Budesonide at different doses for chronic asthma.

BACKGROUND Inhaled budesonide (BUD) is available in a range of doses for treating chronic asthma. OBJECTIVES To quantitatively assess the efficacy and safety of budesonide at different doses in order to establish whether a clinically significant dose response profile exists. SEARCH STRATEGY A search was carried out for Controlled and Randomised Clinical Trials (RCTs) using the Cochrane Airways Group trial register, correspondence with trial authors and the manufacturer. SELECTION CRITERIA Randomised trials in children and adults comparing one dose of budesonide to a second dose in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. DATA COLLECTION AND ANALYSIS One reviewer extracted data; authors were contacted to clarify missing information. Quantitative analyses where undertaken using Review Manager. MAIN RESULTS 24 studies were selected for inclusion in the review (3907 subjects). In non-oral steroid treated, mild to moderately severe asthma no clinically worthwhile differences in FEV1, morning PEFR, symptom scores or rescue beta2 agonist use were apparent across a dose range of 200-1600 mcg/d. However, in moderate to severe asthma there was a significant reduction in the likelihood of trial withdrawal due to asthma exacerbation with BUD 800 mcg/d compared to 200 mcg/d: RR 3.93 (95% CI, 1.4 to 10.9). This result was largely weighted by a single large high quality RCT. In a single study in patients receiving oral corticosteroids, clinically significant improvements favouring high dose BUD (1600 mcg/d) over low dose (200 mcg/d) were apparent for FEV1 and morning PEFR. In two studies there was no dose dependent oral steroid sparing effect for BUD 1600 mcg/d v 800 or 400 mcg/d. Statistically significant, dose dependent suppression of 24 hour urinary free cortisol excretion and serum cortisol post synthetic ACTH infusion over the dose range 800-3200 mcg/d were apparent but the clinical significance of these findings is unclear. REVIEWER'S CONCLUSIONS Budesonide exhibits a clinically significant dose response effect for improvement in FEV1 in severe asthma and reduction of exacerbations in moderate to severe asthma. No significant dose dependent improvements in FEV1, PEFR or symptoms are evident in non-oral steroid treated asthmatics with mild to moderate disease. Dose dependent alterations in sensitive measures of hypothalamic-pituitary-adrenal function were evident but the clinical significance of these changes is unclear.