Abstract
<jats:p>BACKGROUND: Liberation from invasive mechanical ventilation (IMV) is a central therapeutic objective in acute respiratory failure (ARF). While lung-protective ventilation strategies and diaphragm function have received considerable attention as determinants of liberation success, the prognostic role of extrapulmonary thoracic tissue composition remains poorly defined. We examined whether chest computed tomography (CT)-derived thoracic skeletal muscle mass (TMM), subcutaneous fat mass (SFM), and their ratio (muscle-fat ratio: MFR) are associated with IMV outcomes in ARF. METHODS: This secondary analysis of a prospective observational ARF cohort includes patients with a chest CT obtained within 7 days before or 3 days after intubation. TMM, SFM and MFR were derived using validated three-dimensional convolutional neural network-based volumetric segmentation spanning the lung apices to bases. Co-primary outcomes were time to successful ventilator liberation within 60 days and 60-day all-cause mortality. Multivariable Cox and logistic regression models with restricted cubic splines assessed linear and non-linear associations, adjusted for age, sex, and key comorbidities. We performed prespecified BMI-stratified and ARDS subgroup analyses. RESULTS: Among 826 patients with ARF requiring IMV, 238 patients with CT imaging were included for analysis (median age 59.5 years, median BMI 28.7 kg/m^2). A higher MFR was independently associated with faster ventilator liberation (hazard ratio 1.16, 95% confidence interval [CI] 1.02 to 1.32, p=0.023). TMM demonstrated a significant J-shaped non-linear relationship with time to liberation (p for non-linearity=0.019), with delayed liberation at both low and high extremes of TMM. Higher SFM was independently associated with increased 60-day mortality (odds ratio 1.09, 95% CI 1.00 to 1.18, p=0.049). In 81 patients with ARDS, TMM also demonstrated a significant J-shaped non-linear relationship with 60-day mortality (p for non-linearity=0.037). BMI was not significantly associated with either outcome. CONCLUSIONS: Volumetric CT-derived thoracic body composition metrics, particularly MFR and TMM, are independently associated with ventilator liberation and 60-day mortality in ARF, capturing prognostic information not reflected by BMI alone. These findings support the incorporation of automated thoracic body composition analysis into early risk stratification frameworks for mechanically ventilated patients and highlight extrapulmonary tissue composition as an underexplored determinant of IMV outcomes.</jats:p>