Use of a Fixed Combination β₂-Agonist and Steroid Dry Powder Inhaler in Asthma

In many countries the majority of patients with asthma are now treated with inhaled β2-agonists as required and regular inhaled steroids. Compliance with asthma medication is poor, particularly for inhaled steroids, which do not give immediate relief of symptoms. An inhaler combining a β2-agonist and a steroid may improve compliance and give better control of asthma. We have studied the effect of a fixed combination dry powder inhaler (Turbuhaler®) containing terbutaline (250 µg) with budesonide (200 µg) compared with each drug given alone in a double-blind, crossover study in 74 patients with mild to moderate asthma. This was a multicenter study performed in general practice. After a 1-wk run-in period with placebo inhaler, each treatment was given twice daily for 4 wk in randomized order. Patients measured symptom scores and rescue inhaled β2-agonist use and recorded peak expiratory flow (PEF) twice daily. In nine patients recruited to a hospital center, airway responsiveness was measured by the concentration of methacholine required to produce a fall in FEV1 of 20% (PC20) at the end of each treatment period. Of 74 patients randomized, 68 completed all three treatment periods. Their mean age was 37 (18–60) yr and PEF 80 (43–116) % predicted. Combination treatment gave a significant improvement in morning and evening PEF budesonide or terbutaline treatment periods (p < 0.01), and a significant reduction in asthma symptom scores and rescue β2-agonist use (p < 0.05). There was a significant patient preference for the combination inhaler. Measurement of compliance by counting unused doses showed good compliance with no significant difference between treatments. In nine patients who underwent methacholine challenge, both combination and budesonide treatment significantly improved PC20 by almost two doubling dilutions compared with baseline, whereas there was no protection after treatment with terbutaline. The acute protection 1 h after inhalation was significantly greater (p < 0.05) after combination than after terbutaline inhalation. We suggest that a fixed combination inhaler containing a low dose β2-agonist and an inhaled steroid provides a small but significant improvement in the control of mild asthma and may simplify its long-term management.