title: Annual rates of change in pre- vs. post-bronchodilator FEV1 and FVC over 4 years in moderate to very severe COPD.
abstract: While the slope of decline in FEV1 has traditionally been calculated from the post- rather than the pre-bronchodilator measurement in COPD interventional trials, it is not clear whether and to what extent these two slopes differ in symptomatic patients with COPD. Therefore, we used data from the 4-year UPLIFT trial of tiotropium 18 mcg QD vs. placebo to compare annual rates of change in pre- vs. post-bronchodilator FEV1 in 5041 patients with moderate to very severe COPD (mean FEV1 48% pred) in whom the post-bronchodilator FEV1 was measured after 4 inhalations of two different classes of short-acting inhaled bronchodilators at baseline and 1 month and every 6 months post-randomization over 4 years. Linear mixed effects models were used to estimate annual rates of decline in FEV1 and FVC pre- and post-bronchodilator in each treatment group separately, after adjusting for height, gender, smoking status, baseline % predicted FEV1 or FVC, and baseline acute % improvement in lung function. The slopes of the post-bronchodilator FEV1 and FVC were significantly steeper than the pre-bronchodilator slopes regardless of treatment arm (p < 0.001), while the estimated variances of the slopes were similar. Post-bronchodilator increases in FEV1 and FVC diminished progressively and significantly (p < 0.0001) over the 4-year trial, suggesting a possible explanation for the significant differences between the pre- and post-bronchodilator slopes. While the reasons for these differences are not completely clear, they are important to consider when assessing treatment effects on rates of decline in FEV1 and FVC.
authors: David Geffen School of Medicine at UCLA, 10833 Le Conte Ave., Los Angeles, CA 90095, USA. Electronic address: dtashkin@mednet.ucla.edu.
authors: Donald P
authors: DP
authors: Tashkin
authors: Ning
authors: N
authors: Li
authors: David
authors: D
authors: Halpin
authors: Eric
authors: E
authors: Kleerup
authors: Marc
authors: M
authors: Decramer
authors: Bartolome
authors: B
authors: Celli
authors: Robert
authors: R
authors: Elashoff
mesh_terms: D000280:Administration, Inhalation; D000420:Albuterol / Q000008:administration & dosage*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005541:Forced Expiratory Volume / Q000187:drug effects; D006801:Humans; D009241:Ipratropium / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D014797:Vital Capacity / Q000187:drug effects
chemical_list: D001993:Bronchodilator Agents; D009241:Ipratropium; D000420:Albuterol
keywords: COPD; Post-bronchodilator; Slope of FEV(1) decline; UPLIFT
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