0.01]. Smoking was less prevalent among RA controls (60%) and median pack year consumption was lower at 21 (5-60) [p=0.03].Although CCP was only available in a subset of RA-ILD patients (n=100), CCP antibody titres were significantly higher in patients with RA-ILD. The table shows univariate analysis (odds ratios & 95% confidence intervals) and multivariate logistic regression (LR) with & without anti-CCP.

Conclusion: This is the largest and longest multicentre study of factors associated with RA-ILD in the UK. RF and anti-CCP antibodies were both strongly associated with RA-ILD, and may predate articular disease, especially in smokers, with anti-CCP an important and easily measured risk factor for RA-ILD. As smoking is both more prevalent and heavier in males, it may contribute to the increased frequency of RA-ILD in men. As lung abnormalities may also develop before articular symptoms occur, tobacco smoking may precipitate site specific citrullination in the lungs leading to the generation of anti CCP antibodies in early RA. This may alter enzyme expression in the lungs and trigger an abnormal response in genetically susceptible individuals. This suggests a causal role for B cell activation, possibly induced by smoking, in the development of RA-ILD in some patients. A detailed smoking history and titres of anti-CCP antibody should therefore be documented in all RA patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/serological-biomarkers-for-the-development-of-rheumatoid-arthritis-related-interstitial-lung-disease/