C105-09 No Safe Subtype: Survival After Acute Respiratory Failure in Interstitial Lung Disease

Abstract Rationale Acute respiratory failure in interstitial lung disease (ILD) is associated with a high risk of death, yet current understanding of outcomes across ILD subtypes remain limited. Prior studies suggest that idiopathic pulmonary fibrosis (IPF) carries uniquely poor prognosis, while connective-tissue disease-associated ILD (CTD-ILD) may do better because of potentially reversible inflammatory disease. Whether these distinctions influence outcomes in modern critical care is unknown. Clarifying survival patterns across ILD subtypes can refine how prognosis and treatment goals are approached once respiratory failure develops. Methods We conducted a retrospective cohort study of adults with ILD admitted to five hospitals in the Johns Hopkins Health System from 2017-2024 using electronic health record data. Acute respiratory failure was defined as ≥ 24 hours of invasive mechanical ventilation (IMV) or noninvasive ventilation (NIV), which we defined as high-flow nasal oxygen and noninvasive positive-pressure ventilation. ILD was identified and classified into subgroups (IPF/idiopathic interstitial pneumonia IIP, CTD-ILD, exposure-related, sarcoidosis, other) using a prior validated ICD-10 algorithm. The primary outcome was 90-day transplant-free survival (TFS) analyzed with Cox regression adjusted for demographics, comorbidities, hospital type, and illness severity. Results Among 982 patients (median age 70 years, 50% female), 27% had IPF/IIP, 8% CTD-ILD, 6% exposure-related ILD, 17% sarcoidosis, and 42% other ILD. Pre-hospital antifibrotic use occurred only in IPF/IIP (8%), while immunosuppressive therapy use was most common in CTD-ILD (35%). During hospitalization, corticosteroids were administered to 70% of all patients, and IVIG was mainly used in CTD-ILD (15%). By day 90, 47% of patients had died or undergone lung transplantation. Overall transplant-free survival was 44% for patients receiving IMV and 56% for those receiving NIV, with no significant difference by ILD subtype. CTD-ILD had slightly higher unadjusted survival under IMV, but this difference was not significant in adjusted models (Figure 1). Compared with IPF/IIP, adjusted hazard ratios (95% CI) for 90-day TFS were: 0.84 (0.56-1.27) CTD-ILD, 1.14 (0.76-1.72) exposure-related, 1.04 (0.75-1.45) sarcoidosis, and 1.10 (0.88-1.39) other ILD. Conclusions In this multihospital ILD-ICU cohort, outcomes were uniformly poor and mainly determined by the severity of respiratory failure rather than ILD subtype. CTD-ILD showed slightly higher survival on IMV, and overall survival was higher with NIV, but these differences reflected patient selection and illness severity rather than reversibility. These findings challenge assumptions about subtype-based reversibility once respiratory failure develops and highlight the need for early shared decision-making and ICU-specific treatment strategies. This abstract is funded by: National Heart, Lung and Blood Institute 1F32HL182250-01