Therapeutic effect of theophylline on acute exacerbation of chronic obstructive pulmonary disease: A meta‐analysis

Abstract Objective To evaluate the efficacy of theophylline in acute exacerbations of chronic obstructive pulmonary disease (COPD) and provide evidence‐based clinical guidance. Methods Randomized controlled trials (RCTs) on theophylline for acute COPD exacerbations were retrieved from PubMed, Web of Science, Embase, Cochrane Library, China National Knowledge Internet, and Wanfang Database (through November 2024). Studies were screened and data extracted per inclusion criteria. Quality was assessed via the Cochrane risk‐of‐bias tool; meta‐analysis used R 4.2.2. Results This meta‐analysis ultimately included eight RCTs comprising 3133 participants, with 1582 patients allocated to the theophylline experimental group and 1551 to the control group (placebo, normal saline, or standard care). The analysis demonstrated that theophylline significantly improved the clinical treatment efficacy rate—defined as a composite outcome incorporating symptom alleviation, sign reduction, and arterial blood gas improvement—compared to controls (odds ratio [OR] = 3.96, 95% confidence interval [CI]: 2.41–6.50; p < 0.01). Additionally, theophylline significantly increased partial pressure of arterial oxygen levels (mean difference [MD] = 0.08 mmHg, 95% CI: 0.06–0.11; p < 0.01). However, no statistically significant intergroup differences were observed for the partial pressure of arterial carbon dioxide (PaCO 2 ; MD = 0.32 mmHg, 95% CI: −0.04 to 0.68; p = 0.08), forced expiratory volume in 1 s (FEV 1 ; MD = 0.19 L, 95% CI: −0.10 to 0.48; p = 0.20), FEV 1 /forced vital capacity ratio (MD = 10.26%, 95% CI: −2.81 to 23.33; p = 0.12), or adverse reaction incidence (OR = 0.74, 95% CI: 0.36–1.51; p = 0.41). Conclusion Based on the current evidence, theophylline can improve clinical outcomes in acute exacerbations of COPD without increasing adverse effects. However, given the limited number of included studies and potential confounding factors, these findings require further validation through well‐designed, high‐quality RCTs.