Center of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, People's Republic of China.
Center of Medicine Clinical Research, Department of Pharmacy, PLA General Hospital, 28 Fu Xing Road, Beijing 100853, People's Republic of China.
Int Immunopharmacol. 2019 Feb;67:35-45. doi: 10.1016/j.intimp.2018.11.043. Epub 2018 Dec 7.
Recurrent respiratory tract infections (RRTIs) remain a great challenge to pediatricians, because they can increase the risk of various complications and there is no confirmed effective treatment. In the present study, we aimed to assess the effectiveness and safety of pidotimod (PDT), an immunostimulant, in treatment of RRTIs in children aged 14 years and under.
PubMed, EMBASE, Web of Science, Cochrane Library, ClinicalTrials.gov, CBM and CNKI were searched from their inception up to February 2018. All randomized controlled trials (RCTs) using PDT with various treatment durations and enrolling participants <14 years of age were included in the present review. The interventions were PDT plus conventional treatment (e.g. anti-bacterial and antiviral therapy) or PDT alone versus the conventional treatment plus placebo or conventional treatment alone.
A total of 29 RCTs consisting of 4344 pediatric patients were included in this meta-analysis. Ten RCTs were published from Italy, Russia or Greece, and 19 RCTs were published by Chinese groups. However, appropriate randomization methods were only used in 15 trials. Only one study had explicit allocation concealment. Since only eight RCTs were double-blind and placebo controlled, the evidence was not assessed as high quality. The meta-analysis indicates that treatment with PDT resulted in a significant increase in the proportion of participants who had lower RTIs (RR 1.59; 95% CI 1.45-1.74, p < 0.00001) compared with the conventional treatment. PDT could significantly decrease the duration of cough and fever. The number of patients in using antibiotics was also remarkably decreased in the PDT treatment group. Moreover, PDT administration improved the levels of serum immunoglobulin (IgG, IgA, or IgM) and T-lymphocyte subtypes (CD3+, CD4+). Besides, PDT administration did not increase the risk of adverse events of any cause (RR = 1.05, 95% CI 0.72-1.54, p = 0.80).
PDT showed a good efficacy and safety in treatment of pediatric RRTIs. Further high-quality and large-scale RCTs are still required to provide confirmatory evidence.
The protocol of this study can be found at PROSPERO with the registration number of CRD42018093541.
反复呼吸道感染（RRTIs）仍然是儿科医生面临的巨大挑战，因为它们会增加发生各种并发症的风险，而且目前还没有有效的治疗方法。本研究旨在评估免疫刺激剂匹多莫德（PDT）治疗 14 岁及以下儿童 RRTIs 的疗效和安全性。
检索PubMed、EMBASE、Web of Science、Cochrane Library、ClinicalTrials.gov、CBM 和 CNKI 数据库，检索时限均从建库至 2018 年 2 月。纳入 PDT 不同疗程治疗儿童 RRTIs 的随机对照试验（RCTs），并对纳入文献进行方法学质量评价。
共纳入 29 项 RCT，包含 4344 例患儿。10 项 RCT 来自意大利、俄罗斯或希腊，19 项 RCT 来自中国。但仅有 15 项研究报告了随机方法，1 项研究报道了分配隐藏。仅有 8 项 RCT 为双盲、安慰剂对照，因此证据质量不高。Meta 分析结果显示，与常规治疗相比，PDT 治疗可显著增加下呼吸道感染发生率较低的患儿比例（RR 1.59，95%CI 1.45-1.74，p<0.00001），显著缩短咳嗽和发热时间，减少抗生素使用，改善血清免疫球蛋白（IgG、IgA 或 IgM）和 T 淋巴细胞亚群（CD3+、CD4+）水平。此外，PDT 治疗并未增加任何原因不良事件的风险（RR 1.05，95%CI 0.72-1.54，p=0.80）。
PDT 治疗儿童 RRTIs 疗效确切，安全性良好，但仍需要高质量、大样本 RCT 进一步验证。
本研究方案已在 PROSPERO 注册，注册号为 CRD42018093541。
