Spirometric Predictors of Lung Function Decline and Mortality in Early Chronic Obstructive Pulmonary Disease

Rationale: The course of lung function decline for smokers with early airflow obstruction remains undefined. It is also unclear which early spirometric characteristics identify individuals at risk for rapid decline and increased mortality. Objectives: To determine the association between spirometric measures and 5-year decline in FEV1 and 12-year mortality. Methods: We analyzed longitudinal data from the Lung Health Study, a clinical trial of intensive smoking cessation intervention with or without bronchodilator therapy in 5,887 smokers with mild to moderate airflow obstruction. Participants were stratified into bins of baseline FEV1 to FVC ratio, using bins of 5%, and separately into bins of Z-score (difference between actual and predicted FEV1/FVC, normalized to SD of predicted FEV1/FVC). Associations between spirometric measures and FEV1 decline and mortality were determined after adjusting for baseline characteristics and time-varying smoking status. Measurements and Main Results: The cohort was approximately two-thirds male, predominantly of white race (96%), and with mean age of 49 +/- 7 years. In general, individuals with lower lung function by any metric had more rapid adjusted FEV1 decline. A threshold for differential decline was present at FEV1/FVC less than 0.65 (P < 0.001) and Z-score less than -2 (2.3 percentile) (P < 0.001). At year 12, 575 (7.2%) of the cohort had died. Lower thresholds of each spirometric metric were associated with increasing adjusted hazard of death. Conclusions: Smokers at risk or with mild to moderate chronic obstructive pulmonary disease have accelerated lung function decline. Individuals with lower baseline FEV1/FVC have more rapid decline and worse mortality.