Comparison of the variability of the annual rates of change in FEV₁ determined from serial measurements of the pre- versus post-bronchodilator FEV₁ 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 FEV₁ determined from serial measurements of the post-, in preference to the pre-, bronchodilator FEV₁. We therefore compared the yearly slope and the variability of the slope of the pre- versus the post-bronchodilator FEV₁ 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 FEV₁ at baseline (screening visit 2) and all five annual visits. The annual rate of decline in FEV₁ (±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 FEV₁ 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 FEV₁ (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 FEV₁ (range 0.05-0.11 ml/yr). Conversely, the standard deviations of the mean FEV₁ 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 FEV₁. 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 FEV₁. 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.


CONCLUSIONS
Serial measurements of the pre-bronchodilator FEV₁ are generally sufficient for comparing the impact of different interventions on the annual rate of change in FEV₁.
Departments of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. dtashkin@mednet.ucla.edu
Donald P
DP
Tashkin
He-Jing
HJ
Wang
David
D
Halpin
Eric C
EC
Kleerup
John
J
Connett
Ning
N
Li
Robert
R
Elashoff
D000328:Adult; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects / Q000502:physiology*; D006304:Health Status; D006801:Humans; D008168:Lung / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology*; D012129:Respiratory Function Tests / Q000379:methods; D013997:Time Factors
D001993:Bronchodilator Agents