Objective: Forced expiratory volume in one second (FEV₁) remains the standard parameter for assessing airflow limitation, although the most appropriate expression of its decline for prognostic evaluation remains unclear. This study aims to assess the prognostic significance of different annual FEV₁ decline indices for medium- and long-term mortality in COPD.

Methods: 1,247 patients with clinically diagnosed COPD were included, each undergoing at least three annual spirometric evaluations. Six FEV₁ indices were analysed: absolute value, percentage of predicted, z-score, FEV₁ normalized by height squared (FEV₁.Ht−²) and cubed (FEV₁.Ht−³), and FEV₁Q. Longitudinal changes were estimated using random-coefficient models. The primary outcome was all-cause mortality over a 15-year follow-up.

Results: A total of 12,863 person-years were analysed. During the follow-up, 577 patients (46.3%) died. All FEV₁ indices were significantly associated with mortality risk. However, in multivariate analysis, only the annual decline in FEV₁ z-score remained an independent predictor (adjusted hazard ratio 0.104, 95% confidence interval 0.080-0.135, p<0.001). ROC analyses demonstrated that FEV₁ z-score decline provided superior predictive accuracy compared to other indices. A z-score annual decline ≥-0.1969/year was associated with a 4.6-fold increased mortality risk. Additionally, the baseline value of FEV₁.Ht−³ showed greater prognostic value than the other baseline FEV₁ indices.

Conclusion: The annual decline in FEV₁ z-score is the most robust FEV₁ expression predictor of long-term mortality in COPD. These findings suggest that incorporating longitudinal z-score assessments into clinical practice may improve risk stratification and patient management.