Comparative safety and effectiveness of inhaled bronchodilators and corticosteroids for treating asthma–COPD overlap: a systematic review and meta-analysis

Abstract

Objective

To determine the safety and effectiveness of current pharmacotherapies consisting of long-acting beta₂-agonist (LABA) and/or inhaled corticosteroids (ICS) in patients with asthma–COPD overlap.

Data sources

A systematic search was conducted using the PubMed, EMBASE, and Web of Science databases up to June 2018.

Study selections

Only studies comparing the safety and effectiveness of LABA and/or ICS in patients with asthma–COPD overlap were included. A meta-analysis was performed to calculate risk ratio (RR) and 95% confidence interval (CI) using Inverse Variance Random-effects model.

Results

From a total of 3382 articles retrieved, three randomized controlled trials (RCTs), six cohort studies (CS), one nested case control study fulfilled the inclusion criteria for three independent meta-analyses representing 181,603 participants. Three CS results show LABA was associated with decreased risk of myocardial infarction (combined RR: 0.80, 95% CI 0.74–0.87) versus non-LABA use; ICS/LABA was associated with a lower risk of death or hospitalization (combined RR: 0.82, 95% CI 0.75–0.90) compared to no use. Results from RCTs, no clear difference in lung function decline in FEV₁ was found (combined mean difference: 0.08, 95% CI 0.15–0.32) in patients receiving ICS and/or LABA compared to placebo. However, due to lack of data, exacerbations, fractures and nontuberculous mycobacterial pulmonary disease outcomes were not meta-analyzed.

Conclusions

Among patients with asthma–COPD overlap, LABA is associated with decreased risk of myocardial infarction; and the combination therapy of ICS/LABA appears to reduce the risk of death or hospitalization. More studies of quality data and larger number of patients are needed.

REGISTRATION

PROSPERO (CRD42018090863).

Keywords:

• Asthma–COPD overlap
• long-acting beta2-agonist
• inhaled corticosteroids
• systematic review
• meta-analysis

Acknowledgements

The authors would like to thank Allison Farrell, Michelle Swab, and Shannon McAlorum, librarians at Memorial University for their kind dedication and expertise in helping with the literature search strategy.

Authors’ contributions

JEA, JG, LA, J-MG, JF and ZG conceived the study and designed the study protocol. JEA was responsible for registering the study in PROSPERO. JEA developed the search strategy as well as conducted the search strategy with the help of two librarians. JEA, JG, LA, J-MG, JF and ZG conducted the screening and study selection. The inclusion and selection of ACO patients was prior verified by JF. Data analysis and interpretation was carried out by JEA, JG, LA, J-MG, JF and ZG. JEA, JG, LA, J-MG, JF and ZG drafted the manuscript, commented on and approved the final version of the manuscript. ZG is responsible for the study management and coordination and he is also the study guarantor.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Disclaimer

The study funder was not involved in the study design or the writing of the protocol.

Additional information

Funding

This work was supported by a research grant from Canada Research Respiratory Network (CRRN), Ottawa, Canada, (Young Investigator Award, 2017).