EFTHIMIOU and BARNES [1], in their review "Effect of inhaled corticosteroids on bones and growth", referred to our paper "Growth and adrenal suppression in asthmatic children treated with high dose fluticasone propionate" [2] as "anecdotal reports of growth deceleration in asthmatic children treated with inappropriately high doses (i.e. 5±10 times the recommended dose) of inhaled corticosteroids". In our study, the high doses were used as an alternative to oral corticosteroids in a group of

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... dren who had very severe asthma not controlled with lower doses of inhaled corticosteroids, short-and long-acting b-agonists and theophyllines. Frequent attempts were made to step down treatment if the asthma was stable. They should also be aware that the paper was not a study but a series of six case reports, and that case reporting is very important in new drug pharmacovigilance [3]. Fluticasone in doses of up to 1,000 mg . day -1 (five times the recommended dose) is allowed by the British Thoracic Society guidelines (1995) for the treatment of asthma in children and P.J. Barnes himself has stated that "there is no convincing evidence that inhaled steroids even in high dose (2 mg . day -1 ) have effects on ... growth in children" [4]. We conducted a survey of inhaled corticosteroid prescriptions in primary care and found that >30% of all prescriptions for fluticasone are in excess of recommended doses and 4% for $1,000 mg . day -1 (C. Fitzpatrick, personal communication). A survey of specialist paediatric centres in the UK showed that when high doses of inhaled corticosteroids (>1,000 mg . day -1 ) are thought necessary, nearly all choose fluticasone proprionate (W. Lenny, personal communication). Thus, the usage of fluticasone proprionate in high doses in severely asthmatic children is common and not confined to our practice. There are no long-term studies looking at this newest inhaled corticosteroid in high doses, hence the importance of our case reporting, which J. Efthimiou and P.J. Barnes underestimate. All of our cases demonstrated that a very high first-pass hepatic metabolism (99.9%) for fluticasone does not prevent the occurrence of serious systemic effects at high doses ($1,000 mg . day -1 ). This is probably due to the very high lipophilicity of fluticasone (250±300-times greater than beclomethasone or budesonide), which results in a much higher tissue distribution, longer plasma half-life and greater glucocorticoid receptor affinity than budesonide or beclamethasone [5]. Fluticasone is the only inhaled steroid reported to accumulate with repeated >1,000 mg . day -1 dosing in adults [6±11], although no accumulation effect has been detected with a dosage of 400 mg . day -1 in children [12] . Therefore, there is also good pharmacokinetic evidence to support our clinical observations and these factors, in the absence of studies, should be taken into account when choosing an inhaled corticosteroid at a high dose in severely asthmatic children.