The efficacy and safety of azithromycin in treatment for childhood asthma: a systematic review and meta-analysis
Authors: Pan Xiangcheng , Liu Yan , Luo Jiefeng , Li Siyu , Diao Sha , Li Hailong , Huang Liang , Jia Zhijun , Chen Lina , Liu Hanmin , Zhang Lingli 
Published: May 2021

Background: Evidence suggests controversial results based on the
antibacterial and anti-inflammatory effects of azithromycin (AZI) in the
treatment of childhood asthma. This study was to further evaluate the
efficacy and safety of AZI in childhood asthma. Methods: We searched
PubMed, Embase (via Ovid), Cochrane Library, China National Knowledge
Infrastructure, Chinese Scientific Journals database, WANFANG, and
Chinese Biomedical Literature database from inception to November 11,
2020. Randomized controlled trials (RCTs) of AZI versus placebo or one
positive control drug, AZI plus anti-asthma drugs (AADs) versus the same
AADs, and AZI plus AADs versus placebo or one positive control drug plus
the same AADs were included. Primary outcomes were number of
exacerbations (NoE); score of clinical tools to assess asthma control
after treatment; number of days to relieve symptoms with β2 agonist
(DBA); post-treatment lung function indicators, including FEV1% of
predicted value (pFEV1%), FVC% of predicted value (pFVC%), FEV1/FVC%
of predicted value (pFEV1/FVC%), and PEF% of predicted value (pPEF%).
Secondary outcomes were post-treatment fractional exhaled nitric oxide
(FENO); post-treatment eosinophil counts in sputum (sEOS) or blood
(bEOS); author self-reported outcomes related to asthma (AROs); and
adverse events (AEs). Results: 61 eligible reports from 59 studies were
finally included. AZI plus AADs shows no statistically significant
difference in NoE (RR = 0.49; 95% CI, 0.07 – 3.26; P = 0.05) and sEOS
(MD = -1.13%; 95% CI, -3.54% – 1.29%; P = 0.36) compared to AADs
alone. The post-treatment C-ACT score was improved after AZI plus
salmeterol and fluticasone (SF) treatment compared to SF alone (MD =
2.97; 95% CI, 2.39 – 3.54; P < 0.001). Results from three
studies which could not be meta-analyzed showed that AZI may reduce DBA
compared to placebo. AZI combined with AADs could improve post-treatment
pFEV1% (AZI + glucocorticoid (GC) vs GC: MD = 6.92%; 95% CI, 1.47%
– 12.37%; P = 0.01. AZI + leukotriene receptor antagonist (LTRA) vs
LTRA: MD = 24.88%; 95% CI, 21.47% – 28.29%; P < 0.001.
AZI + GC + BA vs GC + BA: MD = 12.40%; 95% CI, 9.72% – 15.08%; P
< 0.001), pFEV1/FVC% (AZI + GC vs GC: MD = 10.24%; 95% CI,
6.44% – 14.03%; P < 0.001. AZI + GC + BA vs GC + BA: MD =
9.05%; 95% CI, 5.66% – 12.44%; P < 0.001. AZI + BA vs
LTRA + BA: MD = 14.48%; 95% CI, 11.84% – 17.12%; P <
0.001), and pPEF% (MD = 7.00%, 95% CI, 2.53% – 11.47%; P = 0.002),
but not improve pFVC% (MD = -10.37; 95% CI, -20.86% – 0.12%; P =
0.05), compared to AADs alone. Post-treatment bEOS was significantly
higher in the AZI group than in the traditional Chinese medicine
compound granules group (MD = 0.07×109/L; 95% CI, 0.05×109 – 0.09×109;
P < 0.001). No statistically significant difference in bEOS
after treatment with AZI plus montelukast (MON) and loratadine (LOR)
compared to MON and LOR (MD = 0.03×109/L; 95% CI, -0.06×109 –
0.12×109; P = 0.50). Meanwhile, AZI combined with AADs did not increase
AEs (RR = 0.76; 95% CI, 0.51 – 1.13; P = 0.17). Conclusions: AZI was
beneficial in improving some clinical symptoms and lung functions in
childhood asthma. AZI did not increase AEs when combined with AADs.