Arch Dis Child 1997;77:124-130 ( August )

Randomised controlled trial of inhaled corticosteroids (fluticasone propionate) in cystic fibrosis

Ian M Balfour-Lynn,^a Nigel J Klein,^b Robert Dinwiddie^a

^a Great Ormond Street Hospital for Children NHS Trust, London: Department of Respiratory Medicine, ^b Department of Immunobiology

Correspondence to: Dr I M Balfour-Lynn, Department of Respiratory Medicine, Great Ormond Street Hospital for Children NHS Trust, Great Ormond Street, London WC1N 3JH.

Accepted 29 April 1997

BACKGROUNDControlling lung inflammation may be the key to improving morbidity and mortality in cystic fibrosis.
OBJECTIVETo assess the effects of inhaled corticosteroids on lung inflammation in cystic fibrosis.
DESIGNDouble blind placebo controlled randomised sequence crossover trial. Fluticasone propionate (400 µg/day) was given as a dry powder inhaler for six weeks with a four week washout period before crossover.
OUTCOME MEASURESSputum inflammatory markers (interleukin-8, tumour necrosis factor- (TNF-) and neutrophil elastaseboth free and bound to ₁-antiprotease), sputum interleukin-10, lung function, and symptomatology.
SUBJECTSTwenty three children from a regional cystic fibrosis centre were enrolled into the study, with mean age 10.3 years (range 7 to 17 years) and mean baseline forced expiratory volume in one second (FEV₁) of 64% (range 21% to 102%) predicted for sex and height. One patient was excluded for non-compliance to the study protocol.
RESULTSNo significant benefit was shown for the use of fluticasone propionate in any of the outcomes. For sputum interleukin-8 there was an estimated true treatment median difference of 142 pg/ml (95% confidence interval (CI) 8 to 2866 pg/ml) in favour of placebo; while for maximal expiratory flow at 25% (MEF_25%) 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 placebo. 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.
CONCLUSIONSLack of benefit from fluticasone propionate was most likely due to failure of the drug to penetrate the viscid mucus lining the airways. It is suggested a large multicentre trial with higher doses given for a longer time by a different delivery system is required to assess efficacy.

Keywords: cystic fibrosis; corticosteroids; inflammation; randomised controlled trial

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© 1997 by Archives of Disease in Childhood
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