Predictive factors and clinical outcomes of progressive pulmonary fibrosis in anti-threonyl (PL7) positive anti-synthetase syndrome.

Objectives: Patients with anti-threonyl (PL7) positive anti-synthetase syndrome (ASS) exhibit a high prevalence of interstitial lung disease (ILD), which can progress to progressive pulmonary fibrosis (PPF) and increased mortality. This study aims to explore the clinical characteristics, imaging features, and predictive factors for PPF.

Methods: A retrospective cohort of PL7-ASS patients at a single tertiary centre between January 2018 and December 2022, was analysed. Clinical, serological, and radiological data were collected at baseline and during follow-up.

Results: The study included 69 PL7-ASS patients with ILD (mean age: 54.5 years; 73.9% female). Baseline CT imaging revealed the following patterns: cellular nonspecific interstitial pneumonia (cNSIP, 29%), fibrotic NSIP (fNSIP, 18.8%), organizing pneumonia (OP, 14.5%), OP-cNSIP overlap (15.9%), OP-fNSIP overlap (14.5%), and usual interstitial pneumonia (UIP, 7.2%). PPF developed in 39.1% of patients. Elevated levels of lactate dehydrogenase (LDH; HR = 1.021, 95% CI: 1.002-1.04, p= 0.031) and carbohydrate antigen 125 (CA125; HR = 1.164, 95% CI: 1.023-1.326, p= 0.022) were identified as independent predictors of PPF. Patients with UIP or OP-NSIP overlap patterns exhibited worse survival (p= 0.0479) and higher PPF prevalence (p= 0.029). Patients who developed PPF had significantly lower survival rates compared with those without PPF (HR = 5.120, 95% CI: 1.566-16.740, p= 0.018).

Conclusion: PL7-ASS patients with ILD are at significant risk of developing PPF, which is associated with poor survival outcomes. Elevated LDH and CA125 levels may serve as reliable predictors of PPF, highlighting importance of early identification and aggressive management strategies.