Yang Qiang, Tang Pingxiu, Zhang Xunyan
Department of Pharmacy, Suining Central Hospital, Suining City, Sichuan Province, China.
PLoS One. 2025 May 6;20(5):e0321984. doi: 10.1371/journal.pone.0321984. eCollection 2025.
The rationale for additional treatment of oral theophylline with inhaled therapy in patients with stable chronic obstructive pulmonary disease (COPD) is unclear. The databases including The Cochrane Library､PubMed､Embase and Web of Science were searched to collect randomized controlled trials (RCTs) involving the inhaled therapy plus additional theophylline therapy for the treatment of patients with stable COPD up to December 31, 2023. The forced expiratory volume in 1 second (FEV1)､forced expiratory volume in 1s% predicted (FEV1% pred)､forced vital capacity (FVC)､FEV1/FVC%､peak expiratory flow rate(PEFR)､exacerbation rate of COPD､COPD related hospital admissions､total symptom score and drug-related adverse reactions were extracted from literatures and the meta-analysis was conducted using the RevMan 5.4 software. 10 RCTs involving 2771 patients were included. The meta-analysis results showed that additional theophylline improved FEV1 with MD 0.08 (95% CI: 0.06 to 0.09, p<0.00001)､FVC with MD 0.13 (95% CI: 0.10 to 0.15, p<0.00001), reduce the risk of exacerbation rate with OR 0.75 (95% CI: 0.60 to 0.94, p=0.01) and COPD related hospital admissions with MD -0.07 (95% CI: -0.13 to -0.01, p=0.01). However, there was no significant difference in FEV1% pred with MD 0.45 (95% CI: -1.41 to 2.30, p=0.64)､FEV1/FVC% with MD -0.24 (95% CI: -3.26 to 2.79, p=0.88) and total symptom score with MD -0.03 (95% CI: -0.14 to 0.09, p=0.65). Furthermore, additional theophylline therapy induced a high incidence of drug-related adverse reactions with OR 1.33 (95% CI: 1.12 to 1.58, p=0.001), especially in gastrointestinal adverse reactions. Oral theophylline could be a supplementary therapeutic option when inhaled therapy is insufficient regarding of improvement in pulmonary function and reducing in exacerbation risk. However, additional theophylline therapy could increase the risk of drug-related adverse reactions and should be concerned.
在稳定期慢性阻塞性肺疾病（COPD）患者中，吸入治疗联合口服茶碱进行额外治疗的基本原理尚不清楚。检索了包括Cochrane图书馆、PubMed、Embase和Web of Science在内的数据库，以收集截至2023年12月31日的涉及吸入治疗加额外茶碱治疗稳定期COPD患者的随机对照试验（RCT）。从文献中提取1秒用力呼气容积（FEV1）、预测的1秒用力呼气容积百分比（FEV1%pred）、用力肺活量（FVC）、FEV1/FVC%、呼气峰值流速（PEFR）、COPD急性加重率、COPD相关住院率、总症状评分和药物相关不良反应，并使用RevMan 5.4软件进行荟萃分析。纳入了10项涉及2771例患者的RCT。荟萃分析结果显示，额外使用茶碱可改善FEV1，MD为0.08（95%CI：0.06至0.09，p<0.00001），改善FVC，MD为0.13（95%CI：0.10至0.15，p<0.00001），降低急性加重率风险，OR为0.75（95%CI：0.60至0.94，p=0.01），降低COPD相关住院率，MD为-0.07（95%CI：-0.13至-0.01，p=0.01）。然而，在预测的FEV1%方面，MD为0.45（95%CI：-1.41至2.30，p=0.64），在FEV1/FVC%方面，MD为-0.24（95%CI：-3.26至2.79，p=0.88），在总症状评分方面，MD为-0.03（95%CI：-0.14至0.09，p=0.65），均无显著差异。此外，额外的茶碱治疗导致药物相关不良反应的发生率较高，OR为1.33（95%CI：1.12至1.58，p=0.001），尤其是胃肠道不良反应。当吸入治疗在改善肺功能和降低急性加重风险方面不足时，口服茶碱可能是一种补充治疗选择。然而，额外的茶碱治疗可能会增加药物相关不良反应的风险，应予以关注。
