Risk factors for incidence of interstitial lung disease in patients with rheumatoid arthritis: a systematic review and meta-analysis

Objectives This study aimed at identifying risk factors for the incidence of interstitial lung disease in patients with rheumatoid arthritis (RA-ILD) by a systematic review and meta-analysis. Methods Information sources : studies published by March 2021 were searched in PubMed, Web of Science, MEDLINE, EMBASE, Cochrane Library and Scopus databases. Eligibility criteria : cohort studies or nested case-control studies that reported OR or HR of risk factors for RA-ILD were included. Two researchers independently screened the studies and extracted data. Synthesis of results : the relative risks (RRs) were introduced to measure the association across studies. Risk bias : quality assessments of included studies were performed using the Newcastle-Ottawa Scale. Based on the result of heterogeneity, the random-effects model or fixed-effects model was chosen in the meta-analysis. Furthermore, a sensitivity analysis was conducted to identify the origins of heterogeneity, and publication bias was evaluated for the factors with no less than five included studies by funnel plots and Egger’s test. Results Among 3075 identified articles, 12 studies met the inclusion criteria. 17 risk factors were included in the meta-analysis. Male (RR 1.94, 95% CI 1.33 to 2.85, p<0.001), elder age (>60 years, RR 1.42, 95% CI 1.05 to 1.94, p=0.02), older RA onset age (RR 1.05, 95% CI 1.01 to 1.10, p=0.02), smoking (RR 1.37, 95% CI 1.09 to 1.71, p=0.006), lung complications (RR 2.72, 95% CI 1.24 to 5.95, p=0.01), rheumatoid nodule (RR 1.85, 95% CI 1.36 to 2.51, p<0.001), leflunomide usage (RR 1.41, 95% CI 1.02 to 1.96, p=0.04) were identified as risk factors of RA-ILD. Conclusion Physicians should be aware that patients with RA with the above risk factors are likely to develop RA-ILD, and perform close ILD screening during follow-ups so that the patients can be early diagnosed and treated, and achieve improved prognosis.