Classification of Airflow Limitation Based on z -Score Underestimates Mortality in Patients with Chronic Obstructive Pulmonary Disease

Rationale Global Lung Function Initiative recommends reporting lung function measures as z-score, and a classification of airflow limitation (AL) based on this parameter has recently been proposed. Objectives To evaluate the prognostic capacity of the AL classifications based on z-score or percentage predicted of FEV1 in patients with chronic obstructive pulmonary disease (COPD). Methods A cohort of 2,614 patients with COPD recruited outside the hospital setting was examined after a mean (± SD) of 57 ± 13 months of follow-up, totaling 10,322 person-years. All-cause mortality was analyzed, evaluating the predictive capacity of several AL staging systems. Measurements and Main Results Based on Global Initiative for Chronic Obstructive Lung Disease guidelines, 461 patients (17.6%) had mild, 1,452 (55.5%) moderate, 590 (22.6%) severe, and 111 (4.2%) very severe AL. According to z-score classification, 66.3% of patients remained with the same severity, whereas 23.7% worsened and 10.0% improved. Unlike other staging systems, patients with severe AL according to z-score had higher mortality than those with very severe AL (increase of risk by 5.2 and 3.9 times compared with mild AL, respectively). The predictive capacity for 5-year survival was slightly higher for FEV1 expressed as percentage of predicted than as z-score (area under the curve: 0.714–0.760 vs. 0.649–0.708, respectively). A severity-dependent relationship between AL grades by z-score and mortality was only detected in patients younger than age 60 years. Conclusions In patients with COPD, the AL classification based on z-score predicts worse mortality than those based on percentage of predicted. It is possible that the z-score underestimates AL severity in patients older than 60 years of age with severe functional impairment.