The effects of macrolides in children with reactive airway disease: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Childhood reactive airway diseases (RADs) are concerning problems in children's airways and may be preceded by bronchiolitis and may progress to childhood asthma. The severity of the disease is indicated by deterioration in pulmonary functions, increased usage of rescue medications, and recurrent wheezing episodes. Macrolides have both antimicrobial and anti-inflammatory functions and have been used as adjunctive therapy in childhood RADs. PATIENTS AND METHODS: We conducted a meta-analysis to evaluate the effect of macrolides in children with RAD. Literature searches were systematically conducted using an electronic database from inception to August 2018. The Cochrane review risk of bias assessment tool was used to assess the quality of each randomized controlled trial. RESULTS: Sixteen randomized controlled trials comprising 1,415 participants were investigated in this meta-analysis. Children treated with macrolide therapy showed significantly better pulmonary functions in both forced expiratory volume in one second (% predicted) (difference in means=-9.77, 95% CI=-14.18 to -5.35, P<0.001; I 2=0%) and forced expiratory flow 25-75 (% predicted) (difference in means=-14.14, 95% CI=-26.11 to -2.18, P=0.02; I 2=29.56%). In addition, the short-acting ß-agonist usage days and recurrent wheezing risk were significantly lowered in children with macrolide treatment (standardized difference in means=-0.34, 95% CI=-0.59 to -0.09, P=0.007, I 2=27.05% and standardized difference in means=-0.53, 95% CI=-0.81 to -0.26, P<0.001, I 2=0%, respectively). Furthermore, the growth of Moraxella catarrhalis from nasal swabs was less in children treated with macrolides (odds ratio=0.19, 95% CI=0.11-0.35, P<0.001). Children who took macrolides had a lower risk of adverse events (risk ratio=0.83, 95% CI=0.70-0.98, P=0.024, I 2=0%). CONCLUSION: This current meta-analysis suggested that adjunctive therapy with macrolides is safe and effective for achieving better outcomes in childhood RAD.

Effects of Macrolide Treatment during the Hospitalization of Children with Childhood Wheezing Disease: A Systematic Review and Meta-Analysis.

Children are susceptible to a variety of respiratory infections. Wheezing is a common sign presented by children with respiratory infections. Asthma, bronchiolitis, and bronchitis are common causes of childhood wheezing disease (CWD) and are regarded as overlapping disease spectra. Macrolides are common antimicrobial agents with anti-inflammatory effects. We conducted a comprehensive literature search and a systematic review of studies that investigated the influences of macrolide treatment on CWD. The primary outcomes were the impact of macrolides on hospitalization courses of patients with CWD. Data pertaining to the study population, macrolide treatment, hospital courses, and recurrences were analyzed. Twenty-three studies with a combined study population of 2210 patients were included in the systematic review. Any kind of benefit from macrolide treatment was observed in approximately two-thirds of the studies (15/23). Eight studies were included in the meta-analysis to investigate the influence of macrolides on the length of stay (LOS), duration of oxygen demand (DOD), symptoms and signs of respiratory distress, and re-admission rates. Although the benefits of macrolide treatment were reported in several of the studies, no significant differences in LOS, DOD, symptoms and signs of respiratory distress, or re-admission rates were observed in patients undergoing macrolide treatment. In conclusion, any kind of benefit of macrolide treatment was observed in approximately two-thirds of the studies; however, no obvious benefits of macrolide treatment were observed in the hospitalization courses of children with CWD. The routine use of macrolides to improve the hospitalization course of children with CWD is not suggested.