Utility of adjunctive macrolide therapy in treatment of children with asthma: a systematic review and meta-analysis

Anar Mikailov,¹ Ilona Kane,² Stephen C Aronoff,³ Raemma Luck,^3,† Michael T DelVecchio<sup>3

1</sup>Beth Israel Deaconess Medical Center, Boston, MA, ²St Christopher's Hospital for Children, Philadelphia, PA, ³Department of Pediatrics, Temple University School of Medicine, Philadelphia, PA, USA

^†Raemma Luck is now deceased

Background: The purpose of this study was to investigate macrolides as an adjunct to an asthma controller regimen in children with asthma.
Methods: Prospective clinical trials of macrolide therapy in children with asthma using outcome measures of change in forced expiratory volume in one second (FEV₁) and/or oral corticosteroid requirement were searched for in PubMed up to December 2009. The reference lists of studies were also included in the analysis, as well as those listed in published meta-analyses.
Results: The literature search yielded 116 studies, six of which were included in this meta-analysis. The change in FEV₁ from baseline with adjunctive use of macrolide therapy in all children was not significant (0.25% predicted; 95% confidence interval [CI] −0.37, 0.86 predicted, P = 0.43); however, the change in FEV₁ among children receiving daily oral corticosteroids was significant (3.89% predicted; 95% CI −0.01, 7.79, P = 0.05). Addition of macrolide therapy to the treatment of children with oral corticosteroid-dependent asthma resulted in a statistically significant decrease in daily corticosteroid dosage (−3.45 mg/day; 95% CI −5.79, −1.09 mg/day, P = 0.004). This reduction in daily corticosteroid dosage was directly proportional to the duration of macrolide therapy (−0.17 mg methylprednisolone per week of macrolide therapy; 95% CI −0.33, −0.021, P = 0.025).
Conclusion: Addition of macrolides to the treatment regimen of children with oral corticosteroid-dependent asthma improves FEV₁ and decreases the daily dosage of corticosteroids required for control in these children. The degree of dose reduction is directly related to the duration of macrolide therapy. Additional large, randomized, placebo-controlled trials of adjunctive macrolide use in children with oral corticosteroid-dependent asthma are required to verify this observation.

Keywords: chronic asthma, macrolides, corticosteroid sparing