β-Blockers and the Rate of Chronic Obstructive Pulmonary Disease Exacerbations

2019 ◽  
Vol 53 (12) ◽  
pp. 1249-1258
Author(s):  
Tracey L. Mersfelder ◽  
Dane L. Shiltz

Objective: To review the rate of exacerbations relative to β-blocker use in patients with chronic obstructive pulmonary disease (COPD). Data Sources: A MEDLINE search (1953 to May 2019) was performed using the search terms beta-blockers, chronic obstructive pulmonary disease, and exacerbations. An EMBASE search was also performed using the search terms chronic obstructive lung disease and beta adrenergic receptor blocking agents (1970 to May 2019). References from the review of literature citations were also identified. Study Selection and Data Extraction: English-language studies assessing COPD exacerbations in patients prescribed a β-blocker were included. Any article not addressing exacerbations was excluded. Data Synthesis: A total of 15 articles were included; 7 articles showed no change, 1 provided mixed results, and 7 indicated a significant decrease in COPD exacerbations in a variety of exacerbation severities. Two of the studies differentiated between cardioselective and noncardioselective β-blockers. Relevance to Patient Care and Clinical Practice: This work represents an initial assessment of the use of β-blockers to reduce COPD exacerbations. The findings raise the question if β-blockers should be used more frequently in patients with COPD. Conclusions: Based on the limited number of studies that address β-blocker use in COPD, it appears that exacerbations are not increased and may be decreased. A randomized, placebo-controlled trial is in progress to possibly provide more definitive answers to this question. Until the trial is complete, β-blockers should not be withheld in COPD patients who have concurrent cardiovascular conditions, especially where there is a mortality benefit.

BMJ Open ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. e053446
Author(s):  
Allison Martin ◽  
Robert J Hancox ◽  
Catherina L Chang ◽  
Richard Beasley ◽  
Jeremy Wrobel ◽  
...  

IntroductionHeart disease in chronic obstructive pulmonary disease (COPD) is a common but neglected comorbidity. Patients with COPD are frequently excluded from clinical trials of treatments aimed at reducing cardiac morbidity and mortality, which has led to undertreatment of cardiovascular disease in patients with COPD. A particular concern in COPD is the underuse of beta (β)-blockers. There is observational evidence that cardioselective β-blockers are safe and may even reduce mortality risk in COPD, although some evidence is conflicting. There is an urgent need to answer the research question: Are cardioselective β-blockers safe and of benefit in people with moderately severe COPD? The proposed study will investigate whether cardioselective β-blocker treatment in patients with COPD reduces mortality and cardiac and respiratory morbidity.Methods and analysesThis is a double-blind, randomised controlled trial to be conducted in approximately 26 sites in Australia, New Zealand, India, Sri Lanka and other countries as required. Participants with COPD will be randomised to either bisoprolol once daily (range 1.25–5 mg, dependent on tolerated dose) or matched placebo, in addition to receiving usual care for their COPD over the study duration of 24 months.The study will enrol 1164 participants with moderate to severe COPD, aged 40–85 years. Participants will be symptomatic from their COPD and have a postbronchodilator forced expiratory volume in 1 s (FEV1) ≥30% and ≤70% predicted and a history of at least one exacerbation requiring systemic corticosteroids, antibiotics or both in the prior 24 months.Ethics and disseminationThe study protocol has been approved by the Sydney Local Health District Human Research Ethics Committee at The Concord Repatriation General Hospital.Trial registration numbersNCT03917914; CTRI/2020/08/027322.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Qingling Li ◽  
Weng Wong ◽  
Andrew Birnberg ◽  
Arindam Chakrabarti ◽  
Xiaoying Yang ◽  
...  

Abstract Background Chronic obstructive pulmonary disease (COPD) exacerbations are heterogenous and profoundly impact the disease trajectory. Bioactive lipid lysophosphatidic acid (LPA) has been implicated in airway inflammation but the significance of LPA in COPD exacerbation is not known. The aim of the study was to investigate the utility of serum LPA species (LPA16:0, 18:0, 18:1, 18:2, 20:4) as biomarkers of COPD exacerbation. Patients and methods LPA species were measured in the baseline placebo sera of a COPD randomized controlled trial. Tertile levels of each LPA were used to assign patients into biomarker high, medium, and low subgroups. Exacerbation rate and risk were compared among the LPA subgroups. Results The levels of LPA species were intercorrelated (rho 0.29–0.91). Patients with low and medium levels of LPA (LPA16:0, 20:4) had significantly higher exacerbation rate compared to the respective LPA-high patients [estimated rate per patient per year (95% CI)]: LPA16:0-low = 1.2 (0.8–1.9) (p = 0.019), LPA16:0-medium = 1.3 (0.8–2.0) (p = 0.013), LPA16:0-high = 0.5 (0.2–0.9); LPA20:4-low = 1.4 (0.9–2.1) (p = 0.0033), LPA20:4-medium = 1.2 (0.8–1.8) (p = 0.0089), LPA20:4-high = 0.4 (0.2–0.8). These patients also had earlier time to first exacerbation (hazard ratio (95% CI): LPA16:0-low = 2.6 (1.1–6.0) (p = 0.028), LPA16:0-medium = 2.7 (1.2–6.3) (p = 0.020); LPA20.4-low = 2.8 (1.2–6.6) (p = 0.017), LPA20:4-medium = 2.7 (1.2–6.4) (p = 0.021). Accordingly, these patients had a significant increased exacerbation risk compared to the respective LPA-high subgroups [odd ratio (95% CI)]: LPA16:0-low = 3.1 (1.1–8.8) (p = 0.030), LPA16:0-medium = 3.0 (1.1–8.3) (p = 0.031); LPA20:4-low = 3.8 (1.3–10.9) (p = 0.012), LPA20:4-medium = 3.3 (1.2–9.5) (p = 0.025). For the other LPA species (LPA18:0, 18:1, 18:2), the results were mixed; patients with low and medium levels of LPA18:0 and 18:2 had increased exacerbation rate, but only LPA18:0-low patients had significant increase in exacerbation risk and earlier time to first exacerbation compared to the LPA18:0-high subgroup. Conclusions The study provided evidence of association between systemic LPA levels and exacerbation in COPD. Patients with low and medium levels of specific LPA species (LPA16:0, 20:4) had increased exacerbation rate, risk, and earlier time to first exacerbation. These non-invasive biomarkers may aid in identifying high risk patients with dysregulated LPA pathway to inform risk management and drug development.


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