Lifestyle and Clinical Risk Factors for Incident Rheumatoid Arthritis-associated Interstitial Lung Disease

Abstract

Objective To determine the association between novel lifestyle factors on risk of rheumatoid arthritis-associated interstitial lung disease (RA-ILD), define the threshold at which smoking increases RA-ILD risk, and calculate the degree to which known lifestyle and clinical factors predict RA-ILD. Methods This nested case-control study matched incident RA-ILD cases to RA non-ILD controls on age, sex, RA duration, rheumatoid factor, and time from exposure assessment to RA-ILD. Exposures included education, body mass index (BMI), smoking, anti-cyclic citrullinated peptide, race, joint erosions, rheumatoid nodules, C-reactive protein (CRP), disease activity score, functional status, disease-modifying anti-rheumatic drug use, and glucocorticoid use. Odds ratios (OR) for each exposure on risk of RA-ILD were obtained from logistic regression models. Area under the curve (AUC) was calculated based all lifestyle and clinical exposures. Results We identified 84 incident RA-ILD cases and 233 matched controls. After adjustment, obesity, high-positive CRP (≥10 mg/L), and poor functional status (MDHAQ ≥1) were associated with increased risk of RA-ILD (OR 2.42, 95% confidence interval [CI] 1.11-5.24 vs. normal BMI; OR 2.61, 95% CI 1.21-5.64 vs. CRP <3mg/L; OR 3.10, 95% CI 1.32-7.26 vs. MDHAQ <0.2). Smoking 30 pack-years or more was strongly associated with risk of RA-ILD compared to nonsmokers (OR 6.06, 95% CI 2.72-13.5). Together, lifestyle and clinical risk factors for RA-ILD had an AUC of 0.79 (95% CI 0.73-0.85). Conclusion Obesity, CRP, functional status, and extensive smoking may be novel risk factors for RA-ILD, useful for RA-ILD risk assessment and prevention. The overall ability to predict RA-ILD remains modest.

Genetically Determined Chronic Low-Grade Inflammation and Hundreds of Health Outcomes in the UK Biobank and the FinnGen Population: A Phenome-Wide Mendelian Randomization Study

“…The results of degenerative macular diseases were different from the MR study of CRP on age-related macular degeneration (AMD) that highlighted higher circulating CRP levels leading to increases in risk for all forms of AMD (38). An observational study showed that baseline CRP levels predicted long-term interstitial lung disease progression, and another found that high-positive CRP was associated with rheumatoid arthritisassociated interstitial lung disease, which also conflicts with our causal evidence (39,40). The observational evidence for the effect of CRP on metatarsalgia, idiopathic pulmonary fibrosis, and disorders of the skin remains lacking.…”

Lifetime risk of rheumatoid arthritis-associated interstitial lung disease in MUC5B mutation carriers

“…We were unable to account for some important risk factors, such as smoking and disease activity, and did not consider other common or rare genetic risk factors,14 17 all of which are likely to further contribute to the risk. We did not have information about histological or radiological patterns of ILD.…”

Towards clinical significance of the MUC5B promoter variant and risk of rheumatoid arthritis-associated interstitial lung disease

“…Previous studies have also identified RA-specific characteristics, such as RA-related autoantibodies and articular disease activity, as risk factors for RA-ILD. [11][12][13][14] Thus, there may be a synergistic relationship between the MUC5B promoter variant and RA for RA-ILD risk. Other established RA-ILD risk factors include older age at RA onset, male sex, cigarette smoking and longer RA duration, among others.…”

“…However, the prevalence of UIP is generally reported to be higher than would be expected by chance alone, considering the independent prevalence of IPF and RA. Previous studies have also identified RA-specific characteristics, such as RA-related autoantibodies and articular disease activity, as risk factors for RA-ILD 11–14. Thus, there may be a synergistic relationship between the MUC5B promoter variant and RA for RA-ILD risk.…”