Acute bronchodilator responses decline progressively over 4 years in patients with moderate to very severe COPD

Abstract

Background: We previously reported a progressive decline in absolute responses of FEV1 and FVC to a near-maximal dose of 2 different short-acting bronchodilators over 4 years. Since varying host factors and the method of expressing the response may impact the time trend of acute bronchodilator responses, we now examined the potential influence of salient host characteristics on changes in bronchodilator responses over time expressed in different ways.

Methods: As part of the 4-year, placebo-controlled Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT) trial, pre- and post-bronchodilator spirometry was performed at baseline and 1 month and every 6 months thereafter. Post-bronchodilator values for FEV1 and FVC were analyzed for subjects completing at least the 1 year visit (Placebo - N = 2463; Tiotropium - N = 2579), stratified by GOLD stage, age, gender and smoking status and expressed as absolute, relative (%) and % predicted changes from pre-bronchodilator values. Annual changes in bronchodilator response were estimated using linear mixed effects models.

Results: For all subjects analyzed, FEV1 and FVC bronchodilator responses showed progressive and highly significant (p < 0.0001) declines over 4 years. Declines were generally larger in patients with severe/very severe than mild/moderate airflow obstruction, in older patients (≥65 yrs) and in former than continuing smokers.

Conclusion: Acute FEV1 and FVC responses to bronchodilators decline significantly over time in COPD patients, whether expressed as absolute, relative or % predicted changes, potentially impacting on the clinical responses to bronchodilator therapy as well as on the annual rate of decline in post-bronchodilator lung function. Clinicaltrials.gov number: NCT00144339.

Figures

Figure 1

Mean absolute bronchodilator responses (±SD) (Δ = post- minus pre-bronchodilator FEV1 and FVC, ml) over 4 years by treatment group separately (placebo and tiotropium). Mean absolute FEV1 responses are shown for the placebo group (A) and the tiotropium group (B) separately. Mean absolute FVC responses are shown for the placebo group (C) and the tiotropium group (D) separately.

Figure 2

Mean percent changes (±SD) (Δ = post - minus pre-bronchodilator FEV1 and FVC, ml/pre-bronchodilator FEV1 and FVC, ml * 100, %) over 4 years by treatment group. Mean relative FEV1 responses (percent changes) are shown for the placebo group (A) and the tiotropium group (B) separately. Mean relative responses (percent changes) in FVC are shown for the placebo group (C) and the tiotropium group (D) separately.

Figure 3

Mean (±SD) % predicted (Δ = post-bronchodilator [% predicted] - minus pre-bronchodilator [% predicted] FEV1 and FVC) bronchodilator responses over 4 years by treatment group. Mean % predicted FEV1 responses are shown for the placebo group (A) and the tiotropium group (B) separately. Mean percent predicted responses in FVC are shown for the placebo group (C) and the tiotropium group (D) separately.