Chest
Volume 145, Issue 4, April 2014, Pages 779-786
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Original Research: Asthma
Adverse Respiratory Effect of Acute β-Blocker Exposure in Asthma: A Systematic Review and Meta-analysis of Randomized Controlled Trials

https://doi.org/10.1378/chest.13-1235Get rights and content

Background

β-Blockers are avoided in asthma over concerns regarding acute bronchoconstriction. Risk is greatest following acute exposure, including the potential for antagonism of β2-agonist rescue therapy.

Methods

A systematic review of databases was performed to identify all randomized, blinded, placebo-controlled clinical trials evaluating acute β-blocker exposure in asthma. Effect estimates for changes in respiratory function, symptoms, and β2-agonist response were pooled using random effects meta-analysis with heterogeneity investigated.

Results

Acute selective β-blockers in the doses given caused a mean change in FEV1 of −6.9% (95% CI, −8.5 to −5.2), a fall in FEV1 of ≥ 20% in one in eight patients (P = .03), symptoms affecting one in 33 patients (P = .18), and attenuation of concomitant β2-agonist response of −10.2% (95% CI, −14.0 to −6.4). Corresponding values for acute nonselective β-blockers in the doses given were −10.2% (95% CI, −14.7 to −5.6), one in nine patients (P = .02), one in 13 patients (P = .14), and −20.0% (95% CI, −29.4 to −10.7). Following investigation of heterogeneity, clear differences were found for celiprolol and labetalol. A dose-response relationship was demonstrated for selective β-blockers.

Conclusions

Selective β-blockers are better tolerated but not completely risk-free. Risk from acute exposure may be mitigated using the smallest dose possible and β-blockers with greater β1-selectivity. β-Blocker-induced bronchospasm responded partially to β2-agonists in the doses given with response blunted more by nonselective β-blockers than selective β-blockers. Use of β-blockers in asthma could possibly be based upon a risk assessment on an individual patient basis.

Section snippets

Materials and Methods

A systematic review of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) databases was performed using a prespecified protocol and search strategy (e-Tables 1, 2) to identify all randomized, blinded, placebo-controlled clinical trials published on or before January 20, 2013, evaluating acute β-blocker exposure (up to 7 days) in asthma. References and full texts were independently screened by a minimum of two reviewers, with agreement based on consensus. References of

Results

Of 1,989 references screened, 32 studies were included (Fig 1, e-Table 37, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41). A total of 16 studies evaluated selective β-blockers, six studies evaluated nonselective β-blockers, and 10 studies evaluated both. No randomized blinded placebo-controlled trials evaluating topical β-blockers in unselected patients were found. For selective β-blockers, 23 studies

Discussion

Acute selective β-blockade in the doses given caused statistically significant mean reductions in FEV1, nonsignificant increases in symptoms, and significant absolute falls in FEV1 of ≥ 20% (affecting 13% of subjects). For mean changes in FEV1 and symptoms, findings were similar to a previous meta-analysis, which evaluated selective β-blockers only and did not include fall in FEV1 of ≥ 20% as an outcome.3 Our findings suggest that, although the mean effects of acute selective β-blockade are

Acknowledgments

Author contributions: Dr Morales is guarantor of the data.

Dr Morales: contributed to conceiving the idea, study design, interpretation of the findings, data analysis, drafting of the manuscript, and approving the final draft.

Dr Jackson: contributed to conceiving the idea, study design, interpretation of the findings, drafting of the manuscript, and approving the final draft.

Dr Lipworth: contributed to study design, interpretation of the findings, drafting of the manuscript, and approving the

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    Funding/Support: This study was funded by a Scottish Government Chief Scientist Office Clinical Academic Fellowship, which provided research costs and support for Dr Morales [Grant CAF/11/07].

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

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