{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T21:18:35Z","timestamp":1775596715018,"version":"3.50.1"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>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\uff64PubMed\uff64Embase 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 (FEV<jats:sub>1<\/jats:sub>)\uff64forced expiratory volume in 1s% predicted (FEV<jats:sub>1<\/jats:sub>% pred)\uff64forced vital capacity (FVC)\uff64FEV<jats:sub>1<\/jats:sub>\/FVC%\uff64peak expiratory flow rate(PEFR)\uff64exacerbation rate of COPD\uff64COPD related hospital admissions\uff64total 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 FEV<jats:sub>1<\/jats:sub> with MD 0.08 (95% CI: 0.06 to 0.09, p&lt;0.00001)\uff64FVC with MD 0.13 (95% CI: 0.10 to 0.15, p&lt;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 FEV<jats:sub>1<\/jats:sub>% pred with MD 0.45 (95% CI: -1.41 to 2.30, p=0.64)\uff64FEV<jats:sub>1<\/jats:sub>\/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.<\/jats:p>","DOI":"10.1371\/journal.pone.0321984","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T18:07:49Z","timestamp":1746814069000},"page":"e0321984","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Effects of additional oral theophylline with inhaled therapy in patients with stable chronic obstructive pulmonary disease: A systematic review and meta-analysis"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7361-6103","authenticated-orcid":true,"given":"Qiang","family":"Yang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingxiu","family":"Tang,","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xunyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"pone.0321984.ref001","doi-asserted-by":"crossref","first-page":"2609","DOI":"10.2147\/COPD.S90148","article-title":"COPD exacerbation frequency and its association with health care resource utilization and costs","volume":"10","author":"AD Dhamane","year":"2015","journal-title":"Int J Chron Obstruct Pulmon Dis"},{"issue":"7","key":"pone.0321984.ref002","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1111\/resp.12780","article-title":"Acute exacerbation of COPD","volume":"21","author":"F.W Ko","year":"2016","journal-title":"Respirology"},{"key":"pone.0321984.ref003","year":"2024"},{"issue":"6","key":"pone.0321984.ref004","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.arbr.2017.03.017","article-title":"Spanish guidelines for management of chronic obstructive pulmonary disease (GesEPOC) 2017. 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