OBJECTIVE: Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety.
METHODOLOGY: In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use.
RESULTS: Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group.
CONCLUSIONS: Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.
BACKGROUND: Theophylline is widely used in the treatment of asthma, and there is evidence that theophylline has anti-inflammatory or immunomodulatory effects. A study was undertaken to determine whether theophylline added to low dose inhaled steroids would be as efficacious as high dose inhaled steroids in asthma.
METHODS: In a study in general practice of 155 recruited asthmatic patients with continuing symptomatic asthma while on 400 microgram beclomethasone dipropionate (BDP) daily and inhaled beta(2) agonist as required, the effect of (1) continuing low dose inhaled steroids alone (LDS, 200 microgram BDP twice daily), (2) low dose inhaled steroids plus low dose theophylline (LDT, 400 mg daily), or (3) high dose inhaled steroids (HDS, 500 microgram BDP) over a six month period was examined.
RESULTS: One hundred and thirty patients completed the study. Between group comparison using analysis of variance showed no overall differences in peak flow measurements, diurnal variation, and symptom scores. Changes in evening peak flows approached significance at the 5% level (p=0.077). The mean improvement in evening peak flow in the LDT compared with the LDS group was 20.6 l/min (95% confidence interval (CI) -2.5 to 38.8). In the LDT group there was an increase in evening peak flows at the end of the study compared with entry values (22.5 l/min), while in the LDS and HDS groups evening peak flows increased by 1.9 and 8.3 l/min, respectively. There was no significant difference in exacerbations or in side effects.
CONCLUSION: There were no overall significant differences between the low dose steroid, low dose steroid with theophylline, and the high dose steroid groups. The greatest within-group improvement in evening peak flows was found after theophylline. A larger study may be necessary to show significant effects.
The anti-asthmatic effects of theophylline may supplement those of inhaled steroids in asthma. The aim of the present trial was to study how the addition of theophylline compares to doubling the dose of inhaled steroid in asthmatics who remain symptomatic on beclomethasone dipropionate (BDP) 400 microg x day(-1). The trial was designed as a randomized, double-blind, parallel-group study in several European countries. Sixty nine patients were treated for 6 weeks with theophylline plus BDP 400 microg x day(-1), compared to 64 patients treated with BDP 800 micro x day(-1). The mean+/-SD serum theophylline concentration was 10.1+/-4.2 mg x L(-1). Lung function measurements were made throughout the study and patients kept daily records of peak expiratory flow (PEF), symptoms and salbutamol usage. Forced expiratory volume in one second and PEF at week 6 were significantly increased by both treatments (p<0.01). PEF variability was reduced by about 30% in both groups. There were significant improvements in asthma symptoms and rescue medication use (p<0.001). There were no significant differences between the treatment groups. The study demonstrated clinical equivalence of theophylline plus beclomethasone dipropionate 400 microg x day(-1) and beclomethasone dipropionate 800 microg x day(-1) in patients whose asthma is not controlled on beclomethasone dipropionate 400 microg x day(-1). The results support the use of theophylline as a steroid-sparing agent. The combination of low-dose inhaled steroid plus theophylline is a suitable treatment for moderate asthma.
BACKGROUND: Inhaled glucosteroids and oral theophylline are widely used to treat asthma. We compared the benefits of adding theophylline to inhaled glucosteroid with those of doubling the dose of inhaled glucosteroid in patients with persistent symptoms despite the use of inhaled glucosteroid.
METHODS: In a double-blind, placebo-controlled trial, we randomly assigned 62 patients to receive either 400 microg of inhaled budesonide (low-dose budesonide) with 250 or 375 mg of theophylline (depending on body weight) or 800 microg of inhaled budesonide (high-dose budesonide). All doses were given twice daily for three months. Lung function was measured serially, and patients kept records of peak expiratory flow, symptoms, and albuterol use. The effects of treatment on endogenous cortisol levels were also assessed.
RESULTS: Both treatments resulted in improvements in lung function that were sustained throughout the study. As compared with treatment with high-dose budesonide, treatment with low-dose budesonide plus theophylline resulted in greater improvements in forced vital capacity (P=0.03) and forced expiratory volume in one second (P= 0.03). There were significant and similar reductions in beta2-agonist use and the variability of peak expiratory flow, a correlate of bronchial hyperresponsiveness and the severity of asthma. Serum cortisol concentrations were significantly reduced in the group given high-dose budesonide (from a mean [+/-SE] of 18.4+/-2.4 microg per deciliter to 15.9+/-2.1 microg per deciliter, P=0.02) but were unchanged in the other group. The median serum theophylline concentration was 8.7 microg per milliliter (therapeutic range, 10 to 20) among those who received theophylline. Both treatments were well tolerated.
CONCLUSIONS: For patients with moderate asthma and persistent symptoms, low-dose inhaled budesonide with theophylline and high-dose inhaled budesonide produced similar benefits. Effects were achieved at theophylline concentrations below the recommended therapeutic range. The addition of low-dose theophylline to inhaled glucosteroid may be preferable to and cheaper than increasing the dose of inhaled glucosteroid.
Recent studies have found that theophylline exerts anti-inflammatory and immunomodulatory effects. This study was performed to compare the efficacy of inhaled corticosteroids (ICS) combined with slow-release theophylline (SRT) with that of double-dose ICS in asthma control, anti-inflammatory activity and safety.
METHODOLOGY:
In a randomized, open, parallel, control trial, 41 patients with asthma were randomly treated with either beclomethasone dipropionate 500 microg b.i.d. (BDP group) or a combination of BDP 250 microg b.i.d and SRT 0.2 g b.i.d. (SRT/BDP group) for 6 weeks. At the start and at the end of treatment, lung function testing and sputum induction were performed, and plasma cortisol levels were measured. Sputum was analyzed for cell differential counts and the interleukin (IL)-5 level. Patients kept a record of peak expiratory flow (PEF), symptom score, and beta2-agonist use.
RESULTS:
Significant increases in the morning and the evening PEF and FEV1 were observed (P < 0.05), together with an obvious reduction in symptom score and beta2-agonist use (P < 0.01). Significant decreases in the percentage eosinophils and IL-5 level in induced sputum also occurred (P < 0.05). However, there was no difference between the two groups for all these parameters. There was no significant change in the plasma cortisol level for either group.
CONCLUSIONS:
Both ICS combined with SRT and double-dose ICS had the same effect on asthma control, improving symptoms and ameliorating lung function. Both therapies had similar anti-airway inflammatory effects and therapeutic safety. Combining SRT with ICS may allow a reduction in ICS dose when treating asthma.