SynthesisPloS one2021
Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis.
Synthesis in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
10 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- A Systematic Review and Meta-Analysis on the Safety and Efficacy of Rosuvastatin as an Adjunctive Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2025Pooled it
- Blood Eosinophils in Chinese COPD Participants and Response to Treatment with Combination Low-Dose Theophylline and Prednisone: A Post-Hoc Analysis of the TASCS Trial.International journal of chronic obstructive pulmonary diseaseTrial
- Comprehensive Evaluation of Storage Stability and Cytotoxicity of Co-Spray-Dried Theophylline Dry Powders for Inhalation: Follow-Up Study.Pharmaceutics · 2026Article
- The role and mechanism of histone deacetylase in COPD.Molecular and cellular biochemistry · 2026Review
- Article
- Determination of Theophylline Across Biological, Environmental and Food Matrices Using Liquid-Phase Microextraction Coupled with LC-MS/MS.Molecules (Basel, Switzerland) · 2025Article
- NLBK alleviates airway remodeling in COPD by inhibiting RXRA-mediated transcription of PLA2G2A.American journal of translational research · 2025Article
- Ultra-High Adsorption Capacity of Core-Shell-Derived Magnetic Zeolite Imidazolate Framework-67 as Adsorbent for Selective Extraction of Theophylline.Molecules (Basel, Switzerland) · 2023Article
- Pharmacological therapy for stable chronic obstructive pulmonary disease.Chronic diseases and translational medicine · 2023Review
- The Role of IL-6 in Cancer Cell Invasiveness and Metastasis-Overview and Therapeutic Opportunities.Cells · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundA 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.
methodWe 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.
resultA 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.
conclusionBased 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.
trial registrationPROSPERO Registration CRD42021224952.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.