Tidal Volume in Idiopathic Pulmonary Fibrosis: Restriction Severity and Prognostic Information Beyond Forced Vital...

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive loss of lung compliance, which raises the elastic work of breathing and alters resting ventilatory strategy. Clinical assessment of IPF still relies on forced manoeuvres, particularly forced vital capacity (FVC), which capture maximal performance rather than this resting adaptation. How tidal volume (VT) evolves over the IPF course is not well characterised. VT and the VT/FVC ratio offer an effort-independent window onto the same physiology, characterised here longitudinally.

We analysed 613 IPF patients enrolled at three European eurIPFreg centres (Giessen, Barcelona, Paris) between 2009 and 2025. Baseline VT, FVC, and VT/FVC were compared between survivors and non-survivors. Transplant-free survival was analysed by Cox regression including age, sex, antifibrotic treatment, log-transformed VT and FVC, and their interaction. Discrimination was assessed by Harrell's C-index with 20-fold cross-validation and time-dependent AUCs. Longitudinal trajectories were modelled over 60 months.

VT followed a dynamic, non-monotonic trajectory consistent with progressive ventilatory adaptation, rising transiently to ~5% above baseline at months 18-21, coincident with the steepest segment of FVC decline (months 6-18), and returning slowly toward baseline thereafter. The VT/FVC ratio rose continuously (+17% at 60 months), the only marker to evolve monotonically, while FVC declined progressively (-8.8%). Higher baseline VT showed a trend toward improved survival (log-rank p = 0.092; HR 0.88, 95% CI 0.75-1.04), and the VT/FVC ratio stratified survival significantly (log-rank p < 0.001), as did baseline FVC (HR 0.59 per unit log-FVC, 95% CI 0.49-0.69; p < 0.001). The VT × FVC interaction approached significance (HR 1.12, 95% CI 0.98-1.30; p = 0.08), suggesting a joint physiological signal. Antifibrotic therapy reduced mortality (HR 0.63, 95% CI 0.50-0.81; p < 0.001).

VT in IPF follows a dynamic, non-monotonic course, rising during the steepest phase of FVC decline and returning toward baseline thereafter, consistent with a ventilatory adaptation in which increased VT serves as a transient lower-cost strategy for maintaining minute ventilation before the elastic load makes it unsustainable. The VT/FVC ratio integrates this rising drive with falling vital capacity, evolves monotonically, and stratifies survival, identifying it as an effort-independent physiological descriptor of restrictive remodelling. Together, VT and VT/FVC enrich the standard FVC-based assessment of IPF by capturing the resting ventilatory dimension of disease progression.