A serum biomarker-based index for predicting progressive pulmonary fibrosis in patients with anti-synthetase syndrome: the LOCCM index.

BACKGROUND: Interstitial lung disease (ILD) is the most prominent clinical feature of antisynthetase syndrome (ASyS), with a subset of patients developing progressive pulmonary fibrosis (PPF), which is associated with a poor prognosis. However, the prevalence, clinical characteristics, and predictive factors of PPF in patients with ASyS remains unclear. METHODS: This longitudinal cohort study retrospectively enrolled 643 patients with ASyS-associated ILD. Clinical data, outcomes, and serum biomarkers were analyzed in patients with PPF. Receiver operating characteristic curves, least absolute shrinkage and selection operator, and logistic regression were used to identify key biomarkers associated with PPF. RESULTS: Fibrotic ILD was observed in 51.2% of patients with ASyS, while PPF was observed in 27.6% of patients with ASyS and fibrotic ILD during follow-up (median, 48.9 months). Patients with PPF were more likely to be male (37.5% vs. 23.2%, p = 0.043), have a smoking history (29.7% vs. 14.3%, p = 0.012), exhibit higher rates of dysphagia (10.9% vs. 2.4%, p = 0.017), and have lower diffusing capacity for carbon monoxide (DLCO, 47.30% vs. 57.00%, p = 0.004) at baseline compared to those without PPF. No association was observed between PPF and anti-aminoacyl transfer RNA synthetase (ARS) antibody specificity (p = 0.164). Patients with PPF had significantly worse prognosis than those without PPF (log-rank test, p < 0.001). Lactate dehydrogenase (LDH), osteopontin, CA15-3, CYFRA21-1, and matrix metalloproteinase-7 (MMP-7) were identified as key biomarkers associated with PPF and incorporated into a LOCCM index (score range: 0-5). Among patients with LOCCM scores ranging from 0 to 5, the proportions of PPF were 0.0%, 4.5%, 13.3%, 35.1%, 65.0%, and 100.0%, respectively. The LOCCM index demonstrated strong predictive power for PPF in patients with ASyS and fibrotic ILD (AUC: 0.865, p < 0.001). Internal validations further confirmed its excellent discriminative performance and good calibration. Longitudinal assessment revealed that LOCCM index scores increased in patients with PPF and decreased in those without PPF. CONCLUSIONS: Approximately half of patients with ASyS-ILD presented with fibrotic ILD, among whom approximately one-quarter developed PPF. The LOCCM index is a promising tool for identifying patients with ASyS at risk for PPF development.