10-Year Follow-Up of Lung Function, Respiratory Symptoms, and Functional Capacity in the COPDGene Study

Rationale: The course of lung function, respiratory symptoms, and functional status over time in people who smoke cigarettes is still incompletely understood. The COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]) study provides a unique cohort to examine these trajectories, and now 10-year follow-up data are available. Objectives: This study aims to provide insight into the progression of spirometric parameters, respiratory symptoms, and functional capacity over 10 years in current and former cigarette smokers. Methods: We analyzed available longitudinal data for COPDGene participants who did not change smoking status over three visits spanning approximately 10 years of follow-up. Change in postbronchodilator forced expiratory volume in 1 second (FEV₁), St. George's Respiratory Questionnaire (SGRQ), and 6-minute walk distance (6MWD) from Phase 1 to Phase 3 were examined using linear mixed models. Terms were included in the models to estimate mean progression separately for current and former cigarette smokers. Models were stratified by baseline Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometry stages as well as by new 2019 COPDGene classification. Results: The mean age at enrollment of the 9,103 participants in this analysis was 59.8 years (SD = 9.2 yr); 46.4% were women, and 32.6% were African American. In all GOLD COPD groups, including participants with normal spirometry, and all groups categorized by 2019 COPDGene classification, FEV₁ decreased, SGRQ increased (indicating higher symptom burden), and 6MWD decreased over the 10-year follow-up period. Current smokers exhibited a greater mean loss of FEV₁ over the study period than former smokers for all groups except those with preserved ratio impaired spirometry. For both SGRQ and 6MWD, rates of progression tended to be similar for former and current smokers except for 6MWD in the highest severity groups, in which former smokers had greater progression. However, this could be impacted by some current smokers with faster progression who had quit smoking and were dropped from analyses. Conclusions: Progression in FEV₁, SGRQ, and 6MWD overall appears to be slow, and the change over time in groups traditionally characterized as not having disease closely mirrors that of the groups with COPD at all GOLD stages. Current cigarette smokers had greater loss of FEV₁ than former smokers, whereas SGRQ and 6MWD changes were more similar between current and former cigarette smokers.