Macrolides may attenuate airway inflammation of bronchiolitis with anti-inflammatory and antiviral effects. But the potential mechanisms of macrolides for bronchiolitis is limited. Therefore, we conducted a meta-analysis to assess effects of macrolides on airway microbiome and cytokine of children with bronchiolitis. PubMed, Embase, Cochrane Central Register of Controlled Trials were searched until May 2018. The reference lists of included studies and pertinent reviews were checked for supplementing our search. Randomized controlled trials (RCTs) which compared macrolides versus placebo assessing the change of microbiome in airway and cytokine were included. A total of 4 RCTs were included in this review. Data analysis showed there was no significant reduction of viruses at 48 hours after azithromycin treatment(p=0.41). There were significant reductions in streptococcus pneumoniae (RR 0.28, 95% CI 0.14 to 0.6, p<0.01), haemophilus influenza (RR 0.35, 95% CI 0.2 to 0.62, p<0.01) and moraxella catarrhalis (RR 0.29, 95% CI 0.17 to 0.5, p<0.01) but no significant reduction of staphylococcus aureus(p=0.28) after the treatment of macrolides. There was a significant decrease in the serum interleukin-8 (IL-8), interleukin-4 (IL-4) and eotaxin following three weeks of clarithromycin therapy. However, there was no significant difference in serum IL-8 level at day 15 after intervention between the azithromycin and control groups, while a significant reduction of nasal lavage IL-8 level was found. The macrolides may reduce the IL-8 in airway and plasma, but failed to have an antiviral effect of macrolides for children with bronchiolitis. This article is protected by copyright. All rights reserved.
OBJECTIVE: To systematically evaluate the clinical effect of azithromycin (AZM) adjuvant therapy in children with bronchiolitis.
METHODS: Related databases were searched for randomized controlled trials (RCTs) on AZM adjuvant therapy in children with bronchiolitis published up to February 17, 2019. RevMan 5.3 was used to perform the Meta analysis.
RESULTS: A total of 14 RCTs were included, with 667 children in the intervention group and 651 in the control group. The pooled effect size showed that in the children with bronchiolitis, AZM adjuvant therapy did not shorten the length of hospital stay (MD=-0.29, 95%CI: -0.62 to 0.04, P=0.08) or oxygen supply time (MD=-0.33, 95%CI: -0.73 to 0.07, P=0.10), while it significantly shortened the time to the relief of wheezing (MD=-1.00, 95%CI: -1.72 to -0.28, P=0.007) and cough (MD=-0.48, 95%CI: -0.67 to -0.29, P<0.00001). The analysis of bacterial colonization revealed that AZM therapy significantly reduced the detection rates of Streptococcus pneumoniae (OR=0.24, 95%CI: 0.11-0.54, P=0.0006), Haemophilus (OR=0.28, 95%CI: 0.14-0.55, P=0.0002), and Moraxella catarrhalis (OR=0.21, 95%CI: 0.11-0.40, P<0.00001) in the nasopharyngeal region.
CONCLUSIONS: AZM adjuvant therapy can reduce the time to the relief of wheezing and cough in children with bronchiolitis, but it has no marked effect on the length of hospital stay and oxygen supply time.
BACKGROUND: Bronchiolitis is a common acute respiratory condition with high prevalence worldwide. This clinically diagnosed syndrome is manifested by tachypnoea (rapid breathing), with crackles or wheeze in young children. In the acute phase of bronchiolitis (≤ 14 days), antibiotics are not routinely prescribed unless the illness is severe or a secondary bacterial infection is suspected. Although bronchiolitis is usually self-limiting, some young children continue to have protracted symptoms (e.g. cough and wheezing) beyond the acute phase and often re-present to secondary care.
OBJECTIVES: To compare the effectiveness of antibiotics versus controls (placebo or no treatment) for reducing or treating persistent respiratory symptoms following acute bronchiolitis within six months of acute illness.
SEARCH METHODS: We searched the following databases: the Cochrane Airways Group Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), Embase (Ovid), the World Health Organization (WHO) trial portal, the Australian and New Zealand Clinical Trials Registry, and ClinicalTrials.gov, up to 26 August 2016.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing antibiotics versus controls (placebo or no treatment) given in the post-acute phase of bronchiolitis (> 14 days) for children younger than two years with a diagnosis of bronchiolitis.
DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies against predefined criteria, and selected, extracted, and assessed data for inclusion. We contacted trial authors for further information.
MAIN RESULTS: In this review update, we added one study with 219 children. A total of two RCTs with 249 children (n = 240 completed) were eligible for inclusion in this review. Both studies contributed to our primary and secondary outcomes, but we assessed the quality of evidence for our three primary outcomes as low, owing to the small numbers of studies and participants; and high attrition in one of the studies. Data show no significant differences between treatment groups for our primary outcomes: proportion of children (n = 249) who had persistent symptoms at follow-up (odds ratio (OR) 0.69, 95% confidence interval (CI) 0.37 to 1.28; fixed-effect model); and number of children (n = 240) rehospitalised with respiratory illness within six months (OR 0.54, 95% CI 0.05 to 6.21; random-effects model). We were unable to analyse exacerbation rate because studies used different methods to report this information. Data showed no significant differences between treatment groups for our secondary outcome: proportion of children (n = 240) with wheeze at six months (OR 0.47, 95% CI 0.06 to 3.95; random-effects model). One study reported bacterial resistance, but only at 48 hours (thus with limited applicability for this review). Another study reported adverse events from which all children recovered and remained in the study.
AUTHORS' CONCLUSIONS: Current evidence is insufficient to inform whether antibiotics should be used to treat or prevent persistent respiratory symptoms in the post-acute bronchiolitis phase. Future RCTs are needed to evaluate the efficacy of antibiotics for reducing persistent respiratory symptoms. This is particularly important in populations with high acute and post-acute bronchiolitis morbidity (e.g. indigenous populations in Australia, New Zealand, and the USA).
Macrolides may attenuate airway inflammation of bronchiolitis with anti-inflammatory and antiviral effects. But the potential mechanisms of macrolides for bronchiolitis is limited. Therefore, we conducted a meta-analysis to assess effects of macrolides on airway microbiome and cytokine of children with bronchiolitis. PubMed, Embase, Cochrane Central Register of Controlled Trials were searched until May 2018. The reference lists of included studies and pertinent reviews were checked for supplementing our search. Randomized controlled trials (RCTs) which compared macrolides versus placebo assessing the change of microbiome in airway and cytokine were included. A total of 4 RCTs were included in this review. Data analysis showed there was no significant reduction of viruses at 48 hours after azithromycin treatment(p=0.41). There were significant reductions in streptococcus pneumoniae (RR 0.28, 95% CI 0.14 to 0.6, p<0.01), haemophilus influenza (RR 0.35, 95% CI 0.2 to 0.62, p<0.01) and moraxella catarrhalis (RR 0.29, 95% CI 0.17 to 0.5, p<0.01) but no significant reduction of staphylococcus aureus(p=0.28) after the treatment of macrolides. There was a significant decrease in the serum interleukin-8 (IL-8), interleukin-4 (IL-4) and eotaxin following three weeks of clarithromycin therapy. However, there was no significant difference in serum IL-8 level at day 15 after intervention between the azithromycin and control groups, while a significant reduction of nasal lavage IL-8 level was found. The macrolides may reduce the IL-8 in airway and plasma, but failed to have an antiviral effect of macrolides for children with bronchiolitis. This article is protected by copyright. All rights reserved.
