■难治性慢性咳嗽(RCC)对患者的健康相关生活质量有重大影响,是临床管理的挑战。然而,RCC的最佳治疗仍存在争议。本研究旨在探讨和比较目前药物治疗RCC的疗效和安全性。
■通过搜索PubMed,WebofScience,Embase,和Ovid数据库从2008年1月1日至2023年3月1日。所有报告疗效或/和安全性结果的随机对照试验(RCT)均纳入贝叶斯网络荟萃分析。这里,我们比较了莱斯特咳嗽问卷(LCQ)的效果,视觉模拟量表(VAS),RCC患者的客观咳嗽频率。此外,我们还比较了不良事件(AE)的发生率,用于安全性分析.PROSPERO注册:CRD42022345940。
■19个符合条件的RCT包括3326名患者和7种药物类别:P2X3拮抗剂,GABA调节剂,瞬态受体电位(TRP)调节剂,NK-1激动剂,阿片类镇痛药,大环内酯,和色甘酸钠。与安慰剂相比,P2X3拮抗剂缓解的LCQ和24h咳嗽频率的平均差异(MD)为1.637(95%CI:0.887-2.387)和-11.042(P=0.035)。与安慰剂相比,GABA调节剂的效应大小(LCQ的MD和咳嗽严重程度VAS)分别为1.347(P=0.003)和-7.843(P=0.003)。在网络荟萃分析中,Gefapixant是RCC患者最有效的治疗方法(累积排序曲线下的表面(SUCRA)在LCQ中为0.711,24h咳嗽频率为0.983,咳嗽严重程度VAS为0.786)。Lesogaberan的疗效优于安慰剂(SUCRA:0.632vs.0.472)在24h咳嗽频率。Eliapixant和lesogaberan在咳嗽严重程度VAS方面的疗效优于安慰剂。然而,TRP调节剂的疗效比安慰剂差。在AE的荟萃分析中,本研究发现P2X3拮抗剂与不良事件有显著相关性(RR:1.129,95%CI:1.012-1.259),尤其是味觉相关的不良事件(RR:6.216,P<0.05)。
■在此网络荟萃分析中,P2X3拮抗剂在疗效方面显示出优势,是目前治疗RCC最有希望的药物。GABA调节剂也显示了对RCC的潜在功效,但具有中央系统的AE。然而,需要重新审视TRP调节剂的作用.需要进一步的研究来确定潜在的受益人群,以优化慢性咳嗽的药理管理。
■国家自然科学基金(81870079),广东省科技计划项目(2021A050520012),国家杰出青年科学基金会孵化计划(GMU2020-207)。
UNASSIGNED: Refractory chronic cough (RCC) has a significant impact on patient\'s health-related quality of life and represents a challenge in clinical management. However, the optimal treatment for RCC remains controversial. This study aimed to investigate and compare the efficacy and safety of the current pharmacological therapeutic options for RCC.
UNASSIGNED: A systematic review was performed by searching PubMed, Web of Science, Embase, and Ovid databases from January 1, 2008 to March 1, 2023. All randomised control trials (RCTs) reporting outcomes of efficacy or/and safety were included in the Bayesian network meta-analysis. Here, we compared the effects on Leicester Cough Questionnaire (LCQ), Visual Analogue Scale (VAS), and objective cough frequency of patients with RCC. Besides, we also compared the incidence of adverse events (AEs) for analysis of safety. PROSPERO registration: CRD42022345940.
UNASSIGNED: 19 eligible RCTs included 3326 patients and 7 medication categories: P2X3 antagonist, GABA modulator, Transient Receptor Potential (TRP) modulator, NK-1 agonist, opioid analgesic, macrolide, and sodium cromoglicate. Compared with placebo, mean difference (MD) of LCQ and 24 h cough frequency for P2X3 antagonist relief were 1.637 (95% CI: 0.887-2.387) and -11.042 (P = 0.035). Compared with placebo, effect sizes (MD for LCQ and cough severity VAS) for GABA modulator were 1.347 (P = 0.003) and -7.843 (P = 0.003). In the network meta-analysis, gefapixant is the most effective treatment for patients with RCC (The Surface Under the Cumulative Ranking Curves (SUCRA) is 0.711 in LCQ, 0.983 in 24 h cough frequency, and 0.786 in cough severity VAS). Lesogaberan had better efficacy than placebo (SUCRA: 0.632 vs. 0.472) in 24 h cough frequency. Eliapixant and lesogaberan had better efficacy than placebo in cough severity VAS. However, TRP modulator had worse efficacy than placebo. In the meta-analysis of AEs, the present study found P2X3 antagonist had a significant correlation to AEs (RR: 1.129, 95% CI: 1.012-1.259), especially taste-related AEs (RR: 6.216, P < 0.05).
UNASSIGNED: In this network meta-analysis, P2X3 antagonist showing advantages in terms of efficacy is currently the most promising medication for treatment of RCC. GABA modulator also showed potential efficacy for RCC but with AEs of the central system. Nevertheless, the role of TRP modulator needed to be revisited. Further research is needed to determine the potential beneficiary population for optimizing the pharmacological management of chronic cough.
UNASSIGNED: National Natural Science Foundation of
China (81870079), Guangdong Science and Technology Project (2021A050520012), Incubation Program of National Science Foundation for Distinguished Young Scholars (GMU2020-207).