David M G Halpin1, Marc Decramer2, Bartolome R Celli3, Achim Mueller4, Norbert Metzdorf5, Donald P Tashkin6. 1. Royal Devon and Exeter Hospital, Barrack Road, Exeter, EX2 5DW, United Kingdom. Electronic address: d.halpin@nhs.net. 2. Respiratory Division, University Hospital, University of Leuven, Herestraat 49, Leuven, Belgium. Electronic address: marc.decramer@uzleuven.be. 3. Brigham and Women's Hospital, Department of Medicine, Pulmonary, 75 Francis Street, Boston, MA 02115, USA. Electronic address: bcelli@partners.org. 4. Biostatistics & Data Sciences, Boehringer Ingelheim, Biberach an der Riss, 88397, Germany. Electronic address: achim.mueller@boehringer-ingelheim.com. 5. Medicine TA Respiratory Diseases, Boehringer Ingelheim, Ingelheim am Rhein, 55216, Germany. Electronic address: norbert.metzdorf@boehringer-ingelheim.com. 6. David Geffen School of Medicine, University of California Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. Electronic address: dtashkin@mednet.ucla.edu.
Abstract
BACKGROUND: COPD exacerbations are associated with accelerated lung function decline, but whether they are causal is unknown. We evaluated the effect of a single exacerbation on rate of lung function change using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial. METHODS: Retrospective analysis of annual rates of decline in FEV1 and FVC before and after a single (and the only) moderate-to-severe exacerbation in patients during UPLIFT® (exacerbator subgroup), compared with changes between the first and second half of the study in a non-exacerbator subgroup. A sensitivity analysis examined annual rates of decline in matched pairs of exacerbators and non-exacerbators. RESULTS: Following the single moderate-to-severe exacerbation, mean annual decline in post-bronchodilator lung function increased compared with the rate of decline before the exacerbation (FEV1 76.5 vs. 39.1 mL/year, p = 0.003; FVC 106.5 vs. 34.7 mL/year, p = 0.011). In non-exacerbators, there were no differences in rates of decline between the first and second halves of the study (post-bronchodilator FEV1 38.2 vs. 41.8 mL/year, FVC 45.3 vs. 43.9 mL/year. Before the single (moderate-to-severe) exacerbation in the exacerbator subgroup, declines in post-bronchodilator FEV1 or FVC were similar to non-exacerbators in the first half of the study; after the single exacerbation they were significantly higher than for non-exacerbators in the second half of the study. The sensitivity analysis showed similar results. CONCLUSION: A single COPD exacerbation may result in significant increase in the rate of decline in lung function.
RCT Entities:
BACKGROUND: COPD exacerbations are associated with accelerated lung function decline, but whether they are causal is unknown. We evaluated the effect of a single exacerbation on rate of lung function change using data from the 4-year Understanding Potential Long-term Impacts on Function with Tiotropium (UPLIFT®) trial. METHODS: Retrospective analysis of annual rates of decline in FEV1 and FVC before and after a single (and the only) moderate-to-severe exacerbation in patients during UPLIFT® (exacerbator subgroup), compared with changes between the first and second half of the study in a non-exacerbator subgroup. A sensitivity analysis examined annual rates of decline in matched pairs of exacerbators and non-exacerbators. RESULTS: Following the single moderate-to-severe exacerbation, mean annual decline in post-bronchodilator lung function increased compared with the rate of decline before the exacerbation (FEV1 76.5 vs. 39.1 mL/year, p = 0.003; FVC 106.5 vs. 34.7 mL/year, p = 0.011). In non-exacerbators, there were no differences in rates of decline between the first and second halves of the study (post-bronchodilator FEV1 38.2 vs. 41.8 mL/year, FVC 45.3 vs. 43.9 mL/year. Before the single (moderate-to-severe) exacerbation in the exacerbator subgroup, declines in post-bronchodilator FEV1 or FVC were similar to non-exacerbators in the first half of the study; after the single exacerbation they were significantly higher than for non-exacerbators in the second half of the study. The sensitivity analysis showed similar results. CONCLUSION: A single COPD exacerbation may result in significant increase in the rate of decline in lung function.
Keywords:
Bronchodilator; COPD; Exacerbation; Lung function decline; PFT; Pulmonary function test; Tiotropium; UPLIFT(®); Understanding Potential Long-term Impacts on Function with Tiotropium
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