High dose versus low dose inhaled corticosteroid as initial starting dose for asthma in adults and children.
BACKGROUND
Inhaled corticosteroids (ICS) form the basis of maintenance therapy in asthma and their efficacy is well established. However, the optimal starting dose of ICS is not clearly established. Recent reviews demonstrate a relatively flat efficacy curve for ICS and increasing side effects with increasing ICS doses. High doses are frequently prescribed and there are now reports of significant side effects occurring with high dose ICS use. These issues demonstrate the need to establish the optimal starting dose of ICS in asthma.


OBJECTIVE
To establish the optimal starting dose of ICS by evaluating the efficacy of initial high dose ICS with low dose ICS in subjects with asthma, not currently on ICS.


METHODS
We searched the Cochrane Airways Group trials register and reference lists of articles. Date of last search: January 2003


METHODS
Randomised controlled trials of two different doses of the same ICS in adults and children with asthma with no concomitant ICS or OCS.


METHODS
Trial quality was assessed and data were extracted independently by two reviewers. Study authors were contacted for confirmation. Trials were analysed according to the following ICS dose comparisons: step down vs constant dose ICS (n=7); high vs moderate (n=11); high vs low (n=9); moderate vs low (n=11); fold change in dose (all studies).


RESULTS
31 papers reporting the results of 26 trials were included in the review. For studies that compared a step down approach to a constant moderate/low ICS dose, there were no significant differences in lung function, symptoms, rescue medications or asthma control between the two treatment approaches. Significant but clinically small improvements in percent predicted FEV(1) ( WMD 5.32, 95% CI 0.65 to 9.99) and non significant improvements in the change in morning PEF were found for high dose ICS compared to moderate dose ICS. There were no significant differences in efficacy between high and low dose ICS. For moderate dose ICS, compared to low dose ICS, there were significant improvements in the change in morning PEF l/min from baseline (WMD 11.14, 95% CI 1.34 to 20.93) and nocturnal symptoms (SMD -0.29, 95% CI -0.53 to -0.06 ). Commencing ICS at double or quadruple a base moderate or low dose had no greater effect than commencing with the base dose. Several studies reported greater improvement in airway hyperresponsiveness for high dose ICS.


CONCLUSIONS
For patients with asthma who require ICS, commencing with a moderate dose ICS is equivalent to commencing with a high dose ICS and down-titrating. The small significant benefits of commencing with a high ICS dose are not of sufficient clinical benefit to warrant its use when compared to moderate or low dose ICS. Initial moderate ICS dose appears to be more effective than initial low ICS dose. High dose ICS may be more effective than moderate or low dose ICS for airway hyperresponsiveness. There is no benefit in doubling or quadrupling ICS in subjects with stable asthma.
Powell
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Gibson
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D000280:Administration, Inhalation; D000328:Adult; D000730:Androstadienes / Q000008:administration & dosage; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy*; D001507:Beclomethasone / Q000008:administration & dosage; D019819:Budesonide / Q000008:administration & dosage; D002648:Child; D000068298:Fluticasone; D006801:Humans; D016032:Randomized Controlled Trials as Topic
D000730:Androstadienes; D018927:Anti-Asthmatic Agents; D019819:Budesonide; D000068298:Fluticasone; D001507:Beclomethasone