Skeletal muscle quality as an independent associated factor of oxygen utilization efficiency in interstitial lung disease: a cardiopulmonary exercise testing study

Abstract Background Reduced exercise capacity in patients with interstitial lung disease (ILD) is associated with poor prognosis. Oxygen pulse (O 2 pulse) reflects exercise circulatory efficiency, but its determinants at submaximal exercise remain unclear. Phase angle (PhA) has recently emerged as a surrogate marker of muscle quality. Objective To investigate the association between lower-limb PhA and submaximal O 2 pulse at the ventilatory threshold (VT), which reflects daily physical activity independent of maximal volitional effort, in patients with ILD. Methods This retrospective study analyzed 111 patients with ILD enrolled in an educational hospitalization program (April 2024–March 2026). Among these, 35 patients completed cardiopulmonary exercise testing (CPET). Lower-limb PhA was assessed via bioelectrical impedance analysis. The association between PhA and O 2 pulse at VT was evaluated using Pearson correlation and multiple regression analysis adjusted for age, %FVC, and tricuspid regurgitation velocity (TRV). Results The analyzed CPET sub-cohort ( n = 35) had a mean age of 69.0 ± 8.4 years, 74.2% male, and %FVC of 85.3 ± 18.1%. Lower-limb PhA was significantly correlated with O 2 pulse at VT ( r = 0.629, p < 0.001). In multiple regression analysis, PhA remained independently associated with O 2 pulse (β = 0.748, p = 0.001), with a model R 2 of 0.433. Conclusions Lower-limb PhA is an independent associated factor of O 2 pulse in patients with mild-to-moderate ILD. Given the cross-sectional and retrospective nature of this study, these findings do not establish causality but suggest that muscle quality may be a relevant clinical indicator that warrants further prospective and interventional investigation.