Inhaled fluticasone at different doses for chronic asthma in adults and children

Background Inhaled fluticasone propionate (FP) is a high-potency inhaled corticosteroid used in the treatment of asthma. Objectives 1. To assess the efficacy and safety outcomes of inhaled fluticasone at different nominal daily doses in the treatment of chronic asthma. 2. To test for the presence of a dose-response effect. Search strategy We searched the Cochrane Airways Group Trials Register (January 2005) and reference lists of articles. We contacted trialists and pharmaceutical companies for additional studies and searched abstracts of major respiratory society meetings (1997 to 2004). Selection criteria Randomised trials in children and adults comparing fluticasone at different nominal daily doses in the treatment of chronic asthma. Two reviewers independently assessed articles for inclusion and methodological quality. Data collection and analysis One reviewer extracted data. These were checked and verified by a second reviewer. Quantitative analyses where undertaken using RevMan (Analyses 1.0.2). Main results Forty-three studies (45 data sets with 8913 participants) met the inclusion criteria. Methodological quality was high. In asthmatics with mild to moderate disease who were not on oral steroids a dose-response effect was present with FP for change in morning peak expiratory flow (PEF). For low doses (100 versus 200 mu g/day) the weighted mean difference (WMD) was 6.29 litres/min, 95% confidence interval (CI) 2.28 to 10.29. Comparing medium (400 to 500 mu g/day) to low dose (200 mu g/day) FP the WMD was 6.46 litres/min (95% CI 3.02 to 9.89); this effect was more pronounced in one trial with more severely asthmatic children. For FP 100 versus 400 to 500 mu g/day the WMD was 8 litres/min (95% CI 1 to 15) and at high versus low doses (800 to 1000 versus 50 to 100 mu g/d) the WMD was 22 litres/min (95% CI 15 to 29). When high and medium doses were compared there was no significant difference in the change in morning PEF: at 400 to 500 versus 800 to 1000 mu g/day the WMD was 0.16 litres/min (95% CI 6.95 to 6.63). There was no dose-response effect on symptoms or rescue beta-2 agonist use. The likelihood of hoarseness and oral candidiasis was significantly greater for the higher doses (800 to 1000 mu g/day). People with oral steroid-dependent asthma treated with FP (2000 mu g/day) were significantly more likely to reduce oral prednisolone than those on 1000 to 1500 mu g/day (Peto odds Ratio 2.8, 95% CI 1.3 to 6.3). The highest dose also allowed a significant reduction in daily oral prednisolone dose compared to 1000 to 1500 mu g/day (WMD 2.0 mg/day, 95% CI 0.1 to 4.0 mg/day). Authors' conclusions Effects of fluticasone are dose dependent but relatively small. At dose ratios of 1: 2, there are significant differences in favour of the higher dose in morning peak flow across the low dose range. The clinical impact of these differences is open to interpretation. Patients with moderate disease achieve similar levels of asthma control on medium doses of fluticasone (400 to 500 mu g/day) as they do on high doses (800 to 1000 mu g/day). More work in severe asthma would help to confirm that doses of FP above 500 mu g/day confer greater benefit in this subgroup than doses of around 200 mu g/day. In oral corticosteroid-dependent asthmatics, reductions in prednisolone requirement may be gained with FP 2000 mu g/day.