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Background Interstitial lung disease (ILD) is a common and potentially life-threatening complication for rheumatoid arthritis (RA) patients. However, there is a lack of clear prognostic factors in rheumatoid arthritis-associated interstitial lung disease (RA-ILD) patients. The purpose of this study was to complete a systematic review and meta-analysis of the factors associated with mortality in RA-ILD patients. Methods Medline, EMBASE and the Cochrane Library were searched up to September 1, 2020. The Newcastle–Ottawa Scale (NOS) was applied to assess the methodological quality of the eligible studies. Study characteristics and magnitude of effect sizes were extracted. Then, pooled hazard ratios (HRs) with the corresponding 95% confidence intervals (CIs) and pooled risk ratios (RRs) with 95% CIs were calculated to assess the factors associated with mortality in RA-ILD. Results Twenty-three of 3463 articles were eligible, and ten factors associated with mortality for RA-ILD were evaluated in the meta-analysis. Older age (HRs = 1.04, 95% CI 1.03–1.05), male sex (HRs = 1.44, 95% CI 1.21–1.73), having a smoking history (HRs = 1.42, 95% CI 1.03–1.96), lower diffusing capacity of the lung for carbon monoxide (DLCO)% predicted (HRs = 0.98, 95% CI 0.97–1.00), forced vital capacity (FVC)% predicted (HRs = 0.99, 95% CI 0.98–1.00), composite physiological index (CPI) (HRs = 1.04, 95% CI 1.02–1.06), usual interstitial pneumonia (UIP) pattern on HRCT (HRs = 1.88, 95% CI 1.14–3.10 and RRs = 1.90, 95% CI 1.50–2.39), emphysema presence (HRs = 2.31, 95% CI 1.58–3.39), and acute exacerbation of ILD (HRs = 2.70, 95% CI 1.67–4.36) were associated with increased mortality in RA-ILD, whereas rheumatoid factor (RF) positive status was not associated. Conclusions Through this systematic review and meta-analysis, we found that older age, male sex, smoking history, higher CPI, lower DLCO% predicted, lower FVC% predicted, UIP pattern on HRCT, emphysema presence and acute exacerbation of ILD were associated with an increased risk of mortality in RA-ILD.

This study aimed to evaluate the role of human epididymis protein 4 (HE4) in the diagnosis and determination of the severity of interstitial lung disease (ILD) in rheumatoid arthritis (RA) patients.HE4 levels in peripheral blood (PB) and bronchoalveolar lavage fluid (BALF) samples were determined via electrochemiluminescence immunoassays in 102 RA patients (46 patients with ILD and 56 patients without ILD) and 51 healthy controls (HCs).Serum HE4 levels were significantly higher in RA-ILD patients (141.8±65.92 pmol/l) than those in the RA-no ILD patients (82.67±26.17 pmol/l) and healthy controls (35.72±7.6 pmol/l) (p0.0001). Consistent with serum HE4 levels, BALF HE4 levels were significantly higher in RA-ILD patients (637.6±154.9 pmol/l) than those in the RA-no ILD patients (427.3±111.2 pmol/l) and healthy controls (206.9±30.46 pmol/l) (p0.0001). In RA-ILD patients, HE4 levels were positively correlated with HRCT (high-resolution computed tomography) fibrosis scores, whereas a significant inverse relationship was found between HE4 levels and lung function parameters (such as, diffusion capacity of the lung for carbon monoxide (DLCO)). The logistic regression analysis showed that high levels of BALF HE4 (≥595 pmol/l) were associated with RA-ILD (odds ratio [OR] =8.09; 95% confidence interval [CI] =1.317-49.682; p=0.024).Serum and BALF HE4 levels were elevated in RA-ILD patients and strongly associated with the severity of ILD, thus supporting their potential clinical value as a new diagnostic aid for patients with RA-ILD.