Yonsei Med J.  2011 Mar;52(2):268-275. 10.3349/ymj.2011.52.2.268.

Addition of Theophylline or Increasing the Dose of Inhaled Corticosteroid in Symptomatic Asthma: A Meta-Analysis of Randomized Controlled Trials

• Wang Y
• Lin K
• Wang C
• Liao X

• KMID: 1779662
• DOI: http://doi.org/10.3349/ymj.2011.52.2.268

Abstract

PURPOSE
Low-dose theophylline has anti-inflammatory effects. The aim of this study was to evaluate the effects of adding theophylline compared with increasing the dose of inhaled corticosteroid (ICS) on symptomatic asthma.
MATERIALS AND METHODS
The associated literature was acquired through deliberate searching and selected based on the established inclusion criteria for publications. The extracted data were further analyzed by a meta-analysis
RESULTS
Four randomized, controlled, parallel studies were selected. Addition of theophylline produced a greater increase of forced expiratory volume in one second as %predicted (FEV1pred) by 2.49% [95% confidence interval (CI) 1.99-3.00; z = 9.70; p < 0.001], compared with increasing the dose of ICS. There was no difference between the two treatments in terms of peak expiratory flow (PEF).
CONCLUSION
Addition of theophylline to ICS has similar therapeutic effects on improving lung function as increasing the dose of ICS in the treatment of symptomatic asthma.

Keyword

Asthma; theophylline; inhaled corticosteroid; meta-analysis

MeSH Terms

Adrenal Cortex Hormones/administration & dosage/*therapeutic use
Anti-Asthmatic Agents/administration & dosage/*therapeutic use
Asthma/*drug therapy
Forced Expiratory Volume/drug effects
Humans
Randomized Controlled Trials as Topic
Theophylline/*therapeutic use
Treatment Outcome

Figure

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  Fig. 1 GINA asthma guidelines: management approach based on control for children > 5 years of age, adolescents and adults. The best-documented treatment for controlling asthma is ICS. Low-dose ICS is recommended as the initial controller treatment at step 2, and low-dose ICS plus LABA is recommended at step 3. GINA, Global Initiative for Asthma; ICS, inhaled corticosteroid; LABA, long acting β2-agonist.

• 

  Fig. 2 The flowchart of the study selection process. ICS, inhaled corticosteroid.

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  Fig. 3 Pooled WMD for the improvement of FEV1pred of eligible studies comparing the addition of theophylline (treatment) with increasing the dose of ICS (control). FEV1pred, forced expiratory volume in one second as %predicted; Theo, theophylline; ICS, inhaled corticosteroid; WMD, weighted mean difference; CI, confidence interval.

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  Fig. 4 Pooled WMD for improvement of morning PEF in eligible studies comparing addition of theophylline (treatment) with increasing the dose of ICS (control). PEF, peak expiratory flow; Theo, theophylline; ICS, inhaled corticosteroid; WMD, weighted mean difference; CI, confidence interval.

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  Fig. 5 Pooled WMD for the improvement of evening PEF of eligible studies comparing addition of theophylline (treatment) with increasing the dose of ICS (control). PEF, peak expiratory flow; Theo, theophylline; ICS, inhaled corticosteroid; WMD, weighted mean difference; CI, confidence interval.

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  Fig. 6 Sensitivity analysis: Pooled WMD for improvement of FEV1pred in eligible studies comparing addition of theophylline (treatment) with increasing the dose of ICS (control) using the random effects model. FEV1pred, forced expiratory volume in one second as %predicted; Theo, theophylline; ICS, inhaled corticosteroid; WMD, weighted mean difference; CI, confidence interval.

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