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Abstract
Introduction Chronic obstructive pulmonary disease (COPD) exacerbations progress the course of disease and impair lung function. Inhaled maintenance therapy reduces exacerbations. It is not yet established which inhaled therapy combination is best to reduce exacerbations, lung function decline and symptom burden.
Methods and analysis MEDLINE, EMBASE and the Cochrane Library will be searched for articles between January 2011 and May 2018 using a pre-specified search strategy. Conference proceedings will be searched. Systematic reviews (with or without meta-analysis), randomised controlled trials (RCTs), cohort studies and case controlled studies comparing six interventions comprising different combinations of long-acting bronchodilators and inhaled corticosteroids in unison or on their own. The primary outcome is the reduction in moderate-to-severe exacerbations. Secondary outcomes include: lung function, quality of life, mortality and other adverse events. Titles and abstracts will screened by the primary researcher. A second reviewer will repeat this on a proportion of records. The Population, Intervention, Comparator, Outcomes and Study framework will be used for data extraction. A network meta-analyses of outcomes from RCTs and real-world evidence will be integrated if feasible. The 95% credible interval will be used to assess the statistical significance of each summary effect. Ranking of interventions will be based on their surface under cumulative ranking area.
Ethics and dissemination COPD exacerbations are burdensome to patients. We aim to report results that provide clinicians with a more informed choice of which inhaled therapy combinations are best to reduce exacerbations, improve disease burden and reduce lung function and exercise capacity decline, compared with the potential harms, in certain populations with COPD.
PROSPERO registration number CRD42018088013.
- COPD
- inhalers
- LABA
- LAMA
- ICS
- exacerbations
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Footnotes
Patient consent for publication Not required.
Contributors AL and ELA drafted the protocol and developed the inclusion/exclusion criteria, the risk of bias assessment tool, the data extraction form and searching with guidance from JKQ. AL registered and updated the review on PROSPERO. AL, ELA, JP, RT, HV and JKQ contributed to the initial scoping discussions of the research, participated in decisions regarding the risk of bias assessment strategies and contributed to drafting the manuscript. JP provided guidance and contributed to the statistical plan. JKQ, AL and ELA participated in the protocol submission. JKQ is the guarantor of the review.
Funding Boehringer Ingelheim Ltd. Bracknell, UK. Writing and research was funded by Boehringer Ingelheim Ltd; however, the publication of study results is not contingent on the sponsor’s approval or censorship of the manuscript.
Competing interests AL was funded by Boehringer Ingelheim Ltd to perform this systematic review and network meta-analysis. ELA has nothing to declare. JP has nothing to declare. RT and HV are employees of Boehringer Ingelheim Ltd. JKQ’s research group has received funding from The Health Foundation, MRC, Wellcome Trust, BLF, GSK, Insmed, AZ and Bayer for other projects, none of which relate to this work. BI have funded this work. JKQ has received funds from AZ, GSK, Chiesi, Teva and BI for Advisory board participation or travel.
Provenance and peer review Not commissioned; externally peer reviewed.