Rationale: The lung diffusing capacity for carbon monoxide (DLco), a metric of gas transfer, provides physiological information distinct from spirometry. While DLco independently predicts mortality in COPD, its integration into the GOLD spirometric staging (% FEV1) to improve risk assessment, remains unexplored.

Objectives: To determine if DLco enhances the predictive power of GOLD spirometric classification for all-cause and respiratory mortality.

Methods: We followed 469 patients (mean age 64 years, 58% FEV1) with complete lung function tests in the Spanish multicenter CHAIN study for up to 10 years, with mortality as the main outcome. Patients were dichotomized based on DLco impairment (< 50% cutoff). A Cox proportional hazard model evaluated the added value of DLco to GOLD FEV1 spirometric staging for all-cause and respiratory mortality. Validation of the results was conducted in the Kingston COPD Canadian cohort (N= 300 patients).

Results: Over time, 184 (39.2%) patients died, 84 (17.9%) from respiratory causes. Adjusted analyses showed DLco <50% independently predicted all-cause [HR=1.83 (95%CI 1.32-2.54, p<0.001)] and respiratory [HR=2.27 (95%CI 1.43-3.60, p<0.001)] mortality. Incorporating DLco <50% increased mortality risk compared to FEV1 alone, particularly in GOLD stages 3 and 4, where survival time decreased by 1.23 years (p=0.002) and 1.25 years (p=0.004) for all-cause and respiratory deaths, respectively. These findings were validated in the Canadian cohort.

Conclusions: Adding DLco to FEV1 enhances the prognostic accuracy of the GOLD spirometric severity classification, especially for patients in GOLD stages 3-4 at higher risk of adverse outcomes.