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Abstract
Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36 months among patients who had high-titer RF seropositivity (≥ 60 IU/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1–6.8; P = 0.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.
Highlights
Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue diseaserelated ILD (CTD-ILD) associated with high morbidity and mortality
Of 294 patients with CTD-ILD, we identified 70 patients (24%) with a multidisciplinary discussion (MDD) diagnosis of RA-ILD (E-Table 1)
When assessing unadjusted lung function changes on serial pulmonary function tests (PFT) measured over 36 months, our study revealed no differences between the high-titer rheumatoid factor (RF) and low-titer RF groups (FVC + 0.05% vs − 4.89%; P = 0.99; FEV1 − 2.38% vs − 1.37%, P = 0.70; FEV1/forced vital capacity (FVC) + 0.50% vs − 0.24%; P = 0.94; and DLCO − 3.96% vs − 5.76%; P = 0.38) (Fig. 2)
Summary
Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue diseaserelated ILD (CTD-ILD) associated with high morbidity and mortality. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. Mediastinal lymph node (MLN) enlargement, which is seen in up to 70% of patients with RA-ILD, has previously been associated with decreased transplant-free survival in ILD14. We assessed whether high-titer RF was associated with CT predictors of ILD progression and mortality amongst patients with RA-ILD, independent of lung disease severity at baseline evaluation
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