Ambroxol hydrochloride and clenbuterol hydrochloride oral solution for wheezing disorders in children in China: evidence mapping and meta-analysis

Objective: To evaluate the efficacy and safety of ambroxol hydrochloride and clenbuterol hydrochloride oral solution (AHCHOS) in pediatric patients with wheezing disorders and provide a comprehensive evidence map of the current clinical status. Methods: A literature search was conducted in PubMed, Embase, Cochrane Library, CNKI, Wanfang, and CBM to identify randomized controlled trials (RCTs) evaluating the efficacy and safety of AHCHOS in children with wheezing disorders. The clinical status was descriptively summarized. Meta-analyses for efficacy and safety outcomes were performed using a random-effects model in Review Manager 5.4. Outcomes were treatment effectiveness, times to symptom and clinical sign resolution, length of hospital stay, and adverse events (AEs). All time-related outcomes were reported in days. Results: A total of 227 RCTs were included in the evidence mapping, 14 of which met the criteria for meta-analysis. Evidence mapping revealed a general increase in the number of studies from 2005 to a peak in 2012, followed by a decline. Most studies were conducted in eastern China, particularly in Henan Province. Meta-analysis results demonstrated that combination therapy with AHCHOS significantly improved the overall response rate [risk ratio (RR) 1.26, 95% confidence interval (CI) 1.10-1.44] and significant effective rate (RR 1.55, 95% CI 1.36-1.76). It also significantly reduced the duration (days) of coughing [mean difference (MD) -1.40, 95% CI -1.75 to -1.06], wheezing (MD -1.88, 95% CI -2.50 to -1.26), cough phlegm (MD -2.00, 95% CI -2.76 to -1.24), wet lung sounds (MD -1.82, 95% CI -2.33 to -1.30), pulmonary rales (MD -2.27, 95% CI -2.90 to -1.64), and hospital stay (MD -1.13, 95% CI -1.45 to -0.82). Furthermore, AHCHOS did not increase the risk of AEs compared with conventional treatment alone. Conclusion: Combination therapy with AHCHOS was associated with modest but statistically significant improvements in symptom resolution and length of hospital stay compared with conventional treatment alone. However, all included studies were conducted in China, which may limit the generalizability of the findings. In addition, no definitive conclusions regarding safety could be drawn due to limited and inconsistent adverse event reporting. Further safety assessments in future trials are warranted. Systematic Review Registration: The protocol has been registered on INPLASY (INPLASY202480121).