RANDOMIZED CONTROLLED TRIAL OF INHALED CORTICOSTEROIDS (FLUTICASONE PROPIONATE) IN CYSTIC-FIBROSIS

Background-Controlling lung inflammation may be the key to improving m orbidity and mortality in cystic fibrosis. Objective-To assess the eff ects of inhaled corticosteroids on lung inflammation in cystic fibrosi s. Design-Double blind placebo controlled randomised sequence crossove r trial. Fluticasone propionate (400 mu g/day) was given as a dry powd er inhaler for six weeks with a four week washout period before crosso ver. Outcome measures-Sputum inflammatory markers (interleukin-8, tumo ur necrosis factor-alpha (TNF-alpha) and neutrophil elastase-both free and bound to alpha(1)-antiprotease), sputum interleukin-10, lung func tion, and symptomatology. Subjects-Twenty three children from a region al cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory v olume in one second (FEV1) of 64% (range 21% to 102%) predicted for se x and height. One patient was excluded for non-compliance to the study protocol. Results-No significant benefit was shown for the use of flu ticasone propionate in any of the outcomes. For sputum interleukin-8 t here was an estimated true treatment median difference of 142 pg/ml (9 5% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; whi le for maximal expiratory flow at 25% (MEF25%) remaining forced vital capacity predicted for sex and height there was a 15 percentage points (pp) (95% CI 4 to 26 pp) mean treatment difference in favour of place bo. Sputum interleukin-10 was undetected in any samples and unaffected by fluticasone propionate. Neither atopic status, baseline FEV1, nor concomitant DNase therapy had any effect on response to treatment. Con clusions-Lack of benefit from fluticasone propionate was most likely d ue to failure of the drug to penetrate the viscid mucus lining the air ways. It is suggested a large multicentre trial with higher doses give n for a longer time by a different delivery system is required to asse ss efficacy.