Department of Intensive Care Unit, Lanzhou University, The First Hospital of Lanzhou University, Lan Zhou, Gansu Province, China.
The Fist Clinical Medical College of the First Hospital of Lanzhou University, Lanzhou University, Lanzhou, Gansu Province, China.
PLoS One. 2021 May 24;16(5):e0251348. doi: 10.1371/journal.pone.0251348. eCollection 2021.
A synergism has been reported between theophylline and corticosteroids, wherein theophylline increases and restores the anti-inflammatory effect of inhaled corticosteroids (ICS) by enhancing histone deacetylase-2 (HDAC) activity. Several studies have explored the efficacy of low-dose theophylline plus ICS therapy on chronic obstructive pulmonary disease (COPD) but the results are discrepant.
We conducted searches in electronic database such as PubMed, Web Of Science, Cochrane Library, and Embase to find out original studies. Stata/SE 15.0 was used to perform all data analysis.
A total of 47,556 participants from 7 studies were included in our analysis and the sample size of each study varied from 24 to 10,816. Theophylline as an add-on therapy to ICS was not associated with the reduction of COPD exacerbations (HR: 1.08, 95% CI: 0.97 to 1.19, I2 = 95.2%). Instead, the theophylline group demonstrated a higher hospitalization rate (HR: 1.12, 95% CI: 1.10 to 1.15, I2 = 20.4%) and mortality (HR: 1.19, 95% CI: 1.14 to 1.25, I2 = 0%). Further, the anti-inflammatory effect of low-dose theophylline as an adjunct to ICS on COPD was controversial. Besides, the theophylline group showed significant improvement in lung function compared with the non-theophylline group.
Based on current evidence, low-dose theophylline as add-on therapy to ICS did not reduce the exacerbation rate. Instead, the hospitalization rate and mortality increased with theophylline. Thus, we do not recommend adding low-dose theophylline to ICS therapy in COPD patients.
PROSPERO Registration CRD42021224952.
茶碱和皮质类固醇之间存在协同作用，茶碱通过增强组蛋白去乙酰化酶-2（HDAC）活性来增加和恢复吸入皮质类固醇（ICS）的抗炎作用。多项研究探索了低剂量茶碱加 ICS 治疗对慢性阻塞性肺疾病（COPD）的疗效，但结果存在差异。
我们在电子数据库（如 PubMed、Web of Science、Cochrane Library 和 Embase）中进行了检索，以查找原始研究。使用 Stata/SE 15.0 进行所有数据分析。
共有 7 项研究的 47,556 名参与者纳入我们的分析，每项研究的样本量从 24 到 10,816 不等。茶碱作为 ICS 的附加治疗与 COPD 加重的减少无关（HR：1.08，95%CI：0.97 至 1.19，I2 = 95.2%）。相反，茶碱组的住院率（HR：1.12，95%CI：1.10 至 1.15，I2 = 20.4%）和死亡率（HR：1.19，95%CI：1.14 至 1.25，I2 = 0%）更高。此外，低剂量茶碱作为 ICS 辅助治疗对 COPD 的抗炎作用存在争议。此外，与非茶碱组相比，茶碱组的肺功能明显改善。
基于现有证据，低剂量茶碱作为 ICS 的附加治疗并不能降低加重率。相反，茶碱的使用会增加住院率和死亡率。因此，我们不建议在 COPD 患者中添加低剂量茶碱到 ICS 治疗中。
PROSPERO 注册 CRD42021224952。
