Bergmann et al. (1989) conducted a single blind parallel group study comparing placebo, nedocromil and beclomethasone 400 g daily. Both drugs were better than placebo. Although there were a few differences between nedocromil and beclomethasone, these favoured beclomethasone when present.
Salmeron et al. (1989) showed that in patients randomised to receive beclomethasone 1500 micro g daily or placebo those in the treatment group had, over an eight week period, significantly less use of extra medication and significantly fewer courses of oral steroids.
Haahtela et al. (1991) studied patients with mild asthma diagnosed within the last 12 months randomised to receive either terbutaline twice daily or budesonide twice daily and followed for 96 weeks. The peak flow readings were significantly better in the budesonide group although there was little difference in symptoms (probably because they were mild to start with).
Haahtela, T., Jarvinen, M., Kava, T., Kiviranta, K., Koskinen, S., Lehtonen, K., Nikander, K., Persson, T., Reinikainene, K., Selroos, O., et al. (1991) Comparison of a beta 2 agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma. New England Journal of Medicine 325:388-392.
Salmeron, S., Guerin, J.C., Godard, P., Renon, D., Henry-Amar, M., Duroux, P. and Taytard, A. (1989) High doses of inhaled corticosteroids in unstable chronic asthma: a multi-center, double-blind, placebo-controlled study. American Review of Respiratory Disease 140:167-171.
The British Thoracic and Tuberculosis Association (1975) conducted a complicated study in which patients were randomised to prednisolone, beclomethasone 800 micro g per day, or betamethasone 800 micro g per day. Their treatment was reduced and so the lowest dose compatible with a clinically stable state was established. They were then left on this dose for 24 weeks during which time they were compared in terms of symptoms, peak flow, and need for additional treatment. No differences in these indices of control were seen.
In a subsequent study (British Thoracic and Tuberculosis Association, 1976) 154 patients on oral steroids were randomised to beclomethasone 1000 micro g four times daily, beclomethasone 200 micro g four times daily, betamethasone 200 micro g four times daily or placebo. Their prednisolone dose was then reduced by 1 mg per week. A greater dose reduction was possible on active treatment than placebo and there was greater benefit with the higher dose of inhaled steroid.
Laursen et al. (1986) studied a group of 50 "steroid dependant" asthmatics. A significantly greater reduction in prednisolone dosage was possible using 1600 micro g of budesonide a day when compared to 400 g per day but the advantage was small.
Hummel and Lehtonen (1992) studied 125 patients on at least 10 mg of prednisolone for at least six months who received either 300 micro g or 1500 micro g of beclomethasone per day and tried to decrease their oral prednisolone over a six month period. There was no difference in the success rate between high and low dose groups.
with oral prednisone in patients starting long-term corticosteroid therapy for asthma. Lancet 469-473.
British Thoracic and Tuberculosis Association (1976) A controlled trial of inhaled corticosteroids in patients receiving prednisone tablets for asthma. British Journal of Diseases of the Chest 70:95-103.
Hummel, S. and Lehtonen, L. (1992) Comparison of oral-steroid sparing by high-dose and low-dose inhaled steroid in maintenance treatment of severe asthma [see comments]. Lancet 340:1483-1487.
Laursen, L.C., Taudorf, E. and Weeke, B. (1986) High-dose inhaled budesonide in treatment of severe steroid-dependent asthma. European Journal of Respiratory Diseases 68:19-28.
Differing steroid preparations
Recommendation:
Willey et al. (1982) compared 400 micro g of beclomethasone per day with 400 micro g of budesonide per day in 30 asthmatics over an eight week period (four week crossover). No clinically significant difference between the treatments was shown.
Ebden et al. (1986) compared high dose beclomethasone with budesonide in 28 patients over six weeks in a double blind, double dummy crossover trial. There was no significant difference in peak flow or symptoms. There were minor differences in serum cortisols (p<0.05) in favour of beclomethasone and frequency of bronchodilator use (p<0.05) in favour of budesonide.
Svensden et al. (1992) compared 800 micro g twice daily of budesonide with 750 micro g of beclomethasone in 36 asthmatics over a six week period. No significant difference between the treatments was shown.
