The authors note that their research had limitations that need to be considered when interpreting the results. For example the included trials used different definitions of asthma exacerbation; for this reason the meta-analyses only included studies that clearly defined and reported this outcome. This was only a small proportion of the 50 eligible trials included in the systematic review.
Other limitations include inconsistent definitions of asthma severity in the individual trials, and the effect of baseline asthma severity on summary treatment effects could not be assessed. In addition studies used different analytic scales for the same outcome measure (e.g. change in baseline FEV1 reported as an absolute figure in some and a percentage in others), which prevented combination of all available data. There was between-study statistical heterogeneity for most outcomes, and the authors suggest the summary effect sizes from the meta-analyses may be overstated. As only peer-reviewed and English-language publications were included, publication bias cannot be excluded.
The authors conclude by discussing the fact that the particular patient subgroups that are more likely to responds to LTRAs remains unclear. They call for professional organisations or expert panels to recommend standardised study protocols, definitions of phenotypes, and outcome measures for the purpose of research and they encourage future researchers to implement these standards.