Forced Vital Capacity Bronchodilator Responsiveness Affects COPD Exacerbations

Forced vital capacity (FVC) bronchodilator responsiveness (BDR) may affect the rate of chronic obstructive pulmonary disease (COPD) exacerbations and may have a role in determining clinical phenotypes of the disease, according to a study published in the Annals of the American Thoracic Society.¹

Data suggests that beta blockers may be beneficial for preventing COPD exacerbations; however, the Beta-Blockers for the Prevention of Acute Exacerbations of Chronic Obstructive Pulmonary Disease (BLOCK COPD; ClinicalTrials.gov Identifier: NCT02587351) study showed that use of the beta-blocker metoprolol is associated with a higher risk of severe COPD exacerbation.^2-4

In the current study, researchers sought to determine the mechanism underlying these results by comparing changes in lung function over the course of the BLOCK COPD trial between treatment groups and by evaluating whether baseline bronchodilator response or early reduction in forced expiratory volume in one second (FEV₁) or FVC was associated with exacerbation risk.¹

The investigators found that over a 336-day treatment period, patients in the metoprolol group had a significantly greater decrease in log-FEV₁, from baseline to day 28 compared with those in the placebo group. Patients in the metoprolol group also had a significantly greater decrease in FVC from baseline to day 14 and 28, and a significantly greater decrease in log-FVC from baseline to visits 42 and 112 than individuals in the placebo group.¹

Notably, there were no associations between early lung function reduction or interactions between lung function reduction and treatment assignment, and time to any or severe/very severe exacerbations. In addition, there were no interactions between the metoprolol group and baseline bronchodilator responsiveness measures on risk or rate of exacerbations. Nevertheless, those with baseline FVC bronchodilator responsiveness had a higher rate of severe/very severe exacerbations.¹

The researchers concluded, “Metoprolol was associated with reduced lung function during the early part of the treatment period [of the BLOCK COPD trial], but these effects were modest and did not persist. Early lung function reduction and baseline bronchodilator responsiveness did not interact with the treatment arm to predict exacerbations; however, baseline FVC bronchodilator responsiveness was associated with a 60% higher rate of severe/very severe exacerbations.”¹

References

1. Parekh TM, Helgeson ES, Connett J, et al. Lung function and the risk of exacerbation in the BLOCK COPD trial. Ann Am Thorac Soc. Published online April 01, 2022. doi:10.1513/AnnalsATS.202109-1042OC
2. Bhatt SP, Wells JM, Kinney GL, et al. β-Blockers are associated with a reduction in COPD exacerbations. Thorax. 2016;71(1):8–14. doi:10.1136/thoraxjnl-2015-207251
3. Du Q, Sun Y, Ding N, Lu L, Chen Y. Beta-blockers reduced the risk of mortality and exacerbation in patients with COPD: a meta-analysis of observational studies. PLOS ONE. 2014;9(11):e113048. doi:10.1371/journal.pone.0113048
4. Dransfield MT, Voelker H, Bhatt SP, et al. Metoprolol for the prevention of acute exacerbations of COPD. New Engl J Med. 2019;381(24):2304–14. doi:10.1056/NEJMoa1908142