Yu Haichuan, Su Xiaojie, Lei Ting, Zhang Lu, Feng Zhouzhou, Zhang Chuchu, Zhang Meng, Wang Yalei, Chen Xinlong, Liu Jian
The First Clinical Medical College of Lanzhou University, Lanzhou, China.
Intensive Care Unit, The First Hospital of Lanzhou University, Lanzhou, China.
Front Pharmacol. 2022 Sep 28;13:950035. doi: 10.3389/fphar.2022.950035. eCollection 2022.
Chronic inflammation is the core mechanism of the development of chronic obstructive pulmonary disease (COPD). Corticosteroid resistance in COPD limits its anti-inflammatory potency. p38 MAPKIs were suggested as an alternative to corticosteroids despite the fact that there is currently no systematic review evaluating existing evidence. This randomized controlled trials (RCT)-based systematic review with meta-analysis was conducted following the PRISMA statement. RCTs were searched and screened from 8 databases. Three types of data, including basic information of included studies, pre-defined outcome data, and quality assessment information were extracted. Pooling values and associated 95 % confidence intervals were deemed as statistically significant only when two-tailed values were smaller than 0.05. This study included 10 RCTs with a total population of 1,751 [age, mean (SD) = 64.39 (8.06)]. Safety and several efficacy indicators of lung function, inflammatory biomarkers, and quality of life were meta-analyzed. Despite the improvement of post-bronchodilator-forced vital capacity (FVC), no difference between p38 MAPKIs and placebo was found in both safety and efficacy. Compared with placebo, p38 MAPKIs are safe but did not show any significant effects in the COPD population. Results of this study should be regarded with caution due to the small number of included studies and heterogeneity from combining different p38 MAPKIs as a whole. PROSPERO #CRD42022302890.
慢性炎症是慢性阻塞性肺疾病（COPD）发展的核心机制。COPD中的糖皮质激素抵抗限制了其抗炎效力。尽管目前尚无系统评价来评估现有证据，但p38丝裂原活化蛋白激酶抑制剂（p38 MAPKIs）被认为是糖皮质激素的替代药物。本基于随机对照试验（RCT）的系统评价及荟萃分析是按照PRISMA声明进行的。从8个数据库中检索并筛选RCT。提取了三种类型的数据，包括纳入研究的基本信息、预先定义的结局数据和质量评估信息。只有当双侧值小于0.05时，合并值及相关的95%置信区间才被视为具有统计学意义。本研究纳入了10项RCT，总样本量为1751例[年龄，均值（标准差）=64.39（8.06）]。对肺功能、炎症生物标志物和生活质量的安全性及多项疗效指标进行了荟萃分析。尽管支气管扩张剂后用力肺活量（FVC）有所改善，但在安全性和疗效方面，p38 MAPKIs与安慰剂之间均未发现差异。与安慰剂相比，p38 MAPKIs是安全的，但在COPD人群中未显示出任何显著效果。由于纳入研究数量较少且将不同的p38 MAPKIs作为一个整体合并存在异质性，本研究结果应谨慎看待。国际前瞻性系统评价注册库编号#CRD42022302890。
