General practices in Nottinghamshire were asked to participate if patient records had been stored for at least a year on an accessible database (Torex, EM IS or Micro Medic). Suitable patients were identified using a stepwise approach combining computerised general practice records and interviews ().
Flow chart showing stepwise participant selection and reasons for exclusions.
The study recruited patients aged 18–70 years with a diagnosis of asthma and currently prescribed 400–1000 μg/day of beclometasone dipropionate or equivalent. Participants had to have evidence of poor adherence, which was defined as having collected less than 70% of the expected number of prescriptions for inhaled corticosteroid in the year prior to the study. They also had to have evidence of poor asthma control which was defined as: having prescriptions for at least two courses of prednisolone or 10 canisters of short-acting β2-agonist in the year prior to the study; and taking four or more rescue puffs of β2-agonist for at least 4 days a week over the previous 4 weeks.
Exclusion criteria included the use of a long-acting β2-agonist, leukotriene antagonist, or oral corticosteroids in the previous 4 weeks, other significant medical problems, smoking history more than 20 pack years, pregnancy, or inadequate contraception in women of childbearing age.
This was a randomised, open-label, parallel group, 6-month study. An independent pharmacist used computer-generated random numbers to randomise each participant to one of two groups.
Participants were provided with one budesonide inhaler containing 100 doses with 200 μg budesonide per puff (Pulmicort Turbohaler® 200 μg, AstraZeneca), and were asked to take one puff twice daily and use their usual short-acting β2-agonist as required.
Participants were provided with one combined budesonide/formoterol inhaler containing 120 doses with 200 μg budesonide and 6 μg formoterol per puff (Symbicort Turbohaler® 200/6 μg, AstraZeneca). They were asked to take one puff once daily and as required, and to use no other inhaler.
The Mini Asthma Quality of Life Questionnaire (MiniAQLQ),20
and the Asthma Control Questionnaire (ACQ)21
were completed by participants. The MiniAQLQ score ranges from 1 to 7, with 1 indicating severely impaired asthma-related quality of life. The ACQ score ranges from 0 to 6, with 6 indicating severely uncontrolled asthma. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured with participants seated, as the best of three readings (MicroLab 3500 spirometer, Micro Medical).
Participants were seen at their general practice for study visits. At the first visit participants completed baseline MiniAQLQ and ACQ, and underwent spirometry. Study medication was then given in exchange for the patients' usual asthma medication, with instructions on its correct use. Participants in the control group kept their usual short-acting β2-agonist.
Participants were asked to contact the study coordinator to arrange a visit when their study inhaler was nearly empty. At these visits a replacement study inhaler was provided and the number of doses remaining in the returned inhaler was counted. The two asthma questionnaires were completed, information about oral steroid use or visits to their GP for asthma-related problems since the last visit were noted, and spirometry was performed. GP records were checked to corroborate the information provided by participants about unscheduled visits. A visit was arranged at 3 months if participants had not requested a new inhaler by that time, and a final visit was scheduled at 6 months. For safety reasons, participants in the active group were asked to contact the study investigator if they used 10 or more puffs of their study inhaler in 1 day.
How this fits in
Poor adherence with inhaled corticosteroid is an important problem in asthma management. Previous approaches to improving adherence have had limited success. This study has shown that using a single inhaler for both maintenance treatment and symptom relief approximately doubled the dose of inhaled corticosteroid taken. This could be a useful strategy to overcome the problems associated with poor adherence with inhaled corticosteroids.
The primary outcome was the difference between the two groups in dose of inhaled budesonide during the 6-month study period. The total dose of budesonide taken by participants was calculated by subtracting the dose of budesonide remaining in the returned inhalers from the total dose of budesonide provided. Participants' average daily dose of budesonide was obtained by dividing the total dose taken by the number of days the participant was in the study.
Secondary outcomes included the difference between the two groups for change in MiniAQLQ and ACQ score, change in mean FEV1, oral corticosteroid use, and participants' visits to the GP for asthma-related problems.
Power calculations were based on the assumption that a 25% difference in the inhaled corticosteroid dose would be clinically important. Assuming an average dose of inhaled budesonide of 45 mg (standard deviation [SD] 10 mg) over the 6 months in the control group, 50 patients in each group gave more than 90% power to detect a 25% difference in corticosteroid dose between the treatment groups. Due to difficulty in recruitment, only 71 participants were enrolled, but the study still had 90% power to detect this difference.
All participants seen at least once after randomisation were included in the analysis. Daily dose of budesonide and change in FEV1, MiniAQLQ, and ACQ scores were compared between groups by unpaired t-test. Average FEV1 over the study period was calculated as the mean of all FEV1 measurements obtained after the first visit. The number of participants who did not complete the study, and the number of participants visiting their GP or requiring oral steroids were compared using χ2test. Mean and 95% confidence intervals (CI) are given where appropriate.