Ulf Harnest

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: Roflumilast is an oral, once-daily phosphodiesterase 4 inhibitor with anti-inflammatory activity in development for the treatment of asthma. Roflumilast was compared with inhaled beclomethasone dipropionate (BDP) in patients with asthma. METHODS: In a double blind, double-dummy, randomized, noninferiority study, 499 patients (forced expiratory volume in 1 s [FEV1] = 50-85% predicted) received roflumilast 500 microg once daily or BDP 200 microg twice daily (400 microg/day) for 12 weeks. Lung function and adverse events were monitored. RESULTS: Roflumilast and BDP significantly improved FEV1 by 12% (270 +/- 30 ml) and 14% (320 +/- 30 ml), respectively (P < 0.0001 vs baseline). Roflumilast and BDP also significantly improved forced vital capacity (FVC) (P < 0.0001 vs baseline). There were no significant differences between roflumilast and BDP with regard to improvement in FEV1 and FVC. Roflumilast and BDP showed small improvements in median asthma symptom scores (-0.82 and -1.00, respectively) and reduced rescue medication use (-1.00 and -1.15 median puffs/day, respectively; P < 0.0001 vs baseline). These small differences between roflumilast and BDP were not considered clinically relevant. Both agents were well tolerated. CONCLUSIONS: Once daily, oral roflumilast 500 microg was comparable with inhaled twice-daily BDP (400 microg/day) in improving pulmonary function and asthma symptoms, and reducing rescue medication use in patients with asthma.

Mometasone furoate (MF) administered by dry powder inhaler (DPI) was composed with budesonide (BUD) Turbuhaler in the treatment of moderate persistent asthma. The patients were randomized to one of four treatment groups: MF DPI (100, 200, 400 microg b.i.d) or BUD Turbuhaler. 400 microg b.i.d in a 12-week, active-controlled, evaluator-blind, multicentre international trial. The primary efficacy variable was the mean change from baseline to endpoint (last treatment visit) in forced expiratory volume in one second (FEV1). Changes in FEV1 showed a statistically significant superiority (p<0.05) of MF DPI 200 and 400 microg b.i.d compared with the BUD Turbuhaler 400 microg b.i.d treatment. Significant superiority (p<0.05) was also seen in scores for several secondary efficacy variables when MF DPI was compared with BUD Turbuhaler treatment. MF DPI 200 microg b.i.d was comparable to MF DPI 400 microg b.i.d in therapeutic benefit. The incidence of oral candidiasis was no more than 3% in any group. All treatments were well tolerated. A total daily dose of 400 microg of mometasone furoate administered by dry powder inhaler provides a well-tolerated treatment for patients with moderate persistent asthma and results in a significantly greater improvement, when compared to a daily dose of 800 microg BUD Turbuhaler in the parameters measured in this study.

&lt;i&gt;Background:&lt;/i&gt; Chronic obstructive pulmonary disease (COPD) management guidelines recommend regular treatment with one or more long-acting bronchodilators for patients with moderate to severe COPD. &lt;i&gt;Objective:&lt;/i&gt; To compare the onset and duration of action of formoterol and tiotropium in patients with COPD. &lt;i&gt;Methods:&lt;/i&gt; This randomized, multicentre, open-label crossover study in 38 patients with COPD (mean age 64 years; mean FEV&lt;sub&gt;1&lt;/sub&gt; 55% predicted) assessed the effect of 7 days of treatment with formoterol (12 µg b.i.d. via Foradil&lt;sup&gt;®&lt;/sup&gt; Aerolizer&lt;sup&gt;®&lt;/sup&gt;) vs. tiotropium (18 µg o.d. via Spiriva&lt;sup&gt;®&lt;/sup&gt; HandiHaler&lt;sup&gt;®&lt;/sup&gt;) on lung function measured over a period of 12 h after the first dose on day 1 and the last dose on day 8. &lt;i&gt;Results:&lt;/i&gt; The primary efficacy variable, FEV&lt;sub&gt;1&lt;/sub&gt;-AUC during the first 2 h post-dose (FEV&lt;sub&gt;1&lt;/sub&gt;-AUC&lt;sub&gt;10–120 min&lt;/sub&gt;), was significantly higher for formoterol compared with tiotropium, with between-treatment differences of 124 ml (p = 0.016) after the first dose and 80 ml (p = 0.036) after 7 days’ treatment in favour of formoterol. FEV&lt;sub&gt;1&lt;/sub&gt; measured 12 h after inhalation did not differ statistically significantly between treatments. Adverse events occurred in 2 (5%) patients after treatment with formoterol and in 5 (12%) patients after treatment with tiotropium. &lt;i&gt;Conclusion:&lt;/i&gt; This study demonstrates faster onset of action and greater bronchodilation of formoterol vs. tiotropium for bronchodilation within the first 2 h of inhalation (FEV&lt;sub&gt;1&lt;/sub&gt;-AUC&lt;sub&gt;10–120 min&lt;/sub&gt;) and comparable bronchodilation 12 h post-inhalation in patients with moderate to severe COPD.