Recommendations:
Boyd et al. (1985) studied 36 patients in a double blind, crossover double dummy study comparing 100 micro g of beclomethasone four times daily with 200 micro g twice daily. There was no difference in five symptoms. Clinic measured peak flow was 19 litres better in the four times daily group. There was no power calculation in this study.
Stiksa and Glennow (1985) studied 20 patients in an open crossover study of budesonide 800 micro g once daily; budesonide 400 micro g twice daily; and beclomethasone 200 micro g four times daily. There was no significant deterioration when on the once daily dose of budesonide. There was no power calculation in this study.
Munch et al. (1982) studied 20 patients in a double blind crossover design taking beclomethasone 200 micro g twice daily versus 100 micro g four times daily. There was no significant difference in peak flow or symptoms. There was no power calculation in this study.
Gagnon et al. (1994) studied 42 patients in a randomised double blind, double dummy crossover study of beclomethasone 500 micro g twice daily versus 1000 micro g in the afternoon versus 1000 micro g immediately before bed. Lung function was slightly better on the twice daily dosing. There was no power calculation in this study.
Toogood et al. (1982) studied 34 subjects who took inhaled budesonide in a complicated single blind randomised study using a block design which allowed comparison of three different budesonide dosages (400, 800, 1600 micro g per day); two dosing schedules (all dosages in the morning or dosages split between morning and evening); and two dosing frequencies (twice daily or four times daily). The results showed that both peak flow and FEV1 increased significantly as budesonide dosage increased; that peak flow, but not FEV1, was better with four times daily dose frequency than twice daily (20 litres per minute); and that there was no significant difference between the dosing schedules.
Gagnon, M., Cote, J., Milot, J., Turcotte, H. and Boulet, L.P. (1994) Comparative safety and efficacy of single or twice daily administration of inhaled beclomethasone in moderate asthma. Chest 105:1732-1737.
Munch, E.P. Taudorf, E. and Weeke, B. (1982) Dose frequency in the treatment of asthmatics with inhaled topical steroid. European Journal of Respiratory Diseases 63 Suppl 12:143-145.
Stiksa, G. and Glennow, C. (1985) Once daily inhalation of budesonide in the treatment of chronic asthma. A clinical comparison. Annals of Allergy 5: 49-51.
Toogood, J.H., Baskerville, J.C., Jennings, B., Lefcoe, N.M. and Johansson, S.A. (1982) Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide. Journal of Allergy and Clinical Immunology 70:388-298.
Toogood et al. (1982) studied 34 subjects who took inhaled budesonide in
a complicated single blind randomised study using a block design which
allowed comparison of three different budesonide dosages (400, 800, 1600 micro g per day); two dosing schedules (all dosages in the morning or dosages split between morning and evening); and two dosing frequencies (twice daily or four times daily). The results showed that both peak flow and FEV1 increased significantly as budesonide dosage increased; that peak flow, but not FEV1, was better with four times daily dose frequency than twice daily; and that there was no significant different between the dosing schedules.
Dahl et al. (1993) (as above) compared four different doses of fluticasone with one dose of belcomethasone in five parallel groups. They showed that fluticasone produced a dose dependent increase in peak flow rates and dose dependent decrease in symptoms.
Barnacle, H.A. (1993) Dose-ranging study of fluticasone propionate in adult patients with moderate asthma. International Study Group. Chest 104:1352-1358.
Toogood, J.H., Baskerville, J.C., Jennings, B., Lefcoe, N.M. and Johansson, S.A. (1982) Influence of dosing frequency and schedule on the response of chronic asthmatics to the aerosol steroid, budesonide. Journal of Allergy and Clinical Immunology 70:388-398.
Recommendation:
Wong et al. (1993) studied patients on high dose inhaled steroids and attempted to reduce the dose using either nedocromil or a placebo in a double blind parallel study. There was little evidence from objective measures that nedocromil was significantly better than placebo. It was more interesting that a lot of the subjects were able to reduce corticosteroid dose considerably in both arms of the study.
Is it effective to double inhaled steroids during inter current illnesses?
How safe are inhaled steroids?
Other inhaled anti-inflammatory agents
Recommendation:
Edwards and Stevens (1993) reported a meta-analysis of nedocromil. The analysis included all double blind, placebo controlled studies supplied and analysed by Fisons. The trials were analysed in five groups only two of which are relevant: group one where nedocromil or placebo was added to baseline treatment with bronchodilators alone (whether oral or inhaled is not stated); and group four where patients were inadequately controlled on inhaled corticosteroids and nedocromil or placebo was added. The analysis did not include any studies comparing the addition of nedocromil against the addition of inhaled steroids. It is not stated what dose of steroids patients in group four were taking.
