6MWT Reveals early physiological impairment in fibrotic interstitial lung diseases

Rationale Early prediction of lung function decline remains challenging in idiopathic pulmonary fibrosis (IPF) and fibrotic interstitial lung diseases (fibrotic ILD). We evaluated whether oxygen desaturation during the 6-minute walk test (6MWT) predicts forced vital capacity (FVC) decline and long-term outcomes. Methods We analyzed data from two independent cohorts: the nationwide Japanese Idiopathic Interstitial Pneumonias (JIPS) Registry and an external IPF cohort (K-Junko Study). Hazard ratios (HRs) were estimated for each 6MWT parameter to identify variables associated with FVC decline and to determine optimal thresholds. Sensitivity analyses were conducted using Fine–Gray models. The performance of the predictive model was assessed using calibration plots and the C-index. Results In JIPS IPF (n=457) and K-Junko IPF (n=318), an SpO₂ change of≤−6% during the 6MWT independently predicted ≥5% FVC decline in both cohorts (JIPS HR 1.292; K-Junko HR 1.480). Moreover, SpO₂ change during the 6MWT was significantly associated with FVC change in the subsequent year, and this association persisted over five consecutive years in JIPS IPF. The nomogram demonstrated moderate discrimination (C-index: 0.619 [training] and 0.632 [validation]) and fair calibration. A composite profile meeting all three criteria (FVC ≥80%, SpO₂ change>−6%, 6MWD ≥420 m) identified patients with favorable transplant-free survival. In JIPS non-IPF fibrotic ILD (n=387), SpO₂ change remained the sole independent predictor of ≥5% FVC decline (HR 1.350). Conclusion SpO₂ change during the 6MWT predicts FVC decline and outcomes across fibrotic ILD, and its incorporation into routine assessment may enable earlier risk stratification and facilitate timely intervention.