Admission-Based Machine-Learning Models for Predicting Mechanical Ventilation and Mortality in Fibrotic Interstitial Lung Disease: A Multicenter Cohort Study with External Validation

Background: Admission-based risk stratification tools are limited for hospitalized patients with fibrotic interstitial lung disease (F-ILD). Aims: To develop and externally validate admission-based machine-learning models for predicting mechanical ventilation (MV), 30-day and 3-month mortality, and long-term all-cause and cause-specific mortality in hospitalized patients with F-ILD. Study Design: Multicenter retrospective cohort study. Methods: This study included hospitalized adults with F-ILD from two tertiary hospitals in China. Clinical characteristics and laboratory test results obtained within 24 hours of admission were used as candidate predictors. Machine-learning models were developed to predict MV, 30-day and 3-month mortality, and long-term all-cause and cause-specific mortality, with internal testing and independent external validation. Model performance, clinical utility, and interpretability were evaluated. Results: A total of 1,272 patients were included (derivation cohort, n = 1,006; external validation cohort, n = 266). In the external validation cohort, the models demonstrated robust discrimination for MV [area under the curve (AUC), 0.913], 30-day mortality (AUC, 0.926), and 3-month mortality (AUC, 0.813). For long-term all-cause mortality, the final model achieved a C-index of 0.768, with time-dependent AUCs of 0.811 at 12 months and 0.768 at 24 months. The corresponding values for cause-specific mortality were 0.768, 0.815, and 0.761, respectively. Lactate dehydrogenase (LDH), neutrophil-to-lymphocyte ratio (NLR), and prognostic nutritional index (PNI) emerged as key predictors of MV and short-term mortality, whereas long-term mortality risk was additionally associated with older age, male sex, smoking history, an idiopathic pulmonary fibrosis phenotype, and lower albumin-to-globulin ratio and platelet-to-white blood cell ratio. Conclusion: Admission-based models demonstrated strong discriminatory performance for predicting MV and mortality in hospitalized patients with F-ILD. Elevated LDH and NLR levels, together with lower PNI, characterized a high-risk profile for acute deterioration and death. Local recalibration may be necessary before implementation in new clinical settings.