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Meta-Analysis
. 2017 Jan 11;1(1):CD001284.
doi: 10.1002/14651858.CD001284.pub2.

Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma

Scott W Kirkland  1 , Christine Vandenberghe  1 , Britt Voaklander  1 , Taylor Nikel  1 , Sandra Campbell  2 , Brian H Rowe  1   3
Affiliations
Meta-Analysis

Combined inhaled beta-agonist and anticholinergic agents for emergency management in adults with asthma

Scott W Kirkland et al. Cochrane Database Syst Rev. .

Abstract

Background: Inhaled short-acting anticholinergics (SAAC) and short-acting beta₂-agonists (SABA) are effective therapies for adult patients with acute asthma who present to the emergency department (ED). It is unclear, however, whether the combination of SAAC and SABA treatment is more effective in reducing hospitalisations compared to treatment with SABA alone.

Objectives: To conduct an up-to-date systematic search and meta-analysis on the effectiveness of combined inhaled therapy (SAAC + SABA agents) vs. SABA alone to reduce hospitalisations in adult patients presenting to the ED with an exacerbation of asthma.

Search methods: We searched MEDLINE, Embase, CINAHL, SCOPUS, LILACS, ProQuest Dissertations & Theses Global and evidence-based medicine (EBM) databases using controlled vocabulary, natural language terms, and a variety of specific and general terms for inhaled SAAC and SABA drugs. The search spanned from 1946 to July 2015. The Cochrane Airways Group provided search results from the Cochrane Airways Group Register of Trials which was most recently conducted in July 2016. An extensive search of the grey literature was completed to identify any other potentially relevant studies.

Selection criteria: Included studies were randomised or controlled clinical trials comparing the effectiveness of combined inhaled therapy (SAAC and SABA) to SABA treatment alone to prevent hospitalisations in adults with acute asthma in the emergency department. Two independent review authors assessed studies for inclusion using pre-determined criteria.

Data collection and analysis: For dichotomous outcomes, we calculated individual and pooled statistics as risk ratios (RR) or odds ratios (OR) with 95% confidence intervals (CI) using a random-effects model and reporting heterogeneity (I²). For continuous outcomes, we reported individual trial results using mean differences (MD) and pooled results as weighted mean differences (WMD) or standardised mean differences (SMD) with 95% CIs using a random-effects model.

Main results: We included 23 studies that involved a total of 2724 enrolled participants. Most studies were rated at unclear or high risk of bias.Overall, participants receiving combination inhaled therapy were less likely to be hospitalised (RR 0.72, 95% CI 0.59 to 0.87; participants = 2120; studies = 16; I² = 12%; moderate quality of evidence). An estimated 65 fewer patients per 1000 would require hospitalisation after receiving combination therapy (95% 30 to 95), compared to 231 per 1000 patients receiving SABA alone. Although combination inhaled therapy was more effective than SABA treatment alone in reducing hospitalisation in participants with severe asthma exacerbations, this was not found for participants with mild or moderate exacerbations (test for difference between subgroups P = 0.02).Participants receiving combination therapy were more likely to experience improved forced expiratory volume in one second (FEV₁) (MD 0.25 L, 95% CI 0.02 to 0.48; participants = 687; studies = 6; I² = 70%; low quality of evidence), peak expiratory flow (PEF) (MD 36.58 L/min, 95% CI 23.07 to 50.09; participants = 1056; studies = 12; I² = 25%; very low quality of evidence), increased percent change in PEF from baseline (MD 24.88, 95% CI 14.83 to 34.93; participants = 551; studies = 7; I² = 23%; moderate quality of evidence), and were less likely to return to the ED for additional care (RR 0.80, 95% CI 0.66 to 0.98; participants = 1180; studies = 5; I² = 0%; moderate quality of evidence) than participants receiving SABA alone.Participants receiving combination inhaled therapy were more likely to experience adverse events than those treated with SABA agents alone (OR 2.03, 95% CI 1.28 to 3.20; participants = 1392; studies = 11; I² = 14%; moderate quality of evidence). Among patients receiving combination therapy, 103 per 1000 were likely to report adverse events (95% 31 to 195 more) compared to 131 per 1000 patients receiving SABA alone.

Authors' conclusions: Overall, combination inhaled therapy with SAAC and SABA reduced hospitalisation and improved pulmonary function in adults presenting to the ED with acute asthma. In particular, combination inhaled therapy was more effective in preventing hospitalisation in adults with severe asthma exacerbations who are at increased risk of hospitalisation, compared to those with mild-moderate exacerbations, who were at a lower risk to be hospitalised. A single dose of combination therapy and multiple doses both showed reductions in the risk of hospitalisation among adults with acute asthma. However, adults receiving combination therapy were more likely to experience adverse events, such as tremor, agitation, and palpitations, compared to patients receiving SABA alone.

PubMed Disclaimer

Conflict of interest statement

SWK: none known

CV: none known

BV: none known

TN: none known

SC: none known

BHR: Since 2013 Dr Rowe has received funding from GSK for speaking, study enrolment fees from MedImmune and funding for research from GSK.

Figures

1
1
Study flow diagram
2
2
Funnel plot of comparison: 1 Hosptialisation rates, outcome: 1.1 Hospitalisation rates
3
3
Risk of bias summary
4
4
Risk of bias graph
1.1
1.1. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 1 Hospitalisation.
1.2
1.2. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 2 Hosptialisation worst‐case scenario.
1.3
1.3. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 3 Total adverse events.
1.4
1.4. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 4 Adverse events: Dry mouth.
1.5
1.5. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 5 Adverse events: Tremor.
1.6
1.6. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 6 Adverse events: Anxiety.
1.7
1.7. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 7 Adverse events: Palpitations.
1.8
1.8. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 8 Adverse events: Nausea.
1.9
1.9. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 9 Adverse events: Headache.
1.10
1.10. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 10 Adverse events: Blurred vision.
1.11
1.11. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 11 Adverse events: Agitation.
1.12
1.12. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 12 FEV₁.
1.13
1.13. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 13 Percent change in FEV₁ (%).
1.14
1.14. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 14 Peak expiratory flow (PEF).
1.15
1.15. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 15 Percent change from baseline PEF (%).
1.16
1.16. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 16 Percent predicted PEF (%).
1.17
1.17. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 17 Additional treatment required in the ED.
1.18
1.18. Analysis
Comparison 1 Combination inhaled therapy versus SABA alone, Outcome 18 Relapse rates.
2.1
2.1. Analysis
Comparison 2 Hospitalisation subgroup analysis, Outcome 1 Mulitple versus single dose.
2.2
2.2. Analysis
Comparison 2 Hospitalisation subgroup analysis, Outcome 2 Co‐interventions received.
2.3
2.3. Analysis
Comparison 2 Hospitalisation subgroup analysis, Outcome 3 Exacerbation severity.
2.4
2.4. Analysis
Comparison 2 Hospitalisation subgroup analysis, Outcome 4 Type of anticholinergic used.
3.1
3.1. Analysis
Comparison 3 Hospitalisation sensitivity analysis, Outcome 1 Risk of bias.
3.2
3.2. Analysis
Comparison 3 Hospitalisation sensitivity analysis, Outcome 2 Fixed effects.
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