The results were analysed in terms of daily dose delivered: 8 mg or 16 mg. The outcome variables considered were: symptoms (the sum of 0-4 scales for patient-perceived severity of asthma and cough, each for both day and night); frequency of use of inhaled bronchodilators; pulmonary function tests (the mean of twice daily PEFR, change in FEV1 from baseline to final visit); and patient opinion (the proportion of patients saying the treatment was very or moderately effective).
Group one data involved 1689 patients, group four 1103. All figures quoted in the results are group mean changes.
In group one severity scores were on average half a scale point better with nedocromil, cough score was 0.3 scale points better, PEFR was ten litres per minute better in the lower dose group only, FEV1 was 0.2 litres better, inhaled bronchodilator use was one puff a day better and patient opinion was 20% better.
In group four severity score was 0.25 scale points better in the high dose group only, cough score was not different from placebo, PEFR was eight litres per minute better in the higher dose group only, FEV1 was not different from placebo, inhaled bronchodilator use was not different from placebo, and patient opinion was 14% better.
Cua-Lim et al. (1986) studied a group of 54 asthmatic patients; nedocromil produced more improvement in symptoms and peak flow readings than placebo.
Greco et al. (1986) studied 130 subjects taking 4 mg of nedocromil four times daily, 2 mg four times daily or placebo; very small benefit of higher dose demonstrated.
van As et al. (1986) compared placebo with nedocromil twice daily and nedocromil four times daily. There were minor benefits compared with placebo with both nedocromil regimes.
Wong et al. (1993) studied patients on high dose inhaled steroids and attempted to reduce the dose using either nedocromil or a placebo in a double blind parallel study. There was little evidence from objective measurement that nedocromil was significantly better than placebo.
Bergmann et al. (1989) compared nedocromil with beclomethasone in a single blind parallel group study comparing placebo, nedocromil and beclomethasone 400 g daily. Both drugs were better than placebo. Where differences between nedocromil and beclomethasone were present, these tended to favour beclomethasone.
Boldy and Ayres (1993) studied 77 patients treated with either nedocromil 4 mg four times daily or sodium cromoglycate 10 mg four times daily (no placebo). There were no clinically significant differences; any slight difference seemed to favour cromoglycate.
Boldy, D.A. and Ayres, J.G. (1993) Nedocromil sodium and sodium cromoglycate in patients aged over 50 years with asthma. Respiratory Medicine 87:517-523.
Chatterjee, P.C., Fyans, P.G. and Chatterjee, S.S., (1986) A trial comparing nedocromil sodium (tilade) and placebo in the management of perennial bronchial-asthma. European Journal of Respiratory Diseases 69 Suppl. 147:314-316.
Cua-Lim, F., Agbayani, B.F. and Lachica, D. (1986) A double-blind comparative trial of nedocromil sodium and placebo in the management of bronchial asthma in patients routinely using oral bronchodilators. European Journal of Respiratory Diseases 69 Suppl. 147:306-310.
Edwards, A.M. and Stevens, M.T. (1993). The clinical efficiency of inhaled nedocromil sodium (Tilade) in the treatment of asthma. European Respiratory Journal 6: 35-41.
Greco, D.B., Negreiros, E.B., Chaieb, J.A., Ferreiralima, P. and Croce, J. (1986) A multicenter double-blind group comparative trial of 2 dose levels of nedocromil sodium and placebo in the management of perennial extrinsic-asthma. European Journal of Respiratory Diseases 69:323-326.
van As, A., Chick, T.W., Bodman, S.F., Storms, W.W., Nathan, R.A., Selner, J.C., Koepke, J.W., Townley, R.G., Bewtra, A.K., Nair, N., et al. (1986) A group comparative study of the safety and efficacy of nedocromil sodium (Tilade) in reversible airways disease: a preliminary report. European Journal of Respiratory Diseases 69 Suppl. 147:143-148.
Wong, C.S., Cooper, S., Britton, J.R. and Tattersfield, A.E. (1993) Steroid sparing effect of nedocromil sodium in asthmatic patients on high doses of inhaled steroids. Clinical and Experimental Allergy 23:370-376.
Blumenthal et al. (1988) showed that sodium cromoglycate works better than placebo and equally well with metered dose inhaler when compared with spinhaler.
inhaler in the treatment of asthma. Journal of Allergy and Clinical Immunology 81:681-687.