Objective  To systematically evaluate the placebo effect and the influencing factors of acute upper respiratory infection (AURI) in children.

Methods  Chinese and English databases including PubMed, Web of Science, the Cochrane Library, Embase, CNKI, VIP, WanFang Data, and CBM were searched from the establishments of the databases to June, 2024. Random controlled trials, in which placebos were used as the control treatment for AURI were included. The literature screening, data extraction and quality assessment were all conducted independently by two reviewers. The systematic review and Meta-analysis were performed by R 4.3.1 software. Subgroup analysis and Meta-regression were used to explore the influencing factors of placebo effect. The outcomes were clinical recovery rate, the recovery  time, and improvement rate of AURI.

Results  A total of 11 studies were included, involving 938 participants in the placebo group. The diseases included in the studies were AURI or its clinical specific manifestations, including the common cold, acute pharyngitis and/or acute tonsillitis. The results of Meta-analysis showed that the conservatively estimated placebo effect of the  recovery  rate of the upper respiratory tract infection after 3 days of treatment was 52.3%[95%CI (42.1%, 65.0%)]. The results of the subgroup analysis show that the placebo effect of acute pharyngitis and/or acute tonsillitis after 5 days of treatment was 53.1%[95%CI (44.7%, 63.2%)]. Subgroup analyses were performed according to different study characteristics, and the results showed the combined effect values were 50.0%[95%CI (42.9%, 58.3%)] for Chinese studies using traditional Chinese medicine and 69.0%[95%CI (61.8%, 77.1%)] for Russian studies using Western medicine. The Meta-regression analysis showed that the publication year and ages could affect the placebo effect. The placebo effect for the cure time of the disease under different definitions of cure (symptoms basically disappear, symptoms completely disappear) were 5.40[95%CI(5.07, 5.72)] days and 9.00 [95%CI(8.17, 9.83)] days, respectively.

Conclusion  AURI in children has a high placebo effect, which means that the results can be used to judge the clinical value of the single-arm studies and to estimate the sample size for future exploratory random controlled trials of placebo..

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