Sarah A Hiles1,2, Vanessa M McDonald3,2,4, Michelle Guilhermino2,5, Guy G Brusselle6,7, Peter G Gibson3,4. 1. Centre of Excellence in Severe Asthma and Priority Research Centre for Healthy Lungs, University of Newcastle, Callaghan, Australia sarah.hiles@newcastle.edu.au. 2. School of Nursing and Midwifery, Faculty of Health, University of Newcastle, Callaghan, Australia. 3. Centre of Excellence in Severe Asthma and Priority Research Centre for Healthy Lungs, University of Newcastle, Callaghan, Australia. 4. Dept of Respiratory and Sleep Medicine, John Hunter Hospital, New Lambton Heights, Australia. 5. Intensive Care Unit, John Hunter Hospital, New Lambton Heights, Australia. 6. Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium. 7. Depts of Epidemiology and Respiratory Medicine, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
Abstract
BACKGROUND: Preventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma. METHOD: We completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes. RESULTS: Three studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated. DISCUSSION: Maintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.
BACKGROUND: Preventing exacerbations is an important goal of asthma treatment. Long-term treatment with azithromycin may help achieve this. Our aim was to conduct a systematic review and individual participant data (IPD) meta-analysis to examine the efficacy of azithromycin in reducing exacerbations in asthma, and in the subphenotypes of noneosinophilic asthma, eosinophilic asthma and severe asthma. METHOD: We completed a systematic search of Embase, MEDLINE, PubMed, Cochrane Library, ClinicalTrials.gov and reference lists of previous systematic reviews in February 2019. We included parallel-group, double-blind, randomised controlled trials in adults comparing at least 8 weeks of azithromycin treatment with placebo, where the outcome of exacerbations was assessed over at least 6 months. Data were extracted from published sources, Cochrane Risk of Bias Tool was applied and IPD were sought from authors. Reviews were undertaken in duplicate. We conducted an IPD meta-analysis on the primary outcome of exacerbations and a random effects meta-analysis for secondary outcomes. RESULTS: Three studies were identified (n=604). In the IPD meta-analysis, treatment with azithromycin was associated with a reduced rate of exacerbations (oral corticosteroid course due to worsening asthma, antibiotic use for lower respiratory tract infection, hospitalisation and/or emergency department visits) in asthma as well as in the noneosinophilic, eosinophilic and severe asthma subgroups. Examining each exacerbation type separately, patients with eosinophilic asthma reported fewer oral corticosteroid courses, and patients with noneosinophilic and severe asthma reported fewer antibiotic courses. Azithromycin was well tolerated. DISCUSSION: Maintenance use of azithromycin reduces exacerbations in patients with eosinophilic, noneosinophilic and severe asthma.
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