Barnes et al. (1993) studied 154 patients in a double blind parallel group design over 2 weeks. They compared 1000 micro g of fluticasone against 2000 micro g of beclomethasone. There was no difference between the groups in terms of beta 2 agonist use, symptoms or peak flow values. Fluticasone had less effect on serum cortisol; the group were unclear about the clinical significance of this.
Dahl et al. (1993) compared four different doses of fluticasone with one dose of beclomethasone in five parallel groups. They showed that fluticasone produced a dose dependent increase in peak flow rates and dose dependent decrease in symptoms.
Fabbri et al. (1993) studied 272 subjects with severe asthma; 1500 micro g of fluticasone per day was slightly better, in terms of lung function and number of exacerbations, than 1500 micro g of beclomethasone per day.
Lundback et al. (1993) studied 585 patients in a randomised, double blind three parallel group study comparing 500 micro g of fluticasone via diskhaler, 500 micro g of fluticasone via metered dose inhaler, and 1000 micro g of beclomethasone via metered dose inhaler. There was no difference in peak flow diaries or need for rescue medication. Morning symptoms were better on beclomethasone and evening symptoms slightly better on fluticasone.
Dahl, R., Lundback, B., Malo, J.L., Mazza, J.A., Nieminen, M.M., Saarelainen, P. and Barnacle, H. (1993) A dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group. Chest 104:1352-1358.
Ebden, P., Jenkins, A., Houston, G. and Davies, B.H. (1986) Comparison of two high dose corticosteroid aerosol treatments, beclomethasone dipropionate (1500 g /day) and budesonide (1600 g/day), for chronic asthma. Thorax 41:869-874.
Fabbri, L., Burge, P.S., Croonenborgh, L., Warlies, F., Weeke, B., Ciaccia, A. and Parker, C. (1993) Comparison of fluticasone propionate with beclomethasone dipropionate in moderate to severe asthma treated for one year. International Study Group. Thorax 48:817-823.
Lundback, B., Alexander, M., Day, J., Hebert, J., Holzer, R., Van Uffelen, R., Kesten S. and Jones, A.L. (1993) Evaluation of fluticasone propionate (500 g day-1) administered either as dry powder via a Diskhaler inhaler or pressurized inhaler and compared with beclomethasone dipropionate (1000 g day-1) administered by pressurized inhaler. Respiratory Medicine 87: 609-20
Svensden, U.G., Frolund, L., Heinig, J.H., Madsen, F., Nielsen, N.H., and Weeke, B. (1992) High dose inhaled steroids in the management of asthma. A comparison of the effects of budesonide and beclomethasone dipropionate on pulmonary function, symptoms, bronchial responsiveness and the adrenal function. Allergy 47:174-180.
Willey, R.F., Godden, D.J., Carmichael, J., Preston, P., Frame, M. and Crompton, G.K. (1982) Comparison of twice daily administration of a new corticosteroid budesonide with beclomethasone dipropionate four times daily in the treatment of chronic asthma. British Journal of Diseases of the Chest 76:61-68.
Addition of inhaled steroids to short acting beta 2 agonists
Recommendation:
Haahtela et al. (1991) looked at additional treatment for "mild" asthmatics defined as those needing to use beta 2 agonists two to three times a day. Patients with mild asthma diagnosed within the last 12 months were randomised to receive either terbutaline twice daily or budesonide twice daily and followed for 96 weeks. The peak flow readings were much better in the budesonide group although there was little difference in symptoms (probably because they were mild to start with).
Lorentzson et al. (1990) studied asthmatics who were not receiving inhaled steroids but needed beta 2 agonists 35 puffs in the run-in week (a mean of five puffs daily). They were randomised to receive placebo; 100 micro g of budesonide twice daily; or 200 micro g budesonide twice daily. The groups on active treatment benefited significantly more than the placebo group; peak flow rose, symptom score fell, and beta 2 agonist use fell. There was no significant difference between the two doses of budesonide.
Lorentzson, S., Boe, J., Eriksson, G. and Persson, G. (1990) Use of inhaled corticosteroids in patients with mild asthma. Thorax 45:733-735.