Smokers, obese people at greater risk of RA-ILD

Individuals with obesity, high-level C-reactive protein (CRP), and poor functional status are more likely to develop incident rheumatoid arthritis-related interstitial lung disease (RA-ILD), a recent study has found. Smoking 30 pack-years or more may also substantially increase the risk of RA-ILD, while lower levels of smoking do not.

“These findings might improve our understanding of RA-ILD pathogenesis and prediction, and also suggest weight loss and smoking cessation might prevent RA-ILD,” the researchers said. “However, all known clinical risk factors for RA-ILD have only a modest ability to predict RA-ILD development.”

In this nested case-control study, incident RA-ILD cases were matched to RA non-ILD controls based on age, sex, RA duration, rheumatoid factor, and time from exposure assessment to RA-ILD. Exposures were as follows: body mass index (BMI), smoking, anticyclic citrullinated peptide antibodies, race, joint erosions, rheumatoid nodules, CRP, disease activity score, functional status, disease-modifying antirheumatic drug use, and glucocorticoid use.

The researchers then obtained odds ratio (OR) for each exposure on RA-ILD risk from logistic regression models and calculated area under the curve (AUC) based on all lifestyle and clinical exposures.

Eighty-four patients with RA-ILD and 233 matched controls were included in the analysis. After adjustment, obesity, high-positive CRP (≥ 10 mg/L), and poor functional status (multidimensional Health Assessment Questionnaire [MDHAQ] ≥1) were found to correlate with a heightened RA-ILD risk (OR vs normal BMI, 2.42, 95 percent confidence interval [CI], 1.11–5.24; OR vs CRP <3 mg/L, 2.61, 95 percent CI, 1.21–5.64; OR vs MDHAQ <0.2, 3.10, 95 percent CI, 1.32–7.26). [J Rheumatol 2021;48:656-663]

“This case-control study discovered several novel predictors for incident RA-ILD, including obesity, higher education level, high-positive CRP, and poor functional status,” said the researchers, noting that that currently known clinical predictors have only a modest ability to predict RA-ILD.

In addition, smoking 30 pack-years or greater strongly correlated with RA-ILD risk relative to never smokers (OR, 6.06, 95 percent CI, 2.72–13.5). Lifestyle and clinical risk factors for RA-ILD jointly had an AUC of 0.79 (95 percent CI, 0.73–0.85).

Previous studies on RA-ILD risk also found an association with smoking, but a few did not. [Arthritis Rheum 1996;39:1711-1719; Ann Rheum Dis 2014;73:1487-1494; Rheumatology 2014;53:1676-1682; Am J Respir Crit Care Med 2015;191:1403-1412; Rheumatology 2010;49:1483-1489; PLoS One 2014;9:e92449; Med Sci Monit 2015;21:708-715]

Such discrepancy could be explained by insufficient smoking history in the negative studies, while the lack of association could have resulted from lack of certain HLA-DR alleles, termed the “shared epitope,” as smoking could increase RA-ILD risk in the presence of the shared epitope, according to the researchers. [Clin Rheumatol 2015;34:1529-1536]

Of note, despite the discovery of the novel risk factors for ILD, they only showed a modest AUC of 0.79. This finding is consistent with previous studies, whose AUC ranged from 0.60 to 0.85, and suggests a need to identify additional risk factors for RA-ILD. [Medicine 2019;98:e17088; Am J Respir Crit Care Med 2015;191:1403-1412; Clin Rheumatol 2015;34:1529-1536]

“Given the poor prognosis and limited available treatment options for RA-ILD, this finding emphasizes the critical need for future studies of clinical, biological, and genetic risk factors for RA-ILD,” the researchers said.