No abstract

Four hundred and sixty nine patients were randomized to receive either 12 micrograms bd of eformoterol (Oxis, Astra Pharmaceuticals Ltd., Kings Langley, U.K.) delivered via Turbohaler or 50 micrograms bd salmeterol (Serevent, Glaxo-Wellcome Ltd., Uxbridge, U.K.) via either the Accuhaler (Glaxo-Wellcome Ltd.) or pressurized metered dose inhaler (pMDI, Glaxo-Wellcome Ltd.) for 8 weeks. This was followed by a 4-week cross-over period when patients who had received salmeterol in the previous 8 weeks were given eformoterol and patients who had received eformoterol were given either salmeterol via the Accuhaler or pMDI to assess patient device and treatment preference. For the primary efficacy variable, the increase in peak expiratory flow (PEF) rate from run-in to 8 weeks, similar significant improvements were seen in all three treatment groups. Eformoterol Turbohaler (FT) achieved a greater increase in morning PEF than salmeterol Accuhaler (SA) from randomisation to 4 weeks; the increase shown in the eformoterol Turbohaler group was 28.9 1 min-1 compared to 19.91 min-1 for the salmeterol Accuhaler group. The addition of eformoterol Turbohaler 12 micrograms bd, to patients' existing asthma therapy was found to have a significantly more beneficial effect on the severity of patients' daytime asthma symptoms than had salmeterol Accuhaler 50 micrograms bd (P = 0.014). Eformoterol Turbohaler reduced the severity of daytime asthma symptoms by 42% after only 4 weeks of treatment. The patients in the eformoterol Turbohaler treated group experienced a higher percentage of days when they were symptom-free and did not use their short-acting bronchodilator to relieve symptoms (32.8, 24.1 and 28.0% in the FT, SA and SM groups, respectively). At 8 weeks there were no significant differences in any of these variables between the three groups. Patients in all the treatment groups gained an additional 1-1.5 nights undisturbed by asthma per week. The changes in sleep disturbance were not significantly different between the three treatment groups. In addition to the therapeutic benefits provided by eformoterol Turbohaler the device (Turbohaler) was the significant preference of patients given both Turbohaler and pMDI (P = 0.0168) and was also considered to be significantly more convenient to carry around than the Accuhaler (P < 0.0001). No other differences were found between the three devices. The results of this study demonstrate that the addition of a long-acting beta 2-agonist is an effective tool for achieving the goals of asthma treatment. Eformoterol via the Turbohaler is at least as effective as salmeterol via either the Accuhaler or the pMDI in achieving these goals.

This double-blind study aimed to determine whether superior asthma control is achieved with budesonide (Pulmicort® Turbohaler®) at a loading dose (LD) (400 I..Ig b.d. ) for 6 weeks, followed by step down to 400 I..Ig nocte for 12 weeks, compared with a static dose (SO) (400 I..Ig nocte) for 18 weeks. A total of 682 patients (mean peak expiratory flow rate (PEFR) 413 I/min), who demonstrated ｾ 15% reversibility in PEFR, were randomised into the study. After 18 weeks, patients experienced improvements in morning PEFR (+45 I/min, both groups), symptom score (LO -0.57, SO -0.49, on a scale of 0-3), sleep disturbance (LO -1.21 nights/week, SO -1.06 nights/week) and ｾ Ｒ Ｍ ｡ ｧ ｯ ｮ ｩ ｳ ｴ use (LO -1.36 puffs/day, SO -1.06 puffs/day), within both groups (each p=0.0001). At 18 weeks, 82% (LO) and 84% (SO) of patients benefited from no nocturnal wakening in the previous 7 days. Overall" at 18 weeks, asthma control was not significantly different between the groups. After 6 weeks, improvements in morning PEFR (LO +361/min, SO +26I/min) and ｾ Ｒ Ｍ ｡ ｧ ｯ ｮ ｩ ｳ ｴ use (LO -1.10 puffs/day, SO -0.94 puffs/day) were greater in the loading dose than in the static dose group (each p<0.05). The greater improvement in morning PEFR in the loading dose group was significant by day 7 (p<0.05). While both regimens are equally effective in achieving asthma control at 18 weeks, early clinical advantage is gained with initial loading dose budesonide (400 I..Ig b.d.).

SUMMARYLong‐acting β2‐agonists (formoterol and salmeterol) represent the latest advance in a series of improvements in β2‐agonist asthma therapy since the introduction of isoprenaline. Traditional inhaled short‐acting β2‐agonists (salbutamol and terbutaline) provide rapid as‐needed symptom relief and short‐term prophylactic protection against bronchoconstriction induced by exercise or other stimuli. Where symptoms are not adequately controlled by corticosteroids alone, inhaled selective long‐acting β2‐agonists are used additionally for maintenance. Salmeterol and formoterol are well tolerated, provide effective long‐term symptom control and reduce the incidence of exacerbations; any development of tolerance or masking of underlying inflammation with continual use does not appear to be clinically relevant. Formoterol is both rapid acting (as fast as salbutamol) and long acting (similar to salmeterol). Increasing clinical evidence suggests that inhaled formoterol is a convenient and well‐tolerated treatment that is effective both for regular maintenance and as‐needed relief of symptoms.