Comparison of the variability of the annual rates of change in FEV(1) determined from serial measurements of the pre- versus post-bronchodilator FEV(1) over 5 years in mild to moderate COPD: Results of the lung health study

BACKGROUND: The impact of interventions on the progressive course of COPD is currently assessed by the slope of the annual decline in FEV(1) determined from serial measurements of the post-, in preference to the pre-, bronchodilator FEV(1). We therefore compared the yearly slope and the variability of the slope of the pre- versus the post-bronchodilator FEV(1) in men and women with mild to moderate COPD who participated in the 5-year Lung Health Study (LHS). METHODS: Data were analyzed from 4484 of the 5887 LHS participants who had measurements of pre- and post-bronchodilator FEV(1) at baseline (screening visit 2) and all five annual visits. The annual rate of decline in FEV(1) (±SE) measured pre- and post-bronchodilator from the first to the fifth annual visit was estimated separately using a random coefficient model adjusted for relevant covariates. Analyses were performed separately within each of the three randomized intervention groups. In addition, individual rates of decline in pre- and post-bronchodilator FEV(1) were also determined for each participant. Furthermore, sample sizes were estimated for determining the significance of differences in slopes of decline between different interventions using pre- versus post-bronchodilator measurements. RESULTS: Within each intervention group, mean adjusted and unadjusted slope estimates were slightly higher for the pre- than the post-bronchodilator FEV(1) (range of differences 2.6-5.2 ml/yr) and the standard errors around these estimates were only minimally higher for the pre- versus the post-bronchodilator FEV(1) (range 0.05-0.11 ml/yr). Conversely, the standard deviations of the mean FEV(1) determined at each annual visit were consistently slightly higher (range of differences 0.011 to 0.035 L) for the post- compared to the pre-bronchodilator FEV(1). Within each group, the proportion of individual participants with a statistically significant slope was similar (varying by only 1.4 to 2.7%) comparing the estimates from the pre- versus the post-bronchodilator FEV(1). However, sample size estimates were slightly higher when the pre- compared to the post-bronchodilator value was used to determine the significance of specified differences in slopes between interventions. CONCLUSION: Serial measurements of the pre-bronchodilator FEV(1) are generally sufficient for comparing the impact of different interventions on the annual rate of change in FEV(1).